20044890	The present study aimed to examine the influence of musical expertise on the metric and semantic aspects of speech processing. In two attentional conditions (metric and semantic tasks), musicians listened to short sentences ending in trisyllabic words that were semantically and/or metrically congruous or incongruous. Both ERPs and behavioral data were analyzed and the results were compared to previous nonmusicians' data. Regarding the processing of meter, results showed that musical expertise influenced the automatic detection of the syllable temporal structure (P200 effect), the integration of metric structure and its influence on word comprehension (N400 effect), as well as the reanalysis of metric violations (P600 and late positivities effects). By contrast, results showed that musical expertise did not influence the semantic level of processing. These results are discussed in terms of transfer of training effects from music to speech processing.	t	\N
20117764	We present new evidence based on fMRI for the existence and neural architecture of an abstract supramodal language system that can integrate linguistic inputs arising from different modalities such that speech and print each activate a common code. Working with sentence material, our aim was to find out where the putative supramodal system is located and how it responds to comprehension challenges. To probe these questions we examined BOLD activity in experienced readers while they performed a semantic categorization task with matched written or spoken sentences that were either well-formed or contained anomalies of syntactic form or pragmatic content. On whole-brain scans, both anomalies increased net activity over non-anomalous baseline sentences, chiefly at left frontal and temporal regions of heteromodal cortex. The anomaly-sensitive sites correspond approximately to those that previous studies (Michael et al., 2001; Constable et al., 2004) have found to be sensitive to other differences in sentence complexity (object relative minus subject relative). Regions of interest (ROIs) were defined by peak response to anomaly averaging over modality conditions. Each anomaly-sensitive ROI showed the same pattern of response across sentence types in each modality. Voxel-by-voxel exploration over the whole brain based on a cosine similarity measure of common function confirmed the specificity of supramodal zones.	t	\N
20146608	The neural responses to sensory consequences of a self-produced motor act are suppressed compared with those in response to a similar but externally generated stimulus. Previous studies in the somatosensory and auditory systems have shown that the motor-induced suppression of the sensory mechanisms is sensitive to delays between the motor act and the onset of the stimulus. The present study investigated time-dependent neural processing of auditory feedback in response to self-produced vocalizations. ERPs were recorded in response to normal and pitch-shifted voice auditory feedback during active vocalization and passive listening to the playback of the same vocalizations. The pitch-shifted stimulus was delivered to the subjects' auditory feedback after a randomly chosen time delay between the vocal onset and the stimulus presentation. Results showed that the neural responses to delayed feedback perturbations were significantly larger than those in response to the pitch-shifted stimulus occurring at vocal onset. Active vocalization was shown to enhance neural responsiveness to feedback alterations only for nonzero delays compared with passive listening to the playback. These findings indicated that the neural mechanisms of auditory feedback processing are sensitive to timing between the vocal motor commands and the incoming auditory feedback. Time-dependent neural processing of auditory feedback may be an important feature of the audio-vocal integration system that helps to improve the feedback-based monitoring and control of voice structure through vocal error detection and correction.	t	\N
20347261	In this study, the subjective and objective voice measures of seven female physical education student teachers during a semester of student teaching were investigated. The participants completed the voice measures at three data collection time points: baseline, middle, and end of the semester. The voice measures included acoustic and aerodynamic data, perceptual rating scales of vocal quality and vocal fatigue, an end-of-semester questionnaire, and the Voice Handicap Index. Results demonstrated that the subjective and objective voice measures changed at the middle and the end of the semester as compared with those at baseline. The change in the voice measures may suggest that the vocal mechanism was adapting to the increased vocal demands of teaching physical education.	t	\N
20411315	Noisy recordings of dialogue often serve as evidence in criminal proceedings. The present article explores the ability of two types of contextual information, currently present in the legal system, to bias subjective interpretations of such evidence. The present experiments demonstrate that the general context of the legal system and the presence of transcripts of the recorded speech are both able to bias interpretations of degraded & benign recordings into interpretable & incriminating. Furthermore we demonstrate a curse of knowledge whereby people become miscalibrated to the true quality of degraded recordings when provided transcripts. Current methods of dealing with auditory evidence are insufficient to mollify the effects of biasing information within the criminal justice system.	t	\N
20433240	On the basis of results from behavioral studies that spatial attention improves the exclusion of external noise in the target region, we predicted that attending to a spatial region would reduce the impact of external noise on the BOLD response in corresponding cortical areas, seen as reduced BOLD responses in conditions with large amounts of external noise but relatively low signal, and increased dynamic range of the BOLD response to variations in signal contrast. We found that, in the presence of external noise, covert attention reduced the trial-by-trial BOLD response by 15.5-18.9% in low signal contrast conditions in V1. It also increased the BOLD dynamic range in V1, V2, V3, V3A/B, and V4 by a factor of at least three. Overall, covert attention reduced the impact of external noise by about 73-85% in these early visual areas. It also increased the contrast gain by a factor of 2.6-3.8.	t	\N
20576373	Patients with systemic lupus erythematosus (SLE) may develop hearing and balance disorders as a result of the immune-mediated inner ear damage due to vasculitis or ototoxicity of drugs used in SLE treatment. The aim of the study was evaluation of the hearing organ disorders in patients with SLE with particular regard to their prevalence and relationship to duration and severity of disease. The severity was assessed from involvement of organs that resulted in poorer SLE outcome, i.e. kidneys and central nervous system (CNS), and from the presence of antibodies associated with unfavourable SLE prognosis. Thirty-five unselected, consecutive patients (33 women, two men, mean age 47.8 years) with SLE diagnosed in compliance to the international diagnostic criteria of the American Rheumatism Association (1982) were enrolled into the study. The control group consisted of 30 otologically healthy persons matched to the SLE group for age and sex. Case history was recorded for all patients from questionnaire data and laryngological examinations were performed, followed by pure-tone, speech and impedance audiometry and auditory brainstem response audiometry (ABR). In the anamnesis 71.4% of patients reported vertigo, 62.9% headaches, 40% tinnitus, 25.7% hyperacusis, 17.1% hearing loss and 2.9% ear fullness. It was found that SLE patients had a significantly poorer mean hearing thresholds than the control group for all frequencies, except for 500; 2000 and 4000 Hz. Longer ABR latency averages were observed in the group of SLE patients compared to control. Ten patients (28.6%) developed high-frequency and symmetric sensorineural hearing loss (SNHL). Significant positive correlation between mean air-conduction hearing thresholds and SLE duration (r = 0.46, p < 0.001) was found. After taking age into consideration, hearing acuity in SLE was related to duration of disease in younger patients. Furthermore, no relation was seen between hearing level and severity of disease. Auditory system involvement ought to be considered as one of elements of the clinical picture of systemic lupus erythematosus while determination of its character, original or secondary, requires further research.	t	\N
20599334	The children with difficulty in receiving sounds presented at rapid rates in speech sounds and language learning period, may have delay in speech sounds and language development due to hearing speech sounds not clearly. Auditory temporal processing (ATP) is the ability to perceive auditory signals of brief duration accurately when presented at rapid rates. ATP can be evaluated by the random gap detection test (RGDT), which detects a brief gap between two stimuli. In this study, we investigated performance of children with previous language delay (PLD), currently having disorders in more than one speech sounds, on random gap detection test (RGDT) and RGDT-expanded (RGDT-EXP) tests. 12 children (8 male, 4 female) with previous language delay (PLD) and complaint of expressing speech sounds distorted, were included into the study. They had applied language training for at least one-year period in the past and in the current time, their language development is normal. They expressed one or more speech sounds as distorted. The control group consisted of 10 normal hearing children with normal phonological development and language matched for age; and who had not PLD (5 male, 5 female). Children language levels were evaluated by Preschool Language Scale-4 test; or Clinical evaluation of language fundamentals, fourth edition (CELF-4) according to child's age. Speech sounds development was assessed by Speech Sound Development Test (SSDT). They were applied RGDT and/if necessary, RGDT-EXP. Each child responded whether he/she heard one or two tones. Their responses were taken as verbally and/or hold up one finger or two fingers. In the second test, they were applied speech discrimination test in quiet environment and in noise. Gap detection thresholds (GDTs) were detected at 500-4000 Hz; and Composite GDTs (CGDTs) were found for the study and control groups. GDT/CGDT > 20 ms was considered as abnormal for temporal processing disorder. In the study group with PLD, mean of the GDTs were all over the normal limits; and in control group, mean of GDTs were all in normal limits. The difference between the mean GDTs of the study group were significantly higher than the control groups at all frequencies of 500-4000 Hz. In PLD group, CGDT (103.53 ± 11.63 ms) was significantly higher than that of the control group, (10.35 ± 0.65 ms) (p=0.021). The children with PLD have difficulties in perception of speech sounds at a certain rate, even they have not language learning difficulties. Therefore, difficulty in distinguishing of speech sounds may cause especially receptive language development delay. We believe that perception of the speech sounds and language in a certain speed; and temporally degraded speech programmes should be incorporated into the training programme and may help to prevent delays.	t	\N
20617885	The present study investigated the effects of auditory selective attention on the processing of syntactic information in music and speech using event-related potentials. Spoken sentences or musical chord sequences were either presented in isolation, or simultaneously. When presented simultaneously, participants had to focus their attention either on speech, or on music. Final words of sentences and final harmonies of chord sequences were syntactically either correct or incorrect. Irregular chords elicited an early right anterior negativity (ERAN), whose amplitude was decreased when music was simultaneously presented with speech, compared to when only music was presented. However, the amplitude of the ERAN-like waveform elicited when music was ignored did not differ from the conditions in which participants attended the chord sequences. Irregular sentences elicited an early left anterior negativity (ELAN), regardless of whether speech was presented in isolation, was attended, or was to be ignored. These findings suggest that the neural mechanisms underlying the processing of syntactic structure of music and speech operate partially automatically, and, in the case of music, are influenced by different attentional conditions. Moreover, the ERAN was slightly reduced when irregular sentences were presented, but only when music was ignored. Therefore, these findings provide no clear support for an interaction of neural resources for syntactic processing already at these early stages.	t	\N
20642737	Acoustic and visual interceptive actions were tested in this research by comparing the performance of blind, blind-folded, and sighted individuals. An indirect interception method was employed in which the participant had to roll an intercepting ball towards a moving target on a perpendicular track. The interception task used conditions that varied the speed, rolling distance, and target size/intensity. While performance was highly consistent and accurate for visual participants in this research, the blind and blind-folded participants demonstrated much more performance variability in response to changes in speed and distance. Manipulation of target size and intensity did not affect judgments, however performance tended to be more accurate at shorter distances and with faster target speeds. Results from this research are discussed in terms of their implications for tau in acoustic interception, and the use of spatial and temporal cues for guiding interceptive actions.	t	\N
20644955	Two experiments investigated the effects of interval duration ratio on perception of local timing perturbations, accuracy of rhythm production, and phase correction in musicians listening to or tapping in synchrony with cyclically repeated auditory two-interval rhythms. Ratios ranged from simple (1:2) to complex (7:11, 5:13), and from small (5:13 = 0.38) to large (6:7 = 0.86). Rhythm production and perception exhibited similar ratio-dependent biases: rhythms with small ratios were produced with increased ratios, and timing perturbations in these rhythms tended to be harder to detect when they locally increased the ratio than when they reduced it. The opposite held for rhythms with large ratios. This demonstrates a close relation between rhythm perception and production. Unexpectedly, however, the neutral "attractor" was not the simplest ratio (1:2 = 0.50) but a complex ratio near 4:7 (= 0.57). Phase correction in response to perturbations was generally rapid and did not show the ratio-dependent biases observed in rhythm perception and production. Thus, phase correction operates efficiently and autonomously even in synchronization with rhythms exhibiting complex interval ratios.	t	\N
20663254	Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex. Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants' level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants' arcuate fasciculus was used to predict their level of cortical suppression in the three conditions. While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient's level of N1 suppression was linearly related to the FA of their arcuate fasciculus. These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination.	t	\N
20665720	The effect of stimulus modulation rate on the underlying neural activity in human auditory cortex is not clear. Human studies (using both invasive and noninvasive techniques) have demonstrated that at the population level, auditory cortex follows stimulus envelope. Here we examined the effect of stimulus modulation rate by using a rare opportunity to record both spiking activity and local field potentials (LFP) in auditory cortex of patients during repeated presentations of an audio-visual movie clip presented at normal, double, and quadruple speeds. Mean firing rate during evoked activity remained the same across speeds and the temporal response profile of firing rate modulations at increased stimulus speeds was a linearly scaled version of the response during slower speeds. Additionally, stimulus induced power modulation of local field potentials in the high gamma band (64-128 Hz) exhibited similar temporal scaling as the neuronal firing rate modulations. Our data confirm and extend previous studies in humans and anesthetized animals, supporting a model in which both firing rate, and high-gamma LFP power modulations in auditory cortex follow the temporal envelope of the stimulus across different modulation rates.	t	\N
20666594	Spoken word recognition is achieved via competition between activated lexical candidates that match the incoming speech input. The competition is modulated by prelexical cues that are important for segmenting the auditory speech stream into linguistic units. One such prelexical cue that listeners rely on in spoken word recognition is phonotactics. Phonotactics defines possible combinations of phonemes within syllables or words in a given language. The present study aimed at investigating both temporal and topographical aspects of the neuronal correlates of phonotactic processing by simultaneously applying ERPs and functional near-infrared spectroscopy (fNIRS). Pseudowords, either phonotactically legal or illegal with respect to the participants' native language, were acoustically presented to passively listening adult native German speakers. ERPs showed a larger N400 effect for phonotactically legal compared to illegal pseudowords, suggesting stronger lexical activation mechanisms in phonotactically legal material. fNIRS revealed a left hemispheric network including fronto-temporal regions with greater response to phonotactically legal pseudowords than to illegal pseudowords. This confirms earlier hypotheses on a left hemispheric dominance of phonotactic processing most likely due to the fact that phonotactics is related to phonological processing and represents a segmental feature of language comprehension. These segmental linguistic properties of a stimulus are predominantly processed in the left hemisphere. Thus, our study provides first insights into temporal and topographical characteristics of phonotactic processing mechanisms in a passive listening task. Differential brain responses between known and unknown phonotactic rules thus supply evidence for an implicit use of phonotactic cues to guide lexical activation mechanisms.	t	\N
20801079	Tinnitus can be considered an auditory phantom percept, in which patients hear an internal sound in the absence of any external sound source, mimicking tonal memory. Tinnitus however can be perceived exclusively uni- or bilaterally. The neurophysiological differences were investigated between unilateral and bilateral tinnitus using LORETA source localized resting state EEG recordings. The difference between unilateral and bilateral tinnitus is reflected by high frequency activity (beta and gamma) in the superior prefrontal gurus, right parahippocampus, right angular gyrus and right auditory cortex. Unilateral tinnitus is characterized by contralateral beta2 in the superior prefrontal gyrus in comparison to bilateral tinnitus, but gamma in comparison to non-tinnitus subjects. Bilateral tinnitus has delta activity in the ventrolateral prefrontal cortex in comparison to unilateral tinnitus, and bilateral beta1 in comparison to non-tinnitus subjects. Bilateral tinnitus is also characterized by bilateral frontopolar beta1 activity. Unilateral and bilateral tinnitus can be differentiated based on their resting state oscillation patterns: beta3 and gamma-band activity in the superior premotor cortex, parahippocampal area and angular gyrus seem to form the core of a spatial localization network involved in tinnitus. These differences should be taken into account when evaluating functional neuroimaging data relating to tinnitus.	t	\N
20808225	The purpose of this study was to examine speech recognition through hearing aids for seven telephone listening conditions. Speech recognition scores were measured for 20 participants in six wireless routing transmission conditions and one acoustic telephone condition. In the wireless conditions, the speech signal was delivered to both ears simultaneously (bilateral speech) or to one ear (unilateral speech). The effect of changing the noise level in the nontest ear during unilateral conditions was also examined. Participants were fitted with hearing aids using both nonoccluding and occluding dome ear tips. Participants were seated in a room with background noise present and speech was transmitted to the participants without additional noise. There was no effect of changing the noise level in the nontest ear and no difference between unilateral wireless routing and acoustic telephone listening. For wireless transmission, bilateral presentation resulted in significantly better speech recognition than unilateral presentation. Bilateral wireless conditions allowed for significantly better recognition than the acoustic telephone condition for participants fitted with occluding ear tips only. Routing the signal to both hearing aids resulted in significantly better speech recognition than unilateral signal routing. Wireless signal routing was shown to be beneficial compared with acoustic telephone listening and in some conditions resulted in the best performance of all of the listening conditions evaluated. However, this advantage was only evident when the signal was routed to both ears and when hearing aid wearers were fitted with occluding domes. Therefore, it is expected that the benefits of this new wireless streaming technology over existing telephone coupling methods will be most evident clinically in hearing aid wearers who require more limited venting than is typically used in open canal fittings.	t	\N
20812786	In contrast to visual object processing, relatively little is known about how the human brain processes everyday real-world sounds, transforming highly complex acoustic signals into representations of meaningful events or auditory objects. We recently reported a fourfold cortical dissociation for representing action (nonvocalization) sounds correctly categorized as having been produced by human, animal, mechanical, or environmental sources. However, it was unclear how consistent those network representations were across individuals, given potential differences between each participant's degree of familiarity with the studied sounds. Moreover, it was unclear what, if any, auditory perceptual attributes might further distinguish the four conceptual sound-source categories, potentially revealing what might drive the cortical network organization for representing acoustic knowledge. Here, we used functional magnetic resonance imaging to test participants before and after extensive listening experience with action sounds, and tested for cortices that might be sensitive to each of three different high-level perceptual attributes relating to how a listener associates or interacts with the sound source. These included the sound's perceived concreteness, effectuality (ability to be affected by the listener), and spatial scale. Despite some variation of networks for environmental sounds, our results verified the stability of a fourfold dissociation of category-specific networks for real-world action sounds both before and after familiarity training. Additionally, we identified cortical regions parametrically modulated by each of the three high-level perceptual sound attributes. We propose that these attributes contribute to the network-level encoding of category-specific acoustic knowledge representations.	t	\N
20844257	It is important to ensure that hearing aid fitting strategies for infants take into account the infant's developing speech perception system. As a way of exploring this issue, this study examined how 6- and 9-month-olds with normal hearing perceive native-language speech in which the natural spectral shape was altered to emphasize either high-frequency (positive spectral tilt) or low-frequency (negative spectral tilt) information. Discrimination was tested using a visual habituation procedure. Forty-eight 6-month-olds and forty-eight 9-month-olds were presented with a fricative contrast, /f/-/s/, in 1 of 3 conditions: (a) as unmodified speech; (b) with a -6 dB/octave tilt; or (c) with a +6 dB/octave tilt. Six-month-olds showed evidence of discriminating /f/-/s/ in all 3 conditions, but 9-month-olds showed such evidence only in the unmodified condition. The findings suggest that the perceptual reorganization that emerges for consonants at the end of the first year affects 9-month-olds' discrimination of native speech sounds. Perceptual reorganization is usually indexed by a decline in the ability to discriminate nonnative speech sounds. In this study, 6-month-olds demonstrated an acoustic-based sensitivity to both modified and unmodified native speech sounds, but 9-month-olds were most sensitive to the unmodified speech sounds that adhered to the native spectral profile.	t	\N
20864070	Auditory and visual processes demonstrably enhance each other based on spatial and temporal coincidence. Our recent results on visual search have shown that auditory signals also enhance visual salience of specific objects based on multimodal experience. For example, we tend to see an object (e.g., a cat) and simultaneously hear its characteristic sound (e.g., "meow"), to name an object when we see it, and to vocalize a word when we read it, but we do not tend to see a word (e.g., cat) and simultaneously hear the characteristic sound (e.g., "meow") of the named object. If auditory-visual enhancements occur based on this pattern of experiential associations, playing a characteristic sound (e.g., "meow") should facilitate visual search for the corresponding object (e.g., an image of a cat), hearing a name should facilitate visual search for both the corresponding object and corresponding word, but playing a characteristic sound should not facilitate visual search for the name of the corresponding object. Our present and prior results together confirmed these experiential association predictions. We also recently showed that the underlying object-based auditory-visual interactions occur rapidly (within 220ms) and guide initial saccades towards target objects. If object-based auditory-visual enhancements are automatic and persistent, an interesting application would be to use characteristic sounds to facilitate visual search when targets are rare, such as during baggage screening. Our participants searched for a gun among other objects when a gun was presented on only 10% of the trials. The search time was speeded when a gun sound was played on every trial (primarily on gun-absent trials); importantly, playing gun sounds facilitated both gun-present and gun-absent responses, suggesting that object-based auditory-visual enhancements persistently increase the detectability of guns rather than simply biasing gun-present responses. Thus, object-based auditory-visual interactions that derive from experiential associations rapidly and persistently increase visual salience of corresponding objects.	t	\N
20883507	The prior entry hypothesis of attention holds that attended stimuli are perceived earlier than unattended stimuli. Whereas this speeding of perceptual processing has been repeatedly demonstrated for spatial attention, it has not been reported within the temporal domain. To fill this gap, we tested whether temporal attention accelerates auditory perceptual processing by employing event-related potentials as on-line indicators of perceptual processing. In a modified oddball paradigm, we presented a single tone in each trial, either a frequent standard tone or an infrequent deviant or target tone. Temporal attention to tones was manipulated via constant foreperiods. We observed that the latency of the N2, an event-related potential reflecting perceptual processing, is shortened by temporal attention. This result provides first evidence for the idea that temporal attention accelerates perceptual processing as suggested by the prior entry hypothesis.	t	\N
20890206	Perception-in-noise deficits have been demonstrated across many populations and listening conditions. Many factors contribute to successful perception of auditory stimuli in noise, including neural encoding in the central auditory system. Physiological measures such as cortical auditory-evoked potentials (CAEPs) can provide a view of neural encoding at the level of the cortex that may inform our understanding of listeners' abilities to perceive signals in the presence of background noise. To understand signal-in-noise neural encoding better, we set out to determine the effect of signal type, noise type, and evoking paradigm on the P1-N1-P2 complex. Tones and speech stimuli were presented to nine individuals in quiet and in three background noise types: continuous speech spectrum noise, interrupted speech spectrum noise, and four-talker babble at a signal-to-noise ratio of -3 dB. In separate sessions, CAEPs were evoked by a passive homogenous paradigm (single repeating stimulus) and an active oddball paradigm. The results for the N1 component indicated significant effects of signal type, noise type, and evoking paradigm. Although components P1 and P2 also had significant main effects of these variables, only P2 demonstrated significant interactions among these variables. Signal type, noise type, and evoking paradigm all must be carefully considered when interpreting signal-in-noise evoked potentials. Furthermore, these data confirm the possible usefulness of CAEPs as an aid to understand perception-in-noise deficits.	t	\N
20932562	Functional neuroimaging studies of syntactic processing have been interpreted as identifying the neural locations of parsing and interpretive operations. However, current behavioral studies of sentence processing indicate that many operations occur simultaneously with parsing and interpretation. In this review, we point to issues that arise in discriminating the effects of these concurrent processes from those of the parser/interpreter in neural measures and to approaches that may help resolve them.	t	\N
20934172	This paper presents the results of three studies of intelligibility and quality of speech recorded through a bone conduction microphone (BCM). All speech signals were captured and recorded using a Temco HG-17 BCM. Twelve locations on or close to the skull were selected for the BCM placement. In the first study, listeners evaluated the intelligibility and quality of the bone conducted speech signals presented through traditional earphones. Listeners in the second study evaluated the intelligibility and quality of signals presented through a loudspeaker. In the third study the signals were reproduced through a bone conduction headset; however, signal evaluation was limited to speech intelligibility only. In all three studies, the Forehead and Temple BCM locations yielded the highest intelligibility and quality rating scores. The Collarbone location produced the least intelligible and lowest quality signals across all tested BCM locations.	t	\N
20950509	To assess the hearing changes associated with sacrificing an intact ossicular chain during cholesteatoma surgery. We reviewed the operation notes of surgical procedures performed by the senior author between October 2000 and April 2006. Thirty-three cases were identified in which cholesteatoma surgery had been performed in the presence of a mobile, intact ossicular chain. One set of case notes was missing; therefore, 32 cases were included in the analysis. The ossicular chain was preserved in 17 cases (14 males and three females) and sacrificed in 15 (eight males and seven females). At the first post-operative assessment, a median air-bone gap deterioration of 3.3 dB was seen in patients in whom the ossicular chain had been sacrificed, while a median air-bone gap improvement of 3.3 dB was seen in those in whom the chain had been preserved. However, multivariable logistic regression analysis suggested that this difference in hearing outcomes was due to pre-operative hearing status, and that preservation of the ossicular chain did not lead to a better outcome. In cholesteatoma surgery, there is at most a marginal benefit in preserving the ossicular chain. In the current study, the better hearing outcomes associated with preservation of the ossicular chain were accounted for by patients' better pre-operative hearing status. This study did not demonstrate a difference in residual disease rate, but was underpowered to do so.	t	\N
20961518	Researchers often conduct visual world studies to investigate how listeners integrate linguistic information with prior context. Such studies are likely to generate anticipatory baseline effects (ABEs), differences in listeners' expectations about what a speaker might mention that exist before a critical speech stimulus is presented. ABEs show that listeners have attended to and accessed prior contextual information in time to influence the processing of the critical speech stimulus. However, further evidence is required to show that the information actually did influence subsequent processing. ABEs can compromise the validity of inferences about information integration if they are not appropriately controlled. We discuss four solutions: statistical estimation, experimental control, elimination of "on-target" trials, and neutral gaze. An experiment compares the performance of these solutions, and suggests that the elimination of on-target trials introduces bias in the direction of ABEs, due to the statistical phenomenon of regression toward the mean. We conclude that statistical estimation, possibly coupled with experimental control, offers the most valid and least biased solution.	t	\N
21060141	To investigate the effects of increased syntactic complexity and utterance length demands on speech production and comprehension in individuals with Parkinson's disease (PD) using behavioral and physiological measures. Speech response latency, interarticulatory coordinative consistency, accuracy of speech production, and response latency and accuracy on a receptive language task were analyzed in 16 individuals with PD and 16 matched control participants. Individuals with PD had higher oral motor coordination variability, took a longer time to initiate speech, and made more errors on the speaking task compared with the control group. They also received lower scores on the 2 complex conditions of the receptive language task. Increased length and syntactic complexity negatively affected performance in both groups of speakers. These findings provide a novel window into the speech deficits associated with PD by examining performance on longer, sentence-level utterances in contrast to earlier investigations of single-word or nonword productions. Speech motor control processes and language comprehension were adversely affected in the majority of our participants with mild to moderate PD compared to the control group. Finally, increased syntactic complexity and sentence length affected both the healthy aging and PD groups' speech production performance at the behavioral and kinematic levels.	t	\N
21067852	Integration of simultaneous auditory and visual information about an event can enhance our ability to detect that event. This is particularly evident in the perception of speech, where the articulatory gestures of the speaker's lips and face can significantly improve the listener's detection and identification of the message, especially when that message is presented in a noisy background. Speech is a particularly important example of multisensory integration because of its behavioural relevance to humans and also because brain regions have been identified that appear to be specifically tuned for auditory speech and lip gestures. Previous research has suggested that speech stimuli may have an advantage over other types of auditory stimuli in terms of audio-visual integration. Here, we used a modified adaptive psychophysical staircase approach to compare the influence of congruent visual stimuli (brief movie clips) on the detection of noise-masked auditory speech and non-speech stimuli. We found that congruent visual stimuli significantly improved detection of an auditory stimulus relative to incongruent visual stimuli. This effect, however, was equally apparent for speech and non-speech stimuli. The findings suggest that speech stimuli are not specifically advantaged by audio-visual integration for detection at threshold when compared with other naturalistic sounds.	t	\N
21073461	Impaired cognitive control has been implicated as an important developmental pathway to attention deficit/hyperactivity disorder (ADHD). Cognitive control is crucial to suppress interference resulting from conflicting information and can be measured by Stroop-like tasks. This study was conducted to gain insight into conflict processing in children with ADHD. Event-related potentials (ERPs) were recorded in an auditory Stroop task. Twenty-four children with ADHD were compared with 24 control children (aged 8-12 years). No deficit in interference control was found on the auditory Stroop task in children with ADHD. Children with ADHD responded more slowly, less accurately and more variably compared to controls. No differences between the groups occurred in the early conflict-related ERPs. However, the difference between the congruent and the incongruent condition in the 450-550 ms time window was absent in the ADHD group compared to controls. In addition, the conflict sustained potential was found frontally in the ADHD group but parietally in the control group. These ERP findings suggest that children with ADHD evaluate conflict to a lesser extent and differ in the way their brains select appropriate responses during conflict compared with controls.	t	\N
21144500	Phonetic variation has been considered a barrier that listeners must overcome in speech perception, but has been proved beneficial in category learning. In this paper, I show that listeners use within-speaker variation to accommodate gross categorical variation. Within the perceptual learning paradigm, listeners are exposed to p-initial words in English produced by a native speaker of French. Critically, listeners are trained on these words with either invariant or highly-variable VOTs. While a gross boundary shift is made for participants exposed to the variable VOTs, no such shift is observed after exposure to the invariant stimuli. These data suggest that increasing variation improves the mapping of perceptually mismatched stimuli.	t	\N
21150681	To evaluate the results of late cochlear implantation in prelingually deaf patients with significant residual hearing loss and to evaluate patient factors relevant to postoperative auditory outcomes in this patient group. Analysis of results of cochlear implantation using postoperative speech perception test scores per each condition. Tertiary referral center. Thirty-two subjects with severe to profound hearing loss that developed before the age of 4. Subjects were implanted at a mean age of 24.8 years (range, 16-44) with Nucleus CI24 (n = 18, 56%), Clarion HiRes 90K (n = 11, 34%), and Medel PULSA (n = 3, 10%) device. Details of etiology, duration of deafness, hearing aid history, hearing thresholds before operation, communication mode, and educational environment were investigated. Speech perception tests were performed preoperatively and 12 months after the operation. Postoperative speech perception test scores between different options within patient group. : The results showed significant improvement in open set speech perception (sentence) scores after the implantation (mean scores from 7.0 to 46.7, p < 0.05). Preoperative hearing of better ear and preoperative speech perception scores correlated with postoperative performances (r = -0.70 and r = 0.46, respectively, p < 0.05). Education and communication mode were also closely related to postoperative performances. In the group with poorer performances, preoperative hearing thresholds were significantly worse than those with better performances, and a larger portion of those patients attended special schools and used sign language. We found that residual auditory capacity in the better ear is an important factor in predicting outcomes after cochlear implantation in patients with prelingual hearing loss.	t	\N
21161816	The present study focuses on language laterality as measured with dichotic listening (DL) to consonant-vowel syllables (CV syllables) in refugees with post-traumatic stress disorder (PTSD). PTSD is associated with impaired callosal transfer and with increased right hemisphere activation and impaired executive skills that could influence the processing of dichotic stimuli. A total of 22 participants with PTSD were compared to 23 participants without a diagnosis of PTSD. All participants had similar experiences of acts of war and political violence. They were tested with dichotic listening to CV syllables with free recall and directed attention following the forced attention paradigm. The PTSD group showed increased right ear advantage due to impaired left ear reporting and also smaller attention modulation compared to the control group, and the performance shared variance with self-report measures of arousal and intrusive memories. The results are discussed towards a model of impaired functionality of the frontal lobe and right hemisphere versus impaired callosal transfer, both yielding predictions for the processing of the left ear input and the ability to attention modulation of the performance.	t	\N
21167923	Psychoacoustic studies have shown that complex tones containing resolved harmonics evoke stronger pitches than complex tones with only unresolved harmonics. Also, unresolved harmonics presented in alternating sine and cosine (ALT) phase produce a doubling of pitch. We examine here whether the temporal pattern of phase-locked neural activity reflected in the scalp recorded human frequency following response (FFR) preserves information relevant to pitch strength, and to the doubling of pitch for ALT stimuli. Results revealed stronger neural periodicity strength for resolved stimuli, although the effect of resolvability was weak compared to the effect observed behaviorally; autocorrelation functions and FFR spectra suggest a different pattern of phase-locked neural activity for ALT stimuli with resolved and unresolved harmonics consistent with the doubling of pitch observed in our behavioral estimates; and the temporal pattern of neural activity underlying pitch encoding appears to be similar at the auditory nerve (auditory nerve model response) and the rostral brainstem level (FFR). These findings suggest that the phase-locked neural activity reflected in the scalp recorded FFR preserves neural information relevant to pitch that could serve as an electrophysiological correlate of the behavioral pitch measure. The scalp recorded FFR may provide for a non-invasive analytic tool to evaluate neural encoding of complex sounds in humans.	t	\N
21178803	To determine the response to treatment of pediatric patients diagnosed with autoimmune inner ear disease. Seven children who presented with sensorineural hearing loss and were diagnosed with autoimmune inner ear disease. Diagnosis through blood testing. Treatment with steroids and/or cytotoxic medication. Improvement in pure-tone average and speech discrimination scores on audiometric testing. Six of the 7 children (85.7%) improved with treatment, and the remaining patient had no measurable progression of disease. Children with autoimmune inner ear disease seem to benefit from treatment with steroids and/or cytotoxic medication. Although such medications must be used with caution in the pediatric population, they should not be withheld simply because of young age.	t	\N
21196054	Humans and other animals can attend to one of multiple sounds and follow it selectively over time. The neural underpinnings of this perceptual feat remain mysterious. Some studies have concluded that sounds are heard as separate streams when they activate well-separated populations of central auditory neurons, and that this process is largely pre-attentive. Here, we argue instead that stream formation depends primarily on temporal coherence between responses that encode various features of a sound source. Furthermore, we postulate that only when attention is directed towards a particular feature (e.g. pitch) do all other temporally coherent features of that source (e.g. timbre and location) become bound together as a stream that is segregated from the incoherent features of other sources.	t	\N
21198980	Important to Western tonal music is the relationship between pitches both within and between musical chords; melody and harmony are generated by combining pitches selected from the fixed hierarchical scales of music. It is of critical importance that musicians have the ability to detect and discriminate minute deviations in pitch in order to remain in tune with other members of their ensemble. Event-related potentials indicate that cortical mechanisms responsible for detecting mistuning and violations in pitch are more sensitive and accurate in musicians as compared with non-musicians. The aim of the present study was to address whether this superiority is also present at a subcortical stage of pitch processing. Brainstem frequency-following responses were recorded from musicians and non-musicians in response to tuned (i.e. major and minor) and detuned (± 4% difference in frequency) chordal arpeggios differing only in the pitch of their third. Results showed that musicians had faster neural synchronization and stronger brainstem encoding for defining characteristics of musical sequences regardless of whether they were in or out of tune. In contrast, non-musicians had relatively strong representation for major/minor chords but showed diminished responses for detuned chords. The close correspondence between the magnitude of brainstem responses and performance on two behavioral pitch discrimination tasks supports the idea that musicians' enhanced detection of chordal mistuning may be rooted at pre-attentive, sensory stages of processing. Findings suggest that perceptually salient aspects of musical pitch are not only represented at subcortical levels but that these representations are also enhanced by musical experience.	t	\N
21211833	Metaphonological tasks, such as rhyme judgment, have been the primary tool for the investigation of the effects of orthographic knowledge on spoken language. However, it has been recently argued that the orthography effect in rhyme judgment does not reflect the automatic activation of orthographic codes but rather stems from sophisticated response strategies. Such a claim stands in sharp contrast with recent findings using event-related brain potentials (ERPs) in lexical and semantic tasks, which were taken to suggest that orthographic information occurs early enough to affect the core process of lexical access. Here, we show that the electrophysiological signature of the orthography effect in rhyme judgment is indeed different from the one obtained in online lexical or semantic tasks. That is, we did not find the orthography effect in the 300-350 ms time window which has previously been shown to process lexical information in the lexico-semantic tasks, but the effect appeared within the 175-250 ms and the 375-750 ms time-windows which we interpreted to reflect segmentation and decisional process, respectively. We conclude that the interactions between phonology and orthography are task-specific. Metaphonological tasks appear of limited use for studying the core processes and interactions that underlie lexical access.	t	\N
21216396	We show that comprehenders' expectations about upcoming discourse coherence relations influence the resolution of local structural ambiguity. We employ cases in which two clauses share both a syntactic relationship and a discourse relationship, and hence in which syntactic and discourse processing might be expected to interact. An off-line sentence-completion study and an on-line self-paced reading study examined readers' expectations for high/low relative-clause attachments following implicit-causality and non-implicit causality verbs (John detests/babysits the children of the musician who…). In the off-line study, the widely reported low-attachment preference for English is observed in the non-implicit causality condition, but this preference gives way to more high attachments in the implicit-causality condition in cases in which (i) the verb's causally implicated referent occupies the high-attachment position and (ii) the relative clause provides an explanation for the event described by the matrix clause (e.g., …who are arrogant and rude). In the on-line study, a similar preference for high attachment emerges in the implicit-causality context-crucially, before the occurrence of any linguistic evidence that the RC does in fact provide an explanation-whereas the low-attachment preference is consistent elsewhere. These findings constitute the first demonstration that expectations about ensuing discourse coherence relationships can elicit full reversals in syntactic attachment preferences, and that these discourse-level expectations can affect on-line disambiguation as rapidly as lexical and morphosyntactic cues.	t	\N
21236276	Categorical perception (CP) is a mechanism whereby non-identical stimuli that have the same underlying meaning become invariantly represented in the brain. Through behavioral identification and discrimination tasks, CP has been demonstrated to occur broadly across the auditory modality, including in perception of speech (e.g. phonemes) and music (e.g. chords) stimuli. Several functional imaging studies have linked CP of speech with activity in multiple regions of the left superior temporal sulcus (STS). As language processing is generally left-hemisphere dominant and, conversely, fine-grained spectral processing shows a right hemispheric bias, we hypothesized that CP of musical stimuli would be associated with right STS activity. Here, we used functional magnetic resonance imaging (fMRI) to test healthy, musically-trained volunteers as they (a) underwent a musical chord adaptation/habituation paradigm and (b) performed an active discrimination task on within- and between-category chord pairs, as well as an acoustically-matched, more continuously-perceived orthogonal sound set. As predicted, greater right STS activity was linked to categorical processing in both experimental paradigms. The results suggest that the left and right STS are functionally specialized and that the right STS may take on a key role in CP of spectrally complex sounds.	t	\N
21236499	To evaluate the audiological outcome of children with congenital cytomegalovirus infection. In a prospective study, the hearing of ninety seven congenitally cytomegalovirus-infected children, born between January 2003 and July 2009, was systematically evaluated until the age of six, applying the Flemish CMV protocol. Depending on the age of the child, the protocol provides hearing evaluation by objective-, play- or conventional audiometry. Symptomatic children with hearing loss at birth were treated with ganciclovir, if parents consented. Seventy children had a pass on initial screening, 27 had unilateral or bilateral hearing loss. Within the normal hearing group, one asymptomatic and two symptomatic children developed late-onset hearing loss. Within the group with hearing loss, 8 children received ganciclovir, while 8 symptomatic and 11 asymptomatic children did not receive ganciclovir. As for the treated group, 37.5% of the children had stable hearing loss, one child had progressive and one child had fluctuating hearing loss. Improvement of hearing threshold occurred in 37.5% of the children. Among the untreated symptomatic children, hearing loss remained stable in 50%, while progression occurred in 37.5%. In the group of asymptomatic children with hearing loss, hearing loss was most commonly stable (72.7%). Within the group of normal hearing ears at birth (n=156), there is a significant better progression in pure tone average for ears of asymptomatic subjects in comparison to ears of symptomatic subjects (p≤0.0001). As for the group of ears with hearing loss at birth (n=38), analysis shows no evidence for a difference in pure tone average progression between the different groups (p=0.38). Cytomegalovirus infection may cause hearing loss, in both symptomatic and asymptomatic children. Our data show a significant difference, between both groups, in the progression of pure tone average of normal hearing ears at birth, in favor of the asymptomatic children. This is not the case for ears with hearing loss at birth. However, this may be due to the small number of ears in this group. Our data show the tendency that treatment with ganciclovir increases the likelihood of improvement and reduces the likelihood of deterioration of the hearing.	t	\N
21241284	Several studies have found that women tend to demonstrate stronger preferences for masculine men as short-term partners than as long-term partners, though there is considerable variation among women in the magnitude of this effect. One possible source of this variation is individual differences in the extent to which women perceive masculine men to possess antisocial traits that are less costly in short-term relationships than in long-term relationships. Consistent with this proposal, here we show that the extent to which women report stronger preferences for men with low (i.e., masculine) voice pitch as short-term partners than as long-term partners is associated with the extent to which they attribute physical dominance and low trustworthiness to these masculine voices. Thus, our findings suggest that variation in the extent to which women attribute negative personality characteristics to masculine men predicts individual differences in the magnitude of the effect of relationship context on women's masculinity preferences, highlighting the importance of perceived personality attributions for individual differences in women's judgments of men's vocal attractiveness and, potentially, their mate preferences.	t	\N
21251921	Recent neuroimaging studies proposed the importance of the anterior auditory pathway for speech comprehension. Its clinical significance is implicated by semantic dementia or pure word deafness. Neurodegenerative or cerebrovascular nature, however, precluded precise localization of the cortex responsible for speech perception. Electrical cortical stimulation could delineate such localization by producing transient, functional impairment. We investigated engagement of the left anterior temporal cortex in speech perception by means of direct electrical cortical stimulation. Subjects were two partial epilepsy patients, who underwent direct cortical stimulation as a part of invasive presurgical evaluations. Stimulus sites were coregistered to presurgical 3D-MRI, and then to MNI standard space for anatomical localization. Separate from the posterior temporal language area, electrical cortical stimulation revealed a well-restricted language area in the anterior part of the superior temporal sulcus and gyrus (aSTS/STG) in both patients. Auditory sentence comprehension was impaired upon electrical stimulation of aSTS/STG. In one patient, additional investigation revealed that the functional impairment was restricted to auditory sentence comprehension with preserved visual sentence comprehension and perception of music and environmental sounds. Both patients reported that they could hear the voice but not understand the sentence well (e.g., heard as a series of meaningless utterance). The standard coordinates of this restricted area at left aSTS/STG well corresponded with the coordinates of speech perception reported in neuroimaging activation studies in healthy subjects. The present combined anatomo-functional case study, for the first time, demonstrated that aSTS/STG in the language dominant hemisphere actively engages in speech perception.	t	\N
21255123	To advance our understanding of the biological basis of speech-in-noise perception, we investigated the effects of background noise on both subcortical- and cortical-evoked responses, and the relationships between them, in normal hearing young adults. The addition of background noise modulated subcortical and cortical response morphology. In noise, subcortical responses were later, smaller in amplitude and demonstrated decreased neural precision in encoding the speech sound. Cortical responses were also delayed by noise, yet the amplitudes of the major peaks (N1, P2) were affected differently, with N1 increasing and P2 decreasing. Relationships between neural measures and speech-in-noise ability were identified, with earlier subcortical responses, higher subcortical response fidelity and greater cortical N1 response magnitude all relating to better speech-in-noise perception. Furthermore, it was only with the addition of background noise that relationships between subcortical and cortical encoding of speech and the behavioral measures of speech in noise emerged. Results illustrate that human brainstem responses and N1 cortical response amplitude reflect coordinated processes with regards to the perception of speech in noise, thereby acting as a functional index of speech-in-noise perception.	t	\N
21261450	Many models of spoken word recognition posit that the acoustic stream is parsed into phoneme level units, which in turn activate larger representations [McClelland, J. L., & Elman, J. L. The TRACE model of speech perception. Cognitive Psychology, 18, 1-86, 1986], whereas others suggest that larger units of analysis are activated without the need for segmental mediation [Greenberg, S. A multitier theoretical framework for understanding spoken language. In S. Greenberg & W. A. Ainsworth (Eds.), Listening to speech: An auditory perspective (pp. 411-433). Mahwah, NJ: Erlbaum, 2005; Klatt, D. H. Speech perception: A model of acoustic-phonetic analysis and lexical access. Journal of Phonetics, 7, 279-312, 1979; Massaro, D. W. Preperceptual images, processing time, and perceptual units in auditory perception. Psychological Review, 79, 124-145, 1972]. Identifying segmental effects in the brain's response to speech may speak to this question. For example, if such effects were localized to relatively early processing stages in auditory cortex, this would support a model of speech recognition in which segmental units are explicitly parsed out. In contrast, segmental processes that occur outside auditory cortex may indicate that alternative models should be considered. The current fMRI experiment manipulated the phonotactic frequency (PF) of words that were auditorily presented in short lists while participants performed a pseudoword detection task. PF is thought to modulate networks in which phoneme level units are represented. The present experiment identified activity in the left inferior frontal gyrus that was positively correlated with PF. No effects of PF were found in temporal lobe regions. We propose that the observed phonotactic effects during speech listening reflect the strength of the association between acoustic speech patterns and articulatory speech codes involving phoneme level units. On the basis of existing lesion evidence, we interpret the function of this auditory-motor association as playing a role primarily in production. These findings are consistent with the view that phoneme level units are not necessarily accessed during speech recognition.	t	\N
21261634	Tones that are self-generated elicit a smaller N1 than externally triggered tones. Typically, however, self-generated tones are also more predictable in time than externally triggered ones. The present study investigated whether the attenuated N1 can be explained by predictability based on the temporal relationship between action and effect. Participants listened to tones that were self-generated by a key-press or preceded by a visual cue. The tones followed the key-presses or cues after a fixed (predictable context) or variable delay (unpredictable context). Tones triggered by a key-press elicited a smaller N1 than tones following a visual cue. This finding suggests that the reduced N1 to self-generated tones is not merely due to the fact that the tone's timing can be predicted based on its temporal relationship to the key-press. Whether a tone was presented in a predictable or an unpredictable context did not affect the N1.	t	\N
21264707	When two targets are presented in rapid succession at the same spatial location, processing of the first is highly efficient, while processing of the second is often profoundly impaired at brief inter-target intervals (attentional blink; AB). While the AB has been shown to impact many processes, it is still unclear whether this includes the ability to shift spatial attention. The present study examined this question using a more sensitive dependent measure than past studies; namely, response times. It also evaluated whether masking of the cue stimulus modulated the effect of the AB on spatial shifts. The results showed significant cueing effects on T2 response times that were strongly modulated by the AB. This supports suggested links between mechanisms underlying object processing and spatial shifts of attention.	t	\N
21264734	The fast and accurate enumeration of a small set of objects, called subitizing, is thought to involve a different mechanism from other numerosity judgments, such as those based on estimation. In this report, we examine the subitizing limit using a novel enumeration task that obtained the perceived locations of enumerated objects. Observers were shown brief masked displays (50, 200, and 350 ms) of 2-9 small black discs randomly placed on a gray screen and then asked to place a marker where each disc had been located. The number of these markers provided an estimate of the number of items processed. This "pointing" methodology enabled observers to accurately "enumerate" displays containing up to six items in contrast with the four-item limit typically found when using standard reporting methods (and replicated here in Experiment 2). These results suggest a different account of the limits found in most subitizing and enumeration studies.	t	\N
21272630	The auditory system can encode interaural delays in highpass-filtered complex sounds by phase locking to their slowly modulating envelopes. Spectrotemporal analysis of interaurally time-delayed highpass waveforms reveals the presence of a concomitant interaural level cue. The current study systematically investigated the contribution of time and concomitant level cues carried by positive and negative envelope slopes of a modified sinusoidally amplitude-modulated (SAM) high-frequency carrier. The waveforms were generated from concatenation of individual modulation cycles whose envelope peaks were extended by the desired interaural delay, allowing independent control of delays in the positive and negative modulation slopes. In experiment 1, thresholds were measured using a 2-interval forced-choice adaptive task for interaural delays in either the positive or negative modulation slopes. In a control condition, thresholds were measured for a standard SAM tone. In experiment 2, decision weights were estimated using a multiple-observation correlational method in a single-interval forced-choice task for interaural delays carried simultaneously by the positive, and independently, negative slopes of the modulation envelope. In experiment 3, decision weights were measured for groups of 3 modulation cycles at the start, middle, and end of the waveform to determine the influence of onset dominance or recency effects. Results were consistent across experiments: thresholds were equal for the positive and negative modulation slopes. Decision weights were positive and equal for the time cue in the positive and negative envelope slopes. Weights were also larger for modulations cycles near the waveform onset. Weights estimated for the concomitant interaural level cue were positive for the positive envelope slope and negative for the negative slope, consistent with exclusive use of time cues.	t	\N
21272930	Using event-related potentials (ERPs), we investigated the N400 (an ERP component that occurs in response to meaningful stimuli) in children aged 8-10 years old and examined relationships between the N400 and individual differences in listening comprehension, word recognition and non-word decoding. Moreover, we tested the claim that the N400 effect provides a valuable indicator of behavioural vocabulary knowledge. Eighteen children were presented with picture-word pairs that were either 'congruent' (the picture depicted the spoken word) or 'incongruent' (they were unrelated). Three peaks were observed in the ERP waveform triggered to the onset of the picture-word stimuli: an N100 in fronto-central channels, an N200 in central-parietal channels and an N400 in frontal, central and parietal channels. In contrast to the N100 peak, the N200 and N400 peaks were sensitive to semantic incongruency with greater peak amplitudes for incongruent than congruent conditions. The incongruency effects for each peak correlated positively with listening comprehension but when the peak amplitudes were averaged across congruent/incongruent conditions they correlated positively with non-word decoding. These findings provide neurophysiological support for the position that sensitivity to semantic context (reflected in the N400 effect) is crucial for comprehension whereas phonological decoding skill relates to more general processing differences reflected in the ERP waveform. There were no correlations between ERP and behavioural measures of expressive or receptive vocabulary knowledge for the same items, suggesting that the N400 effect may not be a reliable estimate of vocabulary knowledge in children aged 8-10 years.	t	\N
21275499	Hearing-aid users' problems with their own voice caused by occlusion are well known. Conversely, it remains essentially undocumented whether hearing-aid users expected not to have occlusion-related problems experience own-voice issues. To investigate this topic, a dedicated Own Voice Qualities (OVQ) questionnaire was developed and used in two experiments with stratified samples. In the main experiment, the OVQ was administered to 169 hearing-aid users (most of whom were expected not to have occlusion-related problems) and to a control group of 56 normally-hearing people. In the follow-up experiment, the OVQ was used in a cross-over study where 43 hearing-aid users rated own voice for an open fitting and a small-vent earmould fitting. The results from the main experiment show that hearing-aid users (without occlusion) have more problems than the normal-hearing controls on several dimensions of own voice. The magnitude of these differences was found to be generally larger than the differences observed between the open fitting and the small-vent fitting in the follow-up experiment. This suggests that own voice is a potentially important concern, even for hearing-aid users who are not expected to have occlusion-related problems.	t	\N
21295773	Does extensive practice reduce or eliminate central interference in dual-task processing? We explored the reorganization of task architecture with practice by combining interference analysis (delays in dual-task experiment) and random-walk models of decision making (measuring the decision and non-decision contributions to RT). The main delay observed in the Psychologically Refractory Period at short stimulus onset asynchronies (SOA) values was largely unaffected by training. However, the range of SOAs over which this interference regime held diminished with learning. This was consistent with an overall shift observed in single-task performance from a highly variable decision time to a reliable (non-decision time) contribution to response time. Executive components involved in coordinating dual-task performance decreased (and became more stable) after extensive practice. The results suggest that extensive practice reduces the duration of central decision stages, but that the qualitative property of central seriality remains a structural invariant.	t	\N
21299376	To implement a fast method for measuring psychophysical tuning curves (PTCs) for use in clinical applications, such as assessment of frequency selectivity and detection of dead regions in the cochlea. The method is based on that described by Sek et al (2005) and has been implemented in software that can be run on a PC with a good-quality sound card. In addition to the main narrowband noise masker, a lowpass noise masker can be generated to prevent detection of a distortion band corresponding to the simple difference tone. The software includes a routine for measuring the absolute threshold at the signal frequency and includes methods for estimating the frequency at the tip of the PTC. A PTC can typically be determined in about three minutes. A small amount of practice (two to three runs) may be required to achieve stable results. The software implementation allows PTCs to be measured quickly without a requirement for specialised equipment.	t	\N
21305548	To investigate the level of hearing loss and the configuration of the mean audiometric curve over the course of Menière's disease, correcting the data according to patient age. A retrospective study of 3,963 hearing tests. Descriptive, longitudinal study of pure-tone audiometries of 237 patients at a tertiary hospital who had been diagnosed with definitive Menière's disease according to the American Academy of Otorhinolaryngology criteria. All audiometric results were age-corrected, and patients were followed for 1 to 31 years. In patients who had undergone surgery, only the data collected before the operation were assessed. In patients with unilateral disease, the mean hearing loss was characteristically low frequency, even in very advanced stages of the disease. Hearing loss was accentuated at 5 and 15 years from onset. In bilateral cases, hearing loss was slightly more severe and the average loss produced a flatter audiometric curve than in unilateral cases. In Menière's disease, audiometry results corrected for patient age show an inherent upward-sloping configuration of the mean audiometric curve at all time points during the disease. The hearing pattern differs between unilateral and bilateral disease. The audiometric curve configuration may be an indicator of future bilateral disease.	t	\N
21305666	Both sighted and blind individuals can readily interpret meaning behind everyday real-world sounds. In sighted listeners, we previously reported that regions along the bilateral posterior superior temporal sulci (pSTS) and middle temporal gyri (pMTG) are preferentially activated when presented with recognizable action sounds. These regions have generally been hypothesized to represent primary loci for complex motion processing, including visual biological motion processing and audio-visual integration. However, it remained unclear whether, or to what degree, life-long visual experience might impact functions related to hearing perception or memory of sound-source actions. Using functional magnetic resonance imaging (fMRI), we compared brain regions activated in congenitally blind versus sighted listeners in response to hearing a wide range of recognizable human-produced action sounds (excluding vocalizations) versus unrecognized, backward-played versions of those sounds. Here, we show that recognized human action sounds commonly evoked activity in both groups along most of the left pSTS/pMTG complex, though with relatively greater activity in the right pSTS/pMTG by the blind group. These results indicate that portions of the postero-lateral temporal cortices contain domain-specific hubs for biological and/or complex motion processing independent of sensory-modality experience. Contrasting the two groups, the sighted listeners preferentially activated bilateral parietal plus medial and lateral frontal networks, whereas the blind listeners preferentially activated left anterior insula plus bilateral anterior calcarine and medial occipital regions, including what would otherwise have been visual-related cortex. These global-level network differences suggest that blind and sighted listeners may preferentially use different memory retrieval strategies when hearing and attempting to recognize action sounds.	t	\N
21309643	To measure the mental health status of deaf adolescents with cochlear implants (CI). STUDY SAMPLE AND DESIGN: We used the "Strengths and Difficulties Questionnaire" (SDQ) to assess the mental health problems of 32 adolescents with CI (mean age 15.0 years) and 212 normal hearing peers (mean age 15.0 years). Parent and teacher ratings for the CI subjects (ES emotional symptoms, HA inattention-hyperactivity, CP conduct-problems and PBS pro-social behavior) did not differ significantly from the results of normal hearing peers. However, teachers rated significantly more cases as having peer problems (PP) and more cases as having very high (clinical) total difficulty scores (TDS) in the CI group. The SDQ results of the CI users correlated significantly with poor results in auditory performance and special school education. The age at CI implantation was not found to be a correlated with emotional, behavioral and social problems. Our findings indicate that the mental health of deaf adolescents with CI is comparable to that of normal hearing peers.	t	\N
21315158	Music perception generally involves processing the frequency relationships between successive pitches and extraction of the melodic contour. Previous evidence has suggested that the 'ups' and 'downs' of melodic contour are categorically and automatically processed, but knowledge of the brain regions that discriminate different types of contour is limited. Here, we examined melodic contour discrimination using multivariate pattern analysis (MVPA) of fMRI data. Twelve non-musicians were presented with various ascending and descending melodic sequences while being scanned. Whole-brain MVPA was used to identify regions in which the local pattern of activity accurately discriminated between contour categories. We identified three distinct cortical loci: the right superior temporal sulcus (rSTS), the left inferior parietal lobule (lIPL), and the anterior cingulate cortex (ACC). These results complement previous findings of melodic processing within the rSTS, and extend our understanding of the way in which abstract auditory sequences are categorized by the human brain.	t	\N
21316354	This study examined the electrophysiological correlates of auditory and visual working memory in children with Specific Language Impairments (SLI). Children with SLI and age-matched controls (11;9-14;10) completed visual and auditory working memory tasks while event-related potentials (ERPs) were recorded. In the auditory condition, children with SLI performed similarly to controls when the memory load was kept low (1-back memory load). As expected, when demands for auditory working memory were higher, children with SLI showed decreases in accuracy and attenuated P3b responses. However, children with SLI also evinced difficulties in the visual working memory tasks. In both the low (1-back) and high (2-back) memory load conditions, P3b amplitude was significantly lower for the SLI as compared to CA groups. These data suggest a domain-general working memory deficit in SLI that is manifested across auditory and visual modalities.	t	\N
21325685	Our auditory system separates and tracks temporally interleaved sound sources by organizing them into distinct auditory streams. This streaming phenomenon is partly determined by physical stimulus properties but additionally depends on the internal state of the listener. As a consequence, streaming perception is often bistable and reversals between one- and two-stream percepts may occur spontaneously or be induced by a change of the stimulus. Here, we used functional MRI to investigate perceptual reversals in streaming based on interaural time differences (ITD) that produce a lateralized stimulus perception. Listeners were continuously presented with two interleaved streams, which slowly moved apart and together again. This paradigm produced longer intervals between reversals than stationary bistable stimuli but preserved temporal independence between perceptual reversals and physical stimulus transitions. Results showed prominent transient activity synchronized with the perceptual reversals in and around the auditory cortex. Sustained activity in the auditory cortex was observed during intervals where the ΔITD could potentially produce streaming, similar to previous studies. A localizer-based analysis additionally revealed transient activity time locked to perceptual reversals in the inferior colliculus. These data suggest that neural activity associated with streaming reversals is not limited to the thalamo-cortical system but involves early binaural processing in the auditory midbrain, already.	t	\N
21327367	Identification of the second of two targets (T1, T2, inserted in a stream of distractors) is impaired when presented within 500 ms after the first (attentional blink, AB). Barring a T1-T2 task-switch, it is thought that T2 must be backward-masked to obtain an AB (Giesbrecht & Di Lollo, Journal of Experimental Psychology: Human Perception and Performance, 24, 1454-1466, 1998). We tested the hypothesis that Giesbrecht & Di Lollo's findings were vitiated by ceiling constraints arising from either response scale (experiment 1) or data limitations (experiment 2). In experiment 1, digit-distractors were replaced with pseudoletters to increase task difficulty, bringing performance below ceiling. An AB occurred without backward masking of T2. In experiment 2, a ceiling-free procedure estimated the number of noise dots needed for 80% T2 identification. An AB was revealed: fewer noise dots were required during the AB period than outside it. Both outcomes confirm that an AB can be obtained without either masking of T2 or task switching.	t	\N
21335029	Brain-computer interface (BCI) is a developing, novel mode of communication for individuals with severe motor impairments or those who have no other options for communication aside from their brain signals. However, the majority of current BCI systems are based on visual stimuli or visual feedback, which may not be applicable for severe locked-in patients that have lost their eyesight or the ability to control their eye movements. In the present study, we investigated the feasibility of using auditory steady-state responses (ASSRs), elicited by selective attention to a specific sound source, as an electroencephalography (EEG)-based BCI paradigm. In our experiment, two pure tone burst trains with different beat frequencies (37 and 43 Hz) were generated simultaneously from two speakers located at different positions (left and right). Six participants were instructed to close their eyes and concentrate their attention on either auditory stimulus according to the instructions provided randomly through the speakers during the inter-stimulus interval. EEG signals were recorded at multiple electrodes mounted over the temporal, occipital, and parietal cortices. We then extracted feature vectors by combining spectral power densities evaluated at the two beat frequencies. Our experimental results showed high classification accuracies (64.67%, 30 commands/min, information transfer rate (ITR) = 1.89 bits/min; 74.00%, 12 commands/min, ITR = 2.08 bits/min; 82.00%, 6 commands/min, ITR = 1.92 bits/min; 84.33%, 3 commands/min, ITR = 1.12 bits/min; without any artifact rejection, inter-trial interval = 6s), enough to be used for a binary decision. Based on the suggested paradigm, we implemented a first online ASSR-based BCI system that demonstrated the possibility of materializing a totally vision-free BCI system.	t	\N
21342695	The purpose of this exploratory study was to assess perceptions of quality of life for individuals with hearing impairment who have not consulted for services and their significant others who are in same-sex relationships vs. those who are in different-sex relationships. Data were collected on a total of 20 older couples: 10 in same-sex relationships and 10 in different-sex relationships. In each of the couples, one member self-identified as having hearing impairment. The couples completed an audiologic evaluation, a disease-specific quality of life questionnaire, and a short, structured interview (which served as a general measure of quality of life). No differences between the groups were found on demographic or audiologic variables. Differences between the groups and within the couples were found on the disease-specific and overall quality of life measures. Participants with hearing impairment in different-sex relationships reported significantly more total consequences of hearing impairment than those in the same-sex relationships. Differences were found in the rate of reporting for various contributors to overall quality of life and consequences of hearing impairment on quality of life. There was more congruity between same-sex couples than different-sex couples. There appear to be important differences in perceptions of both disease-specific and overall quality of life based on sexual orientation for older couples who have not consulted for hearing services. These differences can help inform clinical practice with this under-researched population. Readers will be able to: (1) Describe quality of life variables for individuals with hearing problems in same- and different-sex relationships, (2) understand the differences in quality of life variables between same- and different-sex couples, (3) consider the clinical implications of these quality of life variables.	t	\N
21358012	The aim of the current study is to investigate hearing function in patients with allergic rhinitis. Fifty-eight patients with positive skin prick test (Group 1) (116 ears) and 31 subjects with negative skin prick test (62 ears) as group 2 were included. Pure tone audiometry at 250, 500, 1000, 2000, 4000 and 8000 Hz and immittance measures, including tympanometry and acoustic reflex tests, were performed in both groups. There was statistically significant difference between pure-tone threshold of the group 1 and group 2 at 8000 Hz (p< 0.05). Based on our study, the patients with allergic rhinitis had better hearing than the control group at 8000 Hz.	t	\N
21361412	Perturbation analysis was used to determine the relative contribution of target enhancement and noise cancellation in the identification of rudimentary sound source in noise. In a two-interval, forced-choice procedure, listeners identified the impact sound produced by the larger of two stretched membranes as target. The noise on each presentation was the impact sound of a variable-sized plate. For four of five listeners, the relative weights on the noise were positive indicating enhancement, and for the remaining listeners, they were negative indicating cancellation. The results underscore the difficulty with evaluating models of masking solely in terms of measures of performance accuracy.	t	\N
21361445	Low-frequency masking by intense high-frequency noise bands, referred to as remote masking (RM), was the first evidence to challenge energy-detection models of signal detection. Its underlying mechanisms remain unknown. RM was measured in five normal-hearing young-adults at 250, 350, 500, and 700 Hz using equal-power, spectrally matched random-phase noise (RPN) and low-noise noise (LNN) narrowband maskers. RM was also measured using equal-power, two-tone complex (TC2) and eight-tone complex (TC8). Maskers were centered at 3000 Hz with one or two equivalent rectangular bandwidths (ERBs). Masker levels varied from 80 to 95 dB sound pressure level in 5 dB steps. LNN produced negligible masking for all conditions. An increase in bandwidth in RPN yielded greater masking over a wider frequency region. Masking for TC2 was limited to 350 and 700 Hz for one ERB but shifted to only 700 Hz for two ERBs. A spread of masking to 500 and 700 Hz was observed for TC8 when the bandwidth was increased from one to two ERBs. Results suggest that high-frequency noise bands at high levels could generate significant low-frequency masking. It is possible that listeners experience significant RM due to the amplification of various competing noises that might have significant implications for speech perception in noise.	t	\N
21361446	The additivity of nonsimultaneous masking was studied using Gaussian-shaped tone pulses (referred to as Gaussians) as masker and target stimuli. Combinations of up to four temporally separated Gaussian maskers with an equivalent rectangular bandwidth of 600 Hz and an equivalent rectangular duration of 1.7 ms were tested. Each masker was level-adjusted to produce approximately 8 dB of masking. Excess masking (exceeding linear additivity) was generally stronger than reported in the literature for longer maskers and comparable target levels. A model incorporating a compressive input/output function, followed by a linear summation stage, underestimated excess masking when using an input/output function derived from literature data for longer maskers and comparable target levels. The data could be predicted with a more compressive input/output function. Stronger compression may be explained by assuming that the Gaussian stimuli were too short to evoke the medial olivocochlear reflex (MOCR), whereas for longer maskers tested previously the MOCR caused reduced compression. Overall, the interpretation of the data suggests strong basilar membrane compression for very short stimuli.	t	\N
21368435	A human factors experiment employed a hemi-anechoic sound field in which listeners were required to localize a vehicular backup alarm warning signal (both a standard and a frequency-augmented alarm) in 360-degrees azimuth in pink noise of 60 dBA and 90 dBA. Measures of localization performance included: (1) percentage correct localization, (2) percentage of right--left localization errors, (3) percentage of front-rear localization errors, and (4) localization absolute deviation in degrees from the alarm's actual location. In summary, the data demonstrated that, with some exceptions, normal hearing listeners' ability to localize the backup alarm in 360-degrees azimuth did not improve when wearing augmented hearing protectors (including dichotic sound transmission earmuffs, flat attenuation earplugs, and level-dependent earplugs) as compared to when wearing conventional passive earmuffs or earplugs of the foam or flanged types. Exceptions were that in the 90 dBA pink noise, the flat attenuation earplug yielded significantly better accuracy than the polyurethane foam earplug and both the dichotic and the custom-made diotic electronic sound transmission earmuffs. However, the flat attenuation earplug showed no benefit over the standard pre-molded earplug, the arc earplug, and the passive earmuff. Confusions of front-rear alarm directions were most significant in the 90 dBA noise condition, wherein two types of triple-flanged earplugs exhibited significantly fewer front-rear confusions than either of the electronic muffs. On all measures, the diotic sound transmission earmuff resulted in the poorest localization of any of the protectors due to the fact that its single-microphone design did not enable interaural cues to be heard. Localization was consistently more degraded in the 90 dBA pink noise as compared with the relatively quiet condition of the 60 dBA pink noise. A frequency-augmented backup alarm, which incorporated 400 Hz and 4000 Hz components to exploit the benefits of interaural phase and intensity cues respectively, slightly but significantly improved localization compared with the standard, more narrow-bandwidth backup alarm, and these results have implications for the updating of backup alarm standards.	t	\N
21368442	Numerous studies have shown that the reliability of using laboratory measurements to predict individual or even group hearing protector attenuation for occupationally exposed workers is quite poor. This makes it difficult to properly assign hearing protectors when one wishes to closely match attenuation to actual exposure. An alternative is the use of field-measurement methods, a number of which have been proposed and are beginning to be implemented. We examine one of those methods, namely the field microphone-in-real-ear (F-MIRE) approach in which a dual-element microphone probe is used to measure noise reduction by quickly sampling the difference in noise levels outside and under an earplug, with appropriate adjustments to predict real-ear attenuation at threshold (REAT). We report on experiments that validate the ability of one commercially available F-MIRE device to predict the REAT of an earplug fitted identically for two tests. Results are reported on a representative roll-down foam earplug, stemmed-style pod plug, and pre-molded earplug, demonstrating that the 95% confidence level of the Personal Attenuation Rating (PAR) as a function of the number of fits varies from ± 4.4 dB to ± 6.3 dB, depending on the plug type, which can be reduced to ± 3.1 dB to ± 4.5 dB with a single repeat measurement. The added measurement improves precision substantially. However, the largest portion of the error is due to the user's fitting variability and not the uncertainty of the measurement system. Further we evaluated the inherent uncertainty of F-MIRE vs. the putative "gold standard" REAT procedures finding, that F-MIRE measurement uncertainty is less than one-half that of REAT at most test frequencies. An American National Standards Institute (ANSI) working group (S12/WG11) is currently involved in developing methods similar to those in this paper so that procedures for evaluating and reporting uncertainty on all types of field attenuation measurement systems can be standardized. We conclude that the hearing conservationist now has available a portable, convenient, quick, and easy-to-use system that can improve training and motivation of employees, assign hearing protection devices based on noise exposures, and address other management and compliance issues.	t	\N
21380585	With a new metric called phonological Levenshtein distance (PLD20), the present study explores the effects of phonological similarity and word frequency on spoken word recognition, using polysyllabic words that have neither phonological nor orthographic neighbors, as defined by neighborhood density (the N-metric). Inhibitory effects of PLD20 were observed for these lexical hermits: Close-PLD20 words were recognized more slowly than distant PLD20 words, indicating lexical competition. Importantly, these inhibitory effects were found only for low- (not high-) frequency words, in line with previous findings that phonetically related primes inhibit recognition of low-frequency words. These results indicate that the properties of PLD20--a continuous measure of word-form similarity--make it a promising new metric for quantifying phonological distinctiveness in spoken word recognition research.	t	\N
21382386	Although developmental dyslexia is often referred to as a cross-modal disturbance, tests of different modalities using the same stimuli are lacking. We compared the performance of 23 children with dyslexia and 42 chronologically matched control readers on reading versus repetition tasks and visual versus auditory lexical decision using the same stimuli. With respect to control readers, children with dyslexia were impaired only on stimuli in the visual modality; they had no deficit on the repetition and auditory lexical decision tasks. By applying the rate-amount model (Faust et al., 1999), we showed that performance of children with dyslexia on visual (but not auditory) tasks was associated with that of control readers by a linear relationship (with a 1.78 slope), suggesting that a global factor accounts for visual (but not auditory) task performance. We conclude that the processing of linguistic stimuli in the visual and auditory modalities is carried out by independent processes and that dyslexic children have a selective deficit in the visual modality.	t	\N
21388613	Perceptual implicit memory is typically most robust when the perceptual processing at encoding matches the perceptual processing required during retrieval. A consistent exception is the robust priming that semantic generation produces on the perceptual identification test (Masson & MacLeod, 2002), a finding which has been attributed to either (1) conceptual influences in this nominally perceptual task, or (2) covert orthographic processing during generative encoding. The present experiments assess these possibilities using both auditory and visual perceptual identification, tests in which participants identify auditory words in noise or rapidly-presented visual words. During the encoding phase of the experiments, participants generated some words and perceived others in an intermixed study list. The perceptual control condition was visual (reading) or auditory (hearing), and varied across participants. The reading and hearing conditions exhibited the expected modality-specificity, producing robust intra-modal priming and non-significant cross-modal priming. Priming in the generate condition depended on the perceptual control condition. With a read control condition, semantic generation produced robust visual priming but no auditory priming. With a hear control condition, the results were reversed: semantic generation produced robust auditory priming but not visual priming. This set of results is not consistent with a straightforward application of either the conceptual-influence or covert-orthography account, and implies that the nature of encoding in the generate condition is influenced by the broader list context.	t	\N
21389700	Bone conduction (BC) is the way sound energy is transmitted by the skull bones to the cochlea causing a sound perception. Even if the BC sound transmission involves several pathways including sound pressure induced in the ear canal, inertial forces acting on the middle ear ossicles and cochlear fluids, alteration of the cochlear space, and pressure transmission through the 3rd window of the cochlea, the BC sound ultimately produces a wave motion on the basilar membrane similar to that of air-conducted sound. The efficiency of the BC stimulation is largely dependent on the skull bone where the skull acts as a rigid body at low frequencies and incorporates different types of wave transmission at higher frequencies. The interaural stimulation difference is determined by the difference between contralateral and ipsilateral BC sound transmission: the transcranial BC sound transmission. To benefit from binaural processing, the transcranial transmission should be low, while the same should be high when using BC hearing aids for unilateral deaf subjects. By appropriately positioning the stimulation, high or low transcranial transmission can be achieved.	t	\N
21390207	Human languages evolve continuously, and a puzzling problem is how to reconcile the apparent robustness of most of the deep linguistic structures we use with the evidence that they undergo possibly slow, yet ceaseless, changes. Is the state in which we observe languages today closer to what would be a dynamical attractor with statistically stationary properties or rather closer to a non-steady state slowly evolving in time? Here we address this question in the framework of the emergence of shared linguistic categories in a population of individuals interacting through language games. The observed emerging asymptotic categorization, which has been previously tested--with success--against experimental data from human languages, corresponds to a metastable state where global shifts are always possible but progressively more unlikely and the response properties depend on the age of the system. This aging mechanism exhibits striking quantitative analogies to what is observed in the statistical mechanics of glassy systems. We argue that this can be a general scenario in language dynamics where shared linguistic conventions would not emerge as attractors, but rather as metastable states.	t	\N
21398015	A meaningful interaction with our environment relies on the ability to focus on relevant sensory input and to ignore irrelevant information, i.e. top-down control and attention processes are employed to select from competing stimuli following internal goals. In this, the demands for the recruitment of top-down control processes depend on the relative perceptual salience of the competing stimuli. In the present functional magnetic resonance imaging (fMRI) study, we investigated the recruitment of top-down control processes in response to varying degrees of control demands in the auditory modality. For this purpose, we tested 20 male and 20 female subjects with a dichotic listening paradigm, in which the relative perceptual salience of two simultaneously presented stimuli was systematically manipulated by varying the inter-aural intensity difference (IID) and asking the subjects to selectively attend to either ear. The analysis showed that the interaction between IID and attentional direction involves two networks in the brain. A fronto-parietal network, including the pre-supplementary motor area, anterior cingulate cortex, inferior frontal junction, insula and inferior parietal lobe, was recruited during cognitively demanding conditions and can thus be seen as a top-down cognitive control network. In contrast, a second network including the superior temporal and the post-central gyri was engaged under conditions with low cognitive control demands. These findings demonstrate how cognitive control is achieved through the interplay of distinct brain networks, with their differential engagement determined as a function of the level of competition between the sensory stimuli.	t	\N
21417674	This study was designed to evaluate an automated pure-tone audiometric procedure (AMTAS(®)) for 4-8 year-old children, and a quality assessment method (QUALIND(®)) that predicts the accuracy of the test. Children were tested with AMTAS and conventional manual air-conduction audiometry. A group of adults was tested for comparison. Eighty-one 4-8 year-old children and 15 adults. Most had normal hearing. For most subjects (93% of adults and 91% of children) differences between AMTAS and manual thresholds were similar to differences that occur when two experienced audiologists test the same subjects. QUALIND detected the inaccurate audiograms with a sensitivity of 71% and a specificity of 91%. When inaccurate audiograms identified by QUALIND are excluded, the accuracy of AMTAS is similar to the accuracy of manual audiometry. AMTAS produces accurate air-conduction audiograms in a high proportion of 4-8 year-old children and adults. QUALIND successfully identified most inaccurate AMTAS audiograms. The method can decrease the cost and increase efficiency and accessibility of hearing testing.	t	\N
21420739	Perception of environmental sounds from impacted materials (Wood, Metal and Glass) was examined by conducting a categorization experiment. Stimuli consisted of sound continua evoking progressive transitions between material categories. Results highlighted shallower response curves in subjects with schizophrenia than healthy participants, and are discussed in the framework of Signal Detection Theory and in terms of impaired perception of specific timbre features in schizophrenia.	t	\N
21420989	There is ongoing debate with respect to interpretation of the finding that, in contrast to perceptual size judgments, actions are relatively unaffected by the Müller-Lyer illusion. In normal unrestricted viewing situations observers cannot perform an action directed at an object without simultaneously perceiving the object - this makes it difficult to unequivocally establish whether observed effects are a function of vision for perception, vision for action, a combination of both, or of a single all-purpose visual system. However, there is evidence that observers are capable of performing actions towards objects of which they are not consciously aware, implying that two distinct visual thresholds may exist; one accompanying vision for action and one accompanying vision for perception. To investigate this possibility we created a situation in which visual information was presented below the perception threshold, but above the purported action threshold, allowing examination of action responses independent of contributions from vision for perception. Following a perceptual categorization task, participants performed delayed pointing movements towards briefly exposed masked Müller-Lyer targets of different sizes. When the targets were presented below the perception threshold, participants were unable to discriminate between them, yet their delayed pointing movements were affected by target size (but not the illusion). The results imply that vision for action is functional even after a delay and/or that the pickup of egocentric information is associated with a lower visual threshold than the pickup of allocentric information.	t	\N
21422306	To evaluate the significance of the Carhart notch (a 2-kHz bone conduction threshold dip [2KBD]) in the diagnosis of stapes fixation by comparing its incidence among ears with various ossicular chain abnormalities. Retrospective study. University hospital. A total of 153 ears among 127 consecutive patients with a congenital ossicular anomaly or otosclerosis. The 2KBD depth was defined as the threshold at 2 kHz minus the mean of thresholds at 1 and 4 kHz. The presence of 2KBD (depth, ≥10 dB), 2KBD depth, relationship between 2KBD depth and air-bone gap, and 2-kHz bone conduction recovery after operation were evaluated in a stapes fixation group (which included cases of otosclerosis and congenital stapes fixation), an incudostapedial joint detachment group, and a malleus or incus fixation group. A 2KBD was present in 32 of 102 stapes fixation ears (31.4%), 5 of 19 incudostapedial joint detachment ears (26.3%), and 6 of 20 malleus or incus fixation ears (30.0%) (12 ears had other diagnoses). The mean (SD) 2KBD depths were 17.3 (5.2) dB in the stapes fixation group, 18.5 (2.2) dB in the incudostapedial joint detachment group, and 16.3 (2.1) dB in the malleus or incus fixation group. No statistically significant differences were noted among these 3 groups. No correlation was noted between 2KBD depth and air-bone gap extent. Recovery of 2-kHz bone conduction threshold in the stapes fixation group was less than that in the other 2 groups. Incidence of 2KBD was similar among the stapes fixation, incudostapedial joint detachment, and malleus or incus fixation groups, implying that 2KBD is not a useful predictor of stapes fixation.	t	\N
21424256	Assessing intentions, direction, and velocity of others is necessary for most daily tasks, and such information is often made available by both visual and auditory motion cues. Therefore, it is not surprising our great ability to perceive human motion. Here, we explore the multisensory integration of cues of biological motion walking speed. After testing for audiovisual asynchronies (visual signals led auditory ones by 30 ms in simultaneity temporal windows of 76.4 ms), in the main experiment, visual, auditory, and bimodal stimuli were compared to a standard audiovisual walker in a velocity discrimination task. Results in variance reduction conformed to optimal integration of congruent bimodal stimuli across all subjects. Interestingly, the perceptual judgements were still close to optimal for stimuli at the smallest level of incongruence. Comparison of slopes allows us to estimate an integration window of about 60 ms, which is smaller than that reported in audiovisual speech.	t	\N
21431434	Our objective is to determine whether the degree of endolymphatic hydrops as it is detected in vivo in patients with definite Meniere's disease correlates with audiovestibular function. In this prospective study, 37 patients with definite Meniere's disease according to AAO-HNS criteria were included. Intratympanic contrast enhanced temporal bone MRI was performed using a 3D FLAIR protocol. The degree of endolymphatic hydrops in the cochlea and the vestibulum was graded on a Likert scale (0-3). The degree of hydrops was then analyzed with respect to its correlation with audiometric hearing levels, electrocochleographic SP/AP ratios, interaural amplitude ratios of vestibular evoked myogenic potentials and degree of horizontal semicircular canal paresis on caloric irrigation. There was a significant correlation between the degree of hydrops on the one hand and the averaged hearing level at 0.25-1 and 0.5-3 kHz and the vestibular evoked myogenic potential interaural amplitude ratio on the other hand. A trend toward a correlation was noticed between the hydrops and the caloric response, no correlation was noticed between the hydrops and the SP/AP ratio. The degree of endolymphatic hydrops correlates with a progressive loss of auditory and sacculus function in patients with Meniere`s disease.	t	\N
21432625	Emotional inferences from speech require the integration of verbal and vocal emotional expressions. We asked whether this integration is comparable when listeners are exposed to their native language and when they listen to a language learned later in life. To this end, we presented native and non-native listeners with positive, neutral and negative words that were spoken with a happy, neutral or sad tone of voice. In two separate tasks, participants judged word valence and ignored tone of voice or judged emotional tone of voice and ignored word valence. While native listeners outperformed non-native listeners in the word valence task, performance was comparable in the voice task. More importantly, both native and non-native listeners responded faster and more accurately when verbal and vocal emotional expressions were congruent as compared to when they were incongruent. Given that the size of the latter effect did not differ as a function of language proficiency, one can conclude that the integration of verbal and vocal emotional expressions occurs as readily in one's second language as it does in one's native language.	t	\N
21440971	Congenital amusia manifests as a lifelong difficulty in making sense of musical sound. The extent to which this disorder is accompanied by deficits in visuo-spatial processing is an important question, bearing on the issue of whether pitch processing draws on supramodal spatial representations. The present study assessed different aspects of visuo-spatial processing with a range of tasks (Shepard-Metzler Mental Rotation, Corsi Blocks Task, Visual Patterns Test) in 14 amusics and matched controls. The absence of a group difference on any of these tasks fails to support a previous claim that the disorder is strongly related to deficits in spatial processing. However, a subgroup of amusics, with significantly elevated thresholds on a pitch direction discrimination task relative to the rest of the group, were slower, but equally accurate, at Mental Rotation. This finding is discussed in relation to the nature of supramodal representations of contour and strategies for dynamic mental transformation.	t	\N
21458056	Speech production can be broadly separated into two distinct components: Phonation and Articulation. These two aspects require the efficient control of several phono-articulatory effectors. Speech is indeed generated by the vibration of the vocal-folds in the larynx (F0) followed by ''filtering" by articulators, to select certain resonant frequencies out of that wave (F1, F2, F3, etc.). Recently it has been demonstrated that the motor representation of articulators (lips and tongue) participates in the discrimination of articulatory sounds (lips- and tongue-related speech sounds). Here we investigate whether the results obtained on articulatory sounds discrimination could be extended to phonation by applying a dual-pulse TMS protocol while subjects had to discriminate F0-shifted vocal utterances [a]. Stimulation over the larynx motor representation, compared to the control site (tongue/lips motor cortex), induced a reduction in RT for stimuli including a subtle pitch shift. We demonstrate that vocal pitch discrimination, in analogy with the articulatory component, requires the contribution of the motor system and that this effect is somatotopically organized.	t	\N
21463563	Bone-conduction thresholds have been used in audiologic assessments of both infants and adults to differentiate between conductive and sensorineural hearing losses. However, air- and bone-conduction thresholds estimated for infants with normal hearing using physiological measures have identified an "air-bone gap" in the low frequencies that does not result from conductive hearing impairment but, rather, from maturational differences in sensitivity. This maturational air-bone gap appears to be present up to at least 2 yr of age. Because most infants older than 6 mo of age are clinically assessed behaviorally, rather than physiologically, it is necessary to determine whether a similar maturational air-bone gap is present for behavioral air- and bone-conduction thresholds. The purpose of this study was to estimate behavioral bone-conduction thresholds for infants using a standard clinical visual reinforcement audiometry (VRA) protocol to determine whether frequency-dependent maturational patterns exist as previously reported for physiological bone-conduction thresholds. Behavioral bone-conduction minimum response levels were estimated at 500, 1000, 2000, and 4000 Hz using VRA for each participant. Young (7-15 mo; N = 17) and older (18-30 mo; N = 20) groups of infants were assessed. All infants were screened and considered to be at low risk for hearing loss. Preliminary "normal levels" were determined by calculating the 90th percentile for responses present as a cumulative percentage. Mean bone-conduction thresholds were compared and analyzed using a mixed-model analysis of variance across frequency and age group. Linear regression analysis was also performed to assess the effect of age on bone-conduction thresholds. Results of this study indicate that, when measured behaviorally, infants under 30 mo of age show frequency-dependent bone-conduction thresholds whereby their responses at 500 and 1000 Hz are significantly better than those at 2000 and 4000 Hz. However, thresholds obtained from the younger group of infants (mean age of 10.6 mo) were not significantly different from those obtained from the older group of infants (mean age of 23.0 mo) at any frequency. The findings of the present study are similar to the results obtained from previous physiological studies. Compared to previously documented air-conduction thresholds of infants using similar VRA techniques, a maturational air-bone gap is observed in the low frequencies. Therefore, differences between infant and adult bone-conduction thresholds persist until at least 30 mo of age. As a result, different "normal levels" should be used when assessing bone-conduction hearing sensitivity of infants using behavioral methods.	t	\N
21476653	Different non-exponential decays such as the concave and the convex double sloped decays in the coupled rooms provide distinct sound qualities. These are commonly considered to occur in the less reverberant sub-room and the more reverberant sub-room, respectively. However, numerical simulations and experiments in this paper show that the demarcation line is not located along the physical boundaries (e.g., the partition and the coupling aperture), but in the more reverberant sub-room. The sound field with the concave double sloped decay penetrates into the auxiliary sub-room to an extent which is influenced by the difference between the two natural reverberations of the sub-rooms. Furthermore the sound energy flows in different regions are investigated, demonstrating how energy feedback leads to the concave double sloped decay.	t	\N
21476654	Talkers adjust their vocal effort to communicate at different distances, aiming to compensate for the sound propagation losses. The present paper studies the influence of four acoustically different rooms on the speech produced by 13 male talkers addressing a listener at four distances. Talkers raised their vocal intensity by between 1.3 and 2.2 dB per double distance to the listener and lowered it as a linear function of the quantity "room gain" at a rate of -3.6 dB/dB. There were also significant variations in the mean fundamental frequency, both across distance (3.8 Hz per double distance) and among environments (4.3 Hz), and in the long-term standard deviation of the fundamental frequency among rooms (4 Hz). In the most uncomfortable rooms to speak in, talkers prolonged the voiced segments of the speech they produced, either as a side-effect of increased vocal intensity or in order to compensate for a decrease in speech intelligibility.	t	\N
21476664	The enhancement effect is consistently shown when simultaneously masked stimuli are preceded by the masker alone, with a reduction in the amount of masking relative to when that precursor is absent. One explanation for this effect proposed by Viemeister and Bacon [(1982). J. Acoust. Soc. Am. 71, 1502-1507] is the adaptation of inhibition, which predicts that an enhanced component (the "target") will be effectively more intense within the auditory system than one that has not been enhanced. Forward masking studies have indicated this effect of increased gain; however, other explanations of the enhancement effect have also been suggested. In order to provide an alternative measure of the amount of effective gain for an enhanced target, a subjective binaural centering task was used in which listeners matched the intensities of enhanced and unenhanced 2-kHz tones presented to opposite ears to produce a centered stimulus. The results showed that the enhancement effect produces an effective 4-5 dB increase in the level of the enhanced target. The enhancement effect was also measured using other enhancement paradigms which yielded similar results over a range of levels for the target, supporting an account based on adaptation of inhibition.	t	\N
21477909	Operatic music involves both singing and acting (as well as rich audiovisual background arising from the orchestra and elaborate scenery and costumes) that multiply the mechanisms by which emotions are induced in listeners. The present study investigated the effects of music, plot, and acting performance on emotions induced by opera. There were three experimental conditions: (1) participants listened to a musically complex and dramatically coherent excerpt from Tosca; (2) they read a summary of the plot and listened to the same musical excerpt again; and (3) they re-listened to music while they watched the subtitled film of this acting performance. In addition, a control condition was included, in which an independent sample of participants succesively listened three times to the same musical excerpt. We measured subjective changes using both dimensional, and specific music-induced emotion questionnaires. Cardiovascular, electrodermal, and respiratory responses were also recorded, and the participants kept track of their musical chills. Music listening alone elicited positive emotion and autonomic arousal, seen in faster heart rate, but slower respiration rate and reduced skin conductance. Knowing the (sad) plot while listening to the music a second time reduced positive emotions (peacefulness, joyful activation), and increased negative ones (sadness), while high autonomic arousal was maintained. Watching the acting performance increased emotional arousal and changed its valence again (from less positive/sad to transcendent), in the context of continued high autonomic arousal. The repeated exposure to music did not by itself induce this pattern of modifications. These results indicate that the multiple musical and dramatic means involved in operatic performance specifically contribute to the genesis of music-induced emotions and their physiological correlates.	t	\N
21491357	Obesity may be associated with increased tissue bulk in the laryngeal airway, neck, and chest wall, and as such may affect vocal function. Eight obese and eight nonobese adults participated in this study; the obese participants underwent bariatric surgical procedures. This mixed-design study included cross-sectional analysis for group differences and longitudinal analysis for multidimensional changes in vocal function from four assessments collected over 6 months. No significant differences were detected between groups from the preoperative assessment. Further, no changes were detected over time for acoustic parameters, maximum phonation time, laryngeal airway resistance, and airflow during a sustained vowel for either group. Only minor differences were detected for strain, pitch, and loudness perceptions of voice over time, but not between groups. Phonation threshold pressure (PTP), at comfortable and high pitches (30% and 80% of the F0 range) changed significantly over time, but not between groups. Examination of individual data revealed a trend for PTP at 30% F0 to decrease as body mass index decreased. PTP may be informative for assessing vocal function in clients who present with obesity and voice symptoms.	t	\N
21493300	The aim of this prospective study was to audiologically evaluate consecutive glaucoma patients with or without exfoliation. Prospective study. Glaucoma Unit and Audiology Department at a university hospital. Consecutive subjects with exfoliative glaucoma (XFG) or primary open-angle glaucoma (POAG) aged between 50 and 70 years were enrolled. Auditory thresholds at 0.5, 1.0, 2.0, 4.0, and 8.0 Hz were measured bilaterally. Cochlear activity was assessed by recording distortion product otoacoustic emissions (DPOEs). Functional changes in the retrocochlear auditory pathway were evaluated by auditory brainstem responses (ABRs). One hundred and ten patients with XFG and 85 patients with POAG who presented in a glaucoma clinic were investigated. The mean age of study patients was 66.2 ± 5.6 years; range, 50-70 years). The odds of pathologic ABR central transmission time (interpeak latencies I-III, III-V, and I-V and waves I, III, and V) were 4.34 times higher in patients with XFG than in patients with POAG (95% confidence interval [CI], 2.22-8.49; P < .001). This significant association remained after adjusting for sex and age (odds ratio [OR] 4.12; 95% CI, 2.07-8.22; P < .001). Furthermore, the odds of ABR remained significantly higher in patients with XFG than in patients with POAG (OR 4.36; 95% CI, 2.10-9.06; P < .001) after controlling for systemic diseases (arterial hypertension, coronary heart disease, high cholesterol, and stroke). In the first study to compare XFG and POAG monitoring of the peripheral and central auditory pathway, it has been documented that XFG patients show a greater prevalence of retrocochlear pathology.	t	\N
21493334	To compare noise reduction of commercially available ear-level hearing protection (muffs/inserts) to that of firearm muzzle suppressors. Experimental sound measurements under consistent environmental conditions. None. Muzzle suppressors for 2 pistol and 2 rifle calibers were tested using the Bruel & Kjaer 2209 sound meter and Bruel & Kjaer 4136 microphone calibrated with the Bruel & Kjaer Pistonphone using Military-Standard 1474D placement protocol. Five shots were recorded unsuppressed and 10 shots suppressed under consistent environmental conditions. Sound reduction was then compared with the real-world noise reduction rate of the best available ear-level protectors. All suppressors offered significantly greater noise reduction than ear-level protection, usually greater than 50% better. Noise reduction of all ear-level protectors is unable to reduce the impulse pressure below 140 dB for certain common firearms, an international standard for prevention of sensorineural hearing loss. Modern muzzle-level suppression is vastly superior to ear-level protection and the only available form of suppression capable of making certain sporting arms safe for hearing. The inadequacy of standard hearing protectors with certain common firearms is not recognized by most hearing professionals or their patients and should affect the way hearing professionals counsel patients and the public.	t	\N
21506894	To assess the effect of the static force of a bone vibrator on the results of bone conduction (BC) threshold measurements and comfort. BC thresholds were determined for 40 participants using the standardized P-3333 headband and a leather adjustable headstrap with variable static forces (2.4, 3.4, 4.4, 5.4 N). Comfort ratings were examined using a five-point Likert scale. Mean BC thresholds were within ± 2 dB across all conditions; differences may be considered small enough to be clinically insignificant. Participants experienced significantly greater discomfort with the P-3333 versus the adjustable headstrap. The mean static force of the P-3333 varied considerably and was higher in situ than the calibration standard of 5.4 N. The results suggest that future revisions of relevant international and national standards should address the use of an adjustable headstrap and a static force less than 5.4 N.	t	\N
21512424	To evaluate the outcomes of younger (<60 yr) and older (≥60 yr) patients implanted with the Vibrant Soundbridge (VSB). The aim was to determine if there were differences between groups. A retrospective study was used to evaluate all patients who were implanted and fit with a VSB during 2008 and 2009 at the Department of Otorhinolaryngology-Head and Neck Surgery, Medical University Innsbruck. Differences in audiologic, medical, and surgical outcomes between younger and older patients were evaluated. No patients had major complications during or after the surgical procedure. All patients had a good hearing benefit as supported by improvements in hearing thresholds from the preoperative to the postoperative condition in the sound field. There were differences between groups in speech understanding postoperatively; however, the differences were not statistically significant. All patients had, independent of age, good audiologic benefit from VSB use. Based on the low risk of medical or surgical complications, the easy use of the hearing implant, audiologic improvements, and potential social benefits, we think that the VSB should be regularly offered to adults with hearing loss, whether they are young or old.	t	\N
21517207	The purpose of this study was to examine the effects of expertise on motion anticipation. We conducted 2 experiments in which novices and expert pilots viewed simulated aircraft landing scenes. The scenes were interrupted by the display of a black screen and then started again after a forward or backward shift. The participant's task was to determine whether the moving scene had been shifted forward or backward. A forward misjudgment of the final position of the moving scene was interpreted as a representational momentum (RM) effect. Experiment 1 showed that an RM effect was detected only for experts. The lack of motion anticipation on the part of novices is a surprising result for the RM literature. It could be related to scene unfamiliarity, encoding time, or shift size. Experiment 2 was run with novices only. It was aimed at testing the potential impact of 2 factors on the RM effect: scene encoding time and shift size. As a whole, the results showed that encoding time and shift size are important factors in anticipation processes in realistic dynamic situations.	t	\N
21524739	Word segmentation from continuous speech is a difficult task that is faced by human infants when they start to learn their native language. Several studies indicate that infants might use several different cues to solve this problem, including intonation, linguistic stress, and transitional probabilities between subsequent speech sounds. In this work, a computational model for word segmentation and learning of primitive lexical items from continuous speech is presented. The model does not utilize any a priori linguistic or phonemic knowledge such as phones, phonemes or articulatory gestures, but computes transitional probabilities between atomic acoustic events in order to detect recurring patterns in speech. Experiments with the model show that word segmentation is possible without any knowledge of linguistically relevant structures, and that the learned ungrounded word models show a relatively high selectivity towards specific words or frequently co-occurring combinations of short words.	t	\N
21525779	The results reported in this paper indicate that native speakers of Mandarin Chinese rate the perceptual similarities among the lexical tones of Mandarin differently than do native speakers of American English. Mandarin listeners were sensitive to tone contour while English listeners attended to pitch levels. Chinese listeners also rated tones that are neutralized by phonological tone sandhi rules in Mandarin as more similar to each other than did English speakers--indicating a role of phonology in determining perceptual salience. In two further experiments, we found that some of these differences were eliminated when the listening task focused listeners' attention on the auditory properties of the stimuli, but, interestingly, a degree of language specificity remained even in the most purely psychophysical listening tasks with speech stimuli.	t	\N
21540053	The auditory system faithfully represents sufficient details from sound sources such that downstream cognitive processes are capable of acting upon this information effectively even in the face of signal uncertainty, degradation or interference. This robust sound source representation leads to an invariance in perception vital for animals to interact effectively with their environment. Due to unique nonlinearities in the cochlea, sound representations early in the auditory system exhibit a large amount of variability as a function of stimulus intensity. In other words, changes in stimulus intensity, such as for sound sources at differing distances, create a unique challenge for the auditory system to encode sounds invariantly across the intensity dimension. This challenge and some strategies available to sensory systems to eliminate intensity as an encoding variable are discussed, with a special emphasis upon sound encoding.	t	\N
21543605	The mammalian auditory system contains descending neural pathways, some of which project onto the cochlea via the medial olivocochlear (MOC) system. The function of this efferent auditory system is not entirely clear. Behavioral studies in animals with olivocochlear (OC) lesions suggest that the MOC serves to facilitate sound localization in noise. In the current work, noise-induced OC activity (the OC reflex) and sound-localization performance in noise were measured in normal-hearing humans. Consistent with earlier studies, both measures were found to vary substantially across individuals. Importantly, significant correlations were observed between OC-reflex strength and the effect of noise on sound-localization performance; the stronger the OC reflex, the less marked the effect of noise. These results suggest that MOC activation by noise helps to counteract the detrimental effects of background noise on neural representations of direction-dependent spectral features, which are especially important for accurate localization in the up/down and front/back dimensions.	t	\N
21545768	Previous studies have demonstrated a relation between cognitive capacity, in particular working memory, and the ability to understand speech in noise with different types of hearing aid signal processing. The present study investigates the relation between working memory capacity and the speech recognition performance of persons with hearing impairment under both aided and unaided conditions, following a period of familiarization to both fast- and slow-acting compression settings in the participants' own hearing aids. Speech recognition was tested in modulated and steady state noise with fast and slow compression release settings (for aided conditions) with each of two materials. Working memory capacity was also measured. Thirty experienced hearing aid users with a mean age of 70 yr (SD = 7.8) and pure-tone average hearing threshold across the frequencies 0.25, 0.5, 1, 2, 3, 4, and 6 kHz (PTA7) and for both ears of 45.8 dB HL (SD = 6.6. 9 wk experience with each of fast-acting and slow-acting compression. Speech recognition data were analyzed using repeated measures analysis of variance with the within-subjects factors of material (high constraint, low constraint), noise type (steady state, modulated), and compression (fast, slow), and the between-subjects factor working memory capacity (high, low). With high constraint material, there were three-way interactions including noise type and working memory as well as compression, in aided conditions, and performance level, in unaided conditions, but no effects of either working memory or compression with low constraint material. Investigation of simple main effects showed a significant effect of working memory during speech recognition under conditions of both "high degradation" (modulated noise, fast-acting compression, low signal-to-noise ratio [SNR]) and "low degradation" (steady state noise, slow-acting compression, high SNR). The finding of superior performance of persons with high working memory capacity in modulated noise with fast-acting compression agrees with findings of previous studies including a familiarization period of at least 9 wk, in contrast to studies with familiarization of 4 wk or less that have shown that persons with lower cognitive capacity may benefit from slow-acting compression. Working memory is a crucial factor in speech understanding in noise for persons with hearing impairment, irrespective of whether hearing is aided or unaided. Working memory supports speech understanding in noise under conditions of both "high degradation" and "low degradation." A subcomponent view of working memory may contribute to our understanding of these phenomena. The effect of cognition on speech understanding in modulated noise with fast-acting compression may only pertain after a period of 4-9 wk of familiarization and that prior to such a period, persons with lower cognitive capacity may benefit more from slow-acting compression.	t	\N
21547604	Listeners require context to understand the highly reduced words that occur in casual speech. The present study reports four auditory lexical decision experiments in which the role of semantic context in the comprehension of reduced versus unreduced speech was investigated. Experiments 1 and 2 showed semantic priming for combinations of unreduced, but not reduced, primes and low-frequency targets. In Experiment 3, we crossed the reduction of the prime with the reduction of the target. Results showed no semantic priming from reduced primes, regardless of the reduction of the targets. Finally, Experiment 4 showed that reduced and unreduced primes facilitate upcoming low-frequency related words equally if the interstimulus interval is extended. These results suggest that semantically related words need more time to be recognized after reduced primes, but once reduced primes have been fully (semantically) processed, these primes can facilitate the recognition of upcoming words as well as do unreduced primes.	t	\N
21554838	Tinnitus is a disturbing symptom and is often the main reason for otology referral. It is usually associated with hearing loss of varying aetiology, and is thought to begin in the cochlea, with later abnormal central activity. We hypothesise that tinnitus without hearing loss may be caused by central and subcortical abnormalities and altered outer hair cell function. To compare the auditory brainstem responses, middle latency responses and otoacoustic emissions in normal-hearing individuals with and without tinnitus. The audiological test results of 25 normal hearing subjects with tinnitus (age 18-45 years) were determined, and compared with those of a control group. A statistically significant difference was found between study group tinnitus ears vs control group ears, as regards wave I latency prolongation, shortening of wave V and absolute I-III and I-V interpeak latency, enlargement of wave Na and Pa amplitude, and distortion product and transient evoked otoacoustic emission signal-to-noise ratios. There was no statistically significant difference between unilateral vs bilateral tinnitus ears. The pathogenesis and optimum management of tinnitus are still unclear. It often occurs with primary ear disease, usually associated with hearing loss, but may occur in patients with normal hearing. Observed changes in auditory brainstem and middle latency responses indicate central auditory alterations. Tinnitus involves both peripheral and central activity, and complete audiological and neurophysiological investigation is required. Management should be based on both audiological and neurophysiological findings.	t	\N
21563460	To understand the usage of MP3 and effects on hearing of middle school students in Xi'an, and discuss controlling strategies. Stratified random cluster sampling method was used in the 1567 middle school students in Xi'an through questionnaire survey, ear examination and hearing examination, data were analysed by the SPSS13.0 statistical software. 1) The rate of holding MP3 in the middle school students was 85.2%. Average daily use time was (1.41 +/- 1.11) h. 2) The noise group of pure tone hearing threshold was significantly higher compared with the control group (P<0.01), and increased the detection rate of hearing loss with the increasing use of MP3. 3) The detection rate of symptoms increased with the increasing use of MP3. The usage of MP3 can harm hearing in middle school students, which can result in neurasthenic syndrome.	t	\N
21568377	The ability of listeners with bilateral sensorineural hearing loss to localize a speech source in a multitalker mixture was measured. Five simultaneous words spoken by different talkers were presented over loudspeakers in a small room, and listeners localized one target word. Errors were significantly larger in this group compared to a control group with normal hearing. Localization of the target presented alone was not different between groups. The results suggest that hearing loss does not impair spatial hearing per se, but degrades the spatial representation of multiple simultaneous sounds.	t	\N
21568378	A previous letter by Gee et al. [J. Acoust. Soc. Am. 121, EL1-EL7 (2007)] revealed likely shortcomings in using common, stationary (long-term) spectrum-based measures to quantify the perception of nonlinearly propagated noise. Here, the Glasberg and Moore [J. Audio Eng. Soc. 50, 331-342 (2002)] algorithm for time-varying loudness is investigated. Their short-term loudness, when applied to a shock-containing broadband signal and a phase-randomized signal with equivalent long-term spectrum, does not show a significant difference in loudness between the signals. Further analysis and discussion focus on the possible utility of the instantaneous loudness and the need for additional investigation in this area.	t	\N
21569784	In recent years it has been shown that a disorder in recognizing familiar people can be observed in patients with lesions affecting the anterior parts of the temporal lobes and that these disorders can be multi-modal, simultaneously affecting the visual, auditory and linguistic channels that allow person identification. Several authors have also shown that patients with right anterior temporal atrophy are more impaired in assessing familiarity and in retrieving person-specific semantic information from faces than from names, whereas the opposite pattern of performance can be observed in patients with left temporal lobe atrophy. Voice recognition disorders have been studied much less even despite their clinical and theoretical importance. The aim of the present review, therefore, was to compare recognition of familiar faces and voices, taking into account not only results obtained in individual patients with right anterior temporal lesions, but also those of group studies of unselected right- and left brain-damaged patients and results of experimental investigations conducted on face and voice recognition in normal subjects. Results of the review showed that: (1) voice recognition disorders are mainly due to right temporal lesions, similarly to face recognition disorders; (2) famous voice recognition disorders can be dissociated from unfamiliar voice discrimination impairments; (3) although face and voice recognition disorders tend to co-occur, they can also dissociate and in these patients there is a prevalent involvement of the right fusiform gyrus when face recognition disorders are on the foreground, and of the right superior temporal gyrus when voice recognition disorders are prominent; (4) normal subjects have greater difficulty evaluating familiarity and drawing semantic information from the voices than from the faces of celebrities. These data are at variance with models which assume that familiarity feelings may be generated at the level of person identity nodes (PINs) and that the latter may be considered as modality-free gateways to single semantic systems in which information about people is stored in an amodal format.	t	\N
21586256	In a number of European countries, a functional self-test to screen for hearing impairment is available via telephone and the Internet. The tests estimate speech-reception thresholds using an adaptive procedure in which digit triplets are presented at varying signal-to-noise ratios. In different languages, the stimuli were created either with or without coarticulation; and some implementations use fresh noise samples, while others do not. The present investigation concerns the influence of coarticulation, prosody, and noise freshness on measured thresholds. We performed a laboratory study using 12 normal-hearing listeners. In a blocked design we compared speech-reception thresholds for conditions with and without fresh noise tokens. In each block we used three types of triplets: with coarticulation and prosody, with neither, and without coarticulation but with prosody. Thirty-six thresholds were recorded per subject, and they were analyzed using analyses of variance. The results showed no significant differences among the three triplet conditions. The freshness of the noise did not affect thresholds when, at least, a fresh noise token was used per threshold estimate (23 presentations). Scores dropped significantly when a whole experimental block was performed with a single noise token.	t	\N
21601842	Evolution and the brain have done a marvelous job solving many tricky problems in action control, including problems of learning, hierarchical control over serial behavior, continuous recalibration, and fluency in the face of slow feedback. Given that evolution tends to be conservative, it should not be surprising that these solutions are exploited to solve other tricky problems, such as the design of a communication system. We propose that a mechanism of motor control, paired controller/predictor models, has been exploited for language learning, comprehension, and production. Our account addresses the development of grammatical regularities and perspective, as well as how linguistic symbols become meaningful through grounding in perception, action, and emotional systems.	t	\N
21603614	Recent studies suggest that human auditory perception follows a prolonged developmental trajectory, sometimes continuing well into adolescence. Whereas both sensory and cognitive accounts have been proposed, the development of the ability to base current perceptual decisions on prior information, an ability that strongly benefits adult perception, has not been directly explored. Here we ask whether the auditory frequency discrimination of preschool children also improves when given the opportunity to use previously presented standard stimuli as perceptual anchors, and whether the magnitude of this anchoring effect undergoes developmental changes. Frequency discrimination was tested using two adaptive same/different protocols. In one protocol (with-reference), a repeated 1-kHz standard tone was presented repeatedly across trials. In the other (no-reference), no such repetitions occurred. Verbal memory and early reading skills were also evaluated to determine if the pattern of correlations between frequency discrimination, memory and literacy is similar to that previously reported in older children and adults. Preschool children were significantly more sensitive in the with-reference than in the no-reference condition, but the magnitude of this anchoring effect was smaller than that observed in adults. The pattern of correlations among discrimination thresholds, memory and literacy replicated previous reports in older children. The processes allowing the use of context to form perceptual anchors are already functional among preschool children, albeit to a lesser extent than in adults. Nevertheless, immature anchoring cannot fully account for the poorer frequency discrimination abilities of young children. That anchoring is present among the majority of typically developing preschool children suggests that the anchoring deficits observed among individuals with dyslexia represent a true deficit rather than a developmental delay.	t	\N
21604886	Inhibitory control functions in old age were investigated with the "masked prime" paradigm in which participants executed speeded manual choice responses to simple visual targets. These were preceded--either immediately or at some earlier time--by a backward-masked prime. Young adults produced positive compatibility effects (PCEs)--faster and more accurate responses for matching than for nonmatching prime-target pairs--when prime and target immediately followed each other, and the reverse effect (negative compatibility effect, NCE) for targets that followed the prime after a short interval. Older adults produced similar PCEs to young adults, indicating intact low-level motor activation, but failed to produce normal NCEs even with longer delays (Experiment 1), increased opportunity for prime processing (Experiment 2), and prolonged learning (Experiment 3). However, a fine-grained analysis of each individual's time course of masked priming effects revealed NCEs in the majority of older adults, of the same magnitude as those of young adults. These were significantly delayed (even more than expected on the basis of general slowing), indicating a disproportionate impairment of low-level inhibitory motor control in old age.	t	\N
21616987	This project examined receptive vocabulary treatment outcomes in the two languages of a bilingual preschooler with moderate to severe language impairment. A series of single-subject experimental designs was used to compare English-only (EO) and bilingual (BI) approaches to receptive vocabulary treatment. The participant, Nam, was a boy age 3;11 (years;months) who was learning Vietnamese as a first language at home and English in his early childhood education program. Treatment was implemented by an EO interventionist using a computer interface and prerecorded audio files in Vietnamese and English. The dependent measure was the percentage of items that were correctly identified in each language. Combined studies revealed that the BI approach increased Nam's attention to task and was as effective as the EO approach for increasing his receptive vocabulary in English. Nam made vocabulary gains in both treatment conditions; receptive vocabulary gains were evident in both Vietnamese and English. This project showed that it is feasible for an EO clinician to promote gains in both the home and school languages of a BI child through creative collaborations with BI colleagues and the use of technology. Replication with additional participants and treatment activities is needed to make further generalizations.	t	\N
21623776	Isotretinoin is widely used in the treatment of extensive and nodulocystic acne. The objective of this prospective study was to investigate whether oral isotretinoin could affect the hearing system. Thirty-eight patients with acne vulgaris (76 ears) who were diagnosed and treated at the Department of Dermatology were included in the current study. Study evaluation visits were performed at baseline and at Weeks 1, 2 and 3. Pure-tone averages (PTAs) of air conduction thresholds at 250 Hz (PTA1); 500, 1000, and 2000 Hz (PTA2); 4000, 8000, and 10,000 Hz (PTA3); and 12,500, 16,000, 18,000 and 20,000 Hz (PTA4) for each ear were calculated separately. Assessment of the efficacy was based on the audiometric findings. Compared with pre-treatment evaluation, the PTAs of patients were found to be significantly different at the first week for PTA2 (P = 0.033) and PTA3 (P = 0.001), at the second week for PTA1 (P = 0.036), and at the third week for PTA4 (P = 0.002). Our results suggest that the oral isotretinoin (13-cis retinoic acid), which is a derivative of retinol (vitamin A), improved the hearing level of the patients in all audiometric frequencies in a short-period follow-up.	t	\N
21624926	Cognitive impairment is a core element shared by a large number of different neurological and neuropsychiatric diseases. Irrespective of their different aetiologies and symptomatologies, most appear to converge at the functional deficiency of the auditory-frontal cortex network of auditory discrimination, which indexes cognitive impairment shared by these abnormalities. This auditory-frontal cortical deficiency, and hence cognitive decline, can now be objectively measured with the mismatch negativity and its magnetic equivalent. The auditory-frontal cortical network involved seems, therefore, to play a pivotal, unifying role in the different abnormalities. It is, however, more likely that the dysfunction that can be detected with the mismatch negativity and its magnetoencephalographic equivalent manifests a more widespread brain disorder, namely, a deficient N-methyl-D-aspartate receptor function, shared by these abnormalities and accounting for most of the cognitive decline.	t	\N
21625011	The McGurk effect demonstrates the influence of visual cues on auditory perception. Mismatching information from both sensory modalities can fuse to a novel percept that matches neither the auditory nor the visual stimulus. This illusion is reported in 60-80% of trials. We were interested in the impact of ongoing brain oscillations-indexed by fluctuating local excitability and interareal synchronization-on upcoming perception of identical stimuli. The perception of the McGurk effect is preceded by high beta activity in parietal, frontal, and temporal areas. Beta activity is pronounced in the left superior temporal gyrus (lSTG), which is considered as a site of multimodal integration. This area is functionally (de)coupled to distributed frontal and temporal regions in illusion trials. The disposition to fuse multisensory information is enhanced as the lSTG is more strongly coupled to frontoparietal regions. Illusory perception is accompanied by a decrease in poststimulus theta-band activity in the cuneus, precuneus, and left superior frontal gyrus. Event-related activity in the left middle temporal gyrus is pronounced during illusory perception. Thus, the McGurk effect depends on fluctuating brain states suggesting that functional connectedness of left STS at a prestimulus stage is crucial for an audiovisual percept.	t	\N
21639675	It is well established that in masked priming, a target word (e.g., JUDGE) is primed more effectively by a transposed letter (TL) prime (e.g., jugde) than by an orthographic control prime (e.g., junpe). This is inconsistent with the slot coding schemes used in many models of visual word recognition. Several alternative coding schemes have been proposed in which special bigram detectors for frequently occurring nonadjacent letter combinations are developed as a product of perceptual learning. In order to examine this perceptual learning hypothesis, we asked whether bigram detectors are defined in terms of visuospatial coordinates. Japanese-English bilinguals who were equally familiar with horizontal and vertical text in Japanese demonstrated strong TL priming in both orientations when reading Japanese words, but, when reading English words, the evidence for vertical TL priming was not as strong. However, native English speakers showed a clear TL priming effect with vertically presented English words despite minimal exposure to vertical text, which is not consistent with a perceptual learning account. It is proposed instead that the initial letter array is transformed into an abstract ordinal code (first to last) regardless of orientation and that the speed with which this transformation is carried out depends on the familiarity of the script.	t	\N
21645986	The etiology of developmental dyslexia remains widely debated. An appealing theory postulates that the reading and spelling problems in individuals with dyslexia originate from reduced sensitivity to slow-rate dynamic auditory cues. This low-level auditory deficit is thought to provoke a cascade of effects, including inaccurate speech perception and eventually unspecified phoneme representations. The present study investigated sensitivity to frequency modulation and amplitude rise time, speech-in-noise perception and phonological awareness in 11-year-old children with dyslexia and a matched normal-reading control children. Group comparisons demonstrated that children with dyslexia were less sensitive than normal-reading children to slow-rate dynamic auditory processing, speech-in-noise perception, phonological awareness and literacy abilities. Correlations were found between slow-rate dynamic auditory processing and phonological awareness, and speech-in-noise perception and reading. Yet, no significant correlation between slow-rate dynamic auditory processing and speech-in-noise perception was obtained. Together, these results indicate that children with dyslexia have difficulties with slow-rate dynamic auditory processing and speech-in-noise perception and that these problems persist until sixth grade.	t	\N
21647889	To study to what extent it is possible to achieve identical insertion depths and to maintain the same performance after cochlear reimplantation. Outcome research on a retrospective case series in a tertiary university referral center. Data were collected for 12 adults and three children who underwent reimplantation during the last 3 years with a new HiRes90K device with HiFocus 1J electrode owing to failure of the feed-through seal. Multislice computed tomography scans were used to compare positions of the original and newly placed electrode arrays. The speech-perception scores on a consonant-vowel-consonant word test before and after reimplantation were compared. All reimplantations were successfully performed by two experienced cochlear implantation surgeons, and no complications were observed. Postoperative imaging showed that the average displacement of the new implant was only 0.59 mm. Reactivation of the implant gave immediate open set speech understanding in all patients, and speech perception rapidly returned to the previous level obtained with the original implant within weeks; it was even significantly better at the 3-month follow-up. No relation was found between changes in performance and the amount of displacement of the electrode array. After cochlear reimplantation with the same device, electrode-array position can be accurately replicated and speech perception can be regained or even improved within weeks.	t	\N
21649758	This event-related functional magnetic resonance imaging (fMRI) study was designed in such a manner so as to contribute to the present debate on behavioural and functional transfer effects associated with intensive language training. To address this novel issue, we measured professional simultaneous interpreters and control subjects while they performed a non-verbal auditory discrimination task that primarily relies on attention and categorization functions. The fMRI results revealed that the discrimination of the target stimuli was associated with differential blood oxygen level-dependent responses in fronto-parietal regions between the two groups, even though in-scanner behavioural results did not show significant group differences. These findings are in line with previous observations showing the contribution of fronto-parietal regions to auditory attention and categorization functions. Our results imply that language training modulates brain activity in regions involved in the top-down regulation of auditory functions.	t	\N
21669859	It is generally agreed that considerable amounts of low-level sensory processing of visual stimuli can occur without conscious awareness. On the other hand, the degree of higher level visual processing that occurs in the absence of awareness is as yet unclear. Here, event-related potential (ERP) measures of brain activity were recorded during a sandwich-masking paradigm, a commonly used approach for attenuating conscious awareness of visual stimulus content. In particular, the present study used a combination of ERP activation contrasts to track both early sensory-processing ERP components and face-specific N170 ERP activations, in trials with versus without awareness. The electrophysiological measures revealed that the sandwich masking abolished the early face-specific N170 neural response (peaking at ~170 ms post-stimulus), an effect that paralleled the abolition of awareness of face versus non-face image content. Furthermore, however, the masking appeared to render a strong attenuation of earlier feedforward visual sensory-processing signals. This early attenuation presumably resulted in insufficient information being fed into the higher level visual system pathways specific to object category processing, thus leading to unawareness of the visual object content. These results support a coupling of visual awareness and neural indices of face processing, while also demonstrating an early low-level mechanism of interference in sandwich masking.	t	\N
21675563	This study examined the effects of visual-verbalload (as measured by a visually presented reading-memory task with three levels) on a visual/auditory stimulus-response task. The three levels of load were defined as follows: "No Load" meant no other stimuli were presented concurrently; "Free Load" meant that a letter (A, B, C, or D) appeared at the same time as the visual or auditory stimulus; and "Force Load" was the same as "Free Load," but the participants were also instructed to count how many times the letter A appeared. The stimulus-response task also had three levels: "irrelevant," "compatible," and "incompatible" spatial conditions. These required different key-pressing responses. The visual stimulus was a red ball presented either to the left or to the right of the display screen, and the auditory stimulus was a tone delivered from a position similar to that of the visual stimulus. Participants also processed an irrelevant stimulus. The results indicated that participants perceived auditory stimuli earlier than visual stimuli and reacted faster under stimulus-response compatible conditions. These results held even under a high visual-verbal load. These findings suggest the following guidelines for systems used in driving: an auditory source, appropriately compatible signal and manual-response positions, and a visually simplified background.	t	\N
21676085	The phonological deficit theory of dyslexia assumes that degraded speech sound representations might hamper the acquisition of stable letter-speech sound associations necessary for learning to read. However, there is only scarce and mainly indirect evidence for this assumed letter-speech sound association problem. The present study aimed at clarifying the nature and the role of letter-speech sound association problems in dyslexia by analysing event-related potentials (ERP) of 11-year-old dyslexic children to speech sounds in isolation or combined with letters, which were presented either simultaneously with or 200 ms before the speech sounds. Recent studies with normal readers revealed that letters systematically modulated speech sound processing in an early (mismatch negativity or MMN) and late (Late Discriminatory Negativity or LDN) time-window. The amplitude of the MMN and LDN to speech sounds was enhanced when speech sounds were presented with letters. The dyslexic readers in the present study, however, did not exhibit any early influences of letters on speech sounds even after 4 years of reading instruction, indicating no automatic integration of letters and speech sounds. Interestingly, they revealed a systematic late effect of letters on speech sound processing, probably reflecting the mere association of letters and speech sounds. This pattern is strongly divergent from that observed in age-matched normal readers, who showed both early and late effects, but reminiscent of that observed in beginner normal readers in a previous study (Froyen, Bonte, van Atteveldt & Blomert, 2009). The finding that the quality of letter-speech sound processing is directly related to reading fluency urges further research into the role of audiovisual integration in the development of reading failure in dyslexia.	t	\N
21676091	Early post-natal nutrition influences later development, but there are no studies comparing brain function in healthy infants as a function of dietary intake even though the major infant diets differ significantly in nutrient composition. We studied brain responses (event-related potentials; ERPs) to speech sounds for infants who were fed either breast milk (BF), milk-based formula (MF), or soy formula (SF) during the first 6 months of life. Two syllables presented in an oddball paradigm elicited a late positive wave (P350) from temporal and frontal brain regions involved in language processes. All groups showed significantly greater response amplitudes to the infrequent syllable across sites at 3 months and frontally at 6 months, but significant discrimination at temporal sites was only observed at 6 months in BF infants. Decreases in response amplitudes from 3 to 6 months were greater for the frequently presented syllable, most prominent in BF infants, and greater in females than males. The results indicate greater syllable discrimination in BF than formula-fed infants, but whether this can be attributed to dietary influences alone remains unclear. Feeding method and background factor differences between breastfed and formula-fed infants may also contribute to the observed differences. The general absence of differences between formula-fed groups is notable and suggests that milk-based formula and soy formula equally support brain development and function during the first post-natal 6 months. Finally, the results indicate gender differences in the development of neural and temporal processes involved in sensory discrimination, and suggest that at 6 months these processes are better developed in females.	t	\N
21676999	The conditions of sound fields used in research, especially testing and fitting of hearing aids, are usually simplified or reduced to fundamental physical fields, such as the free or the diffuse sound field. The concepts of such ideal conditions are easily introduced in theoretical and experimental investigations and in models for directional microphones, for example. When it comes to real-world application of hearing aids, however, the field conditions are more complex with regard to specific stationary and transient properties in room transfer functions and the corresponding impulse responses and binaural parameters. Sound fields can be categorized in outdoor rural and urban and indoor environments. Furthermore, sound fields in closed spaces of various sizes and shapes and in situations of transport in vehicles, trains, and aircrafts are compared with regard to the binaural signals. In laboratory tests, sources of uncertainties are individual differences in binaural cues and too less controlled sound field conditions. Furthermore, laboratory sound fields do not cover the variety of complex sound environments. Spatial audio formats such as higher-order ambisonics are candidates for sound field references not only in room acoustics and audio engineering but also in audiology.	t	\N
21678230	Studies of change detection have increased our understanding of attention, perception, and memory. In two innovative experiments we showed that the change detection phenomenon can be used to examine other areas of cognition-specifically, the processing of linguistic and indexical information in spoken words. One hypothesis suggests that cognitive resources must be used to process indexical information, whereas an alternative suggests that it is processed more slowly than linguistic information. Participants performed a lexical decision task and were asked whether the voice presenting the stimuli changed. Nonwords varying in their likeness to real words were used in the lexical decision task to encourage participants to vary the amount of cognitive resources/processing time. More cognitive resources/processing time are required to make a lexical decision with word-like nonwords. Participants who heard word-like nonwords were more likely to detect the change when it occurred (Experiment 1) and were more confident that the voice was the same when it did not change (Experiment 2). These results suggest that indexical information is processed more slowly than linguistic information and demonstrate how change detection can provide insight to other areas of cognition.	t	\N
21681660	Two experiments examined whether perceptual recovery from Korean consonant-cluster simplification is based on language-specific phonological knowledge. In tri-consonantal C1C2C3 sequences such as /lkt/ and /lpt/ in Seoul Korean, either C1 or C2 can be completely deleted. Seoul Koreans monitored for C2 targets (/p/ or / k/, deleted or preserved) in the second word of a two-word phrase with an underlying /l/-C2-/t/ sequence. In Experiment 1 the target-bearing words had contextual lexical-semantic support. Listeners recovered deleted targets as fast and as accurately as preserved targets with both Word and Intonational Phrase (IP) boundaries between the two words. In Experiment 2, contexts were low-pass filtered. Listeners were still able to recover deleted targets as well as preserved targets in IP-boundary contexts, but better with physically-present targets than with deleted targets in Word-boundary contexts. This suggests that the benefit of having target acoustic-phonetic information emerges only when higher-order (contextual and phrase-boundary) information is not available. The strikingly efficient recovery of deleted phonemes with neither acoustic-phonetic cues nor contextual support demonstrates that language-specific phonological knowledge, rather than language-universal perceptual processes which rely on fine-grained phonetic details, is employed when the listener perceives the results of a continuous-speech process in which reduction is phonetically complete.	t	\N
21682395	The perceived negative influence of standard hearing protectors on communication is a common argument for not wearing them. Thus, "augmented" protectors have been developed to improve speech intelligibility. Nevertheless, their actual benefit remains a point of concern. In this paper, speech perception with active earplugs is compared to standard passive custom-made earplugs. The two types of active protectors included amplify the incoming sound with a fixed level or to a user selected fraction of the maximum safe level. For the latter type, minimal and maximal amplification are selected. To compare speech intelligibility, 20 different speech-in-noise fragments are presented to 60 normal-hearing subjects and speech recognition is scored. The background noise is selected from realistic industrial noise samples with different intensity, frequency, and temporal characteristics. Statistical analyses suggest that the protectors' performance strongly depends on the noise condition. The active protectors with minimal amplification outclass the others for the most difficult and the easiest situations, but they also limit binaural listening. In other conditions, the passive protectors clearly surpass their active counterparts. Subsequently, test fragments are analyzed acoustically to clarify the results. This provides useful information for developing prototypes, but also indicates that tests with human subjects remain essential.	t	\N
21682407	When a test sound consisting of pure tones with equal intensities is preceded by a precursor sound identical to the test sound except for a reduction in the intensity of one tone, an auditory "enhancement" phenomenon occurs: In the test sound, the tone which was previously softer stands out perceptually. Here, enhancement was investigated using inharmonic sounds made up of five pure tones well resolved in the auditory periphery. It was found that enhancement can be elicited not only by increases in intensity but also by shifts in frequency. In both cases, when the precursor and test sounds are separated by a 500-ms delay, inserting a burst of pink noise during the delay has little effect on enhancement. Presenting the precursor and test sounds to opposite ears rather than to the same ear significantly reduces the enhancement resulting from increases in intensity, but not the enhancement resulting from shifts in frequency. This difference suggests that the mechanisms of enhancement are not identical for the two types of change. For frequency shifts, enhancement may be partly based on the existence of automatic "frequency-shift detectors" [Demany and Ramos, J. Acoust. Soc. Am. 117, 833-841 (2005)].	t	\N
21688937	Cross-modal temporal recalibration describes a shift in the point of subjective simultaneity (PSS) between 2 events following repeated exposure to asynchronous cross-modal inputs--the adaptors. Previous research suggested that audiovisual recalibration is insensitive to the spatial relationship between the adaptors. Here we show that audiovisual recalibration can be driven by cross-modal spatial grouping. Twelve participants adapted to alternating trains of lights and tones. Spatial position was manipulated, with alternating sequences of a light then a tone, or a tone then a light, presented on either side of fixation (e.g., left tone--left light--right tone--right light, etc.). As the events were evenly spaced in time, in the absence of spatial-based grouping it would be unclear if tones were leading or lagging lights. However, any grouping of spatially colocalized cross-modal events would result in an unambiguous sense of temporal order. We found that adapting to these stimuli caused the PSS between subsequent lights and tones to shift toward the temporal relationship implied by spatial-based grouping. These data therefore show that temporal recalibration is facilitated by spatial grouping.	t	\N
21689988	Mozart's Sonata for Two Pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart Effect. Our previous work revealed that epileptiform discharges in children with epilepsy decrease during and right after listening to Mozart K.448. However, the duration of the effect was not studied. In the study described here, we evaluated the long-term effect of Mozart K.448 on epileptiform discharges in children with epilepsy. Eighteen children with epilepsy whose seizures were clinically well controlled with antiepileptic drugs were included. For each child, EEGs had revealed persistent epileptiform discharges for at least 6 months. These patients listened to Mozart K.448 for 8 minutes once a day before bedtime for 6 months. Epileptiform discharges were recorded and compared before and after 1, 2, and 6 months of listening to Mozart K.448. All of the children remained on the same antiepileptic drug over the 6 months. Relationships between number of epileptiform discharges and foci of discharges, intelligence, epilepsy etiology, age, and gender were analyzed. Epileptiform discharges significantly decreased by 53.2±47.4, 64.4±47.1, and 71.6±45.8%, respectively, after listening to Mozart K.448 for 1, 2, and 6 months. All patients except those with occipital discharges showed a significant decrease in epileptiform discharges. Patients with normal intelligence and idiopathic epilepsy had greater decreases than those with mental retardation and symptomatic epilepsy. Age and gender did not affect the results. We conclude that long-term listening to Mozart K.448 may be effective in decreasing epileptiform discharges in children with epilepsy in a chronologically progressive manner.	t	\N
21700953	We previously reported that fast-moving dot arrays cause orientation-tuned masking of static gratings (D. Apthorp, J. Cass, & D. Alais, 2010), which we attribute to "motion streaks." Using similar "streaky" dot motion, we describe spatial frequency tuning of grating threshold elevations caused by masking (Experiment 1) and adaptation (Experiment 2) to motion. To compare the streaks with psychophysical tunings, we Fourier analyzed time-averaged translating dots, which were bandpass (peaking at ∼2.3 c/deg). Masking, however, was strongest at lower test frequencies (≤1 c/deg) and largely isotropic over orientation, although a small orientation-tuned effect occurred at ∼1.2 c/deg. Results were broadly similar across monoptic and dichoptic conditions. Adaptation to fast motion produced spatially bandpass threshold elevations for parallel test gratings, peaking slightly lower than the peak Fourier frequency, with little elevation below 1 c/deg (unlike the low-pass elevation resulting from masking). Slow adaptation produced little elevation for parallel gratings. For orthogonal test gratings, fast motion adaptation produced low-pass threshold elevations and slow motion produced bandpass elevations, suggesting that separable mechanisms process fast (streaky) and slow motion. The different threshold elevation patterns over spatial frequency for masking and adaptation suggest that the adaptation effects are mainly within-channel suppression, whereas the masking effects may be mainly due to between-channel suppression.	t	\N
21717096	The ocular vestibular evoked myogenic potential (oVEMP) is a relatively new method used to assess otolith-ocular pathways in humans. When elicited using air-conducted (AC) sound stimulation, the oVEMP is thought to reflect mostly saccular activation. However, it has been recently suggested that utricular afferents may also contribute to the AC evoked oVEMP. While previous frequency tuning studies of the AC evoked oVEMP report predominately high frequency sensitivity (>400 Hz), few have included the lower frequencies (<200 Hz) at which it has been proposed the utricle is most sensitive. In this study, ten normal subjects were stimulated with AC sound delivered unilaterally using headphones over frequencies from 50 to 1,200 Hz at a near constant A-weighted intensity of 120 dB peak sound pressure level. For AC stimulation, the oVEMP demonstrated maximum amplitudes around 600 Hz, with a second, smaller peak occurring around 100 Hz. The AC evoked oVEMP tuning has two peaks, a dominant one consistent with excitation of the saccule and a smaller one consistent with excitation of the utricle.	t	\N
21724369	In spite of voice being an important parameter of mate choice, none of the studies have described the acoustic characteristics of the sexually appealing voice. Two hundred adults (100 men and 100 women) in the age range of 18-24 years were asked to narrate a topic, which was recorded directly onto Computerized Speech Lab (CSL) 6103 hardware. Recorded stimuli were presented to the six judges, and they were asked to indicate if the voice is sexually appealing on a five-point rating scale. The voices, which are consistently identified as sexually very attractive and unattractive were subjected to cepstral analysis through CSL. The results of perceptual analysis revealed that 28 of the female voice samples and 39 of the male voice samples were rated as sexually attractive. These ratings were consistent within and across the judges. The cepstral analysis was then performed in all the voice samples and the results of independent t test revealed higher values of cepstral peak parameter (CPP) in the sexually attractive voices in comparison to the other voice samples in both the genders. The obtained results are discussed with respect to the harmonic organization in the voice samples. The results of cepstral analysis in sexually attractive voices revealed higher values of CPP in comparison to the voices rated as sexually not appealing. This could be because of the presence of well-defined harmonic structure evidenced in the sexually appealing voice in comparison to voices rated as very unappealing. Our findings suggest that cepstral analysis is a good indicator of sexually appealing voice.	t	\N
21728456	Cognitive control resolves conflicts between appropriate and inappropriate response tendencies. Is this achieved by a unitary all-purpose conflict control system, or do independent subsystems deal with different aspects of conflicting information? In a fully factorial hybrid prime-Simon task, participants responded to the identity of targets displayed at different nominally irrelevant screen locations, preceded by nominally irrelevant, consciously or nonconsciously perceived primes. The response required by the target's identity could match or mismatch (a) the target's location, and (b) the prime's identity, resulting in potential conflict (a) across and (b) within stimulus domains. Conflict effects were investigated within and across trials. Results suggest that (i) nonconsciously perceived information elicits within-trial control, but--unlike consciously perceived information--no across-trial behavioral modulation; (ii) separate subsystems deal with conflicts arising from different stimulus domains; and (iii) occasional apparent interactions between domains reflect a particular difficulty in reactivating a just-discarded response (reactivation aversion effect, RAE).	t	\N
21728464	Increasing perceptual load reduces the processing of visual stimuli outside the focus of attention, but the mechanism underlying these effects remains unclear. Here we tested an account attributing the effects of perceptual load to modulations of visual cortex excitability. In contrast to stimulus competition accounts, which propose that load should affect simultaneous, but not sequential, stimulus presentations, the visual excitability account makes the novel prediction that load should affect detection sensitivity for both simultaneous and sequential presentations. Participants fixated a stimulus stream, responding to targets defined by either a color (low load) or color and orientation conjunctions (high load). Additionally, detection sensitivity was measured for a peripheral critical stimulus (CS) presented occasionally. Increasing load at fixation reduced sensitivity to the peripheral CSs; this effect was similar regardless of whether CSs were presented simultaneously with central stimuli or during the (otherwise empty) interval between them. Controls ruled out explanations of the results in terms of strategic task prioritization. These findings support a cortical excitability account for perceptual load, challenging stimulus competition accounts.	t	\N
21729437	To describe the effect of age and noise on high frequency hearing thresholds in an Italian population aged 70 years and older, in order to investigate the interaction between presbycusis and noise exposure. We compared 460 subjects: 367 affected by presbycusis alone (204 women and 163 men) and 93 affected by presbycusis and noise exposure (eight women and 85 men). Pure tone average hearing thresholds, for each ear, were compared between groups, and between sexes and ages within groups. A slight threshold difference was found between the two groups at 4 kHz. After adjusting for age and gender, this difference was found to be related only to differing patient age. Men's and women's thresholds differed significantly in both groups, especially at high frequencies, at which threshold deterioration was worse in men than women. The threshold differences between patients with presbycusis with and without noise exposure were limited. Larger studies are needed to assess the relative effects of ageing and noise exposure on hearing thresholds.	t	\N
21750713	In the present study we investigated the capacity of the memory store underlying the mismatch negativity (MMN) response in musicians and nonmusicians for complex tone patterns. While previous studies have focused either on the kind of information that can be encoded or on the decay of the memory trace over time, we studied capacity in terms of the length of tone sequences, i.e., the number of individual tones that can be fully encoded and maintained. By means of magnetoencephalography (MEG) we recorded MMN responses to deviant tones that could occur at any position of standard tone patterns composed of four, six or eight tones during passive, distracted listening. Whereas there was a reliable MMN response to deviant tones in the four-tone pattern in both musicians and nonmusicians, only some individuals showed MMN responses to the longer patterns. This finding of a reliable capacity of the short-term auditory store underlying the MMN response is in line with estimates of a three to five item capacity of the short-term memory trace from behavioural studies, although pitch and contour complexity covaried with sequence length, which might have led to an understatement of the reported capacity. Whereas there was a tendency for an enhancement of the pattern MMN in musicians compared to nonmusicians, a strong advantage for musicians could be shown in an accompanying behavioural task of detecting the deviants while attending to the stimuli for all pattern lengths, indicating that long-term musical training differentially affects the memory capacity of auditory short-term memory for complex tone patterns with and without attention. Also, a left-hemispheric lateralization of MMN responses in the six-tone pattern suggests that additional networks that help structuring the patterns in the temporal domain might be recruited for demanding auditory processing in the pitch domain.	t	\N
21755126	To assess the difficulty of paced auditory serial addition test (PASAT) in a population of high intellectual level, under ideal cognitive testing circumstances. One hundred medical students underwent PASAT testing. They had slept well the night before, they had eaten before the assessment, they were not using any drugs that could affect the central nervous system and they did not have depression, anxiety or any chronic disease. The average result from the three-second version of PASAT was 57.5% and, from the two-second version, it was 44.3%. Even under ideal circumstances, PASAT is a very difficult test for the general population. It may not be ideal for neurologists to screen, assess and follow up patients with cognitive function in multiple sclerosis.	t	\N
21762032	Reaction times for categorization of a probe face according to its sex or fame were contrasted as a function of whether the category of a preceding, sandwich-masked prime face was congruent or incongruent. Prime awareness was measured by the ability to later categorize the primes, and this was close to chance and typically uncorrelated with priming. When prime faces were never presented as visible probes within a test, priming was not reliable; when prime faces were also seen as probes, priming was only reliable if visible and masked presentation of faces were interleaved (not simply if primes had been visible in a previous session). In the latter case, priming was independent of experimentally induced face-response or face-category contingencies, ruling out any simple form of stimulus-response learning. We conclude that the reliable masked congruency priming reflects bindings between stimuli and multiple, abstract classifications that can be generated both overtly and covertly.	t	\N
21762876	Schizophrenia patients have vocal affect (prosody) deficits that are treatment resistant and associated with negative symptoms and poor outcome. The neural correlates of this dysfunction are unclear. Prior study has suggested that schizophrenia vocal affect perception deficits stem from an inability to use acoustic cues, notably pitch, in decoding emotion. Functional magnetic resonance imaging was performed in 24 schizophrenia patients and 28 healthy control subjects, during the performance of a four-choice (happiness, fear, anger, neutral) vocal affect identification task in which items for each emotion varied parametrically in affective salient acoustic cue levels. We observed that parametric increases in cue levels in schizophrenia failed to produce the same identification rate increases as in control subjects. These deficits correlated with diminished reciprocal activation changes in superior temporal and inferior frontal gyri and reduced temporo-frontal connectivity. Task activation also correlated with independent measures of pitch perception and negative symptom severity. These findings illustrate the interplay between sensory and higher-order cognitive dysfunction in schizophrenia. Sensory contributions to vocal affect deficits also suggest that this neurobehavioral marker could be targeted by pharmacological or behavioral remediation of acoustic feature discrimination.	t	\N
21765387	To compare hearing results in patients undergoing ossiculoplasty using either partial ossicular replacement prosthesis (PORP) or total ossicular replacement prosthesis (TORP) with Silastic banding and malleus relocation techniques in cases with malleus and stapes both present and mobile. Prospective nonrandomized clinical study. Tertiary referral center. Five hundred eighty-five patients undergoing ossiculoplasty were enrolled in this study from April 1991 to May 2010. Comparative analyses were made between a group of 304 patients who underwent ossiculoplasty with partial prosthesis positioned from the malleus to the stapes head and 281 patients who underwent ossiculoplasty with total prosthesis positioned from the malleus to the stapes footplate. Preoperative and postoperative audiometric evaluation using conventional audiometry, that is, air-bone gap (ABG), bone-conduction thresholds, and air-conduction thresholds were assessed. In the PORP group, the mean postoperative ABG was 13.1 dB compared with 8.9 dB in the TORP group, (95% confidence interval [CI], 2.2-6.2 dB; p ≤ 0.001). Fifty-four percent of patients from the PORP group had a postoperative ABG of 10 dB or less, compared with 68.9% in the TORP group (mean difference, 14.6%; 95% CI, 6%-23%; p < 0.001). The postoperative ABG was closed to within 20 dB in 70.4% of cases in the PORP group compared with 86.9% in the TORP group (mean difference, 14.5%; 95% CI, 10%-23%; p < 0.001). In patients with an absent incus and intact stapes and malleus, ossicular reconstruction with TORP combined with our malleus relocation and Silastic banding technique results in significantly better hearing outcomes compared with reconstructions with PORP.	t	\N
21767048	The urge to move in response to music, combined with the positive affect associated with the coupling of sensory and motor processes while engaging with music (referred to as sensorimotor coupling) in a seemingly effortless way, is commonly described as the feeling of being in the groove. Here, we systematically explore this compelling phenomenon in a population of young adults. We utilize multiple levels of analysis, comprising phenomenological, behavioral, and computational techniques. Specifically, we show (a) that the concept of the groove is widely appreciated and understood in terms of a pleasurable drive toward action, (b) that a broad range of musical excerpts can be appraised reliably for the degree of perceived groove, (c) that the degree of experienced groove is inversely related to experienced difficulty of bimanual sensorimotor coupling under tapping regimes with varying levels of expressive constraint, (d) that high-groove stimuli elicit spontaneous rhythmic movements, and (e) that quantifiable measures of the quality of sensorimotor coupling predict the degree of experienced groove. Our results complement traditional discourse regarding the groove, which has tended to take the psychological phenomenon for granted and has focused instead on the musical and especially the rhythmic qualities of particular genres of music that lead to the perception of groove. We conclude that groove can be treated as a psychological construct and model system that allows for experimental exploration of the relationship between sensorimotor coupling with music and emotion.	t	\N
21786896	The form of the psychometric function (PF) for auditory frequency discrimination is of theoretical interest and practical importance. In this study, PFs for pure-tone frequency discrimination were measured for several standard frequencies (200-8000 Hz) and levels [35-85 dB sound pressure level (SPL)] in normal-hearing listeners. The proportion-correct data were fitted using a cumulative-Gaussian function of the sensitivity index, d', computed as a power transformation of the frequency difference, Δf. The exponent of the power function corresponded to the slope of the PF on log(d')-log(Δf) coordinates. The influence of attentional lapses on PF-slope estimates was investigated. When attentional lapses were not taken into account, the estimated PF slopes on log(d')-log(Δf) coordinates were found to be significantly lower than 1, suggesting a nonlinear relationship between d' and Δf. However, when lapse rate was included as a free parameter in the fits, PF slopes were found not to differ significantly from 1, consistent with a linear relationship between d' and Δf. This was the case across the wide ranges of frequencies and levels tested in this study. Therefore, spectral and temporal models of frequency discrimination must account for a linear relationship between d' and Δf across a wide range of frequencies and levels.	t	\N
21787870	Repetition has been shown to activate the so-called 'dorsal stream', a network of temporo-parieto-frontal areas subserving the mapping of acoustic speech input onto articulatory-motor representations. Among these areas, a region in the posterior Sylvian fissure at the temporo-parietal boundary (also called 'area Spt') has been suggested to play a central role particularly with increasing computational demands on phonological processing. Most of the relevant evidence stems from tasks requiring metalinguistic processing. To date, the relevance of area Spt in natural phonological operations based on implicit linguistic knowledge has not yet been investigated. We examined two types of phonological processes assumed to be lateralized differently, i.e., the processing of syllabic stress versus subsyllabic segmental processing. In two ways, subjects modified an auditorily presented pseudoword before reproducing it overtly: (a) by a prosodic manipulation involving a stress shift across syllable boundaries, (b) by a segmental manipulation involving a vowel substitution. Manipulation per se was expected to engage area Spt. Segmental compared to prosodic processing was expected to reveal predominantly left lateralized activation, while prosodic compared to segmental processing was expected to result in bilateral or right-lateralized activation. Contrary to expectation, activation in area Spt did not vary with increased phonological processing demand. Instead, area Spt was engaged regardless of whether subjects simply repeated a pseudoword or performed a phonological manipulation before reproduction. However, for both segmental and prosodic stimuli, reproduction after manipulation (compared to repetition) activated the left intraparietal sulcus and left inferior frontal cortex. We propose that these parieto-frontal regions are recruited when the task requires phonological manipulation over and above the more automated transfer of auditory into articulatory verbal codes, which appears to involve area Spt. When directly contrasted with prosodic manipulation, segmental manipulation resulted in increased activation predominantly in left inferior frontal areas. This may be due to an increased demand on phonological sequencing operations at the subsyllabic phoneme level. Contrasted with segmental manipulations, prosodic manipulation did not result in increased activation, which may be due to a lower degree of morphosyntactic and to syllable-level processing.	t	\N
21792976	To evaluate vestibular function in patients with the mitochondrial A3243G mutation. Data from patients with the A3243G mutation attending an academic tertiary referral center were prospectively recorded. The clinical histories of 13 unrelated patients with the mitochondrial A3243G mutation (six mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; and seven maternally inherited diabetes and deafness) were recorded, in particular their history of vestibular symptoms. Vestibular examinations including caloric testing and vestibular evoked myogenic potentials in response to air-conducted sound (ACS-VEMPs) were performed. In seven patients who showed abnormal ACS-VEMP, VEMP in response to galvanic stimuli (galvanic-VEMP) were also recorded. Eleven of the 13 patients had vestibular symptoms. The age of onset of vestibular symptoms was significantly later than the ages of onset of hearing loss and diabetes mellitus (P < .05). Ten of the 13 patients showed abnormal caloric responses, whereas 12 patients showed abnormal ACS-VEMPs on one or both sides. All of the seven patients who underwent galvanic-VEMP testing showed normal responses. The A3243G mutation is associated with vestibular dysfunction involving both the superior and inferior vestibular nerve systems. Furthermore, our results from galvanic-VEMP testing suggests that a labyrinthine lesion is primarily responsible for the symptoms of vestibular dysfunction.	t	\N
21812557	Several perspectives on speech perception posit a central role for the representation of articulations in speech comprehension, supported by evidence for premotor activation when participants listen to speech. However, no experiments have directly tested whether motor responses mirror the profile of selective auditory cortical responses to native speech sounds or whether motor and auditory areas respond in different ways to sounds. We used fMRI to investigate cortical responses to speech and nonspeech mouth (ingressive click) sounds. Speech sounds activated bilateral superior temporal gyri more than other sounds, a profile not seen in motor and premotor cortices. These results suggest that there are qualitative differences in the ways that temporal and motor areas are activated by speech and click sounds: Anterior temporal lobe areas are sensitive to the acoustic or phonetic properties, whereas motor responses may show more generalized responses to the acoustic stimuli.	t	\N
21812560	Complex auditory exposures in ambient environments include systems of not only linguistic but also musical sounds. Because musical exposure is often passive, consisting of listening rather than performing, examining listeners without formal musical training allows for the investigation of the effects of passive exposure on our nervous system without active use. Additionally, studying listeners who have exposure to more than one musical system allows for an evaluation of how the brain acquires multiple symbolic and communicative systems. In the present fMRI study, listeners who had been exposed to Western-only (monomusicals) and both Indian and Western musical systems (bimusicals) since childhood and did not have significant formal musical training made tension judgments on Western and Indian music. Significant group by music interactions in temporal and limbic regions were found, with effects predominantly driven by between-music differences in temporal regions in the monomusicals and by between-music differences in limbic regions in the bimusicals. Effective connectivity analysis of this network via structural equation modeling (SEM) showed significant path differences across groups and music conditions, most notably a higher degree of connectivity and larger differentiation between the music conditions within the bimusicals. SEM was also used to examine the relationships among the degree of music exposure, affective responses, and activation in various brain regions. Results revealed a more complex behavioral-neural relationship in the bimusicals, suggesting that affective responses in this group are shaped by multiple behavioral and neural factors. These three lines of evidence suggest a clear differentiation of the effects of the exposure of one versus multiple musical systems.	t	\N
21812631	To determine administration times for word recognition presented via monitored live voice (MLV) and compact disc (CD) recordings. A quasi-experimental design was used. Fifty-word NU-6 lists were presented in three conditions: (1) MLV, (2) short ISI CD recording, and (3) long ISI CD recording. Listeners with normal hearing (NH) and hearing impairment (HI) participated in this study. Average administration time using MLV was significantly shorter than using recorded word lists for both groups of listeners. MLV presentation to the NH listeners was significantly faster than the MLV presentation to the HI listeners. There were no significant differences between groups in the administration times for any of the recorded lists (long or short ISI). Considerably more variability in administration time was observed for MLV presentation compared to recorded presentations. MLV presentation was about one minute faster than the shortest CD recording of the NU-6 fifty-item word lists, but it was only 49 seconds quicker when administering tests to individuals with hearing loss. Because the majority of our patients are hearing impaired, the difference of 49 seconds is not clinically significant. This difference is even less when 25-item word lists are used.	t	\N
21812635	The objective of this study was to evaluate hearing loss among workers exposed to styrene, alone or with noise. This cross-sectional study was conducted as part of NoiseChem, a European Commission 5th Framework Programme research project, by occupational health institutes in Finland, Sweden, and Poland. Participants' ages ranged from 18-72 years (n = 1620 workers). Participants exposed to styrene, alone or with noise, were from reinforced fiberglass products manufacturing plants (n = 862). Comparison groups were comprised of workers noise-exposed (n = 400) or controls (n = 358). Current styrene exposures ranged from 0 to 309 mg/m(3), while mean current noise levels ranged from 70-84 dB(A). Hearing thresholds of styrene-exposed participants were compared with Annexes A and B from ANSI S3.44, 1996. The audiometric thresholds of styrene exposed workers were significantly poorer than those in published standards. Age, gender, and styrene exposure met the significance level criterion in the multiple logistic regression for the binary outcome 'hearing loss' (P = 0.0000). Exposure to noise (<85 dBA p = 0.0001; ≥85 dB(A) p = 0.0192) interacted significantly with styrene exposure. Occupational exposure to styrene is a risk factor for hearing loss, and styrene-exposed workers should be included in hearing loss prevention programs.	t	\N
21817926	Recent studies have shown that audiovisual synchrony is recalibrated after exposure to asynchronous auditory and visual signals. This temporal recalibration has been shown only under a dual-task situation for speech signals. Here we examined whether the temporal recalibration occurs for audiovisual speech in a single-task situation using an offline adaptation method. In the experiment, participants were exposed to synchronous or asynchronous audiovisual syllables (either congruent or incongruent) for 3 min. The adaptation phase was followed by test trials, in which participants judged whether the auditory or visual stimulus was presented first. Results showed shifts in the point of subjective simultaneity and the sensitivity. Our results suggest that attention to adaptation stimuli is necessary to induce temporal recalibration for speech.	t	\N
21824022	Attentional bias to threatening visual stimuli (words or pictures) is commonly present in anxious individuals, but not in non-anxious people. There is evidence to show that attentional bias to threat can be induced in all individuals when threat is imposed by threat not of symbolic nature, but by cues that predict aversive stimulation (loud noise or electric shock). However, it is not known whether attentional bias in such situations is still influenced by individual differences in anxiety. This question was addressed in two experiments using a spatial cuing task in which visual cues predicted the occurrence of an aversive event consisting of a loud human scream. Speeded attentional engagement to threat cues was positively correlated with trait anxiety in Experiment 1. Experiment 2 showed that speeded attentional engagement was present only in participants selected for high anxiety but not in low-anxious participants. In both experiments, slower disengagement from threat cues was found in all participants, irrespective of their trait anxiety levels.	t	\N
21826005	Reduced hearing ability has been shown to influence various aspects of daily life, such as communication, psychosocial functioning, and working life. The aim of this study is to examine the association between hearing ability in noise and both sick leave and self-reported work productivity. In addition, the relationship between hearing ability and perceived health-caused limitations at work is examined. Data were collected at the baseline measurement of the Dutch "National Longitudinal Study on Hearing" and at each month during a subsequent period of 3 mo. Hearing ability was determined by means of the National Hearing Test, a speech-in-noise test over the Internet using digit triplets. The sample comprised 748 workers (385 with normal hearing ability and 363 with insufficient or poor hearing ability). Linear regression analyses revealed a significant adverse association between reduced hearing ability and self-reported absolute and differential productivity; for every dB signal-to-noise ratio (dB SNR) poorer hearing ability, self-rated absolute productivity for people experiencing little social support decreased by 0.054 points on a scale from 0 to 10 (b = -0.054; 95% confidence interval [CI] = -0.088 to -0.02). For people with less than three other chronic conditions, self-rated differential productivity also decreased significantly with decreasing hearing ability (no chronic conditions: b = -0.048 points/dB SNR on a scale from -10 to + 10, 95% CI = -0.094 to -0.001; one or two other chronic conditions: b = -0.035 points/dB SNR, 95% CI = -0.067 to -0.002). With adjustment for confounders, poorer hearing ability in noise furthermore significantly increased the odds for experiencing limitations (in the type or amount of work one could do) sometimes (odds ratio = 1.14; 95% CI = 1.07-1.21) and often to very often (odds ratio = 1.24; 95% CI = 1.05-1.45) in comparison with experiencing limitation seldom to never. A higher level of need for recovery among people with poorer hearing ability appeared to be one of the factors mediating the higher odds for sick leave of more than 5 days. Reduced hearing ability in noise was significantly associated with a lower self-reported absolute and differential productivity in specific cases. Also, poorer hearing increased the odds for experiencing health-caused limitations in the type or amount of work one can do. The significant relationship between hearing ability and sick leave, which was found when not adjusting for confounders, could partly be explained by a higher need for recovery among people with reduced hearing ability in noise.	t	\N
21832862	To investigate interactions (if any) in the bone-conduction auditory steady-state response (BC ASSR) between multiple brief tones presented simultaneously. 500-, 1,000-, 2,000-, and 4,000-Hz brief tones, repeated at a rate of 77-101 Hz, were presented using a B-71 vibrator. BC ASSR thresholds and amplitudes at 50 dB nHL were measured in two conditions where the stimulus was either presented alone or together with other stimuli. Significantly larger amplitudes in the single-stimulus condition were found at 50 dB nHL. However, there was no significant threshold difference between single- and multiple-stimulus conditions. The BC ASSR thresholds (means ± SD) at 500, 1,000, 2,000, and 4,000 Hz were 96.7 ± 9.7, 75.3 ± 11.5, 65.6 ± 7.4, and 57.8 ± 7.2 dB re 1 μN ppe, respectively. Interactions occurred in the multiple-stimulus condition at high presentation levels, but not at threshold levels. The results of the present study imply that BC ASSR thresholds to multiple brief-tone stimuli can be assessed at the same time, at least in normal-hearing adults.	t	\N
21832892	This report focuses on how speech perception, speech production, language, and literacy performance in adolescence are influenced by a common set of predictor variables obtained during elementary school in a large group of teenagers using cochlear implants (CIs). Time-lag analyses incorporating seven common predictor variables associated with the elementary school test period were evaluated. The elementary school-age variables included five contributors across the performance domains: gender, performance intelligence quotient, family size, socioeconomic status, and duration of deafness (operationally defined as the time period between the age of implantation and the onset of deafness). Regression analyses then examined how communication mode in early elementary grades influenced skills exhibited in high school and how this influence was mediated by information capacity of immediate memory. High correlations occurred between outcome measures collected at CI-E session and similar measures collected at CI-HS (values ranging from 0.75 to 0.83), indicating that the relative standing of individuals on these outcomes is highly stable over time. The best performers in elementary grades exhibit the best outcomes in high school, and early difficulties tend to persist throughout the elementary and high school years. The most highly related outcome areas were language and reading/literacy (values ranging from 0.74 to 0.88). These skills seem closely linked, and CI children who demonstrate the best vocabulary and syntax skills in elementary grades achieved the highest literacy performance in high school. Speech perception and speech production skills are also highly correlated with one another (r = 0.69 to 0.87), suggesting that the most direct result of improved auditory input from a CI is the child's ability to produce intelligible speech. The lowest correlations are observed between reading/literacy and speech perception (r = 0.30 to 0.54) or speech production (values ranging from 0.31 to 0.58). CI-E verbal rehearsal speed is an independent and powerful predictor of each early performance outcome, accounting for between 13% and 30% of the variance in early outcomes above and beyond that accounted for by gender, family size, socioeconomic status, performance intelligence quotient, duration of deafness, and the CI-E sign enhancement ratio. Group mean scores for language, reading, and social adjustment were generally within an SD of normative samples of typically developing age-mates with normal hearing. Use of sign to enhance spoken communication negatively influenced verbal rehearsal speed, which was a strong predictor of all early outcomes, which in turn strongly influenced later outcomes. These analyses suggest that early communication mode exerts a powerful influence on early outcomes that persist into later years. Speech perception, speech intelligibility, language, literacy, and psychosocial adjustment far exceeded that reported for similar groups before the advent of CI technology.	t	\N
21835531	Behavioral and neurophysiological transfer effects from music experience to language processing are well-established but it is currently unclear whether or not linguistic expertise (e.g., speaking a tone language) benefits music-related processing and its perception. Here, we compare brainstem responses of English-speaking musicians/non-musicians and native speakers of Mandarin Chinese elicited by tuned and detuned musical chords, to determine if enhancements in subcortical processing translate to improvements in the perceptual discrimination of musical pitch. Relative to non-musicians, both musicians and Chinese had stronger brainstem representation of the defining pitches of musical sequences. In contrast, two behavioral pitch discrimination tasks revealed that neither Chinese nor non-musicians were able to discriminate subtle changes in musical pitch with the same accuracy as musicians. Pooled across all listeners, brainstem magnitudes predicted behavioral pitch discrimination performance but considering each group individually, only musicians showed connections between neural and behavioral measures. No brain-behavior correlations were found for tone language speakers or non-musicians. These findings point to a dissociation between subcortical neurophysiological processing and behavioral measures of pitch perception in Chinese listeners. We infer that sensory-level enhancement of musical pitch information yields cognitive-level perceptual benefits only when that information is behaviorally relevant to the listener.	t	\N
21840170	This study investigates the effect of consensus training of listeners on intrarater and interrater reliability and agreement of perceptual voice analysis. The use of such training, including a reference voice sample, could be assumed to make the internal standards held in memory common and more robust, which is of great importance to reduce the variability of auditory perceptual ratings. A prospective design with testing before and after training. Thirteen students of audiologopedics served as listening subjects. The ratings were made using a multidimensional protocol with four-point equal-appearing interval scales. The stimuli consisted of text reading by authentic dysphonic patients. The consensus training for each perceptual voice parameter included (1) definition, (2) underlying physiology, (3) presentation of carefully selected sound examples representing the parameter in three different grades followed by group discussions of perceived characteristics, and (4) practical exercises including imitation to make use of the listeners' proprioception. Intrarater reliability and agreement showed a marked improvement for intermittent aphonia but not for vocal fry. Interrater reliability was high for most parameters before training with a slight increase after training. Interrater agreement showed marked increases for most voice quality parameters as a result of the training. The results support the recommendation of specific consensus training, including use of a reference voice sample material, to calibrate, equalize, and stabilize the internal standards held in memory by the listeners.	t	\N
21842332	The visible movement of a talker's face is an influential component of speech perception. However, the ability of this influence to function when large areas of the face (~50%) are covered by simple substantial occlusions, and so are not visible to the observer, has yet to be fully determined. In Experiment 1, both visual speech identification and the influence of visual speech on identifying congruent and incongruent auditory speech were investigated using displays of a whole (unoccluded) talking face and of the same face occluded vertically so that the entire left or right hemiface was covered. Both the identification of visual speech and its influence on auditory speech perception were identical across all three face displays. Experiment 2 replicated and extended these results, showing that visual and audiovisual speech perception also functioned well with other simple substantial occlusions (horizontal and diagonal). Indeed, displays in which entire upper facial areas were occluded produced performance levels equal to those obtained with unoccluded displays. Occluding entire lower facial areas elicited some impairments in performance, but visual speech perception and visual speech influences on auditory speech perception were still apparent. Finally, implications of these findings for understanding the processes supporting visual and audiovisual speech perception are discussed.	t	\N
21846981	The Nucleus Straight Research Array (SRA) cochlear implant has a new 25-mm electrode carrier designed to minimize insertion trauma, in particular allowing easy insertion via the round window. The aims of this study were to measure preoperative to postoperative benefit in terms of speech recognition in quiet and in noise in three groups of patients (electrical complement, EC; electrical stimulation, ES; electro-acoustic stimulation, EAS) with varying levels of low-frequency hearing, and to evaluate the preservation of residual hearing after implantation with the SRA cochlear implant. The study design was prospective with sequential enrolment and within-subject comparisons: 23 adult cochlear implant candidates were divided into three groups according to their level of preoperative residual hearing at 500 Hz (EC ≤50 dB; 50 dB < EAS < 80 dB; ES ≥80 dB). Monosyllabic word recognition using the SRA cochlear implant in combination with residual low-frequency hearing was assessed at 4 and 13 months after implantation. Hearing threshold levels were also monitored over time. Subjects across all three groups had significant improvements in speech recognition scores (i.e. >20 percentage points) both for listening in quiet (71% of subjects) and in noise (100% of subjects). The average score at 4 months after operation for words presented in quiet was 61.7%, and in 10 dB SNR noise 46.5%, compared to 34.4 and 10.6% preoperatively (p < 0.001). All subjects retained measurable hearing at 500 Hz in the implanted ear at 4 months after the operation; mean increases were 19, 29 and 1 dB for the EC, EAS and ES groups (n = 21). Across frequencies of 125-1000 Hz, the median increase in thresholds was 15 dB up to 13 months postoperatively (n = 15). Speech recognition performance of subjects with various levels of residual low-frequency hearing was significantly improved with the SRA cochlear implant. A high level and rate of hearing preservation was achieved with the SRA implanted using a round window surgical technique. Subjects with preoperative low-frequency hearing levels between 50 and 80 dB HL (EAS group) tended to lose more hearing than those with either better or worse hearing.	t	\N
21848924	Tinnitus is characterized by an ongoing conscious perception of a sound in the absence of any external sound source. Chronic tinnitus is notoriously characterized by its resistance to treatment. In the present study the objective was to verify whether the neural generators and/or the neural tinnitus network, evaluated through EEG recordings, change over time as previously suggested by MEG. We therefore analyzed the source-localized EEG recordings of a very homogenous group of left-sided narrow-band noise tinnitus patients. Results indicate that the generators involved in tinnitus of recent onset seem to change over time with increased activity in several brain areas [auditory cortex, supplementary motor area and dorsal anterior cingulate cortex (dACC) plus insula], associated with a decrease in connectivity between the different auditory and nonauditory brain structures. An exception to this general connectivity decrease is an increase in gamma-band connectivity between the left primary and secondary auditory cortex and the left insula, and also between the auditory cortices and the right dorsal lateral prefrontal cortex. These networks are both connected to the left parahippocampal area. Thus acute and chronic tinnitus are related to differential activity and connectivity in a network comprising the auditory cortices, insula, dACC and premotor cortex.	t	\N
21849065	Segregating auditory scenes into distinct objects or streams is one of our brain's greatest perceptual challenges. Streaming has classically been studied with bistable sound stimuli, perceived alternately as a single group or two separate groups. Throughout the last decade different methodologies have yielded inconsistent evidence about the role of auditory cortex in the maintenance of streams. In particular, studies using functional magnetic resonance imaging (fMRI) have been unable to show persistent activity within auditory cortex (AC) that distinguishes between perceptual states. We use bistable stimuli, an explicit perceptual categorization task, and a focused region of interest (ROI) analysis to demonstrate an effect of perceptual state within AC. We find that AC has more activity when listeners perceive the split percept rather than the grouped percept. In addition, within this ROI the pattern of acoustic response across voxels is significantly correlated with the pattern of perceptual modulation. In a whole-brain exploratory test, we corroborate previous work showing an effect of perceptual state in the intraparietal sulcus. Our results show that the maintenance of auditory streams is reflected in AC activity, directly relating sound responses to perception, and that perceptual state is further represented in multiple, higher level cortical regions.	t	\N
21861386	The listener-distinctive features of recognition of different emotional intonations (positive, negative and neutral) of male and female speakers in the presence or absence of background noise were studied in 49 adults aged 20-79 years. In all the listeners noise produced the most pronounced decrease in recognition accuracy for positive emotional intonation ("joy") as compared to other intonations, whereas it did not influence the recognition accuracy of "anger" in 65-79-year-old listeners. The higher emotion recognition rates of a noisy signal were observed for speech emotional intonations expressed by female speakers. Acoustic characteristics of noisy and clear speech signals underlying perception of speech emotional prosody were found for adult listeners of different age and gender.	t	\N
21862447	The distractibility that older adults experience when listening to speech in challenging conditions has been attributed in part to reduced inhibition of irrelevant information within and across sensory systems. Whereas neuroimaging studies have shown that younger adults readily suppress visual cortex activation when listening to auditory stimuli, it is unclear the extent to which declining inhibition in older adults results in reduced suppression or compensatory engagement of other sensory cortices. The current functional magnetic resonance imaging study examined the effects of age and stimulus intelligibility in a word listening task. Across all participants, auditory cortex was engaged when listening to words. However, increasing age and declining word intelligibility had independent and spatially similar effects: both were associated with increasing engagement of visual cortex. Visual cortex activation was not explained by age-related differences in vascular reactivity but rather auditory and visual cortices were functionally connected across word listening conditions. The nature of this correlation changed with age: younger adults deactivated visual cortex when activating auditory cortex, middle-aged adults showed no relation, and older adults synchronously activated both cortices. These results suggest that age and stimulus integrity are additive modulators of crossmodal suppression and activation.	t	\N
21875609	Event-related potential (ERP) evidence indicates that listeners selectively attend to word onsets in continuous speech, but the reason for this preferential processing is unknown. The current study measured ERPs elicited by syllable onsets in an artificial language to test the hypothesis that listeners direct attention to word onsets because their identity is unpredictable. Both before and after recognition training, participants listened to a continuous stream of six nonsense words arranged in pairs, such that the second word in each pair was completely predictable. After training, first words in pairs elicited a larger negativity beginning around 100 ms after onset. This effect was not evident for the completely predictable second words in pairs. These results suggest that listeners are most likely to attend to the segments in speech that they are least able to predict.	t	\N
21877811	The conventional articulation index (AI) measure cannot be applied in situations where non-linear operations are involved and additive noise is present. This is because the definitions of the target and masker signals become vague following non-linear processing, as both the target and masker signals are affected. The aim of the present work is to modify the basic form of the AI measure to account for non-linear processing. This was done using a new definition of the output or effective SNR obtained following non-linear processing. The proposed output SNR definition for a specific band was designed to handle cases where the non-linear processing affects predominantly the target signal rather than the masker signal. The proposed measure also takes into consideration the fact that the input SNR in a specific band cannot be improved following any form of non-linear processing. Overall, the proposed measure quantifies the proportion of input band SNR preserved or transmitted in each band after non-linear processing. High correlation (r = 0.9) was obtained with the proposed measure when evaluated with intelligibility scores obtained by normal-hearing listeners in 72 noisy conditions involving noise-suppressed speech corrupted in four different real-world maskers.	t	\N
21884311	Infants attune to their birth language during the second half of infancy. However, internationally adopted children are often uniquely required to attune to their birth language, and then reattune to their adoptive language. Children who were adopted from India into America at ages 6-60 months (N = 8) and had minimal further exposure to their birth languages were compared to age-matched American non-adopted controls. Without training, neither group could discriminate a phonemic contrast that occurs in their birth language but not in English. However, after training on the contrast, the adopted group (N = 8) improved significantly and discriminated the contrast more accurately than their non-adopted peers. While English had explicitly replaced the birth language of the adopted sample, traces of early exposure conferred privileges on subsequent learning. These findings are consistent with behavioral and neurophysiological data from animals that have identified some of the mechanisms underlying such a 'retention without further use' phenomenon.	t	\N
21895386	An important step in developing a theory of calibration is establishing what it is that participants become calibrated to as a result of feedback. Three experiments used a transfer of calibration paradigm to investigate this issue. In particular, these experiments investigated whether recalibration of perception of length transferred from audition to dynamic (i.e., kinesthetic) touch when objects were grasped at one end (Experiment 1), when objects were grasped at one end and when they were grasped at a different location (i.e., the middle) (Experiment 2), and when false (i.e., inflated) feedback was provided about object length (Experiment 3). In all three experiments, there was a transfer of recalibration of perception of length from audition to dynamic touch when feedback was provided on perception by audition. Such results suggest that calibration is not specific to a particular perceptual modality and are also consistent with previous research that perception of object length by audition and dynamic touch are each constrained by the object's mechanical properties.	t	\N
21898434	To determine the effect of cochlear implantation (CI) on health-related quality of life (HRQoL), tinnitus, and psychological comorbidity in patients with severe to profound postlingual hearing loss and to analyze the relationship between these parameters. Prospective study. Using six validated questionnaires, we evaluated the pre-CI and post-CI scores of HRQoL, tinnitus, perceived stress, symptoms of depression and anxiety, and coping strategies in 43 patients implanted unilaterally with a multichannel implant for at least 6 months. In addition to improvements in hearing, speech understanding, and disease-specific HRQoL, psychological comorbidity was reduced and coping strategies were improved following CI. In the 39 tinnitus patients, their tinnitus was reduced. We found negative correlations between HRQoL and stress, depression, and anxiety. Pre-CI, tinnitus severity did not correlate with HRQoL and psychological comorbidity. However, patients with a high-level tinnitus had lower HRQoL as well as a higher level of perceived stress and anxiety symptoms than patients with a low-level tinnitus and no/incidental tinnitus before CI. Moreover, patients with severe hearing loss had a higher level of perceived symptoms of stress and depression than patients with profound hearing loss before CI. The present study provides evidence that tinnitus and psychological comorbidity may play an important role in the rehabilitation of CI patients, and that there is a correlation between HRQoL and these parameters. In addition to hearing tests, tinnitus, stress, and psychological comorbidity should be assessed using validated questionnaires before and after CI. This will help to improve the rehabilitation process.	t	\N
21902007	The purpose of the present study was to see if 7-10-year-old socially anxious children (n = 26) made systematic errors in identifying and sending emotions in facial expressions, paralanguage, and postures as compared with the more random errors of children who were inattentive-hyperactive (n = 21). It was found that socially anxious children made more errors in identifying anger and fear in children's facial expressions and anger in adults' postures and in expressing anger in their own facial expressions than did their inattentive-hyperactive peers. Results suggest that there may be systematic difficulties specifically in visual nonverbal emotion communication that contribute to the personal and social difficulties socially anxious children experience.	t	\N
21902880	In visual competition, the perception of ambiguous visual patterns changes spontaneously. Although the process causing this perceptual alternation remains unclear, recent evidence suggests various types of non-visual influences in resolving visual ambiguity. In the present study, we investigated cross-modal modulation of a transient stimulus on visual perceptual stability (i.e., alternation frequency). Participants observed an ambiguous visual figure and reported their perceptual alternations. Concurrently, we presented visual and auditory transient events. The results revealed that the auditory as well as visual transient events destabilize the current perception (i.e., they increase alternation frequency) around 0.5-1.5 s after the event. In addition, the magnitudes of auditory and visual effects were comparable and positively correlated within participants. These results suggest that the visual perceptual stability can be under the influence of processes that are shared by different senses.	t	\N
21903084	Rainstorms, insect swarms, and galloping horses produce "sound textures"--the collective result of many similar acoustic events. Sound textures are distinguished by temporal homogeneity, suggesting they could be recognized with time-averaged statistics. To test this hypothesis, we processed real-world textures with an auditory model containing filters tuned for sound frequencies and their modulations, and measured statistics of the resulting decomposition. We then assessed the realism and recognizability of novel sounds synthesized to have matching statistics. Statistics of individual frequency channels, capturing spectral power and sparsity, generally failed to produce compelling synthetic textures; however, combining them with correlations between channels produced identifiable and natural-sounding textures. Synthesis quality declined if statistics were computed from biologically implausible auditory models. The results suggest that sound texture perception is mediated by relatively simple statistics of early auditory representations, presumably computed by downstream neural populations. The synthesis methodology offers a powerful tool for their further investigation.	t	\N
21904250	The diversion of attention from a primary goal by irrelevant events is known as attention capture, and is often followed by a directed action. The hypothesis that corticospinal excitability is modulated by attention capture was tested using transcranial magnetic stimulation. Participants watched a video while sounds were intermittently presented. Motor evoked potentials (MEPs) were elicited in each hand using transcranial magnetic stimulation 1 s after sound onset. MEP amplitudes were assessed as a function of hand (dominant, nondominant), sound location (ipsilateral or contralateral to hand location), and sound sample valence (negative, neutral, positive). Results showed that MEP amplitudes increased during sound presentation, but only for the dominant hand. There were no effects of location or emotional valence. The selective modulation of the dominant hand motor cortex may indicate that auditory events can prime the preferred hand for action.	t	\N
21909974	A key requirement for encoding the auditory environment is the ability to dynamically alter cochlear sensitivity. However, merely attaining a steady state of maximal sensitivity is not a viable solution since the sensory cells and ganglion cells of the cochlea are prone to damage following exposure to loud sound. Most often, such damage is via initial metabolic insult that can lead to cellular death. Thus, establishing the highest sensitivity must be balanced with protection against cellular metabolic damage that can lead to loss of hair cells and ganglion cells, resulting in loss of frequency representation. While feedback mechanisms are known to exist in the cochlea that alter sensitivity, they respond only after stimulus encoding, allowing potentially damaging sounds to impact the inner ear at times coincident with increased sensitivity. Thus, questions remain concerning the endogenous signaling systems involved in dynamic modulation of cochlear sensitivity and protection against metabolic stress. Understanding endogenous signaling systems involved in cochlear protection may lead to new strategies and therapies for prevention of cochlear damage and consequent hearing loss. We have recently discovered a novel cochlear signaling system that is molecularly equivalent to the classic hypothalamic-pituitary-adrenal (HPA) axis. This cochlear HPA-equivalent system functions to balance auditory sensitivity and susceptibility to noise-induced hearing loss, and also protects against cellular metabolic insults resulting from exposures to ototoxic drugs. We review the anatomy, physiology, and cellular signaling of this system, and compare it to similar signaling in other organs/tissues of the body.	t	\N
21914244	How do children develop the mapping between prosody and other levels of linguistic knowledge? This question has received considerable attention in child language research. In the present study two experiments were conducted to investigate four- to five-year-old Mandarin-speaking children's sensitivity to prosody in ambiguity resolution. Experiment 1 used eye-tracking to assess children's use of stress in resolving structural ambiguities. Experiment 2 took advantage of special properties of Mandarin to investigate whether children can use intonational cues to resolve ambiguities involving speech acts. The results of our experiments show that children's use of prosodic information in ambiguity resolution varies depending on the type of ambiguity involved. Children can use prosodic information more effectively to resolve speech act ambiguities than to resolve structural ambiguities. This finding suggests that the mapping between prosody and semantics/pragmatics in young children is better established than the mapping between prosody and syntax.	t	\N
21916216	Processing of auditory information in central nervous system bases on the series of quickly occurring neural processes that cannot be separately monitored using only the fMRI registration. Simultaneous recording of the auditory evoked potentials, characterized by good temporal resolution, and the functional magnetic resonance imaging with excellent spatial resolution allows studying higher auditory functions with precision both in time and space. was to implement the simultaneous AEP-fMRI recordings method for the investigation of information processing at different levels of central auditory system. Five healthy volunteers, aged 22-35 years, participated in the experiment. The study was performed using high-field (3T) MR scanner from Siemens and 64-channel electrophysiological system Neuroscan from Compumedics. Auditory evoked potentials generated by acoustic stimuli (standard and deviant tones) were registered using modified odd-ball procedure. Functional magnetic resonance recordings were performed using sparse acquisition paradigm. The results of electrophysiological registrations have been worked out by determining voltage distributions of AEP on skull and modeling their bioelectrical intracerebral generators (dipoles). FMRI activations were determined on the basis of deviant to standard and standard to deviant functional contrasts. Results obtained from electrophysiological studies have been integrated with functional outcomes. Morphology, amplitude, latency and voltage distribution of auditory evoked potentials (P1, N1, P2) to standard stimuli presented during simultaneous AEP-fMRI registrations were very similar to the responses obtained outside scanner room. Significant fMRI activations to standard stimuli were found mainly in the auditory cortex. Activations in these regions corresponded with N1 wave dipoles modeled based on auditory potentials generated by standard tones. Auditory evoked potentials to deviant stimuli were recorded only outside the MRI scanner. However, deviant stimuli induced significant fMRI activations. They were observed mainly in the anterior cingulate gyrus, insula and parietal lobes. These regions of the brain are related to attention and decision-making processes. The results showed that applied paradigm is suitable for investigation of acoustic processing on the level of auditory cortex. Technique of the simultaneous AEP-fMRI registrations seems to be promising for investigation of more complex nervous processes in central auditory system with good temporo-spatial resolution.	t	\N
21917204	Modern health services need efficient tools for measuring outcomes from interventions, that is, tools of proven efficacy which make minimal demands on the time of clinicians in learning to administer tests and in interpreting results. This paper describes an apparatus designed to meet those requirements. The apparatus administers performance tests of spatial listening for children and adults with unilateral and bilateral cochlear implants. The apparatus was designed with guidance from clinicians. It possesses three key attributes: it is simple to use; the results of tests are scored automatically and are compared with reference data; the apparatus generates comprehensive personalized reports for individual participants that can be included in clinical notes. This paper describes the apparatus and reports results of a test measuring spatial release from masking of speech which illustrates the compatibility between the new apparatus and an older apparatus with which the reference data were gathered.	t	\N
21917210	Bilateral cochlear implants (CIs) have been provided to children who are deaf in both ears with intent to promote binaural hearing. If it is possible to establish binaural hearing with two CIs, these children would be able to make use of interaural level and timing differences to localize sound and to distinguish between sounds separated in space. These skills are central to the ability to attend to one particular sound amidst a number of sound sources. This may be particularly important for children because they are typically learning and interacting in groups. However, the development of binaural processing could be disrupted by effects of bilateral deafness, effects of unilateral CI use, or issues related to the child's age at onset of deafness and age at the time of the first and second cochlear implantation. This research aims to determine whether binaural auditory processing is affected by these variables in an effort to determine the optimal timing for bilateral cochlear implantation in children. It is now clear that the duration of bilateral deafness should be limited in children to restrict reorganization in the auditory thalamo-cortical pathways. It has also been shown that unilateral CI use can halt such reorganization to some extent and promote auditory development. At the same time, however, unilateral input might compromise the development of binaural processing if CIs are provided sequentially. Mismatches in responses from the auditory brainstem and cortex evoked by the first and second CI after a long period of unilateral CI use suggest asymmetry in the bilateral auditory pathways which is significantly more pronounced than in children receiving bilateral implants simultaneously. Moreover, behavioural responses to level and timing differences between implants suggest that these important binaural cues are not being processed normally by children who received a second CI after a long period of unilateral CI use and at older ages. In sum, there may be multiple sensitive periods in the developing auditory system, which must be considered when determining the optimal timing for bilateral cochlear implantation.	t	\N
21918451	To determine whether common approaches to setting stimulus parameters influence the depth of fine structure present in the distortion product otoacoustic emission (DPOAE) response. Because the presence of fine structure has been suggested as a possible source of errors, if one of the common parametric approaches results in reduced fine-structure depth, it may be preferred over other approaches. DPOAE responses were recorded in a group of 21 subjects with normal hearing for 1/3-octave intervals surrounding 3 f2s (1, 2, and 4 kHz) at three L2s (30, 45, and 55 dB SPL). For each f2 and L2 combination, L1 and f2/f1 were set according to three commonly used parametric approaches. These included a simple approach, the approach recommended by Kummer et al., and the approach described by Johnson et al. These three approaches primarily differ in the recommended relationship between L1 and L2. For each parametric approach, DPOAE fine structure was evaluated by varying f2 in small steps. Differences in DPOAE level and DPOAE fine-structure depth across f2, L2, and the various stimulus parameters were evaluated using repeated-measures analysis of variance. As expected, significant variations in DPOAE level were observed across the three parametric approaches. For stimulus levels #45 dB SPL, the simple stimuli resulted in lower DPOAE levels than were observed for other approaches. An unexpected finding was that stimulus parameters developed by Johnson et al., which were believed to produce higher DPOAE levels than other approaches, produced the lowest DPOAE levels of the three approaches when f2 = 4 kHz. Significant differences in fine-structure depth were also observed. Greater fine-structure depth was observed with the simple parameters, although this effect was restricted to L2 # 45 dB SPL. When L2 = 55 dB SPL, all three parametric approaches resulted in equivalent fine-structure depth. A significant difference in fine-structure depth across the 3 f2s was also observed. The interval surrounding 2 kHz was associated with greater fine-structure depth than the intervals surrounding 1 and 4 kHz. The simple stimulus parameters resulted in more fine structure than the other parametric approaches; however, this effect was restricted to L2 # 45 dB SPL. At the moderate stimulus levels used in most clinical applications of DPOAEs (L2 = 55 dB SPL), all three approaches resulted in similar fine-structure depths. These findings suggest that manipulating stimulus parameters, particularly the L1, L2 relationship, is not an effective technique for reducing fine structure, except at the lowest stimulus levels, and that all the common parameters result in equivalent fine structure for moderate stimulus levels. These results also suggest that the stimulus parameters used in future studies of the clinical implications of fine structure may be relatively unimportant, unless stimulus levels #45 dB SPL will be evaluated.	t	\N
21921852	Bilateral stimulation through cochlear implants induces a brain activity pattern closer to the normal one than unilateral stimulation. Although it has been shown that speech comprehension through bilateral cochlear implants leads to better performances than after unilateral implantation, the existence of neural underpinnings of this improvement remains to be studied. We performed an H2O positron emission tomographic study of word recognition in 5 patients with bilateral cochlear implants and 5 normal-hearing controls. Subjects had to distinguish words from nonwords in binaural and monaural conditions. There was no overactivation in patients for binaural stimulation, with a hypoactivation in the right temporal cortex. For monaural stimulation, patients demonstrated more activation contralaterally to the stimulation side in the posterior temporal cortex and in the cerebellum. Binaural stimulation through cochlear implants is advantageous compared with the monaural at the neurofunctional level because the pattern of brain activity is closer to the normal one.	t	\N
21924100	To explore the factors that influence the stability of evaluation results judged by a jury through a standard research on perceptual evaluation measurements of voice quality. Voice samples from 300 patients with dysphonia and 100 control subjects with normal voice were recorded and assessed by a jury composed of 6 experienced listeners from different hospitals. The voice samples were discourse voices and ordered randomly 3 times, and the mean of 3 evaluations using visual analogue scale were the final results. The jury was instructed to classify voice samples according to the G (grade), R (rough) and B (breathy) components of the GRBAS scale on a 4-point scale ranging from 0 for normal to 3 for severe dysphonia. Κ value was used to analyze the concordance of evaluation results and regression analysis was used to research the effects of the extent of voice disorder to the stability of perceptual evaluation. The discordance of evaluation existed both between the jury and in listeners themselves. The concordance of listeners themselves of each evaluation parameter was not bad, good, or even very good, and the concordance of evaluation of G was the best (κ value: 0.46 - 0.85), then R (κ value: 0.41 - 0.84) and B (κ value: 0.41 - 0.81). The concordance between the jury was worse than that in themselves. And except a listener whose concordance of evaluation was under the requirement, the concordance of evaluation of G was the best (κ value: 0.43 - 0.96), then R (κ value: 0.33 - 0.78) and B (κ value: 0.002 - 0.45). The stability of evaluation of normal voice and severe voice disorder was better than mild and moderate voice disorder. The discordance between the jury was the main factor that influence the stability of perceptual evaluation. The evaluation parameters and extent of voice disorder will influence the stability of perceptual evaluation of the jury.	t	\N
21925521	The left inferior frontal gyrus (LIFG) exhibits increased responsiveness when people listen to words composed of speech sounds that frequently co-occur in the English language (Vaden, Piquado, & Hickok, 2011), termed high phonotactic frequency (Vitevitch & Luce, 1998). The current experiment aimed to further characterize the relation of phonotactic frequency to LIFG activity by manipulating word intelligibility in participants of varying age. Thirty six native English speakers, 19-79 years old (mean=50.5, sd=21.0) indicated with a button press whether they recognized 120 binaurally presented consonant-vowel-consonant words during a sparse sampling fMRI experiment (TR=8 s). Word intelligibility was manipulated by low-pass filtering (cutoff frequencies of 400 Hz, 1000 Hz, 1600 Hz, and 3150 Hz). Group analyses revealed a significant positive correlation between phonotactic frequency and LIFG activity, which was unaffected by age and hearing thresholds. A region of interest analysis revealed that the relation between phonotactic frequency and LIFG activity was significantly strengthened for the most intelligible words (low-pass cutoff at 3150 Hz). These results suggest that the responsiveness of the left inferior frontal cortex to phonotactic frequency reflects the downstream impact of word recognition rather than support of word recognition, at least when there are no speech production demands.	t	\N
21932260	Cross-modal processing enables the utilization of information received via different sensory organs to facilitate more complicated human actions. We used functional MRI on early-blind individuals to study the neural processes associated with cross auditory-spatial learning. The auditory signals, converted from echoes of ultrasonic signals emitted from a navigation device, were novel to the participants. The subjects were trained repeatedly for 4 weeks in associating the auditory signals with different distances. Subjects' blood-oxygenation-level-dependent responses were captured at baseline and after training using a sound-to-distance judgment task. Whole-brain analyses indicated that the task used in the study involved auditory discrimination as well as spatial localization. The learning process was shown to be mediated by the inferior parietal cortex and the hippocampus, suggesting the integration and binding of auditory features to distances. The right cuneus was found to possibly serve a general rather than a specific role, forming an occipital-enhanced network for cross auditory-spatial learning. This functional network is likely to be unique to those with early blindness, since the normal-vision counterparts shared activities only in the parietal cortex.	t	\N
21936759	The present study investigated the relationship between non-verbal behaviours and perceptions of the communication abilities of an individual with anomia secondary to traumatic brain injury (TBI). Thirty-four university students studying Communication Sciences and Disorders were randomly assigned to watch or listen to six short clips of an individual with TBI engaged in conversation. Participants rated the individual on communication parameters from a modified version of the Pragmatic Protocol and four other dependent measures of communicative competence. A significant positive correlation was identified between perceptions of gestures and ratings of overall communicative competence, and between perceptions of hand and arm movements and ratings of overall communicative competence. Participant raters who viewed the individual's movements as inappropriate also rated her overall communication abilities less favourably. This finding highlights individuality in perception of communication competence and the importance of assessing communication partners' perceptions in a client's environment to determine socially relevant treatment goals.	t	\N
21939965	Listeners rapidly adjust to talkers' pronunciations, accommodating those pronunciations into the relevant phonemic category to improve subsequent perception. Previous work has suggested that such learning is restricted to pronunciations that are representative of how the speaker talks (Kraljic, Samuel, & Brennan, 2008). If an ambiguous pronunciation, for example, can be attributed to an external source (such as a pen in the speaker's mouth), or if it is preceded by normal pronunciations of the same sound, learning is blocked. In three experiments, we explore this blocking effect in more detail. Our aim is to better understand the nature of the representations underlying the perceptual learning process. Experiment 1 replicates the blocking effect. Experiments 2 and 3 demonstrate that it can be eliminated when certain visual information occurs simultaneously with the auditory signal. The pattern of learning and non-learning is best accounted for by the view that speech perception is mediated by episodic representations that include potentially relevant visual information.	t	\N
21940463	Several studies report that adults and adolescents with reading disabilities also experience difficulties with selective attention. In the present study, event-related brain potentials (ERPs) were used to examine the neural mechanisms of selective attention in kindergarten children at risk for reading disabilities (AR group, n = 8) or on track in early literacy skills (OT group, n = 6) across the first semester of kindergarten. The AR group also received supplemental instruction with the Early Reading Intervention (ERI). Following ERI, the AR group demonstrated improved skills on standardized early literacy measures such that there were no significant differences between the AR and OT groups at posttest or winter follow-up. Analysis of the ERP data revealed that at the start of kindergarten, the AR group displayed reduced effects of attention on sensorineural processing compared to the OT group. Following intervention, this difference between groups disappeared, with the AR group only showing improvements in the effect of attention on sensorineural processing. These data indicate that the neural mechanisms of selective attention are atypical in kindergarten children at risk for reading failure but can be improved by effective reading interventions.	t	\N
21942418	We report a series of experiments designed to demonstrate that the presentation of a sound can facilitate the identification of a concomitantly presented visual target letter in the backward masking paradigm. Two visual letters, serving as the target and its mask, were presented successively at various interstimulus intervals (ISIs). The results demonstrate that the crossmodal facilitation of participants' visual identification performance elicited by the presentation of a simultaneous sound occurs over a very narrow range of ISIs. This critical time-window lies just beyond the interval needed for participants to differentiate the target and mask as constituting two distinct perceptual events (Experiment 1) and can be dissociated from any facilitation elicited by making the visual target physically brighter (Experiment 2). When the sound is presented at the same time as the mask, a facilitatory, rather than an inhibitory effect on visual target identification performance is still observed (Experiment 3). We further demonstrate that the crossmodal facilitation of the visual target by the sound depends on the establishment of a reliable temporally coincident relationship between the two stimuli (Experiment 4); however, by contrast, spatial coincidence is not necessary (Experiment 5). We suggest that when visual and auditory stimuli are always presented synchronously, a better-consolidated object representation is likely to be constructed (than that resulting from unimodal visual stimulation).	t	\N
21945200	The human auditory brainstem is known to be exquisitely sensitive to fine-grained spectro-temporal differences between speech sound contrasts, and the ability of the brainstem to discriminate between these contrasts is important for speech perception. Recent work has described a novel method for translating brainstem timing differences in response to speech contrasts into frequency-specific phase differentials. Results from this method have shown that the human brainstem response is surprisingly sensitive to phase differences inherent to the stimuli across a wide extent of the spectrum. Here we use an animal model of the auditory brainstem to examine whether the stimulus-specific phase signatures measured in human brainstem responses represent an epiphenomenon associated with far-field (i.e., scalp-recorded) measurement of neural activity, or alternatively whether these specific activity patterns are also evident in auditory nuclei that contribute to the scalp-recorded response, thereby representing a more fundamental temporal processing phenomenon. Responses in anaesthetized guinea pigs to three minimally-contrasting consonant-vowel stimuli were collected simultaneously from the cortical surface vertex and directly from central nucleus of the inferior colliculus (ICc), measuring volume conducted neural activity and multiunit, near-field activity, respectively. Guinea pig surface responses were similar to human scalp-recorded responses to identical stimuli in gross morphology as well as phase characteristics. Moreover, surface-recorded potentials shared many phase characteristics with near-field ICc activity. Response phase differences were prominent during formant transition periods, reflecting spectro-temporal differences between syllables, and showed more subtle differences during the identical steady state periods. ICc encoded stimulus distinctions over a broader frequency range, with differences apparent in the highest frequency ranges analyzed, up to 3000 Hz. Based on the similarity of phase encoding across sites, and the consistency and sensitivity of response phase measured within ICc, results suggest that a general property of the auditory system is a high degree of sensitivity to fine-grained phase information inherent to complex acoustical stimuli. Furthermore, results suggest that temporal encoding in ICc contributes to temporal features measured in speech-evoked scalp-recorded responses.	t	\N
21949873	The modulation of brain activity as a function of auditory location was investigated using electro-encephalography in combination with standardized low-resolution brain electromagnetic tomography. Auditory stimuli were presented at various positions under anechoic conditions in free-field space, thus providing the complete set of natural spatial cues. Variation of electrical activity in cortical areas depending on sound location was analyzed by contrasts between sound locations at the time of the N1 and P2 responses of the auditory evoked potential. A clear-cut double dissociation with respect to the cortical locations and the points in time was found, indicating spatial processing (1) in the primary auditory cortex and posterodorsal auditory cortical pathway at the time of the N1, and (2) in the anteroventral pathway regions about 100 ms later at the time of the P2. Thus, it seems as if both auditory pathways are involved in spatial analysis but at different points in time. It is possible that the late processing in the anteroventral auditory network reflected the sharing of this region by analysis of object-feature information and spectral localization cues or even the integration of spatial and non-spatial sound features.	t	\N
21957257	Children use information from both the auditory and visual modalities to aid in understanding speech. A dramatic illustration of this multisensory integration is the McGurk effect, an illusion in which an auditory syllable is perceived differently when it is paired with an incongruent mouth movement. However, there are significant interindividual differences in McGurk perception: some children never perceive the illusion, while others always do. Because converging evidence suggests that the posterior superior temporal sulcus (STS) is a critical site for multisensory integration, we hypothesized that activity within the STS would predict susceptibility to the McGurk effect. To test this idea, we used BOLD fMRI in 17 children aged 6-12 years to measure brain responses to the following three audiovisual stimulus categories: McGurk incongruent, non-McGurk incongruent, and congruent syllables. Two separate analysis approaches, one using independent functional localizers and another using whole-brain voxel-based regression, showed differences in the left STS between perceivers and nonperceivers. The STS of McGurk perceivers responded significantly more than that of nonperceivers to McGurk syllables, but not to other stimuli, and perceivers' hemodynamic responses in the STS were significantly prolonged. In addition to the STS, weaker differences between perceivers and nonperceivers were observed in the fusiform face area and extrastriate visual cortex. These results suggest that the STS is an important source of interindividual variability in children's audiovisual speech perception.	t	\N
21959609	The literature suggests that contralateral acoustic stimulation (CAS) alters the amplitude of the distortion product otoacoustic emissions (DPOAEs), but it is still unknown whether the DPOAE Input/Output (I/O) functions are also affected. To elucidate this aspect of the DPOAEs, the present study assessed the effects of CAS on DPOAE I/O functions at the frequencies of 2 kHz and 4 kHz, in a sample of term neonatal subjects. Sixty randomly selected neonates were included in the study. The DPOAE I/O functions were obtained at 2 kHz and 4 kHz, in the presence of a 60 dB SPL broad band-contralateral white noise, using the TDH39 headphones contralaterally. DPOAEs were recorded up to a stimulus level of L2 = 35 dB peSPL. Significant DPOAE amplitude suppression effects were observed at various L2 stimulus levels for both tested frequencies at 2 and 4 kHz. In contrast, the corresponding DPOAE slopes showed various alterations that were not statistically significant. The data from the present study show that contralateral acoustic stimulation significantly affects only the amplitude of the DPOAE I/O functions; the slope is affected, but not significantly. This observation can shed light on the nature of CAS, suggesting that the latter is primarily a linear phenomenon without the cochlear compression and non-linear components seen in the healthy cochlea. From the available data it is not possible to infer whether the sample size has influenced the obtained results and the study should be repeated with a larger sample size and assessing more frequencies.	t	\N
21964385	Temporal summation of C-fiber evoked responses generates an increase in action potential discharge in second-order neurons and in perceived pain intensity (wind-up). This may be related to the central serotonergic system which modulates and partly inhibits sensory input. Aim of the study was to investigate the relationship between wind-up and serotonergic activity using loudness dependence of auditory evoked potentials (LDAEP). 18 healthy subjects were compared to 18 patients with major depression, a disease with a putative serotonin deficit. They were examined with quantitative sensory testing (QST) using the protocol of the German Research Network on Neuropathic Pain (DFNS), including the wind-up ratio (WUR), LDAEP, and psychometric measurements. We found a slight positive correlation between WUR and LDAEP both in healthy controls and depressed patients combined (r=0.340, p=0.043), indicating that WUR may be modulated by serotonergic activity. It can be concluded that inhibitory control to noxious stimuli is partly associated with the central serotonergic function as indicated by LDAEP.	t	\N
21972849	Filmmakers use continuity editing to engender a sense of situational continuity or discontinuity at editing boundaries. The goal of this study was to assess the impact of continuity editing on how people perceive the structure of events in a narrative film and to identify brain networks that are associated with the processing of different types of continuity editing boundaries. Participants viewed a commercially produced film and segmented it into meaningful events, while brain activity was recorded with functional magnetic resonance imaging (MRI). We identified three degrees of continuity that can occur at editing locations: edits that are continuous in space, time, and action; edits that are discontinuous in space or time but continuous in action; and edits that are discontinuous in action as well as space or time. Discontinuities in action had the biggest impact on behavioral event segmentation, and discontinuities in space and time had minor effects. Edits were associated with large transient increases in early visual areas. Spatial-temporal changes and action changes produced strikingly different patterns of transient change, and they provided evidence that specialized mechanisms in higher order perceptual processing regions are engaged to maintain continuity of action in the face of spatiotemporal discontinuities. These results suggest that commercial film editing is shaped to support the comprehension of meaningful events that bridge breaks in low-level visual continuity, and even breaks in continuity of spatial and temporal location.	t	\N
21973370	Within an auditory channel, the speech waveform contains both temporal envelope (E(O)) and temporal fine structure (TFS) information. Vocoder processing extracts a modified version of the temporal envelope (E') within each channel and uses it to modulate a channel carrier. The resulting signal, E'(Carr), has reduced information content compared to the original "E(O) + TFS" signal. The dynamic range over which listeners make additional use of E(O) + TFS over E'(Carr) cues was investigated in a competing-speech task. The target-and-background mixture was processed using a 30-channel vocoder. In each channel, E(O) + TFS replaced E'(Carr) at either the peaks or the valleys of the signal. The replacement decision was based on comparing the short-term channel level to a parametrically varied "switching threshold," expressed relative to the long-term channel level. Intelligibility was measured as a function of switching threshold, carrier type, target-to-background ratio, and replacement method. Scores showed a dependence on all four parameters. Derived intensity-importance functions (IIFs) showed that E(O) + TFS information from 8-13 dB below to 10 dB above the channel long-term level was important. When E(O) + TFS information was added at the peaks, IIFs peaked around -2 dB, but when E(O) + TFS information was added at the valleys, the peaks lay around +1 dB.	t	\N
21973372	Deutsch's octave illusion occurs when two tones that are spaced an octave apart are repeatedly presented in alternation; the sequence is presented to both ears simultaneously but offset by one tone, so that two dichotic chords are repeatedly presented in alternation. The most common illusory percept consists of an intermittent high tone in one ear alternating with an intermittent low tone in the other ear. The aim of this study was to investigate whether, once the illusory percept has emerged, the illusion will persist when the original sequence is followed by another sequence consisting of the repeated presentation of one of the two dichotic chords. Forty naïve subjects were tested with stimuli consisting first of a priming sequence containing dichotic octaves alternating between ears followed immediately by a test sequence consisting of a single dichotic octave presented repeatedly. The durations of the priming and test sequences were manipulated. The findings showed that the illusory percept is maintained after the switch from alternation to repetition and that the relative length of the priming and test sequences has a negligible influence on the persistence of the illusory percept.	t	\N
21974490	Naive listeners' perceptual assimilations of non-native vowels to first-language (L1) categories can predict difficulties in the acquisition of second-language vowel systems. This study demonstrates that listeners having two slightly different dialects as their L1s can differ in the perception of foreign vowels. Specifically, the study shows that Bohemian Czech and Moravian Czech listeners assimilate Dutch high front vowels differently to L1 categories. Consequently, the listeners are predicted to follow different paths in acquiring these Dutch vowels. These findings underscore the importance of carefully considering the specific dialect background of participants in foreign- and second-language speech perception studies.	t	\N
21981669	The neural representation of segmental and tonal phonological distinctions has been shown by means of the MMN ERP, yet this is not the case for intonational discourse contrasts. In Catalan, a rising-falling intonational sequence can be perceived as a statement or as a counterexpectational question, depending exclusively on the size of the pitch range interval of the rising movement. We tested here, using the MMN, whether such categorical distinctions elicited distinct neurophysiological patterns of activity, supporting their specific neural representation. From a behavioral identification experiment, we set the boundary between the two categories and defined four stimuli across the continuum. Although the physical distance between each pair of stimuli was kept constant, the central pair represented an across-category contrast, whereas the other pairs represented within-category contrasts. These four auditory stimuli were contrasted by pairs in three different oddball blocks. The mean amplitude of the MMN was larger for the across-category contrast, suggesting that intonational contrasts in the target language can be encoded automatically in the auditory cortex. These results are in line with recent findings in other fields of linguistics, showing that, when a boundary between categories is crossed, the MMN response is not just larger but rather includes a separate subcomponent.	t	\N
21985220	The high energy demand of the auditory and visual pathways render these sensory systems prone to diseases that impair mitochondrial function. Primary open-angle glaucoma, a neurodegenerative disease of the optic nerve, has recently been associated with a spectrum of mitochondrial abnormalities. This study sought to investigate auditory processing in individuals with open-angle glaucoma. DESIGN/STUDY SAMPLE: Twenty-seven subjects with open-angle glaucoma underwent electrophysiologic (auditory brainstem response), auditory temporal processing (amplitude modulation detection), and speech perception (monosyllabic words in quiet and background noise) assessment in each ear. A cohort of age, gender and hearing level matched control subjects was also tested. While the majority of glaucoma subjects in this study demonstrated normal auditory function, there were a significant number (6/27 subjects, 22%) who showed abnormal auditory brainstem responses and impaired auditory perception in one or both ears. The finding that a significant proportion of subjects with open-angle glaucoma presented with auditory dysfunction provides evidence of systemic neuronal susceptibility. Affected individuals may suffer significant communication difficulties in everyday listening situations.	t	\N
21987910	When the fundamental frequency (f0) is removed from a complex stimulus, the pitch of the f0 is still perceived by the listener. Through the use of the scalp-recorded frequency-following response, this study examined the relative contributions of thef0 and its harmonics in pitch processing by systematically manipulating the speech stimulus to remove component frequencies. 12 American and 12 Chinese adults were recruited. There were statistically significant effects of pitch strength and frequency error for the experimental-condition factor. There were significantly larger responses to the harmonics-only conditions than those obtained in the f0-only and control conditions. No statistically significant difference was observed between the two groups of participants. These findings indicate that neural responses associated with individual harmonics dominate the pitch processing in the human brainstem, irrespective of whether the listener's native language is nontonal or tonal.	t	\N
22000998	Recent years have seen a growing debate concerning the function of the cerebellum. Here we used a pitch discrimination task and PET to test for cerebellar involvement in the active control of sensory data acquisition. Specifically, we predicted greater cerebellar activity during active pitch discrimination compared to passive listening, with the greatest activity when pitch discrimination was most difficult. Ten healthy subjects were trained to discriminate deviant tones presented with a slightly higher pitch than a standard tone, using a Go/No Go paradigm. To ensure that discrimination performance was matched across subjects, individual psychometric curves were assessed beforehand using a two-step psychoacoustic procedure. Subjects were scanned while resting in the absence of any sounds, while passively listening to standard tones, and while detecting deviant tones slightly higher in pitch among these standard tones at four different performance levels. Consistent with our predictions, 1) passive listening alone elicited cerebellar activity (lobule IX), 2) cerebellar activity increased during pitch discrimination as compared to passive listening (crus I and II, lobules VI, VIIB, and VIIIB), and 3) this increase was correlated with the difficulty of the discrimination task (lobules V, VI, and IX). These results complement recent findings showing pitch discrimination deficits in cerebellar patients (Parsons et al., 2009) and further support a role for the cerebellum in sensory data acquisition. The data are discussed in the light of anatomical and physiological evidence functionally connecting auditory system and cerebellum.	t	\N
22002633	Attentional blink (AB) refers to a phenomenon where the correct identification of a first target (i.e., target) impairs the processing of a second target (i.e., probe) nearby in time. In the present study, we investigate the influence of temporal attention on auditory AB by means of scalp-recorded event-related potentials. Participants were instructed to focus their attention on a particular time interval following the target (i.e., short, middle, or long temporal position) in order to detect the occurrence of the probe in a rapid series of distractor sounds. We found a large probe processing deficit when the probe occurred immediately after the target. This AB decreased as the time interval between the target and the probe increased and coincided with the generation of a positive wave at parietal sites (i.e., P3b). The P3b elicited by the probe peaked earlier when the probe occurred at the designated time than when it occurred at another position in time. The results indicate that temporal attention can be deployed to a particular time, which facilitates short-term consolidation of the probe.	t	\N
22004192	Speech processing requires sensitivity to long-term regularities of the native language yet demands listeners to flexibly adapt to perturbations that arise from talker idiosyncrasies such as nonnative accent. The present experiments investigate whether listeners exhibit dimension-based statistical learning of correlations between acoustic dimensions defining perceptual space for a given speech segment. While engaged in a word recognition task guided by a perceptually unambiguous voice-onset time (VOT) acoustics to signal beer, pier, deer, or tear, listeners were exposed incidentally to an artificial "accent" deviating from English norms in its correlation of the pitch onset of the following vowel (F0) to VOT. Results across four experiments are indicative of rapid, dimension-based statistical learning; reliance on the F0 dimension in word recognition was rapidly down-weighted in response to the perturbation of the correlation between F0 and VOT dimensions. However, listeners did not simply mirror the short-term input statistics. Instead, response patterns were consistent with a lingering influence of sensitivity to the long-term regularities of English. This suggests that the very acoustic dimensions defining perceptual space are not fixed and, rather, are dynamically and rapidly adjusted to the idiosyncrasies of local experience, such as might arise from nonnative-accent, dialect, or dysarthria. The current findings extend demonstrations of "object-based" statistical learning across speech segments to include incidental, online statistical learning of regularities residing within a speech segment.	t	\N
22005285	Feelings of deliciousness during having foods are mainly produced by perceptions of sensory information extracted from foods themselves, such as taste and olfaction. However, environmental factors might modify the feeling of deliciousness. In the present study, we investigated how the condition of audio-visual environments affects the feeling of deliciousness during having sweet foods. Electroencephalograms (EEGs) were recorded from the frontal region of the scalp of healthy participants under virtual scenes of tearoom and construction work, respectively. The participants were asked to rate deliciousness after the recordings. Frequency analyses were performed from the EEGs. During having the foods, occupancy rates of beta frequency band between tearoom scenes and construction work scenes were markedly different, but not in other frequency bands. During having no food, in contrast, there was no difference of occupancy rates in respective frequency bands between the two different scenes. With regard to deliciousness during having sweet foods, all participants rated high scores under the scenes of tearoom than those under the scenes of construction work. Interestingly, there is a positive correlation between occupancy rates of beta frequency band and scores of deliciousness. These findings suggest that comfortable audio-visual environments play an important role in increasing the feeling of deliciousness during having sweet foods, in which beta frequency rhythms may be concerned with producing comprehensive feelings of deliciousness.	t	\N
22005291	Neural sensitivity to acoustic regularities supports fundamental human behaviors such as hearing in noise and reading. Although the failure to encode acoustic regularities in ongoing speech has been associated with language and literacy deficits, how auditory expertise, such as the expertise that is associated with musical skill, relates to the brainstem processing of speech regularities is unknown. An association between musical skill and neural sensitivity to acoustic regularities would not be surprising given the importance of repetition and regularity in music. Here, we aimed to define relationships between the subcortical processing of speech regularities, music aptitude, and reading abilities in children with and without reading impairment. We hypothesized that, in combination with auditory cognitive abilities, neural sensitivity to regularities in ongoing speech provides a common biological mechanism underlying the development of music and reading abilities. We assessed auditory working memory and attention, music aptitude, reading ability, and neural sensitivity to acoustic regularities in 42 school-aged children with a wide range of reading ability. Neural sensitivity to acoustic regularities was assessed by recording brainstem responses to the same speech sound presented in predictable and variable speech streams. Through correlation analyses and structural equation modeling, we reveal that music aptitude and literacy both relate to the extent of subcortical adaptation to regularities in ongoing speech as well as with auditory working memory and attention. Relationships between music and speech processing are specifically driven by performance on a musical rhythm task, underscoring the importance of rhythmic regularity for both language and music. These data indicate common brain mechanisms underlying reading and music abilities that relate to how the nervous system responds to regularities in auditory input. Definition of common biological underpinnings for music and reading supports the usefulness of music for promoting child literacy, with the potential to improve reading remediation.	t	\N
22005389	Several studies demonstrated that active exploration as compared to passive observation of a variety of objects leads to improved performance concerning these actively studied objects later on. These results may be specifically due to an improvement in perceptual recognition but in principle they may also be due to a speeding up of responses to actively studied objects. Recently, however, it was suggested that the benefit of active exploration on perceptual recognition may be restricted to a specific class of (biologically relevant) stimuli. By employing measures derived from signal detection theory we were able to show in all our three experiments that active exploration of virtual 3D objects leads to improved perceptual sensitivity in a subsequent test phase. The improvement with these objects means that the benefit of active exploration is not restricted to a specific class of biologically relevant stimuli. The results of our second experiment further demonstrate that the benefit of active exploration is even strong enough to fully compensate for the effect of perceptual degradation, thereby emphasizing the major impact of active exploration. In our third experiment, we explored the possibility that effects of active exploration might be due to major changes in attentional strategies rather than to the action-related aspect. Results revealed that an attentional requirement left the active-passive difference by and large intact supporting the view that the advantage of active object exploration lies in the action itself.	t	\N
22006524	This article provides a demonstration of an analytical technique that can be used to investigate the causes of perceptual phenomena. The technique is based on the concept of the ideal observer, an optimal signal classifier that makes decisions that maximize the probability of a correct response. To demonstrate the technique, an analysis was conducted to investigate the role of the auditory periphery in the production of temporal masking effects. The ideal observer classified output from four models of the periphery. Since the ideal observer is the best of all possible observers, if it demonstrates masking effects, then all other observers must as well. If it does not demonstrate masking effects, then nothing about the periphery requires masking to occur, and therefore masking would occur somewhere else. The ideal observer exhibited several forward masking effects but did not exhibit backward masking, implying that the periphery has a causal role in forward but not backward masking. A general discussion of the strengths of the technique and supplementary equations are also included.	t	\N
22010902	Language acquisition involves both acquiring a set of words (i.e. the lexicon) and learning the rules that combine them to form sentences (i.e. syntax). Here, we show that consonants are mainly involved in word processing, whereas vowels are favored for extracting and generalizing structural relations. We demonstrate that such a division of labor between consonants and vowels plays a role in language acquisition. In two very similar experimental paradigms, we show that 12-month-old infants rely more on the consonantal tier when identifying words (Experiment 1), but are better at extracting and generalizing repetition-based srtuctures over the vocalic tier (Experiment 2). These results indicate that infants are able to exploit the functional differences between consonants and vowels at an age when they start acquiring the lexicon, and suggest that basic speech categories are assigned to different learning mechanisms that sustain early language acquisition.	t	\N
22015572	Sparse and clustered-sparse temporal sampling fMRI protocols have been devised to reduce the influence of auditory scanner noise in the context of auditory fMRI studies. Here, we report an improvement of the previously established clustered-sparse acquisition scheme. The standard procedure currently used by many researchers in the field is a scanning protocol that includes relatively long silent pauses between image acquisitions (and therefore, a relatively long repetition time or cluster-onset asynchrony); it is during these pauses that stimuli are presented. This approach makes it unlikely that stimulus-induced BOLD response is obscured by scanner-noise-induced BOLD response. It also allows the BOLD response to drop near baseline; thus, avoiding saturation of BOLD signal and theoretically increasing effect size. A possible drawback of this approach is the limited number of stimulus presentations and image acquisitions that are possible in a given period of time, which could result in an inaccurate estimation of effect size (higher standard error). Since this line of reasoning has not yet been empirically tested, we decided to vary the cluster-onset asynchrony (7.5, 10, 12.5, and 15 s) in the context of a clustered-sparse protocol. In this study sixteen healthy participants listened to spoken sentences. We performed whole-brain fMRI group statistics and region of interest analysis with anatomically defined regions of interest (auditory core and association areas). We discovered that the protocol, which included a short cluster-onset asynchrony (7.5 s), yielded more advantageous results than the other protocols, which involved longer cluster-onset asynchrony. The short cluster-onset asynchrony protocol exhibited a larger number of activated voxels and larger mean effect sizes with lower standard errors. Our findings suggest that, contrary to prior experience, a short cluster-onset asynchrony is advantageous because more stimuli can be delivered within any given period of time. Alternatively, a given number of stimuli can be presented in less time, and this broadens the spectrum of possible fMRI applications.	t	\N
22046436	The present study investigated the minimum amount of auditory stimulation that allows differentiation of spoken voices, instrumental music, and environmental sounds. Three new findings were reported. 1) All stimuli were categorized above chance level with 50 ms-segments. 2) When a peak-level normalization was applied, music and voices started to be accurately categorized with 20 ms-segments. When the root-mean-square (RMS) energy of the stimuli was equalized, voice stimuli were better recognized than music and environmental sounds. 3) Further psychoacoustical analyses suggest that the categorization of extremely brief auditory stimuli depends on the variability of their spectral envelope in the used set. These last two findings challenge the interpretation of the voice superiority effect reported in previously published studies and propose a more parsimonious interpretation in terms of an emerging property of auditory categorization processes.	t	\N
22047947	Predictive coding theories posit that the perceptual system is structured as a hierarchically organized set of generative models with increasingly general models at higher levels. The difference between model predictions and the actual input (prediction error) drives model selection and adaptation processes minimizing the prediction error. Event-related brain potentials elicited by sensory deviance are thought to reflect the processing of prediction error at an intermediate level in the hierarchy. We review evidence from auditory and visual studies of deviance detection suggesting that the memory representations inferred from these studies meet the criteria set for perceptual object representations. Based on this evidence we then argue that these perceptual object representations are closely related to the generative models assumed by predictive coding theories.	t	\N
22051554	Relative blindsight is said to occur when different levels of subjective awareness are obtained at equality of objective performance. Using metacontrast masking, Lau and Passingham (2006) reported relative blindsight in normal observers at the shorter of two stimulus-onset asynchronies (SOAs) between target and mask. Experiment 1 replicated the critical asymmetry in subjective awareness at equality of objective performance. We argue that this asymmetry cannot be regarded as evidence for relative blindsight because the observers' responses were based on different attributes of the stimuli (criterion contents) at the two SOAs. With an invariant criterion content (Experiment 2), there was no asymmetry in subjective awareness across the two SOAs even though objective performance was the same. Experiment 3 examined the effect of criterion level on estimates of relative blindsight. Collectively, the present results question whether metacontrast masking is a suitable paradigm for establishing relative blindsight. Implications for theories of consciousness are discussed.	t	\N
22056506	Behavioral and neurophysiological studies have shown an enhancement of visual perception in crossmodal audiovisual stimulation conditions, both for sensitivity and reaction times, when the stimulation in the two sensory modalities occurs in condition of space and time congruency. The purpose of the present work is to verify whether congruent visual and acoustic stimulations can improve the detection of visual stimuli in people affected by low vision. Participants were asked to detect the presence of a visual stimulus (yes/no task) either presented in isolation (i.e., unimodal visual stimulation) or simultaneously with auditory stimuli, which could be placed in the same spatial position (i.e., crossmodal congruent conditions) or in different spatial positions (i.e., crossmodal incongruent conditions). The results show for the first time audiovisual integration effects in low vision individuals. In particular, it has been observed a significant visual detection benefit in the crossmodal congruent as compared to the unimodal visual condition. This effect is selective for visual stimulation that occurs in the portion of visual field that is impaired, and disappears in the region of space in which vision is spared. Surprisingly, there is a marginal crossmodal benefit when the sound is presented at 16 degrees far from the visual stimulus. The observed crossmodal effect seems to be determined by the contribution of both senses to a model of optimal combination, in which the most reliable provides the highest contribution. These results, indicating a significant beneficial effect of synchronous and spatially congruent sounds in a visual detection task, seem very promising for the development of a rehabilitation approach of low vision diseases based on the principles of multisensory integration.	t	\N
22070077	To analyze the hearing loss profiles in patients with tinnitus, and then provide clinical foundation for further studying the etiology and examination methods of tinnitus. Ear specialist examination, acoustic impedance test,normal frequency pure tone audiometry and extended high frequency audiometry were applied to 200 patients with chief complaint of subjective tinnitus. Among the 200 tinnitus cases, 123 (61.5%) patients were diagnosed with unilateral tinnitus, 77 (38.5%) patients with bilateral tinnitus and 46 (23.0%) cases with normal hearing. In those patients with unilateral tinnitus, by comparing the hearing threshold of affected side and contralateral side (0.125-8 kHz), the difference was statistically significant (P < 0.05), but in extended high frequency (> 10 kHz), the difference between two groups was not statistically significant (P > 0.05). There was significant difference in hearing threshold between tinnitus patients with normal and abnormal hearing in normal frequency (P < 0.05), meantime the detection rate in abnormal hearing group was lower than the normal group. Tinnitus can occur in people with normal hearing. Early in tinnitus,further study need be undertaken on whether the audiometry extended high frequency can offer the early evidence of hearing loss for tinnitus patients or not.	t	\N
22072599	Difficulty understanding speech in background noise, even with amplification to restore audibility, is a common problem for hearing-impaired individuals and is especially frequent in older adults. Despite the debilitating nature of the problem the cause is not yet completely clear. This review considers the role of spatial processing ability in understanding speech in noise, highlights the potential impact of disordered spatial processing, and attempts to establish if aging leads to reduced spatial processing ability. Evidence supporting and opposing the hypothesis that spatial processing is disordered among the aging population is presented. With a few notable exceptions, spatial processing ability was shown to be reduced in an older population in comparison to young adults, leading to poorer speech understanding in noise. However, it is argued that to conclude aging negatively effects spatial processing ability may be oversimplified or even premature given potentially confounding factors such as cognitive ability and hearing impairment. Further research is required to determine the effect of aging and hearing impairment on spatial processing and to investigate possible remediation options for spatial processing disorder.	t	\N
22073602	The effectiveness of bone anchored hearing aid (BAHA) for the patients with congenital aural atresia was evaluated by multicenter clinical study in Japan. Twenty patients (17 bilateral and 3 hemilateral) of congenital auricular atresia were registered for this study and finally, 18 of them (15 bilateral and 3 unilateral) were subjected to further evaluation. Primary endpoint of this study was free sound-field pure-tone audiometory and speech threshold hearing test in quiet and noisy circumstances. Secondary endpoint of this study was patient's satisfaction based upon APHAB (Abbreviated Profile of Hearing Aid Benefit) questionnaire survey. These results were compared between before and 12 weeks after BAHA surgery. Both hearing level of pure tone and speech threshold significantly improved after BAHA surgery. APHAB scores also suggested the improvement of the QOL after BAHA usage, except for the scores that concerned with unpleasantness of noisy sound. BAHA is one of the useful options for the treatment of congenital auricular atresia.	t	\N
22080221	Gender is salient, socially critical information obtained from faces and voices, yet the brain processes underlying gender discrimination have not been well studied. We investigated neural correlates of gender processing of voices in two ERP studies. In the first, ERP differences were seen between female and male voices starting at 87 ms, in both spatial-temporal and peak analyses, particularly the fronto-central N1 and P2. As pitch differences may drive gender differences, the second study used normal, high- and low-pitch voices. The results of these studies suggested that differences in pitch produced early effects (27-63 ms). Gender effects were seen on N1 (120 ms) with implicit pitch processing (study 1), but were not seen with manipulations of pitch (study 2), demonstrating that N1 was modulated by attention. P2 (between 170 and 230 ms) discriminated male from female voices, independent of pitch. Thus, these data show that there are two stages in voice gender processing; a very early pitch or frequency discrimination and a later more accurate determination of gender at the P2 latency.	t	\N
22087889	The effect of temporal asymmetry on amplitude modulation detection was studied using sawtooth modulators with rising (ramped) or falling (damped) temporal envelopes within each period of modulation. For pure-tone carriers, damped modulation was more detectable than ramped modulation for a 5-kHz carrier (by a threshold difference of 3.2 dB on average) but not for a 1-kHz carrier. The threshold difference obtained at 5 kHz between the ramped and damped modulators was consistent across modulation rates (8-128 Hz). This carrier frequency dependence suggests that the effect of temporally asymmetry on modulation detection originates from envelope-based, within-channel mechanisms.	t	\N
22087927	Speech-in-noise-measurements are important in clinical practice and have been the subject of research for a long time. The results of these measurements are often described in terms of the speech reception threshold (SRT) and SNR loss. Using the basic concepts that underlie several models of speech recognition in steady-state noise, the present study shows that these measures are ill-defined, most importantly because the slope of the speech recognition functions for hearing-impaired listeners always decreases with hearing loss. This slope can be determined from the slope of the normal-hearing speech recognition function when the SRT for the hearing-impaired listener is known. The SII-function (i.e., the speech intelligibility index (SII) against SNR) is important and provides insights into many potential pitfalls when interpreting SRT data. Standardized SNR loss, sSNR loss, is introduced as a universal measure of hearing loss for speech in steady-state noise. Experimental data demonstrates that, unlike the SRT or SNR loss, sSNR loss is invariant to the target point chosen, the scoring method or the type of speech material.	t	\N
22088028	Monolingual Peruvian Spanish listeners identified natural tokens of the Canadian French (CF) and Canadian English (CE) /ɛ/ and /æ/, produced in five consonantal contexts. The results demonstrate that while the CF vowels were mapped to two different native vowels, /e/ and /a/, in all consonantal contexts, the CE contrast was mapped to the single native vowel /a/ in four out of five contexts. Linear discriminant analysis revealed that acoustic similarity between native and target language vowels was a very good predictor of context-specific perceptual mappings. Predictions are made for Spanish learners of the /ɛ/-/æ/ contrast in CF and CE.	t	\N
22090001	The primary purpose of this study was to evaluate a group of postlingually deafened adults, whose aided speech recognition exceeded commonly accepted candidacy criteria for implantation. The study aimed to define performance and qualitative outcomes of cochlear implants in these individuals compared with their optimally fitted hearing aid(s). Retrospective case series. Tertiary referral center. All postlingually deafened subjects (N = 27), who were unsuccessful hearing aid users implanted between 2000 and 2010 with a preimplantation Hearing in Noise Test (HINT) score of 60% or more were included. We compared patients' preoperative performance (HINT score) with hearing aids to postoperative performance with the cochlear implant after 12 months of device use. In addition, the Hearing Handicap Inventory questionnaire was used to quantify the hearing-related handicap change perceived after the implantation. The study group demonstrated significant postoperative improvement on all outcome measures; most notably, the mean HINT score improved from 68.4% (standard deviation, 8.3) to 91.9% (standard deviation, 9.7). Additionally, there was a significant improvement in hearing-related handicap perceived by all patients. The envelope of implantation candidacy criteria continues to expand as shown by this study's cohort. Patient satisfaction and speech recognition results are very encouraging in support of treating those who currently perform at a level above the conventional candidacy threshold but struggle with optimally fitted hearing aids.	t	\N
22099165	Behavioral and electrophysiological measures of target and distractor processing were examined in an auditory selective attention task before and after three weeks of distractor suppression training. Behaviorally, training improved target recognition and led to less conservative and more rapid responding. Training also effectively shortened the temporal distance between distractors and targets needed to achieve a fixed level of target sensitivity. The effects of training on event-related potentials were restricted to the distracting stimulus: earlier N1 latency, enhanced P2 amplitude, and weakened P3 amplitude. Nevertheless, as distractor P2 amplitude increased, so too did target P3 amplitude, connecting experience-dependent changes in distractor processing with greater distinctiveness of targets in working memory. We consider the effects of attention training on the processing priorities, representational noise, and inhibitory processes operating in working memory.	t	\N
22100742	Tinnitus occurs with or without prior noise exposure (noise-induced tinnitus (NIT) and spontaneous tinnitus (ST)), and is considered a symptom related to permanent hearing impairment (HI) or temporary hearing threshold shift (TTS). To carry out a cross-sectional interview study on TTS, ST and NIT during a standard audiometric screening of 756 7-year-old children in Gothenburg. 41% out of 756 children reported either NIT or ST on several occasions, 17% reported recurrent TTS and 7% failed the audiometry screening. The probability of ST was 27% for children with no HI or TTS (OR=1.23 (95% CI 1.12 to 1.34)) but 63% (OR=1.16 (95% CI 1.02 to 1.33)) if exhibiting both HI and TTS. This study confirms an increased occurrence of spontaneous tinnitus in children with TTS or HI and in children with both TTS and HI, in particular, but also in children with normal hearing. Possibly, tinnitus in young children correlates with stress as in adolescents and adults.	t	\N
22107443	The objective of this study was to compare two recently proposed methods for fast measurements of psychophysical tuning curves (fast-PTCs) in terms of resulting tuning curve features and training effects. Fast-PTCs with swept-noise (SN) and gated-noise (GN) maskers were measured at signal frequencies of 500, 1000, 2000, and 4000 Hz. The effect of amplitude modulating the signal in the GN condition was evaluated. Two PTC runs were obtained for each condition to assess training effects. Eight normally-hearing young adults participated in the study. The SN and GN methods resulted in similar estimates of frequency selectivity when training effects were considered. Amplitude modulating the tone in the GN method reduced the effect of training. On average, SN-PTCs were most repeatable compared to the two other methods and they were not affected by training. Estimation of the shift in the PTC tip frequency was not affected by the measurement method or training effects. Fast-PTC methods resulted in similar estimates of tuning as compared to published notched-noise data. The SN method and the GN procedure with amplitude modulated signals allowed for time-efficient estimation of frequency selectivity that was unaffected by training.	t	\N
22115727	We used a qualitative dissociation procedure to assess semantic priming from spatially attended and unattended masked words. Participants categorized target words that were preceded by parafoveal prime words belonging to either the same (20%) or the opposite (80%) category as the target. Using this paradigm, only non-strategic use of the prime would result in facilitation of the target responses in related trials. Primes were immediately masked or masked with a delay, while spatial attention was allocated to the primes' location or away from the primes' location. Immediate masked, strongly related primes facilitated target responses irrespective of the spatial attention. Delayed masked, related primes led to reversed (strategic) or facilitatory priming depending on whether they were cued or uncued. These findings demonstrate that perceiving a stimulus with or without awareness depends on both stimulus quality and attention orienting and that non-strategic priming can be observed from clear visible but spatially unattended words.	t	\N
22119398	Impairment in long-term memory is one of the most salient alterations in cognitive aging. Findings of age-related deficits in source monitoring and recollection have revealed a selective decline in memory for detailed information. The underlying mechanism of this phenomenon is not well understood. We hypothesized that the influence of task-irrelevant visual stimuli present in our environment interferes with retrieval of detailed memories more for older than younger adults. We compared memory performance on a recall test for visual details when older adult participants' eyes were closed versus performance when their eyes were open and irrelevant visual stimuli were presented. The results showed that the presence of irrelevant visual information diminished long-term memory performance based on an objective measure of recollection for visual details. Comparison of the current results to findings from our earlier study using the same experimental paradigm with younger adults revealed that visual distraction disrupted recollection of relevant details to a greater degree in older than younger adults. This result suggests that visual distraction overwhelms older adults' declining cognitive control resources that are instrumental in the retrieval and selection of mnemonic details. More generally, these findings explicate a mechanistic basis for selective impairment of recollection in normal aging.	t	\N
22124890	Interaural time differences (ITDs) can be used to localize sounds in the horizontal plane. ITDs can be extracted from either the fine structure of low-frequency sounds or from the envelopes of high-frequency sounds. Studies of the latter have included stimuli with periodic envelopes like amplitude-modulated tones or transposed stimuli, and high-pass filtered Gaussian noises. Here, four experiments are presented investigating the perceptual relevance of ITD cues in synthetic and recorded "rustling" sounds. Both share the broad long-term power spectrum with Gaussian noise but provide more pronounced envelope fluctuations than Gaussian noise, quantified by an increased waveform fourth moment, W. The current data show that the JNDs in ITD for band-pass rustling sounds tended to improve with increasing W and with increasing bandwidth when the sounds were band limited. In contrast, no influence of W on JND was observed for broadband sounds, apparently because of listeners' sensitivity to ITD in low-frequency fine structure, present in the broadband sounds. Second, it is shown that for high-frequency rustling sounds ITD JNDs can be as low as 30 μs. The third result was that the amount of dominance for ITD extraction of low frequencies decreases systematically with increasing amount of envelope fluctuations. Finally, it is shown that despite the exceptionally good envelope ITD sensitivity evident with high-frequency rustling sounds, minimum audible angles of both synthetic and recorded high-frequency rustling sounds in virtual acoustic space are still best when the angular information is mediated by interaural level differences.	t	\N
22127548	The present acoustic-phonetic study explores whether voicing and devoicing assimilations of French fricatives are equivalent in magnitude and whether they operate similarly (i.e., complete vs. gradient, obligatory vs. optional, regressive vs. progressive). It concurrently assesses the contribution of speakers' articulation rate to the proportion of voicing (i.e., voicing ratios) in /s/ and /z/ embedded in fricative#stop sequences. Data analyses show that voicing and devoicing assimilation are similar in many regards: the absolute amounts of voicing change are equivalent in magnitude (0.77, 0.78) for the two processes: changes in voicing ratios are accompanied by changes in fricative and preceding vowel durations. These concomitant alterations result in the increased acoustic-phonetic similarity between the assimilated and the non-assimilated forms, suggesting that the two processes might be complete. In addition, the two processes operate regressively and across word-boundary. However, data show that the voicing assimilation of /s/ is not rate dependent, which suggest that it might be obligatory, while the devoicing assimilation of /z/ is rate dependent, which suggest that it might be optional.	t	\N
22133279	To investigate the relationship between plasma reactive oxygen species (ROS) levels and severity of age-related hearing impairment in humans. We recruited 302 adult subjects aged 40-77 years with normal or symmetrical sensorineural hearing loss. The association of plasma ROS levels on pure tone average of low frequencies (PTA-low) and pure tone average of high frequencies (PTA-high) were analyzed. Luminol-dependent chemiluminescence signals, which reflect hydrogen peroxide (H(2)O(2)), hypochlorite (HOCl/OCl(-)) and hydroxyl radicals (•OH) levels, showed significant positive association with PTA-low and PTA-high after adjusting for age, gender, central obesity, systemic diseases, and health-related habits (smoking, drinking, antioxidant intake). Lucigenin-dependent chemiluminescence signals, which mainly reflect superoxide anion (O(2)•(-)) levels, showed significant positive association with PTA-low, but not with PTA-high after adjusting for other variables. We concluded that plasma ROS levels were associated with severity of age-related hearing impairment in humans. Various ROS may differently affect auditory dysfunctions.	t	\N
22162387	In typically developing (TD) individuals, behavioral and event-related potential (ERP) studies suggest that audiovisual (AV) integration enables faster and more efficient processing of speech. However, little is known about AV speech processing in individuals with autism spectrum disorders (ASD). This study examined ERP responses to spoken words to elucidate the effects of visual speech (the lip movements accompanying a spoken word) on the range of auditory speech processing stages from sound onset detection to semantic integration. The study also included an AV condition, which paired spoken words with a dynamic scrambled face in order to highlight AV effects specific to visual speech. Fourteen adolescent boys with ASD (15-17 years old) and 14 age- and verbal IQ-matched TD boys participated. The ERP of the TD group showed a pattern and topography of AV interaction effects consistent with activity within the superior temporal plane, with two dissociable effects over frontocentral and centroparietal regions. The posterior effect (200-300 ms interval) was specifically sensitive to lip movements in TD boys, and no AV modulation was observed in this region for the ASD group. Moreover, the magnitude of the posterior AV effect to visual speech correlated inversely with ASD symptomatology. In addition, the ASD boys showed an unexpected effect (P2 time window) over the frontocentral region (pooled electrodes F3, Fz, F4, FC1, FC2, FC3, FC4), which was sensitive to scrambled face stimuli. These results suggest that the neural networks facilitating processing of spoken words by visual speech are altered in individuals with ASD.	t	\N
22171057	Neural activity in the auditory system decreases with repeated stimulation, matching stimulus probability in multiple timescales. This phenomenon, known as stimulus-specific adaptation, is interpreted as a neural mechanism of regularity encoding aiding auditory object formation. However, despite the overwhelming literature covering recordings from single-cell to scalp auditory-evoked potential (AEP), stimulation timing has received little interest. Here we investigated whether timing predictability enhances the experience-dependent modulation of neural activity associated with stimulus probability encoding. We used human electrophysiological recordings in healthy participants who were exposed to passive listening of sound sequences. Pure tones of different frequencies were delivered in successive trains of a variable number of repetitions, enabling the study of sequential repetition effects in the AEP. In the predictable timing condition, tones were delivered with isochronous interstimulus intervals; in the unpredictable timing condition, interstimulus intervals varied randomly. Our results show that unpredictable stimulus timing abolishes the early part of the repetition positivity, an AEP indexing auditory sensory memory trace formation, while leaving the later part (≈ >200 ms) unaffected. This suggests that timing predictability aids the propagation of repetition effects upstream the auditory pathway, most likely from association auditory cortex (including the planum temporale) toward primary auditory cortex (Heschl's gyrus) and beyond, as judged by the timing of AEP latencies. This outcome calls for attention to stimulation timing in future experiments regarding sensory memory trace formation in AEP measures and stimulus probability encoding in animal models.	t	\N
22172209	Using online measures of familiar word recognition in the looking-while-listening procedure, this prospective longitudinal study revealed robust links between processing efficiency and vocabulary growth from 18 to 30 months in children classified as typically developing (n = 46) and as "late talkers" (n = 36) at 18 months. Those late talkers who were more efficient in word recognition at 18 months were also more likely to "bloom," showing more accelerated vocabulary growth over the following year, compared with late talkers less efficient in early speech processing. Such findings support the emerging view that early differences in processing efficiency evident in infancy have cascading consequences for later learning and may be continuous with individual differences in language proficiency observed in older children and adults.	t	\N
22174701	In this review paper aimed at the non-specialist, we explore the use that neuroscientists and musicians have made of perceptual illusions based on ambiguity. The pivotal issue is auditory scene analysis (ASA), or what enables us to make sense of complex acoustic mixtures in order to follow, for instance, a single melody in the midst of an orchestra. In general, ASA uncovers the most likely physical causes that account for the waveform collected at the ears. However, the acoustical problem is ill-posed and it must be solved from noisy sensory input. Recently, the neural mechanisms implicated in the transformation of ambiguous sensory information into coherent auditory scenes have been investigated using so-called bistability illusions (where an unchanging ambiguous stimulus evokes a succession of distinct percepts in the mind of the listener). After reviewing some of those studies, we turn to music, which arguably provides some of the most complex acoustic scenes that a human listener will ever encounter. Interestingly, musicians will not always aim at making each physical source intelligible, but rather express one or more melodic lines with a small or large number of instruments. By means of a few musical illustrations and by using a computational model inspired by neuro-physiological principles, we suggest that this relies on a detailed (if perhaps implicit) knowledge of the rules of ASA and of its inherent ambiguity. We then put forward the opinion that some degree perceptual ambiguity may participate in our appreciation of music.	t	\N
22177410	The study of the neural basis of syntactic processing has greatly benefited from neuroimaging techniques. Research on syntactic processing in bilinguals has used a variety of techniques, including mainly functional magnetic resonance imaging (fMRI) and event-related potentials (ERP). This paper reports on a functional near-infrared spectroscopy (fNIRS) study on syntactic processing in highly proficient young adult speakers of Portuguese (mother tongue) (L1) and French (second language) (L2). They made a syntactic judgment of visually presented sentences, which either did or did not contain noun-verb agreement violations. The results showed that syntactic processing in both languages resulted in significant activation in anterior frontal regions of the left hemisphere and in the temporal superior posterior areas of the right hemisphere, with a more prominent activation for L2 in some areas. These findings corroborate previously reported neuroimaging evidence, showing the suitability of fNIRS for the study of syntactic processing in the bilingual brain.	t	\N
22178743	Rhythm is a phenomenon that fundamentally affects the perception of events unfolding in time. In language, we define 'rhythm' as the temporal structure that underlies the perception and production of utterances, whereas 'meter' is defined as the regular occurrence of beats (i.e. stressed syllables). In stress-timed languages such as German, this regularity functions as a powerful temporal and structural cue in speech comprehension. Recent evidence shows that it also interacts with higher level linguistic faculties such as syntax (Schmidt-Kassow & Kotz, 2009a). The current ERP experiment investigated the impact of metric structure on lexico-semantic processing, comparing the effects of semantic and metric expectancy in regular and irregular metric sentence contexts. We predicted that (1) semantically unexpected words would result in an increased N400 amplitude and (2) metric context modulates the N400 amplitude. Our results confirm these predictions: semantically unexpected words elicit an N400 that is significantly smaller in a metrically regular than a metrically irregular sentence context. The current findings support the idea that metric regularity enhances the prediction of stress locations in a sentence context, which in turn facilitates lexico-semantic integration.	t	\N
22183282	Different studies have been carried out in order to correlate audiometric thresholds and distortion product otoacoustic emissions measurements (DPOAE). However, high variability and external interferences make hearing thresholds estimates by means of the DPOAE very little sensitive. The aim of this study was to check the correspondence between the pure tone thresholds and the cochlear response thresholds by DPOAE Input/output functions, considering the influence of the following variables: gender, past of acute otitis media, and ear side. Prospective study comprehending 69 normal hearing individuals. Multiple mix regression models were applied to evaluate the correspondence between the two measurements studied. Statistically significant positive correlation was observed among all the frequencies compared (2000, 3000, 4000 e 6000 Hz). The 1 dB HL resolution pure tone thresholds and the above-mentioned variables had a direct impact on the high correlation between the measures studied, and it also reduced response variability. Nevertheless, response variability was still high, limiting the use of DPOAE I/O functions for hearing threshold estimates. We suggest that these variables should be considered for future studies with pure tone thresholds estimations by DPOAE I/O functions.	t	\N
22197571	This study aimed to assess the effect of musical training in statistical learning of tone sequences using Magnetoencephalography (MEG). Specifically, MEG recordings were used to investigate the neural and functional correlates of the pre-attentive ability for detection of deviance, from a statistically learned tone sequence. The effect of long-term musical training in this ability is investigated by means of comparison of MMN in musicians to non-musicians. Both groups (musicians and non-musicians) showed a mismatch negativity (MMN) response to the deviants and this response did not differ amongst them neither in amplitude nor in latency. Another interesting finding of this study is that both groups revealed a significant difference between the standards and the deviants in the response of P50 and this difference was significantly larger in the group of musicians. The increase of this difference in the group of musicians underlies that intensive, specialized and long term exercise can enhance the ability of the auditory cortex to discriminate new auditory events from previously learned ones according to transitional probabilities. A behavioral discrimination task between the standard and the deviant sequences followed the MEG measurement. The behavioral results indicated that the detection of deviance was not explicitly learned by either group, probably due to the lack of attentional resources. These findings provide valuable insights on the functional architecture of statistical learning.	t	\N
22199192	The effects of type of stimuli (i.e., nonspeech vs. speech), speech (i.e., natural vs. synthetic), gender of speaker and listener, speaker (i.e., self vs. other), and frequency alteration in self-produced speech on the late auditory cortical evoked potential were examined. Young adult men (n = 15) and women (n = 15), all with normal hearing, participated. P1-N1-P2 components were evoked with the following stimuli: 723-Hz tone bursts; naturally produced male and female /a/ tokens; synthetic male and female /a/ tokens; an /a/ token self-produced by each participant; and the same /a/ token produced by the participant but with a shift in frequency. In general, P1-N1-P2 component latencies were significantly shorter when evoked with the tonal stimulus versus speech stimuli and natural versus synthetic speech (p < .05). Women had significantly shorter latencies for only the P2 component (p < .05). For the tonal versus speech stimuli, P1 amplitudes were significantly smaller, and N1 and P2 amplitudes were significantly larger (p < .05). There was no significant effect of gender on the P1, N1, or P2 amplitude (p > .05). These findings are consistent with the notion that spectrotemporal characteristics of nonspeech and speech stimuli affect P1-N1-P2 latency and amplitude components.	t	\N
22201556	Congenital amusia is a neurodevelopmental disorder that is characterized primarily by difficulties in the pitch domain. The aim of the present study was to investigate the perception of musical timbre in a group of individuals with congenital amusia by probing discrimination and short-term memory for real-world timbral stimuli as well as examining the ability of these individuals to sort instrumental tones according to their timbral similarity. Thirteen amusic individuals were matched with thirteen non-amusic controls on a range of background variables. The discrimination task included stimuli of two different durations and pairings of instrumental tones that reflected varying distances in a perceptual timbre space. Performance in the discrimination task was at ceiling for both groups. In contrast, amusic individuals scored lower than controls on the short-term timbral memory task. Amusic individuals also performed worse than controls on the sorting task, suggesting differences in the higher-order representation of musical timbre. These findings add to the emerging picture of amusia as a disorder that has consequences for the perception and memory of musical timbre, as well as pitch.	t	\N
22209062	To investigate the relationships between objective measures and the results of subjective assessment of voice quality and speech intelligibility in patients submitted to total laryngectomy and tracheoesophageal (TE) puncture. Retrospective. Twenty patients implanted with voice prosthesis were studied. After surgery, the entire sample performed speech rehabilitation. The assessment protocol included maximum phonation time (MPT), number of syllables per deep breath, acoustic analysis of the sustained vowel /a/ and of a bisyllabic word, perceptual evaluation (pleasantness and intelligibility%), and self-assessment. The correlation between pleasantness and intelligibility% was statistically significant. Both the latter were significantly correlated with the acoustic signal type, the number of formant peaks, and the F2-F1 difference. The intelligibility% and number of formant peaks were significantly correlated with the MPT and number of syllables per deep breath. Moreover, significant correlations were found between the number of formant peaks and both intelligibility% and pleasantness. The higher the number of syllables per deep breath and the longer the MPT, significantly higher was the number of formant peaks and the intelligibility%. The study failed to show significant correlation between patient's self-assessment of voice quality and both pleasantness and communication effectiveness. The multidimensional assessment seems to be a reliable tool to evaluate the TE functional outcome. Particularly, the results showed that both pleasantness and intelligibility of TE speech are correlated to the availability of expired air and the function of the vocal tract.	t	\N
22213748	To determine the efficacy of cochlear implantation (CI) in prelingually deafened adolescent children and to evaluate predictive variables for successful outcomes. Retrospective medical record review. Children aged 10 to 17 years with prelingual hearing loss (mean length of deafness, 11.5 years) who received a unilateral CI (mean age at CI, 12.9 years). Unilateral CI. Standard speech perception testing (Consonant-Nucleus-Consonant [CNC] monosyllabic word test and Hearing in Noise [HINT] sentence test) was performed preoperatively, 1 year postoperatively (year 1), and at the last follow-up/end of the study (EOS). There was a highly significant improvement in speech perception scores for both HINT sentence and CNC word testing from the preoperative testing to year 1 (mean change score, 51.10% and 32.23%, respectively; P < .001) and from the preoperative testing to EOS (mean change score, 60.02% and 38.73%, respectively; P < .001), with a significantly greater increase during the first year (P < .001). In addition, there was a highly significant correlation between improvements in performance scores on the CNC word and HINT sentence speech perception tests and both age at CI and length of deafness at the year 1 testing (P ≤.009) but not from the year 1 testing to EOS testing. Adolescents with progressive deafness and those using oral communication before CI performed significantly better than age-matched peers. Adolescents with prelingual deafness undergoing unilateral CI show significant improvement in objective hearing outcome measures. Patients with shorter lengths of deafness and earlier age at CI tend to outperform their peers. In addition, patients with progressive deafness and those using oral communication have significantly better objective outcomes than their peers.	t	\N
22218296	Visual attention has temporal limitations. In the attentional blink (AB) a stream of stimuli such as letters or digits are presented to a participant on a computer monitor at a rapid rate. Embedded in the stream are two targets that the participant must try to identify. Identification of the second target is severely impaired if it is presented within approximately 500ms of the first target. This is the 'blink' in visual attention. In this study we examined the role of the magnocellular visual pathway in the AB. This fast conducting pathway has high temporal resolution and contrast sensitivity. It is also insensitive to the direction of chromatic contrast, and this attribute was exploited in order to isolate its contributions to temporal attention. Colour defined, luminance noise masked AB streams were compared to AB streams of varying achromatic contrast. The four observers, (2F and 2M) aged between 21 and 35years, had normal visual acuity and colour vision. The colour stimuli produced a similar blink to the moderate contrast achromatic stimuli. This indicates that the magnocellular pathway does not have a privileged role in the attentional blink. We provide an explanation of previous apparently contradictory findings in terms of the role of different types of visual masking in the attentional blink.	t	\N
22232388	The goal of this study was to compare clinical and research-based cochlear implant (CI) measures using telehealth versus traditional methods. This prospective study used an ABA design (A = laboratory, B = remote site). All measures were made twice per visit for the purpose of assessing within-session variability. Twenty-nine adult and pediatric CI recipients participated. Measures included electrode impedance, electrically evoked compound action potential thresholds, psychophysical thresholds using an adaptive procedure, map thresholds and upper comfort levels, and speech perception. Subjects completed a questionnaire at the end of the study. Results for all electrode-specific measures revealed no statistically significant differences between traditional and remote conditions. Speech perception was significantly poorer in the remote condition, which was likely due to the lack of a sound booth. In general, subjects indicated that they would take advantage of telehealth options at least some of the time, if such options were available. Results from this study demonstrate that telehealth is a viable option for research and clinical measures. Additional studies are needed to investigate ways to improve speech perception at remote locations that lack sound booths and to validate the use of telehealth for pediatric services (e.g., play audiometry), sound-field threshold testing, and troubleshooting equipment.	t	\N
22232404	Older adults exhibit difficulty understanding speech that has been experimentally degraded. Age-related changes to the speech mechanism lead to natural degradations in signal quality. We tested the hypothesis that older adults with hearing loss would exhibit declines in speech recognition when listening to the speech of older adults, compared with the speech of younger adults, and would report greater amounts of listening effort in this task. Nineteen individuals with age-related hearing loss completed speech recognition and listening effort scaling tasks. Both were conducted in quiet, when listening to high- and low-predictability phrases produced by younger and older speakers, respectively. No significant difference in speech recognition existed when stimuli were derived from younger or older speakers. However, perceived effort was significantly higher when listening to speech from older adults, as compared with younger adults. For older individuals with hearing loss, natural degradations in signal quality may require greater listening effort. However, they do not interfere with speech recognition-at least in quiet. Follow-up investigation of the effect of speaker age on speech recognition and listening effort under more challenging noise conditions appears warranted.	t	\N
22232413	The ability to detect a tone added to a random masker improves when a preview of the masker is provided. In 2 experiments, the authors explored the role that perceptual organization plays in this release from masking. Detection thresholds were measured in informational masking studies. The maskers were drawn at random prior to each trial. Masker or signal-plus-masker precursors preceded the detection interval, and the time between the precursor and the detection interval was systematically altered. In Experiment 1, the signal frequency was either fixed or random. In Experiment 2, the random masker was composed of harmonics of a common fundamental frequency (F (0)), and the randomly chosen signal frequency was either harmonically related to, or mistuned from, the masker's F (0). For a masker precursor, the release from informational masking withstood longer precursor-detection interval delays (a) when the signal frequency was fixed versus random and (b) when the signal was mistuned relative to a harmonic of the masker's F (0). These results suggest that listeners' ability to attend to the signal may contribute to the long-lived release from masking with a masker precursor.	t	\N
22237163	The aim of this study was to investigate potential effects of age on the ability of normal-hearing (NH) adult listeners to utilize spectral and temporal cues when performing a voice gender identification task. Ten younger and 10 older NH adult listeners were measured on their ability to correctly identify the speaker gender of six different vowel tokens (H-/vowel/-D) when spoken by eight speakers (four male and four female). Spectral (number of channels) and temporal cues (low-pass cut-off frequency for temporal envelope extraction) were systematically manipulated using noiseband vocoding techniques; stimuli contained 1, 4, 8, 16, or 32 spectral channels, while the low-pass cut-off frequency of the temporal envelope filter was 20, 50, 100, 200, or 400 Hz. Furthermore, the fundamental frequencies (F0s) of the vowel tokens were manipulated to create two conditions: "Expanded" (large range of F0 values) and "Compressed" (small range of F0 values). In general, younger listeners performed better than the older listeners but only when stimuli were spectrally degraded. For both the Expanded and Compressed conditions, the overall performance of the younger listeners was better than that of the older listeners, suggesting age-related deficits in both spectral and temporal processing. Furthermore, a significant interaction between age group and temporal envelope cues revealed that older listeners received less benefit from increasing temporal envelope information compared with the benefit observed among younger listeners. In particular, the performance of the younger NH group (collapsed across number of channels), but not the older NH group, improved as the temporal envelope cut-off frequency was increased from 50 to 400 Hz. The results reported here support previous findings of senescent declines in perceiving spectrally reduced speech and temporal amplitude modulation processing. These results suggest that when F0 values are similar to one another, younger listeners can use temporal cues alone to glean voice-pitch information but older listeners exhibit a lessened ability to use such cues. Previous studies have demonstrated the importance of temporal envelope cues in periodicity perception (e.g., gender recognition) by cochlear implant listeners. The results of this study suggest that aging affects the use of such cues, and consequently gender recognition might be poorer among older cochlear implant recipients.	t	\N
22245012	An event-related potential, the Phonological Mapping Negativity (PMN), has been reported to reflect recognition of phonological mismatches in speech stimuli. The purpose of the present study was to explore how the PMN response to the auditory nonsense syllable reflects phonological processing in isolation without the letter prime or lexical/semantic context. Sixty-four nonsense syllable stimuli were composed for each of three stimulus conditions: phonological match (PM), phonological mismatch with similar sound (PMMS), and phonological mismatch with different sound (PMMD), making a total of 192 stimuli. The PMN was measured from fourteen normal-hearing listeners. Electroencephalogram (EEG) activity was recorded while subjects were listening to the stimuli and responding behaviorally. Subjects were asked to determine what vowel-consonant-vowel (VCV) (e.g. /apa/) would be formed from the combination of the preceding vowel (V) (e.g. /a/) and consonant-vowel (CV) (e.g. /pa/), and press a 'correct' or 'incorrect' response button as soon as they decided whether the target VCV stimulus matched their expectation. In this way, along with the PMN, behavioral response accuracy and reaction times were obtained. The results were as follows: (1) PMN amplitude was not different by stimulus condition, (2) PMN amplitude was larger over frontal and central than posterior regions, but not different between the left versus right hemisphere, (3) PMN was detected in the absence of N400, and (4) behavioral responses were more accurate and faster in PMMD than PM and PMMS. Results indicate that the PMN can reflect phonological processing of auditory nonsense syllables in isolation. The scalp distribution of PMN is most dominant in the fronto-central regions without lateralization. Lastly, behavioral response accuracy and reaction times appear to be influenced by the extent of the task difficulty or processing demand rather than by the extent of phonological violation.	t	\N
22247221	We employed a variant of the mask-onset delay paradigm in order to limit the availability of visual information in central and peripheral vision within individual fixations during scene viewing. Subjects viewed full-color scene photos with instructions to search for a target object (Experiment 1) or to study them for a later memory test (Experiment 2). After a fixed interval following the onset of each eye fixation (50-100 ms), the scene was scrambled either in the central visual field or over the entire display. The intact scene was presented when the subject made an eye movement. Our results reconcile different sets of findings from prior research regarding the masking of central and peripheral visual information at different intervals following fixation onset. In particular, we found that when the entire display was scrambled, both search and memory performance were impaired even at relatively long mask-onset intervals. In contrast, when central vision was scrambled, there were subtle impairments that depended on the viewing task. In the 50-ms mask-onset interval, subjects were selectively impaired at identifying, but not in locating, the search target (Experiment 1), while memory performance (Experiment 2) was unaffected in this condition, and hence, the reliance on central and peripheral visual information depends partly on the viewing task.	t	\N
22251050	Given that semantic processes mediate early processes in the elicitation of emotions, we expect that already activated emotion-specific information can influence the elicitation of an emotion. In Experiment 1, participants were exposed to masked International Affective Picture System (IAPS) pictures that elicited either disgust or fear. Following the presentation of the primes, other IAPS pictures were presented as targets that elicited either disgust or fear. The participants' task was to classify the target picture as either disgust or fear evoking. In Experiment 2, we substituted the IAPS primes with facial expressions of either disgust or fear. In Experiment 3, we substituted the IAPS primes with the words disgust or fear. In all three experiments, we found that prime-target combinations of the same emotion were responded to faster than prime-target combinations of different emotions. Our findings suggest that the influence of primes on the elicitation of emotion is mediated by activated schemata or appraisal processes.	t	\N
22253008	Auditory brainstem implants (ABIs) can provide highly beneficial hearing sensations to individuals deafened by bilateral vestibular schwannomas (neurofibromatosis type 2). Relatively little is known about the status of stimulated neurons after long-term ABI use. Direct examination of the cochlear nuclear complex (CN) of one 5-year ABI user indicated no deleterious effect. Recently, we examined the brainstem of a patient who used his ABI daily for 15 years with excellent performance. There was good preservation of CN cell size, morphology, and packing density, a very favorable sign considering that a number of infants are now receiving ABIs.	t	\N
22264101	Our findings show that all cochlear implanted temporal bones had a varied degree of trauma and inflammatory reaction from cochlear implantation. No definitive relationship was observed from our limited number of specimens between residual spiral ganglion cells (SGCs) in implanted temporal bones and clinical speech performance. We hypothesize that there is a relationship between residual SGCs in cochlear implanted temporal bones and clinical speech performance. Our aim was to examine the histopathology of multi-channel cochlear implant temporal bones and to evaluate the relationship of residual SGC counts to clinical hearing performance. Temporal bones from four cochlear implant patients were examined histologically. Comparisons were made between implanted and nonimplanted temporal bones. Clinical performance data were obtained from patient charts. There were varying amounts of inflammation in the basal turn of the cochleae in all four implanted temporal bones. Trauma to the facial nerve at the facial recess was noticed in one case. Surviving dendrites varied from 5% to 30% among four cases, with no relationship to clinical performance. The speech recognition scores, measured with Central Institute of the Deaf (CID) sentence score, varied among patients from 4% to 89%, while the patient with the highest SGCs had the best clinical outcome.	t	\N
22280721	A psychophysical pitch function, describing the relation of perceived magnitude of pitch to the frequency of a pure tone, was determined by absolute magnitude estimation. Pitch estimates were made by listeners with relative pitch and by absolute pitch possessors for 27 tones spanning a frequency range of 31.5-12,500 Hz in 1/3 octave steps. Results show that the pitch function, plotted in log-log coordinates, is steeper below 200 Hz than at higher frequencies. It is hypothesized that the pitch function's bend may reflect the diversity of neurophysiological mechanisms of pitch encoding in frequency ranges below and above 200 Hz. The variation of the function's slope implies that pitch distances between tones with the same frequency ratios are perceived as larger below 200 Hz than at higher frequencies. It is argued that this implication may apply only to a purely sensory concept of pitch distance and cannot be extended to the perception of musical intervals, a phenomenon governed by musical cognitive principles. The results also show that pitch functions obtained for listeners with relative and absolute pitch have a similar shape, which means that quantitative pitch relations determined for both groups of listeners do not differ appreciably along the frequency scale.	t	\N
22289507	In this event-related potential (ERP) study a masking technique that prevents conscious perception of words and non-words through attentional distraction was used to reveal the temporal dynamics of word processing under non-conscious and conscious conditions. In the non-conscious condition, ERP responses differed between masked words and non-words from 112 to 160 ms after stimulus-onset over posterior brain areas. The early onset of the word-non-word differences was compatible with previous studies that reported non-conscious access to orthographic information within this time period. Moreover, source localisations provided evidence for automatic activation of prelexical phonological information, whereas no evidence for non-conscious semantic processing was found. When subjects were informed about the masking technique, lexical differences occurred at later time intervals, suggesting conscious access to additional word related information. These results indicate that early visual word processing does not depend entirely on attentional resources, but that non-conscious processing probably is restricted to rather lower-level linguistic information.	t	\N
22290344	Synesthesia is a sensory disorder where the stimulation of one sensory modality can lead to a reaction in another which would not usually be expected to respond; for instance, someone might see a color on hearing a word such as a day of the week. Disordered perception of sensory information also appears to contribute to the pathophysiology of irritable bowel syndrome (IBS). The purpose of this exploratory study was to ascertain whether these two conditions might be linked in any way. Two hundred consecutive IBS outpatients were screened for synesthesia and compared with 200 matched healthy volunteers (controls). Positive responders were tested for two types of synesthesia (grapheme-color and music-color/shape) using a questionnaire which was repeated after 3 months to test for reproducibility. Of the 200 IBS outpatients screened, 26 (13%) patients and six (3%) controls claimed to be synesthetic (P < 0.001). Reproducibility was more variable in IBS patients than controls but despite this variability, 15 (7.5%) patients compared with 5 (2.5%) controls had greater than 75% consistency (P = 0.036), and 19 (9.5%) patients and 6 (3%) controls had greater than 50% consistency (P = 0.012). A reproducibility of less than 50% was observed in seven (3.5%) patients and no controls (0%) (P = 0.015), and these individuals were classified as having pseudo-synesthesia. IBS patients clearly differ from controls in terms of claiming to have synesthetic experiences. These results justify additional studies on the relationship between IBS and synesthesia to further understand the neural mechanisms underpinning these two conditions and to establish whether they may be linked.	t	\N
22292985	The effects of the use of cochlear implant (CI) on speech intelligibility, speaking rate, and vowel formant characteristics and the relationships between speech intelligibility, speaking rate, and vowel formant characteristics for children are clinically important. The purposes of this study were to report on the comparisons for speaking rate and vowel space area, and their relationship with speech intelligibility, between 24 Mandarin-speaking children with CI and 24 age-sex-education level matched normal hearing (NH) controls. Participants were audio recorded as they read a designed Mandarin intelligibility test, repeated prolongation of each of the three point vowels /i/, /a/, and /u/ five times, and repeated each of three sentences carrying one point vowel five times. Compared to the NH group, the CI group exhibited: (1) mild-to-moderate speech intelligibility impairment; (2) significantly reduced speaking rate mainly due to significantly longer inter-word pauses and larger pause proportion; and (3) significantly less vowel reduction in the horizontal dimension in sustained vowel phonation. The limitations of speech intelligibility development in children after cochlear implantation were related to atypical patterns and to a smaller degree in vowel reduction and slower speaking rate resulting from less efficient articulatory movement transition.	t	\N
22302814	Understanding speech in noisy environments is often taken for granted; however, this task is particularly challenging for people with cochlear hearing loss, even with hearing aids or cochlear implants. A significant limitation to improving auditory prostheses is our lack of understanding of the neural basis for robust speech perception in noise. Perceptual studies suggest the slowly varying component of the acoustic waveform (envelope, ENV) is sufficient for understanding speech in quiet, but the rapidly varying temporal fine structure (TFS) is important in noise. These perceptual findings have important implications for cochlear implants, which currently only provide ENV; however, neural correlates have been difficult to evaluate due to cochlear transformations between acoustic TFS and recovered neural ENV. Here, we demonstrate the relative contributions of neural ENV and TFS by quantitatively linking neural coding, predicted from a computational auditory nerve model, with perception of vocoded speech in noise measured from normal hearing human listeners. Regression models with ENV and TFS coding as independent variables predicted speech identification and phonetic feature reception at both positive and negative signal-to-noise ratios. We found that: (1) neural ENV coding was a primary contributor to speech perception, even in noise; and (2) neural TFS contributed in noise mainly in the presence of neural ENV, but rarely as the primary cue itself. These results suggest that neural TFS has less perceptual salience than previously thought due to cochlear signal processing transformations between TFS and ENV. Because these transformations differ between normal and impaired ears, these findings have important translational implications for auditory prostheses.	t	\N
22304406	Children ask questions and learn from the responses they receive; however, little is known about how children learn from listening to others ask questions. Five experiments examined preschoolers' (N = 179) ability to solve simple problems using information gathered from listening to question-and-answer exchanges between 2 parties present in the same room. Overall, the ability to efficiently use information gathered from overheard exchanges improved between ages 3 and 5. Critically, however, across ages children solved the majority of problems correctly, suggesting preschoolers are capable of learning from others' questions. Moreover, children learned from others' questions without explicit instruction and when engaged in another activity. Implications for the development of problem-solving skills are discussed.	t	\N
22317269	The purpose of this study was to assess normal hearing listeners' performance in detecting a stationary backup alarm signal and to quantify the linear distance at detection point. Detection distances for 12 participants with normal hearing were measured while they were fitted with 7 hearing protectors and while they were unoccluded (open ear). A standard (narrowband) backup alarm signal and a broadband (pulsed white noise) backup alarm signal from Brigade[1] were used. The method of limits, with distance as the physical measurement variable and threshold detection as the task, was employed to find at which distance the participant could first detect the backup alarms. A within-subject Analysis of Variance (ANOVA) revealed a significant main effect of the listening conditions on the detection distance in feet. Post hoc analyses indicated that the Bilsom L3HV conventional passive earmuff (at 1132.2 ft detection distance) was significantly poorer compared to all other HPDs and the open ear in detection distance achieved, and that there were no statistically-significant differences between the unoccluded ear (1652.3 ft), EB-15-Lo BlastPLGTM (1546.2 ft), EB-15-Hi BlastPLGTM (1543.4 ft), E-A-R/3M Combat ArmsTM earplug-nonlinear, level-dependent state (1507.8 ft), E-A-R/3M HiFiTM earplug (1497.7 ft), and Bilsom ImpactTM dichotic electronic earmuff (1567.2 ft). In addition, the E-A-R/3M Combat ArmsTM earplug-passive steady state resulted in significantly longer detection distances than only the open ear condition, at 1474.1 ft versus 1652.3 ft for the open ear. ANOVA also revealed a significant main effect of the backup alarm type on detection distance. The means were 1600.9 ft for the standard (narrowband) backup alarm signal, and a significantly closer 1379.4 ft was required for the Brigade broadband backup alarm signal. For on-ground workers, it is crucial to detect backup alarm signals as far away as possible rather than at close distances since this will provide them more time to react to approaching vehicles. The results of this study suggest that as the attenuation of the hearing protectors increases, precautions should be considered by safety professionals. This is because, as it was the case with the Bilsom passive earmuff and E-A-R/3M Combat ArmsTM earplug-passive steady state, high attenuation minimizes the detection distance and as a result on-foot workers will have less time to react to any approaching vehicle. The main effects of the type of backup alarm signal demonstrated a statistically-significant advantage of the standard backup alarm over the broadband backup alarm on detection distance in feet. The magnitude of the improvement produced by the standard backup alarm was 221.5 feet, a very large margin. For example, with a vehicle backing at 10 mph, the 221.5 ft decrease in detection distance with the Brigade alarm equates to the vehicle arriving 15 seconds sooner at the worker from the point at which its alarm was first heard.	t	\N
22321294	This study was designed to separately test the effect of the cued/cueless nature of deviant stimuli and that of temporal distance between sound and deviance onsets on the mismatch negativity (MMN) as well as to look for discrepancies between behavioural discrimination performances and MMN amplitude when deviants are cueless. Ten healthy adults passively listened to stimuli that were contrasted by the presence or absence of a frequency sweep starting early or late within the sound. Discrimination performances were collected after the electrophysiological sessions. MMNs were much larger for cued than for cueless deviants. The temporal distance between sound and deviance onsets affected MMNs evoked by both cued and cueless deviants, even to the point of abolishing the MMN when cueless deviance occurred late in the stimulus. Behavioural data were at ceiling levels for all conditions, contrasting with the absence of MMN evoked by cueless deviants with late onset. Two mechanisms contribute to the MMN evoked by cued deviants: the memory comparison process and the adaptation/fresh-afferent one. Within the temporal window of integration, the delay at which each component disappears is different. Comparing waveforms evoked by cued versus cueless deviants provides a fairly simple way of isolating the MMN memory-based component.	t	\N
22323627	The ability to detect and track relevant acoustic signals embedded in a background of other sounds is crucial for hearing in complex acoustic environments. This ability is exemplified by a perceptual phenomenon known as "rhythmic masking release" (RMR). To demonstrate RMR, a sequence of tones forming a target rhythm is intermingled with physically identical "Distracter" sounds that perceptually mask the rhythm. The rhythm can be "released from masking" by adding "Flanker" tones in adjacent frequency channels that are synchronous with the Distracters. RMR represents a special case of auditory stream segregation, whereby the target rhythm is perceptually segregated from the background of Distracters when they are accompanied by the synchronous Flankers. The neural basis of RMR is unknown. Previous studies suggest the involvement of primary auditory cortex (A1) in the perceptual organization of sound patterns. Here, we recorded neural responses to RMR sequences in A1 of awake monkeys in order to identify neural correlates and potential mechanisms of RMR. We also tested whether two current models of stream segregation, when applied to these responses, could account for the perceptual organization of RMR sequences. Results suggest a key role for suppression of Distracter-evoked responses by the simultaneous Flankers in the perceptual restoration of the target rhythm in RMR. Furthermore, predictions of stream segregation models paralleled the psychoacoustics of RMR in humans. These findings reinforce the view that preattentive or "primitive" aspects of auditory scene analysis may be explained by relatively basic neural mechanisms at the cortical level.	t	\N
22337498	In this study, the authors (a) investigated whether a group of people with severe aphasia could learn a vocabulary of pantomime gestures through therapy and (b) compared their learning of gestures with their learning of words. The authors also examined whether gesture therapy cued word production and whether naming therapy cued gestures. Fourteen people with severe aphasia received 15 hr of gesture and naming treatments. Evaluations comprised repeated measures of gesture and word production, comparing treated and untreated items. Baseline measures were stable but improved significantly following therapy. Across the group, improvements in naming were greater than improvements in gesture. This trend was evident in most individuals' results, although 3 participants made better progress in gesture. Gains were item specific, and there was no evidence of cross-modality cueing. Items that received gesture therapy did not improve in naming, and items that received naming therapy did not improve in gesture. Results show that people with severe aphasia can respond to gesture and naming therapies. Given the unequal gains, naming may be a more productive therapy target than gesture for many (although not all) individuals with severe aphasia. The communicative benefits of therapy were not examined but are addressed in a follow-up article.	t	\N
22352496	The standard method for the calibration of audiometric bone vibrators requires the use of an artificial mastoid, a device that converts vibratory energy to an electrical analog. The mechanical input impedance of the device is designed to represent the average mechanical impedance of the human head. For calibration purposes, it is not necessary that the coupling device represent the impedance of the head. It is only necessary that it provides a repeatable measurement of the output of the vibrator that can be related to the normal threshold of hearing at each test frequency. In addition to the mechanical output that serves as the stimulus for the hearing test, bone vibrators produce an acoustic signal that is proportional to the mechanical force delivered to the head. By determining the transfer function relating the acoustic sound pressure to the mechanical force, the acoustic signal can serve as a proxy for the vibratory stimulus. This article describes the design and validation of an acoustic coupler for the calibration of audiometric bone vibrators.	t	\N
22352502	The reliability of distortion-product otoacoustic emission (DPOAE) measurements and their relation to loudness measurements was examined in 16 normal-hearing subjects and 58 subjects with hearing loss. The level of the distortion product (L(d)) was compared across two sessions and resulted in correlations that exceeded 0.90. The reliability of DPOAEs was less when parameters from nonlinear fits to the input/output (I/O) functions were compared across visits. Next, the relationship between DPOAE I/O parameters and the slope of the low-level portion of the categorical loudness scaling (CLS) function (soft slope) was assessed. Correlations of 0.65, 0.74, and 0.81 at 1, 2, and 4 kHz were observed between CLS soft slope and combined DPOAE parameters. Behavioral threshold had correlations of 0.82, 0.83, and 0.88 at 1, 2, and 4 kHz with CLS soft slope. Combining DPOAEs and behavioral threshold provided little additional information. Lastly, a multivariate approach utilizing the entire DPOAE I/O function was used to predict the CLS rating for each input level (dB SPL). Standard error of the estimate when using this method ranged from 2.4 to 3.0 categorical units (CU), suggesting that DPOAE I/O functions can predict CLS measures within the CU step size used in this study (5).	t	\N
22352514	Cross-generational and cross-dialectal variation in vowels among speakers of American English was examined in terms of vowel identification by listeners and vowel classification using pattern recognition. Listeners from Western North Carolina and Southeastern Wisconsin identified 12 vowel categories produced by 120 speakers stratified by age (old adults, young adults, and children), gender, and dialect. The vowels /ɝ, o, ʊ, u/ were well identified by both groups of listeners. The majority of confusions were for the front /i, ɪ, e, ɛ, æ/, the low back /ɑ, ɔ/ and the monophthongal North Carolina /aɪ/. For selected vowels, generational differences in acoustic vowel characteristics were perceptually salient, suggesting listeners' responsiveness to sound change. Female exemplars and native-dialect variants produced higher identification rates. Linear discriminant analyses which examined dialect and generational classification accuracy showed that sampling the formant pattern at vowel midpoint only is insufficient to separate the vowels. Two sample points near onset and offset provided enough information for successful classification. The models trained on one dialect classified the vowels from the other dialect with much lower accuracy. The results strongly support the importance of dynamic information in accurate classification of cross-generational and cross-dialectal variations.	t	\N
22352516	This study examined whether speech-on-speech masking is sensitive to variation in the degree of similarity between the target and the masker speech. Three experiments investigated whether speech-in-speech recognition varies across different background speech languages (English vs Dutch) for both English and Dutch targets, as well as across variation in the semantic content of the background speech (meaningful vs semantically anomalous sentences), and across variation in listener status vis-à-vis the target and masker languages (native, non-native, or unfamiliar). The results showed that the more similar the target speech is to the masker speech (e.g., same vs different language, same vs different levels of semantic content), the greater the interference on speech recognition accuracy. Moreover, the listener's knowledge of the target and the background language modulate the size of the release from masking. These factors had an especially strong effect on masking effectiveness in highly unfavorable listening conditions. Overall this research provided evidence that that the degree of target-masker similarity plays a significant role in speech-in-speech recognition. The results also give insight into how listeners assign their resources differently depending on whether they are listening to their first or second language.	t	\N
22352522	Automatic speech recognition (ASR) refers to the task of extracting a transcription of the linguistic content of an acoustical speech signal automatically. Despite several decades of research in this important area of acoustic signal processing, the accuracy of ASR systems is still far behind human performance, especially in adverse acoustic scenarios. In this context, one of the most challenging situations is the one concerning simultaneous speech in cocktail-party environments. Although source separation methods have already been investigated to deal with this problem, the separation process is not perfect and the resulting artifacts pose an additional problem to ASR performance. In this paper, a specific training to improve the percentage of recognized words in real simultaneous speech cases is proposed. The combination of source separation and this specific training is explored and evaluated under different acoustical conditions, leading to improvements of up to a 35% in ASR performance.	t	\N
22352609	There is substantial performance variability among listeners who transcribe degraded speech. Error patterns from 88 listeners who transcribed dysarthric speech were examined to identify differential use of syllabic strength cues for lexical segmentation. Transcripts from listeners were divided into four groups (ranging from Better- to Poorer- performing). Phrases classified as Higher- and Lower-intelligibility were analyzed separately for each performance group to assess the independent variable of severity. Results revealed that all four listener groups used syllabic strength cues for lexical segmentation of Higher-intelligibility speech, but only the Poorer listeners persisted with this strategy for the Lower-intelligibility phrases. This finding and additional analyses suggest testable hypotheses to address the role of cue-use and performance patterns.	t	\N
22353676	Age-related declines in auditory and cognitive processing may contribute to the difficulties with listening in noise that are often reported by older adults. Such difficulties are reported even by those who have relatively good audiograms that could be considered "normal" for their age (ISO 7029-2000 [ISO, 2000]). The Speech, Spatial, and Qualities of Hearing Scale (SSQ; Gatehouse and Noble, 2004) is a questionnaire developed to measure a listener's self-reported ability to hear in a variety of everyday situations, such as those that are challenging for older adults, and it can provide insights into the possible contributions of auditory and cognitive factors to their listening difficulties. The SSQ has been shown to be a sensitive and reliable questionnaire to detect benefits associated with the use of different hearing technologies and potentially other forms of intervention. Establishing how age-matched listeners with audiograms "normal" for their age rate the items on the SSQ could enable an extension of its use in audiological assessment and in setting rehabilitative goals. The main purpose of this study was to investigate how younger and older adults who passed audiometric screening and who had thresholds considered to be "normal" for their age responded on the SSQ. It was also of interest to compare these results to those reported previously for older listeners with hearing loss in an attempt to tease out the relative effects of age and hearing loss. The SSQ was administered to 48 younger (mean age = 19 yr; SD = 1.0) and 48 older (mean age = 70 yr, SD = 4.1) adults with clinically normal audiometric thresholds below 4 kHz. The younger adults were recruited through an introductory psychology course, and the older adults were volunteers from the local community. Both age groups completed the SSQ. The differences between the groups were analyzed. Correlations were used to compare the pattern of results across items for the two age groups in the present study and to assess the relationship between SSQ scores and objective measures of hearing. Comparisons were also made to published results for older adults with hearing loss. The pattern of reported difficulty across items was similar for both age groups, but younger adults had significantly higher scores than older adults on 42 of the 46 items. On average, younger adults scored 8.8 (SD = 0.6) out of 10 and older adults scored 7.7 (SD = 1.2) out of 10. By comparison, scores of 5.5 (SD = 1.9) have been reported for older adults (mean age = 71 yr, SD = 8.1) with moderate hearing loss (Gatehouse and Noble, 2004). By establishing the best scores that could reasonably be expected from younger and older adults with "normal" hearing thresholds, these results provide clinicians with information that should assist them in setting realistic targets for interventions for adults of different ages.	t	\N
22355005	To determine (a) the effect of fundamental frequency (f₀) on speech intelligibility, acceptability, and perceived gender in electrolaryngeal (EL) speakers, and (b) the effect of known gender on speech acceptability in EL speakers. A 2-part study was conducted. In Part 1, 34 healthy adults provided speech recordings using electrolarynges set at 75 Hz, 130 Hz, and 175 Hz, and 36 listeners transcribed the recordings. In Part 2, 22 speech samples were presented to 16 listeners. First, listeners identified the gender of each speaker and judged his or her speech acceptability using rating scales. Second, listeners judged the same samples for speech acceptability when gender information was provided. In Part 1, speakers were significantly more intelligible when using 75-Hz devices. In Part 2, the f₀ of the speech signal significantly impacted listeners' accuracy in perceiving the speaker's gender: In gender-incongruent conditions (males using 175-Hz devices, females using 75-Hz devices), listeners were unable to identify female speakers. Speech acceptability judgments were directly related to intelligibility. Finally, listeners differentially penalized female speakers who used 75-Hz devices when gender information was known. Low f₀ facilitated speech intelligibility. However, at low f₀, listeners were unable to identify females as female, and females were differentially penalized for speech acceptability. Results may have implications for rehabilitation.	t	\N
22355541	The potentiality to find precursors of human language in nonhuman primates is questioned because of differences related to the genetic determinism of human and nonhuman primate acoustic structures. Limiting the debate to production and acoustic plasticity might have led to underestimating parallels between human and nonhuman primates. Adult-young differences concerning vocal usage have been reported in various primate species. A key feature of language is the ability to converse, respecting turn-taking rules. Turn-taking structures some nonhuman primates' adult vocal exchanges, but the development and the cognitive relevancy of this rule have never been investigated in monkeys. Our observations of Campbell's monkeys' spontaneous vocal utterances revealed that juveniles broke the turn-taking rule more often than did experienced adults. Only adults displayed different levels of interest when hearing playbacks of vocal exchanges respecting or not the turn-taking rule. This study strengthens parallels between human conversations and nonhuman primate vocal exchanges.	t	\N
22361165	Sensory-motor interactions between auditory and articulatory representations in the dorsal auditory processing stream are suggested to contribute to speech perception, especially when bottom-up information alone is insufficient for purely auditory perceptual mechanisms to succeed. Here, we hypothesized that the dorsal stream responds more vigorously to auditory syllables when one is engaged in a phonetic identification/repetition task subsequent to perception compared to passive listening, and that this effect is further augmented when the syllables are embedded in noise. To this end, we recorded magnetoencephalography while twenty subjects listened to speech syllables, with and without noise masking, in four conditions: passive perception; overt repetition; covert repetition; and overt imitation. Compared to passive listening, left-hemispheric N100m equivalent current dipole responses were amplified and shifted posteriorly when perception was followed by covert repetition task. Cortically constrained minimum-norm estimates showed amplified left supramarginal and angylar gyri responses in the covert repetition condition at ~100ms from stimulus onset. Longer-latency responses at ~200ms were amplified in the covert repetition condition in the left angular gyrus and in all three active conditions in the left premotor cortex, with further enhancements when the syllables were embedded in noise. Phonetic categorization accuracy and magnitude of voice pitch change between overt repetition and imitation conditions correlated with left premotor cortex responses at ~100 and ~200ms, respectively. Together, these results suggest that the dorsal stream involvement in speech perception is dependent on perceptual task demands and that phonetic categorization performance is influenced by the left premotor cortex.	t	\N
22364395	Young infants perceive an object's trajectory as continuous across occlusion provided the temporal or spatial gap in perception is small. In 3 experiments involving 72 participants the authors investigated the effects of different forms of auditory information on 4-month-olds' perception of trajectory continuity. Provision of dynamic auditory information about the object's trajectory enhanced perception of trajectory continuity. However, a smaller positive effect was also obtained when the sound was continuous but provided no information about the object's location. Finally, providing discontinuous auditory information or auditory information that was dislocated relative to vision had negative effects on trajectory perception. These results are discussed relative to the intersensory redundancy hypothesis and emphasize the need to take an intersensory approach to infant perception.	t	\N
22364434	Vowels with extreme articulatory-acoustic properties act as natural referents. Infant perceptual asymmetries point to an underlying bias favoring these referent vowels. However, as language experience is gathered, distributional frequency of speech sounds could modify this initial bias. The perception of the /i/-/e/ contrast was explored in 144 Catalan- and Spanish-learning infants (2 languages with a different distribution of vowel frequency of occurrence) at 4, 6, and 12 months. The results confirmed an acoustic bias at 4 and 6 months in all infants. However, at 12 months, discrimination was not affected by the acoustic bias but by the frequency of occurrence of the vowel.	t	\N
22366801	Many studies have shown that the visual cortex of blind humans is activated in non-visual tasks. However, the electrophysiological signals underlying this cross-modal plasticity are largely unknown. Here, we characterize the neuronal population activity in the visual and auditory cortex of congenitally blind humans and sighted controls in a complex cognitive task. We recorded magnetoencephalographic responses from participants performing semantic categorization of meaningful sounds that followed the presentation of a semantically related or unrelated haptic object. Source analysis of the spectrally resolved magnetoencephalography data revealed that: (i) neuronal responses to sounds were stronger and longer lasting in the auditory cortex of blind subjects; (ii) auditory stimulation elicited strong oscillatory responses in the visual cortex of blind subjects that closely resembled responses to visual stimulation in sighted humans; (iii) the signal in the gamma frequency range was modulated by semantic congruency between the sounds and the preceding haptic objects; and (iv) signal power in the gamma range was correlated on a trial-by-trial basis between auditory and visual cortex in blind subjects, and the strength of this correlation was modulated by semantic congruency. Our results suggest that specifically oscillatory activity in the gamma range reflects non-visual processing in the visual cortex of blind individuals. Moreover, our results provide evidence that the deprived visual cortex is functionally integrated into a larger network that serves non-visual functions.	t	\N
22367585	In recent years, it has become evident that neural responses previously considered to be unisensory can be modulated by sensory input from other modalities. In this regard, visual neural activity elicited to viewing a face is strongly influenced by concurrent incoming auditory information, particularly speech. Here, we applied an additive-factors paradigm aimed at quantifying the impact that auditory speech has on visual event-related potentials (ERPs) elicited to visual speech. These multisensory interactions were measured across parametrically varied stimulus salience, quantified in terms of signal to noise, to provide novel insights into the neural mechanisms of audiovisual speech perception. First, we measured a monotonic increase of the amplitude of the visual P1-N1-P2 ERP complex during a spoken-word recognition task with increases in stimulus salience. ERP component amplitudes varied directly with stimulus salience for visual, audiovisual, and summed unisensory recordings. Second, we measured changes in multisensory gain across salience levels. During audiovisual speech, the P1 and P1-N1 components exhibited less multisensory gain relative to the summed unisensory components with reduced salience, while N1-P2 amplitude exhibited greater multisensory gain as salience was reduced, consistent with the principle of inverse effectiveness. The amplitude interactions were correlated with behavioral measures of multisensory gain across salience levels as measured by response times, suggesting that change in multisensory gain associated with unisensory salience modulations reflects an increased efficiency of visual speech processing.	t	\N
22371164	The finding that serial recall performance for visually presented items is impaired by concurrently presented task-irrelevant speech or sounds is referred to as the irrelevant-speech/-sound effect (ISE). Substantial evidence has indicated that the impairment of serial rehearsal can result in an ISE, and this may be explained by several models. The present series of experiments has demonstrated an ISE in surprise nonserial recognition tasks in which participants were unaware of the need to maintain a large number of visual items for a later memory test, suggesting that neither the rehearsal nor maintenance of order information is necessary for observing the ISE. This effect was observed for both steady-state and changing-state irrelevant sounds, suggesting that the present results do not derive from a confusion of order information, but instead provide evidence that identity representations can also be impaired by irrelevant sound.	t	\N
22371616	Auditory streaming and visual plaids have been used extensively to study perceptual organization in each modality. Both stimuli can produce bistable alternations between grouped (one object) and split (two objects) interpretations. They also share two peculiar features: (i) at the onset of stimulus presentation, organization starts with a systematic bias towards the grouped interpretation; (ii) this first percept has 'inertia'; it lasts longer than the subsequent ones. As a result, the probability of forming different objects builds up over time, a landmark of both behavioural and neurophysiological data on auditory streaming. Here we show that first percept bias and inertia are independent. In plaid perception, inertia is due to a depth ordering ambiguity in the transparent (split) interpretation that makes plaid perception tristable rather than bistable: experimental manipulations removing the depth ambiguity suppressed inertia. However, the first percept bias persisted. We attempted a similar manipulation for auditory streaming by introducing level differences between streams, to bias which stream would appear in the perceptual foreground. Here both inertia and first percept bias persisted. We thus argue that the critical common feature of the onset of perceptual organization is the grouping bias, which may be related to the transition from temporally/spatially local to temporally/spatially global computation.	t	\N
22371621	Auditory stream segregation involves linking temporally separate acoustic events into one or more coherent sequences. For any non-trivial sequence of sounds, many alternative descriptions can be formed, only one or very few of which emerge in awareness at any time. Evidence from studies showing bi-/multistability in auditory streaming suggest that some, perhaps many of the alternative descriptions are represented in the brain in parallel and that they continuously vie for conscious perception. Here, based on a predictive coding view, we consider the nature of these sound representations and how they compete with each other. Predictive processing helps to maintain perceptual stability by signalling the continuation of previously established patterns as well as the emergence of new sound sources. It also provides a measure of how well each of the competing representations describes the current acoustic scene. This account of auditory stream segregation has been tested on perceptual data obtained in the auditory streaming paradigm.	t	\N
22379692	The attentional blink (AB) is a well-established paradigm in which identification of a target T2 is reduced shortly after presentation of an earlier target T1. An important question concerns the importance of backward masking during the AB. While task switching has been found to be a strong modulator mediating the AB without any masking of T2, the present study investigated whether spatial switching could similarly produce an AB without masking. Using a spatial AB paradigm in which items appeared at different locations; we found (a) a significant AB without backward masking of T2 but no AB when no distractors followed T2, (b) no evidence for Lag 1 sparing. These findings show that when there is a spatial switch between the targets, presenting the distractor following T2 at the same location than T2 (backward masking) is not a necessary condition for the AB to occur, but T2 has to be followed by surrounding distractors (appearing at different locations than T2). This pattern of data confirms that spatial switching is a robust modulator of the AB, but to a less extent than task switching.	t	\N
22384765	Hemodynamic changes can be noninvasively real-time monitored in stroke patients by means of transcranial Doppler sonography (TCD). The aim of this pilot study was to assess hemodynamic changes in both middle cerebral arteries (MCA) in aphasic stroke patients by means of TCD during verbal stimulation. Eight aphasic patients with stroke in the territory of the left MCA were tested by modified Boston Diagnostic Aphasia Examination (BDAE) within 3 days of stroke onset. Both MCA were monitored simultaneously by means of TCD with 2 MHz probes. Basic MCA mean blood flow velocity (MBFV) values were assessed and monitored during verbal stimulation. Verbal stimulation was performed with 30 photos of objects for daily usage, arranged by function. The same test was performed in 16 right-handed healthy controls. In stroke patients, the mean MBFV were 56 cm/s in the left MCA and 56 cm/s in the right MCA. A mean 30% increase was observed in the left MCA and 22% in the right MCA. In healthy controls, a mean 21.7% increase was observed in the left MCA and 18% in the right MCA. A trend toward higher percentage of MBFV increase was observed in the left MCA during verbal stimulations in aphasic patients as compared to control subjects.	t	\N
22390292	Human multisensory systems are known to bind inputs from the different sensory modalities into a unified percept, a process that leads to measurable behavioral benefits. This integrative process can be observed through multisensory illusions, including the McGurk effect and the sound-induced flash illusion, both of which demonstrate the ability of one sensory modality to modulate perception in a second modality. Such multisensory integration is highly dependent upon the temporal relationship of the different sensory inputs, with perceptual binding occurring within a limited range of asynchronies known as the temporal binding window (TBW). Previous studies have shown that this window is highly variable across individuals, but it is unclear how these variations in the TBW relate to an individual's ability to integrate multisensory cues. Here we provide evidence linking individual differences in multisensory temporal processes to differences in the individual's audiovisual integration of illusory stimuli. Our data provide strong evidence that the temporal processing of multiple sensory signals and the merging of multiple signals into a single, unified perception, are highly related. Specifically, the width of right side of an individuals' TBW, where the auditory stimulus follows the visual, is significantly correlated with the strength of illusory percepts, as indexed via both an increase in the strength of binding synchronous sensory signals and in an improvement in correctly dissociating asynchronous signals. These findings are discussed in terms of their possible neurobiological basis, relevance to the development of sensory integration, and possible importance for clinical conditions in which there is growing evidence that multisensory integration is compromised.	t	\N
22390745	The purpose of this study was to investigate the effect of the Global Voice Therapy Model (GVTM) on acoustic, aerodynamic, and perceptual voice measures of four adults seeking voice therapy for a voice disorder. A speech-language pathologist facilitated speaking voice therapy with the four participants using the GVTM. Participants completed acoustic, aerodynamic, and perceptual voice measures at pre- and post-therapy time points. Differences were seen in the voice measures from pre- to post-therapy. The GVTM was successful in facilitating an improvement in the acoustic, aerodynamic, and perceptual measures of the participants.	t	\N
22395654	Tactile sensation, which is one of the earliest developing sensory systems, is very important in the perception of an individual's body and the surrounding physical environment, especially in newborns. However, currently, only little is known about the response of a newborn's brain to tactile sensation. The objective of the present study was to determine the response of a newborn's brain to tactile sensation and to compare the brain responses to various sensory stimuli. Ten healthy newborns, 2-9 days after birth, were enrolled. A multichannel near-infrared spectroscopy system was used to measure brain responses. The probe array covered broad cortical areas, including the parietal, temporal, and occipital areas. We measured cortical hemodynamic changes in response to three different types of stimuli: tactile, auditory, and visual. Activated areas were analyzed by t-tests, and the number of activated channels among the three different stimuli was compared by χ²-tests. The results showed that when the brain responded to each type of stimulation, the corresponding primary sensory area was activated, and tactile stimuli induced broader areas of brain activation than the other two types of stimuli (auditory or visual). Thus, broad brain areas, including the temporal and parietal areas, were activated by tactile stimuli in early newborn periods. These results suggest that there are differences in newborns' reactions to various types of sensory stimuli, which may reflect the importance of tactile sensation in the early newborn period.	t	\N
22403933	Often it is difficult to find a natural explanation as to why a surprising coincidence occurs. In attempting to find one, people may be inclined to accept paranormal explanations. The objective of this study was to investigate whether people with a lower threshold for being surprised by coincidences have a greater propensity to become believers compared to those with a higher threshold. Participants were exposed to artificial coincidences, which were formally defined as less or more probable, and were asked to provide remarkability ratings. Paranormal belief was measured by the Australian Sheep-Goat Scale. An analysis of the remarkability ratings revealed a significant interaction effect between Sheep-Goat score and type of coincidence, suggesting that people with lower thresholds of surprise, when experiencing coincidences, harbor higher paranormal belief than those with a higher threshold. The theoretical aspects of these findings were discussed.	t	\N
22405960	Transcranial magnetic stimulation (TMS) and neuroimaging studies suggest a functional link between the emotion-related brain areas and the motor system. It is not well understood, however, whether the motor cortex activity is modulated by specific emotions experienced during music listening. In 23 healthy volunteers, we recorded the motor evoked potentials (MEP) following TMS to investigate the corticospinal excitability while subjects listened to music pieces evoking different emotions (happiness, sadness, fear, and displeasure), an emotionally neutral piece, and a control stimulus (musical scale). Quality and intensity of emotions were previously rated in an additional group of 30 healthy subjects. Fear-related music significantly increased the MEP size compared to the neutral piece and the control stimulus. This effect was not seen with music inducing other emotional experiences and was not related to changes in autonomic variables (respiration rate, heart rate). Current data indicate that also in a musical context, the excitability of the corticomotoneuronal system is related to the emotion expressed by the listened piece.	t	\N
22405961	Conceptual knowledge is classically supposed to be abstract and represented in an amodal unitary system, distinct from the sensory and motor brain systems. A more recent embodiment view of conceptual knowledge, however, proposes that concepts are grounded in distributed modality-specific brain areas which typically process sensory or action-related object information. Recent neuroimaging evidence suggested the significance of left auditory association cortex encompassing posterior superior and middle temporal gyrus in coding conceptual sound features of everyday objects. However, a causal role of this region in processing conceptual sound information has yet to be established. Here we had the unique chance to investigate a patient, JR, with a focal lesion in left posterior superior and middle temporal gyrus. To test the necessity of this region in conceptual and perceptual processing of sound information we administered four different experimental tasks to JR: Visual word recognition, category fluency, sound recognition and voice classification. Compared with a matched control group, patient JR was consistently impaired in conceptual processing of sound-related everyday objects (e.g., "bell"), while performance for non-sound-related everyday objects (e.g., "armchair"), animals, whether they typically produce sounds (e.g., "frog") or not (e.g., "tortoise"), and musical instruments (e.g., "guitar") was intact. An analogous deficit pattern in JR was also obtained for perceptual recognition of the corresponding sounds. Hence, damage to left auditory association cortex specifically impairs perceptual and conceptual processing of sounds from everyday objects. In support of modality-specific theories, these findings strongly evidence the necessity of auditory association cortex in coding sound-related conceptual information.	t	\N
22410432	This article reports on an investigation of graphophonological processes in deaf readers of French over a 1-year period. Deaf readers are known to have a phonological deficit compared to hearing peers, and conclusions from studies on this question are often conflicting. Among the different types of phonological processing, we can identify graphophonological processes based on correspondences between the oral and the written language. In this investigation, we evaluated graphophonemic and graphosyllabic processes using, in each case, two different tasks varying in their degree of cognitive constraints (CC- vs. CC+). Nineteen 11 year-old deaf students were compared to younger normal readers of the same reading level (RA, n = 17) and to normal readers of the same age (CA, n = 20). Two variables were considered in the analyses: accuracy and response latency. Results show that deaf readers do process written items at the graphophonological level and that graphophonological processes are related to reading ability. Also, results indicate main effects of task (CC- vs. CC+), time (T1 vs. T2), and group. In general, deaf participants' performances are comparable to those of RA and differ from those of CA. Results are discussed within the framework of the study of phonology in deaf readers and its relation to reading acquisition.	t	\N
22411494	To determine the effects of noise and speech style on word learning in typically developing school-age children. Thirty-one participants ages 9;0 (years;months) to 10;11 attempted to learn 2 sets of 8 novel words and their referents. They heard all of the words 13 times each within meaningful narrative discourse. Signal-to-noise ratio (noise vs. quiet) and speech style (plain vs. clear) were manipulated such that half of the children heard the new words in broadband white noise and half heard them in quiet; within those conditions, each child heard one set of words produced in a plain speech style and another set in a clear speech style. Children who were trained in quiet learned to produce the word forms more accurately than those who were trained in noise. Clear speech resulted in more accurate word form productions than plain speech, whether the children had learned in noise or quiet. Learning from clear speech in noise and plain speech in quiet produced comparable results. Noise limits expressive vocabulary growth in children, reducing the quality of word form representation in the lexicon. Clear speech input can aid expressive vocabulary growth in children, even in noisy environments.	t	\N
22411713	This article describes the development and evaluation of The University of Western Ontario (UWO) Plurals Test, which is an English language measure of detection of the word-final fricative cue for plurality. Normative data are provided for 26 listeners with normal hearing and 24 listeners with hearing impairment (children and adults), as are evaluations of the acoustical properties of the stimuli, the test's test-retest reliability, and the test's sensitivity to changes in hearing aid signal processing (e.g., nonlinear frequency compression). Results indicate reliable, repeated outcome measurement at the level of the individual. When compared to a global measure of real-world listening preference, the UWO Plurals Test was found to be somewhat sensitive to the effects of changes in hearing aid signal processing. Findings suggest potential use of the UWO Plurals Test to evaluate aided and unaided ability of listeners between the ages of 6 and 81 years to detect the word-final fricatives /s/ and /z/ as they occur in English plural nouns.	t	\N
22414595	Musicians' skills in auditory processing depend highly on instrument, performance practice, and on level of expertise. Yet, it is not known though whether the style/genre of music might shape auditory processing in the brains of musicians. Here, we aimed at tackling the role of musical style/genre on modulating neural and behavioral responses to changes in musical features. Using a novel, fast and musical sounding multi-feature paradigm, we measured the mismatch negativity (MMN), a pre-attentive brain response, to six types of musical feature change in musicians playing three distinct styles of music (classical, jazz, rock/pop) and in non-musicians. Jazz and classical musicians scored higher in the musical aptitude test than band musicians and non-musicians, especially with regards to tonal abilities. These results were extended by the MMN findings: jazz musicians had larger MMN-amplitude than all other experimental groups across the six different sound features, indicating a greater overall sensitivity to auditory outliers. In particular, we found enhanced processing of pith and sliding up to pitches in jazz musicians only. Furthermore, we observed a more frontal MMN to pitch and location compared to the other deviants in jazz musicians and left lateralization of the MMN to timbre in classical musicians. These findings indicate that the characteristics of the style/genre of music played by musicians influence their perceptual skills and the brain processing of sound features embedded in a musical context. Musicians' brain is hence shaped by the type of training, musical style/genre, and listening experiences.	t	\N
22415447	Although it has been well documented that the spatial inhibitory effect induced by repetition of location (i.e., spatial inhibition of return, or IOR) occurs cross-modally, we do not yet know whether nonspatial (e.g., color-based) repetition-induced inhibition occurs in a cross-modal fashion as well. In the present study, a novel cross-modal paradigm with regard to color-based repetition was adopted. An intervening neutral cue, whose semantic identity was different from those of both the prime and the target, was introduced between the prime and the target in a repetition-priming task. The modalities of the prime, the neutral cue, and the target could be either visual or auditory, and the prime and the target could refer either to the same or to different semantic identities. By adopting this paradigm, we aimed to answer two questions: (1) What are the specific conditions under which cross-modal semantic-based repetition inhibition occurs? (2) Are the representations inhibited in the semantic-based repetition inhibition effect supramodal or modality-specific? Our results suggested that semantic-based repetition inhibition occurs only when the prime and the neutral cue are from the same sensory modality, and it occurs irrespective of whether the modality of the target is cued and irrespective of whether the modality of the target is auditory or visual. Taken together, our results suggest that the occurrence of cross-modal nonspatial repetition inhibition is conditional and that the nonspatial representations inhibited by the repetition inhibition are supramodal.	t	\N
22419678	Infants must learn to make sense of real-world auditory environments containing simultaneous and overlapping sounds. In adults, event-related potential studies have demonstrated the existence of separate preattentive memory traces for concurrent note sequences and revealed perceptual dominance for encoding of the voice with higher fundamental frequency of 2 simultaneous tones or melodies. Here, we presented 2 simultaneous streams of notes (15 semitones apart) to 7-month-old infants. On 50% of trials, either the higher or the lower note was modified by one semitone, up or down, leaving 50% standard trials. Infants showed mismatch negativity (MMN) to changes in both voices, indicating separate memory traces for each voice. Furthermore, MMN was earlier and larger for the higher voice as in adults. When in the context of a second voice, representation of the lower voice was decreased and that of the higher voice increased compared with when each voice was presented alone. Additionally, correlations between MMN amplitude and amount of weekly music listening suggest that experience affects the development of auditory memory. In sum, the ability to process simultaneous pitches and the dominance of the highest voice emerge early during infancy and are likely important for the perceptual organization of sound in realistic environments.	t	\N
22423819	Hearing-aid wearers have reported sound source locations as being perceptually internalized (i.e., inside their head). The contribution of hearing-aid design to internalization has, however, received little attention. This experiment compared the sensitivity of hearing-impaired (HI) and normal-hearing listeners to externalization cues when listening with their own ears and simulated behind-the-ear hearing-aids in increasingly complex listening situations and reduced pinna cues. Participants rated the degree of externalization using a multiple-stimulus listening test for mixes of internalized and externalized speech stimuli presented over headphones. The results showed that HI listeners had a contracted perception of externalization correlated with high-frequency hearing loss.	t	\N
22427328	Imaging studies in blind subjects have consistently shown that sensory and cognitive tasks evoke activity in the occipital cortex, which is normally visual. The precise areas involved and degree of activation are dependent upon the cause and age of onset of blindness. Here, we investigated the cortical language network at rest and during an auditory covert naming task in five bilaterally anophthalmic subjects, who have never received visual input. When listening to auditory definitions and covertly retrieving words, these subjects activated lateral occipital cortex bilaterally in addition to the language areas activated in sighted controls. This activity was significantly greater than that present in a control condition of listening to reversed speech. The lateral occipital cortex was also recruited into a left-lateralized resting-state network that usually comprises anterior and posterior language areas. Levels of activation to the auditory naming and reversed speech conditions did not differ in the calcarine (striate) cortex. This primary 'visual' cortex was not recruited to the left-lateralized resting-state network and showed high interhemispheric correlation of activity at rest, as is typically seen in unimodal cortical areas. In contrast, the interhemispheric correlation of resting activity in extrastriate areas was reduced in anophthalmia to the level of cortical areas that are heteromodal, such as the inferior frontal gyrus. Previous imaging studies in the congenitally blind show that primary visual cortex is activated in higher-order tasks, such as language and memory to a greater extent than during more basic sensory processing, resulting in a reversal of the normal hierarchy of functional organization across 'visual' areas. Our data do not support such a pattern of organization in anophthalmia. Instead, the patterns of activity during task and the functional connectivity at rest are consistent with the known hierarchy of processing in these areas normally seen for vision. The differences in cortical organization between bilateral anophthalmia and other forms of congenital blindness are considered to be due to the total absence of stimulation in 'visual' cortex by light or retinal activity in the former condition, and suggests development of subcortical auditory input to the geniculo-striate pathway.	t	\N
22431327	Previous neuroimaging studies have shown that the patterns of brain activity during the processing of personally relevant names (e.g., own name, friend's name, partner's name, etc.) and the names of famous people (e.g., celebrities) are different. However, it is not known how the activity in this network is influenced by the modality of the presented stimuli. In this fMRI study, we investigated the pattern of brain activations during the recognition of aurally and visually presented full names of the subject, a significant other, a famous person and unknown individuals. In both modalities, we found that the processing of self-name and the significant other's name was associated with increased activation in the medial prefrontal cortex (MPFC). Acoustic presentations of these names also activated bilateral inferior frontal gyri (IFG). This pattern of results supports the role of MPFC in the processing of personally relevant information, irrespective of their modality.	t	\N
22432606	Contact quotient (CQ), measured by electroglottogram (EGG), is a ratio which illustrates the duration of vocal fold contact during one vocal fold period. In the present study CQ(EGG) was calculated from a sustained vowel phonation in three different phonation types (breathy, normal, pressed) at three amplitude threshold levels (25%, 35%, 50%). CQ(EGG) values were compared with experts' perceptual evaluation of the firmness of phonation. The contact time of the vocal folds differed significantly between the different phonation types at all threshold levels (P < 0.01). Perceptual evaluation correlated best with CQ(EGG) at threshold levels 25% and 35%. The results of the linear regression model suggested that by using threshold level 25% the effect of F0 and SPL on CQ(EGG) were not significant.	t	\N
22434397	Female as opposed to male listeners were better able to use a delayed informative cue at the end of a long sentence to report an earlier word which was disrupted by noise. Informative (semantically related) or uninformative (semantically unrelated) word cues were presented 2, 6, or 10 words after a target word whose initial phoneme had been replaced with noise. A total of 84 young adults (45 males) listened to each sentence and then repeated it after its offset. The semantic benefit effect (SBE) was the difference in the accuracy of report of the disrupted target word during informative vs. uninformative sentences. Women had significantly higher SBEs than men even though there were no significant sex differences in terms of number of non-target words reported, the effect of distance between the disrupted target word and the informative cue, or kinds of errors generated. We suggest that the superior ability of women to use delayed semantic information to decode an earlier ambiguous speech signal may be linked to women's tendency to engage the hemispheres more bilaterally than men during word processing. Since the maintenance of semantic context under ambiguous conditions demands more right than left hemispheric resources, this may give women an advantage.	t	\N
22454230	Vibrant Soundbridge (VSB) has been recommended for both adults and children with all types of hearing loss. The aim of this study was to evaluate the objective and subjective benefits with VSB and the difference in benefits for patients with different types of hearing loss. A retrospective case review was conducted on seven consecutive patients who had received VSB implantations at the National University Hospital of Singapore from March 2006 to November 2009. Patients were divided into the Sensorineural Hearing Loss (SNHL) Group and Conductive Hearing Loss (CHL)/Mixed Hearing Loss (MHL) Group. Surgical complications were evaluated, and objective and subjective results were compared between the two groups. No major complications were observed during the follow-up of up to 4 years. Greater objective and subjective benefits were observed in the CHL/MHL Group. Subjective benefits were consistent with objective improvements. Pre-operative counseling for realistic expectations is important, especially for patients with SNHL.	t	\N
22459559	This study examined the role of modality in correct recognition and misinformation acceptance in a naturalistic event cognition task that reflected an everyday life sequence of events. Participants heard, observed or acted out a sequence of events and were tested on memory for these events after being presented with an accurate description of the events or a description containing misinformation. The results indicated that recognition of unaltered information was higher in the enactment condition than the auditory or visual conditions and that this effect persisted over time. Misinformation acceptance for the immediate recognition test was lowest in the auditory condition but this advantage disappeared over time. Modality congruence of the auditory condition with the modality in which misinformation was presented and different retrieval processes underlying recognition of altered and unaltered information may explain these findings.	t	\N
22463939	This case study describes a 45-yr-old female with bilateral, profound sensorineural hearing loss due to Ménière's disease. She received her first cochlear implant in the right ear in 2008 and the second cochlear implant in the left ear in 2010. The case study examines the enhancement to speech recognition, particularly in noise, provided by bilateral cochlear implants. Speech recognition tests were administered prior to obtaining the second implant and at a number of test intervals following activation of the second device. Speech recognition in quiet and noise as well as localization abilities were assessed in several conditions to determine bilateral benefit and performance differences between ears. The results of the speech recognition testing indicated a substantial improvement in the patient's ability to understand speech in noise and her ability to localize sound when using bilateral cochlear implants compared to using a unilateral implant or an implant and a hearing aid. In addition, the patient reported considerable improvement in her ability to communicate in daily life when using bilateral implants versus a unilateral implant. This case suggests that cochlear implantation is a viable option for patients who have lost their hearing to Ménière's disease even when a number of medical treatments and surgical interventions have been performed to control vertigo. In the case presented, bilateral cochlear implantation was necessary for this patient to communicate successfully at home and at work.	t	\N
22465324	Nonverbal emotional vocalizations are one of the most elementary ways of communicating in humans. We examined the impact of sex differences on neural responses to laughter and crying produced by the same and opposite sex. Thirty subjects (15 women) underwent functional magnetic resonance imaging during a sex identification task for laughter, crying, and neutral voices. The parahippocampal gyrus was involved in both men and women while hearing laughter of the same sex, suggesting greater positive emotional processing and greater attention toward emotional context in response to laughter of the same sex than of the opposite sex. The posterior cingulate was involved in both men and women while hearing crying of the opposite sex, suggesting that empathic processing may occur more in response to crying of the opposite sex than of the same sex. Furthermore, brain responses to crying of the opposite sex seem to reflect upon men's efforts to perform emotional regulation and women's empathic concerns.	t	\N
22465475	Neglect is a neurological syndrome characterised by a lack of conscious perception of events localised in the contralesional side of space. Here, we consider the possible multisensory nature of this disorder, critically reviewing the literature devoted to multisensory manifestations and processing in neglect. Although its most striking manifestations have been observed in the visual domain, a number of studies demonstrate that neglect can affect virtually any sensory modality, in particular touch and audition. Furthermore, a few recent studies have reported a correlation in severity between visual and non-visual neglect-related deficits evaluated in the same patients, providing some preliminary support for a multisensory conception of neglect. Sensory stimulation and sensorimotor adaptation techniques, aimed at alleviating neglect, have also been shown to affect several sensory modalities, including some that were not directly affected by the intervention. Finally, in some cases neglect can bias multisensory interactions known to occur in healthy individuals, leading to abnormal behaviour or uncovering multisensory compensation mechanisms. This evidence, together with neurophysiological and neuroimaging data revealing the multisensory role played by the areas that are most commonly damaged in neglect patients, seems to speak in favour of neglect as a multisensory disorder. However, since most previous studies were not conducted with the specific purpose of systematically investigating the multisensory nature of neglect, we conclude that more research is needed to appropriately assess this question, and suggest some methodological guidelines that we hope will help clarify this issue. At present, the conception of neglect as a multisensory disorder remains a promising working hypothesis that may help define the pathophysiology of this syndrome.	t	\N
22476724	That auditory perceptual training may alleviate tinnitus draws on two observations: (1) tinnitus probably arises from altered activity within the central auditory system following hearing loss and (2) sound-based training can change central auditory activity. Training that provides sound enrichment across hearing loss frequencies has therefore been hypothesised to alleviate tinnitus. We tested this prediction with two randomised trials of frequency discrimination training involving a total of 70 participants with chronic subjective tinnitus. Participants trained on either (1) a pure-tone standard at a frequency within their region of normal hearing, (2) a pure-tone standard within the region of hearing loss or (3) a high-pass harmonic complex tone spanning a region of hearing loss. Analysis of the primary outcome measure revealed an overall reduction in self-reported tinnitus handicap after training that was maintained at a 1-month follow-up assessment, but there were no significant differences between groups. Secondary analyses also report the effects of different domains of tinnitus handicap on the psychoacoustical characteristics of the tinnitus percept (sensation level, bandwidth and pitch) and on duration of training. Our overall findings and conclusions cast doubt on the superiority of a purely acoustic mechanism to underpin tinnitus remediation. Rather, the nonspecific patterns of improvement are more suggestive that auditory perceptual training affects impact on a contributory mechanism such as selective attention or emotional state.	t	\N
22480025	In grammar books, the various functions of and as phrasal coordinator and clausal conjunction are treated as standard knowledge. In addition, studies on the uses of and in everyday talk-in-interaction have described its discourse-organizational functions on a more global level. In the phonetic literature, in turn, a range of phonetic forms of and have been listed. Yet, so far few studies have related the phonetic features of and to its function. This contribution surveys a range of phonetic forms of and in a corpus of private American English telephone conversations. It shows that the use of forms such as [ænd], [εn], or [en], among others, is not random but, in essence, correlates with the syntactic-pragmatic scope of and and the cognitive closeness of the items the and connects. This, in turn, allows the phonetic design of and to contribute to the organization of turn-taking. The findings presented are based on conversation-analytic and interactional-linguistic methodology, which includes quantitative analyses.	t	\N
22480027	This paper investigates hearers' use of response tokens (back-channels), in maintaining and differentiating their actions. Initial observations suggest that hearers produce a sequence of phonetically similar responses to disengage from the current topic, and dissimilar responses to engage with the current topic. This is studied systematically by combining detailed interactional and phonetic analysis in a collection of naturally-occurring talk in Norwegian. The interactional analysis forms the basis for labeling actions as maintained ('doing the same') and differentiated ('NOT doing the same'), which is then used as a basis for phonetic analysis. The phonetic analysis shows that certain phonetic characteristics, including pitch, loudness, voice quality and articulatory characteristics, are associated with 'doing the same', as different from 'NOT doing the same'. Interactional analysis gives further evidence of how this differentiation is of systematic relevance in the negotiations of a next turn. This paper addresses phonetic variation and variability by focusing on the relationship between sequence and phonetics in the turn-by-turn development of meaning. This has important implications for linguistic/phonetic research, and for the study of back-channels.	t	\N
22492193	The auditory system codes spatial locations in a way that deviates from the spatial representations found in other modalities. This difference is especially striking in the cortex, where neurons form topographical maps of visual and tactile space but where auditory space is represented through a population rate code. In this hemifield code, sound source location is represented in the activity of two widely tuned opponent populations, one tuned to the right and the other to the left side of auditory space. Scientists are only beginning to uncover how this coding strategy adapts to various spatial processing demands. This review presents the current understanding of auditory spatial processing in the cortex. To this end, the authors consider how various implementations of the hemifield code may exist within the auditory cortex and how these may be modulated by the stimulation and task context. As a result, a coherent set of neural strategies for auditory spatial processing emerges.	t	\N
22500627	Behavior varies from trial to trial even when the stimulus is maintained as constant as possible. In many models, this variability is attributed to noise in the brain. Here, we propose that there is another major source of variability: suboptimal inference. Importantly, we argue that in most tasks of interest, and particularly complex ones, suboptimal inference is likely to be the dominant component of behavioral variability. This perspective explains a variety of intriguing observations, including why variability appears to be larger on the sensory than on the motor side, and why our sensors are sometimes surprisingly unreliable.	t	\N
22501070	Judgments of whether a sinusoidal probe is higher or lower in frequency than the closest partial ("target") in a multi-partial complex are improved when the target is pulsed on and off. These experiments explored the contribution of reduction in perceptual confusion and recovery from adaptation to this effect. In experiment 1, all partials except the target were replaced by noise to reduce perceptual confusion. Performance was much better than when the background was composed of multiple partials. When the level of the target was reduced to avoid ceiling effects, no effect of pulsing the target occurred. In experiment 2, the target and background partials were irregularly and independently amplitude modulated. This gave a large effect of pulsing the target, suggesting that if recovery from adaptation contributes to the effect, amplitude fluctuations do not prevent this. In experiment 3, the background was composed of multiple steady partials, but the target was irregularly amplitude modulated. This gave better performance than when the target was unmodulated and a moderate effect of pulsing the target. It is argued that when the target and background are steady tones, pulsing the target may result both in reduction of perceptual confusion and recovery from adaptation.	t	\N
22501078	Research on children's speech perception and production suggests that consonant voicing and place contrasts may be acquired early in life, at least in word-onset position. However, little is known about the development of the acoustic correlates of later-acquired, word-final coda contrasts. This is of particular interest in languages like English where many grammatical morphemes are realized as codas. This study therefore examined how various non-spectral acoustic cues vary as a function of stop coda voicing (voiced vs. voiceless) and place (alveolar vs. velar) in the spontaneous speech of 6 American-English-speaking mother-child dyads. The results indicate that children as young as 1;6 exhibited many adult-like acoustic cues to voicing and place contrasts, including longer vowels and more frequent use of voice bar with voiced codas, and a greater number of bursts and longer post-release noise for velar codas. However, 1;6-year-olds overall exhibited longer durations and more frequent occurrence of these cues compared to mothers, with decreasing values by 2;6. Thus, English-speaking 1;6-year-olds already exhibit adult-like use of some of the cues to coda voicing and place, though implementation is not yet fully adult-like. Physiological and contextual correlates of these findings are discussed.	t	\N
22501083	This study tested the hypothesis that the reduction in spatial release from masking (SRM) resulting from sensorineural hearing loss in competing speech mixtures is influenced by the characteristics of the interfering speech. A frontal speech target was presented simultaneously with two intelligible or two time-reversed (unintelligible) speech maskers that were either colocated with the target or were symmetrically separated from the target in the horizontal plane. The difference in SRM between listeners with hearing impairment and listeners with normal hearing was substantially larger for the forward maskers (deficit of 5.8 dB) than for the reversed maskers (deficit of 1.6 dB). This was driven by the fact that all listeners, regardless of hearing abilities, performed similarly (and poorly) in the colocated condition with intelligible maskers. The same conditions were then tested in listeners with normal hearing using headphone stimuli that were degraded by noise vocoding. Reducing the number of available spectral channels systematically reduced the measured SRM, and again, more so for forward (reduction of 3.8 dB) than for reversed speech maskers (reduction of 1.8 dB). The results suggest that non-spatial factors can strongly influence both the magnitude of SRM and the apparent deficit in SRM for listeners with impaired hearing.	t	\N
22511719	Monkeys can easily form lasting central representations of visual and tactile stimuli, yet they seem unable to do the same with sounds. Humans, by contrast, are highly proficient in auditory long-term memory (LTM). These mnemonic differences within and between species raise the question of whether the human ability is supported in some way by speech and language, e.g., through subvocal reproduction of speech sounds and by covert verbal labeling of environmental stimuli. If so, the explanation could be that storing rapidly fluctuating acoustic signals requires assistance from the motor system, which is uniquely organized to chain-link rapid sequences. To test this hypothesis, we compared the ability of normal participants to recognize lists of stimuli that can be easily reproduced, labeled, or both (pseudowords, nonverbal sounds, and words, respectively) versus their ability to recognize a list of stimuli that can be reproduced or labeled only with great difficulty (reversed words, i.e., words played backward). Recognition scores after 5-min delays filled with articulatory-suppression tasks were relatively high (75-80% correct) for all sound types except reversed words; the latter yielded scores that were not far above chance (58% correct), even though these stimuli were discriminated nearly perfectly when presented as reversed-word pairs at short intrapair intervals. The combined results provide preliminary support for the hypothesis that participation of the oromotor system may be essential for laying down the memory of speech sounds and, indeed, that speech and auditory memory may be so critically dependent on each other that they had to coevolve.	t	\N
22516238	Over the years, a large body of work on the brain basis of language comprehension has accumulated, paving the way for the formulation of a comprehensive model. The model proposed here describes the functional neuroanatomy of the different processing steps from auditory perception to comprehension as located in different gray matter brain regions. It also specifies the information flow between these regions, taking into account white matter fiber tract connections. Bottom-up, input-driven processes proceeding from the auditory cortex to the anterior superior temporal cortex and from there to the prefrontal cortex, as well as top-down, controlled and predictive processes from the prefrontal cortex back to the temporal cortex are proposed to constitute the cortical language circuit.	t	\N
22516315	The primary goal of this study was to evaluate a nonlinear dynamic approach to the acoustic analysis of dysphonia associated with vocal fold scar and sulcus vocalis. Case-control study. Acoustic voice samples from scar/sulcus patients and age-/sex-matched controls were analyzed using correlation dimension (D2) and phase plots, time-domain based perturbation indices (jitter, shimmer, signal-to-noise ratio [SNR]), and an auditory-perceptual rating scheme. Signal typing was performed to identify samples with bifurcations and aperiodicity. Type 2 and 3 acoustic signals were highly represented in the scar/sulcus patient group. When data were analyzed irrespective of signal type, all perceptual and acoustic indices successfully distinguished scar/sulcus patients from controls. Removal of type 2 and 3 signals eliminated the previously identified differences between experimental groups for all acoustic indices except D2. The strongest perceptual-acoustic correlation in our data set was observed for SNR and the weakest correlation was observed for D2. These findings suggest that D2 is inferior to time-domain based perturbation measures for the analysis of dysphonia associated with scar/sulcus; however, time-domain based algorithms are inherently susceptible to inflation under highly aperiodic (ie, type 2 and 3) signal conditions. Auditory-perceptual analysis, unhindered by signal aperiodicity, is therefore a robust strategy for distinguishing scar/sulcus patient voices from normal voices. Future acoustic analysis research in this area should consider alternative (e.g., frequency- and quefrency-domain based) measures alongside additional nonlinear approaches.	t	\N
22522205	There is ample evidence that individuals with dyslexia have a phonological deficit. A growing body of research also suggests that individuals with dyslexia have problems with categorical perception, as evidenced by weaker discrimination of between-category differences and better discrimination of within-category differences compared to average readers. Whether the categorical perception problems of individuals with dyslexia are a result of their reading problems or a cause has yet to be determined. Whether the observed perception deficit relates to a more general auditory deficit or is specific to speech also has yet to be determined. To shed more light on these issues, the categorical perception abilities of children at risk for dyslexia and chronological age controls were investigated before and after the onset of formal reading instruction in a longitudinal study. Both identification and discrimination data were collected using identical paradigms for speech and non-speech stimuli. Results showed the children at risk for dyslexia to shift from an allophonic mode of perception in kindergarten to a phonemic mode of perception in first grade, while the control group showed a phonemic mode already in kindergarten. The children at risk for dyslexia thus showed an allophonic perception deficit in kindergarten, which was later suppressed by phonemic perception as a result of formal reading instruction in first grade; allophonic perception in kindergarten can thus be treated as a clinical marker for the possibility of later reading problems.	t	\N
22524348	The present manuscript summarizes and discusses the implications of recent neuroimaging studies, which have investigated the relationship between musical expertise and structural, as well as functional, changes in an auditory-related association cortex, namely, the planum temporale (PT). Since the bilateral PT is known to serve as a spectrotemporal processor that supports perception of acoustic modulations in both speech and music, it comes as no surprise that musical expertise corresponds to functional sensitivity and neuroanatomical changes in cortical architecture. In this context, we focus on the following question: To what extent does musical expertise affect the functioning of the left and right plana temporalia? We discuss the relationship between behavioral, hemodynamic, and neuroanatomical data obtained from musicians in light of maturational and developmental issues. In particular, we introduce two studies of our group that show to what extent brains of musicians are more proficient in phonetic task performance.	t	\N
22524375	Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by atypical social and communication skills, repetitive behaviors, and atypical visual and auditory perception. Studies in vision have reported enhanced detailed ("local") processing but diminished holistic ("global") processing of visual features in ASD. Individuals with ASD also show enhanced processing of simple visual stimuli but diminished processing of complex visual stimuli. Relative to the visual domain, auditory global-local distinctions, and the effects of stimulus complexity on auditory processing in ASD, are less clear. However, one remarkable finding is that many individuals with ASD have enhanced musical abilities, such as superior pitch processing. This review provides a critical evaluation of behavioral and brain imaging studies of auditory processing with respect to current theories in ASD. We have focused on auditory-musical processing in terms of global versus local processing and simple versus complex sound processing. This review contributes to a better understanding of auditory processing differences in ASD. A deeper comprehension of sensory perception in ASD is key to better defining ASD phenotypes and, in turn, may lead to better interventions.	t	\N
22529921	Overall success of current tinnitus therapies is low, which may be due to the heterogeneity of tinnitus patients. Therefore, subclassification of tinnitus patients is expected to improve therapeutic allocation, which, in turn, is hoped to improve therapeutic success for the individual patient. The present study aims to define factors that differentially influence subjectively perceived tinnitus loudness and tinnitus-related distress. In a questionnaire-based cross-sectional survey, the data of 4705 individuals with tinnitus were analyzed. The self-report questionnaire contained items about subjective tinnitus loudness, type of onset, awareness and localization of the tinnitus, hearing impairment, chronic comorbidities, sleep quality, and psychometrically validated questionnaires addressing tinnitus-related distress, depressivity, anxiety, and somatic symptom severity. In a binary step-wise logistic regression model, we tested the predictive power of these variables on subjective tinnitus loudness and tinnitus-related distress. The present data contribute to the distinction between subjective tinnitus loudness and tinnitus-related distress. Whereas subjective loudness was associated with permanent awareness and binaural localization of the tinnitus, tinnitus-related distress was associated with depressivity, anxiety, and somatic symptom severity. Subjective tinnitus loudness and the potential presence of severe depressivity, anxiety, and somatic symptom severity should be assessed separately from tinnitus-related distress. If loud tinnitus is the major complaint together with mild or moderate tinnitus-related distress, therapies should focus on auditory perception. If levels of depressivity, anxiety or somatic symptom severity are severe, therapies and further diagnosis should focus on these symptoms at first.	t	\N
22530620	The effortfulness hypothesis implies that difficulty in decoding the surface form, as in the case of age-related sensory limitations or background noise, consumes the attentional resources that are then unavailable for semantic integration in language comprehension. Because ageing is associated with sensory declines, degrading of the surface form by a noisy background can pose an extra challenge for older adults. In two experiments, this hypothesis was tested in a self-paced moving window paradigm in which younger and older readers' online allocation of attentional resources to surface decoding and semantic integration was measured as they read sentences embedded in varying levels of visual noise. When visual noise was moderate (Experiment 1), resource allocation among young adults was unaffected but older adults allocated more resources to decode the surface form at the cost of resources that would otherwise be available for semantic processing; when visual noise was relatively intense (Experiment 2), both younger and older participants allocated more attention to the surface form and less attention to semantic processing. The decrease in attentional allocation to semantic integration resulted in reduced recall of core ideas in both experiments, suggesting that a less organized semantic representation was constructed in noise. The greater vulnerability of older adults at relatively low levels of noise is consistent with the effortfulness hypothesis.	t	\N
22533977	For pediatric cochlear implant (CI) users, CI processor technology, map characteristics, and fitting strategies are known to have a substantial impact on speech perception scores at young ages. It is unknown whether these benefits continue over time as these children reach adolescence. To document changes in CI technology, map characteristics, and speech perception scores in children between elementary grades and high school, and to describe relations between map characteristics and speech perception scores over time. A longitudinal design with participants 8-9-yr-old at session 1 and 15-18-yr-old at session 2. Participants were 82 adolescents with unilateral CIs, who are a subset of a larger longitudinal study. Mean age at implantation was 3.4 yr (range: 1.7-5.4), and mean duration of device use was 5.5 yr (range: 3.8-7.5) at session 1 and 13.3 yr (range: 10.9-15) at session 2. Speech perception tests at sessions 1 and 2 were the Lexical Neighborhood Test (LNT) presented at 70 dB SPL (LNT-70) and Bamford-Kowal-Bench sentences in quiet (BKB-Q) presented at 70 dB SPL. At session 2, the LNT was also administered at 50 dB SPL (LNT-50), and BKB sentences were administered in noise with a +10 dB SNR (BKB-N). CI processor technology type and CI map characteristics (coding strategy, number of electrodes, threshold levels, and comfort levels) were obtained at both sessions. Electrical dynamic range was computed, and descriptive statistics, correlations, and repeated-measures ANOVAs were employed. Participants achieved significantly higher LNT and BKB scores, at 70 dB SPL, at ages 15-18 than at ages 8-9 yr. Forty-two participants had 1-3 electrodes either activated or deactivated in their map between test sessions, and 40 had no change in number of active electrodes (mean change: -0.5; range: -3 to +2). After conversion from arbitrary clinical map units to charge-per-phase in nanocoulombs (nC), no significant difference was found for T levels across time. Average comfort levels (C levels) decreased by 19 nC. Seventy-three participants (89%) upgraded their CI processor technology type. At both sessions, significant correlations were found between electrical dynamic range (EDR) and all speech perception measures except LNT-50 (r range: .31 to .47; p < 0.01). Similarly, significant correlations were also found between C levels and all speech perception measures (r range: .29 to .49; p < 0.01). At session 2, a significant correlation was found between processor technology type and the LNT-50 scores (r = .38; p < 0.01). Significant improvement in speech scores was observed between elementary grades and high school for children who had used a CI since preschool. On average, T levels (nC) and electrode function remained stable for these long-term pediatric users. Analyses of maps did not allow for the determination of the exact cause of C level reductions, though power limitations in new processor systems and changes in perceived loudness over time are possible. Larger EDRs and higher C levels were associated with better speech scores. Newer speech processor technology was associated with better speech scores at a softer level.	t	\N
22542616	Individuals with schizophrenia (SZ) have deviations in auditory perception perhaps attributable to altered neural oscillatory response properties in thalamo-cortical and/or local cortico-cortical circuits. Previous EEG studies of auditory steady-state responses (aSSRs; a measure of sustained neuronal entrainment to repetitive stimulation) in SZ have indicated attenuated gamma range (≈40 Hz) neural entrainment. Stimuli in most such studies have been relatively brief (500-1000 ms) trains of 1 ms clicks or amplitude modulated pure tones (1000 Hz) with short, fixed interstimulus intervals (200-1000 ms). The current study used extended (1500 ms), more aurally dense broadband stimuli (500-4000 Hz noise; previously demonstrated to elicit larger aSSRs) with longer, variable interstimulus intervals (2700-3300 ms). Dense array EEG (256 sensor) was collected while 17 SZ and 16 healthy subjects passively listed to stimuli modulated at 15 different frequencies spanning beta and gamma ranges (16-44 Hz in 2 Hz steps). Results indicate that SZ have augmented aSSRs that were most extreme in the gamma range. Results also constructively replicate previous findings of attenuated low frequency auditory evoked responses (2-8 Hz) in SZ. These findings (i) highlight differential characteristics of low versus high frequency and induced versus entrained oscillatory auditory responses in both SZ and healthy stimulus processing, (ii) provide support for an NMDA-receptor hypofunction-based pharmacological model of SZ, and (iii) report a novel pattern of aSSR abnormalities suggesting that gamma band neural entrainment deviations among SZ may be more complex than previously supposed, including possibly being substantially influenced by physical stimulus properties.	t	\N
22546730	Pseudoneglect is a normal left sided spatial bias observed with attempted bisections of horizontal lines and a normal upward bias observed with attempted bisections of vertical lines. Horizontal pseudoneglect has been attributed to right hemispheric dominance for the allocation of attention. The goal of this study was to test the hypothesis that the upward bias in vertical line bisection may also relate to right hemispheric dominance for the allocation of attention and/or action-intention. Twenty right handed healthy adults were asked to bisect vertical lines presented in the midsagittal plane (center space) and in sagittal planes to the left and right of the midsagittal plane (left and right hemispace) when using a pen held in either the right or left hand. Vertical line bisections were biased upward in all three sagittal planes and higher in left than right hemispace. However, bisections made with the left hand were lower than those made with the right hand. Whereas these results suggest a left hemispace-right hemispheric visuospatial attentional upward bias and a relative left hemispheric-right hand upward action-intentional bias, further studies are needed to document this intentional versus attentional bias and to understand the brain mechanisms that produce these biases.	t	\N
22553024	The temporal context of an acoustic signal can greatly influence its perception. The present study investigated the neural correlates underlying perceptual facilitation by regular temporal contexts in humans. Participants listened to temporally regular (periodic) or temporally irregular (nonperiodic) sequences of tones while performing an intensity discrimination task. Participants performed significantly better on intensity discrimination during periodic than nonperiodic tone sequences. There was greater activation in the putamen for periodic than nonperiodic sequences. Conversely, there was greater activation in bilateral primary and secondary auditory cortices (planum polare and planum temporale) for nonperiodic than periodic sequences. Across individuals, greater putamen activation correlated with lesser auditory cortical activation in both right and left hemispheres. These findings suggest that temporal regularity is detected in the putamen, and that such detection facilitates temporal-lobe cortical processing associated with superior auditory perception. Thus, this study reveals a corticostriatal system associated with contextual facilitation for auditory perception through temporal regularity processing.	t	\N
22553042	Signal duration is important for identifying sound sources and determining signal meaning. Duration-tuned neurons (DTNs) respond preferentially to a range of stimulus durations and maximally to a best duration (BD). Duration-tuned neurons are found in the auditory midbrain of many vertebrates, although studied most extensively in bats. Studies of DTNs across vertebrates have identified cells with BDs and temporal response bandwidths that mirror the range of species-specific vocalizations. Neural tuning to stimulus duration appears to be universal among hearing vertebrates. Herein, we test the hypothesis that neural mechanisms underlying duration selectivity may be similar across vertebrates. We instantiated theoretical mechanisms of duration tuning in computational models to systematically explore the roles of excitatory and inhibitory receptor strengths, input latencies, and membrane time constant on duration tuning response profiles. We demonstrate that models of duration tuning with similar neural circuitry can be tuned with species-specific parameters to reproduce the responses of in vivo DTNs from the auditory midbrain. To relate and validate model output to in vivo responses, we collected electrophysiological data from the inferior colliculus of the awake big brown bat, Eptesicus fuscus, and present similar in vivo data from the published literature on DTNs in rats, mice, and frogs. Our results support the hypothesis that neural mechanisms of duration tuning may be shared across vertebrates despite species-specific differences in duration selectivity. Finally, we discuss how the underlying mechanisms of duration selectivity relate to other auditory feature detectors arising from the interaction of neural excitation and inhibition.	t	\N
22555987	Although it is well known that cisplatin is associated with ototoxicity, there is still a lack of knowledge concerning the ototoxicity of cisplatin, especially in Japanese head and neck cancer patients. The objectives of this study were to determine the incidence rate of cisplatin ototoxicity and to determine the threshold dose causing ototoxicity in the Japanese population. Before-and-after study in a tertiary referral hospital. The distortion product otoacoustic emission (DPOAE) was measured 1 week after each administration of cisplatin in 44 Japanese head and neck cancer patients treated at Kyoto University Hospital. We determined the incidence and threshold dose of cisplatin ototoxicity according to DPOAE data. The incidence of ototoxicity detected by DPOAE was 77.3%. The average DPOAE value was significantly lower in patients who received more than 200 mg/m(2) cisplatin than the baseline DPOAE value. The threshold dose for cisplatin ototoxicity was lower in Japanese patients than in European patients. Our data suggest that Japanese patients are more susceptible to cisplatin-induced ototoxicity. This is presumably caused by a genetic difference.	t	\N
22559374	Previous studies investigating sensitivity to step changes in tempo and prediction of tone onset time have generally utilized isochronous sequences. This study investigates subjects' ability to detect deviations from a gradual change in the tempo of a tone sequence (experiment 1) and their judgment of the perceptually optimal timing of this tone (experiment 2). In experiment 1, inter-onset-intervals within pairs of eight-tone sequences followed a geometric progression to create a gradual tempo change. In one sequence, the final tone was presented either earlier or later than specified by the progression. Subjects performed well at detecting deviations that exaggerated the tempo progression but poorly when it was counteracted. Experiment 2 used similar pairs except that the final tone was always presented earlier in one sequence than the other. Final interval length was adaptively adjusted to subjects' judgments; it was adjudged in best agreement with the progression when its length was roughly half way between the mathematically correct value and the length of the penultimate interval. The data support "multiple-look" and entrainment models of tempo sensitivity and suggest that temporal prediction is based less on the tempo contour of a whole sequence than on the duration of the preceding interval.	t	\N
22559382	Recent evidence suggests that spectral change, as measured by cochlea-scaled entropy (CSE), predicts speech intelligibility better than the information carried by vowels or consonants in sentences. Motivated by this finding, the present study investigates whether intelligibility indices implemented to include segments marked with significant spectral change better predict speech intelligibility in noise than measures that include all phonetic segments paying no attention to vowels/consonants or spectral change. The prediction of two intelligibility measures [normalized covariance measure (NCM), coherence-based speech intelligibility index (CSII)] is investigated using three sentence-segmentation methods: relative root-mean-square (RMS) levels, CSE, and traditional phonetic segmentation of obstruents and sonorants. While the CSE method makes no distinction between spectral changes occurring within vowels/consonants, the RMS-level segmentation method places more emphasis on the vowel-consonant boundaries wherein the spectral change is often most prominent, and perhaps most robust, in the presence of noise. Higher correlation with intelligibility scores was obtained when including sentence segments containing a large number of consonant-vowel boundaries than when including segments with highest entropy or segments based on obstruent/sonorant classification. These data suggest that in the context of intelligibility measures the type of spectral change captured by the measure is important.	t	\N
22561890	The basic deficits underlying the severe and persistent reading difficulties in dyslexia are still highly debated. One of the major topics of debate is whether these deficits are language specific, or affect both verbal and non-verbal stimuli. Recently, Ahissar and colleagues proposed the "anchoring-deficit hypothesis" (Ahissar, Lubin, Putter-Katz, & Banai, 2006), which suggests that dyslexics have a general difficulty in automatic extraction of stimulus regularities from auditory inputs. This hypothesis explained a broad range of dyslexics' verbal and non-verbal difficulties. However, it was not directly tested in the context of reading and verbal memory, which poses the main stumbling blocks to dyslexics. Here we assessed the abilities of adult dyslexics to efficiently benefit from ("anchor to") regularities embedded in repeated tones, orally presented syllables, and written words. We also compared dyslexics' performance to that of individuals with attention disorder (ADHD), but no reading disability. We found an anchoring effect in all groups: all gained from stimulus repetition. However, in line with the anchoring-deficit hypothesis, controls and ADHD participants showed a significantly larger anchoring effect in all tasks. This study is the first that directly shows that the same domain-general deficit, poor anchoring, characterizes dyslexics' performance in perceptual, working memory and reading tasks.	t	\N
22562828	The evidence of a deficit in working memory in specific language impairment (SLI) is of sufficient magnitude to suggest a primary role in developmental language disorder. However, little research has investigated memory in late talkers who recover from their early delay. Drawing on a longitudinal, community sample, this study compared the memory profiles of 3 groups of 5-year-olds: children with SLI who had been identified as late talkers, resolved late talkers (RLTs), and children with typical language development (TLD). Participants were 25 children with SLI, 45 RLTs, and 32 children with TLD. Subtests from the Working Memory Test Battery for Children and the Children's Memory Scale plus recalling sentences and nonword repetition tasks were administered to test the components of Baddeley's working memory model. The SLI group showed significantly poorer performance than the RLT and TLD groups on measures of the phonological loop and episodic buffer. The RLT and TLD groups scored similarly on all memory measures. The results support previous findings that sentence recall and nonword repetition are markers of SLI. Although residual effects of late-talking status may emerge over time, RLTs do not necessarily show memory deficits at 5 years of age despite delayed early vocabulary development.	t	\N
22564904	This investigation examined the effect of repeated exposure to novel and repeated spoken words in typical environments on the intelligibility of 2 synthesized voices and human recorded speech in preschools. Eighteen preschoolers listened to and repeated single words presented in human-recorded speech, DECtalk Paul, and AT&T Voice Michael during 5 experimental sessions. Stimuli consisted of repeated and novel words presented in each speech output condition during each session. Sessions took place in the presence of typically occurring noise in classroom or home settings. There was a significant main effect for voice as participants accurately identified significantly more words in the human-recorded speech and AT&T Voice than in the DECtalk speech output condition. When averaged across speech output conditions, children increased their accuracy as they participated in additional sessions. There was a statistically significant interaction between session and voice. DECtalk had a slightly larger effect of session than did AT&T Voice and human-recorded speech.	t	\N
22568633	Elevated levels of hypoxia-inducible factor 1α (HIF-1α) in middle ear effusion may play an important role in the pathogenesis of bone conduction impairment associated with otitis media with effusion (OME). The mechanism may be related to the up-regulation of nitric oxide (NO) expression. This study was undertaken to investigate the role of HIF-1α in the pathogenesis of sensorineural hearing loss associated with OME. One hundred and eight OME patients were divided into two groups: OME without bone conduction impairment (group 1) and OME with bone conduction impairment (group 2). The levels of HIF-1α, NO, and quinolinic acid (QUIN) in the middle ear effusion and serum of these patients were investigated. The relationship between these factors and the bone conduction threshold (BCT) differences were analyzed. The levels of HIF-1α and NO concentrations in the middle ear effusion were found to be signiﬁcantly higher in group 2 than in group 1 (both p < 0.05). The OME patients' BCT differences at 4000 Hz were correlated with the levels of HIF-1α and the NO concentrations in the middle ear effusion. Furthermore, the HIF-1α levels were correlated with the levels of NO but not with the levels of QUIN in the effusion.	t	\N
22568993	Both 80 Hz auditory steady state responses (ASSRs) and tone burst auditory brainstem responses (ABRs) have been shown to provide reasonable estimates of the behavioral thresholds. Although ASSRs provide statistically objective estimates that can be easily automated by computers, they present no information for the neurophysiological interpretation of the results. ABRs, on the other hand, do not provide easily automated information and usually need expert interpretation of the recorded waveforms. A recently developed continuous loop averaging deconvolution algorithm offers an alternative solution by acquiring slightly jittered 80 Hz quasi auditory steady state responses (QASSRs), thus enabling the acquisition of both recordings simultaneously. The purpose of this study is to investigate a specially developed 80 Hz QASSR paradigm for simultaneous acquisition for both responses for threshold detection purposes. Sixteen ears from eight adults with normal hearing were tested. Amplitude modulated QASSRs were obtained using slightly jittered temporal sequences of tone bursts presented at a mean rate of 78.125 Hz. Four carrier frequencies (500, 1000, 2000, and 4000 Hz) at several stimulus intensity levels were monaurally presented and QASSRs to 128 sweeps blocks were recorded. The ABRs were extracted using the CLAD algorithm. Wave V was visually identified and analyzed in the time domain as in everyday clinical practice. In addition, statistically objective ƒMP computation method was used to automatically detect ABR threshold as well. The QASSRs were analyzed in the frequency domain and magnitudes, phase delays, and thresholds were obtained. Phasor (polar plot) diagrams were constructed. QASSR and ABR hearing thresholds were obtained and compared with behavioral thresholds. Study reveals that the QASSR method provides accurate objective estimation of the audiometric thresholds from extracted ASSRs and latency/amplitude information from extracted ABRs. The largest mean threshold difference for QASSR was within 5 dB for all carrier frequencies including 500 Hz. For auditory threshold estimation in adults with normal hearing, the Hotelling's T-Square test in four dimensions in the frequency domain was more accurate than the ƒMP or visual ABR threshold detection in the time domain. Simultaneously recorded ASSR and ABR from QASSRs provide accurate and effective method for frequency-specific hearing threshold estimation with neurophysiological information in adults with normal hearing. Further research is required for hearing-impaired adults, newborns, and infants.	t	\N
22570723	Multisensory learning and resulting neural brain plasticity have recently become a topic of renewed interest in human cognitive neuroscience. Music notation reading is an ideal stimulus to study multisensory learning, as it allows studying the integration of visual, auditory and sensorimotor information processing. The present study aimed at answering whether multisensory learning alters uni-sensory structures, interconnections of uni-sensory structures or specific multisensory areas. In a short-term piano training procedure musically naive subjects were trained to play tone sequences from visually presented patterns in a music notation-like system [Auditory-Visual-Somatosensory group (AVS)], while another group received audio-visual training only that involved viewing the patterns and attentively listening to the recordings of the AVS training sessions [Auditory-Visual group (AV)]. Training-related changes in cortical networks were assessed by pre- and post-training magnetoencephalographic (MEG) recordings of an auditory, a visual and an integrated audio-visual mismatch negativity (MMN). The two groups (AVS and AV) were differently affected by the training. The results suggest that multisensory training alters the function of multisensory structures, and not the uni-sensory ones along with their interconnections, and thus provide an answer to an important question presented by cognitive models of multisensory training.	t	\N
22571383	Previous studies of source monitoring and auditory hallucinations (AH) have often conflated spatial source (internal-external) with source agency (self-other). Other studies have used suboptimal manipulations of auditory space (e.g., imagine saying vs. saying aloud). We avoided these problems by presenting experimenter-generated stimuli over headphones in the voice of another person so that the location of the voice sounded either internal or external to the participant's head. Participants (N=121) studied 96 words and indicated for each whether it was presented internally or externally (online spatial source monitoring). At test, studied words were presented visually, intermixed randomly with 96 unstudied words. Participants indicated whether each item was old or new (item memory) and whether it was presented internally or externally during study (spatial source memory). Independent measures of memory accuracy and response bias were derived for online source monitoring, item memory and source memory using signal detection theory. Performance on these measures was compared between two groups of 30 participants who scored low or high on a measure of AH proneness. ANOVAs revealed no differences between the high- and low-AH groups in online spatial source monitoring, item memory, or spatial source memory. We found no evidence that proneness to AH in a sample of healthy volunteers was related to any of the measures of spatial source monitoring performance. We recommend that the methods introduced be applied to future investigations of spatial source monitoring with patient groups and with individuals at-risk for psychosis.	t	\N
22584229	Children's language skills develop rapidly with increasing age, and several studies indicate that they use language- and age-specific strategies to understand complex sentences. In the present experiment, functional magnetic resonance imaging (fMRI) and behavioral measures were used to investigate the acquisition of case-marking cues for sentence interpretation in the developing brain of German preschool children with a mean age of 6 years. Short sentences were presented auditorily, consisting of a transitive verb and two case-marked arguments with canonical subject-initial or non canonical object-initial word order. Overall group results revealed mainly left hemispheric activation in the perisylvian cortex with increased activation in the inferior parietal cortex (IPC), and the anterior cingulate cortex (ACC) for object-initial compared to subject-initial sentences. However, single-subject analysis suggested two distinct activation patterns within the group which allowed a classification into two subgroups. One subgroup showed the predicted activation increase in the left inferior frontal gyrus (IFG) for the more difficult object-initial compared to subject-initial sentences, while the other group showed the reverse effect. This activation in the left IFG can be taken to reflect the degree to which adult-like sentence processing strategies, necessary to integrate case-marking information, are applied. Additional behavioral data on language development tests show that these two subgroups differ in their grammatical knowledge. Together with these behavioral findings, the results indicate that the use of a particular processing strategy is not dependent on age as such, but rather on the child's individual grammatical knowledge and the ability to use specific language cues for successful sentence comprehension.	t	\N
22595658	The aim of this experiment was to examine the preattentive processing of syllables in 9-11-year-old children with dyslexia and matched controls using the Mismatch Negativity (MMN), an auditory Event-Related brain potential (ERP) related to preattentive discrimination. Children were presented with a sequence of syllables that included standards (the syllable "Ba") and deviants in vowel frequency, vowel duration and Voice Onset Time (VOT) that were either close to or far from the standard (Small and Large deviants). No between-group differences were found for frequency deviants. However, whilst normal-reading children showed larger MMNs to Large than to Small deviants in vowel duration and VOT, no such deviance size effect was found in children with dyslexia. These results are taken to indicate that the preattentive processing of vowel duration and VOT is impaired in children with dyslexia, with no impairment in the processing of vowel frequency deviants. By revealing processing deficits of both duration and VOT deviants, these results suggest a strong link between acoustical and phonological processing.	t	\N
22609772	Older adults often find it more difficult than younger adults to attend to a target talker when there are other people talking. One possible reason for this difficulty is that it may take them longer to perceptually segregate the target speech from competing speech. This study investigated age-related differences in the time it takes to segregate target speech from either a speech spectrum noise masker or a babble masker (many people talking simultaneously). Specifically, we employed five different delays (0.1 s-1.1 s) between masker onset and target speech onset. Four signal-to-masker ratios were employed at each delay to determine the 50% thresholds for word recognition accuracy when target words were masked by either speech spectrum noise or multi-talker babble. Thresholds for word recognition decreased exponentially as a function of the masker-word-onset delay, at the same rate for younger and older adults, when the masker was speech spectrum noise. When the masker was babble, thresholds for younger adults decreased exponentially with delay at the same rate as they did when the masker was speech spectrum noise. The word recognition thresholds for older adults, however, did not appear to change over the range of delays explored in this study. In addition, the average difference between word recognition thresholds for younger and older adults (younger adult thresholds < older adult thresholds) was significantly larger when the masker was babble than when it was noise. These results indicate that older adults are as fast as younger adults at separating speech from a steady-state noise masker, but are not as capable as younger adults of taking advantage of the delayed onset of the speech target when the masker is babble. The potential contributions of age-related sensory and cognitive declines to these stream segregation effects are discussed. Finally, we conclude that age-related differences in the timeline for stream segregation contribute to the difficulties older adults experience in listening to speech in a background of babble.	t	\N
22633004	While perceiving speech, people see mouth shapes that are systematically associated with sounds. In particular, a vertically stretched mouth produces a /woo/ sound, whereas a horizontally stretched mouth produces a /wee/ sound. We demonstrate that hearing these speech sounds alters how we see aspect ratio, a basic visual feature that contributes to perception of 3D space, objects and faces. Hearing a /woo/ sound increases the apparent vertical elongation of a shape, whereas hearing a /wee/ sound increases the apparent horizontal elongation. We further demonstrate that these sounds influence aspect ratio coding. Viewing and adapting to a tall (or flat) shape makes a subsequently presented symmetric shape appear flat (or tall). These aspect ratio aftereffects are enhanced when associated speech sounds are presented during the adaptation period, suggesting that the sounds influence visual population coding of aspect ratio. Taken together, these results extend previous demonstrations that visual information constrains auditory perception by showing the converse - speech sounds influence visual perception of a basic geometric feature.	t	\N
22641191	The present study uses a systems engineering approach to delineate the relationship between tinnitus and hyperacusis as a result of either hearing loss in the ear or an imbalanced state in the brain. Specifically examined is the input-output function, or loudness growth as a function of intensity in both normal and pathological conditions. Tinnitus reduces the output dynamic range by raising the floor, while hyperacusis reduces the input dynamic range by lowering the ceiling or sound tolerance level. Tinnitus does not necessarily steepen the loudness growth function but hyperacusis always does. An active loudness model that consists of an expansion stage following a compression stage can account for these key properties in tinnitus and hyperacusis loudness functions. The active loudness model suggests that tinnitus is a result of increased central noise, while hyperacusis is due to increased nonlinear gain. The active loudness model also generates specific predictions on loudness growth in tinnitus, hyperacusis, hearing loss or any combinations of the three conditions. These predictions need to be verified by experimental data and have explicit implications for treatment of tinnitus and hyperacusis.	t	\N
22646514	Sensory consequences of our own actions are perceived differently from the sensory stimuli that are generated externally. The present event-related potential (ERP) study examined the neural responses to self-triggered stimulation relative to externally-triggered stimulation as a function of delays between the motor act and the stimulus onset. While sustaining a vowel phonation, subjects clicked a mouse and heard pitch-shift stimuli (PSS) in voice auditory feedback at delays of either 0 ms (predictable) or 500-1000 ms (unpredictable). The motor effect resulting from the mouse click was corrected in the data analyses. For the externally-triggered condition, PSS were delivered by a computer with a delay of 500-1000 ms after the vocal onset. As compared to unpredictable externally-triggered PSS, P2 responses to predictable self-triggered PSS were significantly suppressed, whereas an enhancement effect for P2 responses was observed when the timing of self-triggered PSS was unpredictable. These findings demonstrate the effect of the temporal predictability of stimulus delivery with respect to the motor act on the neural responses to self-triggered stimulation. Responses to self-triggered stimulation were suppressed or enhanced compared with the externally-triggered stimulation when the timing of stimulus delivery was predictable or unpredictable. Enhancement effect of unpredictable self-triggered stimulation in the present study supports the idea that sensory suppression of self-produced action may be primarily caused by an accurate prediction of stimulus timing, rather than a movement-related non-specific suppression.	t	\N
22648606	According to many theories of decision making, of which signal detection theory is the most prominent, randomness is the main factor responsible for imperfect performance. These theories imply that correcting for attenuation due to randomness should result in perfect scores as long as the participants use nonextreme decision criteria. On the basis of a recent advance termed potential performance theory (Trafimow & Rice, Psychological Review 115:447-462, 2008), we performed auditory and visual detection experiments and corrected the scores for attenuation. Most participants in both experiments tended to perform at a less-than-perfect level, even after their scores were corrected. The findings demonstrate that at least one systematic factor influences detection that is not included in signal detection theory.	t	\N
22653919	The authors investigated lengthening effects in child-directed speech (CDS) across the sentence, testing the additive effects on duration of Word Position, Register, Focus, and Sentence Mode (statement/question). Five theater students produced 6 sentences containing 5 monosyllabic words in a simulated dialogue, varying in Register, Focus, and Sentence Mode. The authors segmented a total of 1,800 sentences using forced-alignment tools, and they analyzed the duration of each word. The results show significant effects of Register, Word Position, and their interactions. The simple effect of Register was significant in all 5 word positions, indicating a global elongation effect in CDS. Interestingly, there was no proportional increase of the final word in CDS. In addition, the 3-way interactions Register × Word Position × Focus and Register × Word Position × Sentence Mode were significant, which converge to the conclusion that the utterance-final word in CDS is additively elongated when it is focused and in a statement. Elongation in CDS is a global effect, but the additive effects of duration demonstrated in the authors' data suggest that the effect of enhanced utterance-final lengthening in CDS in naturalistic samples may be a by-product of discourse characteristics of CDS.	t	\N
22664896	To examine the association between dehiscence length in patients with superior semicircular canal dehiscence syndrome and their clinical findings, including objective audiometric and vestibular testing results. Retrospective study. Tertiary referral center. Patients included in this study were diagnosed with superior semicircular canal dehiscence syndrome and underwent surgical repair of the dehiscence through middle fossa craniotomy. The dehiscence length was measured intraoperatively in all cases. Correlation between dehiscence length with pure-tone average (PTA), average bone-conduction threshold, maximal air-bone gap, cervical vestibular evoked myogenic potential thresholds, and presenting signs and symptoms. The correlation between dehiscence length and maximal air-bone gap was statistically significant on both univariate and multivariate regression analyses. The correlations between dehiscence length and PTA, average bone-conduction threshold, cervical vestibular evoked myogenic potential threshold, and presenting signs and symptoms were not statistically significant. The dehiscence length correlated positively with the maximal air-bone gap in patients with superior semicircular canal dehiscence. The correlation was statistically significant. The dehiscence length did not correlate with the other variables examined in this study.	t	\N
22666781	The purpose of the study was to acoustically compare the performance of children who do and do not stutter on diadochokinesis tasks in terms of syllable duration, syllable periods, and peak intensity. In this case-control study, acoustical analyses were performed on 26 children who stutter and 20 aged-matched normally fluent children (both groups stratified into preschoolers and school-aged children) during a diadochokinesis task: the repetition of articulatory segments through a task testing the ability to alternate movements. Speech fluency was assessed using the Fluency Profile and the Stuttering Severity Instrument. The children who stutter and those who do not did not significantly differ in terms of the acoustic patterns they produced in the diadochokinesis tasks. Significant differences were demonstrated between age groups independent of speech fluency. Overall, the preschoolers performed poorer. These results indicate that the observed differences are related to speech-motor age development and not to stuttering itself. Acoustic studies demonstrate that speech segment durations are most variable, both within and between subjects, during childhood and then gradually decrease to adult levels by the age of eleven to thirteen years. One possible explanation for the results of the present study is that children who stutter presented higher coefficients of variation to exploit the motor equivalence to achieve accurate sound production (i.e., the absence of speech disruptions).	t	\N
22672110	Auditory spatial deficits occur frequently after hemispheric damage; a previous case report suggested that the explicit awareness of sound positions, as in sound localisation, can be impaired while the implicit use of auditory cues for the segregation of sound objects in noisy environments remains preserved. By assessing systematically patients with a first hemispheric lesion, we have shown that (1) explicit and/or implicit use can be disturbed; (2) impaired explicit vs. preserved implicit use dissociations occur rather frequently; and (3) different types of sound localisation deficits can be associated with preserved implicit use. Conceptually, the dissociation between the explicit and implicit use may reflect the dual-stream dichotomy of auditory processing. Our results speak in favour of systematic assessments of auditory spatial functions in clinical settings, especially when adaptation to auditory environment is at stake. Further, systematic studies are needed to link deficits of explicit vs. implicit use to disability in everyday activities, to design appropriate rehabilitation strategies, and to ascertain how far the explicit and implicit use of spatial cues can be retrained following brain damage.	t	\N
22686693	The goal of an action can consist of generating a change in the environment (to produce an effect) or changing one's own situation in the environment (to move to a physical target). To investigate whether the mechanisms of effect-directed and target-directed action control are similar, participants performed continuous reversal movements. They either synchronized movement reversals with regularly presented tones (temporal targets) or produced tones at reversals isochronously (temporal effects). In both goal conditions an irrelevant goal characteristic was integrated into the goal representation (loudness, Experiment 1). When targets and effects were presented within the same reversal movement, similarities were enhanced (Experiment 2). When the task posed spatial demands in addition to temporal demands, target- and effect-directed movement kinematics changed equally with tempo (Experiment 3). Correlations between target-directed and effect-directed movements in temporal variability indicated similar timing mechanisms (Experiments 1 and 2). Only gradual differences between target- and effect-directed movements were observed. We conclude that the same mechanisms of action control, including the anticipation of upcoming events, underlie effect-directed and target-directed movements. Ideomotor theories of action control should incorporate action targets as goals similar to action effects.	t	\N
22696248	We examined the effects of hedges and the discourse marker like on how people recalled specific details about precise quantities in spontaneous speech. We found that listeners treated hedged information differently from like-marked information, although both are thought to be indicators of uncertainty or vagueness. In addition, hedges had different effects depending on whether speakers were (1) retelling conversations to another person or (2) answering questions about material they had heard. When retelling to another person, listeners were more likely to report information that was either unmarked or marked with a like than hedged information (Experiment 1). Yet when answering questions by themselves, hedges enhanced memory for details, in comparison with likes (Experiment 2). Hedges appear to provide pragmatic cues about what information is reliable enough to repeat in a conversational context. But although hedged information may be left out, it is not forgotten.	t	\N
22696304	This study determined the effects of phonology and semantics on the distribution of cortical activity to the second of a pair of words in first and second language (mixed pairs). The effects of relative proficiency in the two languages and linguistic setting (monolinguistic or mixed) are reported in a companion paper. Ten early bilinguals and 14 late bilinguals listened to mixed pairs of words in Arabic (L1) and Hebrew (L2) and indicated whether both words in the pair had the same or different meanings. The spatio-temporal distribution of current densities of event-related potentials were estimated for each language and according to semantic and phonologic relationship (same or different) compared with the first word in the pair. During early processing (<300 ms), brain activity in temporal and temporoparietal auditory areas was enhanced by phonologic incongruence between words in the pair and in Wernicke's area by both phonologic and semantic priming. In contrast, brain activities during late processing (>300 ms) were enhanced by semantic incongruence between the two words, particularly in temporal areas and in left hemisphere Broca's and Wernicke's areas. The latter differences were greater when words were in L2. Surprisingly, no significant effects of relative proficiency on processing the second word in the pair were found. These results indicate that the distribution of brain activity to the second of two words presented bilingually is affected differently during early and late processing by both semantic and phonologic priming by- and incongruence with the immediately preceding word.	t	\N
22698777	Functional near-infrared spectroscopy (fNIRS), a non-invasive neuroimaging optical technique which measures the cortical concentration changes in oxygenated and deoxygenated hemoglobin (O(2)Hb and HHb, respectively), has been extensively utilized in language studies. Most of these studies investigated the ventrolateral/dorsolateral cortex responses, while few language studies on the frontopolar cortex are reported. The aim of this study was to investigate by fNIRS the frontopolar cortex response to a letter verbal fluency task (VFT) in single healthy subjects to better understand the symmetry/asymmetry of language processing. The O(2)Hb and HHb changes were measured on 33 University students by a 8-channel fNIRS system. A significant increase in O(2)Hb (p<0.001), accompanied by a smaller significant decrease in HHb (p<0.001), was observed in each measurement point. However, the laterality index of 21 out of the 33 subjects evidenced a hemispheric dominance (right 9, left 12). Although these results have confirmed a bilateral activation over the frontopolar cortex upon VFT, no clear pattern of lateralization was found. Considering the importance of establishing a response pattern related to cognitive functions in clinical populations, the fNIRS investigation of the frontopolar cortex (and other areas involved in language) in single subject and the use of the laterality index are recommended.	t	\N
22699985	To report and review the clinical experiences of patients who required reimplantation from an ongoing trial of patients with partial deafness who were treated with electroacoustic stimulation (EAS) cochlear implantation. Retrospective case series review. Tertiary referral center. Two patients with partial deafness, 1 child and 1 adult, who required reimplantation because of device failure occurring 12 to 18 months after hearing preservation cochlear implantation with a Med-El Sonata Flex-EAS electrode array. Reimplantation (with full insertion) of a Med-El Sonata Flex-EAS array (child) and the new complete cochlear coverage Med-El Sonata Flex-28 electrode array (adult). Surgical techniques used include round window insertion with slow insertion speed and the use of preoperative systemic steroids and preoperative, perioperative, and postimplantation intratympanic steroids. Preservation of residual hearing. Both patients had complete preservation of residual hearing after reimplantation. The adult patient had stable improvement in hearing from 750 to 2,000 Hz of 5 to 10 dB. Both patients reported increased benefit after reimplantation. We report a case series of successful pediatric and adult EAS reimplantation, in the adult hearing improvement after reimplantation with a deep insertion electrode was observed. Reimplantation with preservation of residual hearing in patients with EAS is possible with current surgical hearing preserving techniques and atraumatic electrode arrays of variable length.	t	\N
22709398	Infants begin to segment novel words from speech by 7.5 months, demonstrating an ability to track, encode and retrieve words in the context of larger units. Although it is presumed that word recognition at this stage is a prerequisite to constructing a vocabulary, the continuity between these stages of development has not yet been empirically demonstrated. The goal of the present study is to investigate whether infant word segmentation skills are indeed related to later lexical development. Two word segmentation tasks, varying in complexity, were administered in infancy and related to childhood outcome measures. Outcome measures consisted of age-normed productive vocabulary percentiles and a measure of cognitive development. Results demonstrated a strong degree of association between infant word segmentation abilities at 7 months and productive vocabulary size at 24 months. In addition, outcome groups, as defined by median vocabulary size and growth trajectories at 24 months, showed distinct word segmentation abilities as infants. These findings provide the first prospective evidence supporting the predictive validity of infant word segmentation tasks and suggest that they are indeed associated with mature word knowledge. A video abstract of this article can be viewed at http://www.youtube.com/watch?v=jxzLi5oLZQ8.	t	\N
22717191	Patients with schizophrenia consistently demonstrate information processing abnormalities assessed with visual masking (VM) tasks, and these deficits have been linked to clinical and functional severity. It has been suggested that VM impairments may be a vulnerability marker in individuals at risk for developing psychosis. Forward and backward VM performance was assessed in 72 first-episode (FE) psychosis patients, 98 subjects at risk (AR) for psychosis and 98 healthy controls (HC) using two identification tasks (with either a high- or low-energy mask) and a location task. VM was examined for stability in a subgroup (FE, n=15; AR, n=35; HC, n=21) and assessed relative to clinical and functional measures. In the identification tasks, backward VM deficits were observed in both FE and AR relative to HC whereas forward VM deficits were only present in FE patients compared to HC. In the location task, AR subjects demonstrated superior performance in forward VM relative to HC. VM performance was stable over time, and VM deficits were associated with baseline functional measures and predicted future negative symptom severity in AR subjects. Visual information processing deficits, as indexed by backward VM, are present before and after the onset of frank psychosis, and probably represent a stable vulnerability marker that is associated with negative symptoms and functional decline. Additionally, the paradoxically better performance of AR subjects in select forward tasks suggests that early compensatory changes may characterize an emerging psychotic state.	t	\N
22721630	Vocal expressions commonly elicit activity in superior temporal and inferior frontal cortices, indicating a distributed network to decode vocally expressed emotions. We examined the involvement of this fronto-temporal network for the decoding of angry voices during attention towards (explicit attention) or away from emotional cues in voices (implicit attention) based on a reanalysis of previous data (Frühholz, S., Ceravolo, L., Grandjean, D., 2012. Cerebral Cortex 22, 1107-1117). The general network revealed high interconnectivity of bilateral inferior frontal gyrus (IFG) to different bilateral voice-sensitive regions in mid and posterior superior temporal gyri. Right superior temporal gyrus (STG) regions showed connectivity to the left primary auditory cortex and secondary auditory cortex (AC) as well as to high-level auditory regions. This general network revealed differences in connectivity depending on the attentional focus. Explicit attention to angry voices revealed a specific right-left STG network connecting higher-level AC. During attention to a nonemotional vocal feature we also found a left-right STG network implicitly elicited by angry voices that also included low-level left AC. Furthermore, only during this implicit processing there was widespread interconnectivity between bilateral IFG and bilateral STG. This indicates that while implicit attention to angry voices recruits extended bilateral STG and IFG networks for the sensory and evaluative decoding of voices, explicit attention to angry voices solely involves a network of bilateral STG regions probably for the integrative recognition of emotional cues from voices.	t	\N
22723356	The integration of facial gestures and vocal signals is an essential process in human communication and relies on an interconnected circuit of brain regions, including language regions in the inferior frontal gyrus (IFG). Studies have determined that ventral prefrontal cortical regions in macaques [e.g., the ventrolateral prefrontal cortex (VLPFC)] share similar cytoarchitectonic features as cortical areas in the human IFG, suggesting structural homology. Anterograde and retrograde tracing studies show that macaque VLPFC receives afferents from the superior and inferior temporal gyrus, which provide complex auditory and visual information, respectively. Moreover, physiological studies have shown that single neurons in VLPFC integrate species-specific face and vocal stimuli. Although bimodal responses may be found across a wide region of prefrontal cortex, vocalization responsive cells, which also respond to faces, are mainly found in anterior VLPFC. This suggests that VLPFC may be specialized to process and integrate social communication information, just as the IFG is specialized to process and integrate speech and gestures in the human brain.	t	\N
22724279	The main goal of this study was to investigate the effects of acoustic characteristics, including timbre and fundamental frequency (F0), on the musical pitch discrimination of cochlear implant users. Eight postlingually deafened cochlear implant users were recruited, along with 8 control subjects with normal hearing. Pitch discrimination tests were carried out using test stimuli from 4 musical instruments plus synthetic complex stimuli. Three reference tones with different F0s were used. The mean difference limens were 1.8 to 10.7 semitones in the just-noticeable difference task and 2.1 to 13.6 semitones in the pitch-direction discrimination task for different timbre and F0 combinations. Three-way analysis of variance showed that the acoustic characteristics of the musical stimuli, such as timbre and F0, significantly influenced pitch discrimination performance. Acoustic characteristics determine the complexity of the electrical stimulation pattern, which directly affects performance in pitch discrimination. A place pattern with a clear and regular low-order harmonic structure is most important for good pitch discrimination. A clear F0-related temporal pattern is also useful when the F0 is low. Pitch perception performance will worsen when there is interference in the high-frequency channels.	t	\N
22727355	The objective of this study was to evaluate the relationship between developmental delays and speech perception in pre-lingually deafened cochlear implant recipients. This study was a retrospective review of patient charts conducted at a tertiary referral center. Thirty-five pre-lingually deafened children underwent multichannel cochlear implantation and habilitation at the Kyoto University Hospital Department of Otolaryngology-Head and Neck Surgery. A pre-operative cognitive-adaptive developmental quotient was evaluated using the Kyoto scale of psychological development. Post-operative speech performance was evaluated with speech perception tests two years after cochlear implantation. We computed partial correlation coefficients (controlled for age at the time of implantation and the average pre-operative aided hearing level) between the cognitive-adaptive developmental quotient and speech performance. A developmental delay in the cognitive-adaptive area was weakly correlated with speech perception (partial correlation coefficients for consonant-vowel syllables and phrases were 0.38 and 0.36, respectively). A pre-operative developmental delay was only weakly associated with poor post-operative speech perception in pre-lingually deafened cochlear implant recipients.	t	\N
22728130	The neural processing of auditory information engages pathways that begin initially at the cochlea and that eventually reach forebrain structures. At these higher levels, the computations necessary for extracting auditory source and identity information rely on the neuroanatomical connections between the thalamus and cortex. Here, the general organization of these connections in the medial geniculate body (thalamus) and the auditory cortex is reviewed. In addition, we consider two models organizing the thalamocortical pathways of the non-tonotopic and multimodal auditory nuclei. Overall, the transfer of information to the cortex via the thalamocortical pathways is complemented by the numerous intracortical and corticocortical pathways. Although interrelated, the convergent interactions among thalamocortical, corticocortical, and commissural pathways enable the computations necessary for the emergence of higher auditory perception.	t	\N
22731996	The influence of top-down cognitive control on 2 putatively distinct forms of distraction was investigated. Attentional capture by a task-irrelevant auditory deviation (e.g., a female-spoken token following a sequence of male-spoken tokens)-as indexed by its disruption of a visually presented recall task-was abolished when focal-task engagement was promoted either by increasing the difficulty of encoding the visual to-be-remembered stimuli (by reducing their perceptual discriminability; Experiments 1 and 2) or by providing foreknowledge of an imminent deviation (Experiment 2). In contrast, distraction from continuously changing auditory stimuli ("changing-state effect") was not modulated by task-difficulty or foreknowledge (Experiment 3). We also confirmed that individual differences in working memory capacity--typically associated with maintaining task-engagement in the face of distraction--predict the magnitude of the deviation effect, but not the changing-state effect. This convergence of experimental and psychometric data strongly supports a duplex-mechanism account of auditory distraction: Auditory attentional capture (deviation effect) is open to top-down cognitive control, whereas auditory distraction caused by direct conflict between the sound and focal-task processing (changing-state effect) is relatively immune to such control.	t	\N
22753470	A visual scene is perceived in terms of visual objects. Similar ideas have been proposed for the analogous case of auditory scene analysis, although their hypothesized neural underpinnings have not yet been established. Here, we address this question by recording from subjects selectively listening to one of two competing speakers, either of different or the same sex, using magnetoencephalography. Individual neural representations are seen for the speech of the two speakers, with each being selectively phase locked to the rhythm of the corresponding speech stream and from which can be exclusively reconstructed the temporal envelope of that speech stream. The neural representation of the attended speech dominates responses (with latency near 100 ms) in posterior auditory cortex. Furthermore, when the intensity of the attended and background speakers is separately varied over an 8-dB range, the neural representation of the attended speech adapts only to the intensity of that speaker but not to the intensity of the background speaker, suggesting an object-level intensity gain control. In summary, these results indicate that concurrent auditory objects, even if spectrotemporally overlapping and not resolvable at the auditory periphery, are neurally encoded individually in auditory cortex and emerge as fundamental representational units for top-down attentional modulation and bottom-up neural adaptation.	t	\N
22764349	Presenting synchronous auditory and visual stimuli in separate locations creates the illusion that the sound originates from the direction of the visual stimulus. Participants' auditory localization bias, called the ventriloquism effect, has revealed factors affecting the perceptual integration of audio-visual stimuli. However, many studies on audio-visual processes have focused on performance in simplified experimental situations, with a single stimulus in each sensory modality. These results cannot necessarily explain our perceptual behavior in natural scenes, where various signals exist within a single sensory modality. In the present study we report the contributions of a cognitive factor, that is, the audio-visual congruency of speech, although this factor has often been underestimated in previous ventriloquism research. Thus, we investigated the contribution of speech congruency on the ventriloquism effect using a spoken utterance and two videos of a talking face. The salience of facial movements was also manipulated. As a result, when bilateral visual stimuli are presented in synchrony with a single voice, cross-modal speech congruency was found to have a significant impact on the ventriloquism effect. This result also indicated that more salient visual utterances attracted participants' auditory localization. The congruent pairing of audio-visual utterances elicited greater localization bias than did incongruent pairing, whereas previous studies have reported little dependency on the reality of stimuli in ventriloquism. Moreover, audio-visual illusory congruency, owing to the McGurk effect, caused substantial visual interference to auditory localization. This suggests that a greater flexibility in responding to multi-sensory environments exists than has been previously considered.	t	\N
22768163	Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD.	t	\N
22773778	Because acoustic landscapes are complex and rapidly changing, auditory systems have evolved mechanisms that permit rapid detection of novel sounds, sound source segregation, and perceptual restoration of sounds obscured by noise. Perceptual restoration is particularly important in noisy environments because it allows organisms to track sounds over time even when they are masked. The continuity illusion is a striking example of perceptual restoration with sounds perceived as intact even when parts of them have been replaced by gaps and rendered inaudible by being masked by an extraneous sound. The mechanisms of auditory filling-in are complex and are currently not well-understood. The present study used the high temporal resolution of EEG to examine brain activity related to continuity illusion perception. Masking noise loudness was adjusted individually for each subject so that physically identical sounds on some trials elicited a continuity illusion (failure to detect a gap in a sound) and on other trials resulted in correct gap detection. This design ensured that any measurable differences in brain activity would be due to perceptual differences rather than physical differences among stimuli. We found that baseline activity recorded immediately before presentation of the stimulus significantly predicted the occurrence of the continuity illusion in 10 out of 14 participants based on power differences in γ-band EEG (34-80 Hz). Across all participants, power in the β and γ (12- to 80-Hz range) was informative about the subsequent perceptual decision. These data suggest that a subject's baseline brain state influences the strength of continuity illusions.	t	\N
22774804	The issue investigated in the present research is the nature of the information that is responsible for producing masked priming effects (e.g., semantic information or stimulus-response [S-R] associations) when responding to number stimuli. This issue was addressed by assessing both the magnitude of the category congruence (priming) effect and the nature of the priming distance effect across trials using single-digit primes and targets. Participants made either magnitude (i.e., whether the number presented was larger or smaller than 5) or identification (i.e., press the left button if the number was either a 1, 2, 3, or 4 or the right button if the number was either a 6, 7, 8, or 9) judgments. The results indicated that, regardless of task instruction, there was a clear priming distance effect and a significantly increasing category congruence effect. These results indicated that both semantic activation and S-R associations play important roles in producing masked priming effects.	t	\N
22776903	Stuttering is generally considered to be a speech disorder that affects ∼1% of the global population. Various forms of speech feedback have been shown to reduce overt stuttered speaking, and in particular, second speech signal through speech feedback has drastically reduced utterances of stuttered speech in adults with persistent stuttering. This study reports data for increased overt fluency of speech in an adult stuttering population, whereby the vocalization of the speaker is captured by a microphone or an accelerometer, signal processed, and returned as mechanical tactile speech feedback to the speaker's skin. A repeated measures analysis of variance was used to show that both the microphone and the accelerometer speaking conditions were significantly more fluent than a control (no feedback) condition, with the microphone-driven tactile feedback reducing instances of stuttering by 71% and the accelerometer-driven tactile feedback reducing instances of stuttering by 80%. It is apparent that self-generated tactile feedback can be used to enhance fluency significantly in those who stutter.	t	\N
22777734	A growing literature has suggested that processing of visual information presented near the hands is facilitated. In this study, we investigated whether the near-hands superiority effect also occurs with the hands moving. In two experiments, participants performed a cyclical bimanual movement task requiring concurrent visual identification of briefly presented letters. For both the static and dynamic hand conditions, the results showed improved letter recognition performance with the hands closer to the stimuli. The finding that the encoding advantage for near-hand stimuli also occurred with the hands moving suggests that the effect is regulated in real time, in accordance with the concept of a bimodal neural system that dynamically updates hand position in external space.	t	\N
22788230	Altered auditory feedback can facilitate speech fluency in adults who stutter. However, other findings suggest that adults who stutter show anomalies in 'audiovocal integration', such as longer phonation reaction times to auditory stimuli and less effective pitch tracking. To study audiovocal integration in adults who stutter using the pitch-shift paradigm. Fourteen adult stuttering participants and 16 normally fluent adults produced the vowel /a/while monitoring their own voice through earphones. Unanticipated pitch-shifts were applied in the upward or downward direction for 500 ms. Short latency pitch-shift responses (or pitch-shift responses) were elicited in all participants. In stuttering participants, vocal response onset latency was significantly delayed and amplitude tended to be reduced. Atypical audiovocal responses could be associated with stuttering. It is not clear how audiovocal integration influences stuttering, but could signal inadequate activation of internal models.	t	\N
22796516	In the present study we examined the effect of positional noise on spatial resolution in younger and older observers. We used a yes/no discrimination task in which observers indicated whether the size of two gaps in a Landolt-C-like contour was the same or not. The proportion of trials observers perceived one gap larger was measured when gaps-position was fixed (low positional noise) and random (high positional noise). Specifically, we compared, across conditions and groups, the values of threshold, lower and upper asymptote of the psychometric function. In the younger group, noise does not prevent detection of gap-size difference although sensitivity is lower, as revealed by higher threshold and lower upper asymptote, i.e., the proportion of responses "I see a larger gap" at the largest gap-size difference (asymptotic performance). In the older group detection is prevented, as revealed by threshold, lower and upper asymptote data. This may be because, at stimulus onset, high positional noise has associated coarse filter analysers averaging across the two gaps, which cannot be switched off.	t	\N
22799761	Little is known about how sex influences functional brain maturation. The current study investigated sex differences in the maturation of event-related potential (ERP) amplitudes during an auditory oddball task (N = 170; age = 6-17 years). Performance improved with age. N200 amplitude declined with age: parietal sites showed earlier development than temporal and frontal locations. Girls showed greater bilateral frontal P300 amplitude development, approaching the higher values observed in boys during childhood. After controlling for age, right frontal P300 amplitude was associated with reaction time in girls. The findings demonstrate sex differences in ERP maturation in line with behavioral and neuroimaging studies.	t	\N
22802637	Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca's area in the frontal lobe and Wernicke's area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke's area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms.	t	\N
22805019	To establish the method of conducting electrical evoked middle latency response (EMLR) monitoring in cochlear implantation operation and further to assess the neural response of auditory pathway under electrical stimulation. Twenty cases of cochlear implantation subjects were investigated in this study. Fourteen cases were pre-lingual deaf and 6 were post-lingual deaf. The surface recording electrodes were placed on the patients under general anesthesia, with language processor connected to the triggering port of the auditory evoked potential device. After the electrode was implanted, the electrode No.3 was selected to conduct. The electrically evoked auditory nerve compound active potentials (ECAP) were firstly tested in all patients, thereafter the EABR mode was selected, and the stimulation parameters were changed to EMLR mode with monopole biphasic, alternation stimulation, pulse width from 50 to 100 µs, the stimulation intensity decreased or increased from 20 CL above the strength of the ECAP threshold to the reaction threshold with a step of 5CL. To evaluate the correlation between the ECAP thresholds and EMLR, another 6 cases of normal hearing healthy subjects were recruited to record their short-sound evoked auditory middle-latency response (AMLR), as the control of morphology and latency of MLR by electrical stimulation. The typical AMLR waveforms could be recorded by the composition of five waves in the 6 cases of normal hearing healthy subjects, with an average response threshold of (12.5±8.6) dBnHL, close to the behavioral audiometric threshold (10.8±7.3) dBHL. The EMLR waveforms could be recorded in 20 patients, which was similar to the AMLR waveforms. However, the wave latency and wave interval shortened. There were lower volatility and longer latency in pre-lingual deaf than post-lingual deaf. The EMLR threshold (140.55±9.92) CL was significantly lower than the ECAP threshold (160.75±13.34) CL (t=10.467, P<0.01), a positive correlation between the thresholds was detected (r=0.763, P<0.01). We successfully established the method of EMLR monitoring in cochlear implantation surgery. The EMLR threshold is lower than the ECAP threshold but it is close to the behavioral audiometric threshold; EMLR can provide neural response information closer to the auditory center, and can serve as an effective objective method to evaluate the effect of hearing rehabilitation.	t	\N
22829158	The aim of this study was to describe the outcome and possible complications of subtotal petrosectomy (SP) for Vibrant Soundbridge (VSB) device surgery in a tertiary referral center. A secondary objective was the evaluation of hearing results in a subgroup of subjects who received the VSB device. Between 2009 and early 2011, 22 adult subjects with chronic otitis media (COM) underwent a SP, blind sac closure of the external auditory canal and abdominal fat obliteration to facilitate the application of an active middle ear implant (AMEI) in a staged procedure. Indications consisted of mixed hearing loss after previous tympanomastoplasty and failure of hearing rehabilitation with a hearing aid or bone conduction device in COM. Pre- and postoperative pure-tone audiograms were analyzed in respect to deterioration of inner ear function, unaided and aided (hearing aid, bone-anchored hearing aid and VSB) speech audiograms were compared to verify improvements in communications skills and functional gains. Incidence and type of complications were reviewed. No significant change was observed regarding mean bone conduction thresholds after the first stage procedure. Some minor wound healing problems were noted. Speech perception using the VSB (n = 16) showed a mean aided speech discrimination at 65-dB SPL of 75 % [standard deviation (SD) 28.7], at 80-dB SPL of 90 % (SD 25.1). Our results suggest that for selected patients with open mastoid cavities and chronic middle ear disease, SP with abdominal fat obliteration is an effective and safe technique to facilitate safe AMEI placement.	t	\N
22832675	Auditory-perceptual evaluation of dysphonia may be influenced by the type of speech/voice task used to render judgements during the clinical evaluation, i.e., sustained vowels versus continuous speech. This study explored (a) differences in listener dysphonia severity ratings on the basis of speech/voice tasks, (b) the influence of speech/voice task on dysphonia severity ratings of stimuli that combined sustained vowels and continuous speech, and (c) the differences in inter-rater reliability of dysphonia severity ratings between both speech tasks. Five experienced listeners rated overall dysphonia severity in sustained vowels, continuous speech and concatenated speech samples elicited by 39 subjects with various voice disorders and degrees of hoarseness. Data confirmed that sustained vowels are rated significantly more dysphonic than continuous speech. Furthermore, dysphonia severity in concatenated speech samples is least determined by the sustained vowel. Finally, no significant difference was found in inter-rater reliability between dysphonia severity ratings of sustained vowels versus continuous speech. Based upon the results, both types of speech/voice tasks (i.e., sustained vowel and continuous speech) should be elicited and judged by clinicians in the auditory-perceptual rating of dysphonia severity.	t	\N
22844984	A fundamental issue in the design and the interpretation of experimental studies of perception relates to the question of whether the participants in these experiments could perform the perceptual task assigned to them using another feature, or cue, than that intended by the experimenter. An approach frequently used by auditory- and visual-perception researchers to guard against this possibility involves applying random variations to the stimuli across presentations or trials so as to make the "unwanted" cue unreliable for the participants. However, the theoretical basis of this widespread practice is not well developed. In this article, we describe a 2-channel model based on general principles of psychophysical signal detection theory, which can be used to assess the respective contributions of the unwanted cue and of the primary cue to performance or thresholds measured in perceptual discrimination experiments involving stimulus randomization. Example applications of the model to the analysis of results obtained in representative studies from the auditory- and visual-perception literature are provided. In several cases, the results of the model-based analyses indicate that the effectiveness of the randomization procedure was less than originally assumed by the authors of these studies. These findings underscore the importance of quantifying the potential influence of unwanted cues on the results of psychophysical experiments, even when stimulus randomization is used.	t	\N
22846767	Previous studies have demonstrated that human evaluation of subjective loudness and acoustic comfort depends on a series of factors in a particular situation rather than only on sound pressure levels. In the present study, a large-scale subjective survey has been undertaken on underground shopping streets in Harbin, China, to determine how individual sound sources influence subjective loudness and acoustic comfort evaluation. Based on the analysis of case study results, it has been shown that all individual sound sources can increase subjective loudness to a certain degree. However, their levels of influence on acoustic comfort are different. Background music and the public address system can increase acoustic comfort, with a mean difference of 0.18 to 0.32 and 0.21 to 0.27, respectively, where a five-point bipolar category scale is used. Music from shops and vendor shouts can decrease acoustic comfort, with a mean difference of -0.11 to -0.38 and -0.39 to -0.62, respectively. The feasibility of improving acoustic comfort by changing certain sound sources is thus demonstrated.	t	\N
22866682	Two experiments tested the effects of preview sentences and headings on the quality of college students' outlines of informational texts. Experiment 1 found that performance was much better in the preview sentences condition than in a no-signals condition for both printed text and text-to-speech (TTS) audio rendering of the printed text. In contrast, performance in the headings condition was good for the printed text but poor for the auditory presentation because the TTS software failed to communicate nonverbal information carried by the visual headings. Experiment 2 compared outlining performance for five headings conditions during TTS presentation. Using a theoretical framework, "signaling available, relevant, accessible" (SARA) information, to provide an analysis of the information content of headings in the printed text, the manipulation of the headings systematically restored information that was omitted by the TTS application in Experiment 1. The result was that outlining performance improved to levels similar to the visual headings condition of Experiment 1. It is argued that SARA is a useful framework for guiding future development of TTS software for a wide variety of text signaling devices, not just headings.	t	\N
22891070	Perceptual training with spectrally degraded environmental sounds results in improved environmental sound identification, with benefits shown to extend to untrained speech perception as well. The present study extended those findings to examine longer-term training effects as well as effects of mere repeated exposure to sounds over time. Participants received two pretests (1 week apart) prior to a week-long environmental sound training regimen, which was followed by two posttest sessions, separated by another week without training. Spectrally degraded stimuli, processed with a four-channel vocoder, consisted of a 160-item environmental sound test, word and sentence tests, and a battery of basic auditory abilities and cognitive tests. Results indicated significant improvements in all speech and environmental sound scores between the initial pretest and the last posttest with performance increments following both exposure and training. For environmental sounds (the stimulus class that was trained), the magnitude of positive change that accompanied training was much greater than that due to exposure alone, with improvement for untrained sounds roughly comparable to the speech benefit from exposure. Additional tests of auditory and cognitive abilities showed that speech and environmental sound performance were differentially correlated with tests of spectral and temporal-fine-structure processing, whereas working memory and executive function were correlated with speech, but not environmental sound perception. These findings indicate generalizability of environmental sound training and provide a basis for implementing environmental sound training programs for cochlear implant (CI) patients.	t	\N
22892280	Three studies investigated developmental changes in facial expression processing, between 3 years-of-age and adulthood. For adults and older children, the addition of sunglasses to upright faces caused an equivalent decrement in performance to face inversion. However, younger children showed better classification of expressions of faces wearing sunglasses than children who saw the same faces un-occluded. When the mouth area was occluded with a mask, children under nine years showed no impairment in expression classification, relative to un-occluded faces. An early selective focus of attention on the eyes may be optimal for socialization, but mediate against accurate expression classification. The data support a model in which a threshold level of attentional control must be reached before children can develop adult-like configural processing skills and be flexible in their use of face- processing strategies.	t	\N
22892586	We introduce a new version of the perceptual retouch model. This model was used for explaining properties of temporal interaction of successive objects in reaching conscious representation. The new model incorporates two interactive binding operations - binding features for objects and binding the bound feature-objects with a large scale oscillatory system that corresponds to perceptual consciousness. Here, the typical result of masking experiments - second object advantage in conscious perception - is achieved by applying the effects of a common synchronizing oscillator with a delay. This delayed modulation of each of the feature-binding first-order oscillators that represent emerging and decaying neural activities of each of the objects guarantees that the oscillating synchrony of the feature-neurons of the following object is higher than the synchrony of the feature-neurons of the first presented object. Thus we model the fact that the following object dominates the preceding object in conscious perception. We also show the capacity of the model to simulate illusory misbinding of features from different objects. The third qualitative effect, the relative release of the first object from backward masking is achieved by priming the non-specific oscillatory modulation ahead in time.	t	\N
22894217	Green [J. Acoust. Soc. Am. 87, 2662-2674 (1990)] suggested an efficient, maximum-likelihood-based approach for adaptively estimating thresholds. Such procedures determine the signal strength on each trial by first identifying the most likely psychometric functions among the pre-proposed alternatives based on responses from previous trials, and then finding the signal strength at the "sweet point" on that most likely function. The sweet point is the point on the psychometric function that is associated with the minimum expected variance. Here, that procedure is extended to reduce poor estimates that result from lapses in attention. The sweet points for the threshold, slope, and lapse parameters of a transformed logistic psychometric function are derived. In addition, alternative stimulus placement algorithms are considered. The result is a relatively fast and robust estimation of a three-parameter psychometric function.	t	\N
22894232	Speaker variability and noise are two common sources of acoustic variability. The goal of this study was to examine whether these two sources of acoustic variability affected native and non-native perception of Mandarin fricatives to different degrees. Multispeaker Mandarin fricative stimuli were presented to 40 native and 52 non-native listeners in two presentation formats (blocked by speaker and mixed across speakers). The stimuli were also mixed with speech-shaped noise to create five levels of signal-to- noise ratios. The results showed that noise affected non-native identification disproportionately. By contrast, the effect of speaker variability was comparable between the native and non-native listeners. Confusion patterns were interpreted with reference to the results of acoustic analysis, suggesting native and non-native listeners used distinct acoustic cues for fricative identification. It was concluded that not all sources of acoustic variability are treated equally by native and non-native listeners. Whereas noise compromised non-native fricative perception disproportionately, speaker variability did not pose a special challenge to the non-native listeners.	t	\N
22895701	Critical periods in language acquisition have been discussed primarily with reference to studies of people who are deaf or bilingual. Here, we provide evidence on the opening of sensitivity to the linguistic environment by studying the response to a change of phoneme at a native and nonnative phonetic boundary in full-term and preterm human infants using event-related potentials. Full-term infants show a decline in their discrimination of nonnative phonetic contrasts between 9 and 12 months of age. Because the womb is a high-frequency filter, many phonemes are strongly degraded in utero. Preterm infants thus benefit from earlier and richer exposure to broadcast speech. We find that preterms do not take advantage of this enriched linguistic environment: the decrease in amplitude of the mismatch response to a nonnative change of phoneme at the end of the first year of life was dependent on maturational age and not on the duration of exposure to broadcast speech. The shaping of phonological representations by the environment is thus strongly constrained by brain maturation factors.	t	\N
22897876	Neurophysiological studies of infant speech suggest that mismatch responses (MMRs) have predictive value for later language. Their value, however, is diminished because unexplained differences in the MMR patterns are seen across studies. The current study aimed to identify the functional nature of infant MMRs by recording event-related-potentials (ERPs) to an infrequent English vowel change in internal or final positions of a sequence of ten vowels in six-month-old monolingually and bilingually exposed infants. Increased negativity of the MMR (infrequent minus frequent) was found in final compared to internal positions and correlated with an index of increased attention to the final position. This pattern helps explain the overall greater negativity to the speech sounds in the bilingually exposed female infants. These findings substantially advance our understanding of neural indices of speech perception development and show promise for furthering our understanding of bilingual language development.	t	\N
22907183	Although central nervous system abnormalities are incidentally detected in preoperative brain magnetic resonance imaging (MRI) studies in pediatric cochlear implant (CI) candidates, the clinical significance of the abnormalities remains unclear. We aimed to assess post-implantation auditory and speech performance in patients with brain lesions seen on MRI. Pediatric CI recipients (n = 177) who underwent preoperative MRI scans of the brain between January 2002 and June 2009 were included in this study. Patients with brain lesions on MRI were reviewed and categorized into the following groups: brain parenchymal lesions (focal vs. diffuse), ventriculomegaly, and extra-axial lesion. The main communication mode as well as progress in auditory perception and speech production were evaluated preoperatively and at 3, 6, 12, and 24 months postoperatively. Performance in patients with brain lesions was compared with the age- and sex-matched control group. Various brain lesions were found in 27 out of 177 patients. Children with brain lesions who received CIs showed gradual progress in auditory and speech outcomes for 2 years, though performance was reduced compared with the control group. In addition, there was a significant difference in the main communication mode between the two groups at 2 years following cochlear implantation. This difference was especially significant in patients with diffuse brain parenchymal lesions after further stratification of the brain lesion group. Preoperative brain MRI may have a role in improving the prediction of adverse outcomes in pediatric CI recipients. In particular, children with diffuse brain parenchymal lesions should be counseled regarding the poor prognosis preoperatively, and followed up with special attention.	t	\N
22922236	Cognitive models propose that auditory verbal hallucinations arise through inner speech misidentification. However, such models cannot explain why the voices in hallucinations often have identities different from the hearer. This study investigated whether a general voice identity recognition difficulty might be present in schizophrenia and related to auditory verbal hallucinations. Twenty-five schizophrenia patients and 13 healthy controls were tested on recognition of famous voices. Signal detection theory was used to calculate perceptual sensitivity and response criterion measures. Schizophrenia patients obtained fewer hits and had lower perceptual sensitivity to detect famous voices than healthy controls did. There were no differences between groups in false alarm rate or response criterion. A symptom-based analysis demonstrated that especially those patients with auditory verbal hallucinations performed poorly in the task. The results indicate that patients with hallucinations are impaired at voice identity recognition because of decreased sensitivity, which may result in inner speech misidentification.	t	\N
22922606	To evaluate, with a long-term follow-up, the speech perception and language development in children with cytomegalovirus (CMV)-related deafness after cochlear implantation. A retrospective study on CMV-related profound deafness and cochlear implantation was performed from 1995 to 2010. Six children with an average follow-up of 10 years were included in this research. Medical history, imaging, cognitive delay, speech perception and production data were reviewed. Two of the 6 patients developed a functional language with the use of phrases and word sequences based on morphological and syntactic rules; the others demonstrated the development of a preverbal or transitional language with the use of single words only. Patients with CMV-related deafness benefit from cochlear implantation; however, the expectations of the parents must be evaluated in a series of counseling efforts prior to the surgery.	t	\N
22923209	Autism spectrum disorder is typically associated with social deficits and is often specifically linked to difficulty with processing faces and other socially relevant stimuli. Emerging research has suggested that children with autism might also have deficits in basic perceptual abilities including multisensory processing (e.g., simultaneously processing visual and auditory inputs). The current study examined the relationship between multisensory temporal processing (assessed via a simultaneity judgment task wherein participants were to report whether a visual stimulus and an auditory stimulus occurred at the same time or at different times) and self-reported symptoms of autism (assessed via the Autism Spectrum Quotient questionnaire). Data from over 100 healthy adults revealed a relationship between these two factors as multisensory timing perception correlated with symptoms of autism. Specifically, a stronger bias to perceive auditory stimuli occurring before visual stimuli as simultaneous was associated with greater levels of autistic symptoms. Additional data and analyses confirm that this relationship is specific to multisensory processing and symptoms of autism. These results provide insight into the nature of multisensory processing while also revealing a continuum over which perceptual abilities correlate with symptoms of autism and that this continuum is not just specific to clinical populations but is present within the general population.	t	\N
22925516	We live in a world rich in sensory information, and consequently the brain is challenged with deciphering which cues from the various sensory modalities belong together. Determinations regarding the relatedness of sensory information appear to be based, at least in part, on the spatial and temporal relationships between the stimuli. Stimuli that are presented in close spatial and temporal correspondence are more likely to be associated with one another and thus 'bound' into a single perceptual entity. While there is a robust literature delineating behavioral changes in perception induced by multisensory stimuli, maturational changes in multisensory processing, particularly in the temporal realm, are poorly understood. The current study examines the developmental progression of multisensory temporal function by analyzing responses on an audiovisual simultaneity judgment task in 6- to 23-year-old participants. The overarching hypothesis for the study was that multisensory temporal function will mature with increasing age, with the developmental trajectory for this change being the primary point of inquiry. Results indeed reveal an age-dependent decrease in the size of the 'multisensory temporal binding window', the temporal interval within which multisensory stimuli are likely to be perceptually bound, with changes occurring over a surprisingly protracted time course that extends into adolescence.	t	\N
22926436	The results of two experiments are presented which explore the effect of distractor items on face and voice recognition. Following from the suggestion that voice processing is relatively weak compared to face processing, it was anticipated that voice recognition would be more affected by the presentation of distractor items between study and test compared to face recognition. Using a sequential matching task with a fixed interval between study and test that either incorporated distractor items or did not, the results supported our prediction. Face recognition remained strong irrespective of the number of distractor items between study and test. In contrast, voice recognition was significantly impaired by the presence of distractor items regardless of their number (Experiment 1). This pattern remained whether distractor items were highly similar to the targets or not (Experiment 2). These results offer support for the proposal that voice processing is a relatively vulnerable method of identification.	t	\N
22946856	Motivational interviewing (MI) is a directive, client-centered therapeutic method employed in the treatment of substance abuse, with strong evidence of effectiveness. To date, the sole mechanism of action in MI with any consistent empirical support is "change talk" (CT), which is generally defined as client within-session speech in support of a behavior change. "Sustain talk" (ST) incorporates speech in support of the status quo. MI maintains that during treatment, clients essentially talk themselves into change. Multiple studies have now supported this theory, linking within-session speech to substance use outcomes. Although a causal chain has been established linking therapist behavior, client CT, and substance use outcome, the neural substrate of CT has been largely uncharted. We addressed this gap by measuring neural responses to clients' own CT using magnetoencephalography (MEG), a noninvasive neuroimaging technique with excellent spatial and temporal resolution. Following a recorded MI session, MEG was used to measure brain activity while participants heard multiple repetitions of their CT and ST utterances from that session, intermingled and presented in a random order. Results suggest that CT processing occurs in a right-hemisphere network that includes the inferior frontal gyrus, insula, and superior temporal cortex. These results support a representation of CT at the neural level, consistent with the role of these structures in self-perception. This suggests that during treatment sessions, clinicians who are able to evoke this special kind of language are tapping into neural circuitry that may be essential to behavior change.	t	\N
22951258	Comprehension of spoken narratives requires coordination of multiple language skills. As such, for normal children narrative skills develop well into the school years and, during this period, are particularly vulnerable in the face of brain injury or developmental disorder. For these reasons, we sought to determine the developmental trajectory of narrative processing using longitudinal fMRI scanning. 30 healthy children between the ages of 5 and 18 enrolled at ages 5, 6, or 7, were examined annually for up to 10 years. At each fMRI session, children were presented with a set of five, 30s-long, stories containing 9, 10, or 11 sentences designed to be understood by a 5 year old child. fMRI data analysis was conducted based on a hierarchical linear model (HLM) that was modified to investigate developmental changes while accounting for missing data and controlling for factors such as age, linguistic performance and IQ. Performance testing conducted after each scan indicated well above the chance (p<0.002) comprehension performance. There was a linear increase with increasing age in bilateral superior temporal cortical activation (BAs 21 and 22) linked to narrative processing. Conversely, age-related decreases in cortical activation were observed in bilateral occipital regions, cingulate and cuneus, possibly reflecting changes in the default mode networks. The dynamic changes observed in this longitudinal fMRI study support the increasing role of bilateral BAs 21 and 22 in narrative comprehension, involving non-domain-specific integration in order to achieve final story interpretation. The presence of a continued linear development of this area throughout childhood and teenage years with no apparent plateau, indicates that full maturation of narrative processing skills has not yet occurred and that it may be delayed to early adulthood.	t	\N
22957659	The Adaptive Tests of Temporal Resolution (ATTR©) software provides within-channel (WC) and across-channel (AC) adaptive measures of temporal resolution that are feasible for clinical applications. The purpose of the present study was to obtain normative values for young adults on two of the ATTR tests: the narrow-band noise within-channel (NBN-WC) test and the narrow-band noise across-channel (NBN-AC) test, at different stimulus intensities. Gap detection thresholds were measured at five sensation levels. A Latin square design was used to control for practice effects. The NBN-WC group and the NBN-AC group each consisted of 25 young adults with normal hearing. Gap detection thresholds for both conditions decreased with increasing stimulus intensity, and stimulus intensities above 20 dB SL were not associated with large improvements in performance. Variability was larger in the NBN-AC condition. Values obtained for the NBC-WC condition were very similar to previously reported ATTR results despite equipment and design differences. Results provide normative values for NBN-WC and NBN-AC performance on the ATTR and suggest that the ATTR is a robust test for clinical use.	t	\N
22963230	Properties of auditory working memory for sounds that lack strong semantic associations and are not readily verbalized or sung are poorly understood. We investigated auditory working memory capacity for lists containing 2-6 easily discriminable abstract sounds synthesized within a constrained timbral space, at delays of 1-6 s (Experiment 1), and the effect of greater perceptual variability among list items on capacity estimates at delays of 1-6 s (Experiment 2). Working memory capacity estimates of 1-2 items were found in all conditions and increased significantly as the perceptual variability among the list items increased. Nonetheless, the capacity estimates were smaller than the commonly observed average working memory capacity limit of 3-5 items. Decay profiles in both experiments were comparable with those previously reported in the verbal and auditory working memory literature. The results help define boundary conditions on capacity estimates for nonverbalizable timbres that lack strong long-term memory associations.	t	\N
22978899	A common complaint of the hearing impaired is the inability to understand speech in noisy environments even with their hearing assistive devices. Only a few single-channel algorithms have significantly improved speech intelligibility in noise for hearing-impaired listeners. The current study introduces a cochlear noise reduction algorithm. It is based on a cochlear representation of acoustic signals and real-time derivation of a binary speech mask. The contribution of the algorithm for enhancing word recognition in noise was evaluated on a group of 42 normal-hearing subjects, 35 hearing-aid users, 8 cochlear implant recipients, and 14 participants with bimodal devices. Recognition scores of Hebrew monosyllabic words embedded in Gaussian noise at several signal-to-noise ratios (SNRs) were obtained with processed and unprocessed signals. The algorithm was not effective among the normal-hearing participants. However, it yielded a significant improvement in some of the hearing-impaired subjects under different listening conditions. Its most impressive benefit appeared among cochlear implant recipients. More than 20% improvement in recognition score of noisy words was obtained by 12, 16, and 26 hearing-impaired at SNR of 30, 24, and 18 dB, respectively. The algorithm has a potential to improve speech intelligibility in background noise, yet further research is required to improve its performances.	t	\N
22978901	The auditory octave illusion arises when dichotically presented tones, one octave apart, alternate rapidly between the ears. Most subjects perceive an illusory sequence of monaural tones: A high tone in the right ear (RE) alternates with a low tone, incorrectly localized to the left ear (LE). Behavioral studies suggest that the perceived pitch follows the RE input, and the perceived location the higher-frequency sound. To explore the link between the perceived pitches and brain-level interactions of dichotic tones, magnetoencephalographic responses were recorded to 4 binaural combinations of 2-min long continuous 400- and 800-Hz tones and to 4 monaural tones. Responses to LE and RE inputs were distinguished by frequency-tagging the ear-specific stimuli at different modulation frequencies. During dichotic presentation, ipsilateral LE tones elicited weaker and ipsilateral RE tones stronger responses than when both ears received the same tone. During the most paradoxical stimulus-high tone to LE and low tone to RE perceived as a low tone in LE during the illusion-also the contralateral responses to LE tones were diminished. The results demonstrate modified binaural interaction of dichotic tones one octave apart, suggesting that this interaction contributes to pitch perception during the octave illusion.	t	\N
22981882	Dyslexia is heritable and associated with auditory processing deficits. We investigate whether temporal auditory processing is compromised in young children at-risk for dyslexia and whether it is associated with later language and reading skills. We recorded EEG from 17 months-old children with or without familial risk for dyslexia to investigate whether their auditory system was able to detect a temporal change in a tone pattern. The children were followed longitudinally and performed an intelligence- and language development test at ages 4 and 4.5 years. Literacy related skills were measured at the beginning of second grade, and word- and pseudo-word reading fluency were measured at the end of second grade. The EEG responses showed that control children could detect the temporal change as indicated by a mismatch response (MMR). The MMR was not observed in at-risk children. Furthermore, the fronto-central MMR amplitude correlated with preliterate language comprehension and with later word reading fluency, but not with phonological awareness. We conclude that temporal auditory processing differentiates young children at risk for dyslexia from controls and is a precursor of preliterate language comprehension and reading fluency.	t	\N
22982103	Production of actions is highly dependent on concurrent sensory information. In speech production, for example, movement of the articulators is guided by both auditory and somatosensory input. It has been demonstrated in non-human primates that self-produced vocalizations and those of others are differentially processed in the temporal cortex. The aim of the current study was to investigate how auditory and motor responses differ for self-produced and externally produced speech. Using functional neuroimaging, subjects were asked to produce sentences aloud, to silently mouth while listening to a different speaker producing the same sentence, to passively listen to sentences being read aloud, or to read sentences silently. We show that that separate regions of the superior temporal cortex display distinct response profiles to speaking aloud, mouthing while listening, and passive listening. Responses in anterior superior temporal cortices in both hemispheres are greater for passive listening compared with both mouthing while listening, and speaking aloud. This is the first demonstration that articulation, whether or not it has auditory consequences, modulates responses of the dorsolateral temporal cortex. In contrast posterior regions of the superior temporal cortex are recruited during both articulation conditions. In dorsal regions of the posterior superior temporal gyrus, responses to mouthing and reading aloud were equivalent, and in more ventral posterior superior temporal sulcus, responses were greater for reading aloud compared with mouthing while listening. These data demonstrate an anterior-posterior division of superior temporal regions where anterior fields are suppressed during motor output, potentially for the purpose of enhanced detection of the speech of others. We suggest posterior fields are engaged in auditory processing for the guidance of articulation by auditory information.	t	\N
22984436	Amplitude modulation can serve as a cue for segregating streams of sounds from different sources. Here we evaluate stream segregation in humans using ABA- sequences of sinusoidally amplitude modulated (SAM) tones. A and B represent SAM tones with the same carrier frequency (1000, 4000 Hz) and modulation depth (30, 100%). The modulation frequency of the A signals (f(modA)) was 30, 100 or 300 Hz, respectively. The modulation frequency of the B signals was up to four octaves higher (Δf(mod)). Three different ABA- tone patterns varying in tone duration and stimulus onset asynchrony were presented to evaluate the effect of forward suppression. Subjects indicated their 1- or 2-stream percept on a touch screen at the end of each ABA- sequence (presentation time 5 or 15 s). Tone pattern, f(modA), Δf(mod), carrier frequency, modulation depth and presentation time significantly affected the percentage of a 2-stream percept. The human psychophysical results are compared to responses of avian forebrain neurons evoked by different ABA- SAM tone conditions [1] that were broadly overlapping those of the present study. The neurons also showed significant effects of tone pattern and Δf(mod) that were comparable to effects observed in the present psychophysical study. Depending on the carrier frequency, modulation frequency, modulation depth and the width of the auditory filters, SAM tones may provide mainly temporal cues (sidebands fall within the range of the filter), spectral cues (sidebands fall outside the range of the filter) or possibly both. A computational model based on excitation pattern differences was used to predict the 50% threshold of 2-stream responses. In conditions for which the model predicts a considerably larger 50% threshold of 2-stream responses (i.e., larger Δf(mod) at threshold) than was observed, it is unlikely that spectral cues can provide an explanation of stream segregation by SAM.	t	\N
22992710	Auditory perception of vowels in background noise is enhanced when combined with visually perceived speech features. The objective of this study was to investigate whether the influence of visual cues on vowel perception extends to incongruent vowels, in a manner similar to the McGurk effect observed with consonants. Identification of Dutch front vowels /i, y, e, Y/ that share all features other than height and lip-rounding was measured for congruent and incongruent audiovisual conditions. The audio channel was systematically degraded by adding noise, increasing the reliance on visual cues. The height feature was more robustly carried over through the auditory channel and the lip-rounding feature through the visual channel. Hence, congruent audiovisual presentation enhanced identification, while incongruent presentation led to perceptual fusions and thus decreased identification. Visual cues influence the identification of congruent as well as incongruent audiovisual vowels. Incongruent visual information results in perceptual fusions, demonstrating that the McGurk effect can be instigated by long phonemes such as vowels. This result extends to the incongruent presentation of the visually less reliably perceived height. The findings stress the importance of audiovisual congruency in communication devices, such as cochlear implants and videoconferencing tools, where the auditory signal could be degraded.	t	\N
22993261	Temporal selection poses unique challenges to the perceptual system. Selection is needed to protect goal-relevant stimuli from interference from new sensory input. In addition, contextual information that occurs at the same time as goal-relevant stimuli may be critical for learning. Using fMRI, we characterized how visual cortical regions respond to the temporal selection of auditory and visual stimuli. Critically, we focused on brain regions that are not involved in processing the target itself. Participants pressed a button when they heard a prespecified target tone and did not respond to other tones. Although more attention was directed to auditory input when the target tone was selected, activity in primary visual cortex increased more after target tones than after distractor tones. In contrast to spatial attention, this effect was larger in V1 than in V2 and V3. It was present in regions not typically involved in representing the target stimulus. Additional experiments demonstrated that these effects were not due to multimodal processing, rare targets, or motor responses to the targets. Thus temporal selection of behaviorally relevant stimuli enhances, rather than reduces, activity in perceptual regions involved in processing other information.	t	\N
22995182	Auditory feedback plays an important role in monitoring vocal output and determining when adjustments are necessary. In this study a group of untrained singers participated in a frequency altered feedback experiment to examine if accuracy at matching a note could predict the degree of compensation to auditory feedback that was shifted in frequency. Participants were presented with a target note and instructed to match the note in pitch and duration. Following the onset of the participants' vocalizations their vocal pitch was shifted down one semi-tone at a random time during their utterance. This altered auditory feedback was instantaneously presented back to them through headphones. Results indicated that note matching accuracy did not correlate with compensation magnitude, however, a significant correlation was found between baseline variability and compensation magnitude. These results suggest that individuals with a more stable baseline fundamental frequency rely more on feedforward control mechanisms than individuals with more variable vocal production. This increased weighting of feedforward control means they are less sensitive to mismatches between their intended vocal production and auditory feedback.	t	\N
23000118	Users of a cochlear implant together with a hearing aid in the non-implanted ear currently use devices that were developed separately and are often fitted separately. This results in very different growth of loudness with level in the two ears, potentially leading to decreased wearing comfort and suboptimal perception of interaural level differences. A loudness equalisation strategy, named 'SCORE bimodal', is proposed. It equalises loudness growth for the two modalities using existing models of loudness for acoustic and electric stimulation, and is suitable for implementation in wearable devices. Loudness balancing experiments were performed with six bimodal listeners to validate the strategy. In a first set of experiments, the function of each loudness model used was validated by balancing the loudness of four harmonic complexes of different bandwidths, ranging from 200 Hz to 1000 Hz, separately for each ear. Both the electric and acoustic loudness models predicted the data well. In a second set of experiments, binaural balancing was done for the same stimuli. It was found that SCORE significantly improved binaural balance.	t	\N
23000801	Cochlear implants (CIs) help many deaf children achieve near-normal speech and language (S/L) milestones. Nevertheless, high levels of unexplained variability in S/L outcomes are limiting factors in improving the effectiveness of CIs in deaf children. The objective of this study was to longitudinally assess the role of verbal short-term memory (STM) and working memory (WM) capacity as a progress-limiting source of variability in S/L outcomes after CI in children. Longitudinal study of 66 children with CIs for prelingual severe-to-profound hearing loss. Outcome measures included performance on digit span forward (DSF), digit span backward (DSB), and four conventional S/L measures that examined spoken-word recognition (Phonetically Balanced Kindergarten word test), receptive vocabulary (Peabody Picture Vocabulary Test ), sentence-recognition skills (Hearing in Noise Test), and receptive and expressive language functioning (Clinical Evaluation of Language Fundamentals Fourth Edition Core Language Score; CELF). Growth curves for DSF and DSB in the CI sample over time were comparable in slope, but consistently lagged in magnitude relative to norms for normal-hearing peers of the same age. For DSF and DSB, 50.5% and 44.0%, respectively, of the CI sample scored more than 1 SD below the normative mean for raw scores across all ages. The first (baseline) DSF score significantly predicted all endpoint scores for the four S/L measures, and DSF slope (growth) over time predicted CELF scores. DSF baseline and slope accounted for an additional 13 to 31% of variance in S/L scores after controlling for conventional predictor variables such as: chronological age at time of testing, age at time of implantation, communication mode (auditory-oral communication versus total communication), and maternal education. Only DSB baseline scores predicted endpoint language scores on Peabody Picture Vocabulary Test and CELF. DSB slopes were not significantly related to any endpoint S/L measures. DSB baseline scores and slopes taken together accounted for an additional 4 to 19% of variance in S/L endpoint measures after controlling for the conventional predictor variables. Verbal STM/WM scores, process measures of information capacity, develop at an average rate in the years after cochlear implantation, but were found to consistently lag in absolute magnitude behind those reported for normal-hearing peers. Baseline verbal STM/WM predicted long-term endpoint S/L outcomes, but verbal STM slopes predicted only endpoint language outcomes. Verbal STM/WM processing skills reflect important underlying core elementary neurocognitive functions and represent potential intervention targets for improving endpoint S/L outcomes in pediatric CI users.	t	\N
23014760	In this paper, we present a Bayesian framework for the active multimodal perception of 3-D structure and motion. The design of this framework finds its inspiration in the role of the dorsal perceptual pathway of the human brain. Its composing models build upon a common egocentric spatial configuration that is naturally fitting for the integration of readings from multiple sensors using a Bayesian approach. In the process, we will contribute with efficient and robust probabilistic solutions for cyclopean geometry-based stereovision and auditory perception based only on binaural cues, modeled using a consistent formalization that allows their hierarchical use as building blocks for the multimodal sensor fusion framework. We will explicitly or implicitly address the most important challenges of sensor fusion using this framework, for vision, audition, and vestibular sensing. Moreover, interaction and navigation require maximal awareness of spatial surroundings, which, in turn, is obtained through active attentional and behavioral exploration of the environment. The computational models described in this paper will support the construction of a simultaneously flexible and powerful robotic implementation of multimodal active perception to be used in real-world applications, such as human-machine interaction or mobile robot navigation.	t	\N
23015425	Depth-electrode recordings from the auditory cortex of humans undergoing presurgical evaluation for epilepsy allow the recording of ensemble responses to pitch in the form of local field potentials. These recordings allow another test of the hypothesis that there is a specialized neural ensemble for pitch within auditory cortex. Moreover, the technique allows recordings from multiple sites with millisecond temporal resolution to allow modeling of the effective connectivity between these sites. Here we argue that this takes the form of a hierarchical network of pitch-sensitive regions. Activity can be understood as reflecting predictive coding, in which perceptual predictions and error messages are continuously exchanged between a higher pitch center and lower-level auditory cortex.	t	\N
23025156	Change blindness is the failure of observers to notice otherwise obvious changes to a visual scene when those changes are masked in some way (eg by blotches or a blanking ofthe screen). Typically, change blindness is taken as evidence that our representation of the visual world is capacity limited. The locus of this capacity limit is thought to be visual short-term memory (vSTM). The capacity of vSTM is usually estimated with a high-threshold model which assumes that each element in the stimulus array is either fully encoded or not encoded at all, and, furthermore, that false alarms can arise only by guessing, not by noise. Low-threshold models, by contrast, suggest that false alarms can arise by noise at the level of detection/discrimination and/or decision. In this study, we use a well-controlled stimulus display in which a single element changes over a blanking of the screen and contrast predictions from a popular high-threshold model of vSTM with the predictions of a low-threshold model (specifically, the sample-size model) of visual search and vSTM. The data were better predicted by the low-threshold model.	t	\N
23025164	Cross-sensory correspondences automatically intrude on performance in elaborate laboratory tasks (see Spence 2011 Attention, Perception, & Psychophysics 73 971-995, for a review). Outside such tasks, might they be responsible for some popular misconceptions about natural phenomena? Four simple demonstrations reveal how the correspondences between surface-lightness and weight, and between surface-lightness and auditory pitch, generate misconceptions about the weight and movement of objects and the vocalisations of animals. Specifically, people expect darker objects to be heavier than lighter-coloured objects, to free-fall more quickly, to roll across a table more slowly, and to make lower-pitched vocalisations when they come to life.	t	\N
23028516	We physically interact with external stimuli when they occur within a limited space immediately surrounding the body, i.e., Peripersonal Space (PPS). In the primate brain, specific fronto-parietal areas are responsible for the multisensory representation of PPS, by integrating tactile, visual and auditory information occurring on and near the body. Dynamic stimuli are particularly relevant for PPS representation, as they might refer to potential harms approaching the body. However, behavioural tasks for studying PPS representation with moving stimuli are lacking. Here we propose a new dynamic audio-tactile interaction task in order to assess the extension of PPS in a more functionally and ecologically valid condition. Participants vocally responded to a tactile stimulus administered at the hand at different delays from the onset of task-irrelevant dynamic sounds which gave the impression of a sound source either approaching or receding from the subject's hand. Results showed that a moving auditory stimulus speeded up the processing of a tactile stimulus at the hand as long as it was perceived at a limited distance from the hand, that is within the boundaries of PPS representation. The audio-tactile interaction effect was stronger when sounds were approaching compared to when sounds were receding. This study provides a new method to dynamically assess pps representation: The function describing the relationship between tactile processing and the position of sounds in space can be used to estimate the location of PPS boundaries, along a spatial continuum between far and near space, in a valuable and ecologically significant way.	t	\N
23029113	An auditory neuron can preserve the temporal fine structure of a low-frequency tone by phase-locking its response to the stimulus. Apart from sound localization, however, much about the role of this temporal information for signal processing in the brain remains unknown. Through psychoacoustic studies we provide direct evidence that humans employ temporal fine structure to discriminate between frequencies. To this end we construct tones that are based on a single frequency but in which, through the concatenation of wavelets, the phase changes randomly every few cycles. We then test the frequency discrimination of these phase-changing tones, of control tones without phase changes, and of short tones that consist of a single wavelet. For carrier frequencies below a few kilohertz we find that phase changes systematically worsen frequency discrimination. No such effect appears for higher carrier frequencies at which temporal information is not available in the central auditory system.	t	\N
23029492	Findings on song perception and song production have increasingly suggested that common but partially distinct neural networks exist for processing lyrics and melody. However, the neural substrates of song recognition remain to be investigated. The purpose of this study was to examine the neural substrates involved in the accessing "song lexicon" as corresponding to a representational system that might provide links between the musical and phonological lexicons using positron emission tomography (PET). We exposed participants to auditory stimuli consisting of familiar and unfamiliar songs presented in three ways: sung lyrics (song), sung lyrics on a single pitch (lyrics), and the sung syllable 'la' on original pitches (melody). The auditory stimuli were designed to have equivalent familiarity to participants, and they were recorded at exactly the same tempo. Eleven right-handed nonmusicians participated in four conditions: three familiarity decision tasks using song, lyrics, and melody and a sound type decision task (control) that was designed to engage perceptual and prelexical processing but not lexical processing. The contrasts (familiarity decision tasks versus control) showed no common areas of activation between lyrics and melody. This result indicates that essentially separate neural networks exist in semantic memory for the verbal and melodic processing of familiar songs. Verbal lexical processing recruited the left fusiform gyrus and the left inferior occipital gyrus, whereas melodic lexical processing engaged the right middle temporal sulcus and the bilateral temporo-occipital cortices. Moreover, we found that song specifically activated the left posterior inferior temporal cortex, which may serve as an interface between verbal and musical representations in order to facilitate song recognition.	t	\N
23033450	This study aimed to compare sound production errors arising due to phonological processing impairment with errors arising due to motor speech impairment. Two speakers with similar clinical profiles who produced similar consonant cluster simplification errors were examined using a repetition task. We compared both overall accuracy and acoustic details of hundreds of productions with target consonant clusters to tokens with singletons. Changes in accuracy over the course of the study were also compared. In target words with consonant cluster simplification, the individual whose errors reflected phonological impairment produced articulatory timing consistent with singleton onsets. These productions improved when resyllabification was possible, but error rates were not affected by exposure. In contrast, the individual with motoric-based errors produced simplifications that contained the articulatory timing associated with clusters. Accuracy was not affected by the ability to resyllabify, but it did significantly improve following repeated production. Our findings reveal clear differences between errors arising in phonological processing and in motor planning that reflect the underlying systems. The changes over the course of the study suggest that error types with different sources are responsive to different intervention strategies.	t	\N
23036182	The present event-related potential (ERP) study examined the developmental mechanisms of auditory-vocal integration in normally developing children. Neurophysiological responses to altered auditory feedback were recorded to determine whether they are affected by age and sex. Forty-two children were pairwise matched for sex and were divided into a group of younger (10-12years) and a group of older (13-15years) children. Twenty healthy young adults (20-25years) also participated in the experiment. ERPs were recorded from the participants who heard their voice pitch feedback unexpectedly shifted -50, -100, or -200 cents during sustained vocalization. P1 amplitudes became smaller as subjects increased in age from childhood to adulthood, and males produced larger N1 amplitudes than females. An age-related decrease in the P1-N1 latencies was also found: latencies were shorter in young adults than in school children. A complex age-by-sex interaction was found for the P2 component, where an age-related increase in P2 amplitudes existed only in girls, and boys produced longer P2 latencies than girls but only in the older children. These findings demonstrate that neurophysiological responses to pitch errors in voice auditory feedback depend on age and sex in normally developing children. The present study provides evidence that there is a sex-specific development of the neural mechanisms involved in auditory-vocal integration.	t	\N
23047260	To determine the effect of oral steroid treatment on hearing in unilateral Ménière's disease and endolymphatic hydrops patients. Retrospective chart review. Tertiary referral center. All patients presenting during the 2010 calendar year with confirmed unilateral Ménière's disease or endolymphatic hydrops. Those with a first visit and second visit audiogram (n = 58) were included in the analysis of oral steroid treatment effect. Steroid treatment for hearing loss. Change in hearing, as defined by change in affected ear threshold values or speech discrimination score from pretreatment visit to posttreatment visit. Hearing (threshold, speech discrimination score) in patients' affected ear did not significantly change from first visit to second visit after treatment with steroids relative to patients who did not receive steroid treatment. The results of this and other studies would indicate that a Ménière's disease or endolymphatic hydrops patient is unlikely to experience an improvement in hearing from a short course of oral steroid. Clinically observed temporary improvement did not sustain over several months. Further work to elucidate the mechanisms underlying hearing loss in hydrops, perhaps focusing on the dendrite damage noted in animal models of hydrops, is warranted.	t	\N
23056592	Time-compressed speech, a form of rapidly presented speech, is harder to comprehend than natural speech, especially for non-native speakers. Although it is possible to adapt to time-compressed speech after a brief exposure, it is not known whether additional perceptual learning occurs with further practice. Here, we ask whether multiday training on time-compressed speech yields more learning than that observed during the initial adaptation phase and whether the pattern of generalization following successful learning is different than that observed with initial adaptation only. Two groups of non-native Hebrew speakers were tested on five different conditions of time-compressed speech identification in two assessments conducted 10-14 days apart. Between those assessments, one group of listeners received five practice sessions on one of the time-compressed conditions. Between the two assessments, trained listeners improved significantly more than untrained listeners on the trained condition. Furthermore, the trained group generalized its learning to two untrained conditions in which different talkers presented the trained speech materials. In addition, when the performance of the non-native speakers was compared to that of a group of naïve native Hebrew speakers, performance of the trained group was equivalent to that of the native speakers on all conditions on which learning occurred, whereas performance of the untrained non-native listeners was substantially poorer. Multiday training on time-compressed speech results in significantly more perceptual learning than brief adaptation. Compared to previous studies of adaptation, the training induced learning is more stimulus specific. Taken together, the perceptual learning of time-compressed speech appears to progress from an initial, rapid adaptation phase to a subsequent prolonged and more stimulus specific phase. These findings are consistent with the predictions of the Reverse Hierarchy Theory of perceptual learning and suggest constraints on the use of perceptual-learning regimens during second language acquisition.	t	\N
23059750	The ability to identify stop consonants from brief onset spectra was compared between a group of Chinese children with phonological dyslexia (the PD group, with a mean age of 10 years 4 months) and a group of chronological age-matched control children. The linguistic context, which included vowels and speakers, and durations of stop onset spectra were varied. Children with PD showed lower identification accuracy and exhibited a smaller vowel context effect for some stop-vowel combinations compared with the chronological age-matched control group. Further analyses revealed that the PD group had more variable response patterns, and their responses were less consistent with the acoustic characteristics of stop onset spectra. The results suggest that Chinese children with PD do not show greater sensitivity to allophonic acoustic variability compared with control children and exhibit a generally less robust response pattern to phonetic categories.	t	\N
23085111	Recent electrophysiological studies have reported short latency modulations in cortical regions for multisensory stimuli, thereby suggesting a subcortical, possibly thalamic origin of these modulations. Concurrently, there is an ongoing debate, whether multisensory interplay reflects automatic, bottom-up driven processes or relies on top-down influences. Here, we dissociated the effects of task set and stimulus configurations on BOLD-signals in the human thalamus with event-related functional magnetic resonance imaging (fMRI). We orthogonally manipulated temporal and spatial congruency of audio-visual stimulus configurations, while subjects judged either their temporal or spatial congruency. Voxel-based fMRI results revealed increased fMRI-signals for the temporal versus spatial task in posterior and central thalamus, respectively. A more sensitive region of interest (ROI)-analysis confirmed that the posterior thalamic nuclei showed a preference for the temporal task and central thalamic nuclei for the spatial task. Moreover, the ROI-analysis also revealed enhanced fMRI-signals for spatially incongruent stimuli in the central thalamus. Together, our results demonstrate that both audio-visual stimulus configurations and task-related processing of spatial or temporal stimulus features selectively modulate thalamic processing and thus are in a position to influence cortical processing at an early stage.	t	\N
23088507	Sensitivity to frequency ratios is essential for the perceptual processing of complex sounds and the appreciation of music. This study assessed the effect of ratio simplicity on ratio discrimination for pure tones presented either simultaneously or sequentially. Each stimulus consisted of four 100-ms pure tones, equally spaced in terms of frequency ratio and presented at a low intensity to limit interactions in the auditory periphery. Listeners had to discriminate between a reference frequency ratio of 0.97 octave (about 1.96:1) and target frequency ratios, which were larger than the reference. In the simultaneous condition, the obtained psychometric functions were nonmonotonic: as the target frequency ratio increased from 0.98 octave to 1.04 octaves, discrimination performance initially increased, then decreased, and then increased again; performance was better when the target was exactly one octave (2:1) than when the target was slightly larger. In the sequential condition, by contrast, the psychometric functions were monotonic and there was no effect of frequency ratio simplicity. A control experiment verified that the non-monotonicity observed in the simultaneous condition did not originate from peripheral interactions between the tones. Our results indicate that simultaneous octaves are recognized as "special" frequency intervals by a mechanism that is insensitive to the sign (positive or negative) of deviations from the octave, whereas this is apparently not the case for sequential octaves.	t	\N
23094319	The paper reports on a perception experiment in German that investigated the neuro-cognitive processing of information structural concepts and their prosodic marking using event-related brain potentials (ERPs). Experimental conditions controlled the information status (given vs. new) of referring and non-referring target expressions (nouns vs. adjectives) and were elicited via context sentences, which did not - unlike most previous ERP studies in the field--trigger an explicit focus expectation. Target utterances displayed prosodic realizations of the critical words which differed in accent position and accent type. Electrophysiological results showed an effect of information status, maximally distributed over posterior sites, displaying a biphasic N400--Late Positivity pattern for new information. We claim that this pattern reflects increased processing demands associated with new information, with the N400 indicating enhanced costs from linking information with the previous discourse and the Late Positivity indicating the listener's effort to update his/her discourse model. The prosodic manipulation registered more pronounced effects over anterior regions and revealed an enhanced negativity followed by a Late Positivity for deaccentuation, probably also reflecting costs from discourse linking and updating respectively. The data further lend indirect support for the idea that givenness applies not only to referents but also to non-referential expressions ('lexical givenness').	t	\N
23095266	A retrospective review was performed of patients treated for middle ear cholesteatoma with bone defects of the skull base via a combined transmastoid/middle fossa approach at the University of Tsukuba Hospital from 2006 through 2011 to determine the safety and effectiveness of a combined transmastoid/middle fossa approach for the treatment of cholesteatoma involving the middle cranial fossa. The bone defects of the skull base were reconstructed with a galeal flap pedicled with a parietal branch of the superficial temporal artery and an autologous bone flap. The clinical and radiological data were analyzed. This series included 8 patients (6 men and 2 women) with a mean age of 46.3 years (range 10-67 years). One of the patients preoperatively exhibited meningoencephalocele of the middle fossa skull base, and in the remaining 7 patients, petrous bone involvement such as involvement of the supralabyrinthine cells was observed. The cholesteatoma lesion was totally removed and inner ear function preserved in all the patients. Cerebrospinal fluid leakage was observed in 1 patient during and after the surgery. Neither meningitis nor recurrence was observed in any patient during the follow-up periods (mean 29.4 months, range 6-64 months). The combined transmastoid/middle fossa approach allowed complete removal of cholesteatoma with middle cranial fossa involvement while preserving hearing and preventing postoperative cerebrospinal fluid leakage and meningitis.	t	\N
23102977	For children, learning often occurs in the presence of background noise. As such, there is growing desire to improve a child's access to a target signal in noise. Given adult musicians' perceptual and neural speech-in-noise enhancements, we asked whether similar effects are present in musically-trained children. We assessed the perception and subcortical processing of speech in noise and related cognitive abilities in musician and nonmusician children that were matched for a variety of overarching factors. Outcomes reveal that musicians' advantages for processing speech in noise are present during pivotal developmental years. Supported by correlations between auditory working memory and attention and auditory brainstem response properties, we propose that musicians' perceptual and neural enhancements are driven in a top-down manner by strengthened cognitive abilities with training. Our results may be considered by professionals involved in the remediation of language-based learning deficits, which are often characterized by poor speech perception in noise.	t	\N
23103362	Adolescence is a time of great change in the brain in terms of structure and function. It is possible to track the development of neural function across adolescence using auditory event-related potentials (ERPs). We measured passive auditory ERPs to pure tones and consonant-vowel (CV) syllables in 90 children and adolescents aged 10-18 years, as well as 10 adults. With one exception, the pattern of results were the same for tones and speech: Across adolescence, the P1 ERP peak decreased in size and latency, the N1 increased in size and decreased in latency, the P2 remained constant in size, and the N2 decreased in size but remained stable across adolescence. The exception was P2 latency, which increased for speech but remained stable for tones. Interesting step-like changes were observed for N1 latency for both tones and speech stimuli in 15- to 16-year-olds. These may stem from rapid hormonal changes that affect neurotransmitter activity of the ERP-generating neurons.	t	\N
23103517	The present study builds on our previous study within the framework of Wyer and Collin's comprehension-elaboration theory of humor processing. In this study, an attempt is made to segregate the neural substrates of incongruity detection and incongruity resolution during the comprehension of verbal jokes. Although a number of fMRI studies have investigated the incongruity-resolution process, the differential neurological substrates of comprehension are still not fully understood. The present study utilized an event-related fMRI design incorporating three conditions (unfunny, nonsensical and funny) to examine distinct brain regions associated with the detection and resolution of incongruities. Stimuli in the unfunny condition contained no incongruities; stimuli in the nonsensical condition contained irresolvable incongruities; and stimuli in the funny condition contained resolvable incongruities. The results showed that the detection of incongruities was associated with greater activation in the right middle temporal gyrus and right medial frontal gyrus, and the resolution of incongruities with greater activation in the left superior frontal gyrus and left inferior parietal lobule. Further analysis based on participants' rating scores provided converging results. Our findings suggest a three-stage neural circuit model of verbal humor processing: incongruity detection and incongruity resolution during humor comprehension and inducement of the feeling of amusement during humor elaboration.	t	\N
23106730	The acquisition of the function of case-marking is a key step in the development of sentence processing for German-speaking children since case-marking reveals the relations between sentential arguments. In this study, we investigated the development of the processing of case-marking and argument structures in children at 3, 4;6 and 6 years of age, as well as its processing in adults. Using EEG, we measured event-related potentials (ERPs) in response to object-initial compared to subject-initial German sentences including transitive verbs and case-marked noun phrases referring to animate arguments. We also tested children's behavioral competence in a sentence-picture matching task. Word order and case-marking were manipulated in German main clauses. Adults' behavioral performance was close to perfect and their ERPs revealed a negativity for the processing of the topicalized accusative marked noun phrase (NP1) and no effect for the second NP (NP2) in the object-initial structure. Children's behavioral data showed a significant above-chance outcome in the subject-initial condition for all age groups, but not for the object-initial condition. In contrast to adults, the ERPs of 3-year-olds showed a positivity at NP1, indicating difficulties in processing the non-canonical object-initial structures. Children at the age of 4;6 did not differ in the processing patterns of object-initial vs. subject-initial sentences at NP1 but showed a slight positivity at NP2. This positivity at NP2, which implies syntactic integration difficulties, is more pronounced in 6-year-olds but is absent in adults. At NP1, however, 6-year-olds show the same negativity as adults. In sum, the behavioral and electrophysiological findings demonstrate that children in each age group use different strategies, which are indicative of their developmental stage. While 3-year-olds merely detect differences in the two sentence structures without being able to use this information for sentence comprehension, 4;6-year-olds proceed to use mainly a word-order strategy, processing NP1 in both conditions in the same manner, which leads to processing difficulties upon detecting case-marking cues at NP2. At the age of 6, children are able to use case-marking cues for comprehension but still show enhanced effort for correct thematic-role assignment.	t	\N
23106737	Integrating the multisensory features of talking faces is critical to learning and extracting coherent meaning from social signals. While we know much about the development of these capacities at the behavioral level, we know very little about the underlying neural processes. One prominent behavioral milestone of these capacities is the perceptual narrowing of face-voice matching, whereby young infants match faces and voices across species, but older infants do not. In the present study, we provide neurophysiological evidence for developmental decline in cross-species face-voice matching. We measured event-related brain potentials (ERPs) while 4- and 8-month-old infants watched and listened to congruent and incongruent audio-visual presentations of monkey vocalizations and humans mimicking monkey vocalizations. The ERP results indicated that younger infants distinguished between the congruent and the incongruent faces and voices regardless of species, whereas in older infants, the sensitivity to multisensory congruency was limited to the human face and voice. Furthermore, with development, visual and frontal brain processes and their functional connectivity became more sensitive to the congruence of human faces and voices relative to monkey faces and voices. Our data show the neural correlates of perceptual narrowing in face-voice matching and support the notion that postnatal experience with species identity is associated with neural changes in multisensory processing (Lewkowicz & Ghazanfar, 2009).	t	\N
23110123	The common marmoset (Callithrix jacchus) is a small New World primate that has increasingly been used as a non-human model in the fields of sensory, motor, and cognitive neuroscience. However, little knowledge exists regarding behavioral methods in this species. Developing an understanding of the neural basis of perception and cognition in an animal model requires measurement of both brain activity and behavior. Here we describe an operant conditioning behavioral training method developed to allow controlled psychoacoustic measurements in marmosets. We demonstrate that marmosets can be trained to consistently perform a Go/No-Go auditory task in which a subject licks at a feeding tube when it detects a sound. Correct responses result in delivery of a food reward. Crucially, this operant conditioning task generates little body movement and is well suited for pairing behavior with single-unit electrophysiology. Successful implementation of an operant conditioning behavior opens the door to a wide range of new studies in the field of auditory neuroscience using the marmoset as a model system.	t	\N
23110674	Evaluation of pure-tone audiometry (PTA) in hearing screening of a population with mild to profound intellectual disability (ID). PTA was performed at six frequencies at the screening level 20 dB HL. Referral criteria were threshold levels ≥ 25 dB HL at two or more frequencies for one ear or both. 1478 participants aged 7-91 years were included. 1470 (99.5%) people cooperated in screening of which 1325 (90%) could be tested on both ears at all six frequencies. A majority, 987 (66.8%), performed ordinary PTA, 234 (15.8%) conditioned play audiometry, and 249 (16.9%) behavioural observation audiometry. Six hundred and sixty-nine (45%) passed and 809 (55%) failed according to referral criteria. Of those failing, 441 (54.5%) accepted referral to clinical evaluation. PTA with slight modifications is applicable for screening of a population with mild to profound intellectual disability. The most challenging and time-consuming activity is to introduce the test procedure in a way that reduces anxiety and establishes trust.	t	\N
23116815	The supratemporal plane contains several functionally heterogeneous subregions that respond strongly to speech. Much of the prior work on the issue of speech processing in the supratemporal plane has focused on neural responses to single speech vs. non-speech sounds rather than focusing on higher-level computations that are required to process more complex auditory sequences. Here we examined how information is integrated over time for speech and non-speech sounds by quantifying the BOLD fMRI response to stochastic (non-deterministic) sequences of speech and non-speech naturalistic sounds that varied in their statistical structure (from random to highly structured sequences) during passive listening. Behaviorally, the participants were accurate in segmenting speech and non-speech sequences, though they were more accurate for speech. Several supratemporal regions showed increased activation magnitude for speech sequences (preference), but, importantly, this did not predict sensitivity to statistical structure: (i) several areas showing a speech preference were sensitive to statistical structure in both speech and non-speech sequences, and (ii) several regions that responded to both speech and non-speech sounds showed distinct responses to statistical structure in speech and non-speech sequences. While the behavioral findings highlight the tight relation between statistical structure and segmentation processes, the neuroimaging results suggest that the supratemporal plane mediates complex statistical processing for both speech and non-speech sequences and emphasize the importance of studying the neurocomputations associated with auditory sequence processing. These findings identify new partitions of functionally distinct areas in the supratemporal plane that cannot be evoked by single stimuli. The findings demonstrate the importance of going beyond input preference to examine the neural computations implemented in the superior temporal plane.	t	\N
23117057	Introducing coherent masker envelope modulation to frequency regions neighboring the signal frequency can reduce detection thresholds for a pure-tone signal. Verhey and Ernst (2009) reported that irregular masker modulation conferred greater benefit than regular modulation when the masker was broadband, but that there was no difference when the masker was narrowband. The present study evaluated two possible explanations for this result: one based on modulation adaptation and the other based on the introduction of relatively long-duration modulation minima in the irregular masker modulation condition. The first experiment replicated the results of Verhey and Ernst (2009), but also included conditions in which a 12.5-ms signal was presented in a 12.5-ms modulation minimum, which was exempted from envelope jitter. The second experiment used a continuous masker and suspended jitter during epochs associated with either a 12.5- or 87.5-ms signal. No benefit of masker envelope irregularity before or after the signal was observed in either experiment. These findings are inconsistent with an explanation based on modulation adaptation, implicating instead the introduction of relatively long-duration modulation minima in the large masking release obtained for a long-duration signal in an irregularly modulated masker.	t	\N
23123219	The current study was undertaken to investigate changes in forward masking patterns using on-frequency and off-frequency maskers of 7 and 10 kHz probes in the Sprague-Dawley rat. Off-frequency forward masking growth functions have been shown in humans to be non-linear, while on-frequency functions behave linearly. The non-linear nature of the off-frequency functions is attributable to active processing from the outer hair cells, and was therefore expected to be sensitive to noise-induced cochlear damage. For the study, nine Sprague-Dawley rats' auditory brainstem responses (ABRs) were recorded with and without forward maskers. Forward masker-induced changes in latency and amplitude of the initial positive peak of the rats' auditory brainstem responses were assessed with both off-frequency and on-frequency maskers. The rats were then exposed to a noise designed to induce 20-40 dB of permanent threshold shift. Twenty-one days after the noise exposure, the forward masking growth functions were measured to assess noise-induced changes in the off-frequency and on-frequency forward masking patterns. Pre-exposure results showed compressive non-linear masking effects of the off-frequency conditions on both latency and amplitude of the auditory brainstem response. The noise rendered the off-frequency forward masking patterns more linear, consistent with human behavioral findings. On- and off-frequency forward masking growth functions were calculated, and they displayed patterns consistent with human behavioral functions, both prior to noise and after the noise exposure.	t	\N
23132604	Common-coding theory posits that (1) perceiving an action activates the same representations of motor plans that are activated by actually performing that action, and (2) because of individual differences in the ways that actions are performed, observing recordings of one's own previous behavior activates motor plans to an even greater degree than does observing someone else's behavior. We hypothesized that if observing oneself activates motor plans to a greater degree than does observing others, and if these activated plans contribute to perception, then people should be able to lipread silent video clips of their own previous utterances more accurately than they can lipread video clips of other talkers. As predicted, two groups of participants were able to lipread video clips of themselves, recorded more than two weeks earlier, significantly more accurately than video clips of others. These results suggest that visual input activates speech motor activity that links to word representations in the mental lexicon.	t	\N
23135616	The objective was to develop and evaluate a new sentence test, the Sentence Test with Adaptive Randomized Roving levels, intended to emulate everyday listening experience, using both normal-hearing (NH) and cochlear implant (CI) groups, examining practicality, learning, test-retest variability, and interlist variability. In experiment 1, each of 25 NH adults was tested using five lists, each comprising 30 sentences. One male and one female speaker each spoke 15 sentences. Ten sentences were presented at each of three presentation levels: 50, 65, and 80 dB SPL. The relative level of a speech-shaped noise was varied adaptively to estimate the speech reception threshold (SRT). Counterbalance for list order was achieved by staggering the allocation of lists to participants. To allow assessment of learning effects, no practice was given. The variability of mean SRTs across lists was small, but correction factors were derived for each list so that, after correction, all lists gave the same mean SRT. Test-retest variability was estimated by examining the corrected SRTs for each subject's five lists. In experiment 2, 25 CI users each received one test list after a small amount of practice. Experiment 3 examined the effect of speech rate using time-compressed speech, for age-matched NH and CI users. The mean SRT for the NH participants was approximately -6 dB and was similar for the male and female speakers. There was a small but significant improvement in SRTs between the first and later lists administered, but no further improvement for subsequent lists. On the basis of the variability of the corrected SRTs within each participant, a 2.2 dB difference in SRT is meaningful for comparisons using one test list per condition, for a single participant. The percentage of key words correct varied with presentation level over a 13% range, being best at 65 dB SPL. Only 40% of the CI group achieved an SRT lower than 20 dB for both speakers. There was large individual variability in the SRTs, and SRTs were higher for the female than for the male speaker. For the CI participants, the percentage of key words correct varied markedly with level, from 19% at the lowest level to 57% at the medium level. Time compression had a small effect for NH participants but a very large effect for CI participants. The Sentence Test with Adaptive Randomized Roving levels seems practical to administer and is reasonably sensitive. For NH participants, a 2.2 dB difference in SRT is meaningful for a single list per condition and a single participant. Although learning effects were small for NH participants, it seems prudent to provide some practice sentences when testing hearing-impaired or CI participants. The very large effect of time compression for the CI group has implications for live voice testing of children, because speech rate is only poorly controlled in such testing.	t	\N
23144191	This is the first study on adults' physiological reactivity to infant cry sounds and the association with intended harsh parenting using salivary α-amylase (sAA) as a novel and noninvasive marker of autonomic nervous system activity. The sample consisted of 184 adult twin pairs. In an experimental design, cry sounds were presented and adults' perception and their intended caregiving responses were measured. Saliva samples were collected after each cry sound. For the majority of the sample, a decrease in sAA across the cry paradigm was observed. However, adults who indicated that they would respond in a harsh way to the crying infant were significantly less likely to show a decrease in sAA. Consistent with previous studies on physiological hyperreactivity in abusive parents, these findings suggest that failure to habituate to repeated infant crying may be one of the mediating mechanisms through which excessive, inconsolable, and high-pitched infant crying triggers less optimal caregiving.	t	\N
23145600	Subjective evaluation of acoustics was studied by recording nine concert halls with a simulated symphony orchestra on a seat 12 m from the orchestra. The recorded music was spatially reproduced for subjective listening tests and individual vocabulary profiling. In addition, the preferences of the assessors and objective parameters were gathered. The results show that concert halls were discriminated using perceptual characteristics, such as Envelopment/Loudness, Reverberance, Bassiness, Proximity, Definition, and Clarity. With these perceptual dimensions the preference ratings can be explained. Seventeen assessors were divided into two groups based on their preferences. The first group preferred concert halls with relatively intimate sound, in which it is quite easy to hear individual instruments and melody lines. In contrast, the second group preferred a louder and more reverberant sound with good envelopment and strong bass. Even though all halls were recorded exactly at the same distance, the preference is best explained with subjective Proximity and with Bassiness, Envelopment, and Loudness to some extent. Neither the preferences nor the subjective ratings could be fully explained by objective parameters (ISO3382-1:2009), although some correlations were found.	t	\N
23151776	To examine and compare the family environment of preschool- and school-age children with cochlear implants and assess its influence on children's executive function and spoken language skills. Retrospective between-subjects design. Outpatient research laboratory. Prelingually deaf children with cochlear implants and no additional disabilities and their families. Cochlear implantation and speech-language therapy. Parents completed the Family Environment Scale and the Behavior Rating Inventory of Executive Function (or the preschool version). Children were tested using the Peabody Picture Vocabulary Test-4 and either the Preschool Language Scales-4 or the Clinical Evaluation of Language Fundamentals-4. The family environments of children with cochlear implants differed from normative data obtained from hearing children, but average scores were within 1 standard deviation of norms on all subscales. Families of school-age children reported higher levels of control than those of preschool-age children. Preschool-age children had fewer problems with emotional control when families reported higher levels of support and lower levels of conflict. School-age children had fewer problems with inhibition but more problems with shifting of attention when families reported lower levels of conflict. School-age children's receptive vocabularies were enhanced by families with lower levels of control and higher levels of organization. Family environment and its relation to language skills and executive function development differed across the age groups in this sample of children with cochlear implants. Because family dynamics is one developmental/environmental factor that can be altered with therapy and education, the present results have important clinical implications for family-based interventions for deaf children with cochlear implants.	t	\N
23151778	To present the preliminary results of new malleus replacement prosthesis combined with a total ossicular prosthesis in middle ear reconstruction in patients missing the malleus and stapes. Prospective experimental and nonrandomized clinical study. Tertiary referral center. An original titanium malleus replacement prosthesis (MRP) was designed to be inserted into the external auditory canal and to replace a missing malleus for various middle ear pathologies. The MRP was tested experimentally and clinically. The vibratory properties of the new prosthesis were measured using laser Doppler vibrometry. Ninety patients with missing malleus and stapes, undergoing 92 ossicular reconstructions were enrolled in this study from September 1994 to March 2012. Comparative analyses were made between a group of 34 cases of ossicular reconstructions with total prosthesis (TORP) positioned from the tympanic membrane to the stapes footplate (TM-to-footplate assembly) and a group of 58 cases of ossicular reconstructions with TORP positioned from a newly designed malleus replacement prosthesis (MRP) to the stapes footplate (MRP-to-footplate assembly). Preoperative and postoperative audiometric evaluation using conventional audiometry, that is, air-bone gap (ABG), bone-conduction thresholds (BC), and air-conduction thresholds (AC) were assessed. Experimentally, the vibratory properties of the MRP are promising and remain very good even when the MRP is cemented into the bony canal wall mimicking its complete osseous-integration, if this were to occur. This finding supports the short-term clinical results as in the TM-to-footplate group; the 3-month postoperative mean ABG was 23.3 dB compared with 12.5 dB in the MRP-to-footplate group (difference, 10.8; 95% confidence interval, 4.0-17.6); 37.0% of patients from the TM-to-footplate group had a postoperative ABG of 10 dB or less, and 48.1% of patients had a postoperative ABG of 20 dB or less, as compared with 58.1% and 79.1%, respectively, in the MRP-to-footplate group. The average gain in AC was 11.0 dB in the TM-to-footplate group as compared with 21.3 dB in the MRP-to-footplate group (difference, -10.3; 95% confidence interval, -18.2 to -2.4). The results of this study indicate that superior postoperative hearing thresholds could be achieved using a MRP-to-footplate assembly, compared with a TM-to-footplate assembly in patients with an absent malleus undergoing ossiculoplasty. The postoperative AC thresholds, after 3 months and 1 year, are significantly lower in patients treated with the MRP-to-footplate assembly.	t	\N
23156899	The study presented in this paper aimed to investigate the pattern of semantic priming effects, under masked and unmasked conditions, in the lexical decision task, manipulating type of semantic relation and associative strength. Three different kinds of word relations were examined in two experiments: only-semantically related words [e.g., codo (elbow)-rodilla (knee)] and semantic/associative related words with strong [e.g., mesa (table)-silla (chair) and weak association strength [e.g., sapo (toad)-rana (frog)]. In Experiment 1 a masked priming procedure was used with a prime duration of 56 ms, and in Experiment 2, the prime was presented unmasked for 150 ms. The results showed that there were masked priming effects with strong associates, but no evidence of these effects was found with weak associates or only-semantic related word pairs. When the prime was presented unmasked, the three types of relations produced significant priming effects and they were not influenced by association strength.	t	\N
23165224	This study describes a vocoder-based frequency-lowering system that enhances spectral cues for nonsonorant consonants differing in place of articulation. The goal of this study was to evaluate the efficacy of this system for speech recognition by hearing-impaired listeners. Experiment 1 evaluated fricative consonant recognition in quiet. Eight fricatives in /VCV/ context were used. Experiment 2 evaluated consonant recognition in quiet with 22 consonants. Six listeners with steeply sloping high-frequency sensorineural hearing loss participated in experiment 1. The same six listeners and three additional listeners with flat/mid-frequency sensorineural hearing loss participated in experiment 2. Two processing conditions-frequency lowering and conventional amplification-were tested in each experiment. Insertion gains based on the NAL-RP formula were provided up to 8000 Hz for each processing condition. In addition, speech stimuli were low-pass (LP) filtered at 1000, 1500, and 2000 Hz to evaluate the effect of lack of high-frequency speech information on consonant perception with and without frequency lowering. For these LP speech conditions, amplification was provided up to the cutoff frequencies. Overall percent correct and percent information transmission were calculated for each processing and speech condition. The frequency-lowering system provided significant benefit for the perception of fricative consonants and perception of the place-of-articulation feature for hearing-impaired listeners without affecting their perception of sonorant consonants and other consonant features (i.e., voicing and nasality). The improvement of fricative consonant perception was observed for both wideband and LP speech conditions for the steeply sloping hearing-loss listeners. The results indicate that individuals with unaidable hearing loss above 1000 to 2000 Hz would receive significant benefit with the system compared with conventional amplification for the perception of fricative consonants, and more importantly, significant benefit for the perception of place of articulation.	t	\N
23165382	To objectively determine changes in sensorineural hearing in children with mucopolysaccharidosis (MPS) by comparing audiological data before and after hematopoietic stem cell transplantation (HSCT). Retrospective medical chart analysis. Tertiary referral hospital. Thirty pediatric patients with the diagnosis of MPS who underwent HSCT and had audiological data before and after HSCT. Data were extracted from medical charts for patients seen at our institution from January 1, 1999, to December 1, 2009. Hearing was assessed using behavioral audiometry testing and auditory brainstem responses (ABR) before and after HSCT. Patient demographics, diagnosis, and age at HSCT were also evaluated. Thirty patients with MPS were included. Four (13%) had MPS type 3a, 2 (7%) had MPS type 2, and 24 (80%) had MPS type 1. The average age at HSCT was 19 months (range, 5-44 months). Hearing improvement was evaluated by audiogram (20 patients), ABR (8 patients), and qualitative measures (30 patients). On average, patients did not show improvement on audiogram (P = .28; paired t test). The ABR click threshold improved 19 dB on average (P < .001). Qualitatively, 3 patients had normal hearing before and after HSCT. Of the remaining 27 patients, 20 (67%) showed improvement in sensorineural hearing (P < .001). Five (17%) had hearing loss and did not improve. Two (7%) had worsening hearing. Hematopoietic stem cell transplantation at the age of 25 months or younger was significantly correlated with hearing improvement (P = .03). Hematopoietic stem cell transplantation may provide improvement in MPS-associated sensorineural hearing loss. Hearing improvement is more likely to occur in patients who undergo transplantation at 25 months or younger.	t	\N
23166292	Functional magnetic resonance imaging (fMRI) was employed to identify neural regions engaged during the encoding of contextual features belonging to different modalities. Subjects studied objects that were presented to the left or right of fixation. Each object was paired with its name, spoken in either a male or a female voice. The test requirement was to discriminate studied from unstudied pictures and, for each picture judged old, to retrieve its study location and the gender of the voice that spoke its name. Study trials associated with accurate rather than inaccurate location memory demonstrated enhanced activity in the fusiform and parahippocampal cortex and the hippocampus and reduced activity (a negative subsequent memory effect) in the medial occipital cortex. Successful encoding of voice information was associated with enhanced study activity in the right middle superior temporal sulcus and activity reduction in the right superior frontal cortex. These findings support the proposal that encoding of a contextual feature is associated with enhanced activity in regions engaged during its online processing. In addition, they indicate that negative subsequent memory effects can also demonstrate feature-selectivity. Relative to other classes of study trials, trials for which both contextual features were later retrieved demonstrated enhanced activity in the lateral occipital complex and reduced activity in the temporo-parietal junction. These findings suggest that multifeatural encoding was facilitated when the study item was processed efficiently and study processing was not interrupted by redirection of attention toward extraneous events.	t	\N
23167712	Despite its fundamental relevance for representing the emotional world surrounding us, human affective neuroscience research has widely neglected the auditory system, at least in comparison to the visual domain. Here, we have investigated the spatiotemporal dynamics of human affective auditory processing using time-sensitive whole-head magnetoencephalography. A novel and highly challenging affective associative learning procedure, 'MultiCS conditioning', involving multiple conditioned stimuli (CS) per affective category, was adopted to test whether previous findings from intramodal conditioning of multiple click-tones with an equal number of auditory emotional scenes (Bröckelmann et al., 2011 J. Neurosci., 31, 7801) would generalise to crossmodal conditioning of multiple click-tones with an electric shock as single aversive somatosensory unconditioned stimulus (UCS). Event-related magnetic fields were recorded in response to 40 click-tones before and after four contingent pairings of 20 CS with a shock and the other half remaining unpaired. In line with previous findings from intramodal MultiCS conditioning we found an affect-specific modulation of the auditory N1m component 100-150 ms post-stimulus within a distributed frontal-temporal-parietal neural network. Increased activation for shock-associated tones was lateralised to right-hemispheric regions, whereas unpaired safety-signalling tones were preferentially processed in the left hemisphere. Participants did not show explicit awareness of the contingent CS-UCS relationship, yet behavioural conditioning effects were indicated on an indirect measure of stimulus valence. Our findings imply converging evidence for a rapid and highly differentiating affect-specific modulation of the auditory N1m after intramodal as well crossmodal MultiCS conditioning and a correspondence of the modulating impact of emotional attention on early affective processing in vision and audition.	t	\N
23168357	We investigated gender differences in the identification of personally familiar voices in a gender-balanced sample of 40 listeners. From various types of utterances, listeners had to identify by name 20 speakers (10 female) among a set of 70 possible classmates who were all 12th grade pupils from the same local secondary school. Mean identification rates were 67% from sentences, and around 35% for an isolated /Hello/ or a VCV syllable. Even from non-verbal harrumphs, speakers were identified with an accuracy of 18%, i.e. highly above chance levels. Substantial individual differences were observed between listeners. Importantly, superior overall performance of female listeners was qualified by an interaction between voice gender and listener gender. Male listeners exhibited an own-gender bias (i.e. better identification for male than female voices), whereas female listeners identified voices of both genders at similar levels. Individual own-gender identification biases were correlated with differences in reported contact to a speaker's voice and voice distinctiveness. Overall, the present study establishes a number of factors that account for substantial individual differences in personal voice identification.	t	\N
23169196	Patients with single-sided deafness (SSD), where one ear has an unaidable hearing loss and the other ear has normal or aidable hearing, often complain of difficulties understanding speech and localizing sound sources, and report a higher self-perceived hearing disability. Patients with SSD may benefit from using contralateral routing of signal (CROS) or bilateral contralateral routing of the signal (BiCROS) amplification. Dissatisfaction of previously available (Bi)CROS devices has been reported, such as, interfering transmissions, low-fidelity sound quality, poor "user-friendly" set-up, and a bulky and cosmetically cumbersome appearance. Recent advances in hearing aid technology have improved (Bi)CROS hearing aids; however, these devices have not been experimentally evaluated. We hypothesized that newer technology with reports of improved digital signal processing, wireless transmission, and physical design would be as good, or better than, our participants' previous-generation BiCROS systems. A within-subjects, pretest-posttest design was executed. Thirty-nine veterans (one female, 38 males; mean age = 74 yr, range = 49-85 yr) from the Audiology Section of the Bay Pines Veterans Affair Healthcare System participated. All participants were previously experienced BiCROS hearing aid users with varying degrees of sensorinerual hearing impairment in their better ear. Participants were provided at least 4 wk of consistent use with the new BiCROS. DATA COLLECTION AND ANALYSES: Participants completed three research visits. At Visit 1, with their previous BiCROS, and at Visit 3, with their new BiCROS, the following objective and subjective measures were obtained: (1) soundfield speech-in-noise testing using the Words-In-Noise (WIN) test; (2) speech, spatial, and qualities of the hearing scale (SSQ) questionnaire; (3) selected questions from the MarkeTrak questionnaire; and, (4) three open-ended questions. Data were analyzed using parametric and nonparametric statistics. Overall, the objective (WIN) and subjective (SSQ, MarkeTrak, and open-ended questions) measures indicated that the new BiCROS provided better outcomes than the previous BiCROS system. In addition, an overlap of favorable results was seen across measures. Of the 39 participants, 95% reported improvements with the new BiCROS and chose to utilize the device regularly. The favorable objective and subjective outcomes indicate that the new BiCROS system is as good, or better than, what was previously utilized by our sample of veterans.	t	\N
23174416	Speech contains a variety of acoustic cues to auditory and phonetic contrasts that are exploited by the listener in decoding the acoustic signal. In three experiments, we tried to elucidate whether listeners rely on formant peak frequencies or whole spectrum attributes in vowel discrimination. We created two vowel continua in which the acoustic distance in formant frequencies was constant but the continua differed in spectral moments (i.e., the whole spectrum modeled as a probability density function). In Experiment 1, we measured reaction times and response accuracy while listeners performed a go/no-go discrimination task. The results indicated that the performance of the listeners was based on the spectral moments (especially the first and second moments), and not on formant peaks. Behavioral results in Experiment 2 showed that, when the stimuli were presented in noise eliminating differences in spectral moments between the two continua, listeners employed formant peak frequencies. In Experiment 3, using the same listeners and stimuli as in Experiment 1, we measured an automatic brain potential, the mismatch negativity (MMN), when listeners did not attend to the auditory stimuli. Results showed that the MMN reflects sensitivity only to the formant structure of the vowels. We suggest that the auditory cortex automatically and pre-attentively encodes formant peak frequencies, whereas attention can be deployed for processing additional spectral information, such as spectral moments, to enhance vowel discrimination.	t	\N
23178211	Blind people may compensate for their visual loss by the increased use of auditory spatial information, thus showing normal or even supra-normal ability to localize sources of sound. However, the problem of how blind persons develop and maintain an internal concept of the topography of the auditory space in the absence of calibration by visual information is still unsolved. The present study demonstrated a substantial superiority of blind subjects in perception of auditory motion: The minimum audible movement angle of blind subjects (mean 3°) was about half the value found in matched sighted controls, whereas no such advantage was demonstrable for localization of stationary sound. There were no significant differences between early or congenitally blind subjects and late blind subjects, suggesting that long-term visual deprivation per se, independently of the point in time of its onset, was relevant for the superiority in auditory motion perception. The results were compatible with the hypothesis that in the absence of visual input the calibration of the auditory space is performed by audiomotor feedback, that is, by the evaluation of systematic changes of auditory spatial cues resulting from head and body movements. It is reasonable to assume that with blindness the neuronal circuits specifically concerned with the analysis of auditory motion are more intensely trained than in sighted people. It seems possible that the higher demand of motion analysis associated with blindness is related to processes of reorganization in the brain, as have been previously reported to occur also in areas known to be involved in auditory and/or visual motion analysis in sighted persons.	t	\N
23231122	Measures of spectral ripple resolution have become widely used psychophysical tools for assessing spectral resolution in cochlear-implant (CI) listeners. The objective of this study was to compare spectral ripple discrimination and detection in the same group of CI listeners. Ripple detection thresholds were measured over a range of ripple frequencies and were compared to spectral ripple discrimination thresholds previously obtained from the same CI listeners. The data showed that performance on the two measures was correlated, but that individual subjects' thresholds (at a constant spectral modulation depth) for the two tasks were not equivalent. In addition, spectral ripple detection was often found to be possible at higher rates than expected based on the available spectral cues, making it likely that temporal-envelope cues played a role at higher ripple rates. Finally, spectral ripple detection thresholds were compared to previously obtained speech-perception measures. Results confirmed earlier reports of a robust relationship between detection of widely spaced ripples and measures of speech recognition. In contrast, intensity difference limens for broadband noise did not correlate with spectral ripple detection measures, suggesting a dissociation between the ability to detect small changes in intensity across frequency and across time.	t	\N
23231815	Normal temporal processing is important for the perception of speech in quiet and in difficult listening situations. Temporal resolution is commonly measured using a behavioral gap detection task, where the patient or subject must participate in the evaluation process. This is difficult to achieve with subjects who cannot reliably complete a behavioral test. However, recent research has investigated the use of evoked potential measures to evaluate gap detection. The purpose of the current study was to record N1-P2 responses to gaps in broadband noise in normal hearing young adults. Comparisons were made of the N1 and P2 latencies, amplitudes, and morphology to different length gaps in noise in an effort to quantify the changing responses of the brain to these stimuli. It was the goal of this study to show that electrophysiological recordings can be used to evaluate temporal resolution and measure the influence of short and long gaps on the N1-P2 waveform. This study used a repeated-measures design. All subjects completed a behavioral gap detection procedure to establish their behavioral gap detection threshold (BGDT). N1-P2 waveforms were recorded to the gap in a broadband noise. Gap durations were 20 msec, 2 msec above their BGDT, and 2 msec. These durations were chosen to represent a suprathreshold gap, a near-threshold gap, and a subthreshold gap. Fifteen normal-hearing young adult females were evaluated. Subjects were recruited from the local university community. Latencies and amplitudes for N1 and P2 were compared across gap durations for all subjects using a repeated-measures analysis of variance. A qualitative description of responses was also included. Most subjects did not display an N1-P2 response to a 2 msec gap, but all subjects had present clear evoked potential responses to 20 msec and 2+ msec gaps. Decreasing gap duration toward threshold resulted in decreasing waveform amplitude. However, N1 and P2 latencies remained stable as gap duration changed. N1-P2 waveforms can be elicited by gaps in noise in young normal-hearing adults. The responses are present as low as 2 msec above behavioral gap detection thresholds (BGDT). Gaps that are below BGDT do not generally evoke an electrophysiological response. These findings indicate that when a waveform is present, the gap duration is likely above their BGDT. Waveform amplitude is also a good index of gap detection, since amplitude decreases with decreasing gap duration. Future studies in this area will focus on various age groups and individuals with auditory disorders.	t	\N
23231816	Most cochlear implant (CI) users describe music as a noise-like and unpleasant sound. Using behavioral tests, most prior studies have shown that perception of pitch-based melody and timbre is poor in CI users. This article will focus on cortical encoding of timbre changes in CI users, which may allow us to find solutions to further improve CI benefits. Furthermore, the value of using objective measures to reveal neural encoding of timbre changes may be reflected in this study. A case-control study of the mismatch negativity (MMN) using electrophysiological technique was conducted. To derive MMNs, three randomly arranged oddball paradigms consisting of standard/deviant instrumental pairs: saxophone/piano, cello/trombone, and flute/French horn, respectively, were presented. Ten CI users and ten normal-hearing (NH) listeners participated in this study. After filtering, epoching, and baseline correction, independent component analysis (ICA) was performed to remove artifacts. The averaged waveforms in response to the standard stimuli (STANDARD waveform) and the deviant stimuli (DEVIANT waveform) in each condition were separately derived. The responses from nine electrodes in the fronto-central area were averaged to form one waveform. The STANDARD waveform was subtracted from the DEVIANT waveform to derive the difference waveform, for which the MMN was judged to be present or absent. The measures used to evaluate the MMN included the MMN peak latency and amplitude as well as MMN duration. The MMN, which reflects the ability to automatically detect acoustic changes, was present in all NH listeners but only approximately half of CI users. In CI users with present MMNs, the MMN peak amplitude and duration were significantly smaller and shorter compared to those in NH listeners. Our electrophysiological results were consistent with prior behavioral results that CI users' performance in timbre perception was significantly poorer than that in NH listeners. Our results may suggest that timbre information is poorly registered in the auditory cortex of CI users and the capability of automatic detection of timbre changes is degraded in CI users. Although there are some limitations of the MMN in CI users, along with other objective auditory evoked potential tools, the MMN may be a useful objective tool to indicate the extent of sound registration in auditory cortex in the future efforts of improving CI design and speech strategy.	t	\N
23237416	Children with phonological impairment (PI) often have difficulties perceiving insufficiencies in their own speech. The use of recordings has been suggested as a way of directing the child's attention toward his/her own speech, despite a lack of evidence that children actually recognize their recorded voice as their own. We present two studies of children's self-voice identification, one exploring developmental aspects, and one exploring potential effects of having a PI. The results indicate that children from 4 to 8 years recognize their recorded voice well (around 80% accuracy), regardless of whether they have a PI or not. A subtle change in this ability from 4 to 8 years is observed that could be linked to a development in short-term memory. Clinically, one can indeed expect an advantage of using recordings in therapy; this could constitute an intermediate step toward the more challenging task of online self-monitoring.	t	\N
23238175	To investigate the relationship between the threshold and the interaural amplitude difference ratio (IADR) in cervical vestibular evoked myogenic potential (cVEMP) testing and pursuit the clinical significance of the parameters. cVEMP responses were recorded while the SCM contraction was controlled using a pressure cuff. The intensities of the sound stimulation decreased from 95 dB n HL by 5 dB, until no responses were evoked. Thresholds, interaural threshold difference (ITD), amplitudes, and interaural amplitude difference ratio at the stimulation of 95 dB n HL were calculated and the relationship between them was examined. All subjects showed cVEMP responses bilaterally. Thresholds measured were overall 76 dB n HL and most (92%) ears showed the ITD of 0 or 5 dB. The amplitudes of cVEMP responses showed a positive correlation with the sound intensities, and more specifically with the sound intensity above each threshold value. There was no significant difference in IADR values by the ITD. Based on our study, the ITD is less than 10 dB in most normal subjects and estimation of threshold should be added to cVEMP testing for probing vestibular asymmetry. Getting a threshold might be helpful in determining whether the abnormal interaural amplitude difference ratio is related to the abnormal ITD.	t	\N
23241212	Coloured-hearing (CH) synesthesia is a perceptual phenomenon in which an acoustic stimulus (the inducer) initiates a concurrent colour perception (the concurrent). Individuals with CH synesthesia "see" colours when hearing tones, words, or music; this specific phenomenon suggesting a close relationship between auditory and visual representations. To date, it is still unknown whether the perception of colours is associated with a modulation of brain functions in the inducing brain area, namely in the auditory-related cortex and associated brain areas. In addition, there is an on-going debate as to whether attention to the inducer is necessarily required for eliciting a visual concurrent, or whether the latter can emerge in a pre-attentive fashion. By using the EEG technique in the context of a pre-attentive mismatch negativity (MMN) paradigm, we show that the binding of tones and colours in CH synesthetes is associated with increased MMN amplitudes in response to deviant tones supposed to induce novel concurrent colour perceptions. Most notably, the increased MMN amplitudes we revealed in the CH synesthetes were associated with stronger intracerebral current densities originating from the auditory cortex, parietal cortex, and ventral visual areas. The automatic binding of tones and colours in CH synesthetes is accompanied by an early pre-attentive process recruiting the auditory cortex, inferior and superior parietal lobules, as well as ventral occipital areas.	t	\N
23249352	Psychophysical experiments show that auditory change detection can be disturbed in situations in which listeners have to monitor complex auditory input. We made use of this change deafness effect to segregate the neural correlates of physical change in auditory input from brain responses related to conscious change perception in an fMRI experiment. Participants listened to two successively presented complex auditory scenes, which consisted of six auditory streams, and had to decide whether scenes were identical or whether the frequency of one stream was changed between presentations. Our results show that physical changes in auditory input, independent of successful change detection, are represented at the level of auditory cortex. Activations related to conscious change perception, independent of physical change, were found in the insula and the ACC. Moreover, our data provide evidence for significant effective connectivity between auditory cortex and the insula in the case of correctly detected auditory changes, but not for missed changes. This underlines the importance of the insula/anterior cingulate network for conscious change detection.	t	\N
23258317	Steady state responses (SSRs), between 75 and 110 Hz, evoked by auditory amplitude modulated single or multiple tone stimuli, may be used to estimate objective hearing threshold. The aim of this study was to compare SSRs and click-evoked auditory brainstem responses (ABRs) in both ears of 20 adults (10 males and 10 females, aged between 24 and 36 years) with normal hearing threshold. Mean ABR threshold was found at 21.25 (± 5.9) dB nHL. Mean SSR threshold was found at 15.6 (± 9.6) dB nHL after a single frequency stimulus (1 kHz); at 10.5 (± 18.2) dB nHL and at 7.1 (± 12.4) dB nHL after bifrequency stimulation (0.5 and 2 kHz). SSR thresholds after multifrequency stimulation (0.5, 1, 2 and 4 kHz) were found, respectively, at 12.1 (± 12.9) dB nHL, 12.2 (± 12.8) dB nHL, 12.3 (± 8.3) dB nHL and 18.9 (± 17.2) dB nHL. Mean duration of the recording session was 6 min in the case of ABRs, while it was 25 min in the single frequency condition and 29 min in the multifrequency condition in the case of SSRs. SSRs can be used for frequency-specific objective audiometry. The multifrequency stimulation greatly reduces the whole testing time.	t	\N
23258616	Modern digital hearing aids have provided improved fidelity over those of earlier decades for speech. The same however cannot be said for music. Most modern hearing aids have a limitation of their "front end," which comprises the analog-to-digital (A/D) converter. For a number of reasons, the spectral nature of music as an input to a hearing aid is beyond the optimal operating conditions of the "front end" components. Amplified music tends to be of rather poor fidelity. Once the music signal is distorted, no amount of software manipulation that occurs later in the circuitry can improve things. The solution is not a software issue. Some characteristics of music that make it difficult to be transduced without significant distortion include an increased sound level relative to that of speech, and the crest factor- the difference in dB between the instantaneous peak of a signal and its RMS value. Clinical strategies and technical innovations have helped to improve the fidelity of amplified music and these include a reduction of the level of the input that is presented to the A/D converter.	t	\N
23263015	Anesthesiology requires performing visually oriented procedures while monitoring auditory information about a patient's vital signs. A concern in operating room environments is the amount of competing information and the effects that divided attention has on patient monitoring, such as detecting auditory changes in arterial oxygen saturation via pulse oximetry. The authors measured the impact of visual attentional load and auditory background noise on the ability of anesthesia residents to monitor the pulse oximeter auditory display in a laboratory setting. Accuracies and response times were recorded reflecting anesthesiologists' abilities to detect changes in oxygen saturation across three levels of visual attention in quiet and with noise. Results show that visual attentional load substantially affects the ability to detect changes in oxygen saturation concentrations conveyed by auditory cues signaling 99 and 98% saturation. These effects are compounded by auditory noise, up to a 17% decline in performance. These deficits are seen in the ability to accurately detect a change in oxygen saturation and in speed of response. Most anesthesia accidents are initiated by small errors that cascade into serious events. Lack of monitor vigilance and inattention are two of the more commonly cited factors. Reducing such errors is thus a priority for improving patient safety. Specifically, efforts to reduce distractors and decrease background noise should be considered during induction and emergence, periods of especially high risk, when anesthesiologists has to attend to many tasks and are thus susceptible to error.	t	\N
23268357	Fine structure in the frequency response of distortion product otoacoustic emissions (DPOAEs) can severely limit the usefulness of DPOAEs in estimating auditory thresholds. Here, fine structure is removed by extracting the primary-source DPOAE component using the onset-decomposition technique (Vetešník et al., 2009) and auditory threshold estimates are compared to those obtained from DPOAEs in response to conventional, continuous two-tone stimulation. Auditory thresholds are predicted using the estimated distortion product thresholds (EDPTs), obtained from linear regression of input-output (I/O) functions of DPOAE pressure amplitude versus second-tone stimulus level (Boege and Janssen, 2002). The accuracy of the auditory-threshold predictions is derived by comparison with measured auditory thresholds. The parameters of the two primary stimulus tones of frequency f(1) and f(2) and levels of L(1) and L(2) are chosen as: f(2)/f(1) = 1.2 with 1.5 ≤ f(2) ≤ 2.5 kHz, and L(1) = 0.4L(2) + 39 dB SPL, with 25 ≤ L(2) ≤ 65 dB SPL. Data are from 12 normal-hearing subjects with profound DPOAE fine structure. 255 DPOAE I/O functions were measured for each of the two DPOAE paradigms. An EDPT value was accepted as reliable if: 1) the squared correlation coefficient, r(2) ≥ 0.8, 2) the regression slope, s(I/O) ≥ 0.2 μPa/dB, and 3) the standard deviation of the EDPT, σ(EDPT) ≤ 10 dB. The proportion of rejected I/O functions was 8% for onset-decomposition DPOAEs, and 25% for continuous-tone DPOAEs. Removal of data points from the saturation region of the DPOAE I/O function by an automated algorithm reduced the rejection rate, to zero for onset-decomposition DPOAEs, but to only 13% for continuous-tone DPOAEs. In the absence of saturated DPOAE responses, auditory thresholds were predicted with standard deviation of only 4 dB for onset-decomposition DPOAEs, but 12 dB for continuous-tone DPOAEs. In summary, by extracting the primary-source component of the DPOAE by the method of onset-decomposition it is possible to predict human auditory threshold with hitherto unattainable accuracy.	t	\N
23268783	According to predictive coding models of sensory processing, stimulus expectations have a profound effect on sensory cortical responses. This was supported by experimental results, showing that fMRI repetition suppression (fMRI RS) for face stimuli is strongly modulated by the probability of stimulus repetitions throughout the visual cortical processing hierarchy. To test whether processing of voices is also affected by stimulus expectations, here we investigated the effect of repetition probability on fMRI RS in voice-selective cortical areas. Changing ('alt') and identical ('rep') voice stimulus pairs were presented to the listeners in blocks, with a varying probability of alt and rep trials across blocks. We found auditory fMRI RS in the nonprimary voice-selective cortical regions, including the bilateral posterior STS, the right anterior STG and the right IFC, as well as in the IPL. Importantly, fMRI RS effects in all of these areas were strongly modulated by the probability of stimulus repetition: auditory fMRI RS was reduced or not present in blocks with low repetition probability. Our results revealed that auditory fMRI RS in higher-level voice-selective cortical regions is modulated by repetition probabilities and thus suggest that in audition, similarly to the visual modality, processing of sensory information is shaped by stimulus expectation processes.	t	\N
23274182	Speech recognition is improved when complementary visual information is available, especially under noisy acoustic conditions. Functional neuroimaging studies have suggested that the superior temporal sulcus (STS) plays an important role for this improvement. The spectrotemporal dynamics underlying audiovisual speech processing in the STS, and how these dynamics are affected by auditory noise, are not well understood. Using electroencephalography, we investigated how auditory noise affects audiovisual speech processing in event-related potentials (ERPs) and oscillatory activity. Spoken syllables were presented in audiovisual (AV) and auditory only (A) trials at three different auditory noise levels (no, low, and high). Responses to A stimuli were subtracted from responses to AV stimuli, separately for each noise level, and these responses were subjected to the statistical analysis. Central ERPs differed between the no noise and the two noise conditions from 130 to 150 ms and 170 to 210 ms after auditory stimulus onset. Source localization using the local autoregressive average procedure revealed an involvement of the lateral temporal lobe, encompassing the superior and middle temporal gyrus. Neuronal activity in the beta-band (16 to 32 Hz) was suppressed at central channels around 100 to 400 ms after auditory stimulus onset in the averaged AV minus A signal over the three noise levels. This suppression was smaller in the high noise compared to the no noise and low noise condition, possibly reflecting disturbed recognition or altered processing of multisensory speech stimuli. Source analysis of the beta-band effect using linear beamforming demonstrated an involvement of the STS. Our study shows that auditory noise alters audiovisual speech processing in ERPs localized to lateral temporal lobe and provides evidence that beta-band activity in the STS plays a role for audiovisual speech processing under regular and noisy acoustic conditions.	t	\N
23275424	Fitting a cochlear implant (CI) for optimal speech perception does not necessarily optimize listening effort. This study aimed to show that listening effort may change between CI processing conditions for which speech intelligibility remains constant. Nineteen normal-hearing participants listened to CI simulations with varying numbers of spectral channels. A dual-task paradigm combining an intelligibility task with either a linguistic or nonlinguistic visual response-time (RT) task measured intelligibility and listening effort. The simultaneously performed tasks compete for limited cognitive resources; changes in effort associated with the intelligibility task are reflected in changes in RT on the visual task. A separate self-report scale provided a subjective measure of listening effort. All measures showed significant improvements with increasing spectral resolution up to 6 channels. However, only the RT measure of listening effort continued improving up to 8 channels. The effects were stronger for RTs recorded during listening than for RTs recorded between listening. The results suggest that listening effort decreases with increased spectral resolution. Moreover, these improvements are best reflected in objective measures of listening effort, such as RTs on a secondary task, rather than intelligibility scores or subjective effort measures.	t	\N
23290461	The white matter bundles that underlie comprehension and production of language have been investigated for a number of years. Several studies have examined which fiber bundles (or tracts) are involved in auditory language processing, and which kind of language information is transmitted by which fiber tract. However, there is much debate about exactly which fiber tracts are involved, their precise course in the brain, how they should be named, and which functions they fulfill. Therefore, the present article reviews the available language-related literature, and educes a neurocognitive model of the pathways for auditory language processing. Besides providing an overview of the current methods used for relating fiber anatomy to function, this article details the precise anatomy of the fiber tracts and their roles in phonological, semantic and syntactic processing, articulation, and repetition.	t	\N
23297922	Previous studies have suggested that cochlear implant users may have particular difficulties exploiting opportunities to glimpse clear segments of a target speech signal in the presence of a fluctuating masker. Although it has been proposed that this difficulty is associated with a deficit in linking the glimpsed segments across time, the details of this mechanism are yet to be explained. The present study introduces a method called Zebra-speech developed to investigate the relative contribution of simultaneous and sequential segregation mechanisms in concurrent speech perception, using a noise-band vocoder to simulate cochlear implants. One experiment showed that the saliency of the difference between the target and the masker is a key factor for Zebra-speech perception, as it is for sequential segregation. Furthermore, forward masking played little or no role, confirming that intelligibility was not limited by energetic masking but by across-time linkage abilities. In another experiment, a binaural cue was used to distinguish the target and the masker. It showed that the relative contribution of simultaneous and sequential segregation depended on the spectral resolution, with listeners relying more on sequential segregation when the spectral resolution was reduced. The potential of Zebra-speech as a segregation enhancement strategy for cochlear implants is discussed.	t	\N
23298012	The present study explored the acoustic characteristics of prosodic cues that indicate a speaker's reluctance when giving permission or agreement using a single word ("okay"). Eight speakers (four male, four female) produced the recorded materials that were subsequently validated through a listening experiment using 12 normal-hearing listeners. Acoustic analyses revealed that significantly longer word duration was the cue used most consistently across speakers to communicate reluctance. Voice quality, fundamental voice frequency, and intensity cues also differed significantly between the two prosodic conditions, but the manner in which these cues were applied varied greatly across speakers.	t	\N
23301004	For humans and animals, the ability to discriminate speech and conspecific vocalizations is an important physiological assignment of the auditory system. To reveal the underlying neural mechanism, many electrophysiological studies have investigated the neural responses of the auditory cortex to conspecific vocalizations in monkeys. The data suggest that vocalizations may be hierarchically processed along an anterior/ventral stream from the primary auditory cortex (A1) to the ventral prefrontal cortex. To date, the organization of vocalization processing has not been well investigated in the auditory cortex of other mammals. In this study, we examined the spike activities of single neurons in two early auditory cortical regions with different anteroposterior locations: anterior auditory field (AAF) and posterior auditory field (PAF) in awake cats, as the animals were passively listening to forward and backward conspecific calls (meows) and human vowels. We found that the neural response patterns in PAF were more complex and had longer latency than those in AAF. The selectivity for different vocalizations based on the mean firing rate was low in both AAF and PAF, and not significantly different between them; however, more vocalization information was transmitted when the temporal response profiles were considered, and the maximum transmitted information by PAF neurons was higher than that by AAF neurons. Discrimination accuracy based on the activities of an ensemble of PAF neurons was also better than that of AAF neurons. Our results suggest that AAF and PAF are similar with regard to which vocalizations they represent but differ in the way they represent these vocalizations, and there may be a complex processing stream between them.	t	\N
23306571	The phenomenon of Late-Onset Unilateral Auditory Deprivation was first reported in 1984. However, a high number of unilateral hearing aid fittings are still carried out in cases of bilateral hearing loss, justified by non-auditory factors such as cost, vanity, misinformation and public health policies. To carry out behavioral and electrophysiological assessment of the auditory performance of adults using unilateral amplification compared with individuals exposed to bilateral symmetric auditory stimulation. Thirty five adults, all with symmetric bilateral sensorineural hearing loss, regular users of unilateral hearing aid, bilateral hearing aids and not users of hearing aids, were assessed on behavioral and electrophysiological tests. Variance analysis revealed that in the unilaterally fitted group, P300 latency was significantly greater in ears with auditory deprivation compared with those fitted with the hearing aid (p < 0.05). This same group also had poorer performance on the Sentence Recognition Test in Noise held in free field. These results corroborate findings in the literature showing that unilateral auditory deprivation can lead to physiological and perceptual changes.	t	\N
23307427	Using a tactile variant of the negative-priming paradigm, we analyzed the influence of Gestalt grouping on the ability of participants to ignore distracting tactile information. The distance between participants' hands, to which the target and distractor stimuli were simultaneously delivered, was varied (near/touching hands vs. hands far apart). In addition, the influence of touching hands was controlled, as participants wore gloves and their hands were blocked from vision by a cover. The magnitude of the tactile negative-priming effect was modulated by the interaction between hand separation and whether or not gloves were worn. When the hands were touching, negative priming emerged only while wearing gloves that prevented direct skin-to-skin contact. In contrast, when the separation between the participants' hands was larger, negative priming emerged only when gloves were not worn. This pattern of results is interpreted in terms of the competing influences of two interacting Gestalt principles--namely, connectedness and proximity--on the processing of tactile distractors.	t	\N
23316925	The event-related potential (ERP) correlates of sound detection are attenuated when eliciting sounds coincide with our own actions. The role of attention in this effect was investigated in two experiments by presenting tones separated by random intervals. In the homogeneous condition of Experiments 1 and 2, the same tone was repeated, whereas in the mixed condition of Experiment 1, tones with five different frequencies were presented. Participants performed a time-interval production task by marking intervals with keypresses in Experiment 1, and tried to produce keypress-tone coincidences in Experiment 2. Although the auditory ERPs were attenuated for coincidences, no modulation by the multiplicity of tone frequencies in Experiment 1, or by the task-relevancy of tones and coincidences in Experiment 2, was found. This suggests that coincidence-related ERP attenuation cannot be fully explained by voluntary attentional mechanisms.	t	\N
23321588	To assess the auditory performance of Digisonic(®) cochlear implant users with electric stimulation (ES) and electro-acoustic stimulation (EAS) with special attention to the processing of low-frequency temporal fine structure. Six patients implanted with a Digisonic(®) SP implant and showing low-frequency residual hearing were fitted with the Zebra(®) speech processor providing both electric and acoustic stimulation. Assessment consisted of monosyllabic speech identification tests in quiet and in noise at different presentation levels, and a pitch discrimination task using harmonic and disharmonic intonating complex sounds ( Vaerenberg et al., 2011 ). These tests investigate place and time coding through pitch discrimination. All tasks were performed with ES only and with EAS. Speech results in noise showed significant improvement with EAS when compared to ES. Whereas EAS did not yield better results in the harmonic intonation test, the improvements in the disharmonic intonation test were remarkable, suggesting better coding of pitch cues requiring phase locking. These results suggest that patients with residual hearing in the low-frequency range still have good phase-locking capacities, allowing them to process fine temporal information. ES relies mainly on place coding but provides poor low-frequency temporal coding, whereas EAS also provides temporal coding in the low-frequency range. Patients with residual phase-locking capacities can make use of these cues.	t	\N
23327452	In order to provide effective intervention for children with specific language impairment (SLI), it is crucial that there is an understanding of the underlying deficit in SLI. This study utilized a battery of phonological processing tasks to compare the phonological processing skills of children with SLI to typically-developing peers matched for age or language. The children with SLI had significantly poorer performance than age-matched peers on measures of phonological representations, phonological awareness, rapid automatized naming, phonological short-term memory, and one measure of working memory. Of particular significance, the SLI group also demonstrated significantly weaker performance than language-matched peers on one measure of phonological representations, and one measure of working memory. The findings provide some support for a phonological processing account of SLI and highlight the utility of using tasks that draw on a comprehensive model of speech processing to profile and consider children's phonological processing skills in detail.	t	\N
23331545	The auditory N1 event-related potential has previously been observed to be attenuated for tones that are triggered by human actions. This attenuation is thought to be generated by motor prediction mechanisms and is considered to be important for agency attribution. The present study was designed to rigorously test the notion of action prediction-based sensory attenuation. Participants performed one of four voluntary actions on each trial, with each button associated with either predictable or unpredictable action effects. In addition, actions with each hand could result in action effects that were either congruent or incongruent with hand-specific prediction. We observed no significant differences in N1 amplitude between predictable and unpredictable tones. When contrasting action effects that were congruent or incongruent with hand-specific prediction, we observed significant attenuation for prediction-congruent compared to prediction-incongruent action-effects. These novel findings suggest that accurate action-effect prediction drives sensory attenuation of auditory stimuli. These findings have important implications for understanding the mechanisms of action-effect prediction and sensory attenuation, and may have clinical implications for studies investigating action awareness and agency in schizophrenia.	t	\N
23334356	Several studies have shown that the ability to identify the timbre of musical instruments is reduced in cochlear implant (CI) users compared with normal-hearing (NH) listeners. However, most of these studies have focused on tasks that require specific musical knowledge. In contrast, the present study investigates the perception of timbre by CI subjects using a multidimensional scaling (MDS) paradigm. The main objective was to investigate whether CI subjects use the same cues as NH listeners do to differentiate the timbre of musical instruments. Three groups of 10 NH subjects and one group of 10 CI subjects were asked to make dissimilarity judgments between pairs of instrumental sounds. The stimuli were 16 synthetic instrument tones spanning a wide range of instrument families. All sounds had the same fundamental frequency (261 Hz) and were balanced in loudness and in perceived duration before the experiment. One group of NH subjects listened to unprocessed stimuli. The other two groups of NH subjects listened to the same stimuli passed through a four-channel or an eight-channel noise vocoder, designed to simulate the signal processing performed by a real CI. Subjects were presented with all possible combinations of pairs of instruments and had to estimate, for each pair, the amount of dissimilarity between the two sounds. These estimates were used to construct dissimilarity matrices, which were further analyzed using an MDS model. The model output gave, for each subject group, an optimal graphical representation of the perceptual distances between stimuli (the so-called "timbre space"). For all groups, the first two dimensions of the timbre space were strikingly similar and correlated strongly with the logarithm of the attack time and with the center of gravity of the spectral envelope, respectively. The acoustic correlate of the third dimension differed across groups but only accounted for a small proportion of the variance explained by the MDS solution. Surprisingly, CI subjects and NH subjects listening to noise-vocoded simulations gave relatively more weight to the spectral envelope dimension and less weight to the attack-time dimension when making their judgments than NH subjects listening to unprocessed stimuli. One possible reason for the relatively higher salience of spectral envelope cues in real and simulated CIs may be that the degradation of local fine spectral details produced a more stable spectral envelope across the stimulus duration. The internal representation of musical timbre for isolated musical instrument sounds was found to be similar in NH and in CI listeners. This suggests that training procedures designed to improve timbre recognition in CIs will indeed train CI subjects to use the same cues as NH listeners. Furthermore, NH subjects listening to noise-vocoded sounds appear to be a good model of CI timbre perception as they show the same first two perceptual dimensions as CI subjects do and also exhibit a similar change in perceptual weights applied to these two dimensions. This last finding validates the use of simulations to evaluate and compare training procedures to improve timbre perception in CIs.	t	\N
23336003	A large-scale subjective survey was conducted in six shopping malls in Harbin City, China, to determine the influence of social and behavioural characteristics of users on their evaluation of subjective loudness and acoustic comfort. The analysis of social characteristics shows that evaluation of subjective loudness is influenced by income and occupation, with correlation coefficients or contingency coefficients of 0.10 to 0.40 (p<0.05 or p<0.01). Meanwhile, evaluation of acoustic comfort evaluation is influenced by income, education level, and occupation, with correlation coefficients or contingency coefficients of 0.10 to 0.60 (p<0.05 or p<0.01). The effect of gender and age on evaluation of subjective loudness and acoustic comfort is statistically insignificant. The effects of occupation are mainly caused by the differences in income and education level, in which the effects of income are greater than that of education level. In terms of behavioural characteristics, evaluation of subjective loudness is influenced by the reason for visit, frequency of visit, and length of stay, with correlation coefficients or contingency coefficients of 0.10 to 0.40 (p<0.05 or p<0.01). Evaluation of acoustic comfort is influenced by the reason for visit to the site, the frequency of visit, length of stay, and also season of visit, with correlation coefficients of 0.10 to 0.30 (p<0.05 or p<0.01). In particular, users who are waiting for someone show lower evaluation of acoustic comfort, whereas users who go to shopping malls more than once a month show higher evaluation of acoustic comfort. On the contrary, the influence of the period of visit and the accompanying persons are found insignificant.	t	\N
23339556	This study explored the developmental trends and phonetic category formation in bilingual children and adults. Participants included 30 fluent Spanish-English bilingual children, aged 8-11, and bilingual adults, aged 18-40. All completed gating tasks that incorporated code-mixed Spanish-English stimuli. There were significant differences in performance according to phonotactic construction of the stimuli, with fastest word recognition on words with voiceless initial consonants. Analysis of developmental trends revealed significant differences in children's performance by grade level and fastest recognition on English voiceless initial consonants than Spanish voiceless initial consonants. Differences in voice onset time between English and Spanish may have contributed to quicker recognition of English voiceless consonants than Spanish voiceless consonants. It is also possible that increased exposure to both spoken and written English may account for faster recognition of English voiceless words than Spanish voiceless words. In conclusion, multiple factors may influence perception of a second language.	t	\N
23340379	Since deafness is the most common sensorineural disorder in humans, better understanding of the underlying causes is necessary to improve counseling and rehabilitation. A Dutch family with autosomal dominantly inherited sensorineural hearing loss was clinically and genetically assessed. The MYO6 gene was selected to be sequenced because of similarities with other, previously described DFNA22 phenotypes and a pathogenic c.3610C > T (p.R1204W) mutation was found to co-segregate with the disease. This missense mutation results in a flat configured audiogram with a mild hearing loss, which becomes severe to profound and gently to steeply downsloping later in life. The age-related typical audiograms (ARTA) constructed for this family resemble presbyacusis. Speech audiometry and results of loudness scaling support the hypothesis that the phenotype of this specific MYO6 mutation mimics presbyacusis.	t	\N
23341954	Two experiments investigated deaf individuals' ability to discriminate between same-sex talkers based on vibrotactile stimulation alone. Nineteen participants made same/different judgments on pairs of utterances presented to the lower back through voice coils embedded in a conforming chair. Discrimination of stimuli matched for F0, duration, and perceived magnitude was successful for pairs of spoken sentences in Experiment 1 (median percent correct = 83%) and pairs of vowel utterances in Experiment 2 (median percent correct = 75%). Greater difference in spectral tilt between "different" pairs strongly predicted their discriminability in both experiments. The current findings support the hypothesis that discrimination of complex vibrotactile stimuli involves the cortical integration of spectral information filtered through frequency-tuned skin receptors.	t	\N
23351131	The suppression of the auditory N1 event-related potential (ERP) to self-initiated sounds became a popular tool to tap into sensory-specific forward modeling. It is assumed that processing in the auditory cortex is attenuated due to a match between sensory stimulation and a specific sensory prediction afforded by a forward model of the motor command. The present study shows that N1 suppression was dramatically increased with long (≈ 3 s) stimulus onset asynchronies (SOA), whereas P2 suppression was equal in all SOA conditions (0.8, 1.6, 3.2 s). Thus, the P2 was found to be more sensitive to self-initiation effects than the N1 with short SOAs. Moreover, only the unspecific but not the sensory-specific N1 components were suppressed for self-initiated sounds suggesting that N1-suppression effects mainly reflect an attenuated orienting response. We argue that the N1-suppression effect is a rather indirect measure of sensory-specific forward models.	t	\N
23351849	This work investigates the nature of the comprehension impairment in Wernicke's aphasia (WA), by examining the relationship between deficits in auditory processing of fundamental, non-verbal acoustic stimuli and auditory comprehension. WA, a condition resulting in severely disrupted auditory comprehension, primarily occurs following a cerebrovascular accident (CVA) to the left temporo-parietal cortex. Whilst damage to posterior superior temporal areas is associated with auditory linguistic comprehension impairments, functional-imaging indicates that these areas may not be specific to speech processing but part of a network for generic auditory analysis. We examined analysis of basic acoustic stimuli in WA participants (n = 10) using auditory stimuli reflective of theories of cortical auditory processing and of speech cues. Auditory spectral, temporal and spectro-temporal analysis was assessed using pure-tone frequency discrimination, frequency modulation (FM) detection and the detection of dynamic modulation (DM) in "moving ripple" stimuli. All tasks used criterion-free, adaptive measures of threshold to ensure reliable results at the individual level. Participants with WA showed normal frequency discrimination but significant impairments in FM and DM detection, relative to age- and hearing-matched controls at the group level (n = 10). At the individual level, there was considerable variation in performance, and thresholds for both FM and DM detection correlated significantly with auditory comprehension abilities in the WA participants. These results demonstrate the co-occurrence of a deficit in fundamental auditory processing of temporal and spectro-temporal non-verbal stimuli in WA, which may have a causal contribution to the auditory language comprehension impairment. Results are discussed in the context of traditional neuropsychology and current models of cortical auditory processing.	t	\N
23354172	Visual speech inputs can enhance auditory speech information, particularly in noisy or degraded conditions. The natural statistics of audiovisual speech highlight the temporal correspondence between visual and auditory prosody, with lip, jaw, cheek and head movements conveying information about the speech envelope. Low-frequency spatial and temporal modulations in the 2-7 Hz range are of particular importance. Dyslexic individuals have specific problems in perceiving speech envelope cues. In the current study, we used an audiovisual noise-vocoded speech task to investigate the contribution of low-frequency visual information to intelligibility of 4-channel and 16-channel noise vocoded speech in participants with and without dyslexia. For the 4-channel speech, noise vocoding preserves amplitude information that is entirely congruent with dynamic visual information. All participants were significantly more accurate with 4-channel speech when visual information was present, even when this information was purely spatio-temporal (pixelated stimuli changing in luminance). Possible underlying mechanisms are discussed.	t	\N
23357092	Here we present two experiments investigating the implicit orienting of attention over time by entrainment to an auditory rhythmic stimulus. In the first experiment, participants carried out a detection and discrimination tasks with auditory and visual targets while listening to an isochronous, auditory sequence, which acted as the entraining stimulus. For the second experiment, we used musical extracts as entraining stimulus, and tested the resulting strength of entrainment with a visual discrimination task. Both experiments used reaction times as a dependent variable. By manipulating the appearance of targets across four selected metrical positions of the auditory entraining stimulus we were able to observe how entraining to a rhythm modulates behavioural responses. That our results were independent of modality gives a new insight into cross-modal interactions between auditory and visual modalities in the context of dynamic attending to auditory temporal structure.	t	\N
23362674	It has been shown that humans are able to recognise their own movement. While visual cues have been amply studied, the contribution of auditory cues is not clear. Our aim was to investigate the role of temporal auditory cues in the identification of one's own or others' performance in a complex movement--a golf swing. We investigated whether golfers are able to discriminate between the sounds associated with their own swings and other golfers' swings, by using the relative timing and the overall duration of the movement. The sounds produced by the participants performing 65 m shots have been recorded and used to create the stimuli. The experimental conditions were: participants' swing sounds and the sounds of other golfers having equal both relative timing and overall duration, equal relative timing but different overall duration, different relative timing but equal overall duration, and both different relative timing and overall duration. The task of the participants was to say whether each sound corresponded or did not correspond to their own swing. Results show that golfers are able to recognise their own movements, but they also recognise as their own the sound produced by other athletes having equal both relative timing and overall duration.	t	\N
23363116	Detection thresholds for 100 ms of either 5- or 20-Hz frequency modulation (FM) were measured at various temporal positions within a 600-ms, 4-kHz pure-tone carrier. The results indicated that the temporal position of the signal relative to the fringe influences detection thresholds, including an effect that is reminiscent of auditory backward recognition masking. A task involving frequency increments, rather than sinusoidal FM, yielded similar results. Additional manipulation of total carrier duration indicated that FM detection thresholds improve as the duration of the forward fringe increases, while a backward fringe only degrades performance in the absence of any forward fringe. The results suggest that listeners are insensitive to subtle frequency changes that occur at the onset of a longer stimulus and that the interaction between the opposing effects of the forward and backward fringes is not additive.	t	\N
23363122	The vocal tract length of a speaker is the primary determinant of the range of formant frequencies (FFs) produced by that speaker. Listeners have demonstrated sensitivity to the average FFs produced by voices, for example, in estimating the relative heights of two speakers based on their speech. However, it is not known whether they can learn to identify voices based on the acoustic characteristic associated with the average FFs produced by a voice (this characteristic will be referred to as FF-scaling). To investigate this, a series of vowels corresponding to voices that differed in their average f0 and/or FF-scaling were synthesized. Listeners (n = 71) were trained to identify these voices using a training procedure where, for each trial, they heard the vowels representing a voice and then had to identify the stimulus voice from among a series of candidate voices that differed in terms of their FF-scaling and/or their f0. Results indicate that listeners can identify voices on the basis of FF-scaling quite accurately and consistently after only a short training session and that, although f0 weakly influences these estimates, they are most strongly determined by the stimulus FFs.	t	\N
23363188	Good localization accuracy depends on an auditory spatial map that provides consistent binaural information across frequency and level. This study investigated whether mapping bilateral cochlear implants (CIs) independently contributes to distorted perceptual spatial maps. In a meta-analysis, interaural level differences necessary to perceptually center sound images were calculated for 127 pitch-matched pairs of electrodes; many needed large current adjustments to be perceptually centered. In a separate experiment, lateralization was also found to be inconsistent across levels. These findings suggest that auditory spatial maps are distorted in the mapping process, which likely reduces localization accuracy and target-noise separation in bilateral CIs.	t	\N
23363191	Listeners presented with noise were asked to press a key whenever they heard the vowels [a] or [i:]. The noise had a random spectrum, with levels in 60 frequency bins changing every 0.5 s. Reverse correlation was used to average the spectrum of the noise prior to each key press, thus estimating the features of the vowels for which the participants were listening. The formant frequencies of these reverse-correlated vowels were similar to those of their respective whispered vowels. The success of this response-triggered technique suggests that it may prove useful for estimating other internal representations, including perceptual phenomena like tinnitus.	t	\N
23363193	Speech understanding difficulties for older adults (OAs) are well documented. Very little is known about whether age-related changes affect their speech production as well. Intelligibility of conversational and clear speech sentences produced by five OA talkers was examined. The results of the sentence-in-noise listening tests revealed that OAs enhanced their intelligibility for young adult (YA) listeners through clear speech modifications. Importantly, though, OAs were less effective at improving their speech to benefit listeners compared to YA talkers [reported in Smiljanic and Bradlow, J. Acoust. Soc. Am. 118(3), 1677-1688 (2005)]. The results suggest that auditory and cognitive changes across lifespan can affect OA's speech patterns and intelligibility.	t	\N
23363194	Stilp and Kluender [(2010). Proc. Natl. Acad. Sci. U.S.A. 107(27), 12387-12392] reported measures of sensory change over time (cochlea-scaled spectral entropy, CSE) reliably predicted sentence intelligibility for normal-hearing listeners. Here, implications for listeners with atypical hearing were explored using noise-vocoded speech. CSE was parameterized as Euclidean distances between biologically scaled spectra [measured before sentences were noise vocoded (CSE)] or between channel amplitude profiles in simulated cochlear-implant processing [measured after vocoding (CSE(CI))]. Sentence intelligibility worsened with greater amounts of information replaced by noise; patterns of performance did not differ between CSE and CSE(CI). Results demonstrate the importance of information-bearing change for speech perception in simulated electric hearing.	t	\N
23366748	Emotional arousal, or affective patterns, can be probed using observable bioelectric signals, in particular using the fluctuations of electroencephalographic potentials from the human scalp. Hearing impairment related to increased threshold of audio tone detection may cause the loss of intelligibility of speech resulting in an innate automatic emotional response. An adaptive support vector machine can be trained to identify a subject's unique affective response based upon an audiogram hearing test. This paper presents the efficacy of our model, initial SVM classification data, and discusses potential application.	t	\N
23398728	Superior semi-circular canal dehiscence (SSCD) is a known cause of hearing loss. This study quantifies hearing loss in SSCD ears in a frequency-specific fashion. A meta-analysis of English language literature pertaining to SSCD was performed, with extraction and evaluation of available human audiometric data. Our own institution's case series of SSCD patients was also similarly analysed. Hearing loss in SSCD ears was compared to same patient control ears and to age-matched normative audiometric data. Ears with SSCD had statistically significant worse hearing as compared to both normative data and to own normal ear controls at 2000 Hz and below. The effect appears to diminish with increasing frequency. The presence of statistically significant conductive hearing loss in the low frequencies was confirmed for SSCD ears. SSCD may also predispose ears to high frequency sensorineural hearing loss.	t	\N
23404529	The purpose of the study was to investigate the potential clinical advantages of incorporating a contralateral routing of signals (CROS) microphone in unilateral cochlear implant (CI) users. A prospective study was undertaken on a group of 21 postlingually deafened adults who were all implanted with the same multichannel CI system. Performance with a unilateral CI was compared with performance using both a unilateral implant and a CROS microphone system worn on the opposite site (CI-CROS). Speech understanding using the AzBio sentence was evaluated in quiet, with speech presented at 0° and 270° azimuth in the horizontal plane. Speech understanding in noise was performed with speech at 0°, and noise at 0°, 90°, and 270°. A significant gain in speech understanding using CI-CROS compared to the unilateral CI alone was found in quiet when speech was presented at 270° (average improvement of 8.8%, P < .01). Participants also demonstrated statistically significant improvement using CI-CROS compared with the unilateral CI alone when noise was presented at 90° and speech at 0° (average improvement of 6.7%, P < .01). Adding a contralateral microphone to a unilateral CI resulted in a significant improvement in speech understanding in different conditions. This method could provide a greater cost/benefit ratio than bilateral CIs and be a potential improvement for those who are not candidates for bilateral CIs.	t	\N
23418635	Cochlear implantation (CI) has proven in long term prospective trials to reduce significantly incapacitating tinnitus in single sided deafness (SSD). Discussion arises whether electrical stimulation near the round window (RW) is also able to reduce tinnitus. to assess whether electrical stimulation of the basal first 4 intracochlear electrodes of a CI could sufficiently reduce tinnitus and to compare these results with stimulation with all CI electrodes. 7 patients who met the criteria of severe tinnitus due to SSD were implanted with a Med-El Sonata Ti100 with a FlexSoftTM or Flex24TM electrode. After 4 weeks only the basal electrode pair (E12) nearest to the RW was activated. Each week the following pair was activated until the 4th pair.Thereafter all electrodes were activated. Tinnitus was assessed before CI surgery and before each electrode pair was activated. When all electrodes were fitted, evaluation was done after 1, 3 and 6 months.Tinnitus was assessed with Visual Analogue Scale (VAS) for loudness, psychoacoustic tinnitus loudness comparison at 1 kHz and Tinnitus Questionnaire (TQ) for the effect on quality of life. To evaluate the natural evolution, a tightly matched control group with severe tinnitus due to SSD was followed prospectively. All the tinnitus outcome measures remained unchanged with 1, 2, 3 or 4 activated electrode pairs. With complete CI activation, the tinnitus decreased significantly comparable with earlier reports.Pre-implantation the tinnitus loudness was 8.2/10 on the VAS and was reduced to 4.1/10 6 months postimplantation.Psychometrically the loudness level went from 21.7 dB SL (SD: 16.02) to 7.5 dB SL (SD: 5.24)and the TQ from 60/84 to 39/84. The non-implanted group had no decrease of the tinnitus, the average VAS remained stable at 8.9/10 throughout the follow-up period of 6 months. with the current stimulation parameters electrical stimulation in the first 8e10 mm of the basal part of the scala tympani is insufficient to reduce tinnitus. However, stimulation over the complete CI length yields immediate tinnitus reduction confirming earlier results.	t	\N
23421638	BACKGROUND/STUDY CONTEXT: The perception of naturalistic events depends on the ability to integrate perceptual information from multiple sensory systems. Currently, little is known about how multisensory integration is affected by normal aging. The authors conducted two experiments to investigate audiovisual temporal processing in younger (18-29 years) and older (70+ years) adults. In both experiments, participants were presented with a brief visual stimulus and a brief auditory stimulus separated by various temporal offsets, and participants judged which stimulus was presented first. In Experiment 1, the auditory and visual stimuli were presented from the same perceived location, whereas in Experiment 2 they were presented from different locations. The authors found no effect of stimulus location, and no evidence of age-related declines in performance in either experiment. Older adults appear to retain the ability to discriminate the temporal order of audiovisual stimuli and can perform similarly to younger adults.	t	\N
23422927	Prosody includes suprasegmental components of speech, such as intonation and rate, which add meaning beyond the words being spoken. Sensitivity to pragmatic prosody could improve communication within conversations. These studies investigated adults' and preschoolers' sensitivity to pragmatic prosody. Experiment 1 demonstrated that adults and children comprehend pragmatic prosody; they selected fast actions when descriptions were spoken fast versus when descriptions were spoken slowly. Experiment 2 demonstrated that adults and children spontaneously produce pragmatic prosody-their descriptions of fast actions were faster than their descriptions of slow actions-even when it was not necessary for the task. These studies conclude that children, like adults, are capable of using and producing pragmatic prosody; however, children are less sensitive than adults to subtle prosodic distinctions.	t	\N
23426091	To maintain optimal understanding, persons with sensorineural hearing loss (SNHL) often report a need for increased attention, concentration, and "listening effort" compared with persons without hearing loss. It is generally assumed that this increased effort is related to subjective reports of mental fatigue in persons with hearing loss. Although the benefits of hearing aids for improving intelligibility are well documented, their impact on listening effort and mental fatigue are less clear. This study used subjective and objective measures to examine the effects of hearing aid use and advanced hearing aid features on listening effort and mental fatigue in adults with SNHL. Sixteen adults (aged 47-69 years) with mild to severe sloping SNHL participated. A dual-task paradigm assessed word recognition, word recall, and visual reaction times (RTs) to objectively quantify listening effort and fatigue. Mental fatigue was operationally defined as a decrement in performance over the duration of the experiment (approximately 1 hr). Participants were fitted with study hearing aids and tested unaided and in two aided conditions (omnidirectional and with directional processing and digital noise reduction active). Subjective ratings of listening effort experienced during the day and ratings of fatigue and attentiveness immediately before and after the dual-task were also obtained. Word recall was better and dual-task RTs were significantly faster in the aided compared with unaided conditions, suggesting a decrease in listening effort when listening aided. Word recognition and recall in unaided and aided conditions remained relatively stable over the duration of the dual-task, suggesting these processes were resistant to mental fatigue. In contrast, dual-task RTs systematically increased over the duration of the speech task when listening unaided, consistent with development of mental fatigue. However, dual-task RTs remained stable over time in both aided conditions suggesting that hearing aid use reduced susceptibility to mental fatigue. Subjective ratings of fatigue and attentiveness also increased significantly after completion of the dual-task; however, no differences between unaided and aided subjective ratings were observed. Correlation analyses between subjective and objective measures of listening effort and mental fatigue showed no strong or consistent relationship. Likewise, subject variables such as age and degree of hearing loss showed no strong or consistent relationship to either subjective or objective measures of listening effort or mental fatigue. Results from subjective and select objective measures suggest sustained speech-processing demands can lead to mental fatigue in persons with hearing loss. It is important to note that the use of clinically fit hearing aids may reduce listening effort and susceptibility to mental fatigue associated with sustained speech-processing demands. The present study design did not reveal additional benefits, in terms of reduced listening effort or fatigue, from use of directional processing and digital noise-reduction algorithms. However, experimental design limitations suggest further work in this area is needed. Finally, subjective and objective measures of listening effort and mental fatigue due to sustained speech-processing demands, were not strongly associated, suggesting that these measures may assess different aspects of listening effort and mental fatigue.	t	\N
23438484	Two experiments tested the effect of exposure to masked phobic stimuli at a very brief stimulus onset asynchrony on reducing the subjective experience of fear caused by in vivo exposure to a feared object. In the main experiment, 35 spider-fearful and 35 non-fearful participants were identified with a questionnaire and a behavioural avoidance test (BAT) with a live tarantula. One week later, they were individually administered one of two continuous series of masked images: spiders or flowers. They engaged in the BAT again immediately thereafter. They provided ratings of subjective fear at the end of each BAT (pre- and post-manipulation). Very brief exposure to images of spiders reduced the fearful group's and not the non-fearful group's experience of fear at the end of the BAT. This effect was replicated with another sample of 26 spider-fearful participants from the same population. Theoretical implications are discussed.	t	\N
23442566	Performance in tone perception and production are correlated in prelingually deafened pediatric cochlear implant (CI) users across individuals. Demographic variables, such as age at implantation, contribute to the performance variability. Poor representation of pitch information in CI devices hinders pitch perception and affects perception of lexical tones in cochlear implant users who speak tonal languages. One hundred ten Mandarin-speaking, prelingually deafened CI subjects and 125 typically developing, normal-hearing subjects were recruited from Beijing, China. Lexical tone perception was measured using a computerized tone contrast test. Tone production was judged by native Mandarin-speaking adult listeners as well as analyzed acoustically and with an artificial neural network. A general linear model analysis was performed to determine factors that accounted for performance variability. CI subjects scored ≈ 67% correct on the lexical tone perception task. The degree of differentiation of tones produced by the CI group was significantly lower than the control group as revealed by acoustic analysis. Tone production performance assessed by the neural network was highly correlated with that evaluated by human listeners. There was a moderate correlation between the overall tone perception and production performance across CI subjects. Duration of implant use and age at implantation jointly explained ≈ 29% of the variance in the tone perception performance. Age at implantation was the only significant predictor for tone production performance in the CI subjects. Tone production performance in pediatric CI users is dependent on accurate perception. Early implantation predicts a better outcome in lexical tone perception and production.	t	\N
23446715	It is generally agreed that the auditory perception skills of children with developmental language disorders are more limited than those of typically developing children. It is not easy to determine exactly how the capacity to discriminate and the capacity to pronounce phonemes influence each other in children with language disorders. For most authors, the inability to discriminate certain phonemes accurately causes a developmental delay in pronunciation, whereas others claim the influence is mutual. The aim of this study is to determine in which consonants perceptive difficulty is more likely to occur and in which cases there is a greater probability of difficulty when it comes to articulating them. The sample used in the study consisted of 86 children with a mean age of 4 years and 7 months. The phonological processes involved in simplifying speech were identified. Their errors were used as the basis on which to construct and apply a specific speech perception test. The relationship between the articulatory and perceptive skills of children with substitutive processes were analysed by means of two comparisons: first, in all the processes detected taken as a whole and, second, in the three most frequent substitutive processes. These analyses were carried out to determine whether the nature of the consonant implied a greater probability of perceptive difficulty. The findings provide information about a relation between the articulatory and perceptive skills, and about whether the nature of the consonant determines a higher probability of perceptive or articulatory difficulties. These results can be of value in the assessment, design and effectiveness of speech therapy programmes.	t	\N
23448103	To evaluate the auditory brainstem response (ABR) amplitudes evoked by tone pip and narrowband chirp (NB CE-Chirp) stimuli when testing post-screening newborns and to determine the difference in estimated hearing level correction values. Tests were performed with tone pips and NB CE-Chirps at 4 kHz or 1 kHz. The response amplitude, response quality (Fmp), and residual noise were compared for both stimuli. Thirty babies (42 ears) who passed our ABR discharge criterion at 4 kHz following referral from their newborn hearing screen. Overall, NB CE-Chirp responses were 64% larger than the tone pip responses, closer to those evoked by clicks. Fmp was significantly higher for NB CE-Chirps. It is anticipated that there could be significant reductions in test time for the same signal to noise ratio by using NB CE-Chirps when testing newborns. This effect may vary in practice and is likely to be most beneficial for babies with low amplitude ABR responses. We propose that the ABR nHL threshold to eHL correction for NB CE-Chirps should be approximately 5 dB less than the corrections for tone pips at 4 and 1 kHz.	t	\N
23453221	This study examined the ability of prelingually deaf children with bilateral implants to identify emotion (i.e. happiness or sadness) in speech and music. Participants in Experiment 1 were 14 prelingually deaf children from 5-7 years of age who had bilateral implants and 18 normally hearing children from 4-6 years of age. They judged whether linguistically neutral utterances produced by a man and woman sounded happy or sad. Participants in Experiment 2 were 14 bilateral implant users from 4-6 years of age and the same normally hearing children as in Experiment 1. They judged whether synthesized piano excerpts sounded happy or sad. Child implant users' accuracy of identifying happiness and sadness in speech was well above chance levels but significantly below the accuracy achieved by children with normal hearing. Similarly, their accuracy of identifying happiness and sadness in music was well above chance levels but significantly below that of children with normal hearing, who performed at ceiling. For the 12 implant users who participated in both experiments, performance on the speech task correlated significantly with performance on the music task and implant experience was correlated with performance on both tasks. Child implant users' accurate identification of emotion in speech exceeded performance in previous studies, which may be attributable to fewer response alternatives and the use of child-directed speech. Moreover, child implant users' successful identification of emotion in music indicates that the relevant cues are accessible at a relatively young age.	t	\N
23458475	The purpose of this study was to measure real-ear aided and saturated responses of SpeechEasy™ devices and compare responses while devices delivered altered auditory feedback (AAF) and non-altered feedback (NAF). A repeated measures quasi-experimental design was employed. Ten people fitted with completely-in-the-canal or open fit behind-the-ear devices participated. Probe microphone measures were obtained with speech, and 17 chirp stimuli presented at 75 dB and 85 dB SPL, respectively. Measurements were compared with devices delivering AAF (i.e. delayed and frequency shifted) versus NAF. Maximum outputs were approximately 100-105 dB SPL in the 2000-4000 Hz range. Statistically significant differences in device SPL output as a function of device setting (AAF vs. NAF) were found for seven chirp stimuli (p <.05) when levels were sampled at points that were not temporally aligned with the output chirps but not for speech stimulus (p = .17). Device output varied across individuals and with open fit devices dominated by ear canal resonance effects. Real-ear aided responses were equivalent with speech input when devices delivered AAF and NAF. Real-ear saturated responses were not, however, comparable between AAF and NAF settings and may be underestimated if AAF delay is not accounted for.	t	\N
23461765	Advantages associated with the left ear (right brain hemisphere) have been reported in some studies. Of these, some have specifically suggested that the left ear has a more heightened ability to detect emotional tones. Meanwhile others have pointed to factors such as age and gender as potentially leading to manifestations of human laterality. This study investigates which brain hemisphere is more involved in emotional processing of auditory information in Arab participants. We aimed to replicate the previous studies because no single study has been done in the Arabic region previously. Additionally, people in this region prefer to use the right side of their body, e.g., hand, ear, foot, etc., for most daily tasks. To acquire data a dichotic listening task (DLT) was administered to 28 male and 23 female (Edinburgh, UK) university students aged 19 to 38; 13 were left-handed and 38 were right-handed. The results showed a significant left ear advantage in the auditory processing of emotional information. There was a significant negative correlation between ear preference and handedness. Left ear advantage related only to handedness. Thus right-handed participants were more likely than left-handers to have a left ear advantage. The relationship between ear preference and gender was non-significant. The conclusion that might be drawn from this study is that the left ear (right hemisphere) is more involved in emotional processing than the right ear (left hemisphere), especially for right-handed people.	t	\N
23462430	We set out to determine whether extra-striate ventral stream function was compromised in amblyopia and to compare any observed deficit with previous data on comparable dorsal stream function. We devised a multi-element orientation task where orientation coherence sensitivity could be measured in a comparable way to motion coherence. The use of spatial frequency narrowband elements allowed for accurate correction of any upstream contrast sensitivity influence and ensured that the orientation bandwidth of our elements did not covary with the measured coherence. Using a standard equivalent noise analysis, we varied both the local orientation bandwidth of individual elements as well as the global orientation bandwidth of the element array to obtain estimates of both local and global internal noise and efficiency. The results show that for this ventral stream task there is only a subtle amblyopic deficit in processing global orientation relative to control observers. This deficit is present for both amblyopic and fixing eyes, and appears to reflect poorer efficiency in processing local orientation, suggesting a subtle deficit at the input stage to extra-striate cortex where orientation coherence is processed.	t	\N
23463992	A decision weight analysis is used to investigate transition bandwidths [Berg (2007). J. Acoust. Soc. Am. 121, 3639-2645]. The psychophysical task is similar to a standard profile analysis experiment except that the spacing of the tones comprising the stimuli is linear and very narrow (e.g., 20 Hz). An increment in the level of the central tone constitutes the signal. Pitch cues and single channel energy cues are degraded with randomization procedures. Thresholds increase as the number of tones comprising the stimulus (n) increases up to a transition bandwidth and then decrease or stay constant with further increases in n. It is proposed that the transition bandwidth reflects a discrete change in the underlying process, with a temporal process (e.g., envelope processor) dominating for stimulus bandwidths less than the transition bandwidth and a process of spectral profile analysis at wider bandwidths. Estimates of decision weights support the proposal.	t	\N
23464020	Just noticeable differences in interaural correlation (ρ-jnds) from diffuse sound field reference correlations are obtained. In a three-interval, three-alternative forced-choice procedure, ρ-jnds are measured for positive and negative deviations from nine narrowband reference conditions. Stimuli are 1 equivalent rectangular bandwidth wide noise bursts with center frequencies between 165 and 1500 Hz. The frequency dependent reference correlation (ρref) is determined by the simulated interaural correlation under ideal diffuse sound field conditions. Results show that the interaural correlation at threshold for deviation toward the positive correlation range follows the reference curve in a nonlinear fashion. For deviation toward the negative correlation range the interaural correlation at threshold is further afar the reference curve and does not markedly resemble its trend. The results indicate that the previously found asymmetry for correlation discrimination from uncorrelated broadband stimuli to the positive and negative correlation range becomes less pronounced for narrowband stimuli. For positive deviation, the highest jnds are found for the region where the reference curve occupies the global minimum in ρref; despite that, the interaural correlation at threshold for positive deviation exhibits its lowest value at that point.	t	\N
23464027	Acousticians generally assess the acoustic qualities of a concert hall or any other room using impulse response-based measures such as the reverberation time, clarity index, and others. These parameters are used to predict perceptual attributes related to the acoustic qualities of the room. Various studies show that these physical measures are not able to predict the related perceptual attributes sufficiently well under all circumstances. In particular, it has been shown that physical measures are dependent on the state of occupation, are prone to exaggerated spatial fluctuation, and suffer from lacking discrimination regarding the kind of acoustic stimulus being presented. Accordingly, this paper proposes a method for the derivation of signal-based measures aiming at predicting aspects of room acoustic perception from content specific signal representations produced by a binaural, nonlinear model of the human auditory system. Listening tests were performed to test the proposed auditory parameters for both speech and music. The results look promising; the parameters correlate with their corresponding perceptual attributes in most cases.	t	\N
23464028	Several lines of evidence indicate that auditory temporal resolution improves over childhood, whereas other data implicate the development of processing efficiency. The present study used the masking period pattern paradigm to examine the maturation of temporal processing in normal-hearing children (4.8 to 10.7 yrs) compared to adults. Thresholds for a brief tone were measured at 6 temporal positions relative to the period of a 5-Hz quasi-square-wave masker envelope, with a 20-dB modulation depth, as well as in 2 steady maskers. The signal was a pure tone at either 1000 or 6500 Hz, and the masker was a band of noise, either spectrally wide or narrow (21.3 and 1.4 equivalent rectangular bandwidths, respectively). Masker modulation improved thresholds more for wide than narrow bandwidths, and adults tended to receive more benefit from modulation than young children. Fits to data for the wide maskers indicated a change in window symmetry with development, reflecting relatively greater backward masking for the youngest listeners. Data for children >6.5 yrs of age appeared more adult-like for the 6500- than the 1000-Hz signal. Differences in temporal window asymmetry with listener age cannot be entirely explained as a consequence of a higher criterion for detection in children, a form of inefficiency.	t	\N
23464037	In spoken word identification and memory tasks, stimulus variability from numerous sources impairs performance. In the current study, the influence of foreign-accent variability on spoken word identification was evaluated in two experiments. Experiment 1 used a between-subjects design to test word identification in noise in single-talker and two multiple-talker conditions: multiple talkers with the same accent and multiple talkers with different accents. Identification performance was highest in the single-talker condition, but there was no difference between the single-accent and multiple-accent conditions. Experiment 2 further explored word recognition for multiple talkers in single-accent versus multiple-accent conditions using a mixed design. A detriment to word recognition was observed in the multiple-accent condition compared to the single-accent condition, but the effect differed across the language backgrounds tested. These results demonstrate that the processing of foreign-accent variation may influence word recognition in ways similar to other sources of variability (e.g., speaking rate or style) in that the inclusion of multiple foreign accents can result in a small but significant performance decrement beyond the multiple-talker effect.	t	\N
23466938	Change deafness describes the failure to perceive even intense changes within complex auditory input, if the listener does not attend to the changing sound. Remarkably, previous psychophysical data provide evidence that this effect occurs independently of successful stimulus encoding, indicating that undetected changes are processed to some extent in auditory cortex. Here we investigated cortical representations of detected and undetected auditory changes using electroencephalographic (EEG) recordings and a change deafness paradigm. We applied a one-shot change detection task, in which participants listened successively to three complex auditory scenes, each of them consisting of six simultaneously presented auditory streams. Listeners had to decide whether all scenes were identical or whether the pitch of one stream was changed between the last two presentations. Our data show significantly increased middle-latency Nb responses for both detected and undetected changes as compared to no-change trials. In contrast, only successfully detected changes were associated with a later mismatch response in auditory cortex, followed by increased N2, P3a and P3b responses, originating from hierarchically higher non-sensory brain regions. These results strengthen the view that undetected changes are successfully encoded at sensory level in auditory cortex, but fail to trigger later change-related cortical responses that lead to conscious perception of change.	t	\N
23467170	Cochlear implant (CI) users typically have excellent speech recognition in quiet but struggle with understanding speech in noise. It is thought that broad current spread from stimulating electrodes causes adjacent electrodes to activate overlapping populations of neurons which results in interactions across adjacent channels. Current focusing has been studied as a way to reduce spread of excitation, and therefore, reduce channel interactions. In particular, partial tripolar stimulation has been shown to reduce spread of excitation relative to monopolar stimulation. However, the crucial question is whether this benefit translates to improvements in speech perception. In this study, we compared speech perception in noise with experimental monopolar and partial tripolar speech processing strategies. The two strategies were matched in terms of number of active electrodes, microphone, filterbanks, stimulation rate and loudness (although both strategies used a lower stimulation rate than typical clinical strategies). The results of this study showed a significant improvement in speech perception in noise with partial tripolar stimulation. All subjects benefited from the current focused speech processing strategy. There was a mean improvement in speech recognition threshold of 2.7 dB in a digits in noise task and a mean improvement of 3 dB in a sentences in noise task with partial tripolar stimulation relative to monopolar stimulation. Although the experimental monopolar strategy was worse than the clinical, presumably due to different microphones, frequency allocations and stimulation rates, the experimental partial-tripolar strategy, which had the same changes, showed no acute deficit relative to the clinical.	t	\N
23489145	Under adverse listening conditions, speech comprehension profits from the expectancies that listeners derive from the semantic context. However, the neurocognitive mechanisms of this semantic benefit are unclear: How are expectancies formed from context and adjusted as a sentence unfolds over time under various degrees of acoustic degradation? In an EEG study, we modified auditory signal degradation by applying noise-vocoding (severely degraded: four-band, moderately degraded: eight-band, and clear speech). Orthogonal to that, we manipulated the extent of expectancy: strong or weak semantic context (±con) and context-based typicality of the sentence-last word (high or low: ±typ). This allowed calculation of two distinct effects of expectancy on the N400 component of the evoked potential. The sentence-final N400 effect was taken as an index of the neural effort of automatic word-into-context integration; it varied in peak amplitude and latency with signal degradation and was not reliably observed in response to severely degraded speech. Under clear speech conditions in a strong context, typical and untypical sentence completions seemed to fulfill the neural prediction, as indicated by N400 reductions. In response to moderately degraded signal quality, however, the formed expectancies appeared more specific: Only typical (+con +typ), but not the less typical (+con -typ) context-word combinations led to a decrease in the N400 amplitude. The results show that adverse listening "narrows," rather than broadens, the expectancies about the perceived speech signal: limiting the perceptual evidence forces the neural system to rely on signal-driven expectancies, rather than more abstract expectancies, while a sentence unfolds over time.	t	\N
23495123	We assessed the automaticity of spatial-numerical and spatial-musical associations by testing their intentionality and load sensitivity in a dual-task paradigm. In separate sessions, 16 healthy adults performed magnitude and pitch comparisons on sung numbers with variable pitch. Stimuli and response alternatives were identical, but the relevant stimulus attribute (pitch or number) differed between tasks. Concomitant tasks required retention of either color or location information. Results show that spatial associations of both magnitude and pitch are load sensitive and that the spatial association for pitch is more powerful than that for magnitude. These findings argue against the automaticity of spatial mappings in either stimulus dimension.	t	\N
23503620	Abnormal auditory adaptation is a standard clinical tool for diagnosing auditory nerve disorders due to acoustic neuromas. In the present study we investigated auditory adaptation in auditory neuropathy owing to disordered function of inner hair cell ribbon synapses (temperature-sensitive auditory neuropathy) or auditory nerve fibres. Subjects were tested when afebrile for (i) psychophysical loudness adaptation to comfortably-loud sustained tones; and (ii) physiological adaptation of auditory brainstem responses to clicks as a function of their position in brief 20-click stimulus trains (#1, 2, 3 … 20). Results were compared with normal hearing listeners and other forms of hearing impairment. Subjects with ribbon synapse disorder had abnormally increased magnitude of loudness adaptation to both low (250 Hz) and high (8000 Hz) frequency tones. Subjects with auditory nerve disorders had normal loudness adaptation to low frequency tones; all but one had abnormal adaptation to high frequency tones. Adaptation was both more rapid and of greater magnitude in ribbon synapse than in auditory nerve disorders. Auditory brainstem response measures of adaptation in ribbon synapse disorder showed Wave V to the first click in the train to be abnormal both in latency and amplitude, and these abnormalities increased in magnitude or Wave V was absent to subsequent clicks. In contrast, auditory brainstem responses in four of the five subjects with neural disorders were absent to every click in the train. The fifth subject had normal latency and abnormally reduced amplitude of Wave V to the first click and abnormal or absent responses to subsequent clicks. Thus, dysfunction of both synaptic transmission and auditory neural function can be associated with abnormal loudness adaptation and the magnitude of the adaptation is significantly greater with ribbon synapse than neural disorders.	t	\N
23506662	Various dimensions of auditory processing, especially the perception of speech in the presence of background competition, have been shown to deteriorate with age. A persistent problem in the assessment of these age-related changes has been the high prevalence of age-related high-frequency hearing loss in elderly persons. Some investigators have suggested that a more fruitful approach to the study of age-related decline might be to study middle-aged, rather than elderly, persons, where confounding high-frequency hearing loss is less prevalent. To determine whether an increase in the left-ear disadvantage (LED) in dichotic listening could be demonstrated in a group of middle-aged persons. The N400 component of the auditory event-related potential (AERP) was utilized to evaluate interaural asymmetry in a quasi-dichotic competing speech task. Electrophysiological responses were obtained on a word-pair semantic categorization task presented through a front loudspeaker while the listener ignored competing speech presented through either left (competition left [CL]) or right (competition right [CR]) loudspeakers. Study Samples: Twenty young (18-24 yr) and 20 middle-aged (44-57 yr) females with normal hearing sensitivity. Individual, as well as grand-averaged, AERP waveforms and scalp topographies were analyzed for the word pairs. Peak amplitude and latency measures of the N400 component were subjected to a mixed design analysis of variance (ANOVA). No significant interaural asymmetry was found in the AERP waveform for the reference word condition in either age group. In response to the second word of the pair, however, middle-aged females showed significantly greater N400 negativity in the CR condition than in the CL condition. No significant laterality effect was found in the young females. The study of young versus middle-aged participants may be an effective way of avoiding the confound of high-frequency hearing loss in elderly persons when studying age effects on auditory processing.	t	\N
23507387	It was the aim of this study to delineate the areas along the right superior temporal sulcus (STS) for processing of faces, voices, and face-voice integration using established functional magnetic resonance imaging (fMRI) localizers and to assess their structural connectivity profile with diffusion tensor imaging (DTI). We combined this approach with an fMRI adaptation design during which the participants judged emotions in facial expressions and prosody and demonstrated response habituation in the orbitofrontal cortex (OFC) which occurred irrespective of the sensory modality. These functional data were in line with DTI findings showing separable fiber projections of the three different STS modules converging in the OFC which run through the external capsule for the voice area, through the dorsal superior longitudinal fasciculus (SLF) for the face area and through the ventral SLF for the audiovisual integration area. The OFC was structurally connected with the supplementary motor area (SMA) and activation in these two areas was correlated with faster stimulus evaluation during repetition priming. Based on these structural and functional properties, we propose that the OFC is part of the extended system for perception of emotional information in faces and voices and constitutes a neural interface linking sensory areas with brain regions implicated in generation of behavioral responses.	t	\N
23518401	This study investigated the development of children's skills in identifying ecologically relevant sound objects within naturalistic listening environments, using a non-linguistic analog of the classic 'cocktail-party' situation. Children aged 7-12.5 years completed a closed-set identification task in which brief, commonly encountered environmental sounds were presented at varying signal-to-noise ratios. To simulate the complexity of real-world acoustic environments, target sounds were embedded in either a single, stereophonically presented scene, or in one of two different scenes, with each scene presented to a single ear. Each target sound was either congruent or incongruent with the auditory context. Identification accuracy improved with increasing age, particularly in trials with low signal-to-noise ratios. Performance was most accurate when target sounds were incongruent with the background scene, and when sounds were presented in a single background scene. The presence of two backgrounds disproportionately disrupted children's performance relative to that of previously tested adults, and reduced children's sensitivity to contextual cues. Successful identification of familiar sounds in complex auditory contexts is the outcome of a protracted learning process, with children reaching adult levels of performance after a decade or more of experience.	t	\N
23523270	The ability to perceive and produce speech undergoes important changes in late adulthood. The goal of the present study was to characterize functional and structural age-related differences in the cortical network that support speech perception and production, using magnetic resonance imaging, as well as the relationship between functional and structural age-related changes occurring in this network. We asked young and older adults to observe videos of a speaker producing single words (perception), and to observe and repeat the words produced (production). Results show a widespread bilateral network of brain activation for Perception and Production that was not correlated with age. In addition, several regions did show age-related change (auditory cortex, planum temporale, superior temporal sulcus, premotor cortices, SMA-proper). Examination of the relationship between brain signal and regional and global gray matter volume and cortical thickness revealed a complex set of relationships between structure and function, with some regions showing a relationship between structure and function and some not. The present results provide novel findings about the neurobiology of aging and verbal communication.	t	\N
23534128	The aim of this study was to establish the expression rate of autoimmunity in patients with sudden sensorineural hearing loss and to determine whether a positive marker is associated with a higher rate of hearing recovery after steroid treatment. A prospective study was performed on 137 patients who experienced sudden sensorineural hearing loss and underwent immunoserologic investigations. Autoantibodies evaluated on the day of admission included anti-double-stranded DNA, rheumatoid factor, antiphospholipid immunoglobulins G and M, antinuclear antibody, and complements C3 and C4. Of 137 patients, 75 were male and 62 were female (mean age, 45.1 years). Hearing loss was found on the left side in 61 patients and on the right side in 76 patients. Elevation of at least 1 autoantibody or abnormal complement levels were found in 80 patients (58%), and abnormalities of 2 or more antibodies were found in 28 (20%). There were no statistically significant correlations between autoantibody abnormalities and age, initial hearing level, or positive treatment response. There is no clear evidence of a correlation between autoimmunity and hearing improvement in patients with autoantibody abnormalities. A high (but not significant) expression rate of autoantibody abnormality and complement level was seen in patients with sudden sensorineural hearing loss.	t	\N
23539259	Cochlear implant systems that combine electric and acoustic stimulation in the same ear are now commercially available and the number of patients using these devices is steadily increasing. In particular, electric-acoustic stimulation is an option for patients with severe, high frequency sensorineural hearing impairment. There have been a range of approaches to combining electric stimulation and acoustic hearing in the same ear. To develop a better understanding of fitting practices for devices that combine electric and acoustic stimulation, we conducted a systematic review addressing three clinical questions: what is the range of acoustic hearing in the implanted ear that can be effectively preserved for an electric-acoustic fitting?; what benefits are provided by combining acoustic stimulation with electric stimulation?; and what clinical fitting practices have been developed for devices that combine electric and acoustic stimulation? A search of the literature was conducted and 27 articles that met the strict evaluation criteria adopted for the review were identified for detailed analysis. The range of auditory thresholds in the implanted ear that can be successfully used for an electric-acoustic application is quite broad. The effectiveness of combined electric and acoustic stimulation as compared with electric stimulation alone was consistently demonstrated, highlighting the potential value of preservation and utilization of low frequency hearing in the implanted ear. However, clinical procedures for best fitting of electric-acoustic devices were varied. This clearly identified a need for further investigation of fitting procedures aimed at maximizing outcomes for recipients of electric-acoustic devices.	t	\N
23540912	The present study investigated phonological encoding skills in children who stutter (CWS) and those who do not (CNS). Participants were 9 CWS (M=11.8 years, SD=1.5) and 9 age and sex matched CNS (M=11.8 years, SD=1.5). Participants monitored target phonemes located at syllable onsets and offsets of bisyllabic words. Performance in the phoneme monitoring task was compared to an auditory tone monitoring task. Repeated measures analysis of the response time data revealed significant Group×Task×Position interaction with the CWS becoming progressively slower than the CNS in monitoring subsequent phonemes located within the bisyllabic words; differences were not observed in the auditory tone monitoring task. Repeated measures analysis of the error data indicated that the groups were comparable in the percent errors in phoneme vs. tone monitoring. The CWS group was also significantly slower in a picture naming task compared to the CNS. Present findings suggest that CWS experience temporal asynchronies in one or more processes leading up to phoneme monitoring. The findings are interpreted within the scope of contemporary theories of stuttering. At the end of this activity the reader will be able to: (a) discuss the literature on phonological encoding skills in children who stutter, (b) identify theories of phonological encoding in stuttering, (c) define the process of phonological encoding and its implications for fluent speech, (d) suggest future areas of research in the investigation of phonological encoding abilities in children who stutter.	t	\N
23544047	Because classical music has greatly affected our life and culture in its long history, it has attracted extensive attention from researchers to understand laws behind it. Based on statistical physics, here we use a different method to investigate classical music, namely, by analyzing cumulative distribution functions (CDFs) and autocorrelation functions of pitch fluctuations in compositions. We analyze 1,876 compositions of five representative classical music composers across 164 years from Bach, to Mozart, to Beethoven, to Mendelsohn, and to Chopin. We report that the biggest pitch fluctuations of a composer gradually increase as time evolves from Bach time to Mendelsohn/Chopin time. In particular, for the compositions of a composer, the positive and negative tails of a CDF of pitch fluctuations are distributed not only in power laws (with the scale-free property), but also in symmetry (namely, the probability of a treble following a bass and that of a bass following a treble are basically the same for each composer). The power-law exponent decreases as time elapses. Further, we also calculate the autocorrelation function of the pitch fluctuation. The autocorrelation function shows a power-law distribution for each composer. Especially, the power-law exponents vary with the composers, indicating their different levels of long-range correlation of notes. This work not only suggests a way to understand and develop music from a viewpoint of statistical physics, but also enriches the realm of traditional statistical physics by analyzing music.	t	\N
23544676	Sound sequences, such as music, are usually organized perceptually into concurrent "streams." The mechanisms underlying this "auditory streaming" phenomenon are not completely known. The present study sought to test the hypothesis that synchrony limits listeners' ability to separate sound streams. To test this hypothesis, both perceptual-organization judgments and performance measures were used. In Experiment 1, listeners indicated whether they perceived sequences of alternating or synchronous tones as a single stream or as two streams. In Experiments 2 and 3, listeners detected rare changes in the intensity of "target" tones at one frequency in the presence of synchronous or asynchronous random-intensity "distractor" tones at another frequency. The results of these experiments showed that, for large frequency separations between the tones, the probability of perceiving two streams was lower on average for synchronous than for alternating tones, and that sensitivity to intensity changes in the target sequence was greater for asynchronous than for synchronous distractors. Overall, these results are consistent with the hypothesis that synchrony limits listeners' ability to form separate streams and/or to attend selectively to certain sounds in the presence of other sounds, even when the target and distractor sounds are well separated from each other in frequency.	t	\N
23547103	Intertrial repetition priming plays a striking role in visual search. For instance, when searching for a target with a unique color, performance is substantially better when the specific color of the target repeats on successive trials (Maljkovic & Nakayama, 1994). Recent research has relied on objective measures of performance to show that priming improves the perceptual quality of the repeated target. Here, we examined the relation between priming and conscious perception of the target by adding a subjective measure of perception. We used backward masking to create liminal perception, that is, different levels of subjectively conscious perception of the target using exactly the same stimulus conditions. The displays in either probe trials (in which priming benefits are measured, experiment 1) or in prime trials (in which memory traces are laid down, experiment 2) were masked. The results showed that intertrial priming improves full access to awareness of the repeated target but only for targets that already achieved partial access to awareness. In addition, they show that full awareness of the target is necessary in both the prime and probe trials for intertrial priming effects to emerge. Implications for the role of implicit short-term memory in visual search are discussed.	t	\N
23547105	When two objects are flashed at one location in close temporal proximity in the visual periphery, an intriguing illusion occurs whereby a single flash presented concurrently at another location appears to flash twice (the visual double-flash illusion: Chatterjee et al., 2011, Wilson & Singer, 1981). Here, for the first time, we investigate the time course of the effect, and directly compare it to the time course of the auditory (sound-induced flash illusion) effect, for both fission (single test flash, double inducer) and fusion (double test flash, single inducer) conditions, across stimulus onset asynchronies (SOAs) of 30 to 250 ms. In addition, using a novel audiovisual stimulus, we directly compare the cue strength of the two modalities, and whether they are additive in effect. The results show that the time course of fission and fusion is different for visual inducers, but not for auditory inducers. In audiovisual conditions, in situations of uncertainty, observers tended to follow the more reliable (auditory) cue. There was little evidence for a superadditive effect of auditory and visual cues; rather, observers tended to follow one or the other modality. The results suggest that the visually induced flash illusion and the auditory-induced effect may both stem from perceptual uncertainty, with the difference in time courses attributable to the lower temporal resolution of vision compared to audition.	t	\N
23555217	The processing characteristics of neurons in the central auditory system are directly shaped by and reflect the statistics of natural acoustic environments, but the principles that govern the relationship between natural sound ensembles and observed responses in neurophysiological studies remain unclear. In particular, accumulating evidence suggests the presence of a code based on sustained neural firing rates, where central auditory neurons exhibit strong, persistent responses to their preferred stimuli. Such a strategy can indicate the presence of ongoing sounds, is involved in parsing complex auditory scenes, and may play a role in matching neural dynamics to varying time scales in acoustic signals. In this paper, we describe a computational framework for exploring the influence of a code based on sustained firing rates on the shape of the spectro-temporal receptive field (STRF), a linear kernel that maps a spectro-temporal acoustic stimulus to the instantaneous firing rate of a central auditory neuron. We demonstrate the emergence of richly structured STRFs that capture the structure of natural sounds over a wide range of timescales, and show how the emergent ensembles resemble those commonly reported in physiological studies. Furthermore, we compare ensembles that optimize a sustained firing code with one that optimizes a sparse code, another widely considered coding strategy, and suggest how the resulting population responses are not mutually exclusive. Finally, we demonstrate how the emergent ensembles contour the high-energy spectro-temporal modulations of natural sounds, forming a discriminative representation that captures the full range of modulation statistics that characterize natural sound ensembles. These findings have direct implications for our understanding of how sensory systems encode the informative components of natural stimuli and potentially facilitate multi-sensory integration.	t	\N
23556554	Auditory and visual digit span tests were administered to a group of absolute pitch (AP) possessors, and a group of AP nonpossessors matched for age, and for age of onset and duration of musical training. All subjects were speakers of English. The AP possessors substantially and significantly outperformed the nonpossessors on the auditory test, while the two groups did not differ significantly on the visual test. It is conjectured that a large auditory memory span, including memory for speech sounds, facilitates the development of associations between pitches and their verbal labels early in life, so promoting the acquisition of AP.	t	\N
23556594	Thresholds for sinusoids interaurally in phase (S0) and antiphase (Sπ) were measured in the presence of a diotic notched-noise masker (N0) as a function of notch width. The signal frequency was 250, 500, 1000, or 2000 Hz. For all signal frequencies, the difference between N0S0 and N0Sπ thresholds (binaural masking-level difference, BMLD) decreased continuously as the notch width increased. Model simulations showed that this result cannot be accounted for by a model that only processes the output of the auditory filter centered at the signal frequency, even if the nonlinear behavior of the monaural frequency selectivity or interaural differences in the filter shape are considered. The data were predicted well if a detrimental across-channel process was included, either by an addition of portions of the output of adjacent filters to the output of the on-frequency filter or by a notch-width dependent adverse shift in interaural phase in the binaural stage. The strength of this detrimental across-channel process tends to decrease with increasing signal frequencies.	t	\N
23573184	Stress is prevalent in human life and threatens both physical and mental health; stress coping is thus of adaptive value for individual's survival and well-being. Although there has been extensive research on how the neural and physiological systems respond to stressful stimulation, relatively little is known about how the brain dynamically copes with stress evoked by this stimulation. Here we investigated how stress is relieved by a popular coping behavior, namely, gum chewing. In an fMRI study, we used loud noise as an acute stressor and asked participants to rate their feeling of stress in gum-chewing and no-chewing conditions. The participants generally felt more stressful when hearing noise, but less so when they were simultaneously chewing gum. The bilateral superior temporal sulcus (STS) and the left anterior insula (AI) were activated by noise, and their activations showed a positive correlation with the self-reported feeling of stress. Critically, gum chewing significantly reduced the noise-induced activation in these areas. Psychophysiological interaction (PPI) analysis showed that the functional connectivity between the left AI and the dorsal anterior cingulate cortex (dACC) was increased by noise to a lesser extent when the participants were chewing gum than when not chewing gum. Dynamic causality modeling (DCM) demonstrated that gum chewing inhibited the connectivity from the STS to the left AI. These findings demonstrate that gum chewing relieves stress by attenuating the sensory processing of external stressor and by inhibiting the propagation of stress-related information in the brain stress network.	t	\N
23575462	It would be clinically valuable if an electrophysiological validation of hearing aid effectiveness in conveying speech information could be performed when a device is first provided to the individual after electroacoustic verification. This study evaluated envelope following responses (EFRs) elicited by English vowels in a steady state context and in natural sentences. It was the purpose of this study to determine whether EFRs could be detected rapidly enough to be clinically useful. EFRs were elicited using 5 vowels spanning the English vowel space, /i/, /ε/, /æ/, /(Equation is included in full-text article.)/, and /u/. These were presented either as concatenated steady state vowels (total duration 10.04 seconds) or in three 5-word sentences (total duration 11.77 seconds), where each vowel appeared once per sentence. Single-channel electroencephalogram was recorded from vertex (Cz) to the nape of the neck for 190 and 160 repetitions of the steady state vowels and sentences, respectively. The stimuli were presented at 70 dBA SPL. The fundamental frequency (f0) track from the stimuli was used with a Fourier analyzer to estimate the EFRs to each vowel. Noise amplitudes were also calculated at neighboring frequencies. Fifteen normal-hearing subjects who were 20 to 34 years of age participated in the experiment. In the analysis of steady state vowels, the mean response amplitude of /i/ was statistically the largest at 173 nV. The other 4 steady state vowels did not differ in mean response amplitude, which varied between 73 and 106 nV. In the analysis of vowels from the 3 sentences, the largest response amplitudes tended to be for /u/. Mean amplitudes for /u/ were 164, 111, and 140 nV for the words "booed," "food," and "Sue," respectively. The vowel /u/ produced statistically larger responses than /i/, /ε/, and /(Equation is included in full-text article.)/ when grouped across words, whereas other vowels did not differ. Mean response amplitudes for the other vowel categories in the sentences varied between 82 and 105 nV. All subjects showed significant EFRs in response to the words "Bee's" and "booed," but only 9 subjects showed significant EFRs for "pet," "bed," and "Bob." The authors were readily able to detect significant EFRs elicited by vowels in a steady state context and from 3 natural sentences. These results are promising as an early step in developing a clinical tool for validating that vowel stimuli are at least partially encoded at the level of the auditory brainstem. Future research will require evaluation of the technique with aided listeners, where the natural sentences are expected to be treated as typical speech by hearing aid signal-processing algorithms.	t	\N
23576809	Major depression goes along with affective and social-cognitive deficits. Most research on affective deficits in depression has, however, only focused on unimodal emotion processing, whereas in daily life, emotional perception is often highly dependent on the evaluation of multimodal inputs. We thus investigated emotional audiovisual integration in patients with depression and healthy subjects. Subjects rated the expression of happy, neutral and fearful faces while concurrently being exposed to emotional or neutral sounds. Results demonstrated group differences in left inferior frontal gyrus and inferior parietal cortex when comparing incongruent to congruent happy facial conditions, mainly due to a failure of patients to deactivate these regions in response to congruent stimulus pairs. Moreover, healthy subjects decreased activation in right posterior superior temporal gyrus/sulcus and midcingulate cortex when an emotional stimulus was paired with a neutral rather than another emotional one. In contrast, patients did not show such deactivation when neutral stimuli were integrated. These results demonstrate aberrant neural response in audiovisual processing in depression, indicated by failure to deactivate regions involved in inhibition and salience processing when congruent and neutral audiovisual stimuli pairs are integrated, providing a possible mechanism of constant arousal and readiness to act in this patient group.	t	\N
23591684	Migraine attacks consist of head pain and hypersensitivities to somatosensory, visual, auditory, and olfactory stimuli. Investigating how the migraine brain simultaneously processes and responds to multiple incoming stimuli may yield insights into migraine pathophysiology and migraine symptoms. The presence and intensity of hypersensitivity to one stimulus type are positively associated with the presence and intensity of hypersensitivities to other stimuli and to headache intensity. Furthermore, exposure to visual, auditory, and olfactory stimuli can trigger migraine attacks. These relationships suggest a role for multisensory integration in migraine. Multisensory integration of somatosensory, visual, auditory, and olfactory stimuli by the migraine brain may be an important concept for understanding migraine.	t	\N
23593198	It has been proposed that the loudness dependence of auditory evoked potentials (LDAEP) would be a reliable indicator of central serotonin system activity in humans. Serotonin levels and turnover are also increased by brain-derived neurotrophic factor (BDNF). The aim of the present study was to determine whether there is an association between genetic polymorphisms of BDNF and the LDAEP in healthy Korean young adults. The cohort comprised 211 mentally and physically healthy subjects, all of whom were nonsmokers (111 males, 100 females; age: 20∼32 years). To avoid hormonal effects, the LDAEP was measured during days 2-5 after the beginning of menstruation for female subjects. In addition, BDNF polymorphisms (rs6265, rs2030324, and rs1491850) were genotyped. The strength of the LDAEP differed significantly among the BDNF genotype groups. Furthermore, the distribution of genotypic frequencies differed significantly between subjects with high and low LDAEPs. In particular, subjects with the Val/Met (A/G) genotype for rs6265, the T/T genotype for rs2030324, or the C/C genotype for rs1491850 had a higher LDAEP, indicating lower central serotonergic activity. A low LDAEP was more prevalent than a high LDAEP among those with the C-T haplotype (C genotype for rs2030424 and T genotype for rs1491850). Our results concur with previous findings on BDNF polymorphisms and serotonergic drug responses in psychiatric disorder patients. The present results suggest the possibility that BDNF polymorphisms and LDAEP patterns can predict altered serotonergic activity.	t	\N
23603423	Language is more than a source of information for accessing higher-order conceptual knowledge. Indeed, language may determine how people perceive and interpret visual stimuli. Visual processing in linguistic contexts, for instance, mirrors language processing and happens incrementally, rather than through variously-oriented fixations over a particular scene. The consequences of this atypical visual processing are yet to be determined. Here, we investigated the integration of visual and linguistic input during a reasoning task. Participants listened to sentences containing conjunctions or disjunctions (Nancy examined an ant and/or a cloud) and looked at visual scenes containing two pictures that either matched or mismatched the nouns. Degree of match between nouns and pictures (referential anchoring) and between their expected and actual spatial positions (spatial anchoring) affected fixations as well as judgments. We conclude that language induces incremental processing of visual scenes, which in turn becomes susceptible to reasoning errors during the language-meaning verification process.	t	\N
23613083	The lack of fine structure information in conventional cochlear implant (CI) encoding strategies presumably contributes to the generally poor music perception with CIs. To improve CI users' music perception, a harmonic-single-sideband-encoder (HSSE) strategy was developed , which explicitly tracks the harmonics of a single musical source and transforms them into modulators conveying both amplitude and temporal fine structure cues to electrodes. To investigate its effectiveness, vocoder simulations of HSSE and the conventional continuous-interleaved-sampling (CIS) strategy were implemented. Using these vocoders, five normal-hearing subjects' melody and timbre recognition performance were evaluated: a significant benefit of HSSE to both melody (p < 0.002) and timbre (p < 0.026) recognition was found. Additionally, HSSE was acutely tested in eight CI subjects. On timbre recognition, a significant advantage of HSSE over the subjects' clinical strategy was demonstrated: the largest improvement was 35% and the mean 17% (p < 0.013). On melody recognition, two subjects showed 20% improvement with HSSE; however, the mean improvement of 7% across subjects was not significant (p > 0.090). To quantify the temporal cues delivered to the auditory nerve, the neural spike patterns evoked by HSSE and CIS for one melody stimulus were simulated using an auditory nerve model. Quantitative analysis demonstrated that HSSE can convey temporal pitch cues better than CIS. The results suggest that HSSE is a promising strategy to enhance music perception with CIs.	t	\N
23615803	Although the ferret has become an important model species for studying both fundamental and clinical aspects of spatial hearing, previous behavioral work has focused on studies of sound localization and spatial release from masking in the free field. This makes it difficult to tease apart the role played by different spatial cues. In humans and other species, interaural time differences (ITDs) and interaural level differences (ILDs) play a critical role in sound localization in the azimuthal plane and also facilitate sound source separation in noisy environments. In this study, we used a range of broadband noise stimuli presented via customized earphones to measure ITD and ILD sensitivity in the ferret. Our behavioral data show that ferrets are extremely sensitive to changes in either binaural cue, with levels of performance approximating that found in humans. The measured thresholds were relatively stable despite extensive and prolonged (>16 weeks) testing on ITD and ILD tasks with broadband stimuli. For both cues, sensitivity was reduced at shorter durations. In addition, subtle effects of changing the stimulus envelope were observed on ITD, but not ILD, thresholds. Sensitivity to these cues also differed in other ways. Whereas ILD sensitivity was unaffected by changes in average binaural level or interaural correlation, the same manipulations produced much larger effects on ITD sensitivity, with thresholds declining when either of these parameters was reduced. The binaural sensitivity measured in this study can largely account for the ability of ferrets to localize broadband stimuli in the azimuthal plane. Our results are also broadly consistent with data from humans and confirm the ferret as an excellent experimental model for studying spatial hearing.	t	\N
23616552	The combined use of multisensory signals is often beneficial. Based on neuronal recordings in the superior colliculus of cats, three basic rules were formulated to describe the effectiveness of multisensory signals: the enhancement of neuronal responses to multisensory compared with unisensory signals is largest when signals occur at the same location ("spatial rule"), when signals are presented at the same time ("temporal rule"), and when signals are rather weak ("principle of inverse effectiveness"). These rules are also considered with respect to multisensory benefits as observed with behavioral measures, but do they capture these benefits best? To uncover the principles that rule benefits in multisensory behavior, we here investigated the classical redundant signal effect (RSE; i.e., the speedup of response times in multisensory compared with unisensory conditions) in humans. Based on theoretical considerations using probability summation, we derived two alternative principles to explain the effect. First, the "principle of congruent effectiveness" states that the benefit in multisensory behavior (here the speedup of response times) is largest when behavioral performance in corresponding unisensory conditions is similar. Second, the "variability rule" states that the benefit is largest when performance in corresponding unisensory conditions is unreliable. We then tested these predictions in two experiments, in which we manipulated the relative onset and the physical strength of distinct audiovisual signals. Our results, which are based on a systematic analysis of response time distributions, show that the RSE follows these principles very well, thereby providing compelling evidence in favor of probability summation as the underlying combination rule.	t	\N
23627836	Theories of auditory attention suggest that humans decompose complex auditory input into individual auditory objects, which then compete for attention to dominate auditory perception. Since emotional significance of external stimuli has been argued to provide cues for sensory prioritization and allocation of attention, emotionally salient auditory objects can receive attention to dominate auditory perception. On the basis of the function of audition as an alarm system that informs the organism about its immediate surroundings, and on empirical evidence that emotion can modulate auditory perception, we argue that auditory stimuli with greater emotional saliency would dominate perception in multisource environments. To test our hypothesis, we employed a change detection task in which participants were asked to indicate whether multisource auditory scenes were identical or different. Participants were better at detecting changes at the presence of an emotionally negative environment compared to neutral environment. Further, we found that participants were better at detecting changes of emotionally negative targets compared to neutral targets. Our results demonstrate that detecting changes in auditory scenes is influenced by emotion. The findings are discussed in the light of the theories of auditory attention, emotional modulation of attention, and the adaptive function of emotion for perception.	t	\N
23632885	It has been suggested that an auditory phantom percept is the result of multiple, parallel but overlapping networks. One of those networks encodes tinnitus loudness and is electrophysiologically separable from a nonspecific distress network. The present study investigates how these networks anatomically overlap, what networks are involved, and how and when these networks interact. Electroencephalography data of 317 tinnitus patients and 256 healthy subjects were analyzed, using independent component analysis. Results demonstrate that tinnitus is characterized by at least 2 major brain networks, each consisting of multiple independent components. One network reflects tinnitus distress, while another network reflects the loudness of the tinnitus. The component coherence analysis shows that the independent components that make up the distress and loudness networks communicate within their respective network at several discrete frequencies in parallel. The distress and loudness networks do not intercommunicate for patients without distress, but do when patients are distressed by their tinnitus. The obtained data demonstrate that the components that build up these 2 separable networks communicate at discrete frequencies within the network, and only between the distress and loudness networks in those patients in whom the symptoms are also clinically linked.	t	\N
23632973	The purpose of this study was to determine how the bandwidth of the hearing aid (HA) fitting affects bimodal speech recognition of listeners with a cochlear implant (CI) in one ear and severe-to-profound hearing loss in the unimplanted ear (but with residual hearing sufficient for wideband amplification using National Acoustic Laboratories Revised, Profound [NAL-RP] prescriptive guidelines; unaided thresholds no poorer than 95 dB HL through 2000 Hz). Recognition of sentence material in quiet and in noise was measured with the CI alone and with CI plus HA as the amplification provided by the HA in the high and mid-frequency regions was systematically reduced from the wideband condition (NAL-RP prescription). Modified bandwidths included upper frequency cutoffs of 2000, 1000, or 500 Hz. On average, significant bimodal benefit was obtained when the HA provided amplification at all frequencies with aidable residual hearing. Limiting the HA bandwidth to only low-frequency amplification (below 1000 Hz) did not yield significant improvements in performance over listening with the CI alone. These data suggest the importance of providing amplification across as wide a frequency region as permitted by audiometric thresholds in the HA used by bimodal users.	t	\N
23639338	To investigate auditory perception, speech production, and language ability of prelingually deaf toddlers with cerebral palsy (CP) who were implanted within a sensitive period and who received proper speech therapy. Comparison of their outcomes with age- and sex-matched CI recipients without additional disabilities was also performed. We retrospectively reviewed a cohort of pediatric CI in Samsung Medical Center. Eight CP subjects who received CI before 3 years of age and age-sex matched control recipients who had no additional disabilities except idiopathic sensorineural hearing loss (SNHL) were included for the analysis. Preoperative evaluation included the Categories of Auditory Performance (CAP) score, Korean Version of the Ling's Stage (K-Ling), Sequenced Language Scale for Infants (SELSI), Bailey Scales of Infant Development II assessment, Social Maturity Scale test, and grading of CP severity using severity level and Gross Motor Function Classification System for CP (GMFCS). To measure the outcome, the CAP scores, K-Ling, and SELSI were performed at 3, 6, 12, and 24 months after implantation. Four CP children with outstanding performances showed comparable achievement with matched control recipients. These patients had less severe motor disabilities (mild-moderate severity, GMFCS level 1-3), better social quotient, and better cognitive abilities. Although the others showed poor language abilities and hardly produced meaningful speech, their CAP scores reached 1 or 2 in 24 months after implantation. Deaf children with CP could have various ranges of benefits up to the levels of normal peers whose only disability was hearing loss, when CI was performed within a critical period. Especially, children with mild or moderate CP had a favorable outcome after CI, equivalent to that of normal peers.	t	\N
23653412	It has previously been shown that the perceived roughness of a surface touched by one digit is influenced by the roughness of a different surface touched simultaneously by another digit on the same hand. The present study was designed to examine whether this is the case when surfaces of varying roughness are touched using digits on separate hands. Participants touched pairs of sandpaper surfaces, in sequence, using the same digit, and identified which of the two was rougher. Roughness discrimination was measured in the presence of distractor surfaces touched simultaneously with the target surface, but using a different digit either on the same or on the other hand. The overall perception of roughness of the attended surfaces was better on the left than on the right hand. Perceived roughness also varied systematically with the roughness of the distractor surfaces. Attended surfaces were more likely to be perceived as smoother when they were paired with smooth rather than rough distractors. Likewise, attended surfaces tended to be perceived as rougher with rough distractors. This pattern of results occurred whether the attended and distractor digits were on the same hand or different hands. These data confirm that it is difficult to restrict tactile attention for roughness to a single digit and show that this difficulty extends to restricting attention to a single hand. Furthermore, the effect of a stimulus at an unattended body location was not simply to impair perception in general, but to bias it in the roughness direction of the distractor surface.	t	\N
23654389	Auditory filter bandwidths are measured for a temporal process using an amplitude-modulation detection task. The signal is a 200 Hz wide, sinusoidally amplitude-modulated band of noise centered within an unmodulated notched-noise masker. A modulation rate of 10 Hz is used to avoid possible information loss at more central processing levels for high modulation rates. Threshold functions are obtained for 10-14 notch widths for each of four different center frequencies (0.6, 1, 2, and 4 kHz) to determine the maximum notch width at which the masker has an effect. The ratio of center frequency to maximum notch width is ~2 at all center frequencies. It is proposed that the bandwidths observed in temporal tasks, which are consistently greater than expected from the viewpoint of critical band theory, be characterized as "temporal critical bands." This proposal does not oppose, but provides a complement to the traditional critical band obtained in tasks involving spectral discrimination.	t	\N
23654392	Measurement of sensitivity to differences in the rate of change of auditory signal parameters is complicated by confounds among duration, extent, and velocity of the changing signal. Dooley and Moore [(1988) J. Acoust. Soc. Am. 84(4), 1332-1337] proposed a method for measuring sensitivity to rate of change using a duration discrimination task. They reported improved duration discrimination when an additional intensity or frequency change cue was present. The current experiments were an attempt to use this method to measure sensitivity to the rate of change in intensity and spatial position. Experiment 1 investigated whether duration discrimination was enhanced when additional cues of rate of intensity change, rate of spatial position change, or both were provided. Experiment 2 determined whether participant listening experience or the testing environment influenced duration discrimination task performance. Experiment 3 assessed whether duration discrimination could be used to measure sensitivity to rates of changes in intensity and spatial position for stimuli with lower rates of change, as well as emphasizing the constancy of the velocity cue. Results of these experiments showed that duration discrimination was impaired rather than enhanced by the additional velocity cues. The findings are discussed in terms of the demands of listening to concurrent changes along multiple auditory dimensions.	t	\N
23654413	Inharmonicity of piano tones is an essential property of their timbre that strongly influences the tuning, leading to the so-called octave stretching. It is proposed in this paper to jointly model the inharmonicity and tuning of pianos on the whole compass. While using a small number of parameters, these models are able to reflect both the specificities of instrument design and tuner's practice. An estimation algorithm is derived that can run either on a set of isolated note recordings, but also on chord recordings, assuming that the played notes are known. It is applied to extract parameters highlighting some tuner's choices on different piano types and to propose tuning curves for out-of-tune pianos or piano synthesizers.	t	\N
23656101	In this study, two methods are proposed to modify the normalized covariance metric (NCM) measure to reduce the effects of gain-induced nonlinear distortions introduced by most noise-suppression algorithms. Considering that the gain-induced distortions behave differently dependent on the signal-to-noise ratio between the noise-reduced speech and the noise, the first approach introduces a penalty factor involving this ratio in the modified NCM measure. The second approach deemphasizes segments marked with amplification distortions that contribute less to intelligibility via adaptive thresholding. Significantly higher correlations with intelligibility scores were obtained from the modified NCM measures compared with the original NCM measures.	t	\N
23656102	A reference-free speech quality measure is proposed and assessed for hearing aid applications. The proposed speech quality metric is validated with subjective ratings obtained from hearing impaired listeners under a number of noisy and reverberant conditions. In addition, a comparison is drawn between the proposed measure and a state-of-the-art electroacoustic measure that relies on a clean reference signal. The results showed that the reference-free measure had a lower correlation with the subjective ratings of hearing aid speech quality in comparison to the correlations achieved by the measure utilizing a reference signal. Nevertheless, advantages of the reference-free approach are discussed.	t	\N
23658664	In reverberant rooms with multiple-people talking, spatial separation between speech sources improves recognition of attended speech, even though both the head-shadowing and interaural-interaction unmasking cues are limited by numerous reflections. It is the perceptual integration between the direct wave and its reflections that bridges the direct-reflection temporal gaps and results in the spatial unmasking under reverberant conditions. This study further investigated (1) the temporal dynamic of the direct-reflection-integration-based spatial unmasking as a function of the reflection delay, and (2) whether this temporal dynamic is correlated with the listeners' auditory ability to temporally retain raw acoustic signals (i.e., the fast decaying primitive auditory memory, PAM). The results showed that recognition of the target speech against the speech-masker background is a descending exponential function of the delay of the simulated target reflection. In addition, the temporal extent of PAM is frequency dependent and markedly longer than that for perceptual fusion. More importantly, the temporal dynamic of the speech-recognition function is significantly correlated with the temporal extent of the PAM of low-frequency raw signals. Thus, we propose that a chain process, which links the earlier-stage PAM with the later-stage correlation computation, perceptual integration, and attention facilitation, plays a role in spatially unmasking target speech under reverberant conditions.	t	\N
23665378	The integration of auditory feedback with vocal motor output is important for the control of voice fundamental frequency (F0). We used a pitch-shift paradigm where subjects respond to an alteration, or shift, of voice pitch auditory feedback with a reflexive change in F0. We presented varying magnitudes of pitch shifted auditory feedback to subjects during vocalization and passive listening and measured event related potentials (ERPs) to the feedback shifts. Shifts were delivered at +100 and +400 cents (200 ms duration). The ERP data were modeled with dynamic causal modeling (DCM) techniques where the effective connectivity between the superior temporal gyrus (STG), inferior frontal gyrus and premotor areas were tested. We compared three main factors: the effect of intrinsic STG connectivity, STG modulation across hemispheres and the specific effect of hemisphere. A Bayesian model selection procedure was used to make inference about model families. Results suggest that both intrinsic STG and left to right STG connections are important in the identification of self-voice error and sensory motor integration. We identified differences in left-to-right STG connections between 100 cent and 400 cent shift conditions suggesting that self- and non-self-voice error are processed differently in the left and right hemisphere. These results also highlight the potential of DCM modeling of ERP responses to characterize specific network properties of forward models of voice control.	t	\N
23667666	Audition--what listeners hear--is generally studied in terms of the physical properties of sound stimuli and physiological properties of the auditory system. Based on recent work in vision, we here consider an alternative perspective that sensory percepts are based on past experience. In this framework, basic auditory qualities (e.g., loudness and pitch) are based on the frequency of occurrence of stimulus patterns in natural acoustic stimuli. To explore this concept of audition, we examined five well-documented psychophysical functions. The frequency of occurrence of acoustic patterns in a database of natural sound stimuli (speech) predicts some qualitative aspects of these functions, but with substantial quantitative discrepancies. This approach may offer a rationale for auditory phenomena that are difficult to explain in terms of the physical attributes of the stimuli as such.	t	\N
23678126	For effective interactions with our dynamic environment, it is critical for the brain to integrate motion information from the visual and auditory senses. Combining fMRI and psychophysics, this study investigated how the human brain integrates auditory and visual motion into benefits in motion discrimination. Subjects discriminated the motion direction of audiovisual stimuli that contained directional motion signal in the auditory, visual, audiovisual, or no modality at two levels of signal reliability. Therefore, this 2 × 2 × 2 factorial design manipulated: (1) auditory motion information (signal vs noise), (2) visual motion information (signal vs noise), and (3) reliability of motion signal (intact vs degraded). Behaviorally, subjects benefited significantly from audiovisual integration primarily for degraded auditory and visual motion signals while obtaining near ceiling performance for "unisensory" signals when these were reliable and intact. At the neural level, we show audiovisual motion integration bilaterally in the visual motion areas hMT+/V5+ and implicate the posterior superior temporal gyrus/planum temporale in auditory motion processing. Moreover, we show that the putamen integrates audiovisual signals into more accurate motion discrimination responses. Our results suggest audiovisual integration processes at both the sensory and response selection levels. In all of these regions, the operational profile of audiovisual integration followed the principle of inverse effectiveness, in which audiovisual response suppression for intact stimuli turns into response enhancements for degraded stimuli. This response profile parallels behavioral indices of audiovisual integration, in which subjects benefit significantly from audiovisual integration only for the degraded conditions.	t	\N
23684863	In ordinary conversations, literal meanings of an utterance are often quite different from implicated meanings and the inference about implicated meanings is essentially required for successful comprehension of the speaker's utterances. Inference of finding implicated meanings is based on the listener's assumption that the conversational partner says only relevant matters according to the maxim of relevance in Grice's theory of conversational implicature. To investigate the neural correlates of comprehending implicated meanings under the maxim of relevance, a total of 23 participants underwent an fMRI task with a series of conversational pairs, each consisting of a question and an answer. The experimental paradigm was composed of three conditions: explicit answers, moderately implicit answers, and highly implicit answers. Participants were asked to decide whether the answer to the Yes/No question meant 'Yes' or 'No'. Longer reaction time was required for the highly implicit answers than for the moderately implicit answers without affecting the accuracy. The fMRI results show that the left anterior temporal lobe, left angular gyrus, and left posterior middle temporal gyrus had stronger activation in both moderately and highly implicit conditions than in the explicit condition. Comprehension of highly implicit answers had increased activations in additional regions including the left inferior frontal gyrus, left medial prefrontal cortex, left posterior cingulate cortex and right anterior temporal lobe. The activation results indicate involvement of these regions in the inference process to build coherence between literally irrelevant but pragmatically associated utterances under the maxim of relevance. Especially, the left anterior temporal lobe showed high sensitivity to the level of implicitness and showed increased activation for highly versus moderately implicit conditions, which imply its central role in inference such as semantic integration. The right hemisphere activation, uniquely found in the anterior temporal lobe for highly implicit utterances, suggests its competence for integrating distant concepts in implied utterances under the relevance principle.	t	\N
23691185	Listening to and understanding people in a "cocktail-party situation" is a remarkable feature of the human auditory system. Here we investigated the neural correlates of the ability to localize a particular sound among others in an acoustically cluttered environment with healthy subjects. In a sound localization task, five different natural sounds were presented from five virtual spatial locations during functional magnetic resonance imaging (fMRI). Activity related to auditory stream segregation was revealed in posterior superior temporal gyrus bilaterally, anterior insula, supplementary motor area, and frontoparietal network. Moreover, the results indicated critical roles of left planum temporale in extracting the sound of interest among acoustical distracters and the precuneus in orienting spatial attention to the target sound. We hypothesized that the left-sided lateralization of the planum temporale activation is related to the higher specialization of the left hemisphere for analysis of spectrotemporal sound features. Furthermore, the precuneus - a brain area known to be involved in the computation of spatial coordinates across diverse frames of reference for reaching to objects - seems to be also a crucial area for accurately determining locations of auditory targets in an acoustically complex scene of multiple sound sources. The precuneus thus may not only be involved in visuo-motor processes, but may also subserve related functions in the auditory modality.	t	\N
23694737	Multiple auditory steady-state responses (ASSRs) to air- and bone-conduction stimuli were recorded in young children with otitis media with effusion (OME). After treatment for OME, differences between pre-treatment bone-conduction ASSR levels and post-treatment conditioned orientation reflex (COR) or air-conduction ASSR levels were examined, and compared with ASSR-estimated air-bone gap (ABG) before treatment. Navigator Pro with Master was used to assess the threshold of air- and bone-conduction ASSR in both ears at 500Hz, 1000Hz, 2000Hz and 4000Hz. For bone-conduction ASSR, RadioEar B-71 bone-vibrator placed on the mastoid was used with white-noise masking on the contralateral ear. After ventilation tube placement, the thresholds of COR got closer to those of pre-treatment bone-conduction ASSR in young children with OME. Moreover, post-treatment air-conduction ASSR thresholds also got closer to those of pre-treatment bone-conduction ASSR. The differences between pre-treatment bone-conduction ASSR thresholds and post-treatment COR or air-conduction ASSR thresholds became much smaller than ASSR-estimated ABG before treatment. These findings suggest that bone-conduction ASSR can assess the normal or near normal cochlear sensitivity in young children with conductive hearing loss. It is also suggested that ASSR-estimated ABG can be used clinically to predict their accurate ABG.	t	\N
23694738	The aim of our study is to investigate the relationship between the complaint of speech understanding in noisy environments and the findings of contralateral suppression of transient evoked otoacoustic emissions and speech recognition in noise test methods in individuals with normal hearing. Sixty-nine subjects between 18 and 53 years of age with normal hearing participated in the present study. The subjects were assigned to one of two groups, reported difficulty understanding speech in noise or no reported difficulty understanding speech in noise. After hearing and immitancemetric evaluation, contralateral suppression of transient evoked otoacoustic emissions and speech recognition in noise tests were administered to both groups. Suppression was calculated in half-octave frequency bands centered at 1.0, 1.5, 2.0, 3.0 and 4.0kHz. We found out that the speech recognition in noise scores and contralateral suppression values were lower in subjects with the complaint of speech understanding in noise than those who do not have such complaints. We concluded that the complaint of speech understanding in noise may be related to the medial efferent system dysfunction, so central auditory nervous system.	t	\N
23700960	We investigated the effects of focusing attention towards auditory or somatosensory stimuli on perceptual sensitivity and response bias using a signal detection task. Participants (N = 44) performed an unspeeded detection task in which weak (individually calibrated) somatosensory or auditory stimuli were delivered. The focus of attention was manipulated by the presentation of a visual cue at the start of each trial. The visual cue consisted of the word "warmth" or the word "tone". This word cue was predictive of the corresponding target on two-thirds of the trials. As hypothesised, the results showed that cueing attention to a specific sensory modality resulted in a higher perceptual sensitivity for validly cued targets than for invalidly cued targets, as well as in a more liberal response criterion for reporting stimuli in the valid modality than in the invalid modality. The value of this experimental paradigm for investigating excessive attentional focus or hypervigilance in various non-clinical and clinical populations is discussed.	t	\N
23705807	Cochlear implantation (CI) is a standard treatment for severe-profound sensorineural hearing loss (SNHL). However, consensus has yet to be reached on its effectiveness for hearing loss caused by auditory neuropathy spectrum disorder (ANSD). This review aims to summarize and synthesize current evidence of the effectiveness of CI in improving speech recognition in children with ANSD. Systematic review. A total of 27 studies from an initial selection of 237. All selected studies were observational in design, including case studies, cohort studies, and comparisons between children with ANSD and SNHL. Most children with ANSD achieved open-set speech recognition with their CI. Speech recognition ability was found to be equivalent in CI users (who previously performed poorly with hearing aids) and hearing-aid users. Outcomes following CI generally appeared similar in children with ANSD and SNHL. Assessment of study quality, however, suggested substantial methodological concerns, particularly in relation to issues of bias and confounding, limiting the robustness of any conclusions around effectiveness. Currently available evidence is compatible with favourable outcomes from CI in children with ANSD. However, this evidence is weak. Stronger evidence is needed to support cost-effective clinical policy and practice in this area.	t	\N
23708733	Dyslexic and non-dyslexic readers engaged in a short training aimed at learning eight basic letter-speech sound correspondences within an artificial orthography. We examined whether a letter-speech sound binding deficit is behaviorally detectable within the initial steps of learning a novel script. Both letter knowledge and word reading ability within the artificial script were assessed. An additional goal was to investigate the influence of instructional approach on the initial learning of letter-speech sound correspondences. We assigned children from both groups to one of three different training conditions: (a) explicit instruction, (b) implicit associative learning within a computer game environment, or (c) a combination of (a) and (b) in which explicit instruction is followed by implicit learning. Our results indicated that dyslexics were outperformed by the controls on a time-pressured binding task and a word reading task within the artificial orthography, providing empirical support for the view that a letter-speech sound binding deficit is a key factor in dyslexia. A combination of explicit instruction and implicit techniques proved to be a more powerful tool in the initial teaching of letter-sound correspondences than implicit training alone.	t	\N
23714710	To investigate safety and efficacy of a new transcutaneous bone conduction hearing implant, over a 3-month follow-up period. Prospective, single-subject repeated-measures design in which each subject serves as his/her own control. Departments of Otolaryngology at 4 hospitals in Germany and Austria. Subjects were 12 German-speaking adults who suffered from conductive or mixed hearing loss. The upper bone conduction threshold limit was set to 45 dB HL at frequencies between 500 Hz and 4 kHz. Implantation of a transcutaneous bone conduction hearing implant. Subjects' speech perception (word recognition scores and SRT 50%) and audiometric thresholds (air conduction, bone conduction and sound field at frequencies 500 Hz to 8 kHz) were assessed preoperatively, 1 month postoperatively and 3 months postoperatively. The subjects were monitored for adverse events and given a questionnaire to assess their satisfaction levels. Speech perception as measured by word recognition scores and SRT 50% improved on average about 78.8% and 25 dB HL, respectively, 3 months after implantation. Aided thresholds also improved postoperatively at all tested frequencies and continued to improve from 1 to 3 months postoperatively. Air conduction and bone conduction thresholds showed no significant changes, confirming that subjects' residual unaided hearing was not deteriorated by the treatment. Only minor adverse events were reported and resolved by the end of the study. The new transcutaneous bone conduction implant was demonstrated to be safe and effective in adults up to 3 months of device use.	t	\N
23715097	In this study, we used magnetoencephalography and a mismatch paradigm to investigate speech processing in stroke patients with auditory comprehension deficits and age-matched control subjects. We probed connectivity within and between the two temporal lobes in response to phonemic (different word) and acoustic (same word) oddballs using dynamic causal modelling. We found stronger modulation of self-connections as a function of phonemic differences for control subjects versus aphasics in left primary auditory cortex and bilateral superior temporal gyrus. The patients showed stronger modulation of connections from right primary auditory cortex to right superior temporal gyrus (feed-forward) and from left primary auditory cortex to right primary auditory cortex (interhemispheric). This differential connectivity can be explained on the basis of a predictive coding theory which suggests increased prediction error and decreased sensitivity to phonemic boundaries in the aphasics' speech network in both hemispheres. Within the aphasics, we also found behavioural correlates with connection strengths: a negative correlation between phonemic perception and an inter-hemispheric connection (left superior temporal gyrus to right superior temporal gyrus), and positive correlation between semantic performance and a feedback connection (right superior temporal gyrus to right primary auditory cortex). Our results suggest that aphasics with impaired speech comprehension have less veridical speech representations in both temporal lobes, and rely more on the right hemisphere auditory regions, particularly right superior temporal gyrus, for processing speech. Despite this presumed compensatory shift in network connectivity, the patients remain significantly impaired.	t	\N
23716019	Our environment is richly structured, with objects producing correlated information within and across sensory modalities. A prominent challenge faced by our perceptual system is to learn such regularities. Here, we examined statistical learning and addressed learners' ability to track transitional probabilities between elements in the auditory and visual modalities. Specifically, we investigated whether cross-modal information affects statistical learning within a single modality. Participants were familiarized with a statistically structured modality (e.g., either audition or vision) accompanied by different types of cues in a second modality (e.g., vision or audition). The results revealed that statistical learning within either modality is affected by cross-modal information, with learning being enhanced or reduced according to the type of cue provided in the second modality.	t	\N
23716122	Cross-orientation masking (XOM) occurs when the detection of a test grating is masked by a superimposed grating at an orthogonal orientation, and is thought to reveal the suppressive effects mediating contrast normalization. Medina and Mullen (2009) reported that XOM was greater for chromatic than achromatic stimuli at equivalent spatial and temporal frequencies. Here we address whether the greater suppression found in binocular color vision originates from a monocular or interocular site, or both. We measure monocular and dichoptic masking functions for red-green color contrast and achromatic contrast at three different spatial frequencies (0.375, 0.75, and 1.5 cpd, 2 Hz). We fit these functions with a modified two-stage masking model (Meese & Baker, 2009) to extract the monocular and interocular weights of suppression. We find that the weight of monocular suppression is significantly higher for color than achromatic contrast, whereas dichoptic suppression is similar for both. These effects are invariant across spatial frequency. We then apply the model to the binocular masking data using the measured values of the monocular and interocular sources of suppression and show that these are sufficient to account for color binocular masking. We conclude that the greater strength of chromatic XOM has a monocular origin that transfers through to the binocular site.	t	\N
23716218	High-frequency pure tones (>6 kHz), which alone do not produce salient melodic pitch information, provide melodic pitch information when they form part of a harmonic complex tone with a lower fundamental frequency (F0). We explored this phenomenon in normal-hearing listeners by measuring F0 difference limens (F0DLs) for harmonic complex tones and pure-tone frequency difference limens (FDLs) for each of the tones within the harmonic complexes. Two spectral regions were tested. The low- and high-frequency band-pass regions comprised harmonics 6-11 of a 280- or 1,400-Hz F0, respectively; thus, for the high-frequency region, audible frequencies present were all above 7 kHz. Frequency discrimination of inharmonic log-spaced tone complexes was also tested in control conditions. All tones were presented in a background of noise to limit the detection of distortion products. As found in previous studies, F0DLs in the low region were typically no better than the FDL for each of the constituent pure tones. In contrast, F0DLs for the high-region complex were considerably better than the FDLs found for most of the constituent (high-frequency) pure tones. The data were compared with models of optimal spectral integration of information, to assess the relative influence of peripheral and more central noise in limiting performance. The results demonstrate a dissociation in the way pitch information is integrated at low and high frequencies and provide new challenges and constraints in the search for the underlying neural mechanisms of pitch.	t	\N
23716223	We report a series of psychophysics experiments that investigated listeners' sensitivity to changes in complex acoustic scenes. Specifically, we sought to test the hypothesis that change detection is supported by sensitivity to change-related transients (an abrupt change in stimulus power within a certain frequency band, associated with the appearance or disappearance of a scene element). This hypothesis, in the context of natural scenes, is commonly dismissed on account that the elements of the scene may themselves be characterized by on-going energy fluctuations that would mask any genuine change-related transients. We created artificial 'scenes' populated by multiple pure-tone components. Tones were modulated (by a square wave at a distinct rate) so as to mimic the fluctuation properties of complex sounds. "Change" was defined as the appearance or disappearance of one such element. Importantly, such scenes lack semantic attributes, which may have been a limiting factor in interpreting previous auditory change-detection studies, thus allowing us to probe the low-level, pre-semantic, processes involved in auditory change perception. In Experiment 1 we measured listeners' ability to detect item appearance and disappearance in conditions where change-related transients are masked by a silent gap. In Experiment 2, we investigated the effect of an acoustic distractor - a brief signal that occurs at the time of change, but does not mask any scene components. The data show that gaps adversely affected the processing of item appearance but not disappearance. However, distractors reduced both -appearance and disappearance detection. Together our results suggest a role for sensitivity to transients in the process of auditory change detection, similar to what has been demonstrated for visual change detection.	t	\N
23716230	Advances in the design of cochlear implants (CIs), as well as improved CI surgical techniques, have led to an increase in the number of patients who retain some residual low-frequency acoustic hearing in the implanted ear. Many of these patients also possess some hearing in the unimplanted ear. Although their low-frequency audiometric configurations will likely be asymmetrical across ears, they may nevertheless be able to process interaural time differences (ITDs) which might aid them in localizing sound sources and achieving a spatial release from masking. We recently published research (Brown and Yost 2011) showing how sensitivity to ITD differences was affected when the stimulus bandwidths were varied between the ears, to simulate asymmetrical hearing loss in the low-frequency region. We showed that ITD discrimination thresholds decreased as the bandwidth of the noise presented to one ear increased beyond that presented to the other ear. In the current experiment, we expand upon those conditions to ­further explore ITD processing in the presence of interaural spectral differences. ITD sensitivity was measured when a fixed band of noise was presented to one ear and the center frequency of a spectral band of the same width was moved upward in frequency in the other ear. The data suggest that listeners have difficulty attending to ITD differences in one spectral region when there are other spectral regions that contain conflicting or inconsistent spatial information, which is likely to be the case for many CI patients who possess bilateral residual hearing.	t	\N
23716240	Jørgensen and Dau (J Acoust Soc Am 130:1475-1487, 2011) proposed the speech-based envelope power spectrum model (sEPSM) in an attempt to overcome the limitations of the classical speech transmission index (STI) and speech intelligibility index (SII) in conditions with nonlinearly processed speech. Instead of considering the reduction of the temporal modulation energy as the intelligibility metric, as assumed in the STI, the sEPSM applies the signal-to-noise ratio in the envelope domain (SNRenv). This metric was shown to be the key for predicting the intelligibility of reverberant speech as well as noisy speech processed by spectral subtraction. The key role of the SNRenv metric is further supported here by the ability of a short-term version of the sEPSM to predict speech masking release for different speech materials and modulated interferers. However, the sEPSM cannot account for speech subjected to phase jitter, a condition in which the spectral structure of the intelligibility of speech signal is strongly affected, while the broadband temporal envelope is kept largely intact. In contrast, the effects of this distortion can be predicted -successfully by the spectro-temporal modulation index (STMI) (Elhilali et al., Speech Commun 41:331-348, 2003), which assumes an explicit analysis of the spectral "ripple" structure of the speech signal. However, since the STMI applies the same decision metric as the STI, it fails to account for spectral subtraction. The results from this study suggest that the SNRenv might reflect a powerful decision metric, while some explicit across-frequency analysis seems crucial in some conditions. How such across-frequency analysis is "realized" in the auditory system remains unresolved.	t	\N
23716257	We recently showed that listeners with normal hearing thresholds vary in their ability to direct spatial attention and that ability is related to the fidelity of temporal coding in the brainstem. Here, we recruited additional middle-aged listeners and extended our analysis of the brainstem response, measured using the frequency-following response (FFR). We found that even though age does not predict overall selective attention ability, middle-aged listeners are more susceptible to the detrimental effects of reverberant energy than young adults. We separated the overall FFR into orthogonal envelope and carrier components and used an existing model to predict which auditory channels drive each component. We find that responses in mid- to high-frequency auditory channels dominate envelope FFR, while lower-frequency channels dominate the carrier FFR. Importantly, we find that which component of the FFR predicts selective attention performance changes with age. We suggest that early aging degrades peripheral temporal coding in mid-to-high frequencies, interfering with the coding of envelope interaural time differences. We argue that, compared to young adults, middle-aged listeners, who do not have strong temporal envelope coding, have more trouble following a conversation in a reverberant room because they are forced to rely on fragile carrier ITDs that are susceptible to the degrading effects of reverberation.	t	\N
23716261	Humans and other animals can attend to one of multiple sounds, and -follow it selectively over time. The neural underpinnings of this perceptual feat remain mysterious. Some studies have concluded that sounds are heard as separate streams when they activate well-separated populations of central auditory neurons, and that this process is largely pre-attentive. Here, we propose instead that stream formation depends primarily on temporal coherence between responses that encode various features of a sound source. Furthermore, we postulate that only when attention is directed toward a particular feature (e.g., pitch or location) do all other temporally coherent features of that source (e.g., timbre and location) become bound together as a stream that is segregated from the incoherent features of other sources. Experimental -neurophysiological evidence in support of this hypothesis will be presented. The focus, however, will be on a computational realization of this idea and a discussion of the insights learned from simulations to disentangle complex sound sources such as speech and music. The model consists of a representational stage of early and cortical auditory processing that creates a multidimensional depiction of various sound attributes such as pitch, location, and spectral resolution. The following stage computes a coherence matrix that summarizes the pair-wise correlations between all channels making up the cortical representation. Finally, the perceived segregated streams are extracted by decomposing the coherence matrix into its uncorrelated components. Questions raised by the model are discussed, especially on the role of attention in streaming and the search for further neural correlates of streaming percepts.	t	\N
23720086	The CHRNA4 gene is known to be associated with individual differences in attention. However, its associations with other cognitive functions remain to be elucidated. In the present study, we investigated the effects of genetic variations in CHRNA4 on rapid scene categorization by 100 healthy human participants. In Experiment 1, we also conducted the Attention Network Test (ANT) in order to examine whether the genetic effects could be accounted for by attention. CHRNA4 was genotyped as carrying the TT, CT, or CC allele. The scene categorization task required participants to judge whether the category of a scene image (natural or man-made) was consistent with a cue word displayed at the response phase. The target-mask stimulus onset asynchrony (SOA) ranged from 13 to 93 ms. In comparison with CC-allele carriers, CT- and TT-allele carriers responded more accurately at the long SOA (93 ms) only during natural-scene categorization. In contrast, we observed no consistent association between CHRNA4 and the ANT, and no intertask correlation between scene categorization and the ANT. To validate our natural-scene categorization results, Experiment 2, carried out with an independent sample of 100 participants and a different stimulus set, successfully replicated the association between CHRNA4 genotypes and natural-scene categorization accuracy at long SOAs (67 and 93 ms). Our findings demonstrate, for the first time, that genetic variations in CHRNA4 can moderately contribute to individual differences in natural-scene categorization performance.	t	\N
23727710	Successful interactions between people are dependent on rapid recognition of social cues. We investigated whether head direction--a powerful social signal--is processed in the absence of conscious awareness. We used continuous flash interocular suppression to render stimuli invisible and compared the reaction time for face detection when faces were turned towards the viewer and turned slightly away. We found that faces turned towards the viewer break through suppression faster than faces that are turned away, regardless of eye direction. Our results suggest that detection of a face with attention directed at the viewer occurs even in the absence of awareness of that face. While previous work has demonstrated that stimuli that signal threat are processed without awareness, our data suggest that the social relevance of a face, defined more broadly, is evaluated in the absence of awareness.	t	\N
23734220	To understand why human sensitivity for complex objects is so low, we study how word identification combines eye and ear or parts of a word (features, letters, syllables). Our observers identify printed and spoken words presented concurrently or separately. When researchers measure threshold (energy of the faintest visible or audible signal) they may report either sensitivity (one over the human threshold) or efficiency (ratio of the best possible threshold to the human threshold). When the best possible algorithm identifies an object (like a word) in noise, its threshold is independent of how many parts the object has. But, with human observers, efficiency depends on the task. In some tasks, human observers combine parts efficiently, needing hardly more energy to identify an object with more parts. In other tasks, they combine inefficiently, needing energy nearly proportional to the number of parts, over a 60∶1 range. Whether presented to eye or ear, efficiency for detecting a short sinusoid (tone or grating) with few features is a substantial 20%, while efficiency for identifying a word with many features is merely 1%. Why? We show that the low human sensitivity for words is a cost of combining their many parts. We report a dichotomy between inefficient combining of adjacent features and efficient combining across senses. Joining our results with a survey of the cue-combination literature reveals that cues combine efficiently only if they are perceived as aspects of the same object. Observers give different names to adjacent letters in a word, and combine them inefficiently. Observers give the same name to a word's image and sound, and combine them efficiently. The brain's machinery optimally combines only cues that are perceived as originating from the same object. Presumably such cues each find their own way through the brain to arrive at the same object representation.	t	\N
23742322	This study tested the hypothesis that the reduced spatial release from speech-on-speech masking typically observed in listeners with sensorineural hearing loss results from increased energetic masking. Target sentences were presented simultaneously with a speech masker, and the spectral overlap between the pair (and hence the energetic masking) was systematically varied. The results are consistent with increased energetic masking in listeners with hearing loss that limits performance when listening in speech mixtures. However, listeners with hearing loss did not exhibit reduced spatial release from masking when stimuli were filtered into narrow bands.	t	\N
23742375	This study investigates the effectiveness of three high variability training paradigms in training 42 speakers of American English to correctly perceive and produce Spanish intervocalic /d, r, r/. Since Spanish spirantization and English flapping both affect /d/ intervocalically, the acquisition of the /d/-/r/ contrast proves difficult for English learners of Spanish. The acquisition of the trill /r/ is also problematic because it is a new phoneme for English learners and is articulatorily difficult to produce. Past research reported that high-variability perceptual training improves both perception and production [Bradlow et al., J. Acoust. Soc. Am. 101, 2299-2310 (1997); Wang et al., J. Acoust. Soc. Am. 113, 1033-1043 (2003)] and that production training improves both as well [Hirata, Comp. Assisted Lang. Learning 17, 357-376 (2004)]. However, trainees were able to listen to stimuli during production training, making it unclear whether production training alone transfers to perception. This study systematically controls both training modalities so they can be directly compared and introduces a third training methodology that includes both perception and production. All three training paradigms proved effective. While perception and production trainees primarily made gains in perception, combination trainees made gains in production. The effectiveness of each training modality depended on the nature of the contrast being trained and the modality of the test.	t	\N
23751862	We used magnetoencephalography (MEG) to localize brain activity related to the retention of tones differing in pitch. Participants retained one or two simultaneously presented tones. After a two second interval a test tone was presented and the task was to determine if that tone was in memory. We focused on brain activity during the retention interval that increased as the number of sounds retained in auditory short-term memory (ASTM) increased. Source analyses revealed that the superior temporal gyrus in both hemispheres is involved in ASTM. In the right hemisphere, the inferior temporal gyrus, the inferior frontal gyrus, and parietal structures also play a role. Our method provides good spatial and temporal resolution for investigating neuronal correlates of ASTM and, as it is the first MEG study using a memory load manipulation without using sequences of tones, it allowed us to isolate brain regions that most likely reflect the simple retention of tones.	t	\N
23751864	Neurobiological correlates of adaptation to spectrally degraded speech were investigated with fMRI before and after exposure to a portable real-time speech processor that implements an acoustic simulation model of a cochlear implant (CI). The speech processor, in conjunction with isolating insert earphones and a microphone to capture environment sounds, was worn by participants over a two week chronic exposure period. fMRI and behavioral speech comprehension testing were conducted before and after this two week period. After using the simulator each day for 2h, participants significantly improved in word and sentence recognition scores. fMRI shows that these improvements came accompanied by changes in patterns of neuronal activation. In particular, we found additional recruitment of visual, motor, and working memory areas after the perceptual training period. These findings suggest that the human brain is able to adapt in a short period of time to a degraded auditory signal under a natural learning environment, and gives insight on how a CI might interact with the central nervous system. This paradigm can be furthered to investigate neural correlates of new rehabilitation, training, and signal processing strategies non-invasively in normal hearing listeners to improve CI patient outcomes.	t	\N
23757047	Temporal orienting--that is, selective attention to instants in time--has been shown to modulate performance in terms of faster responses in a variety of paradigms. Electrophysiological recordings have shown that temporal orienting modulates neural processing at early, probably perceptual, and late, probably decision- or response-related, stages. Recently, it was shown that the effect of temporal orienting on early auditory brain potentials is independent of the effect of the physical sound feature intensity. This indicates that temporal orienting might not affect stimulus processing by increasing the sensory gain of attended stimuli. In the present study, we investigated whether the independence of temporal-orienting and sound-intensity effects could be replicated behaviorally. Sequences were presented that were either rhythmic, most likely creating temporal expectations, or arrhythmic, presumably not creating such expectations. As hypothesized, the main effects of temporal expectation and sound intensity on reaction times were independent (Experiment 1). The exact pattern of results was replicated with a slightly altered paradigm (Experiment 2) and with a different kind of task (Experiment 3). In sum, these results corroborate the notion that the effect of temporal orienting might not rely on the same processes as the effect of sound intensity does.	t	\N
23760984	The neural mechanisms of pitch coding have been debated for more than a century. The two main mechanisms are coding based on the profiles of neural firing rates across auditory nerve fibers with different characteristic frequencies (place-rate coding), and coding based on the phase-locked temporal pattern of neural firing (temporal coding). Phase locking precision can be partly assessed by recording the frequency-following response (FFR), a scalp-recorded electrophysiological response that reflects synchronous activity in subcortical neurons. Although features of the FFR have been widely used as indices of pitch coding acuity, only a handful of studies have directly investigated the relation between the FFR and behavioral pitch judgments. Furthermore, the contribution of degraded neural synchrony (as indexed by the FFR) to the pitch perception impairments of older listeners and those with hearing loss is not well known. Here, the relation between the FFR and pure-tone frequency discrimination was investigated in listeners with a wide range of ages and absolute thresholds, to assess the respective contributions of subcortical neural synchrony and other age-related and hearing loss-related mechanisms to frequency discrimination performance. FFR measures of neural synchrony and absolute thresholds independently contributed to frequency discrimination performance. Age alone, i.e., once the effect of subcortical neural synchrony measures or absolute thresholds had been partialed out, did not contribute to frequency discrimination. Overall, the results suggest that frequency discrimination of pure tones may depend both on phase locking precision and on separate mechanisms affected in hearing loss.	t	\N
23761928	In vision, humans use summary statistics (e.g., the average facial expression of a crowd) to efficiently perceive the gist of groups of features. Here, we present direct evidence that ensemble coding is also important for auditory processing. We found that listeners could accurately estimate the mean frequency of a set of logarithmically spaced pure tones presented in a temporal sequence (Experiment 1). Their performance was severely reduced when only a subset of tones from a given sequence was presented (Experiment 2), which demonstrates that ensemble coding is based on a substantial number of the tones in a sequence. This precise ensemble coding occurred despite very limited representation of individual tones from the sequence: Listeners were poor at identifying specific individual member tones (Experiment 3) and at determining their positions in the sequence (Experiment 4). Together, these results indicate that summary statistical coding is not limited to visual processing and is an important auditory mechanism for extracting ensemble frequency information from sequences of sounds.	t	\N
23769004	A 3-year longitudinal study was conducted to investigate changes in vocal quality as a result of singing training at a tertiary level conservatorium in Australia. Singers performed a messa di voce (MDV) at intervals of 6 months over the 3-year period of training. The study investigated the evolving acoustic features of the singers' voices exhibited during the MDV, including sound pressure level (SPL), short-term energy ratio (STER), duration, and vibrato parameters of the fundamental frequency (F0), SPL, and STER. The maximum SPL exhibited a marginal systematic increase over the training period, but the maximum STER did not systematically change. F0 vibrato extent increased significantly, whereas the extent of SPL and STER vibrato did not change significantly.	t	\N
23772828	Noise-induced hearing loss (NIHL) is the most reported occupational health disease in the Netherlands. The internet-based speech-in-noise test Earcheck (Albrecht et al, 2005; Leensen et al, 2011b) is designed to detect beginning NIHL and can be a valuable tool in occupational hearing health surveillance. The aim of this study is to investigate the validity of Earcheck compared to regular screening audiometry. Subjects performed online Earcheck tests at home. The results are compared to a pure-tone screening audiogram obtained during regular occupational health examination. A subgroup performed the measurements twice to assess test-retest reliability. Two hundred and forty-nine male construction employees who recently had a periodic occupational health examination participated. An average learning effect of -1.6 dB was found, that reduced with increasing test number. The test-retest variability was 1.6 dB. Sensitivity to detect beginning NIHL was 68%, with a specificity of 71%. Although sensitivity and specificity values are only moderate, the broad internet application still promises a valuable addition to current practice. The relatively high learning effect indicates that more reliable results can be obtained after a longer test session. When this is put into practice some improvement in sensitivity and specificity may be expected as well.	t	\N
23774181	A linguistic construction is typically viewed as encoding the pairing of syntactic form and semantic information that is independent of the meaning of constituent words. Here with the event-related potentials (ERPs) we demonstrate that such a construction can also encode pragmatic constraints (event likelihood) that immediately influence online sentence comprehension and the associated neural activity. The lian…dou…construction in Chinese (similar to even in English) normally describes an event of low expectedness (a semantic constraint); it also introduces a pragmatic scale implying that any event with a higher likelihood than the event described must occur (pragmatic inference). By embedding a highly likely event (a rich man buying a house) or an underspecified event (a man buying a house) in the construction, we created an incongruent condition and an underspecified condition and compared both with a control condition in which an event of low expectedness (a poor man buying a house) was described. ERPs on the main verb phrases showed an N400 with a maximum in the right hemisphere followed by a late negativity with an anterior maximum for both the incongruent and underspecified conditions, with a larger N400 effect for the former than for the latter. ERPs on the sentence-final phrases showed a sustained negativity for the incongruent, but not for the underspecified condition. The N400 effect may reflect the increased difficulty in unifying the current event into the lian…dou… construction. The late negativity may reflect a second-pass revision according to the likelihood scale to satisfy the pragmatic constraints of the construction.	t	\N
23786393	The purpose of this study was to test the ability to discriminate low-frequency pure-tone stimuli for ears with and without contralateral dead regions, in subjects with bilateral high-frequency hearing loss; we examined associations between hearing loss characteristics and frequency discrimination of low-frequency stimuli in subjects with high-frequency hearing loss. Cochlear dead regions were diagnosed using the TEN-HL test. A frequency discrimination test utilizing an adaptive three-alternative forced choice method provided difference limens for reference frequencies 0.25 kHz and 0.5 kHz. Among 105 subjects with bilateral high-frequency hearing loss, unilateral dead regions were found in 15 subjects. These, and an additional 15 matched control subjects without dead regions, were included in the study. Ears with dead regions performed best at the frequency discrimination test. Ears with a contralateral dead region performed significantly better than ears without a contralateral dead region at 0.5 kHz, the reference frequency closest to the mean audiogram cut-off, while the opposite result was obtained at 0.25 kHz. Results may be seen as sign of a contralateral effect of unilateral dead regions on the discrimination of stimuli with frequencies well below the audiogram cut-off in adult subjects with bilateral high-frequency hearing loss.	t	\N
23786439	Most theories of human language production assume that generating a sentence involves several stages, including an initial stage where the prelinguistic message is determined and a subsequent stage of grammatical encoding. However, it is contentious whether grammatical encoding involves separate stages of grammatical-function assignment and linearization. To address this question, we examined the mapping between the message level and grammatical encoding in two structural priming experiments in which German speakers choose between three different structures expressing ditransitive events. Although speakers showed a tendency to repeat the order of constituents (noun phrase-prepositional phrase, NP-PP, vs. NP-NP), they were additionally primed to repeat the order of thematic roles when constituent structure was constant (NPRECIPIENT-NPTHEME vs. NPTHEME-NPRECIPIENT). Experiment 2 found that the latter effect could not be due to persistence of the order of phrases referring to animate and inanimate entities. These results suggest a direct mapping of thematic roles to word order, consistent with a model in which the message is mapped onto syntactic structure in a single stage.	t	\N
23787044	Coordinating movements to music is often considered a uniquely human skill. A new study dispels this notion by showing that male Australian lyrebirds also perform 'dance' moves which are predictably matched with specific songs in their display routines.	t	\N
23789391	Auditory evoked response and mismatch negativity potential have been studied using the reversed odd-ball paradigm of standard and deviant stimulus presentation. In the experiments, three types of spatial sound stimuli (stationary and moving either gradually or abruptly from the head midline) were presented in three configurations. Each configuration employed one stimulus type as standard and the other two types as deviants. It was demonstrated that the configuration reversals influenced significantly the evoked response and mismatch negativity. The results obtained are discussed as the possible evidence of the categorical perception of auditory motion revealed at the earlier stages of sound processing in the hearing system.	t	\N
23789637	Pickering & Garrod (P&G) put forward the interesting idea that language production relies on forward modeling operating at multiple processing levels. The evidence currently available to substantiate this idea mostly concerns sensorimotor processes and not more abstract linguistic levels (e.g., syntax, semantics, phonology). The predictions that follow from the claim seem too general, in their current form, to guide specific empirical tests.	t	\N
23789872	We welcome the proposal to use forward models to understand predictive processes in language processing. However, Pickering & Garrod (P&G) miss the opportunity to provide a strong framework for future work. Forward models need to be pursued in the context of learning. This naturally leads to questions about what prediction error these models aim to minimize.	t	\N
23790043	Although the target article emphasizes the important role of prediction in language use, prediction may well also play a key role in the initial formation of linguistic representations, that is, in language development. We outline the role of prediction in three relevant language-learning domains: transitional probabilities, statistical preemption, and construction learning.	t	\N
23792078	Abundant evidence from both field and lab studies has established that conspecific vocalizations (CVs) are of critical ecological significance for a wide variety of species, including humans, non-human primates, rodents, and other mammals and birds. Correspondingly, a number of experiments have demonstrated behavioral processing advantages for CVs, such as in discrimination and memory tasks. Further, a wide range of experiments have described brain regions in many species that appear to be specialized for processing CVs. For example, several neural regions have been described in both mammals and birds wherein greater neural responses are elicited by CVs than by comparison stimuli such as heterospecific vocalizations, nonvocal complex sounds, and artificial stimuli. These observations raise the question of whether these regions reflect domain-specific neural mechanisms dedicated to processing CVs, or alternatively, if these regions reflect domain-general neural mechanisms for representing complex sounds of learned significance. Inasmuch as CVs can be viewed as complex combinations of basic spectrotemporal features, the plausibility of the latter position is supported by a large body of literature describing modulated cortical and subcortical representation of a variety of acoustic features that have been experimentally associated with stimuli of natural behavioral significance (such as food rewards). Herein, we review a relatively small body of existing literature describing the roles of experience, learning, and memory in the emergence of species-typical neural representations of CVs and auditory system plasticity. In both songbirds and mammals, manipulations of auditory experience as well as specific learning paradigms are shown to modulate neural responses evoked by CVs, either in terms of overall firing rate or temporal firing patterns. In some cases, CV-sensitive neural regions gradually acquire representation of non-CV stimuli with which subjects have training and experience. These results parallel literature in humans describing modulation of responses in face-sensitive neural regions through learning and experience. Thus, although many questions remain, the available evidence is consistent with the notion that CVs may acquire distinct neural representation through domain-general mechanisms for representing complex auditory objects that are of learned importance to the animal. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives".	t	\N
23792769	This event-related potential (ERP) study examines the time course of context-dependent talker normalization in spoken word identification. We found three ERP components, the N1 (100-220 ms), the N400 (250-500 ms) and the Late Positive Component (500-800 ms), which are conjectured to involve (a) auditory processing, (b) talker normalization and lexical retrieval, and (c) decisional process/lexical selection respectively. Talker normalization likely occurs in the time window of the N400 and overlaps with the lexical retrieval process. Compared with the nonspeech context, the speech contexts, no matter whether they have semantic content or not, enable listeners to tune to a talker's pitch range. In this way, speech contexts induce more efficient talker normalization during the activation of potential lexical candidates and lead to more accurate selection of the intended word in spoken word identification.	t	\N
23809517	Cochlear implantation has significant effects on language abilities and reading skills. The current study compared the reading performance of children with cochlear implants with that of typically developing children in second and third grades. This descriptive-analytic study was performed including 24 children with cochlear implants and 24 typically developing peers. The grade range of the participants was second and third grades. All of students were selected from Tehran city elementary schools. The reading performance of children was assessed by the "Nama" reading test. The results showed that the means of reading scores of typically developed children were significantly greater than the children with cochlear implants (P < 0.01) and there was a significant relationship between reading skills and age of surgery (P < 0.05). Also, there was a significant relationship between reading skills and the period of cochlear implantation (P < 0.05). Children with cochlear implants showed a weak performance in reading skills in comparison to typically developing children due to lower accessibility to phonological information. However, this limitation can be compensated for partly by early surgery. Parents should refer their deaf children for cochlear implantation before the age of language learning.	t	\N
23815480	The origin of the Western preference for consonance remains unresolved, with some suggesting that the preference is innate. In Experiments 1 and 2 of the present study, 6-month-old infants heard six different consonant/dissonant pairs of stimuli, including those tested in previous research. In contrast to the findings of others, infants in the present study failed to listen longer to consonant stimuli. After 3 minutes of exposure to consonant or dissonant stimuli in Experiment 3, 6-month-old infants listened longer to the familiar stimulus, whether consonant or dissonant. Our findings are inconsistent with innate preferences for consonant stimuli. Instead, the effect of short-term exposure is consistent with the view that familiarity underlies the origin of the Western preference for consonant intervals.	t	\N
23819616	In an earlier study ( Beach et al, 2012 ), detailed noise exposure measurements were obtained through individual dosimetry. In this further analysis of the data we ask the question "Can the effort required to converse in noise be used to estimate the experienced A-weighted noise level?" The noise levels experienced during specific activities were obtained from the analysis of dosimetry results from personal noise exposure meters worn by study participants. The measured noise levels from particular events were compared to a subjectively judged 'loudness rating' reported by the person wearing the dosimeter during the measured event. Volunteers (females = 20, males = 22) between 18 and 35 years (average age = 26.8) willing to wear dosimeters and keep a simple activity log. The relation between the objectively measured and the subjectively judged levels was consistent for the group over a large number of events. The subjective loudness rating index was shown to be a convenient tool that can be utilized for the retrospective estimation of noise levels from individual activities.	t	\N
23824440	In this study, the authors examined the effects of aging and residual hearing on the identification of acoustically similar and dissimilar vowels in adults with postlingual deafness who use hearing aids (HAs) and/or cochlear implants (CIs). The authors used two groups of acoustically similar and dissimilar vowels to assess vowel identification. Also, the Consonant-Nucleus-Consonant Word Recognition Test (Peterson & Lehiste, 1962) and sentences from the Hearing in Noise Test (Nilsson, Soli, & Sullivan, 1994) were administered. Forty CI recipients with postlingual deafness (ages 31-81 years) participated in the study. Acoustically similar vowels were more difficult to identify than acoustically dissimilar vowels. With increasing age, performance deteriorated when identifying acoustically similar vowels. Vowel identification was also affected by the use of a contralateral HA and the degree of residual hearing prior to implantation. Moderate correlations were found between speech perception and vowel identification performance. Identification performance was affected by the acoustic similarity of the vowels. Older adults experienced more difficulty identifying acoustically similar confusable vowels than did younger adults. The findings might lend support to the ease of language understanding model (Ronnberg, Rudner, Foo, & Lunner, 2008), which proposes that the quality and perceptual robustness of acoustic input affects speech perception.	t	\N
23833281	The relations of phonological, orthographic, and morphological awareness and vocabulary to word reading and spelling were examined for 304 first-grade children who were receiving differentiated instruction in a Response to Intervention (RtI) model of instruction. First-grade children were assessed on their phonological, orthographic, and morphological awareness; expressive vocabulary; word reading; and spelling. Year-end word reading and spelling were outcome variables, and phonological, orthographic, and morphological awareness; expressive vocabulary; and RtI status (Tiers 1, 2, & 3) were predictor variables. The 3 linguistic awareness skills were unique predictors of word reading, and phonological and orthographic awareness were unique predictors of spelling. The contributions that these linguistic awareness skills and vocabulary made to word reading and spelling did not differ by children's RtI tier status. These results, in conjunction with previous studies, suggest that even beginning readers and spellers draw on multiple linguistic awareness skills for their word reading and spelling regardless of their level of literacy abilities. Educational implications are discussed.	t	\N
23833989	To investigate hidden hearing loss in tinnitus patients with normal audiograms by means of auditory brainstem response (ABR) and explore the origin of tinnitus. Pure tone thresholds, ABR thresholds, amplitude of wave I and wave V of ABR were analyzed in 40 tinnitus patients and 15 controls. There was no significantly difference in pure tone thresholds and ABR thresholds between those tinnitus patients and controls while a reduced amplitude of wave I and normal amplitude of wave V of ABR in the tinnitus patients became evident. Tinnitus patients with normal audiograms have hidden hearing loss at the level of primary auditory nerve and the generation of tinnitus is likely attributed to a homeostatic response of neurons in brainstem.	t	\N
23846434	CHENFIT-AMP is a novel nonlinear strategy that combines the fitting (gain prescription) and amplification (gain implementation) procedures for cochlear hearing loss. The fitting part of CHENFIT-AMP prescribes gain for outer hair cell (OHC) and inner hair cell (IHC) loss, respectively. The gain for OHC loss varies with the cochlear gain decided by the value of OHC loss and the input level. The gain for IHC loss varies with the value of IHC loss only and will be limited to a constant if there is a "dead region." The amplification part of CHENFIT-AMP is responsible for estimating the input level and cochlear gain based on Chen's loudness model. CHENFIT-AMP is evaluated with four typical audiograms and nine individual audiograms. A widely used nonlinear fitting procedure, NAL-NL2, is evaluated to compare prescription results with CHENFIT-AMP; a standard nonlinear amplification algorithm, multichannel compression (MCC), with the parameters provided by NAL-NL2, is also evaluated to compare amplification results with CHENFIT-AMP. For long-term average speech spectrum (LTASS) inputs, CHENFIT-AMP generally prescribes similar gain as NAL-NL2 for the typical audiograms; however, gain prescribed by CHENFIT-AMP is more individualized than NAL-NL2 for the individual audiograms, especially when the audiograms have big deviations in the slope. For LTASS-shaped noise input, the gain implemented by MCC with parameters provided by NAL-NL2 cannot completely realize the gain prescribed by NAL-NL2. For speech sentence inputs, average ratings by subjects indicated that amplification by CHENFIT-AMP was preferred and led to a louder perception than that by MCC with parameters from NAL-NL2.	t	\N
23846719	Inner speech is one of the most common, but least investigated, mental activities humans perform. It is an internal copy of one's external voice and so is similar to a well-established component of motor control: corollary discharge. Corollary discharge is a prediction of the sound of one's voice generated by the motor system. This prediction is normally used to filter self-caused sounds from perception, which segregates them from externally caused sounds and prevents the sensory confusion that would otherwise result. The similarity between inner speech and corollary discharge motivates the theory, tested here, that corollary discharge provides the sensory content of inner speech. The results reported here show that inner speech attenuates the impact of external sounds. This attenuation was measured using a context effect (an influence of contextual speech sounds on the perception of subsequent speech sounds), which weakens in the presence of speech imagery that matches the context sound. Results from a control experiment demonstrated this weakening in external speech as well. Such sensory attenuation is a hallmark of corollary discharge.	t	\N
23847464	Evaluating series of complex sounds like those in speech and music requires sequential comparisons to extract task-relevant relations between subsequent sounds. With the present functional magnetic resonance imaging (fMRI) study, we investigated whether sequential comparison of a specific acoustic feature within pairs of tones leads to a change in lateralized processing in the auditory cortex (AC) of humans. For this we used the active categorization of the direction (up vs. down) of slow frequency modulated (FM) tones. Several studies suggest that this task is mainly processed in the right AC. These studies, however, tested only the categorization of the FM direction of each individual tone. In the present study we ask the question whether the right lateralized processing changes when, in addition, the FM direction is compared within pairs of successive tones. For this we use an experimental approach involving contralateral noise presentation in order to explore the contributions made by the left and right AC in the completion of the auditory task. This method has already been applied to confirm the right-lateralized processing of the FM direction of individual tones. In the present study, the subjects were required to perform, in addition, a sequential comparison of the FM direction in pairs of tones. The results suggest a division of labor between the two hemispheres such that the FM direction of each individual tone is mainly processed in the right AC whereas the sequential comparison of this feature between tones in a pair is probably performed in the left AC.	t	\N
23850664	Over the last four decades, a range of different neuroimaging tools have been used to study human auditory attention, spanning from classic event-related potential studies using electroencephalography to modern multimodal imaging approaches (e.g., combining anatomical information based on magnetic resonance imaging with magneto- and electroencephalography). This review begins by exploring the different strengths and limitations inherent to different neuroimaging methods, and then outlines some common behavioral paradigms that have been adopted to study auditory attention. We argue that in order to design a neuroimaging experiment that produces interpretable, unambiguous results, the experimenter must not only have a deep appreciation of the imaging technique employed, but also a sophisticated understanding of perception and behavior. Only with the proper caveats in mind can one begin to infer how the cortex supports a human in solving the "cocktail party" problem. This article is part of a Special Issue entitled Human Auditory Neuroimaging.	t	\N
23855264	Accurate tuning is an important aspect of singing in harmony in the context of a choir or vocal ensemble. Tuning and 'pitch drift' are concerning factors in performance for even the most accomplished professional choirs when singing a cappella (unaccompanied). In less experienced choirs tuning often lacks precision, typically because individual singers have not developed appropriate listening skills. In order to investigate accuracy of tuning in ensemble singing situations, a chorally appropriate reference is required against which frequency measurements can be made. Since most basic choral singing involves chords in four parts, a four-part reference template is used in which the fundamental frequencies of the notes in each chord can be accurately set. This template can now be used in experiments where three of the reference parts are tuned in any musical temperament (tuning system), in this case equal and just temperaments, and played over headphones to a singer to allow her/his tuning strategy to be investigated. This paper describes a practical implementation of a four-part choral synthesis system in Pure Data (Pd) and its use in an investigation of tuning of notes by individual singers using an exercise originally written to explore pitch drift in a cappella choral singing.	t	\N
23859060	To examine the relationship between portable digital audio player listening behaviours and (1) measured sound pressure levels, (2) audiometric measures, (3) self-reported hearing loss symptoms. A questionnaire to evaluate listening behaviours, including self-reported hearing loss symptoms and listening duration/volume settings. Multivariate regression analysis was used to determine the relationship between these variables, audiometric evaluation, calculated exposure levels, Lex(8hr), and measured sound pressure levels, Leq(32sec). This study included 103 males and 134 female subjects aged 10 to 17 years. Calculated Lex(8hr) and measured Leq(32sec) levels increased with age and self-reported usage time. Audiometric thresholds averaged over 4 and 8 kHz were higher when usage exceeded five years as compared to less than one year. Higher measured sound pressure levels were associated with worse audiometric thresholds at (0.5, 1, 2 kHz, averaged) and 4 kHz. Self-reported hearing loss symptoms were reported by 33% to 50% of subjects. In this cohort sample, our results support a statistical association between hearing acuity and (1) Self-reported weekly usage in hours; (2) Tightness of fit; (3) Years of usage; and (4) Measured sound pressure levels. Generalizing these results beyond the current sample would require additional research.	t	\N
23862816	Tone-in-noise detection has been studied for decades; however, it is not completely understood what cue or cues are used by listeners for this task. Model predictions based on energy in the critical band are generally more successful than those based on temporal cues, except when the energy cue is not available. Nevertheless, neither energy nor temporal cues can explain the predictable variance for all listeners. In this study, it was hypothesized that better predictions of listeners' detection performance could be obtained using a nonlinear combination of energy and temporal cues, even when the energy cue was not available. The combination of different cues was achieved using the logarithmic likelihood-ratio test (LRT), an optimal detector in signal detection theory. A nonlinear LRT-based combination of cues was proposed, given that the cues have Gaussian distributions and the covariance matrices of cue values from noise-alone and tone-plus-noise conditions are different. Predictions of listeners' detection performance for three different sets of reproducible noises were computed with the proposed model. Results showed that predictions for hit rates approached the predictable variance for all three datasets, even when an energy cue was not available.	t	\N
23862818	A number of precedence-effect models have been developed to simulate the robust localization performance of humans in reverberant conditions. Although they are able to reduce reverberant information for many conditions, they tend to fail for ongoing stimuli with truncated on/offsets, a condition human listeners master when localizing a sound source in the presence of a reflection, according to a study by Dizon and Colburn [J. Acoust. Soc. Am. 119, 2947-2964 (2006)]. This paper presents a solution for this condition by using an autocorrelation mechanism to estimate the delay and amplitude ratio between the leading and lagging signals. An inverse filter is then used to eliminate the lag signal, before it is localized with a standard localization algorithm. The current algorithm can operate on top of a basic model of the auditory periphery (gammatone filter bank, half-wave rectification) to simulate psychoacoustic data by Braasch et al. [Acoust. Sci. Tech. 24, 293-303 (2003)] and Dizon and Colburn. The model performs robustly with these on/offset truncated and interaural level difference based stimuli and is able to demonstrate the Haas effect.	t	\N
23862821	In noise repetition-detection tasks, listeners have to distinguish trials of continuously running noise from trials in which noise tokens are repeated in a cyclic manner. Recently, it has been shown that using the exact same noise token across several trials ("reference noise") facilitates the detection of repetitions for this token [Agus et al. (2010). Neuron 66, 610-618]. This was attributed to perceptual learning. Here, the nature of the learning was investigated. In experiment 1, reference noise tokens were embedded in trials with or without cyclic presentation. Naïve listeners reported repetitions in both cases, thus responding to the reference noise even in the absence of an actual repetition. Experiment 2, with the same listeners, showed a similar pattern of results even after the design of the experiment was made explicit, ruling out a misunderstanding of the task. Finally, in experiment 3, listeners reported repetitions in trials containing the reference noise, even before ever hearing it presented cyclically. The results show that listeners were able to learn and recognize noise tokens in the absence of an immediate repetition. Moreover, the learning mandatorily interfered with listeners' ability to detect repetitions. It is concluded that salient perceptual changes accompany the learning of noise.	t	\N
23862833	Effective communication between staff members is key to patient safety in hospitals. A variety of patient care activities including admittance, evaluation, and treatment rely on oral communication. Surprisingly, published information on speech intelligibility in hospitals is extremely limited. In this study, speech intelligibility measurements and occupant evaluations were conducted in 20 units of five different U.S. hospitals. A variety of unit types and locations were studied. Results show that overall, no unit had "good" intelligibility based on the speech intelligibility index (SII > 0.75) and several locations found to have "poor" intelligibility (SII < 0.45). Further, occupied spaces were found to have 10%-15% lower SII than unoccupied spaces on average. Additionally, staff perception of communication problems at nurse stations was significantly correlated with SII ratings. In a targeted second phase, a unit treated with sound absorption had higher SII ratings for a larger percentage of time as compared to an identical untreated unit. Taken as a whole, the study provides an extensive baseline evaluation of speech intelligibility across a variety of hospitals and unit types, offers some evidence of the positive impact of absorption on intelligibility, and identifies areas for future research.	t	\N
23862901	Categorical perception experiments were performed on an English /b-p/ voice onset time (VOT) continuum with native (American English) and non-native (Korean) listeners to examine whether and how phonetic categorization is modulated by prosodic boundary and language experience. Results demonstrated perceptual shifting according to prosodic boundary strength: A longer VOT was required to identify a sound as /p/ after an intonational phrase than a word boundary, regardless of the listeners' language experience. This suggests that segmental perception is modulated by the listeners' computation of an abstract prosodic structure reflected in phonetic cues of phrase-final lengthening and domain-initial strengthening, which are common across languages.	t	\N
23862903	A previous report [Margolis and Stiepan (2012). "Acoustic method for calibration of audiometric bone vibrators," J. Acoust. Soc. Am. 131, 1221-1225] described a reliable, inexpensive, acoustic method for calibration of audiometric bone vibrators. As a follow up to that report harmonic distortion measurements were made with the standard electromechanical method and the acoustic method using five Radioear B71 vibrators and one Radioear B81 prototype vibrator. Lower distortion was seen for measurements made with the acoustic method compared to the electromechanical method and for the Radioear B81 vibrator compared to the Radioear B71 vibrator.	t	\N
23865332	Masking therapy can make patients accustom to tinnitus. This therapy is safe and easy to implement, so that it has become a widely used treatment of curing tinnitus. According to surveys of tinnitus sounds, cicada sound is one of the most usual tinnituses. Meanwhile, we have not hitherto found published papers concerning how to synthesize cicada sound and to use it to ameliorate tinnitus. Inspired by the human acoustics theory, we proposed a method to synthesize medical masking sound and to realize the diversity by illustrating the process of synthesizing various cicada sounds. In addition, energy attenuation problem in spectrum shifting process has been successfully solved. Simulation results indicated that the proposed method achieved decent results and would have practical value for the future applications.	t	\N
23867553	We study the developmental trajectory of morphology and function of the superior temporal cortex (STC) in children (8-9 years), adolescents (14-15 years) and young adults. We analyze cortical surface landmarks and functional MRI (fMRI) responses to voices, other natural categories and tones and examine how hemispheric asymmetry and inter-subject variability change across age. Our results show stable morphological asymmetries across age groups, including a larger left planum temporale and a deeper right superior temporal sulcus. fMRI analyses show that a rightward lateralization for voice-selective responses is present in all groups but decreases with age. Furthermore, STC responses to voices change from being less selective and more spatially diffuse in children to highly selective and focal in adults. Interestingly, the analysis of morphological landmarks reveals that inter-subject variability increases during development in the right--but not in the left--STC. Similarly, inter-subject variability of cortically-realigned functional responses to voices, other categories and tones increases with age in the right STC. Our findings reveal asymmetric developmental changes in brain regions crucial for auditory and voice perception. The age-related increase of inter-subject variability in right STC suggests that anatomy and function of this region are shaped by unique individual developmental experiences.	t	\N
23882002	To determine the relative importance of acoustic parameters (fundamental frequency [F0], formant frequencies [FFs], aperiodicity, and spectrum level [SL]) on voice gender perception, the authors used a novel parameter-morphing approach that, unlike spectral envelope shifting, allows the application of nonuniform scale factors to transform formants and more direct comparison of parameter impact. In each of 2 experiments, 16 listeners with normal hearing (8 female, 8 male) classified voice gender for morphs between female and male speakers, using syllable tokens from 2 male-female speaker pairs. Morphs varied single acoustic parameters (Experiment 1) or selected combinations (Experiment 2), keeping residual parameters androgynous, as determined in a baseline experiment. The strongest cue related to gender perception was F0, followed by FF and SL. Aperiodicity did not systematically influence gender perception. Morphing F0 and FF in conjunction produced convincing changes in perceived gender-changes that were equivalent to those for Full morphs interpolating all parameters. Despite the importance of F0, morphing FF and SL in combination produced effective changes in voice gender perception. The most important single parameters for gender perception are, in order, F0, FF, and SL. At the same time, F0 and vocal tract resonances have a comparable impact on voice gender perception.	t	\N
23883861	The observation that near-threshold low-contrast visual distractors can equally influence perceptual state and goal-directed motor responses was recently taken as an argument against a sharp separation between a conscious vision for perception and an unconscious vision for action. However, data supporting the dual visual system theory have principally involved high-contrast stimuli. In the present study, we assessed the effect of varying the contrast of a near-threshold visual distractor while keeping its visibility constant with backward noise masks. Eight participants performed fast manual reaching movements toward a highly visible target while subsequently reporting the presence/absence of a near-threshold distractor appearing at the opposite location with respect to the body midline. For all distractor contrasts, hand trajectory deviations toward the distractor were observed when the distractor was present and detected. When the distractor remained undetected deviations also occurred, but for higher contrasts. The subliminal motor effect traditionally observed in visual masking studies may therefore primarily depend on the luminance contrast of the interfering stimuli. These results suggest that dissociations between perceptual and motor responses can be explained by a single-signal model involving differential thresholds for perception and action that are specifically modulated as a function of both the requirements of the task and the contrast level of the stimuli. Such modulation is compatible with neurophysiological accounts of visual masking in which feedforward activation to--and feedback activation from--higher visual areas are correlated with the actual presence of the stimulation and its conscious perception, respectively.	t	\N
23902521	This study investigated the effect of electrode configuration, stimulus rate, and EEG rejection level on the efficiency of ABR testing in babies. ABR to click stimuli at 40 dB nHL were simultaneously recorded from two electrode configurations, ipsilateral mastoid to high forehead (Mi-Fh) and nape to high forehead (N-Fh), with two EEG rejection levels (± 5 μV and ± 10 μV). Stimulus rates were between 39.1 and 69.1 per second. Efficiency was measured by confidence in the ABR for a given test time. Thirty babies who had passed a targeted newborn hearing screen with ABR thresholds ≤ 40 dB nHL. The N-Fh configuration, as expected, gave on average a larger response amplitude compared to the Mi-Fh configuration but was only marginally significantly better in terms of test efficiency. There was no significant effect of stimulus rate on test efficiency between 39.1/s and 59.1/s. The lower ± 5 μV EEG rejection level was more test efficient. This study provides some evidence that, for ABR threshold testing in babies, alternatives of ipsilateral mastoid or nape electrode and a range of stimulus rates have little or no effect on test efficiency. The results support the use of low EEG rejection limits.	t	\N
23915050	In everyday listening situations, we need to constantly switch between alternative sound sources and engage attention according to cues that match our goals and expectations. The exact neuronal bases of these processes are poorly understood. We investigated oscillatory brain networks controlling auditory attention using cortically constrained fMRI-weighted magnetoencephalography/EEG source estimates. During consecutive trials, participants were instructed to shift attention based on a cue, presented in the ear where a target was likely to follow. To promote audiospatial attention effects, the targets were embedded in streams of dichotically presented standard tones. Occasionally, an unexpected novel sound occurred opposite to the cued ear to trigger involuntary orienting. According to our cortical power correlation analyses, increased frontoparietal/temporal 30-100 Hz gamma activity at 200-1400 msec after cued orienting predicted fast and accurate discrimination of subsequent targets. This sustained correlation effect, possibly reflecting voluntary engagement of attention after the initial cue-driven orienting, spread from the TPJ, anterior insula, and inferior frontal cortices to the right FEFs. Engagement of attention to one ear resulted in a significantly stronger increase of 7.5-15 Hz alpha in the ipsilateral than contralateral parieto-occipital cortices 200-600 msec after the cue onset, possibly reflecting cross-modal modulation of the dorsal visual pathway during audiospatial attention. Comparisons of cortical power patterns also revealed significant increases of sustained right medial frontal cortex theta power, right dorsolateral pFC and anterior insula/inferior frontal cortex beta power, and medial parietal cortex and posterior cingulate cortex gamma activity after cued versus novelty-triggered orienting (600-1400 msec). Our results reveal sustained oscillatory patterns associated with voluntary engagement of auditory spatial attention, with the frontoparietal and temporal gamma increases being best predictors of subsequent behavioral performance.	t	\N
23920156	The current study investigated the role of resumption in the interpretation of object relative clauses (RCs) in Persian-speaking children. Sixty-four (N=64) children aged 3;2-6;0 (M=4;8) completed a referent selection task that tested their comprehension of subject RCs, gapped object RCs, and object RCs containing either a resumptive pronoun or an object clitic. The results showed that the presence of a resumptive element (pronoun or clitic) had a facilitative effect on children's processing of object RCs. In both cases object RCs with resumptive elements were interpreted more accurately than gapped subject and object RCs, suggesting that resumptive elements ease processing burden in syntactically complex contexts because they provide local cues to thematic role assignment.	t	\N
23926291	Previously, Gygi and Shafiro (2011) found that when environmental sounds are semantically incongruent with the background scene (e.g., horse galloping in a restaurant), they can be identified more accurately by young normal-hearing listeners (YNH) than sounds congruent with the scene (e.g., horse galloping at a racetrack). This study investigated how age and high-frequency audibility affect this Incongruency Advantage (IA) effect. In Experiments 1a and 1b, elderly listeners ( N = 18 for 1a; N = 10 for 1b) with age-appropriate hearing (EAH) were tested on target sounds and auditory scenes in 5 sound-to-scene ratios (So/Sc) between -3 and -18 dB. Experiment 2 tested 11 YNH on the same sound-scene pairings lowpass-filtered at 4 kHz (YNH-4k). The EAH and YNH-4k groups exhibited an almost identical pattern of significant IA effects, but both were at approximately 3.9 dB higher So/Sc than the previously tested YNH listeners. However, the psychometric functions revealed a shallower slope for EAH listeners compared with YNH listeners for the congruent stimuli only, suggesting a greater difficulty for the EAH listeners in attending to sounds expected to occur in a scene. These findings indicate that semantic relationships between environmental sounds in soundscapes are mediated by both audibility and cognitive factors and suggest a method for dissociating these factors.	t	\N
23927115	Laback et al. [(2011). J. Acoust. Soc. Am. 129, 888-897] investigated the additivity of nonsimultaneous masking using short Gaussian-shaped tones as maskers and target. The present study involved Gaussian stimuli to measure the additivity of simultaneous masking for combinations of up to four spectrally separated maskers. According to most basilar membrane measurements, the maskers should be processed linearly at the characteristic frequency (CF) of the target. Assuming also compression of the target, all masker combinations should produce excess masking (exceeding linear additivity). The results for a pair of maskers flanking the target indeed showed excess masking. The amount of excess masking could be predicted by a model assuming summation of masker-evoked excitations in intensity units at the target CF and compression of the target, using compressive input/output functions derived from the nonsimultaneous masking study. However, the combinations of lower-frequency maskers showed much less excess masking than predicted by the model. This cannot easily be attributed to factors like off-frequency listening, combination tone perception, or between-masker suppression. It was better predicted, however, by assuming weighted intensity summation of masker excitations. The optimum weights for the lower-frequency maskers were smaller than one, consistent with partial masker compression as indicated by recent psychoacoustic data.	t	\N
23927133	Much recent interest surrounds listeners' abilities to adapt to various transformations that distort speech. An extreme example is spectral rotation, in which the spectrum of low-pass filtered speech is inverted around a center frequency (2 kHz here). Spectral shape and its dynamics are completely altered, rendering speech virtually unintelligible initially. However, intonation, rhythm, and contrasts in periodicity and aperiodicity are largely unaffected. Four normal hearing adults underwent 6 h of training with spectrally-rotated speech using Continuous Discourse Tracking. They and an untrained control group completed pre- and post-training speech perception tests, for which talkers differed from the training talker. Significantly improved recognition of spectrally-rotated sentences was observed for trained, but not untrained, participants. However, there were no significant improvements in the identification of medial vowels in /bVd/ syllables or intervocalic consonants. Additional tests were performed with speech materials manipulated so as to isolate the contribution of various speech features. These showed that preserving intonational contrasts did not contribute to the comprehension of spectrally-rotated speech after training, and suggested that improvements involved adaptation to altered spectral shape and dynamics, rather than just learning to focus on speech features relatively unaffected by the transformation.	t	\N
23933145	Prepulse inhibition (PPI) of startle is a measure of inhibitory function in which a weak leading stimulus suppresses the startle response to an intense stimulus. Usually, startle blink reflexes to an intense sound are used for measuring PPI. A recent magnetoencephalographic study showed that a similar phenomenon is observed for auditory change-related cortical response (Change-N1m) to an abrupt change in sound features. It has been well established that nicotine enhances PPI of startle. Therefore, in the present magnetoencephalographic study, the effects of acute nicotine on PPI of the Change-N1m were studied in 12 healthy subjects (two females and 10 males) under a repeated measures and placebo-controlled design. Nicotine (4 mg) was given as nicotine gum. The test Change-N1m response was elicited with an abrupt increase in sound pressure by 6 dB in a continuous background sound of 65 dB. PPI was produced by an insertion of a prepulse with a 3-dB-louder or 6-dB-weaker sound pressure than the background 75 ms before the test stimulus. Results show that nicotine tended to enhance the test Change-N1m response and significantly enhanced PPI for both prepulses. Therefore, nicotine's enhancing effect on PPI of the Change-N1m was similar to that on PPI of the startle. The present results suggest that the two measures share at least some mechanisms.	t	\N
23973563	The physical intensity of a sound, usually expressed in dB on a logarithmic ratio scale, can easily be measured using technical equipment. Loudness is the perceptual correlate of sound intensity, and is usually determined by means of some sort of psychophysical scaling procedure. The interrelation of sound intensity and perceived loudness is still a matter of debate, and the physiological correlate of loudness perception in the human auditory pathway is not completely understood. Various studies indicate that the activation in human auditory cortex is more a representation of loudness sensation rather than of physical sound pressure level. This raises the questions (1), at what stage or stages in the ascending auditory pathway is the transformation of the physical stimulus into its perceptual correlate completed, and (2), to what extent other factors affecting individual loudness judgements might modulate the brain activation as registered by auditory neuroimaging. An overview is given about recent studies on the effects of sound intensity, duration, bandwidth and individual hearing status on the activation in the human auditory system, as measured by various approaches in auditory neuroimaging. This article is part of a Special Issue entitled Human Auditory Neuroimaging.	t	\N
23974947	Tonal music is characterized by a continuous flow of tension and resolution. This flow of tension and resolution is closely related to processes of expectancy and prediction and is a key mediator of music-evoked emotions. However, the neural correlates of subjectively experienced tension and resolution have not yet been investigated. We acquired continuous ratings of musical tension for four piano pieces. In a subsequent functional magnetic resonance imaging experiment, we identified blood oxygen level-dependent signal increases related to musical tension in the left lateral orbitofrontal cortex (pars orbitalis of the inferior frontal gyrus). In addition, a region of interest analysis in bilateral amygdala showed activation in the right superficial amygdala during periods of increasing tension (compared with decreasing tension). This is the first neuroimaging study investigating the time-varying changes of the emotional experience of musical tension, revealing brain activity in key areas of affective processing.	t	\N
23990061	We aim to evaluate the incidence and clinical manifestations of sensorineural hearing loss (SNHL) in adult patients with acute otitis media (AOM). Seventy-five patients (age > 18 years; 83 ears) diagnosed with AOM between January 2008 and March 2011 at our clinic were enroled and retrospectively reviewed. We detected audiometrically confirmed SNHL during the course of AOM in eight patients. The clinical course, treatment, and audiometric final outcome of each case were reviewed. SNHL was associated with AOM in 8 out of 83 ears (9.3%). The mean age of patients was 57.5 years, and the mean follow-up period was 21.1 months (range 0.6-46.3 months). The most common symptom was tinnitus. Mean bone conduction hearing threshold was 39.5 dB in pure tone audiometry. All patients showed high-frequency HL, and three showed pan-frequency HL. All patients were treated with oral antibiotics at the initial visit. Seven ears were treated with a combination of oral steroids. Myringotomy was also performed. Seven of eight patients showed improvement; however, 8 kHz thresholds were not improved. This suggested that the inflammation spread through the round window. The mean duration of recovery was 18.6 days. SNHL associated with AOM in adult patients occurs during the early phases of the disease course. High-frequency hearing was commonly affected and was well treated with oral antibiotics, myringotomy, and steroid therapy. Audiometry can be helpful for treating adult patients with AOM. Active treatment, including myringotomy, should be performed during the early phase, if SNHL is suspected.	t	\N
23992133	The development of presbycusis, or age-related hearing loss, is determined by a combination of genetic and environmental factors. The auditory periphery exhibits a progressive bilateral, symmetrical reduction of auditory sensitivity to sound from high to low frequencies. The central auditory nervous system shows symptoms of decline in age-related cognitive abilities, including difficulties in speech discrimination and reduced central auditory processing, ultimately resulting in auditory perceptual abnormalities. The pathophysiological mechanisms of presbycusis include excitotoxicity, oxidative stress, inflammation, aging and oxidative stress-induced DNA damage that results in apoptosis in the auditory pathway. However, the originating signals that trigger these mechanisms remain unclear. For instance, it is still unknown whether insulin is involved in auditory aging. Auditory aging has preclinical lesions, which manifest as asymptomatic loss of periphery auditory nerves and changes in the plasticity of the central auditory nervous system. Currently, the diagnosis of preclinical, reversible lesions depends on the detection of auditory impairment by functional imaging, and the identification of physiological and molecular biological markers. However, despite recent improvements in the application of these markers, they remain under-utilized in clinical practice. The application of antisenescent approaches to the prevention of auditory aging has produced inconsistent results. Future research will focus on the identification of markers for the diagnosis of preclinical auditory aging and the development of effective interventions.	t	\N
23992488	The state of hearing in 75-year old persons was measured in a population based epidemiological study with the aim of studying if hearing had changed during a time span of 29 years. An epidemiological study of generational effects in three age cohorts. Three age cohorts were included: cohort 1 (n: 267) born in 1976-77, cohort 4 (n: 197) in 1990-91, and cohort 6 (n: 570) in 2005. The same test procedures using pure-tone audiometry and a short questionnaire were applied to the three cohorts of 75-year old residents in the same city. The hearing was essentially unchanged during the span of the investigation-almost three decades. Low-frequency hearing was up to about 10 dB poorer in the most recently studied cohort compared to the previously studied cohorts. The reason for this difference is considered to depend on methodological factors. Self-assessed hearing and tinnitus was mainly unchanged, or had minor changes both to the better and to the worse. The hearing, both measured with pure-tone audiometry and with a short questionnaire, of 75-year old persons has not changed at all, or only marginally, over three decades.	t	\N
23994183	Speech comprehension relies on auditory as well as visual information, and is enhanced in healthy subjects, when audiovisual (AV) information is present. Patients with schizophrenia have been reported to have problems regarding this AV integration process, but little is known about which underlying neural processes are altered. Functional magnetic resonance imaging was performed in 15 schizophrenia patients (SP) and 15 healthy controls (HC) to study functional connectivity of Broca's area by means of a beta series correlation method during perception of audiovisually presented bisyllabic German nouns, in which audio and video either matched or did not match. Broca's area of SP showed stronger connectivity with supplementary motor cortex for incongruent trials whereas HC connectivity was stronger for congruent trials. The right posterior superior temporal sulcus (RpSTS) area showed differences in connectivity for congruent and incongruent trials in HC in contrast to SP where the connectivity was similar for both conditions. These smaller differences in connectivity in SP suggest a less adaptive processing of audiovisually congruent and incongruent speech. The findings imply that AV integration problems in schizophrenia are associated with maladaptive connectivity of Broca's and RpSTS area in particular when confronted with incongruent stimuli. Results are discussed in light of recent AV speech perception models.	t	\N
23998484	Electrode impedance increases following implantation and undergoes transitory reduction with onset of electrical stimulation. The studies in this paper measured the changes in access resistance and polarization impedance in vivo before and following electrical stimulation, and recorded the time course of these changes. Impedance measures recorded in (a) four cats following 6 months of cochlear implant use, and (b) three cochlear implant recipients with 1.5-5 years cochlear implant experience. Both the experimental and clinical data exhibited a reduction in electrode impedance, 20 and 5% respectively, within 15-30 minutes of stimulation onset. The majority of these changes occurred through reduction in polarization impedance. Cessation of stimulation was followed by an equivalent rise in impedance measures within 6-12 hours. Stimulus-induced reductions in impedance exhibit a rapid onset and are evident in both chronic in vivo models tested, even several years after implantation. Given the impedance changes were dominated by the polarization component, these findings suggest that the electrical stimulation altered the electrode surface rather than the bulk tissue and fluid in the cochlea.	t	\N
24001008	Classical theories of semantic memory assume that concepts are represented in a unitary amodal memory system. In challenging this classical view, pure or hybrid modality-specific theories propose that conceptual representations are grounded in the sensory-motor brain areas, which typically process sensory and action-related information. Although neuroimaging studies provided evidence for a functional-anatomical link between conceptual processing of sensory or action-related features and the sensory-motor brain systems, it has been argued that aspects of such sensory-motor activation may not directly reflect conceptual processing but rather strategic imagery or postconceptual elaboration. In the present ERP study, we investigated masked effects of acoustic and action-related conceptual features to probe unconscious automatic conceptual processing in isolation. Subliminal feature-specific ERP effects at frontocentral electrodes were observed, which differed with regard to polarity, topography, and underlying brain electrical sources in congruency with earlier findings under conscious viewing conditions. These findings suggest that conceptual acoustic and action representations can also be unconsciously accessed, thereby excluding any postconceptual strategic processes. This study therefore further substantiates a grounding of conceptual and semantic processing in action and perception.	t	\N
24002965	Dual-system models of visual category learning posit the existence of an explicit, hypothesis-testing reflective system, as well as an implicit, procedural-based reflexive system. The reflective and reflexive learning systems are competitive and neurally dissociable. Relatively little is known about the role of these domain-general learning systems in speech category learning. Given the multidimensional, redundant, and variable nature of acoustic cues in speech categories, our working hypothesis is that speech categories are learned reflexively. To this end, we examined the relative contribution of these learning systems to speech learning in adults. Native English speakers learned to categorize Mandarin tone categories over 480 trials. The training protocol involved trial-by-trial feedback and multiple talkers. Experiments 1 and 2 examined the effect of manipulating the timing (immediate vs. delayed) and information content (full vs. minimal) of feedback. Dual-system models of visual category learning predict that delayed feedback and providing rich, informational feedback enhance reflective learning, while immediate and minimally informative feedback enhance reflexive learning. Across the two experiments, our results show that feedback manipulations that targeted reflexive learning enhanced category learning success. In Experiment 3, we examined the role of trial-to-trial talker information (mixed vs. blocked presentation) on speech category learning success. We hypothesized that the mixed condition would enhance reflexive learning by not allowing an association between talker-related acoustic cues and speech categories. Our results show that the mixed talker condition led to relatively greater accuracies. Our experiments demonstrate that speech categories are optimally learned by training methods that target the reflexive learning system.	t	\N
24003904	In a system where tens of thousands of words are made up of a limited number of phonemes, many words are bound to sound alike. This similarity of the words in the lexicon as characterized by phonological neighbourhood density (PhND) has been shown to affect speed and accuracy of word comprehension and production. Whereas there is a consensus about the interfering nature of neighbourhood effects in comprehension, the language production literature offers a more contradictory picture with mainly facilitatory but also interfering effects reported on word production. Here we report both of these two types of effects in the same study. Multiple regression mixed models analyses were conducted on PhND effects on errors produced in a naming task by a group of 21 participants with aphasia. These participants produced more formal errors (interfering effect) for words in dense phonological neighbourhoods, but produced fewer nonwords and semantic errors (a facilitatory effect) with increasing density. In order to investigate the nature of these opposite effects of PhND, we further analysed a subset of formal errors and nonword errors by distinguishing errors differing on a single phoneme from the target (corresponding to the definition of phonological neighbours) from those differing on two or more phonemes. This analysis confirmed that only formal errors that were phonological neighbours of the target increased in dense neighbourhoods, while all other errors decreased. Based on additional observations favouring a lexical origin of these formal errors (they exceeded the probability of producing a real-word error by chance, were of a higher frequency, and preserved the grammatical category of the targets), we suggest that the interfering effect of PhND is due to competition between lexical neighbours and target words in dense neighbourhoods.	t	\N
24003982	This study employed Boothroyd and Nittrouer's k (1988) to directly quantify effectiveness in native versus non-native listeners' use of semantic cues. Listeners were presented speech-perception-in-noise sentences processed at three levels of concurrent multi-talker babble and reverberation. For each condition, 50 sentences with multiple semantic cues and 50 with minimum semantic cues were randomly presented. Listeners verbally reported and wrote down the target words. The metric, k, was derived from percent-correct scores for sentences with and without semantics. Ten native and 33 non-native listeners participated. The presence of semantics increased recognition benefit by over 250% for natives, but access to semantics remained limited for non-native listeners (90-135%). The k was comparable across conditions for native listeners, but level-dependent for non-natives. The k for non-natives was significantly different from 1 in all conditions, suggesting semantic cues, though reduced in importance in difficult conditions, were helpful for non-natives. Non-natives as a group were not as effective in using semantics to facilitate English sentence recognition as natives. Poor listening conditions were particularly adverse to the use of semantics in non-natives, who may rely on clear acoustic-phonetic cues before benefitting from semantic cues when recognizing connected speech.	t	\N
24005532	It has been hypothesized that selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction can occur more frequently in patients with higher central serotonergic activity, and that this higher serotonergic activity can induce inhibition of sexual desire, ejaculation, and orgasm. Thus, the aim of this study was to determine the relationship between SSRI-induced sexual dysfunction and increased serotonin. Event-related potentials for the loudness dependence of auditory evoked potentials (LDAEP) were measured in 46 patients at a single time point. The subjects' scores on the Hamilton Depression Rating Scale and Antidepressant Side-Effect Checklist were also determined by the investigators at the same time point. All patients had received SSRI monotherapy. Overall, 37 % (17/46) of the patients experienced some form of SSRI-induced sexual dysfunction: lack of sexual desire, impotence, orgasm, and menstrual abnormality or mastalgia were experienced by 21.7, 8.3, 15.2, and 20.6 % of the patients, respectively. The subjects were thus divided into two groups-those with and without sexual dysfunction-and their data were compared. There was a tendency for the LDAEP to be lower in the group with sexual dysfunction (1.04 ± 0.77 μV) than the group without sexual dysfunction (1.45 ± 0.86 μV), although the difference was not statistically significant (p = 0.086). Furthermore, the distribution of the frequency of SSRI-induced sexual dysfunction differed marginally significantly between patients with low and high LDAEP, dichotomized according to the median LDAEP on the Cz electrode (χ (2) = 3.664, p = 0.056). There was a relatively high frequency of SSRI-induced sexual dysfunction in patients with low LDAEP.	t	\N
24009759	Recent studies employing speech stimuli to investigate 'cocktail-party' listening have focused on entrainment of cortical activity to modulations at syllabic (5 Hz) and phonemic (20 Hz) rates. The data suggest that cortical modulation filters (CMFs) are dependent on the sound-frequency channel in which modulations are conveyed, potentially underpinning a strategy for separating speech from background noise. Here, we characterize modulation filters in human listeners using a novel behavioral method. Within an 'inverted' adaptive forced-choice increment detection task, listening level was varied whilst contrast was held constant for ramped increments with effective modulation rates between 0.5 and 33 Hz. Our data suggest that modulation filters are tonotopically organized (i.e., vary along the primary, frequency-organized, dimension). This suggests that the human auditory system is optimized to track rapid (phonemic) modulations at high sound-frequencies and slow (prosodic/syllabic) modulations at low frequencies.	t	\N
24022792	Processing multiple complex features to create cohesive representations of objects is an essential aspect of both the visual and auditory systems. It is currently unclear whether these processes are entirely modality specific or whether there are amodal processes that contribute to complex object processing in both vision and audition. We investigated this using a dual-stream target detection task in which two concurrent streams of novel visual or auditory stimuli were presented. We manipulated the degree to which each stream taxed processing conjunctions of complex features. In two experiments, we found that concurrent visual tasks that both taxed conjunctive processing strongly interfered with each other but that concurrent auditory and visual tasks that both taxed conjunctive processing did not. These results suggest that resources for processing conjunctions of complex features within vision and audition are modality specific.	t	\N
24023379	Effects of clicks and tonebursts on early and late auditory middle latency response (AMLR) components were evaluated in young and older cigarette smokers and nonsmokers. Participants ( n = 49) were categorized by smoking and age into 4 groups: (a) older smokers, (b) older nonsmokers, (c) young smokers, and (d) young nonsmokers. Monaural, 2-channel AMLRs were acquired from Fz and Cz electrodes with 3 stimuli (clicks, 500 Hz, and 3000 Hz). Group differences included significantly higher V-Na amplitude in young adults and shorter Pb latency in older nonsmokers. Young smokers had a significantly higher Nb-Pb amplitude and shorter Nb latency than other groups. Toneburst stimuli yielded significantly longer V, Na, and Pa latencies compared to clicks. Pb latency was shorter at Fz than at Cz. Relative amplitudes were significantly higher at Fz than at Cz overall; Pa-Nb and Nb-Pb were significantly lower for 3000 Hz than for 500 Hz and clicks. Responses from young smokers revealed a higher amplitude and shorter latency for later AMLR waves, reflecting an arousal effect of smoking in cortical and subcortical generators. AMLR differences in older adults may be due to age-related neurochemical changes in the central nervous system. Stimulus and electrode differences plus smoking and aging effects can guide neurodiagnostic AMLR protocols, especially in young adult smokers.	t	\N
24026024	To standardize the information for families of children having functional surgery for middle ear malformations, we describe the audiometric results of the subgroup of patients with the most favorable anatomic conditions: viable auditory canal, intact tympanic membrane, mobile stapes, and corresponding to a Jahrsdoerfer score of 8 or higher. Case series, tertiary referral center. Charts of patients undergoing functional surgery for congenital middle ear malformations were reviewed for demographic data, preoperative Jahrsdoerfer score, ossicular chain status, type of ossiculoplasty, and audiometric data before and 6 months postsurgery. Eighteen consecutive interventions were performed on 13 patients (average age of 9 years, 8 girls and 5 boys) between 2004 and 2011. The ossiculoplasties performed were as follows: incus repositioning (4), double-layer tragal cartilage (5), intact native chain reconstruction (3), and partial ossicular prosthesis (6). Mean air bone gap (ABG) was 40.8 ± 12.4 dB preoperatively and 20.9 ± 12.9 dB postoperatively (p < 0.0001). Preoperative and postoperatively mean air conduction PTA thresholds were 49.9 ± 9.5 and 30.0 ± 14.1 dB, respectively (p < 0.0001). All ears operated on except one had air conduction improvement. There were no complications. Functional surgery for congenital middle ear malformations gives variable hearing outcomes. In this study, with the most favorable anatomic conditions, 12 ears (67%) of 18 had air conduction improvement below 30 dB.	t	\N
24028890	Most hearing aid prescriptions focus on the optimization of a metric derived from the long-term average spectrum of speech, and do not consider how the prescribed values might distort the temporal envelope shape. A growing body of evidence suggests that such distortions can lead to systematic errors in speech perception, and therefore hearing aid prescriptions might benefit by including preservation of the temporal envelope shape in their rationale. To begin to explore this possibility, we designed a genetic algorithm (GA) to find the multiband compression settings that preserve the shape of the original temporal envelope while placing that envelope in the listener's audiometric dynamic range. The resulting prescription had a low compression threshold, short attack and release times, and a combination of compression ratio and gain that placed the output signal within the listener's audiometric dynamic range. Initial behavioral tests of individuals with impaired hearing revealed no difference in speech-in-noise perception between the GA and the NAL-NL2 prescription. However, gap detection performance was superior with the GA in comparison to NAL-NL2. Overall, this work is a proof of concept that consideration of temporal envelope distortions can be incorporated into hearing aid prescriptions.	t	\N
24041778	Congenital amusia is a neuro-developmental disorder of music perception and production. Recent findings have demonstrated that this deficit is linked to an impaired short-term memory for tone sequences. As it has been shown before that non-musicians' implicit knowledge of musical regularities can improve short-term memory for tone information, the present study investigated if this type of implicit knowledge could also influence amusics' short-term memory performance. Congenital amusics and their matched controls, who were non-musicians, had to indicate whether sequences of five tones, presented in pairs, were the same or different; half of the pairs respected musical regularities (tonal sequences) and the other half did not (atonal sequences). As previously reported for non-musician participants, the control participants showed better performance (as measured with d') for tonal sequences than for atonal ones. While this improvement was not observed in amusics, both control and amusic participants showed faster response times for tonal sequences than for atonal sequences. These findings suggest that some implicit processing of tonal structures is potentially preserved in congenital amusia. This observation is encouraging as it strengthens the perspective to exploit implicit knowledge to help reducing pitch perception and memory deficits in amusia.	t	\N
24043402	Our previous studies using fMRI have demonstrated that activations in human auditory cortex (AC) are strongly dependent on the characteristics of the task. The present study tested whether source estimation of scalp-recorded event-related potentials (ERPs) can be used to investigate task-dependent AC activations. Subjects were presented with frequency-varying two-part tones during pitch discrimination, pitch n-back memory, and visual tasks identical to our previous fMRI study (Rinne et al., J Neurosci 29:13338-13343, 2009). ERPs and their minimum-norm source estimates in AC were strongly modulated by task at 200-700 ms from tone onset. As in the fMRI study, the pitch discrimination and pitch memory tasks were associated with distinct AC activation patterns. In the pitch discrimination task, increased activity in the anterior AC was detected relatively late at 300-700 ms from tone onset. Therefore, this activity was probably not associated with enhanced pitch processing but rather with the actual discrimination process (comparison between the two parts of tone). Increased activity in more posterior areas associated with the pitch memory task, in turn, occurred at 200-700 ms suggesting that this activity was related to operations on pitch categories after pitch analysis was completed. Finally, decreased activity associated with the pitch memory task occurred at 150-300 ms consistent with the notion that, in the demanding pitch memory task, spectrotemporal analysis is actively halted as soon as category information has been obtained. These results demonstrate that ERP source analysis can be used to complement fMRI to investigate task-dependent activations of human AC.	t	\N
24043565	What conditions, if any, can fully prevent attentional capture (i.e., involuntary allocation of spatial attention to an irrelevant object) has been a matter of debate. In a previous study, Folk, Ester, and Troemel (Psychonomic Bulletin & Review 16:127-132, 2009) suggested that attentional capture can be blocked entirely when attention is already engaged in a different object. This conclusion relied on the finding that in a search for a known-color target in a rapid serial visual presentation stream, a peripheral distractor with the target color did not further impair target identification performance when a distractor also with the target color that appeared in the stream had already captured attention. In the present study, we argue that this conclusion is unwarranted, because the effects of the central and peripheral distractors could not be disentangled. In order to isolate the effect of the peripheral distractor, we introduced a distractor-target letter compatibility manipulation. Our results showed that the peripheral distractor summoned attention, irrespective of whether attention had just been engaged. We conclude that neither spatially focused attention nor attentional engagement is sufficient to prevent attentional capture.	t	\N
24055624	This study investigated the perceptual relationship between acoustic and electric stimuli presented to CI users with functional contralateral hearing. Fourteen subjects with unilateral profound deafness implanted with a MED-EL CI scaled the perceptual differences between pure tones presented to the acoustic hearing ear and electric biphasic pulse trains presented to the implanted ear. The differences were analyzed with a multidimensional scaling (MDS) analysis. Additionally, speech performance in noise was tested using sentence material presented in different spatial configurations while patients listened with both their acoustic hearing and implanted ears. Results of alternating least squares scaling (ALSCAL) analysis consistently demonstrate that a change in place of stimulation is in the same perceptual dimension as a change in acoustic frequency. However, the relative perceptual differences between the acoustic and the electric stimuli varied greatly across subjects. A degree of perceptual separation between acoustic and electric stimulation (quantified by relative dimensional weightings from an INDSCAL analysis) was hypothesized that would indicate a change in perceptual quality, but also be predictive of performance with combined acoustic and electric hearing. Perceptual separation between acoustic and electric stimuli was observed for some subjects. However, no relationship between the degree of perceptual separation and performance was found.	t	\N
24059596	To establish the reliability and validity of an automated hearing screening test system for children. Cross-sectional within a comparative study of subjects. Subjects were 325 first-grade and second-grade children (6-10 years old) from primary schools in Shenzhen, China. Using the conventional pure-tone screening test with the pass/refer criterion set as 25 dB HL, as the 'gold standard", the sensitivity and specificity of the automated hearing screening test was 0.63 and 0.82, respectively. No specific pattern in the failure rates was observed to relate to the students' grade. There was no statistically significant age effect or gender effect. The results suggest that with further improvement in terms of its sensitivity and specificity, it may be feasible to use the automated hearing screening test system to conduct routine school hearing screenings.	t	\N
24067501	To confirm an increased susceptibility to informational masking among individuals with single-sided deafness (SSD). To demonstrate a reduction in informational masking when SSD is treated with an integrated bone conduction hearing aid (IBC). To identify the acoustic cues that contribute to IBC-aided masking release. To determine the effects of device experience on the IBC advantage. Informational masking was evaluated with the coordinate-response measure. Participants performed the task by reporting color and number coordinates that changed randomly within target sentences. The target sentences were presented in free field accompanied by zero to three distracting sentences. Target and distracting sentences were spoken by different talkers and originated from different source locations, creating two sources of information for auditory streaming. Susceptibility to informational masking was inferred from the error rates of unaided SSD patients relative to normal controls. These baseline measures were derived by testing inexperienced IBC users without the device on the day of their initial fitting. The benefits of IBC-aided listening were assessed by measuring the aided performance of users who had at least 3 months' device experience. The acoustic basis of the listening advantage was isolated by correlating response errors with the voice pitch and location of distracting sentences. The effects of learning on cue effectiveness were evaluated by comparing the error rates of experienced and inexperienced users. Unaided SSD participants (inexperienced users) performed as well as normal controls when tested without distracting sentences but produced significantly higher error rates when tested with distracting sentences. Most errors involved responding with coordinates that were contained in distracting sentences. This increased susceptibility to informational masking was significantly reduced when experienced IBC users were tested with the device. The listening advantage was most strongly correlated with the availability of voice pitch cues, although performance was also influenced by the location of distracting sentences. Directional asymmetries appear to be dictated by location-dependent cues that are derived from the distinctive transmission characteristics of IBC stimulation. Experienced users made better use of these cues than inexperienced users. These results suggest that informational masking is a significant source of communication impairment among individuals with SSD. Despite the lateralization of auditory function, unaided SSD subjects experience informational masking when distractors occur in either the deaf or normal spatial hemifield. Restoration of aural sensitivity in the deaf hemifield with an IBC enhances speech intelligibility under complex listening conditions, presumably by providing additional sound-segregation cues that are derived from voice pitch and spatial location. The optimal use of these cues is not immediate, but a significant listening advantage is observed after 3 months of unstructured use.	t	\N
24071587	Stereo vision has a well-known anisotropy: At low frequencies, horizontally oriented sinusoidal depth corrugations are easier to detect than vertically oriented corrugations (both defined by horizontal disparities). Previously, Serrano-Pedraza and Read (2010) suggested that this stereo anisotropy may arise because the stereo system uses multiple spatial-frequency disparity channels for detecting horizontally oriented modulations but only one for vertically oriented modulations. Here, we tested this hypothesis using the critical-band masking paradigm. In the first experiment, we measured disparity thresholds for horizontal and vertical sinusoids near the peak of the disparity sensitivity function (0.4 cycles/°), in the presence of either broadband or notched noise. We fitted the power-masking model to our results assuming a channel centered on 0.4 cycles/°. The estimated channel bandwidths were 2.95 octaves for horizontal and 2.62 octaves for vertical corrugations. In our second experiment we measured disparity thresholds for horizontal and vertical sinusoids of 0.1 cycles/° in the presence of band-pass noise centered on 0.4 cycles/° with a bandwidth of 0.5 octaves. This mask had only a small effect on the disparity thresholds, for either horizontal or vertical corrugations. We simulated the detection thresholds using the power-masking model with the parameters obtained in the first experiment and assuming either single-channel and multiple-channel detection. The multiple-channel model predicted the thresholds much better for both horizontal and vertical corrugations. We conclude that the human stereo system must contain multiple independent disparity channels for detecting horizontally oriented and vertically oriented depth modulations.	t	\N
24073696	To investigate the effects of emotional music on visual processes, we analyzed visual evoked magnetic fields (VEF) on listening to emotional music in 14 healthy subjects. Positive and negative pieces of music were delivered during VEF recording following stimulation by emotionally neutral pictures of faces and landscapes. VEF components at 100 (M100) and 150 (M170)ms after stimulus onset were analyzed, and the estimated current strength for M170 following face stimulation was enhanced with negative compared to positive music in the right hemisphere. The equivalent current dipole for M100 and M170 was estimated in the primary visual cortex (V1) and inferior temporal area (IT), respectively. The present results indicate that background music showed a top-down control of the visual processes in IT, which is a core site responsible for the interpretation of facial expression. The emotional contents of music could alter visual processes, especially those involving the face.	t	\N
24076424	For much of the past 30 years, investigations of auditory perception and language have been enhanced or even driven by the use of functional neuroimaging techniques that specialize in localization of central responses. Beginning with investigations using positron emission tomography (PET) and gradually shifting primarily to usage of functional magnetic resonance imaging (fMRI), auditory neuroimaging has greatly advanced our understanding of the organization and response properties of brain regions critical to the perception of and communication with the acoustic world in which we live. As the complexity of the questions being addressed has increased, the techniques, experiments and analyses applied have also become more nuanced and specialized. A brief review of the history of these investigations sets the stage for an overview and analysis of how these neuroimaging modalities are becoming ever more effective tools for understanding the auditory brain. We conclude with a brief discussion of open methodological issues as well as potential clinical applications for auditory neuroimaging. This article is part of a Special Issue entitled Human Auditory Neuroimaging.	t	\N
24076425	Harmonic complexes that generate highly modulated temporal envelopes on the basilar membrane (BM) mask a tone less effectively than complexes that generate relatively flat temporal envelopes, because the non-linear active gain of the BM selectively amplifies a low-level tone in the dips of a modulated masker envelope. The present study examines a similar effect in speech recognition. Speech reception thresholds (SRTs) were measured for a voice masked by harmonic complexes with partials in sine phase (SP) or in random phase (RP). The masker's fundamental frequency (F0) was 50, 100 or 200 Hz. SRTs were considerably lower for SP than for RP maskers at 50-Hz F0, but the two converged at 100-Hz F0, while at 200-Hz F0, SRTs were a little higher for SP than RP maskers. The results were similar whether the target voice was male or female and whether the masker's spectral profile was flat or speech-shaped. Although listening in the masker dips has been shown to play a large role for artificial stimuli such as Schroeder-phase complexes at high levels, it contributes weakly to speech recognition in the presence of harmonic maskers with different crest factors at more moderate sound levels (65 dB SPL).	t	\N
24086676	The auditory illusory perception "scale illusion" occurs when a tone of ascending scale is presented in one ear, a tone of descending scale is presented simultaneously in the other ear, and vice versa. Most listeners hear illusory percepts of smooth pitch contours of the higher half of the scale in the right ear and the lower half in the left ear. Little is known about neural processes underlying the scale illusion. In this magnetoencephalographic study, we recorded steady-state responses to amplitude-modulated short tones having illusion-inducing pitch sequences, where the sound level of the modulated tones was manipulated to decrease monotonically with increase in pitch. The steady-state responses were decomposed into right- and left-sound components by means of separate modulation frequencies. It was found that the time course of the magnitude of response components of illusion-perceiving listeners was significantly correlated with smooth pitch contour of illusory percepts and that the time course of response components of stimulus-perceiving listeners was significantly correlated with discontinuous pitch contour of stimulus percepts in addition to the contour of illusory percepts. The results suggest that the percept of illusory pitch sequence was represented in the neural activity in or near the primary auditory cortex, i.e., the site of generation of auditory steady-state response, and that perception of scale illusion is maintained by automatic low-level processing.	t	\N
24089491	The strategies by which the central nervous system decodes the properties of sensory stimuli, such as sound source location, from the responses of a population of neurons are a matter of debate. We show, using the average firing rates of neurons in the inferior colliculus (IC) of awake rabbits, that prevailing decoding models of sound localization (summed population activity and the population vector) fail to localize sources accurately due to heterogeneity in azimuth tuning across the population. In contrast, a maximum-likelihood decoder operating on the pattern of activity across the population of neurons in one IC accurately localized sound sources in the contralateral hemifield, consistent with lesion studies, and did so with a precision consistent with rabbit psychophysical performance. The pattern decoder also predicts behavior in response to incongruent localization cues consistent with the long-standing "duplex" theory of sound localization. We further show that the pattern decoder accurately distinguishes two concurrent, spatially separated sources from a single source, consistent with human behavior. Decoder detection of small amounts of source separation directly in front is due to neural sensitivity to the interaural decorrelation of sound, at both low and high frequencies. The distinct patterns of IC activity between single and separated sound sources thereby provide a neural correlate for the ability to segregate and localize sources in everyday, multisource environments.	t	\N
24095845	Pitch is derived by the auditory system through complex spectrotemporal processing. Pitch extraction is thought to depend on both spectral cues arising from lower harmonics that are resolved by cochlear filters in the inner ear, and on temporal cues arising from the pattern of action potentials contained in the cochlear output. Adults are capable of extracting pitch in the absence of robust spectral cues, taking advantage of the temporal cues that remain. However, recent behavioral evidence suggests that infants have difficulty discriminating between stimuli with different pitches when resolvable spectral cues are absent. In the current experiments, we used the mismatch negativity (MMN) component of the event related potential derived from electroencephalographic (EEG) recordings to examine a cortical representation of pitch discrimination for iterated rippled noise (IRN) stimuli in 4- and 8-month-old infants. IRN stimuli are pitch-evoking sounds generated by repeatedly adding a segment of white noise to itself at a constant delay. We created IRN stimuli (delays of 5 and 6ms creating pitch percepts of 200 and 167Hz) and high-pass filtered them to remove all resolvable spectral pitch cues. In experiment 1, we did not find EEG evidence that infants could detect the change in the pitch of these IRN stimuli. However, in Experiment 2, after a brief period of pitch-priming during which we added a sine wave component to the IRN stimulus at its perceived pitch, infants did show significant MMN in response to pitch changes in the IRN stimuli with sine waves removed. This suggests that (1) infants can use temporal cues to process pitch, although such processing is not mature and (2) that a short amount of pitch-priming experience can alter pitch representations in auditory cortex during infancy.	t	\N
24105268	This study examined the ability of click auditory brainstem response (ABR) undertaken below the age of 6 months (from expected date of delivery) to differentiate between conductive and sensorineural hearing loss (SNHL), using the latency of wave V measured 20 dB above threshold. Subjects were recruited if they had an ABR threshold of ≥ 40 dB nHL and ≤ 70 dB nHL in one or both ears measured below the age of 6 months and they had also attended follow-up appointments for behavioral assessment of their hearing in which the type of hearing loss had been confirmed. Forty-five children (84 ears) with SNHL, 82 children (141 ears) with temporary conductive hearing loss (TCHL), and 5 children (10 ears) with permanent conductive hearing loss (PCHL) were recruited. The differences between mean wave V latencies measured 20 dB above ABR threshold were examined using the independent t-test for the groups of cases with SNHL, TCHL, and PCHL. Signal-detection theory was used to examine the relationship between sensitivity and specificity when the latency of wave V 20 dB above threshold was used to identify the presence of SNHL. Receiver operating characteristics were generated and the coordinates of the curve examined for the best compromise between sensitivity and false-alarm rate. The specificity, positive predictive value, and probability of missing a true case were determined for the most promising criteria. There were significant differences between the two groups with SNHL and TCHL. The mean latency of wave V 20 dB above threshold was 1 msec shorter in those with SNHL compared with those with TCHL. There were significant differences between children with PCHL and SNHL but no difference between those with PCHL and TCHL. When a criterion of < 7.6 msec was chosen to predict the presence of SNHL the test sensitivity was 0.98, test specificity 0.71, and positive predictive value was 0.66. Nine out of 10 of those with a latency 20 dB above threshold of < 7.0 msec had an SNHL. The latency of wave V 20 dB above threshold measured using click ABR is a useful indicator of the type of hearing loss in babies referred from newborn hearing screening.	t	\N
24108804	Synchronizing movements with rhythmic inputs requires tight coupling of sensory and motor neural processes. Here, using a novel approach based on the recording of steady-state-evoked potentials (SS-EPs), we examine how distant brain areas supporting these processes coordinate their dynamics. The electroencephalogram was recorded while subjects listened to a 2.4-Hz auditory beat and tapped their hand on every second beat. When subjects tapped to the beat, the EEG was characterized by a 2.4-Hz SS-EP compatible with beat-related entrainment and a 1.2-Hz SS-EP compatible with movement-related entrainment, based on the results of source analysis. Most importantly, when compared with passive listening of the beat, we found evidence suggesting an interaction between sensory- and motor-related activities when subjects tapped to the beat, in the form of (1) additional SS-EP appearing at 3.6 Hz, compatible with a nonlinear product of sensorimotor integration; (2) phase coupling of beat- and movement-related activities; and (3) selective enhancement of beat-related activities over the hemisphere contralateral to the tapping, suggesting a top-down effect of movement-related activities on auditory beat processing. Taken together, our results are compatible with the view that rhythmic sensorimotor synchronization is supported by a dynamic coupling of sensory and motor related activities.	t	\N
24110502	Bone-conducted ultrasound (BCU) is perceived even by the profoundly sensorineural deaf. A novel hearing aid using the perception of amplitude-modulated BCU (BCU hearing aid: BCUHA) has been developed. However, there is room for improvement particularly in terms of articulation and sound quality. BCU speech is accompanied by a strong high-pitched tone and contain some distortion. In this study, transposed modulation, that can be expected to reduce the high-pitched tone was newly employed as a modulation method in the BCUHA, and its resulting articulation, intelligibility and sound quality were evaluated. The results showed that transposed modulation showed nearly equal articulation and intelligibility scores to and better sound quality than the existing method, DSB-TC modulation. These results provide useful information for further development of the BCUHA.	t	\N
24111102	Auditory Brainstem Responses (ABRs) are commonly used in clinical practice to determine hearing impairments and hearing thresholds. Although many research groups work on automatic recognition of ABRs - in order to decrease the acquisition times - measures to determine the quality of ABR measurements objectively are still missing. In fact, recently released new standards for electroencephalographic measurements in auditory examinations require an objective measurement quality assessment for neurodiagnostic devices. Thus there is a pressing need for the development and evaluation of such a quality control. In this study, we propose (a) a novel technique for the assessment of the ABR measurement quality and (b) evaluate and compare this technique to two other approaches which have been suggested in literature as required by the new standards.	t	\N
24116424	Speech reception thresholds were obtained in normally hearing listeners for sentence targets masked by harmonic complexes constructed with different phase relationships. Maskers had either a constant fundamental frequency (F0), or had F0 changing over time, following a pitch contour extracted from natural speech. The median F0 of the target speech was very similar to that of the maskers. In experiment 1 differences in the masking produced by Schroeder positive and Schroeder negative phase complexes were small (around 1.5 dB) for moderate levels [60 dB sound pressure level (SPL)], but increased to around 6 dB for maskers at 80 dB SPL. Phase effects were typically around 1.5 dB larger for maskers that had naturally varying F0 contours than for maskers with constant F0. Experiment 2 showed that shaping the long-term spectrum of the maskers to match the target speech had no effect. Experiment 3 included additional phase relationships at moderate levels and found no effect of phase. Therefore, the phase relationship within harmonic complexes appears to have only minor effects on masking effectiveness, at least at moderate levels, and when targets and maskers are in the same F0 range.	t	\N
24121087	Functional hemispheric differences for speech and language processing have been traditionally studied by using verbal dichotic-listening paradigms. The commonly observed right-ear preference for the report of dichotically presented syllables is taken to reflect the left hemispheric dominance for speech processing. However, the results of recent functional imaging studies also show that both hemispheres - not only the left - are engaged by dichotic listening, suggesting a more complex relationship between behavioral laterality and functional hemispheric activation asymmetries. In order to more closely examine the hemispheric differences underlying dichotic-listening performance, we report an analysis of functional magnetic resonance imaging (fMRI) data of 104 right-handed subjects, for the first time combining an interhemispheric difference and conjunction analysis. This approach allowed for a distinction of homotopic brain regions which showed symmetrical (i.e., brain region significantly activated in both hemispheres and no activation difference between the hemispheres), relative asymmetrical (i.e., activated in both hemispheres but significantly stronger in one than the other hemisphere), and absolute asymmetrical activation patterns (i.e., activated only in one hemisphere and this activation is significantly stronger than in the other hemisphere). Symmetrical activation was found in large clusters encompassing temporal, parietal, inferior frontal, and medial superior frontal regions. Relative and absolute left-ward asymmetries were found in the posterior superior temporal gyrus, located adjacent to symmetrically activated areas, and creating a lateral-medial gradient from symmetrical towards absolute asymmetrical activation within the peri-Sylvian region. Absolute leftward asymmetry was also found in the post-central and medial superior frontal gyri, while rightward asymmetries were found in middle temporal and middle frontal gyri. We conclude that dichotic listening engages a bihemispheric cortical network, showing a symmetrical and mostly leftward asymmetrical pattern. The here obtained functional (a)symmetry map might serve as a basis for future studies which - by studying the relevance of the here identified regions - clarify the relationship between behavioral laterality measures and hemispheric asymmetry.	t	\N
24121711	The purpose of this study was to investigate the influence of contingent auditory feedback on the development of infant reaching. Eleven full-term infants were observed biweekly from the age of 10 weeks to 16 weeks, and their arm kinematics were recorded. Auditory feedback that was contingent on arm kinematics was provided in the form of: (a) the mother's voice; and (b) musical tones. Results showed that providing auditory feedback (mother's voice or musical tones): (i) increased the amplitude of exploratory arm movements before the onset of reaching; and (ii) increased the number of reaches at the onset of reaching. These results show that infants are able to use contingent auditory feedback to explore the relevant possibilities for action that are subsequently shaped into goal-directed movements.	t	\N
24122619	To determine the effectiveness of simultaneous versus sequential bilateral cochlear implantation on postoperative outcomes in children with bilateral deafness and to evaluate the impact of the inter-implant interval and age at second implantation on postoperative outcomes in children who already received their first cochlear implant. PubMed, Embase, and Web of Science. All studies comparing the effects of simultaneous with sequential bilateral cochlear implantation on postoperative outcomes and those evaluating the impact of the inter-implant interval and age at second implantation were retrieved. Four studies compared the effects of simultaneous with sequential bilateral cochlear implantation. All studies lacked randomization. Of these, three reported better speech perception and expressive language development at one year of bilateral experience for simultaneous cochlear implantation. Of the nineteen publications on the impact of the inter-implant interval on postoperative outcomes, the risk of bias was low-moderate for seven studies which were derived from five different study populations. In two of these populations no impact of the inter-implant interval was found, while in three a longer inter-implant interval was associated with poorer speech and language development. Observational studies suggest that simultaneous implantation in children may be associated with improved speech and language development, and that a prolonged inter-implant interval between both implantations may have a negative impact on these postoperative outcomes. Randomized trials are, however, needed to demonstrate whether simultaneous implantation indeed is superior to sequential bilateral implantation in children with bilateral deafness. NA.	t	\N
24125574	It is not unusual to find it stated as a fact that the left hemisphere is specialized for the processing of rapid, or temporal aspects of sound, and that the dominance of the left hemisphere in the perception of speech can be a consequence of this specialization. In this review we explore the history of this claim and assess the weight of this assumption. We will demonstrate that instead of a supposed sensitivity of the left temporal lobe for the acoustic properties of speech, it is the right temporal lobe which shows a marked preference for certain properties of sounds, for example longer durations, or variations in pitch. We finish by outlining some alternative factors that contribute to the left lateralization of speech perception.	t	\N
24125858	Auditory verbal hallucinations (AVHs) are the experience of hearing voices in the absence of any speaker, often associated with a schizophrenia diagnosis. Prominent cognitive models of AVHs suggest they may be the result of inner speech being misattributed to an external or non-self source, due to atypical self- or reality monitoring. These arguments are supported by studies showing that people experiencing AVHs often show an externalising bias during monitoring tasks, and neuroimaging evidence which implicates superior temporal brain regions, both during AVHs and during tasks that measure verbal self-monitoring performance. Recently, efficacy of noninvasive neurostimulation techniques as a treatment option for AVHs has been tested. Meta-analyses show a moderate effect size in reduction of AVH frequency, but there has been little attempt to explain the therapeutic effect of neurostimulation in relation to existing cognitive models. This article reviews inner speech models of AVHs, and argues that a possible explanation for reduction in frequency following treatment may be modulation of activity in the brain regions involving the monitoring of inner speech.	t	\N
24132709	Three cross-modal priming experiments examined the influence of preexposure to pictures and printed words on the speed of spoken word recognition. Targets for auditory lexical decision were spoken Dutch words and nonwords, presented in isolation (Experiments 1 and 2) or after a short phrase (Experiment 3). Auditory stimuli were preceded by primes, which were pictures (Experiments 1 and 3) or those pictures' printed names (Experiment 2). Prime-target pairs were phonologically onset related (e.g., pijl-pijn, arrow-pain), were from the same semantic category (e.g., pijl-zwaard, arrow-sword), or were unrelated on both dimensions. Phonological interference and semantic facilitation were observed in all experiments. Priming magnitude was similar for pictures and printed words and did not vary with picture viewing time or number of pictures in the display (either one or four). These effects arose even though participants were not explicitly instructed to name the pictures and where strategic naming would interfere with lexical decision making. This suggests that, by default, processing of related pictures and printed words influences how quickly we recognize spoken words.	t	\N
24165303	Distortion-product otoacoustic emissions (DPOAEs) collected after sound pressure level (SPL) calibration are susceptible to standing waves that affect measurements at the plane of the probe microphone due to overlap of incident and reflected waves. These standing-wave effects can be as large as 20 dB, and may affect frequencies both above and below 4 kHz. It has been shown that forward pressure level (FPL) calibration minimizes standing-wave effects by isolating the forward-propagating component of the stimulus. Yet, previous work has failed to demonstrate more than a small difference in test performance and behavioral-threshold prediction with DPOAEs after SPL and FPL calibration. One potential limitation in prior studies is that measurements were restricted to octave and interoctave frequencies; as a consequence, data were not necessarily collected at the standing-wave null frequency. In the present study, DPOAE responses were measured with f2 set to each participant's standing-wave frequency in an effort to increase the possibility that differences in test performance and threshold prediction would be observed for SPL and FPL calibration methods. Data were collected from 42 normal-hearing participants and 93 participants with hearing loss. DPOAEs were measured with f2 set to 4 kHz and at each participant's notch frequency after SPL and FPL calibration. DPOAE input/output functions were obtained from -10 to 80 dB in 5 dB steps for each calibration/stimulus condition. Test performance was evaluated using clinical decision theory. Both area under receiver operating characteristic curves for all stimulus levels and cumulative distributions when L2 = 50 dB (a level at which the best performance was observed regardless of calibration method) were used to evaluate the accuracy with which auditory status was determined. A bootstrap procedure was used to evaluate the significance of the differences in test performance between SPL and FPL calibrations. DPOAE predictions of behavioral threshold were evaluated by correlating actual behavioral thresholds and predicted thresholds using a multiple linear regression model. First, larger DPOAE levels were measured after SPL calibration than after FPL calibration, which demonstrated the expected impact of standing waves. Second, for both FPL and SPL calibration, test performance was best for moderate stimulus levels. Third, differences in test performance between calibration methods were evident at low- and high-stimulus levels. Fourth, there were small but statistically significant improvements in test performance after FPL calibration for clinically relevant conditions. Fifth, calibration method had no effect on threshold prediction. Standing waves after SPL calibration have an impact on DPOAE levels. Although the effect of calibration method on test performance was small, test performance was better after FPL calibration than after SPL calibration. There was no effect of calibration method on predictions of behavioral threshold.	t	\N
24167235	A phonological deficit is thought to affect most individuals with developmental dyslexia. The present study addresses whether the phonological deficit is caused by difficulties with perceptual learning of fine acoustic details. A demanding test of nonverbal auditory memory, "noise learning," was administered to both adults with dyslexia and control adult participants. On each trial, listeners had to decide whether a stimulus was a 1-s noise token or 2 abutting presentations of the same 0.5-s noise token (repeated noise). Without the listener's knowledge, the exact same noise tokens were presented over many trials. An improved ability to perform the task for such "reference" noises reflects learning of their acoustic details. Listeners with dyslexia did not differ from controls in any aspect of the task, qualitatively or quantitatively. They required the same amount of training to achieve discrimination of repeated from nonrepeated noises, and they learned the reference noises as often and as rapidly as the control group. However, they did show all the hallmarks of dyslexia, including a well-characterized phonological deficit. The data did not support the hypothesis that deficits in basic auditory processing or nonverbal learning and memory are the cause of the phonological deficit in dyslexia.	t	\N
24174656	Despite the prevalence of poverty worldwide, little is known about how early socioeconomic adversity affects auditory brain function. Socioeconomically disadvantaged children are underexposed to linguistically and cognitively stimulating environments and overexposed to environmental toxins, including noise pollution. This kind of sensory impoverishment, we theorize, has extensive repercussions on how the brain processes sound. To characterize how this impoverishment affects auditory brain function, we compared two groups of normal-hearing human adolescents who attended the same schools and who were matched in age, sex, and ethnicity, but differed in their maternal education level, a correlate of socioeconomic status (SES). In addition to lower literacy levels and cognitive abilities, adolescents from lower maternal education backgrounds were found to have noisier neural activity than their classmates, as reflected by greater activity in the absence of auditory stimulation. Additionally, in the lower maternal education group, the neural response to speech was more erratic over repeated stimulation, with lower fidelity to the input signal. These weaker, more variable, and noisier responses are suggestive of an inefficient auditory system. By studying SES within a neuroscientific framework, we have the potential to expand our understanding of how experience molds the brain, in addition to informing intervention research aimed at closing the achievement gap between high-SES and low-SES children.	t	\N
24180796	This article investigates the relationship between the shape of the mouthpiece and its acoustical properties in brass instruments. The hypothesis is that not only different volumes but also particular cup shapes affect the embouchure and the tone quality in both a physical and perceivable way. Three professional trumpet players were involved, and two different internal cup contours characterized by a "U" and a "V" shape with two types of throat junction (round and sharp) were chosen, based on a Vincent Bach 1 [1/2] C medium mouthpiece. A third intermediate contour was designed as a combination of these. Over 600 sound samples were produced under controlled conditions, the study involving four different stages: (1) Simulation of air-flow, (2) analysis of the sound spectra, (3) study of the players' subjective responses, and (4) perceptual analysis of their timbral differences. Results confirm the U shape is characterized by a stronger air recirculation and produces stronger spectral components above 8 kHz, compared to the V shape. A round throat junction may also be preferable to a sharp one in terms of playability. There is moderate agreement on the aural perception of these differences although the verbal attributes used to qualify these are not shared.	t	\N
24181980	The role of visual cues in native listeners' perception of speech produced by nonnative speakers has not been extensively studied. Native perception of English sentences produced by native English and Korean speakers in audio-only and audiovisual conditions was examined. Korean speakers were rated as more accented in audiovisual than in the audio-only condition. Visual cues enhanced word intelligibility for native English speech but less so for Korean-accented speech. Reduced intelligibility of Korean-accented audiovisual speech was associated with implicit visual biases, suggesting that listener-related factors partially influence the efficiency of audiovisual integration for nonnative speech perception.	t	\N
24184174	Expert musicians are able to time their actions accurately and consistently during a musical performance. We investigated how musical expertise influences the ability to reproduce auditory intervals and how this generalises across different techniques and sensory modalities. We first compared various reproduction strategies and interval length, to examine the effects in general and to optimise experimental conditions for testing the effect of music, and found that the effects were robust and consistent across different paradigms. Focussing on a 'ready-set-go' paradigm subjects reproduced time intervals drawn from distributions varying in total length (176, 352 or 704 ms) or in the number of discrete intervals within the total length (3, 5, 11 or 21 discrete intervals). Overall, Musicians performed more veridical than Non-Musicians, and all subjects reproduced auditory-defined intervals more accurately than visually-defined intervals. However, Non-Musicians, particularly with visual stimuli, consistently exhibited a substantial and systematic regression towards the mean interval. When subjects judged intervals from distributions of longer total length they tended to regress more towards the mean, while the ability to discriminate between discrete intervals within the distribution had little influence on subject error. These results are consistent with a Bayesian model that minimizes reproduction errors by incorporating a central tendency prior weighted by the subject's own temporal precision relative to the current distribution of intervals. Finally a strong correlation was observed between all durations of formal musical training and total reproduction errors in both modalities (accounting for 30% of the variance). Taken together these results demonstrate that formal musical training improves temporal reproduction, and that this improvement transfers from audition to vision. They further demonstrate the flexibility of sensorimotor mechanisms in adapting to different task conditions to minimise temporal estimation errors.	t	\N
24192718	Dexamethasone administered prior to cochlear implantation has been shown to reduce the loss of residual hearing in experimental settings. However, its effect on the tissue response around the implant has not been extensively studied. In this study dexamethasone sodium phosphate was administered to guinea pigs via local delivery to the round window (2% dexamethasone for 120 min prior to surgery, 'local 2/120', or 20% dexamethasone for 30 min prior to surgery) or intravenously (2 mg/kg dexamethasone for 60 min) prior to implantation. Auditory brainstem responses (ABR) were monitored for 3 months, after which the cochleae were embedded in Spurr's resin and sectioned. The extent of the tissue response and the survival of the neurosensory structures were analysed. Both local 2/120 and systemically delivered dexamethasone improved ABR thresholds when compared with control animals. Systemic dexamethasone also reduced the tissue response around the electrode. This suggests that whilst both locally and systemically administered dexamethasone can protect residual hearing after cochlear implantation, their effects upon the tissue response to implantation may differ.	t	\N
24198087	Cognitive skills, such as processing speed, memory functioning, and the ability to divide attention, are known to diminish with aging. The present study shows that, despite these changes, older adults can successfully compensate for degradations in speech perception. Critically, the older participants of this study were not pre-selected for high performance on cognitive tasks, but only screened for normal hearing. We measured the compensation for speech degradation using phonemic restoration, where intelligibility of degraded speech is enhanced using top-down repair mechanisms. Linguistic knowledge, Gestalt principles of perception, and expectations based on situational and linguistic context are used to effectively fill in the inaudible masked speech portions. A positive compensation effect was previously observed only with young normal hearing people, but not with older hearing-impaired populations, leaving the question whether the lack of compensation was due to aging or due to age-related hearing problems. Older participants in the present study showed poorer intelligibility of degraded speech than the younger group, as expected from previous reports of aging effects. However, in conditions that induce top-down restoration, a robust compensation was observed. Speech perception by the older group was enhanced, and the enhancement effect was similar to that observed with the younger group. This effect was even stronger with slowed-down speech, which gives more time for cognitive processing. Based on previous research, the likely explanations for these observations are that older adults can overcome age-related cognitive deterioration by relying on linguistic skills and vocabulary that they have accumulated over their lifetime. Alternatively, or simultaneously, they may use different cerebral activation patterns or exert more mental effort. This positive finding on top-down restoration skills by the older individuals suggests that new cognitive training methods can teach older adults to effectively use compensatory mechanisms to cope with the complex listening environments of everyday life.	t	\N
24198324	Temporal pole (TP) cortex is associated with higher-order sensory perception and/or recognition memory, as human patients with damage in this region show impaired performance during some tasks requiring recognition memory (Olson et al. 2007). The underlying mechanisms of TP processing are largely based on examination of the visual nervous system in humans and monkeys, while little is known about neuronal activity patterns in the auditory portion of this region, dorsal TP (dTP; Poremba et al. 2003). The present study examines single-unit activity of dTP in rhesus monkeys performing a delayed matching-to-sample task utilizing auditory stimuli, wherein two sounds are determined to be the same or different. Neurons of dTP encode several task-relevant events during the delayed matching-to-sample task, and encoding of auditory cues in this region is associated with accurate recognition performance. Population activity in dTP shows a match suppression mechanism to identical, repeated sound stimuli similar to that observed in the visual object identification pathway located ventral to dTP (Desimone 1996; Nakamura and Kubota 1996). However, in contrast to sustained visual delay-related activity in nearby analogous regions, auditory delay-related activity in dTP is transient and limited. Neurons in dTP respond selectively to different sound stimuli and often change their sound response preferences between experimental contexts. Current findings suggest a significant role for dTP in auditory recognition memory similar in many respects to the visual nervous system, while delay memory firing patterns are not prominent, which may relate to monkeys' shorter forgetting thresholds for auditory vs. visual objects.	t	\N
24210181	A time interval between the onset and the offset of a continuous sound (filled interval) is often perceived to be longer than a time interval between two successive brief sounds (empty interval) of the same physical duration. The present study examined whether and how this phenomenon, sometimes called the filled duration illusion (FDI), occurs for short time intervals (40-520 ms). The investigation was conducted with the method of adjustment (Experiment 1) and the method of magnitude estimation (Experiment 2). When the method of adjustment was used, the FDI did not appear for the majority of the participants, but it appeared clearly for some participants. In the latter case, the amount of the FDI increased as the interval duration lengthened. The FDI was more likely to occur with magnitude estimation than with the method of adjustment. The participants who showed clear FDI with one method did not necessarily show such clear FDI with the other method.	t	\N
24218156	Declarative memory evaluation is an essential step in the clinical and neuropsychological assessment of a variety of neurological disorders. It typically addresses the issue of normality/abnormality of an individual's performance. Another clinical application of the neuropsychological assessment of declarative memory is the longitudinal evaluation of an individual's performance change. In fact, in a variety of neurological conditions repeated assessments are needed to evaluate the modifications of a memory disorder as a function of time or in response to a pharmacological or rehabilitation treatment. This study was aimed at collecting data for measuring and interpreting performance change on a memory test for verbal material. For this purpose, we administered to 100 healthy subjects (age range 20-80 years; years of formal education range 8-17 years) three parallel forms of a test requiring the immediate and delayed recall of a 15-word list. The subjects performed the recall test three times (each time with a different list) at least 1 week apart. The order of the lists was randomized across subjects. Results revealed that performance on the three lists was highly correlated and did not vary as a function of the order of presentation. However, accuracy of recall was slightly better on a list compared to the others. Based on a method devised by Payne and Jones (J Clin Psychol 13:115-121, 1957), we provide normative data for establishing whether a discrepancy in recall accuracy on two versions of the test exceeds the discrepancy expected based on the performance of normal controls.	t	\N
24218332	Sound localization is important for orienting and focusing attention and for segregating sounds from different sources in the environment. In humans, horizontal sound localization mainly relies on interaural differences in sound arrival time and sound level. Despite their perceptual importance, the neural processing of interaural time and level differences (ITDs and ILDs) remains poorly understood. Animal studies suggest that, in the brainstem, ITDs and ILDs are processed independently by different specialized circuits. The aim of the current study was to investigate whether, at higher processing levels, they remain independent or are integrated into a common code of sound laterality. For that, we measured late auditory cortical potentials in response to changes in sound lateralization elicited by perceptually matched changes in ITD and/or ILD. The responses to the ITD and ILD changes exhibited significant morphological differences. At the same time, however, they originated from overlapping areas of the cortex and showed clear evidence for functional coupling. These results suggest that the auditory cortex contains an integrated code of sound laterality, but also retains independent information about ITD and ILD cues. This cue-related information might be used to assess how consistent the cues are, and thus, how likely they would have arisen from the same source.	t	\N
24224991	Today's compression hearing aids with noise reduction systems may not manage transient noises effectively because of the short duration of these sounds compared to the onset times of the compressors and/or noise reduction algorithms. The current study was designed to evaluate the effect of a transient noise reduction (TNR) algorithm on listening comfort, speech intelligibility in quiet, and preferred wearer gain in the presence of transients. A single-blinded, repeated-measures design was used. Thirteen experienced hearing aid users with bilaterally symmetrical (≤7.5 dB) sensorineural hearing loss participated in the study. Speech identification in quiet (no transient noise) was identical between the TNR On and the TNR Off conditions. The participants showed subjective preference for the TNR algorithm when "comfortable listening" was used as the criterion. Participants preferred less gain than the default prescription in the presence of transient noise sounds. However, the preferred gain was 2.9 dB higher when the TNR was activated than when it was deactivated. This translated to 12.1% improvement in phoneme identification over the TNR Off condition for soft speech. This study demonstrated that the use of the TNR algorithm would not negatively affect speech identification. The results also suggested that this algorithm may improve listening comfort in the presence of transient noise sounds and ensure consistent use of prescribed gain. Such an algorithm may ensure more consistent audibility across listening environments.	t	\N
24225652	The aim of this study was to comprehensively evaluate the auditory phenotype in Niemann-Pick disease, type C1 (NPC1), to understand better the natural history of this complex, heterogeneous disorder, and to define further the baseline auditory deficits associated with NPC1 so that use of potentially ototoxic interventions (e.g., 2-hydroxypropyl-ß-cyclodextrin) may be more appropriately monitored and understood. Fifty patients with NPC1 ranging in age from 4 months to 21 years (mean = 9.3 years) enrolled in a natural history/observational study at the National Institutes of Health. The auditory test battery included, when possible, immittance audiometry, pure-tone and speech audiometry, otoacoustic emission testing, and a neurotologic auditory brainstem response study. Longitudinal data were collected on a subset of patients. Over half of the cohort exhibited hearing loss involving the high frequencies ranging from a slight to moderate degree, and 74% of patients presented with clinically significant hearing loss involving the frequencies most important to speech understanding (0.5, 1, 2, 4 kHz). Despite the heterogeneity of the sample, results among patients were sufficiently consistent to implicate retrocochlear dysfunction in the majority (66%) of individuals, with (22%) or without (44%) accompanying cochlear involvement. Some patients (10%) presented with a profile for auditory neuropathy spectrum disorder. The combination of cross-sectional and longitudinal data indicates these patients are at risk for a progressive decline in auditory function. This is the largest cohort of patients with NPC1 evaluated comprehensively for auditory dysfunction, and results implicate the pathological processes of NPC1 in the manifestation of hearing loss. Patients with NPC1 should be monitored audiologically throughout their lives, beginning at the time of diagnosis. Clinicians and researchers should be aware of this historically overlooked aspect of the phenotype.	t	\N
24227733	Previous imaging studies of congenital blindness have studied individuals with heterogeneous causes of blindness, which may influence the nature and extent of cross-modal plasticity. Here, we scanned a homogeneous group of blind people with bilateral congenital anophthalmia, a condition in which both eyes fail to develop, and, as a result, the visual pathway is not stimulated by either light or retinal waves. This model of congenital blindness presents an opportunity to investigate the effects of very early visual deafferentation on the functional organization of the brain. In anophthalmic animals, the occipital cortex receives direct subcortical auditory input. We hypothesized that this pattern of subcortical reorganization ought to result in a topographic mapping of auditory frequency information in the occipital cortex of anophthalmic people. Using functional MRI, we examined auditory-evoked activity to pure tones of high, medium, and low frequencies. Activity in the superior temporal cortex was significantly reduced in anophthalmic compared with sighted participants. In the occipital cortex, a region corresponding to the cytoarchitectural area V5/MT+ was activated in the anophthalmic participants but not in sighted controls. Whereas previous studies in the blind indicate that this cortical area is activated to auditory motion, our data show it is also active for trains of pure tone stimuli and in some anophthalmic participants shows a topographic mapping (tonotopy). Therefore, this region appears to be performing early sensory processing, possibly served by direct subcortical input from the pulvinar to V5/MT+.	t	\N
24230923	The Rey Auditory-Verbal Learning Test is an easy to administer test that assesses many memory domains and is, therefore, widely used in the area of clinical neuropsychology. The purpose of this study was to provide normative data for an elderly population living in Spain. The sample of this study was comprised of 156 volunteers over 60 years of age, which were grouped into six different age groups. These groups comprised of 10 participants between the ages of 61 and 65 in the first group, 23 participants (66-70) in the second, 28 participants (71-75) in the third, 35 participants (76-80) in the fourth, 32 participants (81-85)in the fifth and 28 participants (86-95) in the sixth group. Demographic data were collected and means, deviations, and ranges of all the measures were evaluated. Normative data were calculated from the percentiles, and then converted into age-corrected scaled scores with a mean of 10 and a standard deviation of 3.	t	\N
24231418	In the basic sciences, many researchers now use gap pre-pulse inhibition of the acoustic startle reflex (GPIAS) to determine if an animal has tinnitus after exposure to an ototoxic drug or intense noise. Tinnitus is assumed to be present if the silent gap in an ongoing narrow band noise (NBN) fails to suppress the startle reflex response evoked by an intense noise burst. The lack of gap pre-pulse inhibition presumably occurs because tinnitus fills in the silent intervals in the background noise. To test the perceptual aspects of this hypothesis, we asked hearing impaired subjects with tinnitus if they could perceive 50 ms silent intervals presented in a NBN, which was located above, below or at the subject's tinnitus pitch. The same tests were performed on normal hearing subjects without tinnitus. All subjects, with and without tinnitus, could detect the 50 ms gaps. Thus, using the stimulus parameters similar to those employed in animal and human GPIAS studies, we found that the tinnitus percept does not fill in the silent interval in a perceptual gap detection task; however, these finding do not rule out the possibility that tinnitus interferes with pre-attentive filtering of sensory stimuli in the GPIAS sensorimotor gating paradigm.	t	\N
24232066	Compare preoperative and postoperative performance in patients undergoing cochlear implantation (CI) for unilateral severe-to-profound sensorineural hearing loss (single-sided deafness, SSD). IRB-approved, prospective Tertiary center Twenty-nine patients have undergone CI for SSD. SSD was due to Ménière's disease (MD) in 10 subjects; these also suffered from recalcitrant vertigo spells and in these 10 patients along with 2 others the CI was placed simultaneous with a labyrinthectomy. CI with or without labyrinthectomy. CNC word and AzBio sentences in quiet were administered to the implanted ear. A multiple-loudspeaker sound localization test was administered in the bilateral listening condition. All data were collected preoperatively and 3, 6, and 12 months postoperatively with postoperative data available for 19 subjects. Additionally, a tinnitus handicap questionnaire is administered pre- and 12-months post-operatively. CNC word and AzBio sentence scores showed improvement in the implanted ear. Sound localization appeared to improve in an experience-dependent fashion in some patients. Most patients reported diminished tinnitus after cochlear implantation. All patients undergoing labyrinthectomy experienced resolution of vertigo attacks. CI restores auditory function to the deafened ear. Additionally, the binaural input appears to improve sound localization for most patients. In patients with severe hearing loss and recalcitrant vertigo attacks because of MD, simultaneous labyrinthectomy and CI effectively relieves vertigo attacks and improves auditory function.	t	\N
24234167	Are listeners able to adapt to a foreign-accented speaker who has, as is often the case, an inconsistent accent? Two groups of native Dutch listeners participated in a cross-modal priming experiment, either in a consistent-accent condition (German-accented items only) or in an inconsistent-accent condition (German-accented and nativelike pronunciations intermixed). The experimental words were identical for both groups (words with vowel substitutions characteristic of German-accented speech); additional contextual words differed in accentedness (German-accented or nativelike words). All items were spoken by the same speaker: a German native who could produce the accented forms but could also pass for a Dutch native speaker. Listeners in the consistent-accent group were able to adapt quickly to the speaker (i.e., showed facilitatory priming for words with vocalic substitutions). Listeners in the inconsistent-accent condition showed adaptation to words with vocalic substitutions only in the second half of the experiment. These results indicate that adaptation to foreign-accented speech is rapid. Accent inconsistency slows listeners down initially, but a short period of additional exposure is enough for them to adapt to the speaker. Listeners can therefore tolerate inconsistency in foreign-accented speech.	t	\N
24238764	Two experiments examined when monolingual, English-learning 19-month-old infants learn a second object label. Two experimenters sat together. One labeled a novel object with one novel label, whereas the other labeled the same object with a different label in either the same or a different language. Infants were tested on their comprehension of each label immediately following its presentation. Infants mapped the first label at above chance levels, but they did so with the second label only when requested by the speaker who provided it (Experiment 1) or when the second experimenter labeled the object in a different language (Experiment 2). These results show that 19-month-olds learn second object labels but do not readily generalize them across speakers of the same language. The results highlight how speaker and language spoken guide infants' acceptance of second labels, supporting sociopragmatic views of word learning.	t	\N
24256043	The procedure maximally retains the physiological structure of the middle ear and external auditory canal, thus effectively improving the patient's hearing ability. We explored the clinical outcomes of treating chronic suppurative otitis media using improved intact canal wall radical mastoidectomy with sandwich graft tympanoplasty. We chose to perform intact canal wall radical mastoidectomy with sandwich graft tympanoplasty in patients with chronic suppurative otitis media. A total of 170 patients were included in the study. Statistical analysis was carried out using software SPSS18.0, adjusted with the chi-squared test. In all, 140 cases were shown to have been treated effectively (82.35%, 140/170). The increased auditory threshold of preoperative bone conduction was not related to the duration of disease and/or the presence of cholesteatoma (p > 0.05), but was associated with ossicular chain disruption or fixation (p < 0.05), specifically the ossicular chain destruction/absorption, granulation tissue wrapping, and consequent fixation. During the procedure, the sleeve-like pedicle flap of external auditory canal and tympanic membrane is covered with graft, allowing good fixation with maintenance of the tympanic membrane's natural shape. The auditory threshold test revealed equal or above normal levels (30 dB) for 126 cases (74.12%, 126/170). The primary healing rate of tympanic membrane achieved was 96.47% (164/170).	t	\N
24258458	While bilateral cochlear implants (CIs) provide some binaural benefits, these benefits are limited compared to those observed in normal-hearing (NH) listeners. The large frequency-to-electrode allocation bandwidths (BWs) in CIs compared to auditory filter BWs in NH listeners increases the interaural fluctuation rate available for binaural unmasking, which may limit binaural benefits. The purpose of this work was to investigate the effect of interaural fluctuation rate on correlation change discrimination and binaural masking-level differences in NH listeners presented a CI simulation using a pulsed-sine vocoder. In experiment 1, correlation-change just-noticeable differences (JNDs) and tone-in-noise thresholds were measured for narrowband noises with different BWs and center frequencies (CFs). The results suggest that the BW, CF, and/or interaural fluctuation rate are important factors for correlation change discrimination. In experiment 2, the interaural fluctuation rate was systematically varied and dissociated from changes in BW and CF by using a pulsed-sine vocoder. Results indicated that the interaural fluctuation rate did not affect correlation change JNDs for correlated reference noises; however, slow interaural fluctuations increased correlation change JNDs for uncorrelated reference noises. In experiment 3, the BW, CF, and vocoder pulse rate were varied while interaural fluctuation rate was held constant. JNDs increased for increasing BW and decreased for increasing CF. In summary, relatively fast interaural fluctuation rates are not detrimental for detecting changes in interaural correlation. Thus, limiting factors to binaural benefits in CI listeners could be a result of other temporal and/or spectral deficiencies from electrical stimulation.	t	\N
24260183	In the real world, human speech recognition nearly always involves listening in background noise. The impact of such noise on speech signals and on intelligibility performance increases with the separation of the listener from the speaker. The present behavioral experiment provides an overview of the effects of such acoustic disturbances on speech perception in conditions approaching ecologically valid contexts. We analysed the intelligibility loss in spoken word lists with increasing listener-to-speaker distance in a typical low-level natural background noise. The noise was combined with the simple spherical amplitude attenuation due to distance, basically changing the signal-to-noise ratio (SNR). Therefore, our study draws attention to some of the most basic environmental constraints that have pervaded spoken communication throughout human history. We evaluated the ability of native French participants to recognize French monosyllabic words (spoken at 65.3 dB(A), reference at 1 meter) at distances between 11 to 33 meters, which corresponded to the SNRs most revealing of the progressive effect of the selected natural noise (-8.8 dB to -18.4 dB). Our results showed that in such conditions, identity of vowels is mostly preserved, with the striking peculiarity of the absence of confusion in vowels. The results also confirmed the functional role of consonants during lexical identification. The extensive analysis of recognition scores, confusion patterns and associated acoustic cues revealed that sonorant, sibilant and burst properties were the most important parameters influencing phoneme recognition. . Altogether these analyses allowed us to extract a resistance scale from consonant recognition scores. We also identified specific perceptual consonant confusion groups depending of the place in the words (onset vs. coda). Finally our data suggested that listeners may access some acoustic cues of the CV transition, opening interesting perspectives for future studies.	t	\N
24271979	Integrating visual and auditory language information is critical for reading. Suppression and congruency effects in audiovisual paradigms with letters and speech sounds have provided information about low-level mechanisms of grapheme-phoneme integration during reading. However, the central question about how such processes relate to reading entire words remains unexplored. Using ERPs, we investigated whether audiovisual integration occurs for words already in beginning readers, and if so, whether this integration is reflected by differences in map strength or topography (aim 1); and moreover, whether such integration is associated with reading fluency (aim 2). A 128-channel EEG was recorded while 69 monolingual (Swiss)-German speaking first-graders performed a detection task with rare targets. Stimuli were presented in blocks either auditorily (A), visually (V) or audiovisually (matching: AVM; nonmatching: AVN). Corresponding ERPs were computed, and unimodal ERPs summated (A + V = sumAV). We applied TANOVAs to identify time windows with significant integration effects: suppression (sumAV-AVM) and congruency (AVN-AVM). They were further characterized using GFP and 3D-centroid analyses, and significant effects were correlated with reading fluency. The results suggest that audiovisual suppression effects occur for familiar German and unfamiliar English words, whereas audiovisual congruency effects can be found only for familiar German words, probably due to lexical-semantic processes involved. Moreover, congruency effects were characterized by topographic differences, indicating that different sources are active during processing of congruent compared to incongruent audiovisual words. Furthermore, no clear associations between audiovisual integration and reading fluency were found. The degree to which such associations develop in beginning readers remains open to further investigation.	t	\N
24278326	The purpose of this study was to design and to verify a new hearing-aid fitting strategy (Aescu HRL-1) based on the acoustic features of Mandarin. The subjective and objective outcomes were compared to those fitted with NAL-NL1 (National Acoustic Laboratory Non-Linear, version1) in Mandarin-speaking hearing-aid users. Fifteen subjects with sensorineural hearing loss participated in this preliminary study. Each subject wore a pair of four-channel hearing aids fitted with the Aescu HRL-1 and NAL-NL1 prescriptions alternatively for 1 month. Objective and subjective tests including the Mandarin Monosyllable Recognition Test (MMRT), Mandarin Hearing in Noise Test (MHINT), International Outcome Inventory for Hearing Aids (IOI-HA), and a sound-quality questionnaire were used to evaluate the performance of the two prescriptions. The mean MMRT scores were 79.9% and 81.1% for NAL-NL1 and Aescu HRL-1 respectively. They are not statistically different. The corresponding MHINT signal-to-noise ratios were 0.87 and 0.85 dB, also, no significant difference was found between these two strategies. However, in subjective questionnaires, overall, the sound-quality and IOI-HA scores were higher for Aescu HRL-1. The speech recognition performance based on Aescu HRL-1 is as good as that of NAL-NL1 for Mandarin-speaking hearing-aid users. Moreover, the subjects generally responded that Aescu HRL-1 provides a more natural, richer, and better sound quality than does NAL-NL1.	t	\N
24296543	The acoustic basis of intelligibility associated with varied clear speech instructions was studied. Twelve healthy speakers read 18 sentences in 'habitual', 'clear', 'hearing impaired' and 'overenunciate' conditions. The latter 3 conditions are varieties of clear speech. Acoustic measures included tense and lax vowel space area, a measure of vowel spectral change, articulation rate and sentence-level vocal intensity. Sentences were mixed with multitalker babble to prevent ceiling effects and were orthographically transcribed by 40 listeners. Percent-correct scores were obtained for each speaker and condition. Regression analyses were used to quantify relationships between acoustic measures and intelligibility. Univariate regressions indicated that greater magnitudes of acoustic change in nonhabitual conditions were associated with greater increases in intelligibility. Multivariate regression analysis further indicated that lax vowel space, articulation rate and vocal intensity were significant predictors of intelligibility. Acoustic variables associated with intelligibility differed depending on whether relationships were examined using univariate or multivariate statistics. Multivariate statistics indicated that articulation rate was the strongest predictor of improvements in intelligibility above and beyond all other variables studied. The findings have implications for optimizing therapeutic use of clear speech for clinical populations.	t	\N
24302571	The activity of sensory neural populations carries information about the environment. This may be extracted from neural activity using different strategies. In the auditory brainstem, a recent theory proposes that sound location in the horizontal plane is decoded from the relative summed activity of two populations in each hemisphere, whereas earlier theories hypothesized that the location was decoded from the identity of the most active cells. We tested the performance of various decoders of neural responses in increasingly complex acoustical situations, including spectrum variations, noise, and sound diffraction. We demonstrate that there is insufficient information in the pooled activity of each hemisphere to estimate sound direction in a reliable way consistent with behavior, whereas robust estimates can be obtained from neural activity by taking into account the heterogeneous tuning of cells. These estimates can still be obtained when only contralateral neural responses are used, consistently with unilateral lesion studies. DOI: http://dx.doi.org/10.7554/eLife.01312.001.	t	\N
24311693	Dyslexia is a severe and persistent reading and spelling disorder caused by impairment in the ability to manipulate speech sounds. We combined functional magnetic resonance brain imaging with multivoxel pattern analysis and functional and structural connectivity analysis in an effort to disentangle whether dyslexics' phonological deficits are caused by poor quality of the phonetic representations or by difficulties in accessing intact phonetic representations. We found that phonetic representations are hosted bilaterally in primary and secondary auditory cortices and that their neural quality (in terms of robustness and distinctness) is intact in adults with dyslexia. However, the functional and structural connectivity between the bilateral auditory cortices and the left inferior frontal gyrus (a region involved in higher-level phonological processing) is significantly hampered in dyslexics, suggesting deficient access to otherwise intact phonetic representations.	t	\N
24312408	Nucleus cochlear implant systems incorporate a fast-acting front-end automatic gain control (AGC), sometimes called a compression limiter. The objective of the present study was to determine the effect of replacing the front-end compression limiter with a newly proposed envelope profile limiter. A secondary objective was to investigate the effect of AGC speed on cochlear implant speech intelligibility. The envelope profile limiter was located after the filter bank and reduced the gain when the largest of the filter bank envelopes exceeded the compression threshold. The compression threshold was set equal to the saturation level of the loudness growth function (i.e. the envelope level that mapped to the maximum comfortable current level), ensuring that no envelope clipping occurred. To preserve the spectral profile, the same gain was applied to all channels. Experiment 1 compared sentence recognition with the front-end limiter and with the envelope profile limiter, each with two release times (75 and 625 ms). Six implant recipients were tested in quiet and in four-talker babble noise, at a high presentation level of 89 dB SPL. Overall, release time had a larger effect than the AGC type. With both AGC types, speech intelligibility was lower for the 75 ms release time than for the 625 ms release time. With the shorter release time, the envelope profile limiter provided higher group mean scores than the front-end limiter in quiet, but there was no significant difference in noise. Experiment 2 measured sentence recognition in noise as a function of presentation level, from 55 to 89 dB SPL. The envelope profile limiter with 625 ms release time yielded better scores than the front-end limiter with 75 ms release time. A take-home study showed no clear pattern of preferences. It is concluded that the envelope profile limiter is a feasible alternative to a front-end compression limiter.	t	\N
24317426	Previous research demonstrates that meaningfully related sounds enhance visual sensitivity to point-light displays of human movement. Here we report two psychophysical studies that investigated whether, and if so when, this facilitation is modulated by the temporal relationship between auditory and visual stimuli. In Experiment 1, participants detected point-light walkers in masks while listening to footsteps that were either synchronous or out-of-phase with point-light footfalls. The relative timing of auditory and visual walking did not impact performance. Experiment 2 further tested the importance of multisensory timing by disrupting the rhythm of the auditory and visual streams. Participants detected point-light walkers while listening to footstep or tone sounds that were either synchronous or temporally random with regards to point-light footfalls. Heard footsteps improved visual sensitivity over heard tones regardless of timing. Taken together, these results suggest that during the detection of others' actions, the perceptual system makes use of meaningfully related sounds whether or not they are synchronous. These results are discussed in relation to the unity assumption theory as well as recent empirical data that suggest that temporal correspondence is not always a critical factor in multisensory perception and integration.	t	\N
24329490	To link outcome measures used in audiological research to the ICF classification and thereby describe audiological research from the ICF perspective. Through a peer-reviewed or a joint linking procedure, link outcome measures to the ICF classification system using standardized ICF linking rules. Additional linking rules were developed in combination with the established rules to overcome difficulties when connecting audiological data to ICF. Absolute and relative frequencies of ICF categories were reported. The identified outcome measures from the previous study (Part I) constituted the empirical material. In total, 285 ICF categories were identified. The most prevalent categories were related to listening, hearing functions, auditory perceptions, emotions and the physical environment, such as noise and hearing aids. Categories related to communication showed lower relative frequencies, as did categories related to the social and attitudinal environment. Based on the linked outcome measures, communication as a research topic is subordinated to other research topics. The same conclusion can be drawn for research targeting the social and attitudinal environment of adults with HL. Difficulties in the linking procedure were highlighted and discussed, and suggestions for future revisions of the ICF from the audiological perspective were described.	t	\N
24333301	Mutations in the connexin 26 gene (GJB2) are the most common genetic cause of deafness, leading to congenital bilateral non-syndromic sensorineural hearing loss. Here we report the generation of a mouse model for a connexin 26 (Cx26) mutation, in which cre-Sox10 drives excision of the Cx26 gene from non-sensory cells flanking the auditory epithelium. We determined that these conditional knockout mice, designated Gjb2-CKO, have a severe hearing loss. Immunocytochemistry of the auditory epithelium confirmed absence of Cx26 in the non-sensory cells. Histology of the organ of Corti and the spiral ganglion neurons (SGNs) performed at ages 1, 3, or 6 months revealed that in Gjb2-CKO mice, the organ of Corti began to degenerate in the basal cochlear turn at an early stage, and the degeneration rapidly spread to the apex. In addition, the density of SGNs in Rosenthal's canal decreased rapidly along a gradient from the base of the cochlea to the apex, where some SGNs survived until at least 6 months of age. Surviving neurons often clustered together and formed clumps of cells in the canal. We then assessed the influence of brain derived neurotrophic factor (BDNF) gene therapy on the SGNs of Gjb2-CKO mice by inoculating Adenovirus with the BDNF gene insert (Ad.BDNF) into the base of the cochlea via the scala tympani or scala media. We determined that over-expression of BDNF beginning around 1 month of age resulted in a significant rescue of neurons in Rosenthal's canal of the cochlear basal turn but not in the middle or apical portions. This data may be used to design therapies for enhancing the SGN physiological status in all GJB2 patients and especially in a sub-group of GJB2 patients where the hearing loss progresses due to ongoing degeneration of the auditory nerve, thereby improving the outcome of cochlear implant therapy in these ears.	t	\N
24342151	The purpose of the study was to identify structural brain differences in school-age children with residual speech sound errors. Voxel based morphometry was used to compare gray and white matter volumes for 23 children with speech sound errors, ages 8;6-11;11, and 54 typically speaking children matched on age, oral language, and IQ. We hypothesized that regions associated with production and perception of speech sounds would differ between groups. Results indicated greater gray matter volumes for the speech sound error group relative to typically speaking controls in bilateral superior temporal gyrus. There was greater white matter volume in the corpus callosum for the speech sound error group, but less white matter volume in right lateral occipital gyrus. Results may indicate delays in neuronal pruning in critical speech regions or differences in the development of networks for speech perception and production.	t	\N
24344364	Previous studies in both humans and animals have documented improved performance following discrimination training. This enhanced performance is often associated with cortical response changes. In this study, we tested the hypothesis that long-term speech training on multiple tasks can improve primary auditory cortex (A1) responses compared to rats trained on a single speech discrimination task or experimentally naïve rats. Specifically, we compared the percent of A1 responding to trained sounds, the responses to both trained and untrained sounds, receptive field properties of A1 neurons, and the neural discrimination of pairs of speech sounds in speech trained and naïve rats. Speech training led to accurate discrimination of consonant and vowel sounds, but did not enhance A1 response strength or the neural discrimination of these sounds. Speech training altered tone responses in rats trained on six speech discrimination tasks but not in rats trained on a single speech discrimination task. Extensive speech training resulted in broader frequency tuning, shorter onset latencies, a decreased driven response to tones, and caused a shift in the frequency map to favor tones in the range where speech sounds are the loudest. Both the number of trained tasks and the number of days of training strongly predict the percent of A1 responding to a low frequency tone. Rats trained on a single speech discrimination task performed less accurately than rats trained on multiple tasks and did not exhibit A1 response changes. Our results indicate that extensive speech training can reorganize the A1 frequency map, which may have downstream consequences on speech sound processing.	t	\N
24344815	Dyslexia is commonly attributed to a phonological deficit, but whether it effectively compromises the phonological grammar or lower level systems is rarely explored. To address this question, we gauge the sensitivity of dyslexics to grammatical phonological restrictions on spoken onset clusters (e.g., bl in block). Across languages, certain onsets are preferred to others (e.g., blif ≻ bnif ≻ bdif, where ≻ indicates a preference). Here, we show that dyslexic participants (adult native speakers of Hebrew) are fully sensitive to these phonological restrictions, and they extend them irrespective of whether the onsets are attested in their language (e.g., bnif vs. bdif) or unattested (e.g., mlif vs. mdif). Dyslexics, however, showed reduced sensitivity to phonetic contrasts (e.g., blif vs. belif; ba vs. pa). Together, these results suggest that the known difficulties of dyslexics in speech processing could emanate not from the phonological grammar, but rather from lower level impairments to acoustic/phonetic encoding, lexical storage, and retrieval.	t	\N
24349414	The diagnosis of tinnitus relies on self-report. Psychoacoustic measurements of tinnitus pitch and loudness are essential for assessing claims and discriminating true from false ones. For this reason, the quantification of tinnitus remains a challenging research goal. We aimed to: (1) assess the precision of a new tinnitus likeness rating procedure with a continuous-pitch presentation method, controlling for music training, and (2) test whether tinnitus psychoacoustic measurements have the sensitivity and specificity required to detect people faking tinnitus. Musicians and non-musicians with tinnitus, as well as simulated malingerers without tinnitus, were tested. Most were retested several weeks later. Tinnitus pitch matching was first assessed using the likeness rating method: pure tones from 0.25 to 16 kHz were presented randomly to participants, who had to rate the likeness of each tone to their tinnitus, and to adjust its level from 0 to 100 dB SPL. Tinnitus pitch matching was then assessed with a continuous-pitch method: participants had to match the pitch of their tinnitus to an external tone by moving their finger across a touch-sensitive strip, which generated a continuous pure tone from 0.5 to 20 kHz in 1-Hz steps. The predominant tinnitus pitch was consistent across both methods for both musicians and non-musicians, although musicians displayed better external tone pitch matching abilities. Simulated malingerers rated loudness much higher than did the other groups with a high degree of specificity (94.4%) and were unreliable in loudness (not pitch) matching from one session to the other. Retest data showed similar pitch matching responses for both methods for all participants. In conclusion, tinnitus pitch and loudness reliably correspond to the tinnitus percept, and psychoacoustic loudness matches are sensitive and specific to the presence of tinnitus.	t	\N
24350693	To investigate the predicted threshold shift associated with the use of nonlinear hearing aids fitted to the NAL-NL2 or the DSL m[i/o] prescription for children with the same audiograms. For medium and high input levels, we asked: (1) How does predicted asymptotic threshold shifts (ATS) differ according to the choice of prescription? (2) How does predicted ATS vary with hearing level for gains prescribed by the two prescriptions? A mathematical model consisting of the modified power law combined with equations for predicting temporary threshold shift (Macrae, 1994b) was used to predict ATS. Predicted threshold shift were determined for 57 audiograms at medium and high input levels. For the 57 audiograms, DSL m[i/o] gains for high input levels were associated with increased risk relative to NAL-NL2. The variation of ATS with hearing level suggests that NAL-NL2 gains became unsafe when hearing loss > 90 dB HL. The gains prescribed by DSL m[i/o] became unsafe when hearing loss > 80 dB HL at a medium input level, and > 70 dB HL at a high input level. There is a risk of damage to hearing for children using nonlinear amplification. Vigilant checking for threshold shift is recommended.	t	\N
24357104	Middle ear disease is the primary cause of hearing loss in children and has a significant impact on language development and academic performance. Multiple prognostic factors have previously been examined, but there is little published data regarding frequency-specific hearing outcomes. To examine the relationship between type I tympanoplasty in a pediatric population and frequency-specific hearing changes, as well as the relationship between several prognostic factors and graft retention. Retrospective medical chart review (February 2006 to October 2011) of 492 consecutive pediatric otolaryngology patients undergoing type I tympanoplasty for tympanic membrane (TM) perforation of any etiology at a tertiary-care pediatric otolaryngology practice. Type I tympanoplasty. Preoperative and postoperative audiometric data were collected for patients undergoing successful TM repair. It was hypothesized before data collection that conductive hearing would improve at all frequencies with no significant change in sensorineural hearing. Data collected included air conduction at 250 to 8000 Hz, speech reception thresholds, bone conduction at 500 to 4000 Hz, and air-bone gap at 500 to 4000 Hz. Demographic data obtained included sex, age, size, mechanism, location of perforation, and operative repair technique. Of 492 patients, 320 were excluded; results were thus examined for 172 patients. Surgery was successful for 73.8% of patients. Perforation size was significantly associated with repair success (mean [SD] surgical success rate of 38.6% [15.3%] vs surgical failure rate of 31.4% [15.0%]; P < .01); however, mean (SD) age (9.02 [3.89] years [surgical success] vs 8.52 [3.43] years [surgical failure]; P > .05) and repair technique (medial [73.08%] vs lateral [76.47%] graft success; P > .99) were not. Air conduction significantly improved from 250 to 2000 Hz (P < .001), did not significantly improve at 4000 Hz (P = .08), and there was a nonsignificant decline at 8000 Hz (P = .12). Speech reception threshold significantly improved (20 vs 15 dB; P < .001). This large review found an association of TM perforation size with surgical success and an improvement in speech reception threshold, air conduction at 250 to 2000 Hz, air-bone gap at 500 to 2000 Hz, and worsening bone conduction at 4000 Hz. Patients with high-frequency hearing loss due to TM perforation should not anticipate significant recovery from type I tympanoplasty. Hearing loss at higher frequencies may require postoperative hearing rehabilitation.	t	\N
24364392	Previous research has shown that damage to the left temporal pole (LTP) is associated with impaired retrieval of words for unique entities, including names of famous people and landmarks. However, it is not known whether retrieving names for famous melodies is associated with the LTP. The aim of this study was to investigate the hypothesis that damage to the LTP would be associated with impaired naming of famous musical melodies. A Melody Naming Test was administered to patients with LTP damage, brain damaged comparison (BDC) patients, and normal comparison participants (NC). The test included various well-known melodies (e.g., "Pop Goes the Weasel"). After hearing each melody, participants were asked to rate their familiarity with the melody and identify it by name. LTP patients named significantly fewer melodies than BDC and NC participants. Recognition of melodies did not differ significantly between groups. The findings suggest that LTP supports retrieval of names for famous melodies. More broadly, these results extend support for the theoretical notion that LTP is important for retrieving proper names for unique concepts, irrespectively of stimulus modality or category.	t	\N
24366693	The visual cues involved in auditory speech processing are not restricted to information from lip movements but also include head or chin gestures and facial expressions such as eyebrow movements. The fact that visual gestures precede the auditory signal implicates that visual information may influence the auditory activity. As visual stimuli are very close in time to the auditory information for audiovisual syllables, the cortical response to them usually overlaps with that for the auditory stimulation; the neural dynamics underlying the visual facilitation for continuous speech therefore remain unclear. In this study, we used a three-word phrase to study continuous speech processing. We presented video clips with even (without emphasis) phrases as the frequent stimuli and with one word visually emphasized by the speaker as the non-frequent stimuli. Negativity in the resulting ERPs was detected after the start of the emphasizing articulatory movements but before the auditory stimulus, a finding that was confirmed by the statistical comparisons of the audiovisual and visual stimulation. No such negativity was present in the control visual-only condition. The propagation of this negativity was observed between the visual and fronto-temporal electrodes. Thus, in continuous speech, the visual modality evokes predictive coding for the auditory speech, which is analysed by the cerebral cortex in the context of the phrase even before the arrival of the corresponding auditory signal.	t	\N
24372066	In this study, 35 young, healthy adults were tested on whether speech-like stimuli evoke a unique response in the auditory efferent system. To this end, descending cortical influences on medial olivocochlear (MOC) activity were indirectly evaluated by studying the effects of contralateral suppression on distortion product otoacoustic emissions (DPOAEs) under four conditions: (a) in the absence of any contralateral noise (Baseline), (b) presence of contralateral broadband noise (Noise Baseline), (c) vowel discrimination-in-noise task (VDN) and (d) tone discrimination-in-noise (TDN) task. A statistically significant release from suppression was evident across all tested DPOAE frequencies (1, 1.5 and 2 kHz) only for the VDN task (p < 0.05), which yielded greater release from suppression than the TDN task. These findings indicate that during active listening in the presence of noise, the MOC activity may be differentially modulated depending on the type of stimulus (vowel vs. tone). Specifically, in the presence of background noise, vowels may show a greater release from suppression in the cochlea than frequency, intensity and duration matched tones.	t	\N
24376601	During sentence production, linguistic information (semantics, syntax, phonology) of words is retrieved and assembled into a meaningful utterance. There is still debate on how we assemble single words into more complex syntactic structures such as noun phrases or sentences. In the present study, event-related potentials (ERPs) were used to investigate the time course of syntactic planning. Thirty-three volunteers described visually animated scenes using naming formats varying in syntactic complexity: from simple words ('W', e.g., "triangle", "red", "square", "green", "to fly towards"), to noun phrases ('NP', e.g., "the red triangle", "the green square", "to fly towards"), to a sentence ('S', e.g., "The red triangle flies towards the green square."). Behaviourally, we observed an increase in errors and corrections with increasing syntactic complexity, indicating a successful experimental manipulation. In the ERPs following scene onset, syntactic complexity variations were found in a P300-like component ('S'/'NP'>'W') and a fronto-central negativity (linear increase with syntactic complexity). In addition, the scene could display two actions - unpredictable for the participant, as the disambiguation occurred only later in the animation. Time-locked to the moment of visual disambiguation of the action and thus the verb, we observed another P300 component ('S'>'NP'/'W'). The data show for the first time evidence of sensitivity to syntactic planning within the P300 time window, time-locked to visual events critical of syntactic planning. We discuss the findings in the light of current syntactic planning views.	t	\N
24376662	Previous research suggests that deficits in attention-emotion interaction are implicated in schizophrenia symptoms. Although disruption in auditory processing is crucial in the pathophysiology of schizophrenia, deficits in interaction between emotional processing of auditorily presented language stimuli and auditory attention have not yet been clarified. To address this issue, the current study used a dichotic listening task to examine 22 patients with schizophrenia and 24 age-, sex-, parental socioeconomic background-, handedness-, dexterous ear-, and intelligence quotient-matched healthy controls. The participants completed a word recognition task on the attended side in which a word with emotionally valenced content (negative/positive/neutral) was presented to one ear and a different neutral word was presented to the other ear. Participants selectively attended to either ear. In the control subjects, presentation of negative but not positive word stimuli provoked a significantly prolonged reaction time compared with presentation of neutral word stimuli. This interference effect for negative words existed whether or not subjects directed attention to the negative words. This interference effect was significantly smaller in the patients with schizophrenia than in the healthy controls. Furthermore, the smaller interference effect was significantly correlated with severe positive symptoms and delusional behavior in the patients with schizophrenia. The present findings suggest that aberrant interaction between semantic processing of negative emotional content and auditory attention plays a role in production of positive symptoms in schizophrenia. (224 words).	t	\N
24384081	Large variations in perceptual directional microphone benefit, which far exceed the variation expected from physical performance measures of directional microphones, have been reported in the literature. The cause for the individual variation has not been systematically investigated. To determine the factors that are responsible for the individual variation in reported perceptual directional benefit. A correlational study. Physical performance measures of the directional microphones obtained after they had been fitted to individuals, cognitive abilities of individuals, and measurement errors were related to perceptual directional benefit scores. Fifty-nine hearing-impaired adults with varied degrees of hearing loss participated in the study. All participants were bilaterally fitted with a Motion behind-the-ear device (500 M, 501 SX, or 501 P) from Siemens according to the National Acoustic Laboratories' non-linear prescription, version two (NAL-NL2). Using the Bamford-Kowal-Bench (BKB) sentences, the perceptual directional benefit was obtained as the difference in speech reception threshold measured in babble noise (SRTn) with the devices in directional (fixed hypercardioid) and in omnidirectional mode. The SRTn measurements were repeated three times with each microphone mode. Physical performance measures of the directional microphone included the angle of the microphone ports to loudspeaker axis, the frequency range dominated by amplified sound, the in situ signal-to-noise ratio (SNR), and the in situ three-dimensional, articulation-index weighted directivity index (3D AI-DI). The cognitive tests included auditory selective attention, speed of processing, and working memory. Intraparticipant variation on the repeated SRTn's and the interparticipant variation on the average SRTn were used to determine the effect of measurement error. A multiple regression analysis was used to determine the effect of other factors. Measurement errors explained 52% of the variation in perceptual directional microphone benefit (95% confidence interval [CI]: 34-78%), while another 37% of variation was explained primarily by the physical performance of the directional microphones after they were fitted to individuals. The most contributing factor was the in situ 3D AI-DI measured across the low frequencies. Repeated SRTn measurements are needed to obtain a reliable indication of the perceptual directional benefit in an individual. Further, to obtain optimum benefit from directional microphones, the effectiveness of the microphones should be maximized across the low frequencies.	t	\N
24386719	Listener retention of silent, gap-length duration was studied. Just noticeable differences (JNDs) for gap length within standard and comparison stimuli were obtained for intervals with and without intervening noise bursts, including a condition with gapped intervening bursts. Outcomes indicate that gap duration itself can be determinant. Also, JNDs were similar whether intervening stimuli were present or absent, differing from results reported for pitch, loudness, and timbre retention. The latter suggests additional/alternative cortical resources might be employed for retention of auditory-temporal information.	t	\N
24408329	To investigate the auditory behavior of patients with chronic renal failure (CRF) undergoing kidney transplantation. Thirty patients were evaluated, 10 (33.33%) females and 20 (66.67%) males, aging from 13 to 26 years (average, 16.97 years; standard deviation, 3.60 years). Patients underwent the following procedures: anamnesis, otolaryngological examination, audiological evaluation (pure tone and high frequency), acoustic impedance measurements and central auditory processing evaluation. A control group was used to compare the high-frequency audiometry results. The following observations were made: absence of auditory complaints at the time of anamnesis; pure-tone audiometry was predominantly normal; patients presented lower hearing levels at the high-frequency audiometry, when compared to the control group, and as for the acoustic impedance measurements, curves of the type A were predominant; there was a change of the central auditory processing for 14 patients (46.67%) in the Staggered Spondaic Word Test (SSW); there was a significant difference between the age variable and the result of the pure-tone audiometry, that is, hearing sensitivity in thresholds from 250Hz to 8,000Hz decreased with advancing age; and the relation between the type of donor and the SSW test result was significant. Rates were higher when the patients had been transplanted from deceased donors compared to living donors. There were no changes in conventional audiological and high-frequency evaluation, or in the central auditory processing. Professionals involved in the care of kidney transplantation recipients must be better informed about the care, prevention, and early identification of auditory disorders.	t	\N
24408330	The objective of this research was to assess the auditory abilities of Portuguese children and compare such abilities to the score of the Scale of Auditory Behaviors (SAB). Fifty-one children were evaluated with audiometry, speech audiometry, acoustic immittance measures, and eight behavioral tests involving dichotic listening, monotic listening, temporal processing, and sound localization. Their parents filled in the SAB questionnaire adapted to European A. SAB scores and auditory tests scores were submitted to Pearson's correlation coefficient. There is significant correlation between the score on SAB questionnaire and the auditory processing tests. The greatest coefficient was observed in temporal processing test (p=0.000). There was correlation between the score of SAB and the performance in auditory processing tests, suggesting that the SAB may be used for auditory processing screening.	t	\N
24413019	The neural underpinnings of auditory information processing have often been investigated using the odd-ball paradigm, in which infrequent sounds (deviants) are presented within a regular train of frequent stimuli (standards). Traditionally, this paradigm has been applied using either high temporal resolution (EEG) or high spatial resolution (fMRI, PET). However, used separately, these techniques cannot provide information on both the location and time course of particular neural processes. The goal of this study was to investigate the neural correlates of auditory processes with a fine spatio-temporal resolution. A simultaneous auditory evoked potentials (AEP) and functional magnetic resonance imaging (fMRI) technique (AEP-fMRI), together with an odd-ball paradigm, were used. Six healthy volunteers, aged 20-35 years, participated in an odd-ball simultaneous AEP-fMRI experiment. AEP in response to acoustic stimuli were used to model bioelectric intracerebral generators, and electrophysiological results were integrated with fMRI data. fMRI activation evoked by standard stimuli was found to occur mainly in the primary auditory cortex. Activity in these regions overlapped with intracerebral bioelectric sources (dipoles) of the N1 component. Dipoles of the N1/P2 complex in response to standard stimuli were also found in the auditory pathway between the thalamus and the auditory cortex. Deviant stimuli induced fMRI activity in the anterior cingulate gyrus, insula, and parietal lobes. The present study showed that neural processes evoked by standard stimuli occur predominantly in subcortical and cortical structures of the auditory pathway. Deviants activate areas non-specific for auditory information processing.	t	\N
24419006	Three experiments investigated the role of memory and rehearsal in a dichotic emotion recognition task by manipulating the response procedure as well as the interval between encoding and retrieval while taking into account order of report. For all experiments, right-handed undergraduates were presented with dichotic pairs of the words bower, dower, power, and tower pronounced in a sad, angry, happy, or neutral tone of voice. Participants were asked to report the two emotions presented on each trial by clicking on the corresponding drawings or words on a computer screen, either following no delay or a five second delay. Experiment 1 applied the delay conditions as a between-subjects factor whereas it was a within-subject factor in Experiment 2. In Experiments 1 and 2, more correct responses occurred for the left than the right ear, reflecting a left ear advantage (LEA) that was slightly larger with a nonverbal than a verbal response. The LEA was also found to be larger with no delay than with the 5s delay. In addition, participants typically responded first to the left ear stimulus. In fact, the first response produced a LEA whereas the second response produced a right ear advantage. Experiment 3 involved a concurrent task during the delay to prevent rehearsal. In Experiment 3, the pattern of results supported the claim that rehearsal could account for the findings of the first two experiments. The findings are interpreted in the context of the role of rehearsal and memory in models of dichotic listening.	t	\N
24429136	How humans solve the cocktail party problem remains unknown. However, progress has been made recently thanks to the realization that cortical activity tracks the amplitude envelope of speech. This has led to the development of regression methods for studying the neurophysiology of continuous speech. One such method, known as stimulus-reconstruction, has been successfully utilized with cortical surface recordings and magnetoencephalography (MEG). However, the former is invasive and gives a relatively restricted view of processing along the auditory hierarchy, whereas the latter is expensive and rare. Thus it would be extremely useful for research in many populations if stimulus-reconstruction was effective using electroencephalography (EEG), a widely available and inexpensive technology. Here we show that single-trial (≈60 s) unaveraged EEG data can be decoded to determine attentional selection in a naturalistic multispeaker environment. Furthermore, we show a significant correlation between our EEG-based measure of attention and performance on a high-level attention task. In addition, by attempting to decode attention at individual latencies, we identify neural processing at ∼200 ms as being critical for solving the cocktail party problem. These findings open up new avenues for studying the ongoing dynamics of cognition using EEG and for developing effective and natural brain-computer interfaces.	t	\N
24429520	Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere. Although various theories have been proposed to unite perception and production, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system. Although recent evidence indicates that speech perception occurs bilaterally, prevailing models maintain that the speech sensory-motor system is left lateralized and facilitates the transformation from sensory-based auditory representations to motor-based production representations. However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging. Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural responses during both perception and production in an overt word-repetition task. Using a non-word transformation task, we show that bilateral sensory-motor responses can perform transformations between speech-perception- and speech-production-based representations. These results establish a bilateral sublexical speech sensory-motor system.	t	\N
24431427	The new DSM-5 diagnostic criteria for autism spectrum disorders (ASDs) include sensory disturbances in addition to the well-established language, communication, and social deficits. One sensory disturbance seen in ASD is an impaired ability to integrate multisensory information into a unified percept. This may arise from an underlying impairment in which individuals with ASD have difficulty perceiving the temporal relationship between cross-modal inputs, an important cue for multisensory integration. Such impairments in multisensory processing may cascade into higher-level deficits, impairing day-to-day functioning on tasks, such as speech perception. To investigate multisensory temporal processing deficits in ASD and their links to speech processing, the current study mapped performance on a number of multisensory temporal tasks (with both simple and complex stimuli) onto the ability of individuals with ASD to perceptually bind audiovisual speech signals. High-functioning children with ASD were compared with a group of typically developing children. Performance on the multisensory temporal tasks varied with stimulus complexity for both groups; less precise temporal processing was observed with increasing stimulus complexity. Notably, individuals with ASD showed a speech-specific deficit in multisensory temporal processing. Most importantly, the strength of perceptual binding of audiovisual speech observed in individuals with ASD was strongly related to their low-level multisensory temporal processing abilities. Collectively, the results represent the first to illustrate links between multisensory temporal function and speech processing in ASD, strongly suggesting that deficits in low-level sensory processing may cascade into higher-order domains, such as language and communication.	t	\N
24437771	Auditory deprivation and stimulation can change the threshold of the acoustic middle ear reflex as well as loudness in adult listeners. However, it has remained unclear whether changes in these measures are due to the same mechanism. In this study, deprivation was achieved using a monaural earplug that was worn by listeners for 7 days. Acoustic reflex thresholds (ARTs) and categorical loudness ratings were measured using a blinded design in which the experimenter was unaware of which ear had been plugged. Immediately after terminating unilateral deprivation, ARTs were obtained at a lower sound pressure level in the ear that had been fitted with an earplug and at a higher sound pressure level in the control ear. In contrast, categorical judgments of loudness changed in the same direction in both ears with a given stimulus level reported as louder after unilateral deprivation. The relationship between changes to the ART and loudness judgments was not statistically significant. For both the ARTs and the categorical loudness judgments, most of the changes had disappeared within 24 h after earplug removal. The changes in ARTs, as a consequence of unilateral sound deprivation, are consistent with a gain control mechanism; however, the lack of relationship with the categorical loudness judgments, and the different pattern of findings for each measure, suggests the possibility of multiple gain mechanisms.	t	\N
24437774	The discrimination of interaural phase differences (IPDs) requires accurate binaural temporal processing and has been used as a measure of sensitivity to temporal envelope and temporal fine structure (TFS). Previous studies found that TFS-IPD discrimination declined with age and with sensorineural hearing loss (SNHL), but age and SNHL have often been confounded. The aim of this study was to determine the independent contributions of age and SNHL to TFS and envelope IPD discrimination by using a sample of adults with a wide range of ages and SNHL. A two-interval, two-alternative forced-choice procedure was used to measure IPD discrimination thresholds for 20-Hz amplitude-modulated tones with carrier frequencies of 250 or 500 Hz when the IPD was in either the stimulus envelope or TFS. There were positive correlations between absolute thresholds and TFS-IPD thresholds, but not envelope-IPD thresholds, when age was accounted for. This supports the idea that SNHL affects TFS processing independently to age. Age was positively correlated with envelope-IPD thresholds at both carrier frequencies and TFS-IPD thresholds at 500 Hz, when absolute thresholds were accounted for. These results suggest that age negatively affects the binaural processing of envelope and TFS at some frequencies independently of SNHL.	t	\N
24441742	Abnormal hearing tests have been noted in human immunodeficiency virus (HIV)-infected patients in several studies, but the nature of the hearing deficit has not been clearly defined. The authors performed a cross-sectional study of both HIV+ and HIV- individuals in Tanzania by using an audiological test battery. The authors hypothesized that HIV+ adults would have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls. In addition, they anticipated that the prevalence of abnormal hearing assessments would increase with antiretroviral therapy (ART) use and treatment for tuberculosis (TB). Pure-tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and a gap-detection test were performed using a laptop-based hearing testing system on 751 subjects (100 HIV- in the United States, plus 651 in Dar es Salaam, Tanzania, including 449 HIV+ [130 ART- and 319 ART+], and 202 HIV-, subjects. No U.S. subjects had a history of TB treatment. In Tanzania, 204 of the HIV+ and 23 of the HIV- subjects had a history of TB treatment. Subjects completed a video and audio questionnaire about their hearing, as well as a health history questionnaire. HIV+ subjects had reduced DPOAE levels compared with HIV- subjects, but their hearing thresholds, tympanometry results, and gap-detection thresholds were similar. Within the HIV+ group, those on ART reported significantly greater difficulties understanding speech in noise, and were significantly more likely to report that they had difficulty understanding speech than the ART- group. The ART+ group had a significantly higher mean gap-detection threshold compared with the ART- group. No effects of TB treatment were seen. The fact that the ART+/ART- groups did not differ in measures of peripheral hearing ability (DPOAEs, thresholds), or middle ear measures (tympanometry), but that the ART+ group had significantly more trouble understanding speech and had higher gap-detection thresholds indicates a central processing deficit. These data suggest that: (1) hearing deficits in HIV+ individuals could be a CNS side effect of HIV infection, (2) certain ART regimens might produce CNS side effects that manifest themselves as hearing difficulties, and/or (3) some ART regimens may treat CNS HIV inadequately, perhaps due to insufficient CNS drug levels, which is reflected as a central hearing deficit. Monitoring of central hearing parameters could be used to track central effects of either HIV or ART.	t	\N
24447236	This discussion paper aims to synthesise the literature on patient-centred care from a range of health professions and to relate this to the field of rehabilitative audiology. Through review of the literature, this paper addresses five questions: What is patient-centred care? How is patient-centred care measured? What are the outcomes of patient-centred care? What are the factors contributing to patient-centred care? What are the implications for audiological rehabilitation? Literature review and synthesis. Publications were identified by structured searches in PubMed, Cinahl, Web of Knowledge, and PsychInfo, and by inspecting the reference lists of relevant articles. Few publications from within the audiology profession address this topic and consequently a review and synthesis of literature from other areas of health were used to answer the proposed questions. This paper concludes that patient-centred care is in line with the aims and scope of practice for audiological rehabilitation. However, there is emerging evidence that we still need to inform the conceptualisation of patient-centred audiological rehabilitation. A definition of patient-centred audiological rehabilitation is needed to facilitate studies into the nature and outcomes of it in audiological rehabilitation practice.	t	\N
24456399	Crossmodal integration of auditory and visual information, such as phonemes and graphemes, is a critical skill for fluent reading. Previous work has demonstrated that white matter connectivity along the arcuate fasciculus (AF) is predicted by reading skill and that crossmodal processing particularly activates the posterior STS (pSTS). However, the relationship between this crossmodal activation and white matter integrity has not been previously reported. We investigated the interrelationship of crossmodal integration, both in terms of behavioral performance and pSTS activity, with AF tract coherence using a rhyme judgment task in a group of 47 children with a range of reading abilities. We demonstrate that both response accuracy and pSTS activity for crossmodal (auditory-visual) rhyme judgments was predictive of fractional anisotropy along the left AF. Unimodal (auditory-only or visual-only) pSTS activity was not significantly related to AF connectivity. Furthermore, activity in other reading-related ROIs did not show the same AV-only AF coherence relationship, and AV pSTS activity was not related to connectivity along other language-related tracts. This study is the first to directly show that crossmodal brain activity is specifically related to connectivity in the AF, supporting its role in phoneme-grapheme integration ability. More generally, this study helps to define an interdependent neural network for reading-related integration.	t	\N
24488957	In categorical perception (CP), continuous physical signals are mapped to discrete perceptual bins: mental categories not found in the physical world. CP has been demonstrated across multiple sensory modalities and, in audition, for certain over-learned speech and musical sounds. The neural basis of auditory CP, however, remains ambiguous, including its robustness in nonspeech processes and the relative roles of left/right hemispheres; primary/nonprimary cortices; and ventral/dorsal perceptual processing streams. Here, highly trained musicians listened to 2-tone musical intervals, which they perceive categorically while undergoing functional magnetic resonance imaging. Multivariate pattern analyses were performed after grouping sounds by interval quality (determined by frequency ratio between tones) or pitch height (perceived noncategorically, frequency ratios remain constant). Distributed activity patterns in spheres of voxels were used to determine sound sample identities. For intervals, significant decoding accuracy was observed in the right superior temporal and left intraparietal sulci, with smaller peaks observed homologously in contralateral hemispheres. For pitch height, no significant decoding accuracy was observed, consistent with the non-CP of this dimension. These results suggest that similar mechanisms are operative for nonspeech categories as for speech; espouse roles for 2 segregated processing streams; and support hierarchical processing models for CP.	t	\N
24489819	This study tested the hypothesis that the previously reported advantage of musicians over non-musicians in understanding speech in noise arises from more efficient or robust coding of periodic voiced speech, particularly in fluctuating backgrounds. Speech intelligibility was measured in listeners with extensive musical training, and in those with very little musical training or experience, using normal (voiced) or whispered (unvoiced) grammatically correct nonsense sentences in noise that was spectrally shaped to match the long-term spectrum of the speech, and was either continuous or gated with a 16-Hz square wave. Performance was also measured in clinical speech-in-noise tests and in pitch discrimination. Musicians exhibited enhanced pitch discrimination, as expected. However, no systematic or statistically significant advantage for musicians over non-musicians was found in understanding either voiced or whispered sentences in either continuous or gated noise. Musicians also showed no statistically significant advantage in the clinical speech-in-noise tests. Overall, the results provide no evidence for a significant difference between young adult musicians and non-musicians in their ability to understand speech in noise.	t	\N
24490946	Studies of face recognition in older adults (60 years of age and older) report increases in false alarms over younger adults (usually 18-30 years of age), but no age differences in hits. To examine this phenomenon, we compared older and younger adults in categorical perception of faces. We hypothesized that face representations in older adults would be broadly tuned, resulting in overlapping representations, manifested by a shallower slope in identity categorization than in younger adults, and age-related reductions in the advantage for between-categories, as compared with within-category, face discrimination. We morphed faces to change linearly from one identity to another. We used familiar or unfamiliar faces in separate conditions to examine the role of familiarity. Categorical perception was assessed in an identity-classification task and a discrimination task. Older adults showed a shallower slope and poorer discrimination compared with younger adults, and both groups exhibited better performance with familiar than unfamiliar faces. Enhanced discriminability for between-categories as compared with within-category faces was seen for both familiar and unfamiliar faces in younger adults, but only for familiar faces in older adults. The more broadly tuned representations of unfamiliar faces in older adults may lead to misidentification and greater false alarms for unfamiliar faces, but not for familiar faces.	t	\N
24496288	This study evaluated effects of nonlinear frequency compression (NLFC) processing in children with hearing loss for consonant identification in quiet and for spondee identification in competing noise or speech. It was predicted that participants would benefit from NLFC for consonant identification in quiet when access to high-frequency information was critical, but that NLFC would be less beneficial, or even detrimental, when identification relied on mid-frequency cues. Further, it was hypothesized that NLFC could result in greater susceptibility to masking in the spondee task. The rationale for these predictions is that improved access to high-frequency information comes at the cost of decreased spectral resolution. A repeated-measures design compared speech-perception outcomes in 17 pediatric hearing aid users (9 to 17 years of age) wearing Naida V SP "laboratory" hearing aids with NLFC on and off. Data were also collected in an initial baseline session in which children wore their personal hearing aids. Children with a wide range of audiometric configurations were included, but all participants were full-time users of hearing aids with active NLFC. For each hearing aid condition, speech perception was assessed in the sound field by using a closed-set 12-alternative consonant-vowel identification measure in quiet, and a closed-set four-alternative spondee-identification measure in a speech-shaped noise or in a two-talker speech masker. No significant differences in performance were observed between laboratory hearing aid conditions with NLFC activated or deactivated for either speech-perception measure. An unexpected finding was that the majority of participants had no difficulty identifying the high-frequency consonant /s/ even when NLFC was deactivated. Investigation into individual differences revealed that subjects with a greater difference in audible bandwidth with NLFC on versus NLFC off were less likely to demonstrate improvements in high-frequency consonant identification in quiet, but were more likely to demonstrate improvements in spondee identification in speech-shaped noise. Group results observed in the initial baseline assessment using personal aids fitted with more aggressive NLFC settings than used in laboratory aids indicated better consonant identification accuracy in quiet. However, spondee identification in the two-talker masker was poorer with personal compared with laboratory hearing aids. Comparisons across personal and laboratory hearing aids are tempered, however, by the potential of an order effect. The observation of comparable performance with NLFC on and NLFC off in the laboratory aids provides evidence that NLFC is neither detrimental nor advantageous when modest in strength. Results with personal hearing aids fitted with stronger compression settings than laboratory aids (NLFC on) highlight the critical need for further research to determine the impact of NLFC processing on speech perception for a wider range of speech-perception measures and compression settings.	t	\N
24503772	The bone-anchored hearing device (BAHD) was not introduced in China until 2010. To our knowledge, this is the first study to assess the efficacy of Chinese Mandarin-speaking patients with bilateral aural atresia. To evaluate the speech recognition of Chinese Mandarin-speaking patients with BAHDs as well as patients' satisfaction using 2 questionnaires. A retrospective case review of 16 patients with bilateral aural atresia conducted at a tertiary referral center. A BAHD was implanted during auricle reconstruction surgery or after the auricle was rebuilt. A surgical method to combine the BAHD implantation with the second stage of ear reconstruction was introduced. Speech audiometry test and mean pure-tone threshold results were compared among patients with unaided hearing and those with BAHDs. Scores from the BAHD user questionnaire and Glasgow Children's Benefit Inventory (GCBI) were used to measure patients' satisfaction and subjective health benefit. The mean (SD) speech discrimination scores measured in a sound field with a presentation level of 45 dB HL (hearing level) were 6.7% (7.4%) unaided and 86.5% (4.4%) with a BAHD. Scores with a presentation level of 65 dB HL were 56.5% (7.4%) unaided and 90.1% (3.4%) with a BAHD. The speech reception threshold was 60.6 (7.5) dB HL unaided and 24.7 (5.0) dB HL with a BAHD. The mean (SD) pure-tone threshold of the patients was 61.6 (7.8) dB HL unaided and 23.8 (5.9) dB HL with a BAHD. The BAHD application questionnaire demonstrated excellent patient satisfaction. The mean (SD) benefit score of GCBI was 45.6 (14.4). For aural atresia, the BAHD has been one of the most reliable methods of auditory rehabilitation. It can improve the patient's word recognition performance and quality of life. The technique of BAHD implantation combined with auricular reconstruction in a 2-stages-in-1 surgery and the modified incision of patients with reconstructed auricle proved to be safe and effective.	t	\N
24508369	Acoustic communication requires gathering, transforming, and interpreting diverse sound cues. To achieve this, all the spatial and temporal features of complex sound stimuli must be captured in the firing patterns of the primary sensory neurons and then accurately transmitted along auditory pathways for additional processing. The mammalian auditory system relies on several synapses with unique properties in order to meet this task: the auditory ribbon synapses, the endbulb of Held, and the calyx of Held. Each of these synapses develops morphological and electrophysiological characteristics that enable the remarkably precise signal transmission necessary for conveying the miniscule differences in timing that underly sound localization. In this article, we review the current knowledge of how these synapses develop and mature to acquire the specialized features necessary for the sense of hearing.	t	\N
24508791	Amblyopia is a developmental disorder that results in both monocular and binocular deficits. Although traditional treatment in clinical practice (i.e., refractive correction, or occlusion by patching and penalization of the fellow eye) is effective in restoring monocular visual acuity, there is little information on how binocular function, especially stereopsis, responds to traditional amblyopia treatment. We aim to evaluate the effects of perceptual learning on stereopsis in observers with amblyopia in the current study. Eleven observers (21.1 ± 5.1 years, six females) with anisometropic or ametropic amblyopia were trained to judge depth in 10 to 13 sessions. Red-green glasses were used to present three different texture anaglyphs with different disparities but a fixed exposure duration. Stereoacuity was assessed with the Fly Stereo Acuity Test and visual acuity was assessed with the Chinese Tumbling E Chart before and after training. Averaged across observers, training significantly reduced disparity threshold from 776.7″ to 490.4″ (P < 0.01) and improved stereoacuity from 200.3″ to 81.6″ (P < 0.01). Interestingly, visual acuity also significantly improved from 0.44 to 0.35 logMAR (approximately 0.9 lines, P < 0.05) in the amblyopic eye after training. Moreover, the learning effects in two of the three retested observers were largely retained over a 5-month period. Perceptual learning is effective in improving stereo vision in observers with amblyopia. These results, together with previous evidence, suggest that structured monocular and binocular training might be necessary to fully recover degraded visual functions in amblyopia. Chinese Abstract.	t	\N
24514158	This study analyses the meaning spaces of German pitch contours using two modes of melodic movement: continuous or in steps of sustained pitch. Both the continuous and stepped movements are represented by a set of five basic patterns, the latter being derived from the former. Thirty-six German native speakers judged the pattern sets on a 12-scale semantic differential. The semantic profiles confirm that stepped contours can be conceived of as stylized intonation, in a formal as well as in a functional sense. On the one hand, continuous (non-stylized) and stepped (stylized) contours are assigned different overall meanings (especially on the scales astonished - commonplace and interested - not interested). On the other hand, listeners organize the two contour sets in a similar fashion, which speaks in favour of parallel pattern inventories of continuous and stepped movement, respectively. However, the meaning space of the stylized patterns is affected by formal restrictions, for instance in the step transformation of continuous rises.	t	\N
24525262	What are the temporal dynamics of perceptual sampling during visual search tasks, and how do they differ between a difficult (or inefficient) and an easy (or efficient) task? Does attention focus intermittently on the stimuli, or are the stimuli processed continuously over time? We addressed these questions by way of a new paradigm using periodic fluctuations of stimulus information during a difficult (color-orientation conjunction) and an easy (+ among Ls) search task. On each stimulus, we applied a dynamic visual noise that oscillated at a given frequency (2-20 Hz, 2-Hz steps) and phase (four cardinal phase angles) for 500 ms. We estimated the dynamics of attentional sampling by computing an inverse Fourier transform on subjects' d-primes. In both tasks, the sampling function presented a significant peak at 2 Hz; we showed that this peak could be explained by nonperiodic search strategies such as increased sensitivity to stimulus onset and offset. Specifically in the difficult task, however, a second, higher-frequency peak was observed at 9 to 10 Hz, with a similar phase for all subjects; this isolated frequency component necessarily entails oscillatory attentional dynamics. In a second experiment, we presented difficult search arrays with dynamic noise that was modulated by the previously obtained grand-average attention sampling function or by its converse function (in both cases omitting the 2 Hz component to focus on genuine oscillatory dynamics). We verified that performance was higher in the latter than in the former case, even for subjects who had not participated in the first experiment. This study supports the idea of a periodic sampling of attention during a difficult search task. Although further experiments will be needed to extend these findings to other search tasks, the present report validates the usefulness of this novel paradigm for measuring the temporal dynamics of attention.	t	\N
24533757	The effect of deactivating indiscriminable cochlear implant (CI) electrodes for unilaterally implanted adults was evaluated using the BKB (Bamford-Kowal-Bench) sentence test in quiet and in pink noise (signal-to-noise ratio of +10dBA) and the adaptive Coordinate Response Measure (CRM). Each CI recipient who failed electrode differentiation (ED) in at least one electrode-pair, based on results of a pure-tone pitch-ranking task received two research programmes to try out in a cross-over study. Research programmes (RP) either employed discriminable electrodes only or the most discriminable two-thirds of the electrodes in the electrode array for CI recipients failing ED for more than a third of the electrodes. The participants were also asked to subjectively report improvement of or decline in sound quality in everyday listening situations. There was significant improvement in CRM speech reception thresholds (SRTs) (Z = -3.24, N = 15, P = 0.001), BKB sentence scores in quiet (t = 3.17, df = 24, P < 0.005) and also in pink noise (t = 2.26, df = 19, P < 0.005) after deactivating indiscriminable electrodes.	t	\N
24548324	Not much is known about how people comprehend ironic utterances, and to date, most studies have simply compared processing of ironic versus non-ironic statements. A key aspect of the graded salience hypothesis, distinguishing it from other accounts (such as the standard pragmatic view and direct access view), is that it predicts differences between processing of familiar and unfamiliar ironies. Specifically, if an ironic utterance is familiar, then the ironic interpretation should be available without the need for extra inferential processes, whereas for unfamiliar ironies, the literal interpretation would be computed first, and a mismatch with context would lead to a re-interpretation of the statement as being ironic. We recorded participants' eye movements while they were reading (Experiment 1), and electrical brain activity while they were listening to (Experiment 2), familiar and unfamiliar ironies compared to non-ironic controls. Results show disruption to eye movements and an N400-like effect for unfamiliar ironies only, supporting the predictions of the graded salience hypothesis. In addition, in Experiment 2, a late positivity was found for both familiar and unfamiliar ironic materials, compared to non-ironic controls. We interpret this positivity as reflecting ongoing conflict between the literal and ironic interpretations of the utterance.	t	\N
24557002	The rapidly evolving field of early diagnostics after the introduction of newborn hearing screening requires rapid, valid, and objective methods, which have to be thoroughly evaluated in adults before use in infants. The aim was to study cross-correlation analysis of interleaved auditory brainstem responses (ABRs) in a wide dynamic range in normal-hearing adults. Off-line analysis allowed for comparison with psychoacoustical click threshold (PCT), pure-tone threshold, and determination of ABR input/output function. Specifically, nonfiltered and band-pass filtered ABRs were studied in various time segments along with time elapsed for ensemble of sweeps reaching a specific detection criterion. Fourteen healthy normal-hearing subjects (18 to 35 years of age, 50% females) without any history of noise exposure participated. They all had pure-tone thresholds better than 20 dB HL (125 to 8000 Hz). ABRs were recorded in both ears using 100 μsec clicks, from 71.5 dB nHL down to -18.5 dB nHL, in 10 dB steps (repetition rate, 39 Hz; time window, 15 msec; filter, 30 to 8000 Hz). The number of sweeps increased from 2000 at 71.5 dB nHL, up to 30000 at -18.5 dB nHL. Each sweep was stored in a data base for off-line analysis. Cross-correlation analysis between two subaverages of interleaved responses was performed in the time domain for nonfiltered and digitally band-pass filtered (300 to 1500 Hz) entire and time-windowed (1 to 11 and 5 to 11 msec) responses. PCTs were measured using a Bekesy technique with the same insert phone and stimulus as used for the ABR (repetition rate, 20 Hz). Time elapsed (≈ number of accepted sweeps/repetition rate) for the ensemble of sweeps needed to reach a cross-correlation coefficient (ρ) of 0.70 (=3.7 dB signal-to-noise ratio [SNR]) was analyzed. Mean cross-correlation coefficients exceeded 0.90 in both ears at stimulus levels ≥11.5 dB nHL for the entire nonfiltered ABR. At 1.5 dB nHL, mean(SD) ρ was 0.53(0.32) and 0.44(0.40) for left and right ears, respectively (n = 14) (=0 dB SNR). In comparison, mean(SD) PCT was -1.9(2.9) and -2.5(3.2) dB nHL for left and right ears, respectively (n = 14), while mean pure-tone average (500 to 2000 Hz) was 2.5 dB HL (n = 28). Almost no effect of band-pass filtering or reduced analysis time window existed. Average time elapsed needed to reach ρ = 0.70 was approximately 20 seconds or less at stimulus levels ≥41.5 dB nHL, and ≈30 seconds at 31.5 dB nHL. The average (interpolated) stimulus level corresponding to ρ=0.70 for the entire nonfiltered ABR was 6.5 dB nHL (n = 28), which coincided with the estimated psychoacoustical threshold for single clicks. ABR could be identified in a short period of time using cross-correlation analysis between interleaved responses. The average stimulus level corresponding to 0 dB SNR in the entire nonfiltered ABR occurred at 1.5 dB nHL, 4 dB above the average PCT. The mean input/output function for the ensemble of sweeps required to reach ρ = 0.70 increased monotonically with increasing stimulus level, in parallel with the ABR based on all sweeps (≥1.5 dB nHL). Time domain cross-correlation analysis of ABR might form the basis for automatic response identification and future threshold-seeking procedures.	t	\N
24564623	To evaluate the hearing of adolescents with diabetes mellitus type 1(DM1) by otoacoustic emissions (OAEs), and by comparing different tests with pure-tone audiometry to identify potential early cochlear impairments. Pure-tone audiometry, transient evoked otoacoustic emissions (TEOAEs), and distortion product otoacoustic emissions (DPOAEs) were performed in a group of adolescents with and without DM1. Clinical characteristics, disease duration, and glycated haemoglobin levels were studied. Participants were 40 adolescents with DM1 and 40 healthy subjects. Sensorineural hearing loss, affecting frequencies of 6000 and 8000 Hz, was found only in DM1 subjects when compared to the controls (7.7% vs. 0%, p < 0.05). A higher prevalence of cochlear damage was detected by DPOAE responses, 32% belonging from the diabetic group, vs. 3.7% in the control group. Absent TEOAE responses were observed in only three individuals, all from the diabetic group (5.1% of the tests performed in the diabetic group). Additionally, hearing thresholds were better in diabetic subjects with good control when compared to ones with regular or poor control (p = 0.00). Hearing thresholds were higher in poorly controlled diabetics when compared to subjects with good (p = 0.000) or regular control (p = 0.006). Early evidence of cochlear damage was detected in adolescents with DM1 leading to hearing loss at high frequencies. Abnormal DPOAEs responses were found more frequently than the alterations in TEOAEs and pure-tone audiometry, suggesting that DPOAEs evaluation is the most sensitive and it could be used for monitoring the progression of cochlear damage during the early stages of hearing impairment.	t	\N
24564624	Detailed information on the hearing threshold levels (HTLs) of young Australians was gathered as part of a large-scale study of the relationship between HTL and leisure-noise exposure in young Australians. HTL data for the study population (18-35 year olds) was carefully collected, as well as otoscopy, tympanometry, contra-lateral acoustic reflexes, and otoacoustic emissions (transient and distortion product), together with a comprehensive hearing health history - both past and present. The sample cohort consisted of 1407 individuals, females and males. Prior to analysis, HTL data were filtered according to both a 'Low' and 'High' set of exclusion criteria. The results obtained for both high-screen and low-screen datasets were around +5 dB above the traditionally accepted values of audiometric zero. This is consistent with previous published reports. Comparison with 'ISO 7029 Acoustics: Statistical distribution of hearing thresholds as a function of age' indicated that threshold values for this dataset have a similar distribution to those of the Standard. This data provides a suitable reference HTL ('normative') database for young Australians.	t	\N
24564688	To characterize the impulse noise exposure and auditory risk for youth recreational firearm users engaged in outdoor target shooting events. The youth shooting positions are typically standing or sitting at a table, which places the firearm closer to the ground or reflective surface when compared to adult shooters. Acoustic characteristics were examined and the auditory risk estimates were evaluated using contemporary damage-risk criteria for unprotected adult listeners and the 120-dB peak limit suggested by the World Health Organization (1999) for children. Impulses were generated by 26 firearm/ammunition configurations representing rifles, shotguns, and pistols used by youth. Measurements were obtained relative to a youth shooter's left ear. All firearms generated peak levels that exceeded the 120 dB peak limit suggested by the WHO for children. In general, shooting from the seated position over a tabletop increases the peak levels, LAeq8 and reduces the unprotected maximum permissible exposures (MPEs) for both rifles and pistols. Pistols pose the greatest auditory risk when fired over a tabletop. Youth should utilize smaller caliber weapons, preferably from the standing position, and always wear hearing protection whenever engaging in shooting activities to reduce the risk for auditory damage.	t	\N
24568928	A new study reports that activations of superior temporal regions for speech are normal in dyslexia, although being less well connected to downstream frontal regions. These findings support the hypothesis of a deficit in the access to phonological representations rather than in the representations themselves.	t	\N
24569986	Viewing behavior exhibits temporal and spatial structure that is independent of stimulus content and task goals. One example of such structure is horizontal biases, which are likely rooted in left-right asymmetries of the visual and attentional systems. Here, we studied the existence, extent, and mechanisms of this bias. Left- and right-handed subjects explored scenes from different image categories, presented in original and mirrored versions. We also varied the spatial spectral content of the images and the timing of stimulus onset. We found a marked leftward bias at the start of exploration that was independent of image category. This left bias was followed by a weak bias to the right that persisted for several seconds. This asymmetry was found in the majority of right-handers but not in left-handers. Neither low- nor high-pass filtering of the stimuli influenced the bias. This argues against mechanisms related to the hemispheric segregation of global versus local visual processing. Introducing a delay in stimulus onset after offset of a central fixation spot also had no influence. The bias was present even when stimuli were presented continuously and without any requirement to fixate, associated to both fixation- and saccade-contingent image changes. This suggests the bias is not caused by structural asymmetries in fixation control. Instead the pervasive horizontal bias is compatible with known asymmetries of higher-level attentional areas related to the detection of novel events.	t	\N
24580021	To evaluate the impact on voice of 2 hours of continuous oral reading. Fifty normophonic women underwent two sessions of voice loading in which the required intensity level varied: 60-65 dB(A) for the first session, and 70-75 dB(A) for the second session. Ten expert judges evaluated the breathiness of one sentence recorded before and after each loading session. Pairs of stimuli were presented randomly to the judges, who were asked to designate the breathiest sample. A significant decrease in breathiness was observed following both sessions, suggesting an improvement of voice subsequent to loading. When comparing the two intensity levels, no difference was found for breathiness after vocal loading.	t	\N
24584899	The ability of humans to echolocate has been recognized since the 1940s. Little is known about what determines individual differences in echolocation ability, however. Although hearing ability has been suggested as an important factor in blind people and sighted-trained echolocators, there is evidence to suggest that this may not be the case for sighted novices. Therefore, non-auditory aspects of human cognition might be relevant. Previous brain imaging studies have shown activation of the early 'visual', i.e. calcarine, cortex during echolocation in blind echolocation experts, and also during visual imagery in blind and sighted people. Therefore, here we investigated the relationship between echolocation ability and vividness of visual imagery (VVI). Twenty-four sighted echolocation novices completed Marks' (Br J Psychol 1:17-24, 1973) VVI questionnaire and they also performed an echolocation size-discrimination task. Furthermore, they participated in a battery of auditory tests that determined their ability to detect fluctuations in sound frequency and intensity, as well as hearing differences between the right and left ear. A correlational analysis revealed a significant relationship between participants' VVI and echolocation ability, i.e. participants with stronger VVI also had higher echolocation ability, even when differences in auditory abilities were taken into account. In terms of underlying mechanisms, we suggest that either the use of visual imagery is a strategy for echolocation, or that visual imagery and echolocation both depend on the ability to recruit calcarine cortex for cognitive tasks that do not rely on retinal input.	t	\N
24588528	To investigate the occurrence of 27 chronic medical conditions in a cohort of adults with and without hearing impairment, and to examine the association between these conditions and hearing ability. The National Longitudinal Study on Hearing (NL-SH study) is a large prospective study among adults aged 18 to 70 years, conducted via the internet in the Netherlands. Hearing ability was measured with a digits-in-noise test and comorbidity was assessed through self-report. Cross-sectional data of 890 hearing-impaired and 975 normally-hearing adults were analyzed. Both descriptive statistics and multinomial logistic regression analyses were conducted. Of the NL-SH participants with insufficient or poor hearing ability, 78.5% reported to suffer from at least one additional chronic condition. This proportion was larger than in the normally-hearing group (68.6% with one or more chronic conditions and 37.7% with two or more). After adjustment for age and gender, 'dizziness causing falling', 'diabetes' and 'arthritis types other than osteoarthritis and rheumatic arthritis' were significantly associated with poor hearing ability. Our results show that some previously reported associations do not only occur in older age groups, but also in younger cohorts. Comorbidity is relevant in the rehabilitation (multi-disciplinary care) and the clinical encounter.	t	\N
24598525	Changes in amplitude and frequency jointly determine much of the communicative significance of complex acoustic signals, including human speech. We have previously described responses of neurons in the core auditory cortex of awake rhesus macaques to sinusoidal amplitude modulation (SAM) signals. Here we report a complementary study of sinusoidal frequency modulation (SFM) in the same neurons. Responses to SFM were analogous to SAM responses in that changes in multiple parameters defining SFM stimuli (e.g., modulation frequency, modulation depth, carrier frequency) were robustly encoded in the temporal dynamics of the spike trains. For example, changes in the carrier frequency produced highly reproducible changes in shapes of the modulation period histogram, consistent with the notion that the instantaneous probability of discharge mirrors the moment-by-moment spectrum at low modulation rates. The upper limit for phase locking was similar across SAM and SFM within neurons, suggesting shared biophysical constraints on temporal processing. Using spike train classification methods, we found that neural thresholds for modulation depth discrimination are typically far lower than would be predicted from frequency tuning to static tones. This "dynamic hyperacuity" suggests a substantial central enhancement of the neural representation of frequency changes relative to the auditory periphery. Spike timing information was superior to average rate information when discriminating among SFM signals, and even when discriminating among static tones varying in frequency. This finding held even when differences in total spike count across stimuli were normalized, indicating both the primacy and generality of temporal response dynamics in cortical auditory processing.	t	\N
24606277	While many studies have assessed the efficacy of similarity-based cues for auditory stream segregation, much less is known about whether and how the larger-scale structure of sound sequences support stream formation and the choice of sound organization. Two experiments investigated the effects of musical melody and rhythm on the segregation of two interleaved tone sequences. The two sets of tones fully overlapped in pitch range but differed from each other in interaural time and intensity. Unbeknownst to the listener, separately, each of the interleaved sequences was created from the notes of a different song. In different experimental conditions, the notes and/or their timing could either follow those of the songs or they could be scrambled or, in case of timing, set to be isochronous. Listeners were asked to continuously report whether they heard a single coherent sequence (integrated) or two concurrent streams (segregated). Although temporal overlap between tones from the two streams proved to be the strongest cue for stream segregation, significant effects of tonality and familiarity with the songs were also observed. These results suggest that the regular temporal patterns are utilized as cues in auditory stream segregation and that long-term memory is involved in this process.	t	\N
24606289	For assessing hearing aid algorithms, a method is sought to shift the threshold of a speech-in-noise test to (mostly positive) signal-to-noise ratios (SNRs) that allow discrimination across algorithmic settings and are most relevant for hearing-impaired listeners in daily life. Hence, time-compressed speech with higher speech rates was evaluated to parametrically increase the difficulty of the test while preserving most of the relevant acoustical speech cues. A uniform and a non-uniform algorithm were used to compress the sentences of the German Oldenburg Sentence Test at different speech rates. In comparison, the non-uniform algorithm exhibited greater deviations from the targeted time compression, as well as greater changes of the phoneme duration, spectra, and modulation spectra. Speech intelligibility for fast Oldenburg sentences in background noise at different SNRs was determined with 48 normal-hearing listeners. The results confirmed decreasing intelligibility with increasing speech rate. Speech had to be compressed to more than 30% of its original length to reach 50% intelligibility at positive SNRs. Characteristics influencing the discrimination ability of the test for assessing effective SNR changes were investigated. Subjective and objective measures indicated a clear advantage of the uniform algorithm in comparison to the non-uniform algorithm for the application in speech-in-noise tests.	t	\N
24606291	The present study investigated the importance of overall segment amplitude and intrinsic segment amplitude modulation of consonants and vowels to sentence intelligibility. Sentences were processed according to three conditions that replaced consonant or vowel segments with noise matched to the long-term average speech spectrum. Segments were replaced with (1) low-level noise that distorted the overall sentence envelope, (2) segment-level noise that restored the overall syllabic amplitude modulation of the sentence, and (3) segment-modulated noise that further restored faster temporal envelope modulations during the vowel. Results from the first experiment demonstrated an incremental benefit with increasing resolution of the vowel temporal envelope. However, amplitude modulations of replaced consonant segments had a comparatively minimal effect on overall sentence intelligibility scores. A second experiment selectively noise-masked preserved vowel segments in order to equate overall performance of consonant-replaced sentences to that of the vowel-replaced sentences. Results demonstrated no significant effect of restoring consonant modulations during the interrupting noise when existing vowel cues were degraded. A third experiment demonstrated greater perceived sentence continuity with the preservation or addition of vowel envelope modulations. Overall, results support previous investigations demonstrating the importance of vowel envelope modulations to the intelligibility of interrupted sentences.	t	\N
24606310	Musicians have been shown to better perceive pitch and timbre cues in speech and music, compared to non-musicians. It is unclear whether this "musician advantage" persists under conditions of spectro-temporal degradation, as experienced by cochlear-implant (CI) users. In this study, gender categorization was measured in normal-hearing musicians and non-musicians listening to acoustic CI simulations. Recordings of Dutch words were synthesized to systematically vary fundamental frequency, vocal-tract length, or both to create voices from the female source talker to a synthesized male talker. Results showed an overall musician effect, mainly due to musicians weighting fundamental frequency more than non-musicians in CI simulations.	t	\N
24606491	This research employed a forward-masking paradigm to estimate the current spread of monopolar (MP) and bipolar (BP) maskers, with current amplitudes adjusted to elicit the same loudness. Since the spatial separation between active and return electrodes is smaller in BP than in MP configurations, the BP current spread is more localized and presumably superior in terms of speech intelligibility. Because matching the loudness requires higher current in BP than in MP stimulation, previous forward-masking studies show that BP current spread is not consistently narrower across subjects or electrodes within a subject. The present forward-masking measures of current spread differ from those of previous studies by using the same BP probe electrode configuration for both MP and BP masker configurations, and adjusting the current levels of the MP and BP maskers so as to match them in loudness. With this method, the estimate of masker current spread would not be contaminated by differences in probe current spread. Forward masking was studied in four cochlear implant patients, two females and two males, with speech recognition scores higher than 50%; that is, their auditory-nerve survival status was more than adequate to carry out the experiments. The data showed that MP and BP masker configurations produce equivalent masking patterns (and current spreads) in three participants. A fourth participant displayed asymmetrical patterns with enhancement rather than masking in some cases, especially when the probe and masker were at the same location. This study showed equivalent masking patterns for MP and BP maskers when the BP masker current amplitude was increased to match the loudness of the MP masker, and the same BP probe configuration is used with both maskers. This finding could help to explain why cochlear implant users often fail to accrue higher speech intelligibility benefit from BP stimulation.	t	\N
24610168	Longitudinal analysis of audiometric data of a large population of noise-exposed workers provides insight into the development of noise-induced hearing loss (NIHL) as a function of noise exposure and age, particularly during the first decade of noise exposure. Data of pure-tone audiometry of 17,930 construction workers who underwent periodic occupational hearing screening at least twice during a 4-year period were available for analysis. These concerned all follow-up measurements of the baseline cohort described by Leensen et al. (Int Arch Occup Environ Health 84:577-590, 2011). Linear mixed models explored the relationship between the annual rate of change in hearing and noise exposure level, exposure duration, and age. Data of 3,111 workers who were tested on three occasions were used to investigate the pattern of hearing loss development. The mean annual deterioration in hearing in this study population was 0.54 dB/yr, and this became larger with increasing noise exposure level and increasing age. Remarkably, during the first decade of noise exposure, an improvement in hearing threshold levels (HTLs) was observed. The change in hearing over three measurements showed a concave development of hearing loss as a function of time, which corresponds to NIHL development. Overall, hearing deteriorated over the measurement period. Because HTLs at follow-up were better than those obtained at baseline, no statement can be made about the NIHL development during the first decade of noise exposure. This improvement in HTLs rather resembles the result of measurement variation in occupational screening audiometry than an actual improvement in hearing ability.	t	\N
24611446	The role in which two tones are first encountered in an unattended oddball sequence affects how deviance detection, reflected by mismatch negativity, treats them later when the roles reverse: a "primacy bias." We tested whether this effect is modulated by previous behavioral relevance assigned to the two tones. To this end, sequences in which the roles of the two tones alternated were preceded by a go/no-go task in which tones were presented with equal probability. Half of the participants were asked to respond to the short sounds, the other half to long sounds. Primacy bias was initially abolished but returned dependent upon the go-stimulus that the participant was assigned. Results demonstrate a long-term impact of prior learning on deviance detection, and that even when prior importance/equivalence is learned, the bias ultimately returns. Results are discussed in terms of persistent go-stimulus specific changes in responsiveness to sound.	t	\N
24616979	The aim of this study is to evaluate the development of auditory performance and speech intelligibility within the first year after hearing aid fitting in children with moderate or severe hearing loss, investigate the effects of hearing level on auditory performance and speech intelligibility and provide a clinical database for their hearing and speech habilitation. Twenty-nine children participated in this study, ranging in age at hearing aid fitting from 3 to 8 years old with a mean of 5. 6 years old. 19 were boys and 10 were girls. According to their hearing level, they were divided into two groups. 14 children were in group of moderate hearing loss (41-60 dB HL). 15 children were in group of severe hearing loss (61-80 dB HL). The categories of auditory performance (CAP) and speech intelligibility rating (SIR) were used to evaluate their auditory performance and speech intelligibility. The evaluation was performed before hearing aid fitting and 1, 3, 6, 9, 12 months after fitting. There was significant difference in mean score of CAP between group of moderate hearing loss and severe hearing loss before hearing aid fitting (P < 0.05). However, no significant differences were observed between these two groups at 1, 3, 6, 9, 12 months after fitting (P > 0.05). There was also significant difference in mean score of SIR between group of moderate hearing loss and severe hearing loss before hearing aid fitting (P < 0.05). How ever, no significant differences were also observed between these two groups at 1, 3, 6, 9, 12 months after fitting (P > 0.05). The mean scores of CAP for group of moderate hearing loss at 6, 9, 12 months after fitting were significantly superior in comparison with the score before hearing aid fitting (P < 0.05). The mean scores of SIR for group of moderate hearing loss at 6, 9, 12 months after fitting were significantly superior in comparison with the score before hearing aid fitting (P < 0.05); the mean score at 12 months after fitting was also significantly superior in comparison with the score at 1 month after fitting (P < 0.05). The mean scores of CAP for group of severe hearing loss at 3, 6, 9, 12 months after fitting were significantly superior in comparison with the score before hearing aid fitting (P < 0.05); the mean scores at 9,12 months after fitting were significantly superior in comparison with the score at 1 month after fitting (P < 0.05). The mean scores of SIR for group of severe hearing loss at 3, 6, 9, 12 months after fitting were significantly superior in comparison with the score before hearing aid fitting (P < 0.05); the mean scores at 6, 9, 12 months after fitting were also significantly superior in comparison with the score at 1 month after fitting (P < 0.05). Auditory performance and speech intelligibility in children with moderate or severe hearing loss improved significantly within the first year after hearing aid fitting. The development followed different trajectory.	t	\N
24621149	Since being approved in 2009, bilateral simultaneous cochlear implantation (CI) has been the standard treatment for children in the UK who meet the criteria for CI. The aim was to report surgical outcomes of bilateral CI in the UK. Between January 2010 and December 2011, 14 UK CI centres collected data prospectively: demographics, aetiology, use of imaging, device type, surgery duration, use of intra-operative electrophysiology, length of stay, and post-operative complications. 1397 CI procedures in 961 CI recipients were included; 436 bilateral simultaneous, 394 bilateral sequential, and 131 unilateral. The majority (85%) were congenitally deaf. The commonest causes of acquired deafness were meningitis and cytomegalovirus infection. The median age for congenitally deaf bilateral simultaneous CI was 2.2 years, mean surgical duration 4.5 hours. 6.3% surgeries were day case procedures. Eight cases (2.0%) of planned bilateral CI had unilateral surgery. The overall major complication rate was 1.6% (0.9% excluding device failures), including explantation due to infection (0.2%), cerebrospinal fluid leak (0.2%), and meningitis (0.1%). There were no permanent facial nerve palsies and no deaths. Sixty-two (6.5%) immediate minor complications included 12 (1.3%) children with significant vestibular impairment. The complication rate was similar following bilateral CI compared to sequential and unilateral CI, and is comparable to other published series. This prospective multi-centre audit provides evidence that bilateral paediatric CI is a safe procedure in the UK, thus endorsing its role as a major therapeutic intervention in childhood deafness.	t	\N
24626890	Auditory steady-state responses (ASSR) are an important tool to detect objectively frequency-specific hearing thresholds. Pure-tone audiometry is the gold-standard for hearing evaluation, although sometimes it may be inconclusive, especially in children and uncooperative adults. Compare pure tone thresholds (PT) with ASSR thresholds in normal hearing subjects. In this prospective cross-sectional study we included 26 adults (n = 52 ears) of both genders, without any hearing complaints or otologic diseases and normal puretone thresholds. All subjects had clinical history, otomicroscopy, audiometry and immitance measurements. This evaluation was followed by the ASSR test. The mean pure-tone and ASSR thresholds for each frequency were calculated. The mean difference between PTand ASSR thresholdswas 7,12 for 500 Hz, 7,6 for 1000 Hz, 8,27 for 2000 Hz and 9,71 dB for 4000 Hz. There were no difference between PT and ASSR means at either frequency. ASSR thresholds were comparable to pure-tone thresholds in normal hearing adults. Nevertheless it should not be used as the only method of hearing evaluation.	t	\N
24627225	The goal of this study was to tease apart the roles of phonological awareness (pA) and phonological short-term memory (pSTM) in sentence comprehension, sentence production, and word reading. Children 6- to 10-years of age (N = 377) completed standardized tests of pA ('Elision') and pSTM ('Nonword Repetition') from the Comprehensive Test of Phonological Processing. Concepts and Following Directions (CFD) and Formulated Sentences (FS) were taken from the Clinical Evaluation of Language Fundamentals-Fourth Edition, as measures of sentence comprehension and production, respectively. Children also completed the Word Identification (Word Id) and Word Attack (Word Att) subtests of the Woodcock Reading Mastery Test-Third Edition. Hierarchical multiple regression analyses controlling for age and nonverbal IQ revealed that Elision was the only significant predictor of CFD and FS. While Elision was the strongest predictor of Word Id and Word Att, Nonword Repetition accounted for additional variance in both reading measures. These results emphasize the usefulness of breaking down phonological processing into multiple components and they also have implications language and reading disordered populations.	t	\N
24630052	To investigate the clinical usefulness of the LS-chirp auditory brainstem response for estimation of behavioral thresholds in young children with mild to severe hearing losses. 68 infants (136 ears) aged 6-12 months (mean age=9.2 months) with bilateral mild to severe hearing losses were studied at Children's Hospital of Fudan University. In all cases, the children were referred for LS-chirp ABR and visual reinforcement audiometric (VRA) measurements. The low-frequency band chirp (LF-chirp) thresholds (frequency band=0.1-0.85kHz) were compared to the average VRA thresholds (frequency band=0.25-0.5kHz), whereas the high-frequency band chirp (HF-chirp) thresholds (frequency band=1-10kHz) were compared to the average VRA thresholds (frequency band=1-4kHz) using statistical correlation coefficient values. The LS-chirp ABR thresholds are very close to behavioral hearing levels. The mean differences between chirp-ABR and VRA thresholds were within 5dBHL for all measurements. The smallest mean threshold difference (<3dBHL) was obtained for the severe hearing loss group. The correlation coefficient values (r) were 0.97 at low-frequency and high-frequency bands. For each carrier frequency, the best correlations between chirp-ABR thresholds and VRA thresholds were obtained at VRA frequency of 0.25kHz/LF-chirp (r=0.98) and VRA frequency of 1kHz/HF-chirp (r=0.98). This study demonstrates the effectiveness using chirp-ABR predicted frequency-specific thresholds, especially of low and middle frequencies. LS-chirp ABR thresholds determined behavioral thresholds in patients with severe hearing losses were better than for mild hearing losses. The use of a chirp-ABR testing ensures higher sensitivity and accuracy than that of auditory stead-state evoked response (ASSR) for measuring frequency-specific thresholds in young children.	t	\N
24631260	The left anterior temporal lobe (LATL) is robustly implicated in semantic processing by a growing body of literature. However, these results have emerged from two distinct bodies of work, addressing two different processing levels. On the one hand, the LATL has been characterized as a 'semantic hub׳ that binds features of concepts across a distributed network, based on results from semantic dementia and hemodynamic findings on the categorization of specific compared to basic exemplars. On the other, the LATL has been implicated in combinatorial operations in language, as shown by increased activity in this region associated with the processing of sentences and of basic phrases. The present work aimed to reconcile these two literatures by independently manipulating combination and concept specificity within a minimal MEG paradigm. Participants viewed simple nouns that denoted either low specificity (fish) or high specificity categories (trout) presented in either combinatorial (spotted fish/trout) or non-combinatorial contexts (xhsl fish/trout). By combining these paradigms from the two literatures, we directly compared the engagement of the LATL in semantic memory vs. semantic composition. Our results indicate that although noun specificity subtly modulates the LATL activity elicited by single nouns, it most robustly affects the size of the composition effect when these nouns are adjectivally modified, with low specificity nouns eliciting a much larger effect. We conclude that these findings are compatible with an account in which the specificity and composition effects arise from a shared mechanism of meaning specification.	t	\N
24632323	This study investigated audiovisual synchrony perception in a rhythmic context, where the sound was not consequent upon the observed movement. Participants judged synchrony between a bouncing point-light figure and an auditory rhythm in two experiments. Two questions were of interest: (1) whether the reference in the visual movement, with which the auditory beat should coincide, relies on a position or a velocity cue; (2) whether the figure form and motion profile affect synchrony perception. Experiment 1 required synchrony judgment with regard to the same (lowest) position of the movement in four visual conditions: two figure forms (human or non-human) combined with two motion profiles (human or ball trajectory). Whereas figure form did not affect synchrony perception, the point of subjective simultaneity differed between the two motions, suggesting that participants adopted the peak velocity in each downward trajectory as their visual reference. Experiment 2 further demonstrated that, when judgment was required with regard to the highest position, the maximal synchrony response was considerably low for ball motion, which lacked a peak velocity in the upward trajectory. The finding of peak velocity as a cue parallels results of visuomotor synchronization tasks employing biological stimuli, suggesting that synchrony judgment with rhythmic motions relies on the perceived visual beat.	t	\N
24636747	Similar to other zona pellucida mutations in the alpha-tectorin (TECTA) gene, the p.Y1870C alteration in DFNA8/12 causes prelingual, nonsyndromic, autosomal dominant hearing loss. Here we investigated the effect of p.Y1870C on reverse transduction by audiometric studies in the family. Pure tone audiometry, brainstem evoked response audiometry, the Freiburger test for speech understanding and transient evoked and distortion product otoacoustic emissions were assessed in three available affected members bearing p.Y1870C. Pure tone audiometry showed U-shaped curves with moderate to severe degrees of hearing impairment confirmed by brainstem evoked response audiometry. Transient evoked and distortion product otoacoustic emissions were completely absent in all affected family members whereas word recognition scores were up to 95%. Although the missense p.Y1870C TECTA mutation leads to complete failure of the cochlear amplifier in humans, very high speech perception scores can be achieved with appropriate therapy.	t	\N
24639033	Although individuals with autism are known to have significant communication problems, the cellular mechanisms responsible for impaired communication are poorly understood. Valproic acid (VPA) is an anticonvulsant that is a known risk factor for autism in prenatally exposed children. Prenatal VPA exposure in rats causes numerous neural and behavioral abnormalities that mimic autism. We predicted that VPA exposure may lead to auditory processing impairments which may contribute to the deficits in communication observed in individuals with autism. In this study, we document auditory cortex responses in rats prenatally exposed to VPA. We recorded local field potentials and multiunit responses to speech sounds in primary auditory cortex, anterior auditory field, ventral auditory field. and posterior auditory field in VPA exposed and control rats. Prenatal VPA exposure severely degrades the precise spatiotemporal patterns evoked by speech sounds in secondary, but not primary auditory cortex. This result parallels findings in humans and suggests that secondary auditory fields may be more sensitive to environmental disturbances and may provide insight into possible mechanisms related to auditory deficits in individuals with autism.	t	\N
24647432	Different brain areas integrate information over different timescales, and this capacity to accumulate information increases from early sensory areas to higher order perceptual and cognitive areas. It is currently unknown whether the timescale capacity of each brain area is fixed or whether it adaptively rescales depending on the rate at which information arrives from the world. Here, using functional MRI, we measured brain responses to an auditory narrative presented at different rates. We asked whether neural responses to slowed (speeded) versions of the narrative could be compressed (stretched) to match neural responses to the original narrative. Temporal rescaling was observed in early auditory regions (which accumulate information over short timescales) as well as linguistic and extra-linguistic brain areas (which can accumulate information over long timescales). The temporal rescaling phenomenon started to break down for stimuli presented at double speed, and intelligibility was also impaired for these stimuli. These data suggest that 1) the rate of neural information processing can be rescaled according to the rate of incoming information, both in early sensory regions as well as in higher order cortexes, and 2) the rescaling of neural dynamics is confined to a range of rates that match the range of behavioral performance.	t	\N
24657592	Fragile X syndrome (FXS) is a common inherited cause of intellectual disability that results from a CGG repeat expansion in the FMR1 gene. Large repeat expansions trigger both transcriptional and translational suppression of Fragile X protein (FMRP) production. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is an allelic neurodegenerative disease caused by smaller "pre-mutation" CGG repeat expansions that enhance FMR1 transcription but lead to translational inefficiency and reduced FMRP expression in animal models. Sensorimotor gating as measured by pre-pulse inhibition (PPI) is altered in both FXS patients and Fmr1 knock out (KO) mice. Similarly, FXTAS patients have demonstrated PPI deficits. Recent work suggests there may be overlapping synaptic defects between Fmr1 KO and CGG knock-in premutation mouse models (CGG KI). We therefore sought to interrogate PPI in CGG KI mice. Using a quiet PPI protocol more akin to human testing conditions, we find that Fmr1 KO animals have significantly impaired PPI. Using this same protocol, we find CGG KI mice demonstrate an age-dependent impairment in PPI compared to wild type (WT) controls. This study describes a novel phenotype in CGG KI mice that can be used in future therapeutic development targeting premutation associated symptoms.	t	\N
24660803	This study investigates the extent to which age-related language processing difficulties are due to a decline in sensory processes or to a deterioration of cognitive factors, specifically, attentional control. Two facets of attentional control were examined: inhibition of irrelevant information and divided attention. Younger and older adults were asked to categorize the initial phoneme of spoken syllables ("Was it m or n?"), trying to ignore the lexical status of the syllables. The phonemes were manipulated to range in eight steps from m to n. Participants also did a discrimination task on syllable pairs ("Were the initial sounds the same or different?"). Categorization and discrimination were performed under either divided attention (concurrent visual-search task) or focused attention (no visual task). The results showed that even when the younger and older adults were matched on their discrimination scores: (1) the older adults had more difficulty inhibiting lexical knowledge than did younger adults, (2) divided attention weakened lexical inhibition in both younger and older adults, and (3) divided attention impaired sound discrimination more in older than younger listeners. The results confirm the independent and combined contribution of sensory decline and deficit in attentional control to language processing difficulties associated with aging. The relative weight of these variables and their mechanisms of action are discussed in the context of theories of aging and language.	t	\N
24663012	The present study aimed to vocally assess a group of rock singers who use growl voice and reinforced falsetto. A group of 21 rock singers and a control group of 18 pop singers were included. Singing and speaking voice was assessed through acoustic, perceptual, functional and laryngoscopic analysis. No significant differences were observed between groups in most of the analyses. Acoustic and perceptual analysis of the experimental group demonstrated normality of speaking voice. Endoscopic evaluation showed that most rock singers presented during singing voice a high vertical laryngeal position, pharyngeal compression and laryngeal supraglottic compression. Supraglottic activity during speaking voice tasks was also observed. However, overall vocal fold integrity was demonstrated in most of the participants. Slightly abnormal observations were demonstrated in few of them. Singing voice handicap index revealed that the most affected variable was the physical sphere, followed by the social and emotional spheres. Although growl voice and reinforced falsetto represent laryngeal and pharyngeal hyperfunctional activity, they did not seem to contribute to the presence of any major vocal fold disorder in our subjects. Nevertheless, we cannot rule out the possibility that more evident vocal fold disorders could be found in singers who use these techniques more often and during a longer period of time.	t	\N
24672005	The inner ear receives two types of efferent feedback from the brainstem: one pathway provides gain control on outer hair cells' contribution to cochlear amplification, and the other modulates the excitability of the cochlear nerve. Although efferent feedback can protect hair cells from acoustic injury and thereby minimize noise-induced permanent threshold shifts, most prior studies focused on high-intensity exposures (>100 dB SPL). Here, we show that efferents are essential for long-term maintenance of cochlear function in mice aged 1 year post-de-efferentation without purposeful acoustic overexposure. Cochlear de-efferentation was achieved by surgical lesion of efferent pathways in the brainstem and was assessed by quantitative analysis of immunostained efferent terminals in outer and inner hair cell areas. The resultant loss of efferent feedback accelerated the age-related amplitude reduction in cochlear neural responses, as seen in auditory brainstem responses, and increased the loss of synapses between hair cells and the terminals of cochlear nerve fibers, as seen in confocal analysis of the organ of Corti immunostained for presynaptic and postsynaptic markers. This type of neuropathy, also seen after moderate noise exposure, has been termed "hidden hearing loss", because it does not affect thresholds, but can be seen in the suprathreshold amplitudes of cochlear neural responses, and likely causes problems with hearing in a noisy environment, a classic symptom of age-related hearing loss in humans. Since efferent reflex strength varies among individuals and can be measured noninvasively, a weak reflex may be an important risk factor, and prognostic indicator, for age-related hearing impairment.	t	\N
24681401	Voice control is critical to communication. To date, studies have used behavioral, electrophysiological and functional data to investigate the neural correlates of voice control using perturbation tasks, but have yet to examine the interactions of these neural regions. The goal of this study was to use structural equation modeling of functional neuroimaging data to examine network properties of voice with and without perturbation. Results showed that the presence of a pitch shift, which was processed as an error in vocalization, altered connections between right STG and left STG. Other regions that revealed differences in connectivity during error detection and correction included bilateral inferior frontal gyrus, and the primary and pre motor cortices. Results indicated that STG plays a critical role in voice control, specifically, during error detection and correction. Additionally, pitch perturbation elicits changes in the voice network that suggest the right hemisphere is critical to pitch modulation.	t	\N
24681402	Converging evidence suggests that understanding our first-language (L1) results in reactivation of experiential sensorimotor traces in the brain. Surprisingly, little is known regarding the involvement of these processes during second-language (L2) processing. Participants saw L1 or L2 words referring to entities with a typical location (e.g., star, mole) (Experiment 1 & 2) or to an emotion (e.g., happy, sad) (Experiment 3). Participants responded to the words' ink color with an upward or downward arm movement. Despite word meaning being fully task-irrelevant, L2 automatically activated motor responses similar to L1 even when L2 was acquired rather late in life (age >11). Specifically, words such as star facilitated upward, and words such as root facilitated downward responses. Additionally, words referring to positive emotions facilitated upward, and words referring to negative emotions facilitated downward responses. In summary our study suggests that reactivation of experiential traces is not limited to L1 processing.	t	\N
24684405	We sought to determine whether the results of audiological tests and tinnitus characteristics, particularly tinnitus pitch and minimum masking level (MML), depend on tinnitus etiology, and what other etiology-specific tinnitus characteristics there are. The patients answered questions concerning tinnitus laterality, duration, character, aggravation, alleviation, previous treatment, and circumstances of onset. The results of tympanometry, pure-tone audiometry, distortion-product otoacoustic emissions, tinnitus likeness spectrum, MML, and uncomfortable loudness level were evaluated. Patients with several tinnitus etiological factors were excluded. The remaining participants were divided into groups according to medical history: acute acoustic trauma: 67 ears; chronic acoustic trauma: 82; prolonged use of oral estrogen and progesterone contraceptives: 46; Ménière's disease: 25; congenital hearing loss: 19; sensorineural sudden deafness: 40; dull head trauma: 19; viral labyrinthitis: 53; stroke: 6; presbycusis: 152. Data of 509 ears were analysed. Tinnitus pitch was highest in patients with acute acoustic trauma and lowest in patients receiving estrogen and progesterone. MML was lowest after acute acoustic trauma and in congenital hearing loss, and highest after a stroke and in the case of presbytinnitus. Tinnitus pitch and MML are etiology dependent.	t	\N
24686520	PURPOSE The purpose of this study was to investigate how linguistic knowledge interacts with indexical knowledge in older children's perception under demanding listening conditions created by extensive talker variability. METHOD Twenty-five 9- to 12-year-old children, 12 from North Carolina (NC) and 13 from Wisconsin (WI), identified 12 vowels in isolated /hVd/ words produced by 120 talkers representing the 2 dialects (NC and WI), both genders, and 3 age groups (generations) of residents from the same geographic locations as the listeners. RESULTS Identification rates were higher for responses to talkers from the same dialect as the listeners and for female speech. Listeners were sensitive to systematic positional variations in vowels and their dynamic structure (formant movement) associated with generational differences in vowel pronunciation resulting from sound change in a speech community. Overall identification rate was 71.7%, which is 8.5% lower than for the adults responding to the same stimuli in Jacewicz and Fox (2012). CONCLUSION Typically developing older children were successful in dealing with both phonetic and indexical variation related to talker dialect, gender, and generation. They were less consistent than the adults, most likely because of less efficient encoding of acoustic-phonetic information in the speech of multiple talkers and relative inexperience with indexical variation.	t	\N
24686901	PURPOSE The aim of this study was to evaluate the understanding of English sentences produced by native (English) and nonnative (Spanish) talkers by listeners with normal hearing (NH) and listeners with cochlear implants (CIs). METHOD Sentence recognition in noise was measured in adult subjects with CIs and subjects with NH, all of whom were native talkers of American English. Test sentences were from the Hearing in Noise Test (HINT) database and were produced in English by four native and eight nonnative talkers. Subjects also rated the intelligibility and accent for each talker. RESULTS The speech recognition thresholds in noise of subjects with CIs and subjects with NH were 4.23 dB and 1.32 dB poorer with nonnative talkers than with native talkers, respectively. Performance was significantly correlated with talker intelligibility and accent ratings for subjects with CIs but only correlated with talker intelligibility ratings for subjects with NH. For all subjects, performance with individual nonnative talkers was significantly correlated with talkers' number of years of residence in the United States. CONCLUSION CI users exhibited a larger deficit in speech understanding with nonnative talkers than did subjects with NH, relative to native talkers. Nonnative talkers' experience with native culture contributed strongly to speech understanding in noise, intelligibility ratings, and accent ratings of both listeners with NH and listeners with CIs.	t	\N
24686915	The purpose of this study was to develop a task to evaluate children's English and Spanish speech perception abilities in either noise or competing speech maskers. Eight bilingual Spanish-English and 8 age-matched monolingual English children (ages 4.9-16.4 years) were tested. A forced-choice, picture-pointing paradigm was selected for adaptively estimating masked speech reception thresholds. Speech stimuli were spoken by simultaneous bilingual Spanish-English talkers. The target stimuli were 30 disyllabic English and Spanish words, familiar to 5-year-olds and easily illustrated. Competing stimuli included either 2-talker English or 2-talker Spanish speech (corresponding to target language) and spectrally matched noise. For both groups of children, regardless of test language, performance was significantly worse for the 2-talker than for the noise masker condition. No difference in performance was found between bilingual and monolingual children. Bilingual children performed significantly better in English than in Spanish in competing speech. For all listening conditions, performance improved with increasing age. Results indicated that the stimuli and task were appropriate for speech recognition testing in both languages, providing a more conventional measure of speech-in-noise perception as well as a measure of complex listening. Further research is needed to determine performance for Spanish-dominant listeners and to evaluate the feasibility of implementation into routine clinical use.	t	\N
24687018	Although a number of questionnaires are available to assess hearing aid benefit and general hearing disability, relatively few investigate spatial hearing ability in more complex listening situations. The aim of this study was to document the performance of individuals with normal hearing using the Spatial Hearing Questionnaire (SHQ; Tyler, Perreau, & Ji, 2009) and to compare performance with published data from cochlear implant (CI) users. Fifty-one participants with normal hearing participated. All participants completed the 24-item SHQ. Also, a factor analysis and reliability tests were performed. Performance on the SHQ was high (87%) for the participants with normal hearing. Subjective ratings varied across different listening situations: Understanding speech in quiet (98%) was rated higher than sound localization (84%) and understanding speech in a background of noise (85%). Compared with previously published data (Tyler, Perreau, & Ji, 2009), listeners with normal hearing rated their spatial hearing ability significantly better than bilateral and unilateral CI users. Results confirmed that the SHQ is a reliable measure of spatial hearing ability for listeners with normal hearing. Overall, results indicated that the SHQ is able to capture expected differences between individuals with normal hearing and CI users. These new data can be used as targets following the provision of hearing devices.	t	\N
24687041	To describe the inheritance patterns and auditory phenotype features of 3 Canadian families with mutations in 2 X-linked "deafness" genes (DFNX). Audiological, medical, and family histories were collected and family members interviewed to compare hearing thresholds and case histories between cases with mutations in SMPX versus POU3F4. The family pedigrees reveal characteristic X-linked inheritance patterns. Phenotypic features associated with the SMPX (DFNX4) mutation include early onset in males with rapid progression from mild and flat to sloping sensorineural loss, with highly variable onset and hearing loss severity in females. In contrast, phenotypic features associated with the POU3F4 (DFNX2) mutation are characterized by an early onset, mixed hearing loss with fluctuation in males, and a normal hearing phenotype reported for females. The study shows how this unique inheritance pattern and both gender and mutation-specific phenotype variations can alert audiologists to the presence of X-linked genetic etiologies in their clinical practice. By incorporating this knowledge into clinical decision making, audiologists can facilitate the early identification of X-linked hearing loss and contribute to the effective team management of affected families.	t	\N
24704377	Perceptual synchrony and multisensory integration both vary as a function of stimulus onset asynchrony, but evidences from behavioral, patient, and lesion studies all support some dissociation between these two processes. Although it has been found that both perceptual synchrony and multisensory integration are recalibrated after exposure to asynchronous multisensory stimuli, no studies have directly compared these two recalibration patterns. We addressed this by using McGurk speech and requiring participants to perform simultaneity judgments and a syllable identification task in separate sessions. The results revealed that after exposure to asynchrony, both perceptual synchrony and McGurk fusion shifted toward the temporal lag. The recalibration aftereffects (i.e., the magnitude of shifts) of these two processes have no significant difference and correlation. In addition, McGurk fusion increased strongly at the direction of the temporal lag, which could not be fully explained by fusion shifts. Thus, the present research implies that recalibration patterns of explicit and implicit timing represented by perceptual synchrony and multisensory integration have both similarity and difference.	t	\N
24709357	Although there is an extensive literature on the study of the neural correlates of consciousness (NCC) this is a subject that is far from being considered over. In this paper we present a novel experimental paradigm, based on binocular rivalry, to study internally and externally generated conscious experiences. We called this procedure bimodal rivalry. In addition, and assuming the non-linear nature of the EEG signals, we propose the use of fractal dimension to characterize the complexity of the EEG signal associated with each percept. Analysis of the data showed a significant difference in complexity between the internally generated and externally generated percepts. Moreover, EEG complexity was dissimilar for externally generated auditory and visual percepts. These results support fractal dimension analyses as a new tool to characterize conscious perception.	t	\N
24715101	The current study investigated the mechanism underlying subliminal inhibition using the negative compatibility effect (NCE) paradigm. We hypothesized that a decrease in prime activation affects the subsequent inhibitory process, delaying onset of inhibition and reducing its strength. Two experiments tested this hypothesis using arrow stimuli as primes and targets. Two different irrelevant masks (i.e., a mask sharing no prime features) were presented in succession in each trial to not only ensure that primes were processed subliminally, but also avoid feature updating between primes and masks. Prime/target compatibility and prime background density were manipulated in Experiment 1. Results showed that under subliminal inhibitory condition, the NCE disappears when the density increases (i.e., pixel density in the prime's background of 25 %) in Experiment 1. However, when we fixed the prime's background at the density of 25 % and manipulated prime/target compatibility as well as inter-stimuli-interval (ISI) between mask and target in Experiment 2, behavioral results showed marginally significant NCEs in the 150-ms ISI condition. Electrophysiological evidence showed the lateralized readiness potential for compatible trials was significantly more positive than that for incompatible trials during the two consecutive time windows (i.e., 400-450 and 450-500 ms) in the 150-ms ISI condition. In addition, the NCE size was significant smaller in Experiment 2 than in Experiment 1. All of the results support predictions of the continuous subliminal inhibitory mechanism hypothesis which posits that decreases in prime activation strength lead to delay in inhibitory onset and decline in inhibitory strength.	t	\N
24727491	The binaural cues used by terrestrial animals for sound localization in azimuth may not always suffice for accurate sound localization underwater. The purpose of this research was to examine the theoretical limits of interaural timing and level differences available underwater using computational and physical models. A paired-hydrophone system was used to record sounds transmitted underwater and recordings were analyzed using neural networks calibrated to reflect the auditory capabilities of terrestrial mammals. Estimates of source direction based on temporal differences were most accurate for frequencies between 0.5 and 1.75 kHz, with greater resolution toward the midline (2°), and lower resolution toward the periphery (9°). Level cues also changed systematically with source azimuth, even at lower frequencies than expected from theoretical calculations, suggesting that binaural mechanical coupling (e.g., through bone conduction) might, in principle, facilitate underwater sound localization. Overall, the relatively limited ability of the model to estimate source position using temporal and level difference cues underwater suggests that animals such as whales may use additional cues to accurately localize conspecifics and predators at long distances.	t	\N
24735233	The dichotic listening task is typically administered by presenting a consonant-vowel (CV) syllable to each ear and asking the participant to report the syllable heard most clearly. The results tend to show more reports of the right ear syllable than of the left ear syllable, an effect called the right ear advantage (REA). The REA is assumed to be due to the crossing over of auditory fibres and the processing of language stimuli being lateralised to left temporal areas. However, the tendency for most dichotic listening experiments to use only CV syllable stimuli limits the extent to which the conclusions can be generalised to also apply to other speech phonemes. The current study re-examines the REA in dichotic listening by using both CV and vowel-consonant (VC) syllables and combinations thereof. Results showed a replication of the REA response pattern for both CV and VC syllables, thus indicating that the general assumption of left-side localisation of processing can be applied for both types of stimuli. Further, on trials where a CV is presented in one ear and a VC is presented in the other ear, the CV is selected more often than the VC, indicating that these phonemes have an acoustic or processing advantage.	t	\N
24735850	To form a coherent percept of the environment, the brain needs to bind sensory signals emanating from a common source, but to segregate those from different sources [1]. Temporal correlations and synchrony act as prominent cues for multisensory integration [2-4], but the neural mechanisms by which such cues are identified remain unclear. Predictive coding suggests that the brain iteratively optimizes an internal model of its environment by minimizing the errors between its predictions and the sensory inputs [5,6]. This model enables the brain to predict the temporal evolution of natural audiovisual inputs and their statistical (for example, temporal) relationship. A prediction of this theory is that asynchronous audiovisual signals violating the model's predictions induce an error signal that depends on the directionality of the audiovisual asynchrony. As the visual system generates the dominant temporal predictions for visual leading asynchrony, the delayed auditory inputs are expected to generate a prediction error signal in the auditory system (and vice versa for auditory leading asynchrony). Using functional magnetic resonance imaging (fMRI), we measured participants' brain responses to synchronous, visual leading and auditory leading movies of speech, sinewave speech or music. In line with predictive coding, auditory leading asynchrony elicited a prediction error in visual cortices and visual leading asynchrony in auditory cortices. Our results reveal predictive coding as a generic mechanism to temporally bind signals from multiple senses into a coherent percept.	t	\N
24736111	The aim of this study was to determine the relationship between serum albumin, affective prosody, and symptoms of attention-deficit hyperactivity disorder (ADHD) found coincidentally in a recently published study. Here, serum albumin levels were assessed as a covariate. Twenty healthy male adults (controls) and 20 adult male patients with ADHD participated in the study on two study days. Serum albumin levels and performance in an affective prosody task were assessed, and correlations were determined. Serum albumin had a significant correlation with performance on an affective prosody task on both of the 2 study days. The same correlations were not significant in the healthy control group. There was no difference in the serum albumin level between patients with ADHD and healthy controls. The association between serum albumin and affective prosody in adults with ADHD is a novel finding. However, to date, there is no clear theory that explains this association. Future research should analyze whether serum albumin influences causes changes in performance in affective prosody using experimental designs.	t	\N
24736186	We investigated whether unattended visual, auditory and tactile stimuli compete for capacity-limited early sensory processing across senses. In three experiments, we probed competitive audio-visual, visuo-tactile and audio-tactile stimulus interactions. To this end, continuous visual, auditory and tactile stimulus streams ('reference' stimuli) were frequency-tagged to elicit steady-state responses (SSRs). These electrophysiological oscillatory brain responses indexed ongoing stimulus processing in corresponding senses. To induce competition, we introduced transient frequency-tagged stimuli in same and/or different senses ('competitors') during reference presentation. Participants performed a separate visual discrimination task at central fixation to control for attentional biases of sensory processing. A comparison of reference-driven SSR amplitudes between competitor-present and competitor-absent periods revealed reduced amplitudes when a competitor was presented in the same sensory modality as the reference. Reduced amplitudes indicated the competitor's suppressive influence on reference stimulus processing. Crucially, no such suppression was found when a competitor was presented in a different than the reference modality. These results strongly suggest that early sensory competition is exclusively modality-specific and does not extend across senses. We discuss consequences of these findings for modeling the neural mechanisms underlying intermodal attention.	t	\N
24738537	Neuroscientific and musicological approaches to music cognition indicate that listeners familiarized in the Western tonal tradition expect a musical phrase boundary at predictable time intervals. However, phrase boundary prediction processes in music remain untested. We analyzed event-related potentials (ERPs) and event-related induced power changes at the onset and offset of a boundary pause. We made comparisons with modified melodies, where the pause was omitted and filled by tones. The offset of the pause elicited a closure positive shift (CPS), indexing phrase boundary detection. The onset of the filling tones elicited significant increases in theta and beta powers. In addition, the P2 component was larger when the filling tones started than when they ended. The responses to boundary omission suggest that listeners expected to hear a boundary pause. Therefore, boundary prediction seems to coexist with boundary detection in music segmentation.	t	\N
24744448	Interest in the perception of the material of objects has been growing. While material perception is a critical ability for animals to properly regulate behavioral interactions with surrounding objects (e.g., eating), little is known about its underlying processing. Vision and audition provide useful information for material perception; using only its visual appearance or impact sound, we can infer what an object is made from. However, what material is perceived when the visual appearance of one material is combined with the impact sound of another, and what are the rules that govern cross-modal integration of material information? We addressed these questions by asking 16 human participants to rate how likely it was that audiovisual stimuli (48 combinations of visual appearances of six materials and impact sounds of eight materials) along with visual-only stimuli and auditory-only stimuli fell into each of 13 material categories. The results indicated strong interactions between audiovisual material perceptions; for example, the appearance of glass paired with a pepper sound is perceived as transparent plastic. Rating material-category likelihoods follow a multiplicative integration rule in that the categories judged to be likely are consistent with both visual and auditory stimuli. On the other hand, rating-material properties, such as roughness and hardness, follow a weighted average rule. Despite a difference in their integration calculations, both rules can be interpreted as optimal Bayesian integration of independent audiovisual estimations for the two types of material judgment, respectively.	t	\N
24750038	Alarms are ubiquitous in anaesthetic practice, but their net effect on anaesthesiologists' performance and patient safety is debated. In this study, 27 anaesthesiologists performed two simulation sessions in random order; one session was programmed to include an alarm condition, with a standard, frequent, clearly audible alarm sound. During these sessions, adverse events were simulated and anaesthesiologists' response times to these events were recorded. Perceived workload was assessed with the NASA Task Load Index. Response times to adverse events and perceived workload were similar in both groups. Pooled response times to atrial fibrillation and desaturation were fast, with a median (range [IQR]) of 8 (4-14 [1-41]) s and 9 (6-16 [1-44]) s, respectively. Pooled response times to an ST segment elevation on the ECG and an obstructed intravenous line were significantly slower, with median (IQR[range]) times of 34 (21-76[4-300]) s and 227 (95-399 [2-600]) s, respectively (p < 0.001). This study shows that in a simulated anaesthesia environment, response times to adverse events are similar in the absence or presence of an audible alarm, and that response times to various critical events differ.	t	\N
24751750	To prospectively evaluate hearing outcomes in patients with osteogenesis imperfecta undergoing primary stapes surgery and to isolate prognostic factors for success. A nonrandomized, open, prospective case series. A tertiary referral center. Twenty-five consecutive patients who underwent 32 primary stapedotomies for osteogenesis imperfecta with evidence of stapes fixation and available postoperative pure-tone audiometry. Primary stapedotomy with vein graft interposition and reconstruction with a regular Teflon piston or bucket handle-type piston. Preoperative and postoperative audiometric evaluation using conventional 4-frequency (0.5, 1, 2, and 4 kHz) audiometry. Air-conduction thresholds, bone-conduction thresholds, and air-bone gap were measured. The overall audiometric results as well as the results of audiometric evaluation at 3 months and at least 1 year after surgery were used. Overall, postoperative air-bone gap closure to within 10 dB was achieved in 88% of cases. Mean (standard deviation) gain in air-conduction threshold was 22 (9.4) dB for the entire case series, and mean (standard deviation) air-bone gap closure was 22 (9.0) dB. Backward multivariate logistic regression showed that a model with preoperative air-bone gap closure and intraoperatively established incus length accurately predicts success after primary stapes surgery. Stapes surgery is a feasible and safe treatment option in patients with osteogenesis imperfecta. Success is associated with preoperative air-bone gap and intraoperatively established incus length.	t	\N
24754219	Diachronic velar palatalization is taken as the case study for modeling the emergence of a new phoneme category. The spread of a palatalized variant through the lexicon is treated as a stochastic classification task for the listener/learner. The model combines two measures of similarity to determine classification within an exemplar-theoretic framework: acoustic distance and phonotactic expectation. There are three model outcomes: contrast, allophony, or contextual neutralization between the plain and palatalized velars. It is shown, through a series of simulations, that these can be predicted from the distribution of sounds within the pre-change lexicons, namely, the ratio of the /k-vowel/ sequences containing naturally palatalizing vowels (i, I, e), to those containing non-palatalizers. "Unnatural" phonotactic associations can arise in individual lexicons, but are sharply limited due to the large size of the lexicon and the local nature of the phoneme changes. "Anti-natural" distributions, which categorically violate the proposed implicational relationship between palatalization and frontness/height, are absent. This work provides an explicit and restrictive model of phoneme change. The results also serve as an existence proof for an outcome-blind mechanism of avoiding over-generation.	t	\N
24755208	A wide range of literature is available on the features of ataxic dysarthria, investigating segmental and prosodic characteristics by acoustic and perceptual means. However, very few studies have been published that look closely at the relationship between the observed phonetic disturbances and their perceptual sequelae, particularly in the area of prosody. The aim of the current study was therefore to examine the stress production of eight individuals with ataxic dysarthria and matched healthy controls, and to relate the results of phonological and perceptual evaluations to phonetic performances to better understand the relationship between these three components for speech outcomes. Speakers performed a sentence stress task which was analysed phonologically in terms of inventory, distribution, implementation and function of pitch accentuation. These data were then evaluated in relation to previously published phonetic and perceptual results on the same speaker group by the authors. Results indicated that the speakers with ataxia used a wide range of pitch patterns, but pitch-accented a higher number of words, and produced shorter phrases. The increased number of pitch accents per phrase was furthermore reflected in a reduced percentage of de-accented words in post-focal position. Perceptual results established this pattern as the main cause for listener errors in identifying the intended stressed item in an utterance. In addition, the performances of two speakers are discussed in greater detail. Although they were unable to de-accent, they nevertheless marked stress appropriately through phonetic compensatory strategies. After reading this article the reader will be able to (1) explain the relevance of phonology and phonetics in the perception of stress production in ataxic dysarthria; (2) describe the different levels of intonational analysis; and (3) understand the observed intonation patterns in ataxic dysarthria as well as the compensatory mechanisms speakers may adopt to produce stress.	t	\N
24763046	Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI.	t	\N
24764261	We investigated the relative effects of simple and complex auditory-visual discrimination training using an adapted alternating treatments design to establish derived stimulus relations in 2 children who had been diagnosed with autism and 1 typically developing peer. Emergence of untrained conditional relations was observed after training in both conditions, with a possible advantage of simple-sample training for 1 participant. Results of generalization and follow-up probes were mixed.	t	\N
24769166	Although alterations of the limbic system have been linked to tinnitus persistence, the neural networks underlying such alteration are unclear. The present study investigated the effect of tinnitus on emotional processing in middle-aged adults using functional magnetic resonance imaging and stimuli from the International Affective Digital Sounds database. There were three groups of participants: bilateral hearing loss with tinnitus (TIN), age- and gender-matched controls with bilateral hearing loss without tinnitus (HL) and matched normal hearing controls without tinnitus (NH). In the scanner, subjects rated sounds as pleasant, unpleasant, or neutral. The TIN and NH groups, but not the HL group, responded faster to affective sounds compared to neutral sounds. The TIN group had elevated response in bilateral parahippocampus and right insula compared to the NH group, and left parahippocampus compared to HL controls for pleasant relative to neutral sounds. A region-of-interest analysis detected increased activation for NH controls in the right amygdala when responding to affective stimuli, but failed to find a similar heightened response in the TIN and HL groups. All three groups showed increased response in auditory cortices for the affective relative to neutral sounds comparisons. Our results suggest that the emotional processing network is altered in tinnitus to rely on the parahippocampus and insula, rather than the amygdala, and this alteration may maintain a select advantage for the rapid processing of affective stimuli despite the hearing loss. The complex interaction of tinnitus and the limbic system should be accounted for in development of new tinnitus management strategies.	t	\N
24769280	Lexical access during speech comprehension comprises numerous computations, including activation, competition, and selection. The spatio-temporal profile of these processes involves neural activity in peri-auditory cortices at least as early as 200 ms after stimulation. Their oscillatory dynamics are less well understood, although reports link alpha band de-synchronization with lexical processing. We used magnetoencephalography (MEG) to examine whether these alpha-related oscillations reflect the speed of lexical access, as would be predicted if they index lexical activation. In an auditory semantic priming protocol, monosyllabic nouns were presented while participants performed a lexical decision task. Spatially-localizing beamforming was used to examine spectro-temporal effects in left and right auditory cortex time-locked to target word onset. Alpha and beta de-synchronization (10-20 Hz ERD) was attenuated for words following a related prime compared to an unrelated prime beginning about 270 ms after stimulus onset. This timing is consistent with how information about word identity unfolds incrementally in speech, quantified in information-theoretic terms. These findings suggest that alpha de-synchronization during auditory word processing is associated with early stages of lexical access.	t	\N
24769430	In this study meaningful social stimuli were used as probes in a task requiring the judgment of semantic appropriateness to investigate contextual integration ability to test the ability of people with Williams syndrome (WS) to integrate information, as opposed to the use of meaningless syllables in audiovisual studies (the McGurk effect). Participants were presented with background auditory primes followed by targets that were either congruent or incongruent with the prime. Two modes of target were presented: a visual target (AV task) or an auditory target (AA task). Participants were asked to respond yes to contextually appropriate pairs and no to those that were contextually inappropriate. The congruency effect was measured as an index of successful central coherence. Similar to normally developing controls, people with WS showed shorter response latencies and greater accuracy in recognizing congruent pairs compared with incongruent pairs. Their performance did not differ from that of controls matched by mental age, but was inferior to that of controls matched by chronological age. The results revealed generalized contextual integration for auditory primes in both tasks, consistent with previous studies using visual presentation of social-related stimuli in people with WS (Hsu, 2013a, 2013c). Further demonstration of the presence of a modality effect on contextual coherence implies that cross-modal learning may be advantageous compared with unimodal learning.	t	\N
24783989	To assist the human operator, modern auditory interfaces increasingly rely on sound spatialisation to display auditory information and warning signals. However, we often operate in environments that apply vibrations to the whole body, e.g. when driving a vehicle. Here, we report three experiments investigating the effect of sinusoidal vibrations along the vertical axis on spatial hearing. The first was a free-field, narrow-band noise localisation experiment with 5- Hz vibration at 0.88 ms(-2). The other experiments used headphone-based sound lateralisation tasks. Experiment 2 investigated the effect of vibration frequency (4 vs. 8 Hz) at two different magnitudes (0.83 vs. 1.65 ms(-2)) on a left-right discrimination one-interval forced-choice task. Experiment 3 assessed the effect on a two-interval forced-choice location discrimination task with respect to the central and two peripheral reference locations. In spite of the broad range of methods, none of the experiments show a reliable effect of whole-body vibrations on localisation performance. We report three experiments that used both free-field localisation and headphone lateralisation tasks to assess their sensitivity to whole-body vibrations at low frequencies. None of the experiments show a reliable effect of either frequency or magnitude of whole-body vibrations on localisation performance.	t	\N
24809252	The aim of this work was to investigate perceived loudness change in response to melodies that increase (up-ramp) or decrease (down-ramp) in acoustic intensity, and the interaction with other musical factors such as melodic contour, tempo, and tonality (tonal/atonal). A within-subjects design manipulated direction of linear intensity change (up-ramp, down-ramp), melodic contour (ascending, descending), tempo, and tonality, using single ramp trials and paired ramp trials, where single up-ramps and down-ramps were assembled to create continuous up-ramp/down-ramp or down-ramp/up-ramp pairs. Twenty-nine (Exp 1) and thirty-six (Exp 2) participants rated loudness continuously in response to trials with monophonic 13-note piano melodies lasting either 6.4s or 12s. Linear correlation coefficients >.89 between loudness and time show that time-series loudness responses to dynamic up-ramp and down-ramp melodies are essentially linear across all melodies. Therefore, 'indirect' loudness change derived from the difference in loudness at the beginning and end points of the continuous response was calculated. Down-ramps were perceived to change significantly more in loudness than up-ramps in both tonalities and at a relatively slow tempo. Loudness change was also greater for down-ramps presented with a congruent descending melodic contour, relative to an incongruent pairing (down-ramp and ascending melodic contour). No differential effect of intensity ramp/melodic contour congruency was observed for up-ramps. In paired ramp trials assessing the possible impact of ramp context, loudness change in response to up-ramps was significantly greater when preceded by down-ramps, than when not preceded by another ramp. Ramp context did not affect down-ramp perception. The contribution to the fields of music perception and psychoacoustics are discussed in the context of real-time perception of music, principles of music composition, and performance of musical dynamics.	t	\N
24809744	Since Köhler's experiments in the 1920s, researchers have demonstrated a correspondence between words and shapes. Dubbed the "Bouba-Kiki" effect, these auditory-visual associations extend across cultures and are thought to be universal. More recently the effect has been shown in other modalities including taste, suggesting the effect is independent of vision. The study presented here tested the "Bouba-Kiki" effect in the auditory-haptic modalities, using 2D cut-outs and 3D models based on Köhler's original drawings. Presented with shapes they could feel but not see, sighted participants showed a robust "Bouba-Kiki" effect. However, in a sample of people with a range of visual impairments, from congenital total blindness to partial sight, the effect was significantly less pronounced. The findings suggest that, in the absence of a direct visual stimulus, visual imagery plays a role in crossmodal integration.	t	\N
24811450	Mice are emerging as an important behavioral model for studies of auditory perception and acoustic communication. These mammals frequently produce ultrasonic vocalizations, although the details of how these vocalizations are used for communication are not entirely understood. An important step in determining how they might be differentiating their calls is to measure discrimination and identification of the dimensions of various acoustic stimuli. Here, behavioral operant conditioning methods were employed to assess frequency difference limens for pure tones. We found that their thresholds were similar to those in other rodents but higher than in humans. We also asked mice, in an identification paradigm, whether they would use frequency or duration differences to classify stimuli varying on those two dimensions. We found that the mice classified the stimuli based on frequency rather than duration.	t	\N
24815249	Personal audio refers to the creation of a listening zone within which a person, or a group of people, hears a given sound program, without being annoyed by other sound programs being reproduced in the same space. Generally, these different sound zones are created by arrays of loudspeakers. Although these devices have the capacity to achieve different sound zones in an anechoic environment, they are ultimately used in normal rooms, which are reverberant environments. At high frequencies, reflections from the room surfaces create a diffuse pressure component which is uniform throughout the room volume and thus decreases the directional characteristics of the device. This paper shows how the reverberant performance of an array can be modeled, knowing the anechoic performance of the radiator and the acoustic characteristics of the room. A formulation is presented whose results are compared to practical measurements in reverberant environments. Due to reflections from the room surfaces, pressure variations are introduced in the transfer responses of the array. This aspect is assessed by means of simulations where random noise is added to create uncertainties, and by performing measurements in a real environment. These results show how the robustness of an array is increased when it is designed for use in a reverberant environment.	t	\N
24815280	Recent studies on binary masking techniques make the assumption that each time-frequency (T-F) unit contributes an equal amount to the overall intelligibility of speech. The present study demonstrated that the importance of each T-F unit to speech intelligibility varies in accordance with speech content. Specifically, T-F units are categorized into two classes, speech-present T-F units and speech-absent T-F units. Results indicate that the importance of each speech-present T-F unit to speech intelligibility is highly related to the loudness of its target component, while the importance of each speech-absent T-F unit varies according to the loudness of its masker component. Two types of mask errors are also considered, which include miss and false alarm errors. Consistent with previous work, false alarm errors are shown to be more harmful to speech intelligibility than miss errors when the mixture signal-to-noise ratio (SNR) is below 0 dB. However, the relative importance between the two types of error is conditioned on the SNR level of the input speech signal. Based on these observations, a mask-based objective measure, the loudness weighted hit-false, is proposed for predicting speech intelligibility. The proposed objective measure shows significantly higher correlation with intelligibility compared to two existing mask-based objective measures.	t	\N
24815292	Behind-the-ear (BTE) processors of cochlear implant (CI) devices offer little to almost no protection from wind noise in most incidence angles. To assess speech intelligibility, eight CI recipients were tested in 3 and 9 m/s wind. Results indicated that speech intelligibility decreased substantially when the wind velocity, and in turn the wind sound pressure level, increased. A two-microphone wind noise suppression strategy was developed. Scores obtained with this strategy indicated substantial gains in speech intelligibility over other conventional noise reduction strategies tested.	t	\N
24820112	This study aimed to propose an ototoxicity grading system sensitive to the effect of ototoxicity on specific daily life situations like speech intelligibility and the perception of ultra-high sounds and to test its feasibility compared to current criteria. Pure tone averages (PTAs) for speech perception (1-2-4 kHz) and ultra-high frequencies (8-10-12.5 kHz) were incorporated. Threshold shift and hearing level posttreatment were taken into account. Criteria were tested on head and neck cancer patients treated with (chemo-)radiotherapy ([C]RT) and compared with the Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) and the American Speech-Language-Hearing Association criteria (ASHA). Grades 1 and 2 were based on threshold shifts from baseline (in dB) and subjective complaints. Grades 3 and 4 were defined as treatment-induced hearing loss of ≥ 35 dB at PTA 1-2-4 kHz and ≥ 70 dB at PTA 1-2-4 kHz, respectively. In high-dose cisplatin CRT incidences by the new criteria, CTCAEv4 and ASHA were comparable (78%-88%). In RT and low-dose cisplatin CRT, incidences were 36% to 39% in the new criteria versus 22% to 53% in CTCAEv4 and ASHA. The new criteria show an increased sensitivity to ototoxicity compared to CTCAEv4 and ASHA and provide insight into the effect of hearing loss on certain daily life situations. The new grading system seems feasible for clinic and research purposes.	t	\N
24834939	Our results indicated that electric acoustic stimulation (EAS) is beneficial for Japanese-speaking patients, including those with less residual hearing at lower frequencies. Comparable outcomes for the patients with less residual hearing indicated that current audiological criteria for EAS could be expanded. Successful hearing preservation results, together with the progressive nature of loss of residual hearing in these patients, mean that minimally invasive full insertion of medium/long electrodes in cochlear implantation (CI) surgery is a desirable solution. The minimally invasive concepts that have been obtained through EAS surgery are, in fact, crucial for all CI patients. This study was conducted to evaluate hearing preservation results and speech discrimination outcomes of hearing preservation surgeries using medium/long electrodes. A total of 32 consecutive minimally invasive hearing preservation CIs (using a round window approach with deep insertion of a flexible electrode) were performed in 30 Japanese patients (two were bilateral cases), including patients with less residual hearing. Hearing preservation rates as well as speech discrimination/perception scores were investigated on a multicenter basis. Postoperative evaluation after full insertion of the flexible electrodes (24 mm, 31.5 mm) showed that residual hearing was well preserved in all 32 ears. In all patients, speech discrimination and perception scores were improved postoperatively.	t	\N
24840132	Helmets provide soldiers with ballistic and fragmentation protection but impair auditory spatial processing. Missed auditory information can be fatal for a soldier; therefore, helmet design requires compromise between protection and optimal acoustics. Twelve soldiers localised two sound signals presented from six azimuth angles and three levels of elevation presented at two intensity levels and with three background noises. Each participant completed the task while wearing no helmet and with two U.S. Army infantry helmets - the Personnel Armor System for Ground Troops (PASGT) helmet and the Advanced Combat Helmet (ACH). Results showed a significant effect of helmet type on the size of both azimuth and elevation error. The effects of level, background noise, azimuth and elevation were found to be significant. There was no effect of sound signal type. As hypothesised, localisation accuracy was greatest when soldiers did not wear helmet, followed by the ACH. Performance was worst with the PASGT helmet.	t	\N
24840711	Test data were used to explore the neurocognitive processing of a group of children with cochlear implants (CIs) whose language development is below expectations. This cross-sectional study examines the relationship between neurocognitive processing, as assessed by the Kaufman Assessment Battery for Children-Second Edition, and verbal language standard scores, assessed using either the Comprehensive Assessment of Spoken Language or the Clinical Evaluation of Language Fundamentals in 22 school-age children with CIs. Processing scores of CI recipients with language scores below expectations were compared to those of children meeting or exceeding language expectations. Multiple linear regression estimated the associations of simultaneous and sequential processing with language scores. Though simultaneous processing scores between the two groups were similar, the mean sequential processing score (91.2) in the below expectations group (n = 13) was significantly lower (P = 0.002) than that of children (n = 9) meeting expectations (110.8). After adjusting for age at implantation, a 10-point higher sequential processing score was associated with a 7.4 higher language score (P = 0.027). Simultaneous processing capacity was at least within the average range of cognitive performance, and was not associated with language performance in children with CIs. Conversely, reduced sequential processing capacity was significantly associated with lower language scores. Neurocognitive skills, specifically cognitive sequencing, serial ordering, and auditory-verbal memory may be targets for therapeutic intervention. Intensive cognitive and educational habilitation and in milieu intervention may improve language learning in children with CIs.	t	\N
24841996	Auditory objects, like their visual counterparts, are perceptually defined constructs, but nevertheless must arise from underlying neural circuitry. Using magnetoencephalography (MEG) recordings of the neural responses of human subjects listening to complex auditory scenes, we review studies that demonstrate that auditory objects are indeed neurally represented in auditory cortex. The studies use neural responses obtained from different experiments in which subjects selectively listen to one of two competing auditory streams embedded in a variety of auditory scenes. The auditory streams overlap spatially and often spectrally. In particular, the studies demonstrate that selective attentional gain does not act globally on the entire auditory scene, but rather acts differentially on the separate auditory streams. This stream-based attentional gain is then used as a tool to individually analyze the different neural representations of the competing auditory streams. The neural representation of the attended stream, located in posterior auditory cortex, dominates the neural responses. Critically, when the intensities of the attended and background streams are separately varied over a wide intensity range, the neural representation of the attended speech adapts only to the intensity of that speaker, irrespective of the intensity of the background speaker. This demonstrates object-level intensity gain control in addition to the above object-level selective attentional gain. Overall, these results indicate that concurrently streaming auditory objects, even if spectrally overlapping and not resolvable at the auditory periphery, are individually neurally encoded in auditory cortex, as separate objects.	t	\N
24847936	False physiologic monitor alarms are extremely common in the hospital environment. High false alarm rates have the potential to lead to alarm fatigue, leading nurses to delay their responses to alarms, ignore alarms, or disable them entirely. Recent evidence from the U.S. Food and Drug Administration (FDA) and The Joint Commission has demonstrated a link between alarm fatigue and patient deaths. Yet, very little scientific effort has focused on the rigorous quantitative measurement of alarms and responses in the hospital setting. We developed a system using multiple temporarily mounted, minimally obtrusive video cameras in hospitalized patients' rooms to characterize physiologic monitor alarms and nurse responses as a proxy for alarm fatigue. This allowed us to efficiently categorize each alarm's cause, technical validity, actionable characteristics, and determine the nurse's response time. We describe and illustrate the methods we used to acquire the video, synchronize and process the video, manage the large digital files, integrate the video with data from the physiologic monitor alarm network, archive the video to secure servers, and perform expert review and annotation using alarm "bookmarks." We discuss the technical and logistical challenges we encountered, including the root causes of hardware failures as well as issues with consent, confidentiality, protection of the video from litigation, and Hawthorne-like effects. The description of this video method may be useful to multidisciplinary teams interested in evaluating physiologic monitor alarms and alarm responses to better characterize alarm fatigue and other patient safety issues in clinical settings.	t	\N
24848460	Behavioral and neural findings demonstrate that animals can locate low-frequency sounds along the azimuth by detecting microsecond interaural time differences (ITDs). Information about ITDs is also available in the amplitude modulations (i.e., envelope) of high-frequency sounds. Since medial superior olivary (MSO) neurons encode low-frequency ITDs, we asked whether they employ a similar mechanism to process envelope ITDs with high-frequency carriers, and the effectiveness of this mechanism compared with the process of low-frequency sound. We developed a novel hybrid in vitro dynamic-clamp approach, which enabled us to mimic synaptic input to brain-slice neurons in response to virtual sound and to create conditions that cannot be achieved naturally but are useful for testing our hypotheses. For each simulated ear, a virtual sound, computer generated, was used as input to a computational auditory-nerve model. Model spike times were converted into synaptic input for MSO neurons, and ITD tuning curves were derived for several virtual-sound conditions: low-frequency pure tones, high-frequency tones modulated with two types of envelope, and speech sequences. Computational models were used to verify the physiological findings and explain the biophysical mechanism underlying the observed ITD coding. Both recordings and simulations indicate that MSO neurons are sensitive to ITDs carried by spectrotemporally complex virtual sounds, including speech tokens. Our findings strongly suggest that MSO neurons can encode ITDs across a broad-frequency spectrum using an input-slope-based coincidence-detection mechanism. Our data also provide an explanation at the cellular level for human localization performance involving high-frequency sound described by previous investigators.	t	\N
24851353	The purpose of this chapter is to describe the vocabulary development and promising, evidence-based vocabulary interventions for English learners (ELs) from preschool through second grade. To achieve this purpose, we have taken six steps. First, we describe the elements of language development in the native language (L1) and a second language (L2) and how these elements relate to three phases of reading development (i.e., the prereading phase, the learning to read phase, and the reading to learn phase). We contend that in order for ELs to succeed in school, they need a strong language foundation prior to entering kindergarten. This language foundation needs to continue developing during the "learning to read" and "reading to learn" phases. Second, we describe the limitations of current practice in preschool for ELs related to vocabulary instruction and to family involvement to support children's language development. Third, we report curricular challenges faced by ELs in early elementary school, and we relate these challenges to the increase in reading and language demands outlined in the Common Core State Standards (CCSS). Specific language activities that can help meet some of the demands are provided in a table. Fourth, we synthesize the research on evidence-based vocabulary instruction and intervention and discuss implications for practice with ELs. Fifth, we describe two intervention projects under development that have the potential to improve EL vocabulary and language proficiency in the early grades. We conclude with a summary of the chapter and provide additional resources on the topic.	t	\N
24856412	The objective of this study was to examine the relationship between perceived discrimination and psychotic experiences (PE) using validated measures of discrimination and a racially/ethnically diverse population-level sample. Data were drawn from two population-level surveys (The National Latino and Asian American Survey and The National Survey of American Life), which were analyzed together using survey weights and stratification variables. The analytic sample (N=8990) consisted of Latino, Asian, African-American, and Afro-Caribbean adults living in the United States. Separate unadjusted and adjusted multivariable logistic regression models were used, first to examine the crude bivariate relationship between perceived discrimination and PE, and second to examine the relationship adjusting for demographic variables. Adjusted logistic regression models were also used to examine the relationships between perceived discrimination and specific sub-types of PE (auditory and visual hallucinatory experiences, and delusional ideation). When compared to individuals who did not report any discrimination, those who reported the highest levels of discrimination were significantly more likely to report both 12-month PE (Adjusted OR=4.590, p<0.001) and lifetime PE (adjusted OR=4.270, p<0.001). This held true for visual hallucinatory experiences (adjusted OR=3.745, p<0.001), auditory hallucinatory experiences (adjusted OR=5.649, p<0.001), and delusional ideation (adjusted OR=7.208, p<0.001). Perceived discrimination is associated with the increased probability of reporting psychotic experiences in a linear Fashion in the US general population.	t	\N
24861540	Considerable evidence suggests that performance across a variety of cognitive tasks is effectively supported by the use of verbal and nonverbal strategies. Studies exploring the usefulness of such strategies in children with specific language impairment (SLI) are scarce and report inconsistent findings. To examine the effects of induced labelling and auditory cues on the performance of children with and without SLI during a categorization task. Sixty-six school-age children (22 with SLI, 22 age-matched controls, 22 language-matched controls) completed three versions of a computer-based categorization task: one baseline, one requiring overt labelling and one with auditory cues (tones) on randomized trial blocks. Labelling had no effect on performance for typically developing children but resulted in lower accuracy and longer reaction time in children with SLI. The presence of tones had no effect on accuracy but resulted in faster reaction time and post-error slowing across groups. Verbal strategy use was ineffective for typically developing children and negatively affected children with SLI. All children showed faster performance and increased performance monitoring as a result of tones. Overall, effects of strategy use in children appear to vary based on task demands, strategy domain, age and language ability. Results suggest that children with SLI may benefit from auditory cues in their clinical intervention but that further research is needed to determine when and how verbal strategies might similarly support performance in this population.	t	\N
24867743	The prevalence of deformational plagiocephaly has risen dramatically in recent years, now affecting 15 percent or more of infants. Prior research using developmental scales suggests that these children may be at elevated risk for developmental delays. However, the low positive predictive value of such instruments in identifying long-term impairment, coupled with their poor reliability in infants, warrants the development of methods to more precisely measure brain function in craniofacial patients. Event-related potentials offer a direct measure of cortical activity that is highly applicable to young populations and has been implemented in other disorders to predict long-term cognitive functioning. The current study used event-related potentials to contrast neural correlates of auditory perception in infants with deformational plagiocephaly and typically developing children. Event-related potentials were recorded while 16 infants with deformational plagiocephaly and 18 nonaffected controls passively listened to speech sounds. Given prior research suggesting their association with subsequent functioning, analyses focused on the P150 and N450 event-related potential components. Deformational plagiocephaly patients and normal controls showed comparable cortical responses to speech sounds at both auditory event-related potential components. Children with deformational plagiocephaly demonstrate neural responses to language that are consistent with normative expectations and comparable to those of typical children. These results indicate that head shape deformity secondary to supine sleep is not associated with impairments in auditory processing. The applicability of the current methods in early infancy suggests that electrophysiologic brain recordings represent a promising method of monitoring brain development in children with cranial disorders. Risk, II.	t	\N
24869441	Hearing preservation surgery requires specially a traumatic technique. Having some preoperative anatomical data of the size of patient's cochlea surgeon can design his or her insertion depth. In the study we have evaluated a relation between hearing preservation rate and angular insertion depth estimated intraoperatively and postoperatively having measured insertion angle from radiological assessment and calculations given by Escude. There has not been no statistically significant difference between insertion depth angle, either estimated intraoperatively and measured and calculated post-operatively, and hearing preservation rate in the group. This analysis confirms a traumaticy of insertion in hearing preservation surgery.	t	\N
24869443	To establish whether complex signal processing is beneficial for users of bone anchored hearing aids. Review and analysis of two studies from our own group, each comparing a speech processor with basic digital signal processing (either Baha Divino or Baha Intenso) and a processor with complex digital signal processing (either Baha BP100 or Baha BP110 power). The main differences between basic and complex signal processing are the number of audiologist accessible frequency channels and the availability and complexity of the directional multi-microphone noise reduction and loudness compression systems. Both studies show a small, statistically non-significant improvement of speech understanding in quiet with the complex digital signal processing. The average improvement for speech in noise is +0.9 dB, if speech and noise are emitted both from the front of the listener. If noise is emitted from the rear and speech from the front of the listener, the advantage of the devices with complex digital signal processing as opposed to those with basic signal processing increases, on average, to +3.2 dB (range +2.3 … +5.1 dB, p ≤ 0.0032). Complex digital signal processing does indeed improve speech understanding, especially in noise coming from the rear. This finding has been supported by another study, which has been published recently by a different research group. When compared to basic digital signal processing, complex digital signal processing can increase speech understanding of users of bone anchored hearing aids. The benefit is most significant for speech understanding in noise.	t	\N
24908093	Inconsistent information from different modalities can be delusive for perception. This phenomenon can be observed with simultaneously presented inconsistent numbers of brief flashes and short tones. The conflict of bimodal information is reflected in double flash or fission, and flash fusion illusions, respectively. The temporal resolution of the vision system plays a fundamental role in the development of these illusions. As the parallel, dorsal and ventral pathways have different temporal resolution we presume that these pathways play different roles in the illusions. We used pathway-optimized stimuli to induce the illusions on separately driven visual streams. Our results show that both pathways support the double flash illusion, while the presence of the fusion illusion depends on the activated pathway. The dorsal pathway, which has better temporal resolution, does not support fusion, while the ventral pathway which has worse temporal resolution shows fusion strongly.	t	\N
24909603	The current pupillometry study examined the impact of speech-perception training on word recognition and cognitive effort in older adults with hearing loss. Trainees identified more words at the follow-up than at the baseline session. Training also resulted in an overall larger and faster peaking pupillary response, even when controlling for performance and reaction time. Perceptual and cognitive capacities affected the peak amplitude of the pupil response across participants but did not diminish the impact of training on the other pupil metrics. Thus, we demonstrated that pupillometry can be used to characterize training-related and individual differences in effort during a challenging listening task. Importantly, the results indicate that speech-perception training not only affects overall word recognition, but also a physiological metric of cognitive effort, which has the potential to be a biomarker of hearing loss intervention outcome.	t	\N
24911919	It is usually easy to understand speech, but when several people are talking at once it becomes difficult. The brain must select one speech stream and ignore distracting streams. We tested a theory about the neural and computational mechanisms of attentional selection. The theory is that oscillating signals in brain networks phase-lock with amplitude fluctuations in speech. By doing this, brain-wide networks acquire information from the selected speech, but ignore other speech signals on the basis of their non-preferred dynamics. Two predictions were supported: first, attentional selection boosted the power of neuroelectric signals that were phase-locked with attended speech, but not ignored speech. Second, this phase selectivity was associated with better recall of the attended speech.	t	\N
24919347	Auditory stimuli often facilitate visual perception. Audiovisual integration requires spatial and/or temporal proximity between visual and auditory stimuli; additionally, sensory processing speed affects the audiovisual integration process. In the present study we examined the relationship between processing speed and the auditory facilitation effect on visual representations by manipulating dot quantity patterns. We hypothesized that the auditory facilitation effect would be observed in longer interstimulus interval conditions with more dot quantities. This is because more processing time would be required to integrate visual and auditory stimuli. During a backward masking paradigm used in experiment 1, the auditory facilitation effect depended on dot quantity among patterns and the interval between visual stimuli and masks. Moreover, differences in processing time required to integrate visual and auditory stimuli between dot quantities was confirmed from a same-different discrimination task in experiment 2. Therefore, dot quantity affects sensory processing time, and a longer processing time is required for integrating visual and auditory stimuli when visual dot quantity is high.	t	\N
24920615	The human voice carries speech as well as important nonlinguistic signals that influence our social interactions. Among these cues that impact our behavior and communication with other people is the perceived emotional state of the speaker. A theoretical framework for the neural processing stages of emotional prosody has suggested that auditory emotion is perceived in multiple steps (Schirmer and Kotz, 2006) involving low-level auditory analysis and integration of the acoustic information followed by higher-level cognition. Empirical evidence for this multistep processing chain, however, is still sparse. We examined this question using functional magnetic resonance imaging and a continuous carry-over design (Aguirre, 2007) to measure brain activity while volunteers listened to non-speech-affective vocalizations morphed on a continuum between anger and fear. Analyses dissociated neuronal adaptation effects induced by similarity in perceived emotional content between consecutive stimuli from those induced by their acoustic similarity. We found that bilateral voice-sensitive auditory regions as well as right amygdala coded the physical difference between consecutive stimuli. In contrast, activity in bilateral anterior insulae, medial superior frontal cortex, precuneus, and subcortical regions such as bilateral hippocampi depended predominantly on the perceptual difference between morphs. Our results suggest that the processing of vocal affect recognition is a multistep process involving largely distinct neural networks. Amygdala and auditory areas predominantly code emotion-related acoustic information while more anterior insular and prefrontal regions respond to the abstract, cognitive representation of vocal affect.	t	\N
24923315	The present study examines the articulation and acoustics of the typologically rare and understudied 'whistled' fricative sound in Xitsonga, a Southern Bantu language. Using ultrasound imaging and video recording, we examine the lingual and labial articulation of the whistled fricative. For the acoustic analysis, we employ the multitaper spectral analysis, which ensures reliable spectral estimates. The results revealed an interplay between multiple articulators involved in the production of the sound: the retroflex lingual gesture and the narrowing of the lower lip toward the upper teeth. Acoustically, the spectra of the whistled fricative are more peaked and compact than the acoustically similar palatoalveolar fricative, and the differences manifest themselves most clearly in two acoustic parameters, dynamic amplitude (Ad) and M2 (variance). The acoustic differences are also manifested in F2 and F3 in the surrounding vowels. Additionally, the 'whistled' fricative in Xitsonga is not quite whistled, contrary to the label given to the sound in previous studies. Building on the current articulatory and acoustic results, we discuss two different aerodynamic models for the whistled fricatives in Southern Bantu languages and conclude that the whistled fricative in Xitsonga is best characterized as a retroflex segment accompanied by weak whistling.	t	\N
24923465	It has been suggested that high-frequency audiometry (HFA) could represent a useful preventive measure in exposed workers. The aim was to investigate the effects of age, ultrasound and noise on high-frequency hearing thresholds. We tested 24 industrial ultrasound-exposed subjects, 113 industrial noise-exposed subjects and 148 non-exposed subjects. Each subject was tested with both conventional-frequency (0.125-8 kHz) and high-frequency (9-18 kHz) audiometry. The hearing threshold at high frequency deteriorated as a function of age, especially in subjects more than 30 years old. The ultrasound-exposed subjects had significantly higher hearing thresholds than the non-exposed ones at the high frequencies, being greatest from 10 to 14 kHz. This hearing loss was already significantly evident in subjects with exposure <5 years and increased with years of exposure and advancing age. The noise exposure group had significantly higher hearing thresholds than the non-exposed group at the conventional frequencies 4 and 6 kHz and at the high frequency of 14 kHz. After stratification for age, there was a significant difference between the two groups at 9-10 and 14-15 kHz only for those under 30 years of age. Multivariate analysis indicated that age was the primary predictor, and noise and ultrasound exposure the secondary predictors of hearing thresholds in the high-frequency range. The results suggest that HFA could be useful in the early diagnosis of noise-induced hearing loss in younger groups of workers (under 30 years of age).	t	\N
24923619	The investigators compared event-related potential (ERP) amplitudes and event-related oscillations across a broad frequency range during an auditory oddball task using a comprehensive analysis approach to describe shared and unique neural auditory processing characteristics among healthy subjects (HP), schizophrenia probands (SZ) and their first-degree relatives, and bipolar disorder I with psychosis probands (BDP) and their first-degree relatives. This Bipolar-Schizophrenia Network on Intermediate Phenotypes sample consisted of clinically stable SZ (n = 229) and BDP (n = 188), HP (n = 284), first-degree relatives of schizophrenia probands (n = 264), and first-degree relatives of bipolar disorder I with psychosis probands (n = 239). They were administered an auditory oddball task in the electroencephalography environment. Principal components analysis derived data-driven frequency bands evoked power. Spatial principal components analysis reduced ERP and frequency data to component waveforms for each subject. Clusters of time bins with significant group differences on response magnitude were assessed for proband/relative differences from HP and familiality. Nine variables survived a linear discriminant analysis between HP, SZ, and BDP. Of those, two showed evidence (deficit in relatives and familiality) as genetic risk markers more specific to SZ (N1, P3b), one was specific to BDP (P2) and one for psychosis in general (N2). This study supports for both shared and unique deficits in early sensory and late cognitive processing across psychotic diagnostic groups. Additional ERP and time-frequency component alterations (frontal N2/P2, late high, early, mid, and low frequency) may provide insight into deficits in underlying neural architecture and potential protective/compensatory mechanisms in unaffected relatives.	t	\N
24933411	Cortical auditory evoked potentials (CAEPs) were obtained for vowel tokens presented in an oddball stimulus paradigm. Perceptual measures of vowel discrimination were obtained using a visually-reinforced head-turn paradigm. The hypothesis was that CAEP latencies and amplitudes would differ as a function of vowel type and be correlated with perceptual performance. Twenty normally hearing infants aged 4-12 months were evaluated. CAEP component amplitudes and latencies were measured in response to the standard, frequent token /a/ and for infrequent, deviant tokens /i/, /o/ and /u/, presented at rates of 1 and 2 tokens/s. The perceptual task required infants to make a behavioral response for trials that contained two different vowel tokens, and ignore those in which the tokens were the same. CAEP amplitudes were larger in response to the deviant tokens, when compared to the control condition in which /a/ served as both standard and deviant. This was also seen in waveforms derived by subtracting the response to standard /a/ from the responses to deviant tokens. CAEP component latencies in derived responses at 2/s also demonstrated some sensitivity to vowel contrast type. The average hit rate for the perceptual task was 68.5%, with a 25.7% false alarm rate. There were modest correlations of CAEP amplitudes and latencies with perceptual performance. The CAEP amplitude differences for vowel contrasts could be used as an indicator of the underlying neural capacity to encode spectro-temporal differences in vowel sounds. This technique holds promise for translation to clinical methods for evaluating speech perception.	t	\N
24936778	To understand the third mobile window effect of chronic otitis media with cholesteatoma with inner ear fistula on the bone conduction threshold, we examined changes in the bone conduction audiogram after tympanoplasty with mastoidectomy for chronic otitis media with cholesteatoma with canal fistula. Retrospective case review. Tertiary referral center. According to the intraoperative classification of Dornhoffer and Milewski, we focused especially on Type IIa (anatomic bony fistula with no perilymph leak). We checked the bone conduction threshold at least 3 times: just before, just after, and 6 months after surgery in 20 ears with Type IIa lateral semicircular canal fistula. Tympanoplasty with mastoidectomy. Bone conduction thresholds before and after tympanoplasty with mastoidectomy. Compared with the preoperative bone conduction threshold, 6 cases were better, 12 cases were unchanged, and 2 cases were worse within the first postoperative week. Finally, 1 case was better, 15 cases were unchanged, and 4 cases were worse at the sixth postoperative month. Patients with a better bone conduction threshold in the low-tone frequencies immediately after surgery had a tendency to show no preoperative fistula symptoms. Postoperative spontaneous nystagmus had a tendency to be observed in patients with a worse bone conduction threshold in the high-tone frequencies. The better bone conduction threshold at low-tone frequencies immediately after tympanoplasty with mastoidectomy and no preoperative fistula symptoms might imply the third mobile window theory. The worse bone conduction threshold in high-tone frequencies with spontaneous nystagmus after surgery might indicate inner ear damage.	t	\N
24937187	Change deafness is the failure to notice changes in an auditory scene. In this study, we sought to determine if change deafness is a perceptual error, rather than only a reflection of verbal memory limitations. We also examined how successful encoding of objects within a scene is related to successful detection of changes. Event-related potentials (ERPs) were recorded while listeners completed a change-detection and an object-encoding task with scenes composed of recognizable sounds or unrecognizable temporally scrambled versions of the recognizable sounds. More change deafness occurred for the unrecognizable, compared to recognizable sounds, indicating that change deafness is a perceptual error and not solely a product of verbal memory. ERPs from both the recognizable and unrecognizable scenes revealed an enhanced P3b (at PZ/1/2, POZ/3/4 from 350 to 750ms) to detected changes, a marker that conscious change detection has occurred. Recognizable scenes resulted in an enhanced T400 (at T8/TP8, C6/CP6 from 315 to 660ms) to detected changes, possibly indicating activation of established memory representations. Unrecognizable scenes elicited an enhanced P3a (at FCZ/1/2 from 280 to 600ms) to detected changes, indicating enhanced orienting to acoustic change. Performance on the object-encoding task revealed that change deafness was reduced, but not eliminated, when performance on the object-encoding task was accurate.	t	\N
24937544	Executive functions (EF) are cognitive capacities that allow for planned, controlled behavior and strongly correlate with academic abilities. Several extracurricular activities have been shown to improve EF, however, the relationship between musical training and EF remains unclear due to methodological limitations in previous studies. To explore this further, two experiments were performed; one with 30 adults with and without musical training and one with 27 musically trained and untrained children (matched for general cognitive abilities and socioeconomic variables) with a standardized EF battery. Furthermore, the neural correlates of EF skills in musically trained and untrained children were investigated using fMRI. Adult musicians compared to non-musicians showed enhanced performance on measures of cognitive flexibility, working memory, and verbal fluency. Musically trained children showed enhanced performance on measures of verbal fluency and processing speed, and significantly greater activation in pre-SMA/SMA and right VLPFC during rule representation and task-switching compared to musically untrained children. Overall, musicians show enhanced performance on several constructs of EF, and musically trained children further show heightened brain activation in traditional EF regions during task-switching. These results support the working hypothesis that musical training may promote the development and maintenance of certain EF skills, which could mediate the previously reported links between musical training and enhanced cognitive skills and academic achievement.	t	\N
24949818	During childhood, verbal learning and memory are important for academic performance. Recent functional MRI studies have reported on the functional correlates of verbal memory proficiency, but few have reported the underlying structural correlates. The present study sought to test the relationship between fronto-temporal white matter integrity and verbal memory proficiency in children. Diffusion weighted images were collected from 17 Black children (age 8-11 years) who also completed the California Verbal Learning Test. To index white matter integrity, fractional anisotropy values were calculated for bilateral uncinate fasciculus. The results revealed that low anisotropy values corresponded to poor verbal memory, whereas high anisotropy values corresponded to significantly better verbal memory scores. These findings suggest that a greater degree of myelination and cohesiveness of axonal fibers in uncinate fasciculus underlie better verbal memory proficiency in children.	t	\N
24952106	This study evaluated the clinical effectiveness of wireless contralateral routing of offside signals hearing aids (CROS) in patients with severe to profound unilateral sensorineural hearing loss (USNHL). Twenty-one patients with USNHL were enrolled in this prospective study. The change of subjective satisfaction was evaluated using three questionnaires (K-HHIE, K-IOI-HA, K-SSQ). Changes in objective measurements were evaluated with sound localization test (SLT) and hearing in noise test (HINT). These tests were performed at pre-CROS fitting, 2 and 4 weeks after use of CROS. Subjects were grouped according to the age: young (<40 years) vs. old (≥40 years) group. The average K-HHIE and K-SSQ scores significantly improved with the use of CROS. SLT result revealed that hit rate and error degree improved in the young group and lateralization ability improved in both groups. In quiet environments, the reception threshold for speech also indicated a significant benefit in the young group. When the noise was presented to the normal ear, HINT revealed benefit of CROS, while loss of performance with CROS use was significant when noise was presented to the impaired ear. Wireless CROS provided increased satisfaction and overall improvement of localization and hearing. Although true binaural hearing cannot be obtained, CROS is a practical option for rehabilitation of USNHL.	t	\N
24959621	Accurate and effective voice activity detection (VAD) is a fundamental step for robust speech or speaker recognition. In this study, we proposed a hierarchical framework approach for VAD and speech enhancement. The modified Wiener filter (MWF) approach is utilized for noise reduction in the speech enhancement block. For the feature selection and voting block, several discriminating features were employed in a voting paradigm for the consideration of reliability and discriminative power. Effectiveness of the proposed approach is compared and evaluated to other VAD techniques by using two well-known databases, namely, TIMIT database and NOISEX-92 database. Experimental results show that the proposed method performs well under a variety of noisy conditions.	t	\N
24960432	Research on unconscious or unaware vision has demonstrated that unconscious processing can be flexibly adapted to the current goals of human agents. The present review focuses on one area of research, masked visual priming. This method uses visual stimuli presented in a temporal sequence to lower the visibility of one of these stimuli. In this way, a stimulus can be masked and even rendered invisible. Despite its invisibility, a masked stimulus if used as a prime can influence a variety of executive functions, such as response activation, semantic processing, or attention shifting. There are also limitations on the processing of masked primes. While masked priming research demonstrates the top-down dependent usage of unconscious vision during task-set execution it also highlights that the set-up of a new task-set depends on conscious vision as its input. This basic distinction captures a major qualitative difference between conscious and unconscious vision.	t	\N
24961249	The sound-induced flash illusion (SIFI) is a multisensory perceptual phenomenon in which the number of brief visual stimuli perceived by an observer is influenced by the number of concurrently presented sounds. While the strength of this illusion has been shown to be modulated by the temporal congruence of the stimuli from each modality, there is conflicting evidence regarding its dependence upon their spatial congruence. We addressed this question by examining SIFIs under conditions in which the spatial reliability of the visual stimuli was degraded and different sound localization cues were presented using either free-field or closed-field stimulation. The likelihood of reporting a SIFI varied with the spatial cue composition of the auditory stimulus and was highest when binaural cues were presented over headphones. SIFIs were more common for small flashes than for large flashes, and for small flashes at peripheral locations, subjects experienced a greater number of illusory fusion events than fission events. However, the SIFI was not dependent on the spatial proximity of the audiovisual stimuli, but was instead determined primarily by differences in subjects' underlying sensitivity across the visual field to the number of flashes presented. Our findings indicate that the influence of auditory stimulation on visual numerosity judgments can occur independently of the spatial relationship between the stimuli.	t	\N
24972303	Groove-based rhythm is a basic and much appreciated feature of Western popular music. It is commonly associated with dance, movement and pleasure and is characterized by the repetition of a basic rhythmic pattern. At various points in the musical course, drum breaks occur, representing a change compared to the repeated pattern of the groove. In the present experiment, we investigated the brain response to such drum breaks in a repetitive groove. Participants were scanned with functional magnetic resonance imaging (fMRI) while listening to a previously unheard naturalistic groove with drum breaks at uneven intervals. The rhythmic pattern and the timing of its different parts as performed were the only aspects that changed from the repetitive sections to the breaks. Differences in blood oxygen level-dependent activation were analyzed. In contrast to the repetitive parts, the drum breaks activated the left cerebellum, the right inferior frontal gyrus (RIFG), and the superior temporal gyri (STG) bilaterally. A tapping test using the same stimulus showed an increase in the standard deviation of inter-tap-intervals in the breaks versus the repetitive parts, indicating extra challenges for auditory-motor integration in the drum breaks. Both the RIFG and STG have been associated with structural irregularity and increase in musical-syntactical complexity in several earlier studies, whereas the left cerebellum is known to play a part in timing. Together these areas may be recruited in the breaks due to a prediction error process whereby the internal model is being updated. This concurs with previous research suggesting a network for predictive feed-forward control that comprises the cerebellum and the cortical areas that were activated in the breaks.	t	\N
24972535	The aim of this study was to establish a multiparameter voice assessment profile using objective multiparameter test and subjective voice quality assessment. We assessed 50 patients with voice disorders before and after operation. The assessment incorporates (1) subjective voice quality assessment, (2) patients' self-assessment, and (3) objective acoustic analysis. The subjective voice quality assessment uses GRABS system to evaluates the grade of hoarseness (G), proposed by the Japanese Society for Logopedics and Phoniatrics. Patients' self-assessment is modified based on the Chinese version of voice handicap index (VHI) scale, composed of functional (F), physiological (P), emotional (E) part, and a total score (T). The acoustical analysis evaluate the patients' voice sample by voice analysis software "Dr. Speech". Three parameters, jitter (J), shimmer(S), and normalized noise energy (NNE), were taken in analysis. We observed high correlations among subentries F, P, and the total score TvH of the VHI scale in patients' subjective assessment. Parameter E does not correlate well with other assessed parameters. The Chinese version of VHI, which incorporate multifactors including age, education, and especially the cultural difference may account for the inconsistent correction in parameter E. In the objective acoustic analysis, high correlation among the three parameters J, S, and NNE is observed. Systemic assessment combining a subjective voice quality assessment, an objective acoustic analysis, and a self-assessment is helpful in clinical practice in the diagnosis and treatment for voice disorders. The E component in VHI scale assessment may not be a reliable parameter to evaluate treatment outcome.	t	\N
24975453	The Hearing Implant Sound Quality Index (HISQUI19) seems to be a valid tool for quantifying the self-perceived level of auditory benefit that cochlear implant (CI) users experience in everyday listening situations. Additional research is, however, required. To develop and validate a user-friendly instrument for quantifying the self-perceived level of auditory benefit that CI users experience in everyday listening situations. This was an explorative, uncontrolled, single-group, cross-sectional study. Items for the HISQUI19 were decided upon using user input and verified by professionals. The HISQUI19 was assessed on 75 CI users from hearing implant centres in Germany and Austria to determine the questions. The HISQUI19, consisting of 19 items scored on a 7-point Likert scale, was validated. Subjects older than 60 years at time of implantation did not have significantly higher mean values than subjects younger than 60 years. Gender and whether subjects are unilateral or bilateral implant CI users did not influence self-perceived functioning. Subjects with ≤20 years of hearing loss reported no significantly higher functioning than those with >20 years of hearing loss.	t	\N
24980742	The motivation for infants' non-word vocalizations in the second half of the first year of life and later is unclear. This study of hearing infants and infants with profound hearing loss with and without cochlear implants addressed the hypothesis that vocalizations are primarily motivated by auditory feedback. Early access to cochlear implants has created unique conditions of auditory manipulation that permit empirical tests of relations between auditory perception and infant behavior. Evidence from two separate tests of the research hypothesis showed that, before cochlear implantation, infants with profound hearing loss vocalized significantly less often than hearing infants; however, soon after cochlear implantation, they vocalized at levels commensurate with hearing peers. In contrast, vocal behaviors that are typically considered reflexive or emotion-based signals (e.g., crying) were infrequent overall and did not vary with auditory access. These results support the hypothesis that auditory feedback is a critical component motivating early vocalization frequency.	t	\N
24990679	The human music faculty might have evolved from rudimentary components that occur in non-human animals. The evolutionary history of these rudimentary perceptual features is not well understood and rarely extends beyond a consideration of vertebrates that possess a cochlea. One such antecedent is a preferential response to what humans perceive as consonant harmonic sounds, which are common in many animal vocal repertoires. We tested the phonotactic response of female túngara frogs (Physalaemus pustulosus) to variations in the frequency ratios of their harmonically structured mating call to determine whether frequency ratio influences attraction to acoustic stimuli in this vertebrate that lacks a cochlea. We found that the ratio of frequencies present in acoustic stimuli did not influence female response. Instead, the amount of inner ear stimulation predicted female preference behaviour. We conclude that the harmonic relationships that characterize the vocalizations of these frogs did not evolve in response to a preference for frequency intervals with low-integer ratios. Instead, the presence of harmonics in their mating call, and perhaps in the vocalizations of many other animals, is more likely due to the biomechanics of sound production rather than any preference for 'more musical' sounds.	t	\N
24993544	Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category- exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1), and this occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech are discussed.	t	\N
24993633	To compare the Naida CI UltraZoom adaptive beamformer and T-Mic settings in a real life environment. Speech reception thresholds (SRTs) were measured in a moderately reverberant room, using the German Oldenburger sentence test. The speech signal was always presented from the front loudspeaker at 0° azimuth and fixed masking noise was presented either simultaneously from all eight loudspeakers around the subject at 0°, ±45°, ±90°, ±135°, and 180° azimuth or from five loudspeakers positioned at ±70°, ±135°, and 180° azimuth. In the third test setup, an additional roving noise was added to the six loudspeaker arrangement. There was a significant difference in mean SRTs between the Naida CI T-Mic and UltraZoom in each of the three test setups. The largest improvements were seen in the six speaker roving and fixed noise conditions. Adding ClearVoice to the Naida CI T-Mic setting significantly improved the SRT in both fixed noise conditions, but not in the roving noise condition. In each setup, the lowest SRTs were obtained with the UltraZoom plus ClearVoice setting. The degree of improvement was consistent with previous beamforming studies. In the most challenging listening situation, with noise from eight speakers and speech and noise presented coincidentally from the front, UltraZoom still provided a significant benefit. When a moving noise source was added, the improvement in SRT provided by UltraZoom was maintained. When tested in challenging and realistic noise environments, the Naida CI UltraZoom adaptive beamformer resulted in significantly lower mean SRTs than when the T-Mic alone was used.	t	\N
24995902	Neuroplasticity (NPL), neuromodulation (NM), and neuroprotection (NPT) are ongoing biophysiological processes that are linked together in sensory systems, the goal being the maintenance of a homeostasis of normal sensory function in the central nervous system. It is hypothesized that when the balance between excitatory - inhibitory action is broken in sensory systems, predominantly due to neuromodulatory activity with reduced induced inhibition and excitation predominates, sensory circuits become plastic with adaptation at synaptic levels to environmental inputs(1). Tinnitus an aberrant auditory sensation, for all clinical types, is clinically considered to reflect a failure of NPL, NM, and NPT to maintain normal auditory function at synaptic levels in sensory cortex and projected to downstream levels in the central auditory system in brain and sensorineural elements in ear. Clinically, the tinnitus sensation becomes behaviorally manifest with varying degrees of annoyance, reflecting a principle of sensory physiology that each sensation has components, i.e. sensory, affect/behavior, psychomotor and memory. Modalities of tinnitus therapies, eg instrumentation, pharmacology, surgery, target a particular component of tinnitus, with resultant activation of neuromodulators at multiple neuromodulatory centers in brain and ear. Effective neuromodulation at sensory neuronal synaptic levels results in NPL in sensory cortex, NPT and tinnitus relief. Functional brain imaging, metabolic (PET brain) and electrophysiology quantitative electroencephalography (QEEG) data in a cochlear implant soft failure patient demonstrates what is clinically considered to reflect NPL, NM, NPT. The reader is provided with a rationale for tinnitus diagnosis and treatment, with a focus on ES, reflecting the biology underlying NPL, NM, NPT.	t	\N
25013945	Music as alternate engagement (MAE) can be used effectively to distract children during painful or anxiety-provoking medical procedures. For such interventions to be successful, it would seem important to assess the degree to which a child can attend to musical stimuli. The purposes of this study were as follows: (a) To establish construct validity by determining the extent to which the Music Attentiveness Screening Assessment (MASA) measures auditory attention; and (b) to gather evidence regarding MASA test-retest and inter-observer reliability. The Auditory Attention (AA) subtest from the NEPSY-II (NEPSY, Second Edition) and the two items from MASA were administered to a nonclinical sample of children (N = 50) aged 5 to 9 years. There was a statistically significant proportion of AA score variance shared with MASA (both items), R (2) = .21, F(2, 47) = 6.34, p = .004. Test-retest reliability on the first MASA item was moderately high (Pearson r = .84) while on the second item it was lower (r = .63). Similarly, interobserver agreement was high for Item I (intraclass correlation coefficient [ICC] = .95) and lower for Item II (ICC = .71). Evidence suggests that MASA measures, at least in part, auditory attention. Despite this finding, a large proportion of unexplained variance remains. Furthermore, reliability estimates (test-retest and interobserver agreement) differ between both items. These findings are discussed with particular attention paid to the ways in which MASA should be revised and further study conducted.	t	\N
25016092	Lesion and neuroimaging studies indicate that the insula mediates motor aspects of speech production, specifically, articulatory control. Although it has direct connections to Broca's area, the canonical speech production region, the insula is also broadly connected with other speech and language centres, and may play a role in coordinating higher-order cognitive aspects of speech and language production. The extent of the insula's involvement in speech and language processing was assessed using the Activation Likelihood Estimation (ALE) method. Meta-analyses of 42 fMRI studies with healthy adults were performed, comparing insula activation during performance of language (expressive and receptive) and speech (production and perception) tasks. Both tasks activated bilateral anterior insulae. However, speech perception tasks preferentially activated the left dorsal mid-insula, whereas expressive language tasks activated left ventral mid-insula. Results suggest distinct regions of the mid-insula play different roles in speech and language processing.	t	\N
25026154	The purpose of this study was to compare 3 T and 1.5 T fMRI results during emotional music listening. Stimuli comprised of psychoacoustically balanced instrumental musical pieces, with three different affective expressions (fear, neutral, joy). Participants (N=32) were split into two groups, one subjected to fMRI scanning using 3 T and another group scanned using 1.5 T. Whole brain t-tests (corrected for multiple comparisons) compared joy and fear in each of the two groups. The 3 T group showed significant activity differences between joy and fear localized in bilateral superficial amygdala, bilateral hippocampus and bilateral auditory cortex. The 1.5 T group showed significant activity differences between joy and fear localized in bilateral auditory cortex and cuneus. This is the first study to compare results obtained under different field strengths with regard to affective processes elicited by means of auditory/musical stimulation. The findings raise concern over false negatives in the superficial amygdala and hippocampus in affective studies conducted under 1.5 T and caution that imaging improvements due to increasing magnetic field strength can be influenced by region-specific characteristics.	t	\N
25031365	The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive.	t	\N
25032683	Categorization is an important cognitive process. However, the correct categorization of a stimulus is often challenging because categories can have overlapping boundaries. Whereas perceptual categorization has been extensively studied in vision, the analogous phenomenon in audition has yet to be systematically explored. Here, we test whether and how human subjects learn to use category distributions and prior probabilities, as well as whether subjects employ an optimal decision strategy when making auditory-category decisions. We asked subjects to classify the frequency of a tone burst into one of two overlapping, uniform categories according to the perceived tone frequency. We systematically varied the prior probability of presenting a tone burst with a frequency originating from one versus the other category. Most subjects learned these changes in prior probabilities early in testing and used this information to influence categorization. We also measured each subject's frequency-discrimination thresholds (i.e., their sensory uncertainty levels). We tested each subject's average behavior against variations of a Bayesian model that either led to optimal or sub-optimal decision behavior (i.e. probability matching). In both predicting and fitting each subject's average behavior, we found that probability matching provided a better account of human decision behavior. The model fits confirmed that subjects were able to learn category prior probabilities and approximate forms of the category distributions. Finally, we systematically explored the potential ways that additional noise sources could influence categorization behavior. We found that an optimal decision strategy can produce probability-matching behavior if it utilized non-stationary category distributions and prior probabilities formed over a short stimulus history. Our work extends previous findings into the auditory domain and reformulates the issue of categorization in a manner that can help to interpret the results of previous research within a generative framework.	t	\N
25033791	Noise has the potential to impair cognitive performance. For nonnative speakers, the effect of noise on performance is more severe than their native counterparts. What remains unknown is the effectiveness of countermeasures such as noise attenuating devices in such circumstances. Therefore, the main aim of the present research was to examine the effectiveness of active noise attenuating countermeasures in the presence of simulated aircraft noise for both native and nonnative English speakers. Thirty-two participants, half native English speakers and half native German speakers completed four recognition (cued) recall tasks presented in English under four different audio conditions, all in the presence of simulated aircraft noise. The results of the research indicated that in simulated aircraft noise at 65 dB(A), performance of nonnative English speakers was poorer than for native English speakers. The beneficial effects of noise cancelling headphones in improving the signal to noise ratio led to an improved performance for nonnative speakers. These results have particular importance for organizations operating in a safety-critical environment such as aviation.	t	\N
25046122	Behavioral investigations of the acquisition of some have shown that children favor its logical interpretation (some and possibly all). Adults, however, use the pragmatic interpretation (some but not all) derived by a scalar implicature. Certain experimental manipulations increase children's rates of adult-like responses, indicating that children are capable of computing implicatures. A functional MRI (fMRI) study examining adults linked the left inferior frontal gyrus (IFG) to implicature computation, and prefrontal regions, the left middle frontal gyrus (MFG), and medial frontal gyrus (MeFG), to processing the mismatch between implicatures and the context in which they were presented. In the current fMRI study, we aimed to determine whether children's failure to give pragmatic interpretations to some results from a failure in implicature computation or in implicature-mismatch processing. We explored children's brain activations with the same experimental task administered to adults. In a region-of-interest analysis, children showed an activational pattern similar to the one observed in adults in the left IFG with increased activations for the implicature conditions. By contrast, in the left MFG, children showed decreased activation for the mismatched implicatures compared with matched and no implicature conditions. No difference between the conditions was observed in the MeFG. For both implicature conditions, no activation in the left IFG was observed when comparing adults and children directly. However, for mismatched implicatures, adults showed greater activation in the prefrontal regions compared with children. Our results suggest that children may have an adult-like computation of implicatures (even when their behavior does not necessarily indicate that), but they fail in resolving implicature-mismatch situations.	t	\N
25056109	There is converging evidence for the notion that pain affects a broad range of attentional domains. This study investigated the influence of pain on the involuntary capture of attention as indexed by the P3a component in the event-related potential derived from the electroencephalogram. Participants performed in an auditory oddball task in a pain-free and a pain condition during which they submerged a hand in cold water. Novel, infrequent and unexpected auditory stimuli were presented randomly in a series of frequent standard and infrequent target tones. P3a and P3b amplitudes were observed to novel, unexpected and target-related stimuli, respectively. Both electrophysiological components were characterized by reduced amplitudes in the pain compared with the pain-free condition. Hit rate and reaction time to target stimuli did not differ between the two conditions presumably because the experimental task was not difficult enough to exceed attentional capacities under pain conditions. These results indicate that voluntary attention serving the maintenance and control of ongoing information processing (reflected by the P3b amplitude) is impaired by pain. In addition, the involuntary capture of attention and orientation to novel, unexpected information (measured by the P3a) is also impaired by pain. Thus, neurophysiological measures examined in this study support the theoretical positions proposing that pain can reduce attentional processing capacity. These findings have potentially important implications at the theoretical level for our understanding of the interplay of pain and cognition, and at the therapeutic level for the clinical treatment of individuals experiencing ongoing pain.	t	\N
25064434	The present magnetoencephalography study used the cortically constrained minimum-norm estimates of human brain activity to elucidate functional roles of neural generators for detecting different magnitudes of lexical tones changes. A multiple-deviant oddball paradigm was used in which the syllable "yi" with a low-dipping tone (T3) was the common standard sound and the same syllable with a high-level tone (T1) or a high-rising tone (T2) were the large and small deviant sounds, respectively. The data revealed a larger magnetic mismatch field (MMNm) for large deviant in the left hemisphere. The source analysis also confirmed that the MMNm to lexical tone changes was generated in bilateral superior temporal gyri and only the large deviant revealed left lateralization. A set of frontal generators was activated at a later time and revealed differential sensitivities to the degree of deviance. The left anterior insula, the right anterior cingulate cortex, and the right ventral orbital frontal cortex were activated when detecting a large deviant, whereas the right frontal-opercular region was sensitive to the small deviant. These frontal generators were thought to be associated with various top-down mechanisms for attentional modulation. The time frequency (TF) analysis showed that large deviants yielded large theta band (5-7Hz) activity over the left anterior scalp and the left central scalp, while small deviants yielded large alpha band activity (9-11Hz) over the posterior scalp. The results of TF analyses implied that mechanisms of working memory and functional inhibition involved in the processes of acoustic change detection.	t	\N
25074900	Studies of visual masking have provided a wide range of important insights into the processes involved in visual coding. However, very few of these studies have employed natural scenes as masks. Little is known on how the particular features found in natural scenes affect visual detection thresholds and how the results obtained using unnatural masks relate to the results obtained using natural masks. To address this issue, this paper describes a psychophysical study designed to obtain local contrast detection thresholds for a database of natural images. Via a three-alternative forced-choice experiment, we measured thresholds for detecting 3.7 cycles/° vertically oriented log-Gabor noise targets placed within an 85 × 85-pixels patch (1.9° patch) drawn from 30 natural images from the CSIQ image database (Larson & Chandler, Journal of Electronic Imaging, 2010). Thus, for each image, we obtained a masking map in which each entry in the map denotes the root mean squared contrast threshold for detecting the log-Gabor noise target at the corresponding spatial location in the image. From qualitative observations we found that detection thresholds were affected by several patch properties such as visual complexity, fineness of textures, sharpness, and overall luminance. Our quantitative analysis shows that except for the sharpness measure (correlation coefficient of 0.7), the other tested low-level mask features showed a weak correlation (correlation coefficients less than or equal to 0.52) with the detection thresholds. Furthermore, we evaluated the performance of a computational contrast gain control model that performed fairly well with an average correlation coefficient of 0.79 in predicting the local contrast detection thresholds. We also describe specific choices of parameters for the gain control model. The objective of this database is to provide researchers with a large ground-truth dataset in order to further investigate the properties of the human visual system using natural masks.	t	\N
25080602	In an ever-changing environment, selecting appropriate responses in conflicting situations is essential for biological survival and social success and requires cognitive control, which is mediated by dorsomedial prefrontal cortex (DMPFC) and dorsolateral prefrontal cortex (DLPFC). How these brain regions communicate during conflict processing (detection, resolution, and adaptation), however, is still unknown. The Stroop task provides a well-established paradigm to investigate the cognitive mechanisms mediating such response conflict. Here, we explore the oscillatory patterns within and between the DMPFC and DLPFC in human epilepsy patients with intracranial EEG electrodes during an auditory Stroop experiment. Data from the DLPFC were obtained from 12 patients. Thereof four patients had additional DMPFC electrodes available for interaction analyses. Our results show that an early θ (4-8 Hz) modulated enhancement of DLPFC γ-band (30-100 Hz) activity constituted a prerequisite for later successful conflict processing. Subsequent conflict detection was reflected in a DMPFC θ power increase that causally entrained DLPFC θ activity (DMPFC to DLPFC). Conflict resolution was thereafter completed by coupling of DLPFC γ power to DMPFC θ oscillations. Finally, conflict adaptation was related to increased postresponse DLPFC γ-band activity and to θ coupling in the reverse direction (DLPFC to DMPFC). These results draw a detailed picture on how two regions in the prefrontal cortex communicate to resolve cognitive conflicts. In conclusion, our data show that conflict detection, control, and adaptation are supported by a sequence of processes that use the interplay of θ and γ oscillations within and between DMPFC and DLPFC.	t	\N
25090306	It is widely acknowledged that individuals with elevated depressive symptoms exhibit deficits in inter-personal communication. Research has primarily focused on speech production in individuals with elevated depressive symptoms. Little is known about speech perception in individuals with elevated depressive symptoms, especially in challenging listening conditions. Here, we examined speech perception in young adults with low- or high-depressive (HD) symptoms in the presence of a range of maskers. Maskers were selected to reflect various levels of informational masking (IM), which refers to cognitive interference due to signal and masker similarity, and energetic masking (EM), which refers to peripheral interference due to signal degradation by the masker. Speech intelligibility data revealed that individuals with HD symptoms did not differ from those with low-depressive symptoms during EM, but they exhibited a selective deficit during IM. Since IM is a common occurrence in real-world social settings, this listening deficit may exacerbate communicative difficulties.	t	\N
25092665	What do we hear when someone speaks and what does auditory cortex (AC) do with that sound? Given how meaningful speech is, it might be hypothesized that AC is most active when other people talk so that their productions get decoded. Here, neuroimaging meta-analyses show the opposite: AC is least active and sometimes deactivated when participants listened to meaningful speech compared to less meaningful sounds. Results are explained by an active hypothesis-and-test mechanism where speech production (SP) regions are neurally re-used to predict auditory objects associated with available context. By this model, more AC activity for less meaningful sounds occurs because predictions are less successful from context, requiring further hypotheses be tested. This also explains the large overlap of AC co-activity for less meaningful sounds with meta-analyses of SP. An experiment showed a similar pattern of results for non-verbal context. Specifically, words produced less activity in AC and SP regions when preceded by co-speech gestures that visually described those words compared to those words without gestures. Results collectively suggest that what we 'hear' during real-world speech perception may come more from the brain than our ears and that the function of AC is to confirm or deny internal predictions about the identity of sounds.	t	\N
25096108	The summation of loudness across ears is often studied by measuring the level difference required for equal loudness (LDEL) of monaural and diotic sounds. Typically, the LDEL is ∼5-6 dB, consistent with the idea that a diotic sound is ∼1.5 times as loud as the same sound presented monaurally at the same level, as predicted by the loudness model of Moore and Glasberg [J. Acoust. Soc. Am. 121, 1604-1612 (2007)]. One might expect that the LDEL would be <5-6 dB for hearing-impaired listeners, because loudness recruitment leads to a more rapid change of loudness for a given change in level. However, previous data sometimes showed similar LDEL values for normal-hearing and hearing-impaired listeners. Here, the LDEL was measured for hearing-impaired listeners using narrowband and broadband noises centered at 500 Hz, where audiometric thresholds were near-normal, and at 3000 or 4000 Hz, where audiometric thresholds were elevated. The mean LDEL was 5.6 dB at 500 Hz and 4.2 dB at the higher center frequencies. The results were predicted reasonably well by an extension of the loudness model of Moore and Glasberg.	t	\N
25096138	The effects of audiovisual versus auditory training for speech-in-noise identification were examined in 60 young participants. The training conditions were audiovisual training, auditory-only training, and no training (n = 20 each). In the training groups, gated consonants and words were presented at 0 dB signal-to-noise ratio; stimuli were either audiovisual or auditory-only. The no-training group watched a movie clip without performing a speech identification task. Speech-in-noise identification was measured before and after the training (or control activity). Results showed that only audiovisual training improved speech-in-noise identification, demonstrating superiority over auditory-only training.	t	\N
25113242	This study investigates the influence of rhythmic expectancies on language processing. It is assumed that language rhythm involves an alternation of strong and weak beats within a linguistic domain. Hence, in some contexts rhythmically induced stress shifts occur in order to comply with the Rhythm Rule. In English, this rule operates to prevent clashes of stressed adjacent syllables or lapses of adjacent unstressed syllables. While previous studies investigated effects on speech production and perception, this study focuses on brain responses to structures either obeying or deviating from this rule. Event-related potentials show that rhythmic regularity is relevant for language processing: rhythmic deviations evoked different ERP components reflecting the deviance from rhythmic expectancies. An N400 effect found for shifted items reflects higher costs in lexical processing due to stress deviation. The overall results disentangle lexical and rhythmical influences on language processing and complement the findings of previous studies on rhythmical processing.	t	\N
25118042	To compare the fitting time requirements and the efficiency in achieving improvements in speech perception during the first 6 months after initial stimulation of computer-assisted fitting with the Fitting to Outcome eXpert' (FOX) and a standard clinical fitting procedure. Twenty-seven post-lingually deafened adults, newly implanted recipients of the Advanced Bionics HiRes 90K™ cochlear implant from Germany, the UK, and France took part in a controlled, randomized, clinical study. Speech perception was measured for all participants and fitting times were compared across groups programmed using FOX and conventional programming methods. The fitting time for FOX was significantly reduced at 14 days (P < 0.001) but equivalent over the 6-month period. The groups were not well matched for duration of deafness; therefore, speech perception could not be compared across groups. Despite including more objective measures of performance than a standard fitting approach and the adjustment of a greater range of parameters during initial fitting, FOX did not add to the overall fitting time when compared to the conventional approach. FOX significantly reduced the fitting time in the first 2 weeks and by providing a standard fitting protocol, reduced variability across centres. FOX computer-assisted fitting can be successfully used at switch on, in different clinical environments, reducing fitting time in the first 2 weeks and is efficient at providing a usable program.	t	\N
25121623	The current study provides evidence that the absence of a syntactically expected item leads to a sustained cognitive processing demand. Event-related potentials were measured at the omission of a syntactically expected object argument in a speech sequence. English monolingual adults listened to paired sentences. The first sentence in the pair established a context. The second sentence provided a response to the first sentence that was either grammatically correct by containing an overt object argument in the form of a pronoun, or was syntactically unacceptable by omitting the expected object pronoun. Event-related potentials measured at the omission of the object argument showed a prolonged positivity for 100-600 ms with a broad scalp distribution, and for 600-1000 ms with a focus in the anterior region. This observed omitted stimulus potential may contain characteristics of the P300 component, associated with the detection of the deviation of an expected stimulus, and the classical P600 related to syntactic reanalysis. Further, the late anterior P600 may indicate an increased memory demand in sentence comprehension. Thus, this linguistic omitted stimulus potential is a cognitive indicator of language processing that can be used to investigate the organization of linguistic knowledge.	t	\N
25126691	To evaluate the relationship between conductive hearing loss and maxillary constriction. A total of 120 people, aged from 7 to 40 years, who were referred to an audiologist when taking out health insurance or for school pre-registration check-up, were selected for this study. A total of 60 participants who had hearing threshold levels greater than 15 dB in both ears were chosen as the conductive hearing loss group. The remaining 60, with normal hearing thresholds of less than 15 dB, were used as the control group. All participants were referred to an orthodontic clinic. Participants who had a posterior crossbite and high palatal vault were considered to suffer from maxillary constriction. There were no significant differences between the sex ratios and mean ages of the groups. However, participants with conductive hearing loss were 3.5 times more likely than controls to suffer from maxillary constriction. Patients who suffer from conductive hearing loss are likely to show a maxillary abnormality when examined by an orthodontist.	t	\N
25139422	We investigated global integration (wrap-up) processes at the boundaries of musical phrases by comparing the effects of well and non-well formed phrases on event-related potentials time-locked to two boundary points: the onset and the offset of the boundary pause. The Closure Positive Shift, which is elicited at the boundary offset, was not modulated by the quality of phrase structure (well vs. non-well formed). In contrast, the boundary onset potentials showed different patterns for well and non-well formed phrases. Our results contribute to specify the functional meaning of the Closure Positive Shift in music, shed light on the large-scale structural integration of musical input, and raise new hypotheses concerning shared resources between music and language.	t	\N
25150964	Timbre is an important attribute of sound both in music and nature. Previously, using an operant conditioning paradigm, we found that black-capped chickadees and humans show similar response patterns in discriminating triadic chords of the same timbre and transferred this discrimination to a novel key center (novel absolute pitch). The current study examined how varying the timbre of the chords influenced discrimination. Using a similar operant conditioning procedure, we trained humans (Experiment 1) and chickadees (Experiments 2 and 3) to discriminate a major chord from 6 other chord types that had semitone deviations from the major chord. The pattern of errors of the 2 species replicated our previous findings. We then tested participants with novel timbres. We found that humans readily transferred their discrimination to novel timbres, suggesting they were attending to triadic pitch relations. The chickadees failed to transfer to novel timbres, suggesting they were using a different strategy to perform the original chord discrimination. We conducted an acoustic analysis examining frequency ranges that are biologically relevant to chickadees. We found that the relative intensity within each chord of the frequencies used in black-capped chickadee song significantly correlated with chickadees' percent response during probe testing. In Experiment 3, we trained a new set of chickadees by including either expanded pitch or timbre training before testing. Although chickadees showed some transfer to novel chords following this expanded training, we found that neither type of expanded training helped the chickadees when probe tested with novel stimuli.	t	\N
25151640	Congenital amusia has been described as a lifelong deficit of music perception and production, notably including amusic individuals' difficulties to recognize a familiar tune without the aid of lyrics. The present study aimed to evaluate whether amusic individuals might have acquired long-term knowledge of familiar music, and to test for the minimal amount of acoustic information necessary to access this knowledge (if any) in amusia. Segments of familiar and unfamiliar instrumental musical pieces were presented with increasing duration (250, 500, 1000 msec etc.), and participants provided familiarity judgments for each segment. Results showed that amusic individuals succeeded in differentiating familiar from unfamiliar excerpts with as little acoustic information as did control participants (i.e., within 500 msec). The findings reveal that amusic individuals have stored musical pieces in long-term memory (LTM), and, together with other recent findings, they suggest that congenital amusia might impair conscious access to music processing rather than music processing per se.	t	\N
25158372	Cortical auditory-evoked potentials (CAEPs), an objective measure of human speech encoding in individuals with normal or impaired auditory systems, can be used to assess the outcomes of hearing aids and cochlear implants in infants, or in young children who cannot co-operate for behavioural speech discrimination testing. The current study aimed to determine whether naturally produced speech stimuli /m/, /g/ and /t/ evoke distinct CAEP response patterns that can be reliably recorded and differentiated, based on their spectral information and whether the CAEP could be an electrophysiological measure to differentiate between these speech sounds. CAEPs were recorded from 18 school-aged children with normal hearing, tested in two groups: younger (5 - 7 years) and older children (8 - 12 years). Cortical responses differed in their P1 and N2 latencies and amplitudes in response to /m/, /g/ and /t/ sounds (from low-, mid- and high-frequency regions, respectively). The largest amplitude of the P1 and N2 component was for /g/ and the smallest was for /t/. The P1 latency in both age groups did not show any significant difference between these speech sounds. The N2 latency showed a significant change in the younger group but not in the older group. The N2 latency of the speech sound /g/ was always noted earlier in both groups. This study demonstrates that spectrally different speech sounds are encoded differentially at the cortical level, and evoke distinct CAEP response patterns. CAEP latencies and amplitudes may provide an objective indication that spectrally different speech sounds are encoded differently at the cortical level.	t	\N
25158615	To evaluate methods for measuring long-term benefits of cochlear implantation in a patient with single-sided deafness (SSD) with respect to spatial hearing and to document improved quality of life because of reduced tinnitus. A single adult male with profound right-sided sensorineural hearing loss and normal hearing in the left ear who underwent right-sided cochlear implantation. The subject was evaluated at 6, 9, 12, and 18 months after implantation on speech intelligibility with specific target-masker configurations, sound localization accuracy, audiologic performance, and tinnitus handicap. Testing conditions involved the acoustic (NH) ear only, the cochlear implant (CI) ear (acoustic ear plugged), and the bilateral condition (CI+NH). Measures of spatial hearing included speech intelligibility improvement because of spatial release from masking (SRM) and sound localization. In addition, traditional measures known as "head shadow," "binaural squelch," and "binaural summation" were evaluated. The best indicator for improved speech intelligibility was SRM, in which both ears are activated, but the relative locations of target and masker(s) are manipulated. Measures that compare performance with a single ear to performance using bilateral auditory input indicated evidence of the ability to integrate inputs across the ears, possibly reflecting early binaural processing, with 12 months of bilateral input. Sound localization accuracy improved with addition of the implant, and a large improvement with respect to tinnitus handicap was observed. Cochlear implantation resulted in improved sound localization accuracy when compared with performance using only the NH ear, and reduced tinnitus handicap was observed with use of the implant. The use of SRM addresses some of the current limitations of traditional measures of spatial and binaural hearing, as spatial cues related to target and maskers are manipulated, rather than the ear(s) tested. Sound testing methods and calculations described here are therefore recommended for assessing performance of a larger sample size of individuals with SSD who receive a CI.	t	\N
25167217	Objective To investigate the effect of increasing phase duration (pulse width, T-pulse) using a biphasic pulse composed of an initial anodic active phase followed by a balancing cathodic phase on the electrically evoked auditory brainstem responses (eABRs) recorded at the time of cochlear implantation. Design eABRs recorded during 188 surgeries for cochlear implantation from 1999 to 2006 in a single center were retrospectively reviewed by two independent observers. All patients were fitted with a NEURELEC cochlear implant (CI) device, initially DIGISONIC(®) then DIGISONIC SP(®) (2004-2006). Result Immediately following cochlear implantation, stimulation by the CI resulted in reliable wave III and V eABR waveforms (mean wave III latency 2.23 ± 0.38 ms SD and wave V latency 4.28 ± 0.42 ms SD). Latencies followed an apical to basal gradient (0.32 ms increase in mean eV latency and 0.12 ms for eIII latency). With increasing phase duration, wave III and wave V latencies significantly decreased in association with a shortening of the eIII-eV interwave gap, while amplitudes of both waves increased. Conclusion The impact of increasing phase duration on latency and amplitude of brainstem responses in a large set of patients implanted with NEURELEC CIs was reported.	t	\N
25170794	The neural resonance theory of musical meter explains musical beat tracking as the result of entrainment of neural oscillations to the beat frequency and its higher harmonics. This theory has gained empirical support from experiments using simple, abstract stimuli. However, to date there has been no empirical evidence for a role of neural entrainment in the perception of the beat of ecologically valid music. Here we presented participants with a single pop song with a superimposed bassoon sound. This stimulus was either lined up with the beat of the music or shifted away from the beat by 25% of the average interbeat interval. Both conditions elicited a neural response at the beat frequency. However, although the on-the-beat condition elicited a clear response at the first harmonic of the beat, this frequency was absent in the neural response to the off-the-beat condition. These results support a role for neural entrainment in tracking the metrical structure of real music and show that neural meter tracking can be disrupted by the presentation of contradictory rhythmic cues.	t	\N
25176617	Verbal memory is a fundamental prerequisite for language learning. This study investigated 7-month-olds' (N = 62) ability to remember the identity and order of elements in a multisyllabic word. The results indicate that infants detect changes in the order of edge syllables, or the identity of the middle syllables, but fail to encode the order of middle syllables. This suggests that the representational format of multisyllabic words is determined by core mnemonic biases, which favor accurate encoding of edges and limits the encoding of temporal order for internal segments. The studies support accounts proposing that content and order are encoded separately; in addition, the data show that this dissociation occurs early in development.	t	\N
25185802	In two studies based on Stanley Milgram's original pilots, we present the first systematic examination of cyranoids as social psychological research tools. A cyranoid is created by cooperatively joining in real-time the body of one person with speech generated by another via covert speech shadowing. The resulting hybrid persona can subsequently interact with third parties face-to-face. We show that naïve interlocutors perceive a cyranoid to be a unified, autonomously communicating person, evidence for a phenomenon Milgram termed the "cyranic illusion." We also show that creating cyranoids composed of contrasting identities (a child speaking adult-generated words and vice versa) can be used to study how stereotyping and person perception are mediated by inner (dispositional) vs. outer (physical) identity. Our results establish the cyranoid method as a unique means of obtaining experimental control over inner and outer identities within social interactions rich in mundane realism.	t	\N
25188354	Although active listening is an influential behavior, which can affect the social responses of others, the neural correlates underlying its perception have remained unclear. Sensing active listening in social interactions is accompanied by an improvement in the recollected impressions of relevant experiences and is thought to arouse positive feelings. We therefore hypothesized that the recognition of active listening activates the reward system, and that the emotional appraisal of experiences that had been subject to active listening would be improved. To test these hypotheses, we conducted functional magnetic resonance imaging (fMRI) on participants viewing assessments of their own personal experiences made by evaluators with or without active listening attitude. Subjects rated evaluators who showed active listening more positively. Furthermore, they rated episodes more positively when they were evaluated by individuals showing active listening. Neural activation in the ventral striatum was enhanced by perceiving active listening, suggesting that this was processed as rewarding. It also activated the right anterior insula, representing positive emotional reappraisal processes. Furthermore, the mentalizing network was activated when participants were being evaluated, irrespective of active listening behavior. Therefore, perceiving active listening appeared to result in positive emotional appraisal and to invoke mental state attribution to the active listener.	t	\N
25190323	In a standard center cueing paradigm, participants are asked to identify a target object presented either to the left or the right of a center cue (e.g., eye gaze, head-turn, arrow, etc.). When the center cue is non-predictive (e.g., the arrow points to the correct location of the target only 50 % of the time), the target can still be identified faster at the validly cued location than at the invalidly cued location. However, the abrupt onset of an object can elicit reflexive attention orientation. It is important to investigate whether this abrupt onset effect interferes with the cueing effect elicited by center cues because this interference effect, if it exists, should be controlled for in order to improve the test validity of the center cueing task. In an attentional cueing paradigm, we examined how the abrupt appearance of an exogenous target object mitigates the influence of center cues involving either a head turn (Experiment 1) or an arrow (Experiment 2). In Experiment 1, a non-predictive head-turn cue was followed by a target object (circle or square) presented in the left or right visual field. In the non-distractor condition, the target object was presented by itself. In this case, it is assumed that the sudden appearance of the target provides an orienting cue to the observer. To equalize the cueing effect of the target object, we presented a competing distractor object (triangle) in the opposite visual field to the target object. The participant's task was to categorize the target object as either a circle or square while ignoring the non-target triangle object in the opposite visual field. In Experiment 2, the arrow version of the cued recognition task was used, in which a single-headed arrow pointed to the object. The results from both experiments showed that both the non-predictive head-turn and arrow cues produced a reliable cueing effect in the distractor and non-distractor conditions. However, the magnitude of the cueing effect was greater in the distractor condition than in the non-distractor condition, suggesting that the abrupt onset of the target object acts like an exogenous signal, thereby reducing the impact of the internal head turn and arrow cues.	t	\N
25190394	Factors that might affect perceptual pitch match between acoustic and electric stimulation were examined in 25 bimodal listeners using magnitude estimation. Pre-operative acoustic thresholds in both ears, and duration of severe-profound loss, were first examined as correlates with degree of match between the measured pitch and that predicted by the spiral ganglion frequency-position model. The degree of match was examined with respect to (1) the ratio between the measured and predicted pitch percept on the most apical electrode and (2) the ratio between the slope of the measured and predicted pitch function. Second, effect of listening experience was examined to assess whether adaptation occurred over time to match the frequency assignment to electrodes. Pre-experience pitch estimates on the apical electrode were within the predicted range in only 28% of subjects, and the slope of the electrical pitch function was lower than predicted in all except one subject. Subjects with poorer hearing tended to have a lower pitch and a shallower electrical pitch function than predicted by the model. Pre-operative hearing thresholds in the contralateral ear and hearing loss duration were not correlated with the degree of pitch match, and there was no significant group effect of listening experience.	t	\N
25190407	Normal-hearing (NH) listeners make use of context, speech redundancy and top-down linguistic processes to perceptually restore inaudible or masked portions of speech. Previous research has shown poorer perception and restoration of interrupted speech in CI users and NH listeners tested with acoustic simulations of CIs. Three hypotheses were investigated: (1) training with CI simulations of interrupted sentences can teach listeners to use the high-level restoration mechanisms more effectively, (2) phonemic restoration benefit, an increase in intelligibility of interrupted sentences once its silent gaps are filled with noise, can be induced with training, and (3) perceptual learning of interrupted sentences can be reflected in clinical speech audiometry. To test these hypotheses, NH listeners were trained using periodically interrupted sentences, also spectrally degraded with a noiseband vocoder as CI simulation. Feedback was presented by displaying the sentence text and playing back both the intact and the interrupted CI simulation of the sentence. Training induced no phonemic restoration benefit, and learning was not transferred to speech audiometry measured with words. However, a significant improvement was observed in overall intelligibility of interrupted spectrally degraded sentences, with or without filler noise, suggesting possibly better use of restoration mechanisms as a result of training.	t	\N
25194209	Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way.	t	\N
25196041	Cognitive enhancement resulting from nicotinic acetylcholine receptor stimulation may be evidenced by increased efficiency of the auditory-frontal cortex network of auditory discrimination, which is impaired in schizophrenia, a cognitive disorder associated with excessive tobacco use. Investigating automatic (preattentive) detection of acoustic change with the mismatch negativity (MMN) brain event-related potential in response to nicotine in individuals with varying baseline levels of auditory discrimination may provide useful insight into the cholinergic regulation of this neural network and its potential amelioration with novel nicotinic agents. Sixty healthy, non-smoking male volunteers were presented with an 'optimal' multi-feature MMN paradigm in a randomized, placebo controlled double-blind design with 6 mg of nicotine gum. Participants with low, medium, and high baseline amplitudes responded differently to nicotine (vs. placebo), and nicotine response was feature specific. Whereas MMN in individuals with high amplitudes was diminished by nicotine, MMN increased in those with low amplitudes. Nicotine effects were not shown in medium amplitude participants. These findings provide preliminary support for the role of nicotinic neurotransmission in sensory memory processing of auditory change and suggest that nicotinic receptor modulation can both enhance and diminish change detection, depending on baseline MMN and its eliciting stimulus feature.	t	\N
25201816	Evidence suggests that deafness-induced changes in visual perception, cognition and attention may compensate for a hearing loss. Such alterations, however, may also negatively influence adaptation to a cochlear implant. This study investigated whether involuntary attentional capture by salient visual stimuli is altered in children who use a cochlear implant. Thirteen experienced implant users (aged 8-16 years) and age-matched normally hearing children were presented with a rapid sequence of simultaneous visual and auditory events. Participants were tasked with detecting numbers presented in a specified color and identifying a change in the tonal frequency whilst ignoring irrelevant visual distractors. Compared to visual distractors that did not possess the target-defining characteristic, target-colored distractors were associated with a decrement in visual performance (response time and accuracy), demonstrating a contingent capture of involuntary attention. Visual distractors did not, however, impair auditory task performance. Importantly, detection performance for the visual and auditory targets did not differ between the groups. These results suggest that proficient cochlear implant users demonstrate normal capture of visuospatial attention by stimuli that match top-down control settings.	t	\N
25208843	When an action produces an effect, both events are perceived to be shifted in time toward each other. This shift is called Intentional Binding (IB) effect. First evidence shows that this shift does not depend on the statistical predictability of the produced effect's identity (Desantis, Hughes, & Waszak, 2012). We confirm this result by comparing the perceived duration of action-effect intervals before valid and invalid action effects using the method of constant stimuli. The perceived duration of action-effect intervals did not differ for valid and invalid effects. This result was true for different durations of the action-effect interval (Experiments 1-4: 250 ms, Experiments 1 & 2: 400 ms), different effect modalities (Experiments 1 & 3: visual, Experiments 2-4: auditive), and two types of validity variations (Experiments 1 & 2: 80% valid, Experiments 3 & 4: 100% valid vs. random). We validated our results by using a clock paradigm and a numerical duration estimation task (Experiment 4). We conclude that the IB effect is not the result of internal prediction due to action-effect bindings, but might rely on higher-order processes.	t	\N
25214304	Prior studies of spatial negative priming indicate that distractor-assigned keypress responses are inhibited as part of visual, but not auditory, processing. However, recent evidence suggests that static keypress responses are not directly activated by spatially presented sounds and, therefore, might not call for an inhibitory process. In order to investigate the role of response inhibition in auditory processing, we used spatially directed responses that have been shown to result in direct response activation to irrelevant sounds. Participants localized a target sound by performing manual joystick responses (Experiment 1) or head movements (Experiment 2B) while ignoring a concurrent distractor sound. Relations between prime distractor and probe target were systematically manipulated (repeated vs. changed) with respect to identity and location. Experiment 2A investigated the influence of distractor sounds on spatial parameters of head movements toward target locations and showed that distractor-assigned responses are immediately inhibited to prevent false responding in the ongoing trial. Interestingly, performance in Experiments 1 and 2B was not generally impaired when the probe target appeared at the location of the former prime distractor and required a previously withheld and presumably inhibited response. Instead, performance was impaired only when prime distractor and probe target mismatched in terms of location or identity, which fully conforms to the feature-mismatching hypothesis. Together, the results suggest that response inhibition operates in auditory processing when response activation is provided but is presumably too short-lived to affect responding on the subsequent trial.	t	\N
25215617	Previous studies of frequency discrimination training (FDT) for tinnitus used repetitive task-based training programmes relying on extrinsic factors to motivate participation. Studies reported limited improvement in tinnitus symptoms. To evaluate FDT exploiting intrinsic motivations by integrating training with computer-gameplay. Sixty participants were randomly assigned to train on either a conventional task-based training, or one of two interactive game-based training platforms over six weeks. Outcomes included assessment of motivation, tinnitus handicap, and performance on tests of attention. Participants reported greater intrinsic motivation to train on the interactive game-based platforms, yet compliance of all three groups was similar (∼ 70%) and changes in self-reported tinnitus severity were not significant. There was no difference between groups in terms of change in tinnitus severity or performance on measures of attention. FDT can be integrated within an intrinsically motivating game. Whilst this may improve participant experience, in this instance it did not translate to additional compliance or therapeutic benefit. ClinicalTrials.gov NCT02095262.	t	\N
25218167	Knowing the context of a discourse is an essential prerequisite for comprehension. Here we used functional magnetic resonance imaging (fMRI) to disclose brain networks supporting context-dependent speech comprehension. During fMRI, 20 participants listened to 1-min spoken narratives preceded by pictures that were either contextually matching or mismatching with the narrative. Matching pictures increased narrative comprehension, decreased hemodynamic activity in Broca׳s area, and enhanced its functional connectivity with left anterior superior frontal gyrus, bilateral inferior parietal cortex, as well as anterior and posterior cingulate cortex. Further, the anterior (BA 45) and posterior (BA 44) portions of Broca׳s area differed in their functional connectivity patterns. Both BA 44 and BA 45 have shown increased connectivity with right angular gyrus and supramarginal gyrus. Whereas BA 44 showed increased connectivity with left angular gyrus, left inferior/middle temporal gyrus and left postcentral gyrus, BA 45 showed increased connectivity with right posterior cingulate cortex, right anterior inferior frontal gyrus, lateral occipital cortex and anterior cingulate cortex. Our results suggest that a fronto-parietal functional network supports context-dependent narrative comprehension, and that Broca׳s area is involved in resolving ambiguity from speech when appropriate contextual cues are lacking.	t	\N
25223106	A sound's duration provides important information about the event producing it. Although many of the sounds we hear every day are 'percussive' in nature (ie resulting from two objects impacting) and therefore exhibit decaying/damped amplitude envelopes, perceptual experiments frequently use tones synthesized with 'flat' or abruptly ending envelopes. Such sounds afford an estimation strategy involving calculating the elapsed time between tone onset and offset--a strategy that would be problematic for ecologically pervasive decaying sounds. Here we compare duration judgments for tones with percussive (ie gradually decaying) and flat (ie abruptly ending) amplitude envelopes, finding evidence for the use of different strategies. This result is discussed in terms of its implications for dominant theories and models of sensory perception that are often assessed using artificial sounds (ie 'flat tones') affording strategies that may not be optimal or even available for everyday listening.	t	\N
25224031	In human and nonhuman primates, the cortical motor system comprises a collection of brain areas primarily related to motor control. Existing evidence suggests that no other mammalian group has the number, extension, and complexity of motor-related areas observed in the frontal lobe of primates. Such diversity is probably related to the wide behavioral flexibility that primates display. Indeed, recent comparative anatomical, psychophysical, and neurophysiological studies suggest that the evolution of the motor cortical areas closely correlates with the emergence of high cognitive abilities. Advances in understanding the cortical motor system have shown that these areas are also related to functions previously linked to higher-order associative areas. In addition, experimental observations have shown that the classical distinction between perceptual and motor functions is not strictly followed across cortical areas. In this paper, we review evidence suggesting that evolution of the motor system had a role in the shaping of different cognitive functions in primates. We argue that the increase in the complexity of the motor system has contributed to the emergence of new abilities observed in human and nonhuman primates, including the recognition and imitation of the actions of others, speech perception and production, and the execution and appreciation of the rhythmic structure of music.	t	\N
25226375	We seek to determine the extent of age-related decline in speech perception performance among cochlear implant recipients as quantified by various metrics. Retrospective chart review. Tertiary referral center. The records of 70 postlingually deafened adults who received cochlear implants between 2004 and 2013 were reviewed. Unilateral cochlear implantation. Postoperative AzBio and Consonant-Nucleus-Consonant (CNC) scores at greater than 3 months postactivation. Group analyses comparing patients aged 65 years and older (elderly) with younger adult patients (control). In addition, multivariate linear regression analyses were performed that incorporated preoperative pure-tone audiograms, duration of deafness, duration of follow-up, sex, and laterality of the implanted ear to quantitate the dependence of AzBio and CNC results on age at implantation (AAI). Performance on AzBio for the control and elderly groups were 74.6% ± 4.1% and 59.5% ± 4.5% (p = 0.032), respectively. Performance on CNC scores were 63.9% ± 3.4% and 55.3% ± 3.3% (p = 0.098), respectively. Multiple linear regression showed a significant correlation of AzBio with AAI, whereas CNC did not correlate significantly (correlation coefficients = -0.006 and -0.003, p = 0.019 and 0.081, respectively). Patients implanted at a later age performed more poorly on AzBio sentences. A similar trend was noted with CNC scores although not significant. The variability in correlation coefficients and significance between both speech perception tests and AAI suggests that, as patients age, their performance on each individual test will be affected to a varying degree.	t	\N
25234731	Mandarin Chinese is a lexical tone language that has four tones, with a change in tone denoting a change in lexical meaning. There are few studies regarding lexical tone identification abilities in deafened children using either cochlear implants (CIs) or hearing aids (HAs). Furthermore, no study has compared the lexical tone identification abilities of deafened children with their hearing devices turned on and off. The present study aimed to investigate the lexical tone identification abilities of deafened children with CIs or HAs. Forty prelingually deafened children (20 with CIs and 20 with HAs) participated in the study. In the HA group, 20 children were binaurally aided. In the CI group, all of the children were unilaterally implanted. All of the subjects completed a computerized lexical tone pairs test with their hearing devices turned on and off. The correct answers of all items were recorded as the total score and the correct answers of the tone pairs were recorded as subtotal scores. No significant differences in the tone pair identification scores were found between the CI group and HA group either with the devices turned on or off (t=1.62, p=0.11; t=1.863, p=0.07, respectively). The scores in the aided condition were higher than in the unaided condition regardless of the device used (t=22.09, p<0.001, in the HA group; t=20.20, p<0.001, in the CI group). Significantly higher scores were found in the tone pairs that contained tone 4. Age at fitting of the devices was correlated with tone identification abilities in both the CI and HA groups. Other demographic factors were not correlated with tone identification ability. The hearing device, whether a hearing aid or cochlear implant, is beneficial for tone identification. The lexical tone identification abilities were similar regardless of whether the subjects wore a HA or CI. Lexical tone pairs with different durations and dissimilar tone contour patterns are more easily identified. Receiving devices at earlier age tends to produce better lexical tone identification abilities in prelingually deafened children.	t	\N
25234885	This study examined the ability of listeners to utilize syntactic structure to extract a target stream of speech from among competing sounds. Target talkers were identified by voice or location, which was held constant throughout a test utterance, and paired with correct or incorrect (random word order) target sentence syntax. Both voice and location provided reliable cues for identifying target speech even when other features varied unpredictably. The target sentences were masked either by predominantly energetic maskers (noise bursts) or by predominantly informational maskers (similar speech in random word order). When the maskers were noise bursts, target sentence syntax had relatively minor effects on identification performance. However, when the maskers were other talkers, correct target sentence syntax resulted in significantly better speech identification performance than incorrect syntax. Furthermore, conformance to correct syntax alone was sufficient to accurately identify the target speech. The results were interpreted as supporting the idea that the predictability of the elements comprising streams of speech, as manifested by syntactic structure, is an important factor in binding words together into coherent streams. Furthermore, these findings suggest that predictability is particularly important for maintaining the coherence of an auditory stream over time under conditions high in informational masking.	t	\N
25235005	The contribution of recovered envelopes (RENVs) to the utilization of temporal-fine structure (TFS) speech cues was examined in normal-hearing listeners. Consonant identification experiments used speech stimuli processed to present TFS or RENV cues. Experiment 1 examined the effects of exposure and presentation order using 16-band TFS speech and 40-band RENV speech recovered from 16-band TFS speech. Prior exposure to TFS speech aided in the reception of RENV speech. Performance on the two conditions was similar (∼50%-correct) for experienced listeners as was the pattern of consonant confusions. Experiment 2 examined the effect of varying the number of RENV bands recovered from 16-band TFS speech. Mean identification scores decreased as the number of RENV bands decreased from 40 to 8 and were only slightly above chance levels for 16 and 8 bands. Experiment 3 examined the effect of varying the number of bands in the TFS speech from which 40-band RENV speech was constructed. Performance fell from 85%- to 31%-correct as the number of TFS bands increased from 1 to 32. Overall, these results suggest that the interpretation of previous studies that have used TFS speech may have been confounded with the presence of RENVs.	t	\N
25243615	It is well established that categorising the emotional content of facial expressions may differ depending on contextual information. Whether this malleability is observed in the auditory domain and in genuine emotion expressions is poorly explored. We examined the perception of authentic laughter and crying in the context of happy, neutral and sad facial expressions. Participants rated the vocalisations on separate unipolar scales of happiness and sadness and on arousal. Although they were instructed to focus exclusively on the vocalisations, consistent context effects were found: For both laughter and crying, emotion judgements were shifted towards the information expressed by the face. These modulations were independent of response latencies and were larger for more emotionally ambiguous vocalisations. No effects of context were found for arousal ratings. These findings suggest that the automatic encoding of contextual information during emotion perception generalises across modalities, to purely non-verbal vocalisations, and is not confined to acted expressions.	t	\N
25247311	Neonatal necrotizing enterocolitis (NEC) is associated with an increased incidence of poor neurodevelopment. The knowledge of underlying neurophysiology is very limited, and the influence of NEC on the preterm brainstem is very poorly understood. To assess the effect of NEC on the immature auditory brainstem by excluding any possible confounding effect of preterm birth. We recorded and analyzed brainstem auditory evoked response (BAER) at different click rates in preterm babies (30-34 weeks gestation) after NEC. The results were compared with those in age-matched healthy preterm babies who had no NEC. At click rate 21/s, the latencies of BAER waves I and III in the preterm NEC babies were similar to those babies without NEC. However, wave V latency was longer in the NEC babies than in those without NEC. The I-V interpeak interval was also longer in the NEC babies than in those without NEC. These abnormalities were persistent at higher click rates 51 and 91/s. Wave I amplitude in the preterm NEC babies did not differ significantly from that in those without NEC, but wave III and V amplitudes were smaller than in those without NEC at all 21-91/s clicks. Compared with healthy preterm babies, preterm babies after NEC showed a major increase in wave V latency and I-V interval at all 21-91/s clicks. Brainstem auditory function is impaired in preterm NEC babies after excluding the possible confounding effect of preterm birth. Neonatal NEC and associated perinatal conditions adversely affect the premature brainstem.	t	\N
25248101	Using an auditory variant of task switching, we examined the ability to intentionally switch attention in a dichotic-listening task. In our study, participants responded selectively to one of two simultaneously presented auditory number words (spoken by a female and a male, one for each ear) by categorizing its numerical magnitude. The mapping of gender (female vs. male) and ear (left vs. right) was unpredictable. The to-be-attended feature for gender or ear, respectively, was indicated by a visual selection cue prior to auditory stimulus onset. In Experiment 1, explicitly cued switches of the relevant feature dimension (e.g., from gender to ear) and switches of the relevant feature within a dimension (e.g., from male to female) occurred in an unpredictable manner. We found large performance costs when the relevant feature switched, but switches of the relevant feature dimension incurred only small additional costs. The feature-switch costs were larger in ear-relevant than in gender-relevant trials. In Experiment 2, we replicated these findings using a simplified design (i.e., only within-dimension switches with blocked dimensions). In Experiment 3, we examined preparation effects by manipulating the cueing interval and found a preparation benefit only when ear was cued. Together, our data suggest that the large part of attentional switch costs arises from reconfiguration at the level of relevant auditory features (e.g., left vs. right) rather than feature dimensions (ear vs. gender). Additionally, our findings suggest that ear-based target selection benefits more from preparation time (i.e., time to direct attention to one ear) than gender-based target selection.	t	\N
25255036	In human face-to-face communication, language comprehension is a multi-modal, situated activity. However, little is known about how we combine information from different modalities during comprehension, and how perceived communicative intentions, often signaled through visual signals, influence this process. We explored this question by simulating a multi-party communication context in which a speaker alternated her gaze between two recipients. Participants viewed speech-only or speech+gesture object-related messages when being addressed (direct gaze) or unaddressed (gaze averted to other participant). They were then asked to choose which of two object images matched the speaker's preceding message. Unaddressed recipients responded significantly more slowly than addressees for speech-only utterances. However, perceiving the same speech accompanied by gestures sped unaddressed recipients up to a level identical to that of addressees. That is, when unaddressed recipients' speech processing suffers, gestures can enhance the comprehension of a speaker's message. We discuss our findings with respect to two hypotheses attempting to account for how social eye gaze may modulate multi-modal language comprehension.	t	\N
25261772	Amazing progress has been made in providing useful hearing to hearing-impaired individuals using cochlear implants, but challenges remain. One such challenge is understanding the effects of partial degeneration of the auditory nerve, the target of cochlear implant stimulation. Here we review studies from our human and animal laboratories aimed at characterizing the health of the implanted cochlea and the auditory nerve. We use the data on cochlear and neural health to guide rehabilitation strategies. The data also motivate the development of tissue-engineering procedures to preserve or build a healthy cochlea and improve performance obtained by cochlear implant recipients or eventually replace the need for a cochlear implant. This article is part of a Special Issue entitled <Lasker Award>.	t	\N
25263528	Although children can use social categories to intelligently select informants, children's preference for in-group informants has not been consistently demonstrated across age and context. This research clarifies the extent to which children use social categories to guide learning by presenting participants with a live or video-recorded action demonstration by a linguistic in-group and/or out-group model. Participants' (N = 104) propensity to imitate these actions was assessed. Nineteen-month-olds did not selectively imitate the actions of the in-group model in live contexts, though in-group preferences were found after watching the demonstration on video. Three-year-olds selectively imitated the actions demonstrated by the in-group member regardless of context. These results indicate that in-group preferences have a more nuanced effect on social learning than previous research has indicated.	t	\N
25269621	Despite the fact that no invariant acoustic property corresponds to a single stop consonant coupled with different vowels (e.g., [da], [de], and [du]), adults effortlessly identify the same consonant embedded in different syllables. In so doing, they solve the invariance problem. Can 3- and 6-month-olds solve it as well? To answer this question, we developed a novel methodology based on pupillometry. In Experiment 1, we demonstrated for the first time that infants are sensitive to the distinction between frequent and infrequent acoustic stimuli, showing greater pupil dilation in response to infrequent stimuli. Building on this effect, in Experiment 2, we showed that 6-month-olds, but not 3-month-olds, solve the invariance problem. Moreover, this ability develops before, and therefore independently of, the ability to produce well-formed syllables.	t	\N
25275862	To compare within-subject bilateral-binaural and bimodal complementary abilities between bimodal (cochlear implant and hearing aid; CI/HA) and bilateral CI hearing (CI/CI), thereby enabling better-informed counseling of experienced CI/HA users contemplating contralateral implantation. Comparative within-subject case review. Outpatient hearing clinic. Ten experienced adult CI/HA users with severe-to-profound hearing loss in the HA ear, who converted to CI/CI between 2 and 11 years after initial implantation. Task-specific testing of bilateral-binaural hearing (sound lateralization, binaural summation/redundancy/unmasking, head-shadow effect), bimodal complementary benefit (contribution of low-frequency information), and a self-report Speech, Spatial, and Qualities of Hearing (SSQ) questionnaire, all before and 1 year after contralateral cochlear implantation. Test result differences between CI/HA and CI/CI conditions. CI/CI hearing was better than CI/HA for speech lateralization and for perception of semantically unpredictable sentences in speech noise with speech at 0 degrees and noise at +90 degrees azimuth on the old CI side. CI/HA was better than CI/CI only for differences between perception of natural prosody speech and of speech with flattened fundamental frequency (F0) contour with speech and noise in front (at 0 degrees azimuth). Total scores on the SSQ questionnaire were higher in CI/CI than in CI/HA users. Counseling regarding contralateral implantation for CI/HA users with severe-to-profound hearing loss in the HA ear, though generally positive, should consider individual functional needs, and cover expectations about the expected trade-off between gaining improved understanding and speech lateralization in challenging listening conditions and losing some low-frequency cues still available with CI/HA hearing.	t	\N
25280122	Both psychological stress and predictive signals relating to expected sensory input are believed to influence perception, an influence which, when disrupted, may contribute to the generation of auditory hallucinations. The effect of stress and semantic expectation on auditory perception was therefore examined in healthy participants using an auditory signal detection task requiring the detection of speech from within white noise. Trait anxiety was found to predict the extent to which stress influenced response bias, resulting in more anxious participants adopting a more liberal criterion, and therefore experiencing more false positives, when under stress. While semantic expectation was found to increase sensitivity, its presence also generated a shift in response bias towards reporting a signal, suggesting that the erroneous perception of speech became more likely. These findings provide a potential cognitive mechanism that may explain the impact of stress on hallucination-proneness, by suggesting that stress has the tendency to alter response bias in highly anxious individuals. These results also provide support for the idea that top-down processes such as those relating to semantic expectation may contribute to the generation of auditory hallucinations.	t	\N
25281311	Interactions between ourselves and the external world are mediated by a multisensory representation of the space surrounding the body, i.e. the peripersonal space (PPS). In particular, a special interplay is observed among tactile stimuli delivered on a body part, e.g. the hand, and visual or auditory external inputs presented close, but not far, from the same body part, e.g. within hand PPS. This coding of multisensory stimuli as a function of their distance from the hand has a role in upper limb actions. However, it remains unclear whether PPS representation affects the motor system only when stimuli occur specifically at the hand location or when they move within a continuous portion of space where the hand can potentially act. Here, in order to study these two alternatively hypotheses, we assessed the critical distance at which moving sounds have a direct effect on hand corticospinal excitability by using Transcranial Magnetic Stimulation (TMS). Specifically, TMS single pulses were delivered when a sound source was perceived at six different positions in space: from very close to subjects' hand (15 cm) to far away (90 cm). Moreover, sound direction was manipulated to test if stimuli approaching and receding from the hand might have the same relevance for the motor system. MEPs amplitude was enhanced when sounds were delivered within a limited distance from the hand (around 60 cm) as compared to when the sounds were beyond this space. This effect captures the spatial boundaries within which PPS representation modulates hand cortico-motor excitability. This spatially-dependent modulation of corticospinal activity was not further affected by the sound direction. Such findings support a strict link between the multisensory representation of the space around the body and the motor representation of potential approaching or defensive acts within that space.	t	\N
25282057	A fundamental question in language development is how infants start to assign meaning to words. Here, using three Electroencephalogram (EEG)-based measures of brain activity, we establish that preverbal 11-month-old infants are sensitive to the non-arbitrary correspondences between language sounds and concepts, that is, to sound symbolism. In each trial, infant participants were presented with a visual stimulus (e.g., a round shape) followed by a novel spoken word that either sound-symbolically matched ("moma") or mismatched ("kipi") the shape. Amplitude increase in the gamma band showed perceptual integration of visual and auditory stimuli in the match condition within 300 msec of word onset. Furthermore, phase synchronization between electrodes at around 400 msec revealed intensified large-scale, left-hemispheric communication between brain regions in the mismatch condition as compared to the match condition, indicating heightened processing effort when integration was more demanding. Finally, event-related brain potentials showed an increased adult-like N400 response - an index of semantic integration difficulty - in the mismatch as compared to the match condition. Together, these findings suggest that 11-month-old infants spontaneously map auditory language onto visual experience by recruiting a cross-modal perceptual processing system and a nascent semantic network within the first year of life.	t	\N
25301567	Previous research has shown that the human auditory system continuously monitors its acoustic environment, detecting a variety of irregularities (e.g., deviance from prior stimulation regularity in pitch, loudness, duration, and (perceived) sound source location). Detection of irregularities can be inferred from a component of the event-related brain potential (ERP), referred to as the mismatch negativity (MMN), even in conditions in which participants are instructed to ignore the auditory stimulation. The current study extends previous findings by demonstrating that auditory irregularities brought about by a change in room acoustics elicit a MMN in a passive oddball protocol (acoustic stimuli with differing room acoustics, that were otherwise identical, were employed as standard and deviant stimuli), in which participants watched a fiction movie (silent with subtitles). While the majority of participants reported no awareness for any changes in the auditory stimulation, only one out of 14 participants reported to have become aware of changing room acoustics or sound source location. Together, these findings suggest automatic monitoring of room acoustics.	t	\N
25305712	The pathophysiology of nonfluent primary progressive aphasia (nfvPPA) remains poorly understood. Here, we compared quantitatively speech parameters in patients with nfvPPA versus healthy older individuals under altered auditory feedback, which has been shown to modulate normal speech output. Patients (n=15) and healthy volunteers (n=17) were recorded while reading aloud under delayed auditory feedback [DAF] with latency 0, 50 or 200 ms and under DAF at 200 ms plus 0.5 octave upward pitch shift. DAF in healthy older individuals was associated with reduced speech rate and emergence of speech sound errors, particularly at latency 200 ms. Up to a third of the healthy older group under DAF showed speech slowing and frequency of speech sound errors within the range of the nfvPPA cohort. Our findings suggest that (in addition to any anterior, primary language output disorder) these key features of nfvPPA may reflect distorted speech input signal processing, as simulated by DAF. DAF may constitute a novel candidate pathophysiological model of posterior dorsal cortical language pathway dysfunction in nfvPPA.	t	\N
25306203	Reduced auditory P300 amplitude is a robust schizophrenia deficit exhibiting the qualities of a viable genetic endophenotype. These include heritability, test-retest reliability, and trait-like stability. Recent evidence suggests that P300 may also serve as a predictive biomarker for transition to psychosis during the schizophrenia prodrome. Historically, the utility of the P300 has been limited by its clinical nonspecificity, cross-site measurement variability, and required EEG expertise. The Consortium on the Genetics of Schizophrenia (COGS-2) study provided an opportunity to examine the consistency of the measure across multiple sites with varying degrees of EEG experience, and to identify important modulating factors that contribute to measurement variability. Auditory P300 was acquired from 649 controls and 587 patients at 5 sites. An overall patient deficit was observed with effect size 0.62. Each site independently observed a significant patient deficit, but site differences also existed. In patients, site differences reflected clinical differences in positive symptomatology and functional capacity. In controls, site differences reflected differences in racial stratification, smoking and substance use history. These factors differentially suppressed the P300 response, but only in control subjects. This led to an attenuated patient-control difference among smokers and among African Americans with history of substance use. These findings indicate that the P300 can be adequately assessed quantitatively, across sites, without substantial EEG expertise. Measurements are suitable for both genetic endophenotype analyses and studies of psychosis risk and conversion. However, careful attention must be given to selection of appropriate comparison samples to avoid misleading false negative results.	t	\N
25313714	Perception of spoken language requires attention to acoustic as well as visible phonetic information. This article reviews the known differences in audiovisual speech perception in children with autism spectrum disorders (ASD) and specifies the need for interventions that address this construct. Elements of an audiovisual training program are described. This researcher-developed program delivered via an iPad app presents natural speech in the context of increasing noise, but supported with a speaking face. Children are cued to attend to visible articulatory information to assist in perception of the spoken words. Data from four children with ASD ages 8-10 are presented showing that the children improved their performance on an untrained auditory speech-in-noise task.	t	\N
25319676	Subjective tinnitus is the perception of sound in the absence of a corresponding external sound for which there is no known medical etiology. For a minority of individuals with tinnitus, the condition impacts their ability to lead a normal lifestyle and is severely debilitating. There is no known cure for tinnitus, so current therapy focuses on reducing the effect of tinnitus on the patient's quality of life. Tinnitus retraining therapy (TRT) uses nonpsychiatric tinnitus-specific educational counseling and sound therapy in a habituation-based protocol to reduce the patient's tinnitus-evoked negative reaction to, and awareness of, the tinnitus, with the ultimate goal of reducing the tinnitus impact on the patient's quality of life. Some studies support the efficacy of TRT, but no trial to date has compared TRT with the current standard of care or evaluated the separate contributions of TRT counseling and sound therapy. The Tinnitus Retraining Therapy Trial (TRTT) is a randomized, double-blind, placebo-controlled, multicenter trial for individuals with intolerable tinnitus. The TRTT is enrolling active-duty and retired military personnel and their dependents with functionally adequate hearing sensitivity and severe tinnitus at US Air Force, Navy, and Army medical centers. Eligible study participants are randomized to TRT, partial TRT, or standard care to determine the efficacy of TRT and its components (TRT counseling and sound therapy). The primary outcome is change in score on the Tinnitus Questionnaire assessed longitudinally between baseline and follow-up (3, 6, 12, and 18 months following treatment). Secondary outcomes include subscale score changes in the Tinnitus Questionnaire, overall and subscale score changes in the Tinnitus Functional Index and Tinnitus Handicap Inventory, and change in the visual analog scale of the TRT Interview Form. Audiological outcomes include tinnitus pitch and loudness match and measures of loudness discomfort levels. The incidence of depression as a safety measure is assessed at each visit using the Beck Depression Inventory Fast Screen. Clinicaltrials.gov NCT01177137.	t	\N
25324150	Recent literature reviews have highlighted the need to better understand the relation between speaker and listener behavior when teaching learners with autism spectrum disorders (ASD). The current study used a modified parallel-treatments design to compare directly the degree to which tact and listener behavior emerged during instruction in the opposite relation for 4 children with ASD. Results showed tact training to be either equally or more efficient than listener training for all participants. However, varied patterns of emergent responding across participants indicate a need for further research. Data on collateral responding during instruction did not suggest that the presence or absence of overt collateral behaviors were predictive of emergence. The results highlight the importance for clinicians and educators to assess emergent tact and listener repertoires periodically.	t	\N
25324726	Our concepts of sound localization in the vertebrate brain are widely based on the general assumption that both the ability to detect air-borne sounds and the neuronal processing are homologous in archosaurs (present day crocodiles and birds) and mammals. Yet studies repeatedly report conflicting results on the neuronal circuits and mechanisms, in particular the role of inhibition, as well as the coding strategies between avian and mammalian model systems. Here we argue that mammalian and avian phylogeny of spatial hearing is characterized by a convergent evolution of hearing air-borne sounds rather than by homology. In particular, the different evolutionary origins of tympanic ears and the different availability of binaural cues in early mammals and archosaurs imposed distinct constraints on the respective binaural processing mechanisms. The role of synaptic inhibition in generating binaural spatial sensitivity in mammals is highlighted, as it reveals a unifying principle of mammalian circuit design for encoding sound position. Together, we combine evolutionary, anatomical and physiological arguments for making a clear distinction between mammalian processing mechanisms and coding strategies and those of archosaurs. We emphasize that a consideration of the convergent nature of neuronal mechanisms will significantly increase the explanatory power of studies of spatial processing in both mammals and birds.	t	\N
25325783	Visual crowding is generally thought to affect recognition mostly or only at the level of feature combination. Calling this assertion into question, recent studies have shown that if a target object and its flankers belong to different categories crowding is weaker than if they belong to the same category. Nevertheless, these results can be explained in terms of featural differences between categories. The current study tests if category-level (i.e., high-level) interference in crowding occurs when featural differences are controlled for. First, replicating previous results, we found lower critical spacing for targets and flankers belonging to different categories. Second, we observed the same, albeit weaker, category-specific effect when objects in both categories had the exact same feature set, suggesting that category-specific effects persist even when featural differences are fully controlled for. Third, we manipulated the semantic content of the flankers while keeping their feature set constant, by using upright or rotated objects, and found that meaning modulated crowding. An exclusively feature-based account of crowding would predict no differences due to such changes in meaning. We conclude that crowding results from not only the well-documented feature-level interactions but also additional interactions at a level where objects are grouped by meaning.	t	\N
25326606	What is the perceptual fate of invisible stimuli-are they processed at all and does their processing have consequences for the perception of other stimuli? As has been shown previously in the somatosensory system, even stimuli that are too weak to be consciously detected can influence our perception: Subliminal stimulation impairs perception of near-threshold stimuli and causes a functional deactivation in the somatosensory cortex. In a recent study, we showed that subliminal visual stimuli lead to similar responses, indicated by an increase in alpha-band power as measured with electroencephalography (EEG). In the current study, we investigated whether a behavioral inhibitory mechanism also exists within the visual system. We tested the detection of peripheral visual target stimuli under three different conditions: Target stimuli were presented alone or embedded in a concurrent train of subliminal stimuli either at the same location as the target or in the opposite hemifield. Subliminal stimuli were invisible due to their low contrast, not due to a masking procedure. We demonstrate that target detection was impaired by the subliminal stimuli, but only when they were presented at the same location as the target. This finding indicates that subliminal, low-intensity stimuli induce a similar inhibitory effect in the visual system as has been observed in the somatosensory system. In line with previous reports, we propose that the function underlying this effect is the inhibition of spurious noise by the visual system.	t	\N
25332098	Development and evolution of auditory hindbrain nuclei are two major unsolved issues in hearing research. Recent characterization of transgenic mice identified the rhombomeric origins of mammalian auditory nuclei and unraveled genes involved in their formation. Here, we provide an overview on these data by assembling them into rhombomere-specific gene regulatory networks (GRNs), as they underlie developmental and evolutionary processes. To explore evolutionary mechanisms, we compare the GRNs operating in the mammalian auditory hindbrain with data available from the inner ear and other vertebrate groups. Finally, we propose that the availability of genomic sequences from all major vertebrate taxa and novel genetic techniques for non-model organisms provide an unprecedented opportunity to investigate development and evolution of the auditory hindbrain by comparative molecular approaches. The dissection of the molecular mechanisms leading to auditory structures will also provide an important framework for auditory processing disorders, a clinical problem difficult to tackle so far. These data will, therefore, foster basic and clinical hearing research alike.	t	\N
25344346	It is increasingly recognized that motor routines dynamically shape the processing of sensory inflow (e.g., when hand movements are used to feel a texture or identify an object). In the present research, we captured the shaping of auditory perception by movement in humans by taking advantage of a specific context: music. Participants listened to a repeated rhythmical sequence before and after moving their bodies to this rhythm in a specific meter. We found that the brain responses to the rhythm (as recorded with electroencephalography) after body movement were significantly enhanced at frequencies related to the meter to which the participants had moved. These results provide evidence that body movement can selectively shape the subsequent internal representation of auditory rhythms.	t	\N
25346316	In the United States, falls are the leading cause of accidental deaths in adults aged over 65 years. Epidemiologic studies indicate that there is a correlation between hearing loss and the risk of falling among older people. The vestibular, proprioceptive, and visual systems are known to contribute to postural stability, but the contribution of audition to maintaining balance has not yet been determined. Cross-sectional study to measure postural stability in bilateral hearing-aid users aged over 65 years in aided and unaided conditions. Balance was assessed using the Romberg on foam test and the tandem stance test. Tests were administered in the presence of a point-source broadband white-noise sound (0-4 kHz) source in both unaided and aided conditions in the dark. Subjective measures of balance were made using the Activities-specific Balance Confidence Scale. Performance was significantly better in the aided than the unaided condition (P = 0.005 for both tests). No statistically significant relationship between improvement in balance, and hearing was identified. Participants did not report that they perceived a difference in balance between the two conditions. These results indicate that hearing aids are a novel treatment modality for imbalance in older adults with hearing loss and suggest that wearing hearing aids may offer a significant public-health benefit for avoiding falls in this population.	t	\N
25350757	This study used event-related potentials (ERPs) to assess effects of low-level prenatal lead exposure on auditory recognition memory in 2-month-old infants. Infants were divided into four groups according to cord-blood lead concentration: (1) <2.00 μ g/dL, (2) 2.00-2.99 μ g/dL, (3) 3.0-3.7 μ g/dL, and (4) ≥3.7 μ g/dL. The first group showed the normally expected differences in P2, P750, and late slow wave (LSW) amplitudes elicited by mothers' and strangers' voices. These differences were not observed for one or more ERP components in the other groups. Thus, there was electrophysiological evidence of poorer auditory recognition memory at 2 months with cord-blood lead ≥2.00 μ g/dL.	t	\N
25358027	To evaluate a speech-processing strategy in which the lowest frequency channel is conveyed using an asymmetric pulse shape and "phantom stimulation", where current is injected into one intra-cochlear electrode and where the return current is shared between an intra-cochlear and an extra-cochlear electrode. This strategy is expected to provide more selective excitation of the cochlear apex, compared to a standard strategy where the lowest-frequency channel is conveyed by symmetric pulses in monopolar mode. In both strategies all other channels were conveyed by monopolar stimulation. Within-subjects comparison between the two strategies. Four experiments: (1) discrimination between the strategies, controlling for loudness differences, (2) consonant identification, (3) recognition of lowpass-filtered sentences in quiet, (4) sentence recognition in the presence of a competing speaker. Eight users of the Advanced Bionics CII/Hi-Res 90k cochlear implant. Listeners could easily discriminate between the two strategies but no consistent differences in performance were observed. The proposed method does not improve speech perception, at least in the short term.	t	\N
25358716	Information processing of all acoustic stimuli involves temporal lobe regions referred to as auditory cortices, which receive direct afferents from the auditory thalamus. However, the perception of music (as well as speech or spoken language) is a complex process that also involves secondary and association cortices that conform a large functional network. Using different analytical techniques and stimulation paradigms, several studies have shown that certain areas are particularly sensitive to specific acoustic characteristics inherent to music (e.g., rhythm). This chapter reviews the functional anatomy of the auditory cortices, and highlights specific experiments that suggest the existence of distinct cortical networks for the perception of music and speech.	t	\N
25373970	Otoacoustic emission (OAE) tests of the medial-olivocochlear reflex (MOCR) in humans were assessed for viability as clinical assays. Two reflection-source OAEs [TEOAEs: transient-evoked otoacoustic emissions evoked by a 47 dB sound pressure level (SPL) chirp; and discrete-tone SFOAEs: stimulus-frequency otoacoustic emissions evoked by 40 dB SPL tones, and assessed with a 60 dB SPL suppressor] were compared in 27 normal-hearing adults. The MOCR elicitor was a 60 dB SPL contralateral broadband noise. An estimate of MOCR strength, MOCR%, was defined as the vector difference between OAEs measured with and without the elicitor, normalized by OAE magnitude (without elicitor). An MOCR was reliably detected in most ears. Within subjects, MOCR strength was correlated across frequency bands and across OAE type. The ratio of across-subject variability to within-subject variability ranged from 2 to 15, with wideband TEOAEs and averaged SFOAEs giving the highest ratios. MOCR strength in individual ears was reliably classified into low, normal, and high groups. SFOAEs using 1.5 to 2 kHz tones and TEOAEs in the 0.5 to 2.5 kHz band gave the best statistical results. TEOAEs had more clinical advantages. Both assays could be made faster for clinical applications, such as screening for individual susceptibility to acoustic trauma in a hearing-conservation program.	t	\N
25385771	The ability to perceive a regular beat in music and synchronize to this beat is a widespread human skill. Fundamental to musical behaviour, beat and meter refer to the perception of periodicities while listening to musical rhythms and often involve spontaneous entrainment to move on these periodicities. Here, we present a novel experimental approach inspired by the frequency-tagging approach to understand the perception and production of rhythmic inputs. This approach is illustrated here by recording the human electroencephalogram responses at beat and meter frequencies elicited in various contexts: mental imagery of meter, spontaneous induction of a beat from rhythmic patterns, multisensory integration and sensorimotor synchronization. Collectively, our observations support the view that entrainment and resonance phenomena subtend the processing of musical rhythms in the human brain. More generally, they highlight the potential of this approach to help us understand the link between the phenomenology of musical beat and meter and the bias towards periodicities arising under certain circumstances in the nervous system. Entrainment to music provides a highly valuable framework to explore general entrainment mechanisms as embodied in the human brain.	t	\N
25385777	Physiological rhythms are sensitive to social interactions and could contribute to defining social rhythms. Nevertheless, our knowledge of the implications of breathing in conversational turn exchanges remains limited. In this paper, we addressed the idea that breathing may contribute to timing and coordination between dialogue partners. The relationships between turns and breathing were analysed in unconstrained face-to-face conversations involving female speakers. No overall relationship between breathing and turn-taking rates was observed, as breathing rate was specific to the subjects' activity in dialogue (listening versus taking the turn versus holding the turn). A general inter-personal coordination of breathing over the whole conversation was not evident. However, specific coordinative patterns were observed in shorter time-windows when participants engaged in taking turns. The type of turn-taking had an effect on the respective coordination in breathing. Most of the smooth and interrupted turns were taken just after an inhalation, with specific profiles of alignment to partner breathing. Unsuccessful attempts to take the turn were initiated late in the exhalation phase and with no clear inter-personal coordination. Finally, breathing profiles at turn-taking were different than those at turn-holding. The results support the idea that breathing is actively involved in turn-taking and turn-holding.	t	\N
25401380	Interference between a target and simultaneous maskers occurs both at the cochlear level through energetic masking and more centrally through informational masking (IM). Hence, quantifying the amount of IM requires a strict control of the energetic component. Presenting target and maskers on different sides (i.e., dichotically) reduces energetic masking but provides listeners with important lateralization cues that also drastically reduce IM. The main purpose of this study (Experiment 1) was to evaluate a "switch" manipulation aiming at restoring most of the IM despite dichotic listening. Experiment 2 was designed to investigate the source of the difficulty induced by this switching dichotic condition. In Experiment 1, the authors presented 60 normal-hearing young adults with a detection task in which a regularly repeating target was embedded in a randomly varying background masker. The authors evaluated spatial masking release induced by three different dichotic listening conditions in comparison with a diotic baseline. Dichotic stimuli were presented in either a nonswitching or a switching condition. In the latter case, the presentation sides of dichotic target and maskers alternated several times throughout 10 sec sequences. The impact of the number of switches on IM was investigated parametrically, with both pure and complex tone sequences. In Experiment 2, the authors compared performance of 13 young, normal-hearing listeners in a monotic and dichotic version of the rapidly switching condition, using pure-tone sequences. When target and maskers switched rapidly within sequences, IM was significantly stronger than in nonswitching dichotic sequences and was comparable with the masking effect induced by diotic sequences. Furthermore, Experiment 2 suggests that rapidly switching target and maskers prevent listeners from relying on lateralization cues inherent to the dichotic condition, hence preserving important amounts of IM. This paradigm thus provides an original tool to isolate IM in signal and maskers having overlapping spectra.	t	\N
25412406	Speech comprehension studies have generally focused on the isolation and function of regions with positive blood oxygen level dependent (BOLD) signals with respect to a resting baseline. Although regions with negative BOLD signals in comparison to a resting baseline have been reported in language-related tasks, their relationship to regions of positive signals is not fully appreciated. Based on the emerging notion that the negative signals may represent an active function in language tasks, the authors test the hypothesis that negative BOLD signals during receptive language are more associated with comprehension than content-free versions of the same stimuli. Regions associated with comprehension of speech were isolated by comparing responses to passive listening to natural speech to two incomprehensible versions of the same speech: one that was digitally time reversed and one that was muffled by removal of high frequencies. The signal polarity was determined by comparing the BOLD signal during each speech condition to the BOLD signal during a resting baseline. As expected, stimulation-induced positive signals relative to resting baseline were observed in the canonical language areas with varying signal amplitudes for each condition. Negative BOLD responses relative to resting baseline were observed primarily in frontoparietal regions and were specific to the natural speech condition. However, the BOLD signal remained indistinguishable from baseline for the unintelligible speech conditions. Variations in connectivity between brain regions with positive and negative signals were also specifically related to the comprehension of natural speech. These observations of anticorrelated signals related to speech comprehension are consistent with emerging models of cooperative roles represented by BOLD signals of opposite polarity.	t	\N
25415467	To determine differences in speech perception outcomes for patients who received a CI422 and a Contour cochlear implant. Retrospective case review. Tertiary referral center. Thirty-two adults who underwent cochlear implantation. Cochlear implantation using a CI422 or Contour device. Bamford-Kowal-Bench (BKB) speech perception scores at 3 and 9 months after activation. The mean BKB scores at 3 months for the CI422 device were 86.0% in quiet and 55.1% in noise. This compares with 86.0% in quiet and 62.3% in noise for the Contour device. At 9 months, the mean BKB scores were 85.9% in quiet and 67.1% in noise for the CI422 and 90.1% in quiet and 77.6% in noise for the Contour device. There was no statistically significant difference (p > 0.05) between speech perception outcomes at 3 or 9 months. This study suggests that CI422 and Contour electrode both improve speech perception outcomes postoperatively, and there does not appear to be any significant difference in outcome between the two types of devices.	t	\N
25415938	Embodied music cognition stresses the role of the human body as mediator for the encoding and decoding of musical expression. In this paper, we set up a low dimensional functional model that accounts for 70% of the variability in the expressive body movement responses to music. With the functional principal component analysis, we modeled individual body movements as a linear combination of a group average and a number of eigenfunctions. The group average and the eigenfunctions are common to all subjects and make up what we call the commonalities. An individual performance is then characterized by a set of scores (the individualities), one score per eigenfunction. The model is based on experimental data which finds high levels of coherence/consistency between participants when grouped according to musical education. This shows an ontogenetic effect. Participants without formal musical education focus on the torso for the expression of basic musical structure (tempo). Musically trained participants decode additional structural elements in the music and focus on body parts having more degrees of freedom (such as the hands). Our results confirm earlier studies that different body parts move differently along with the music.	t	\N
25421408	Individuals lip read themselves more accurately than they lip read others when only the visual speech signal is available (Tye-Murray et al., Psychonomic Bulletin & Review, 20, 115-119, 2013). This self-advantage for vision-only speech recognition is consistent with the common-coding hypothesis (Prinz, European Journal of Cognitive Psychology, 9, 129-154, 1997), which posits (1) that observing an action activates the same motor plan representation as actually performing that action and (2) that observing one's own actions activates motor plan representations more than the others' actions because of greater congruity between percepts and corresponding motor plans. The present study extends this line of research to audiovisual speech recognition by examining whether there is a self-advantage when the visual signal is added to the auditory signal under poor listening conditions. Participants were assigned to sub-groups for round-robin testing in which each participant was paired with every member of their subgroup, including themselves, serving as both talker and listener/observer. On average, the benefit participants obtained from the visual signal when they were the talker was greater than when the talker was someone else and also was greater than the benefit others obtained from observing as well as listening to them. Moreover, the self-advantage in audiovisual speech recognition was significant after statistically controlling for individual differences in both participants' ability to benefit from a visual speech signal and the extent to which their own visual speech signal benefited others. These findings are consistent with our previous finding of a self-advantage in lip reading and with the hypothesis of a common code for action perception and motor plan representation.	t	\N
25436670	Sound waves emitted by two or more simultaneous sources reach the ear as one complex waveform. Auditory scene analysis involves parsing a complex waveform into separate perceptual representations of the sound sources [Bregman, A. S. Auditory scene analysis: The perceptual organization of sounds. London: MIT Press, 1990]. Harmonicity provides an important cue for auditory scene analysis. Normally, harmonics at integer multiples of a fundamental frequency are perceived as one sound with a pitch corresponding to the fundamental frequency. However, when one harmonic in such a complex, pitch-evoking sound is sufficiently mistuned, that harmonic emerges from the complex tone and is perceived as a separate auditory object. Previous work has shown that the percept of two objects is indexed in both children and adults by the object-related negativity component of the ERP derived from EEG recordings [Alain, C., Arnott, S. T., & Picton, T. W. Bottom-up and top-down influences on auditory scene analysis: Evidence from event-related brain potentials. Journal of Experimental Psychology: Human Perception and Performance, 27, 1072-1089, 2001]. Here we examine the emergence of object-related responses to an 8% harmonic mistuning in infants between 2 and 12 months of age. Two-month-old infants showed no significant object-related response. However, in 4- to 12-month-old infants, a significant frontally positive component was present, and by 8-12 months, a significant frontocentral object-related negativity was present, similar to that seen in older children and adults. This is in accordance with previous research demonstrating that infants younger than 4 months of age do not integrate harmonic information to perceive pitch when the fundamental is missing [He, C., Hotson, L., & Trainor, L. J. Maturation of cortical mismatch mismatch responses to occasional pitch change in early infancy: Effects of presentation rate and magnitude of change. Neuropsychologia, 47, 218-229, 2009]. The results indicate that the ability to use harmonic information to segregate simultaneous sounds emerges at the cortical level between 2 and 4 months of age.	t	\N
25445239	In this study we validate passive language fMRI protocols designed for clinical application in pediatric epilepsy surgical planning as they do not require overt participation from patients. We introduced a set of quality checks that assess reliability of noninvasive fMRI mappings utilized for clinical purposes. We initially compared two fMRI language mapping paradigms, one active in nature (requiring participation from the patient) and the other passive in nature (requiring no participation from the patient). Group-level analysis in a healthy control cohort demonstrated similar activation of the putative language centers of the brain in the inferior frontal (IFG) and temporoparietal (TPG) regions. Additionally, we showed that passive language fMRI produced more left-lateralized activation in TPG (LI=+0.45) compared to the active task; with similarly robust left-lateralized IFG (LI=+0.24) activations using the passive task. We validated our recommended fMRI mapping protocols in a cohort of 15 pediatric epilepsy patients by direct comparison against the invasive clinical gold-standards. We found that language-specific TPG activation by fMRI agreed to within 9.2mm to subdural localizations by invasive functional mapping in the same patients, and language dominance by fMRI agreed with Wada test results at 80% congruency in TPG and 73% congruency in IFG. Lastly, we tested the recommended passive language fMRI protocols in a cohort of very young patients and confirmed reliable language-specific activation patterns in that challenging cohort. We concluded that language activation maps can be reliably achieved using the passive language fMRI protocols we proposed even in very young (average 7.5 years old) or sedated pediatric epilepsy patients.	t	\N
25449865	Utilizing the high temporal resolution of event-related potentials (ERPs), we examined the effects of temporal reliability of sounds on visual detection. Significantly faster reaction times to visual target stimuli were observed when reliable temporal information was provided by a task-irrelevant auditory stimulus. Three main ERP components related to the effects of auditory temporal reliability were found: the first at 180-240 ms over a wide central area, the second at 300-400 ms over an anterior area, and the third at 300-380 ms over bilateral temporal areas. Our results support the hypothesis that temporal reliability affects visual detection and indicate that auditory facilitation of visual detection is partly due to spread of attention and thus results from implicit temporal linking of auditory and visual information at a relatively late processing stage.	t	\N
25473957	To examine the differences in quality of life for vestibular schwannoma patients undergoing conservative management, gamma knife, and surgery. Vestibular schwannoma patients without a diagnosis of NF2. Vestibular schwannoma treatment or conservative management. Penn Acoustic Neuroma Quality of Life (PANQOL) survey scores (0-100). One hundred eighty-six patients (98 conservative, 49 gamma knife, 39 surgery) were included. Mean patient age (years) of the surgery group (49 ± 14) was significantly younger than both the conservative (58 ± 13) and gamma knife group (59 ± 12) (p < 0.001). Mean follow-up time was 2.6 years.Tumor size (mm) was found to be significantly different between the conservative (8 ± 4.8), gamma knife (18 ± 5.9), and surgery (22 ± 8.3) groups (p < 0.001). Speech recognition threshold and speech discrimination percentage were significantly better for the conservative group compared to the gamma knife or surgery groups (p < 0.001).The hearing domain scores seemed better for the conservative group (62 ± 26) when compared to the surgery group (47 ± 25). The general and total domain scores were similar for all treatment groups, whereas the quality-of-life scores for gamma knife and surgery were similar. Although surgery groups' significantly larger tumors and worse hearing were apparent in specific PANQOL domains, all patients achieved a similar general level of quality of life.	t	\N
25474416	One of the major complaints of people with a single-sided deafness is the inability to localize sound sources. Evidence suggests that subjects with a hearing loss can benefit from the use of a cochlear implant (CI) in sound localization. This study aimed to determine the effect of CI use on localization ability in unilaterally deafened subjects. Sixteen adult subjects with postlingual unilateral deafness, fitted with a CI on the deaf side, were included in this study. The auditory speech sounds evaluation (A§E) localization test was used to determine localization with a CI on (binaural) and a CI off (monaural). The root mean square error was used as a measure of the subject's localization performance. Stratified analyses were performed to test the influence of gender, age of implantation (<55 years and >55 years), and the duration of deafness (<10 years and >10 years) on localization ability. Subjects with a CI on localized significantly better than without a CI. Gender, age, and the duration of deafness had no effect on the localization ability of the subjects. Cochlear implantation is effective in improving localization abilities in subjects with unilateral deafness. The root mean square error dropped significantly with binaural hearing compared to monaural hearing.	t	\N
25477777	For multimodal Human-Computer Interaction (HCI), it is very useful to identify the modalities on which the user is currently processing information. This would enable a system to select complementary output modalities to reduce the user's workload. In this paper, we develop a hybrid Brain-Computer Interface (BCI) which uses Electroencephalography (EEG) and functional Near Infrared Spectroscopy (fNIRS) to discriminate and detect visual and auditory stimulus processing. We describe the experimental setup we used for collection of our data corpus with 12 subjects. On this data, we performed cross-validation evaluation, of which we report accuracy for different classification conditions. The results show that the subject-dependent systems achieved a classification accuracy of 97.8% for discriminating visual and auditory perception processes from each other and a classification accuracy of up to 94.8% for detecting modality-specific processes independently of other cognitive activity. The same classification conditions could also be discriminated in a subject-independent fashion with accuracy of up to 94.6 and 86.7%, respectively. We also look at the contributions of the two signal types and show that the fusion of classifiers using different features significantly increases accuracy.	t	\N
25480056	Mounting evidence suggests that listeners perceptually compensate for the adverse effects of reverberation in rooms when listening to speech monaurally. However, it is not clear whether the underlying perceptual mechanism would be at all effective in the high levels of stimulus uncertainty that are present in everyday listening. Three experiments investigated monaural compensation with a consonant identification task in which listeners heard different speech on each trial. Consonant confusions frequently arose when a greater degree of reverberation was added to a test-word than to its surrounding context, but compensation became apparent in conditions where the context reverberation was increased to match that of the test-word; here, the confusions were largely resolved. A second experiment shows that information from the test-word itself can also effect compensation. Finally, the time course of compensation was examined by applying reverberation to a portion of the preceding context; consonant identification improves as this portion increases in duration. These findings indicate a monaural compensation mechanism that is likely to be effective in everyday listening, allowing listeners to recalibrate as their reverberant environment changes.	t	\N
25486827	Temporal summation in masking has been measured simultaneously with a resolution of the masker's spectral structure to find psychoacoustic characteristics for estimation of speech intelligibility, to detect the manifestation of peripheral processes in auditory perception in humans. For this, detection thresholds of a test signal with different durations were determined. The test signal was pulse with a Gaussian envelope and a sine-wave carrier. It was presented simultaneously with a noise masker. The minimal pulse duration was inversely proportional to width of the critical bands of hearing, formed at the pulse's center frequency. The maximal pulse duration always was 50 ms. We adopted pulses with duration of 1-10 ms as a model of consonants and pulses with duration of 20-50 ms as a model of vowels. The band pass noises with rippled structure of the amplitude spectrum of two types were used as maskers. The central frequency of one masker coincided with a spectral hump and the central frequency of the other--with the spectral failure. If the pulses and maskers central frequencies were equal, the first and second maskers were called on- and - off- maskers. If the auditory system could discriminate the rippled structure of the masker's spectra, the difference in the detection thresholds of the pulses, which was presented with each of the maskers, was not equal to zero. The difference in the detection thresholds allows us to estimate resolution of the masker's spectra, i.e. frequency selectivity. Changes in the pulse's and masker's central frequencies allow us to evaluate the hearing ability in certain frequency domain. Changes in the masker's levels allow us to find influence of nonlinear dynamic properties of cochlea on temporal summation and frequency selectivity. This paper presents the results of measurements of temporal summation in masking, obtained in two frequency domains 2 and 4 kHz, in 4 subjects with normal hearing and in 1 subject with age-related hearing loss, who complained about deterioration of speech intelligibility. It has been found an increasing temporal summation and an improving the resolution of the rippled structure of the amplitude spectra for the maskers with average levels. We believe, the reasons could be found in the properties of the peripheral pulse coding, such as (1) the stabilization zones of excitation of the basilar.membrane, the range of the characteristic frequencies and the number of excited auditory nerve fibers and the number ofspikes, generated by fibers, due to the nonlinearity of the dynamic properties of the cochlea, (2) increasing synchronization of a reaction of the excited fibers and shortening in time of this reaction, due to thefiber's refractory properties.	t	\N
25514452	Temporal processing ability has been linked to speech understanding ability and older adults often complain of difficulty understanding speech in difficult listening situations. Temporal processing can be evaluated using gap detection procedures. There is some research showing that gap detection can be evaluated using an electrophysiological procedure. However, there is currently no research establishing gap detection threshold using the N1-P2 response. The purposes of the current study were to 1) determine gap detection thresholds in younger and older normal-hearing adults using an electrophysiological measure, 2) compare the electrophysiological gap detection threshold and behavioral gap detection threshold within each group, and 3) investigate the effect of age on each gap detection measure. This study utilized an older adult group and younger adult group to compare performance on an electrophysiological and behavioral gap detection procedure. The subjects in this study were 11 younger, normal-hearing adults (mean = 22 yrs) and 11 older, normal-hearing adults (mean = 64.36 yrs). All subjects completed an adaptive behavioral gap detection procedure in order to determine their behavioral gap detection threshold (BGDT). Subjects also completed an electrophysiologic gap detection procedure to determine their electrophysiologic gap detection threshold (EGDT). Older adults demonstrated significantly larger gap detection thresholds than the younger adults. However, EGDT and BGDT were not significantly different in either group. The mean difference between EGDT and BGDT for all subjects was 0.43 msec. Older adults show poorer gap detection ability when compared to younger adults. However, this study shows that gap detection thresholds can be measured using evoked potential recordings and yield results similar to a behavioral measure.	t	\N
25517630	Auditory processing disorder patients may have deficits in auditory temporal resolution. This study explored: (1) the ear specific norms for young adults using the adaptive tests of temporal resolution (ATTR); (2) the reliability of ATTR using two different modes of stimuli presentation; and (3) the concurrent validity of ATTR with reference to the gaps-in-noise (GIN) test. GIN and ATTR were administered through a standard audiometer and headphones. As ATTR can also be completed using a computer with commercially available headphones, thresholds from these two variants were compared. Thirty normal-hearing young adults were recruited. The mean ATTR gap detection thresholds (GDTs) derived under audiometer administration were 4.60 ms (SD 1.49) and 4.97 ms (SD 1.98) for the left and right ear, respectively. The approximated threshold (A. th.), an equivalent measure to the GDT in the GIN, mean values were 5.37 ms (SD 0.98) and 5.33 ms (SD 1.07) for left and right ears, respectively. No significant threshold difference was found between the ATTR variants. A positive, moderate correlation was found, and Bland-Altman plot analysis revealed good agreement, between GDT and A.th. ATTR and GIN results were moderately associated. Moreover, the ATTR was found to have high test-retest reliability and high specificity for the current participants.	t	\N
25521593	A new approach for the segregation of monaural sound mixtures is presented based on the principle of temporal coherence and using auditory cortical representations. Temporal coherence is the notion that perceived sources emit coherently modulated features that evoke highly-coincident neural response patterns. By clustering the feature channels with coincident responses and reconstructing their input, one may segregate the underlying source from the simultaneously interfering signals that are uncorrelated with it. The proposed algorithm requires no prior information or training on the sources. It can, however, gracefully incorporate cognitive functions and influences such as memories of a target source or attention to a specific set of its attributes so as to segregate it from its background. Aside from its unusual structure and computational innovations, the proposed model provides testable hypotheses of the physiological mechanisms of this ubiquitous and remarkable perceptual ability, and of its psychophysical manifestations in navigating complex sensory environments.	t	\N
25534365	The temporal masking curve (TMC) method is a behavioral technique for inferring human cochlear compression. The method relies on the assumptions that in the absence of compression, forward-masking recovery is independent of masker level and probe frequency. The present study aimed at testing the validity of these assumptions. Masking recovery was investigated for eight listeners with sensorineural hearing loss carefully selected to have absent or nearly absent distortion product otoacoustic emissions. It is assumed that for these listeners basilar membrane responses are linear, hence that masking recovery is independent of basilar membrane compression. TMCs for probe frequencies of 0.5, 1, 2, 4, and 6 kHz were available for these listeners from a previous study. The dataset included TMCs for masker frequencies equal to the probe frequencies plus reference TMCs measured using a high-frequency probe and a low, off-frequency masker. All of the TMCs were fitted using linear regression, and the resulting slope and intercept values were taken as indicative of masking recovery and masker level, respectively. Results for on-frequency TMCs suggest that forward-masking recovery is generally independent of probe frequency and of masker level and hence that it would be reasonable to use a reference TMC for a high-frequency probe to infer cochlear compression at lower frequencies. Results further show, however, that reference TMCs were sometimes shallower than corresponding on-frequency TMCs for identical probe frequencies, hence that compression could be overestimated in these cases. We discuss possible reasons for this result and the conditions when it might occur.	t	\N
25536846	We explored the functional units of speech segmentation in Japanese using dichotic presentation and a detection task requiring no intentional sublexical analysis. Indeed, illusory perception of a target word might result from preattentive migration of phonemes, morae, or syllables from one ear to the other. In Experiment I, Japanese listeners detected targets presented in hiragana and/or kanji. Phoneme migrations did occur, suggesting that orthography-independent sublexical constituents play some role in segmentation. However, syllable and especially mora migrations were more numerous. This pattern of results was not observed in French speakers (Experiment 2), suggesting that it reflects native segmentation in Japanese. To control for the intervention of kanji representations (many words are written in kanji, and one kanji often corresponds to one syllable), in Experiment 3, Japanese listeners were presented with target loanwords that can be written only in katakana. Again, phoneme migrations occurred, while the first mora and syllable led to similar rates of illusory percepts. No migration occurred for the second, "special" mora (/J/ or/N/), probably because this constitutes the latter part of a heavy syllable. Overall, these findings suggest that multiple units, such as morae, syllables, and even phonemes, function independently of orthographic knowledge in Japanese preattentive speech segmentation.	t	\N
25546030	A study was conducted to determine whether modifications to input compression and input frequency response characteristics can improve music-listening satisfaction in cochlear implant users. Experiment 1 compared three pre-processed versions of music and speech stimuli in a laboratory setting: original, compressed, and flattened frequency response. Music excerpts comprised three music genres (classical, country, and jazz), and a running speech excerpt was compared. Experiment 2 implemented a flattened input frequency response in the speech processor program. In a take-home trial, participants compared unaltered and flattened frequency responses. Ten and twelve adult Nucleus Freedom cochlear implant users participated in Experiments 1 and 2, respectively. Experiment 1 revealed a significant preference for music stimuli with a flattened frequency response compared to both original and compressed stimuli, whereas there was a significant preference for the original (rising) frequency response for speech stimuli. Experiment 2 revealed no significant mean preference for the flattened frequency response, with 9 of 11 subjects preferring the rising frequency response. Input compression did not alter music enjoyment. Comparison of the two experiments indicated that individual frequency response preferences may depend on the genre or familiarity, and particularly whether the music contained lyrics.	t	\N
25556198	The auditory steady-state response, which measures the ability of neural ensembles to entrain to rhythmic auditory stimuli, has been used in human electroencephalogram studies to assess sensory processing and electrical oscillatory deficits. Patients with schizophrenia show a deficit in auditory steady-state response at 40 Hz, and therefore this may be a useful biomarker to study this disorder. We used auditory steady-state response recordings from the primary auditory cortex, hippocampus, and vertex electroencephalogram sites in awake behaving rats to determine whether pharmacological impairment of excitatory or inhibitory neurotransmission mimics auditory steady-state response abnormalities in schizophrenia. We found the most robust response to auditory stimuli in the primary auditory cortex, in line with previous studies suggesting this region is the primary generator of the auditory steady-state response in humans. Acute MK-801 (0.1mg/kg i.p.) increased primary auditory cortex intertrial coherence during auditory steady-state response at 20 and 40 Hz. Chronic MK-801 (21-day exposure at this daily dose) had no significant effect on 40-Hz auditory steady-state response. Furthermore, we found no effect of acute or chronic picrotoxin (a GABA-A antagonist) on intertrial coherence. Our data indicate that acute N-methyl-d-aspartate receptor antagonism increases synchronous activity in the primary auditory cortex in a frequency-specific manner, supporting the widely held view that acute N-methyl-d-aspartate antagonism augments gamma oscillations. Thus, rodent auditory steady-state response could be a valuable method to study the cortical ability to support synchronous activity at specific frequencies.	t	\N
25561538	Some of the psychological abilities that underlie human speech are shared with other species. One hallmark of speech is that linguistic context affects both how speech sounds are categorized into phonemes, and how different versions of phonemes are produced. We here confirm earlier findings that swamp sparrows categorically perceive the notes that constitute their learned songs and then investigate how categorical boundaries differ according to context. We clustered notes according to their acoustic structure, and found statistical evidence for clustering into 10 population-wide note types. Examining how three related types were perceived, we found, in both discrimination and labeling tests, that an "intermediate" note type is categorized with a "short" type when it occurs at the beginning of a song syllable, but with a "long" type at the end of a syllable. In sum, three produced note-type clusters appear to be underlain by two perceived categories. Thus, in birdsong, as in human speech, categorical perception is context-dependent, and as is the case for human phonology, there is a complex relationship between underlying categorical representations and surface forms. Our results therefore suggest that complex phonology can evolve even in the absence of rich linguistic components, like syntax and semantics.	t	\N
25565661	The objective of this study was to examine the hypothesis that between-channel gap detection, which includes between-frequency and between-ear gap detection, and perception of stop consonants, which is mediated by the length of voice-onset time (VOT), share common mechanisms, namely relative-timing operation in monitoring separate perceptual channels. The authors measured gap detection thresholds and identification functions of /ba/ and /pa/ along VOT in 49 native young adult Japanese listeners. There were three gap detection tasks. In the between-frequency task, the leading and trailing markers differed in terms of center frequency (Fc). The leading marker was a broadband noise of 10 to 20,000 Hz. The trailing marker was a 0.5-octave band-passed noise of 1000-, 2000-, 4000-, or 8000-Hz Fc. In the between-ear task, the two markers were spectrally identical but presented to separate ears. In the within-frequency task, the two spectrally identical markers were presented to the same ear. The /ba/-/pa/ identification functions were obtained in a task in which the listeners were presented synthesized speech stimuli of varying VOTs from 10 to 46 msec and asked to identify them as /ba/ or /pa/. The between-ear gap thresholds were significantly positively correlated with the between-frequency gap thresholds (except those obtained with the trailing marker of 4000-Hz Fc). The between-ear gap thresholds were not significantly correlated with the within-frequency gap thresholds, which were significantly correlated with all the between-frequency gap thresholds. The VOT boundaries and slopes of /ba/-/pa/ identification functions were not significantly correlated with any of these gap thresholds. There was a close relation between the between-ear and between-frequency gap detection, supporting the view that these two types of gap detection share common mechanisms of between-channel gap detection. However, there was no evidence for a relation between the perception of stop consonants and the between-frequency/ear gap detection in native Japanese speakers.	t	\N
25571013	Binaural beat (BB) illusions are experienced as continuous central pulsations when two sounds with slightly different frequencies are delivered to each ear. It has been shown that steady-state auditory evoked potentials (AEPs) to BBs can be captured and investigated. The authors recently developed a new method of evoking transient AEPs to binaural beats using frequency modulated stimuli. This methodology was able to create single BBs in predetermined intervals with varying carrier frequencies. This study examines the effects of the BB duration and the frequency modulating component of the stimulus on the binaural beats and their evoked potentials. Normal hearing subjects were tested with a set of four durations (25, 50, 100, and 200 ms) with two stimulation configurations, binaural dichotic (binaural beats) and diotic (frequency modulation). The results obtained from the study showed that out of the given durations, the 100 ms beat, was capable of evoking the largest amplitude responses. The frequency modulation effect showed a decrease in peak amplitudes with increasing beat duration until their complete disappearance at 200 ms. Even though, at 200 ms, the frequency modulation effects were not present, the binaural beats were still perceived and captured as evoked potentials.	t	\N
25571287	The pathologic auditory sensation in decompensated tinnitus patients is accompanied by the inability to habituate even temporary to this sound. This disability might originate from simultaneous activation of brain areas for the appraisal of the stimulus valence as, e.g., the limbic system. This coactivation of limbic areas is likely to modulate the degree and persistence of selective attention assigned to the tinnitus stream, which in turn could also explain interindividual differences in tinnitus loudness perception. Preliminary studies demonstrate that the amount of allocated attention and the habituation deficit can be mapped to changes in auditory late evoked responses (ALRs). Utilizing a numerical model for the simulation of ALRs we were able to predict a general habituation behavior in two patient groups with different degrees of tinnitus severity. Evaluating the instantaneous phase of simulated and measured ALRs by its von Mises concentration parameter, we verify a habituation deficit relative to the degree of decompensation and thus provide additional support for our neurofunctional model of limbic influences on neural processing of sensory information.	t	\N
25577901	People with one eye show altered sensory processing. Such changes might reflect a central reweighting of sensory information that might impact on how multisensory cues are integrated. We assessed whether people who lost an eye early in life differ from controls with respect to audiovisual integration. In order to quantify the relative weightings assigned to each sensory system, participants were asked to spatially localize audiovisual events that have been previously shown to be optimally combined and perceptually fused from the point of view of location in a normal population, where the auditory and visual components were spatially disparate. There was no difference in the variability of localizing unimodal visual and auditory targets by people with one eye compared to controls. People with one eye did however, demonstrate slower reaction times to localize visual stimuli compared to auditory stimuli and were slower than binocular and eye-patched control groups. When localizing bimodal targets, the weightings assigned to each sensory modality in both people with one eye and controls were predictable from their unimodal performance, in accordance with Maximum Likelihood Estimation and the time it took all three groups to localize the bimodal targets was faster than for vision alone. Regardless of demonstrating a longer response time to visual stimuli, people with one eye appear to integrate the auditory and visual components of multisensory events optimally when determining spatial location.	t	\N
25597464	There is a paucity of published studies examining how children with hearing loss understand speech over the telephone. Previous studies on adults with hearing aids have suggested that adults with bilateral hearing aids experience significant difficulty recognizing speech on the telephone when listening with one ear, but the provision of telephone input to both ears substantially improved speech understanding. The objectives of this study were to measure speech recognition in quiet and in noise for a group of older children with hearing loss over the telephone and to evaluate the effects of binaural hearing (e.g., DuoPhone) on speech recognition over the telephone. A cross-sectional, repeated-measures design was used in this study. A total of 14 children, ages 6-14 yr, participated in the study. Participants were obtained using convenience sampling from a nonprofit clinic population. Speech recognition in quiet and in noise with binaural versus monaural telephone input was compared in pediatric participants. Monosyllabic word recognition was assessed in quiet and classroom noise set at 50 dBA in conditions with monaural and binaural (DuoPhone) telephone input. The children's speech recognition in quiet and in noise was significantly better with binaural telephone input relative to monaural telephone input. To obtain optimal performance on the telephone, the following considerations may apply: (1) use of amplification with binaural streaming capabilities (e.g., DuoPhone), (2) counseling of family and children on how to best use the telephone, (3) provision of telecoil with microphone attenuation for improved signal-to-noise ratio, and (4) use of probe tube measures to verify the appropriateness of the telephone programs.	t	\N
25597465	In order to differentiate between a conductive hearing loss (CHL) and a sensorineural hearing loss (SNHL) in the hearing-impaired individual, we compared thresholds to air conduction (AC) and bone conduction (BC) auditory stimulation. The presence of a gap between these thresholds (an air-bone gap) is taken as a sign of a CHL, whereas similar threshold elevations reflect an SNHL. This is based on the assumption that BC stimulation directly excites the inner ear, bypassing the middle ear. However, several of the classic mechanisms of BC stimulation such as ossicular chain inertia and the occlusion effect involve middle ear structures. An additional mode of auditory stimulation, called soft tissue conduction (STC; also called nonosseous BC) has been demonstrated, in which the clinical bone vibrator elicits hearing when it is applied to soft tissue sites on the head, neck, and thorax. The purpose of this study was to assess the relative contributions of threshold determinations to stimulation by STC, in addition to AC and osseous BC, to the differential diagnosis between a CHL and an SNHL. Baseline auditory thresholds were determined in normal participants to AC (supra-aural earphones), BC (B71 bone vibrator at the mastoid, with 5 N application force), and STC (B71 bone vibrator) to the submental area and to the submandibular triangle with 5 N application force) stimulation in response to 0.5, 1.0, 2.0, and 4.0 kHz tones. A CHL was then simulated in the participants by means of an ear plug. Separately, an SNHL was simulated in these participants with 30 dB effective masking. STUDY SAMPLE consisted of 10 normal-hearing participants (4 males; 6 females, aged 20-30 yr). AC, BC, and STC thresholds were determined in the initial normal state and in the presence of each of the simulations. The earplug-induced CHL simulation led to a mean AC threshold elevation of 21-37 dB (depending on frequency), but not of BC and STC thresholds. The masking-induced SNHL led to a mean elevation of AC, BC, and STC thresholds (23-36 dB, depending on frequency). In each type of simulation, the BC threshold shift was similar to that of the STC threshold shift. These results, which show a similar threshold shift for STC and for BC as a result of these simulations, together with additional clinical and laboratory findings, provide evidence that BC thresholds likely represent the threshold of the nonosseous BC (STC) component of multicomponent BC at the BC stimulation site, and thereby succeed in clinical practice to contribute to the differential diagnosis. This also provides evidence that STC (nonosseous BC) stimulation at low intensities probably does not involve components of the middle ear, represents true cochlear function, and therefore can also contribute to a differential diagnosis (e.g., in situations where the clinical bone vibrator cannot be applied to the mastoid or forehead with a 5 N force, such as in severe skull fracture).	t	\N
25605693	Tetramethylpyrazine has been suggested to have a therapeutic effect on impaired hearing that is induced by aminoglycoside antibiotics. However, its effectiveness on streptomycin ototoxicity and its cellular mechanisms are relatively unknown. Here we investigate the protective effect of tetramethylpyrazine on streptomycin-induced ototoxicity in guinea pig cochlea. Prospective randomized laboratory study. Hearing Research Laboratory of China Medical University. Adult guinea pigs were randomized to 4 groups. Hearing sensitivity of guinea pigs was tested by auditory brainstem response measurements before streptomycin exposure and again 10 days later. The cochlear tissues were prepared for electron microscopy and immunohistochemical staining of heat shock protein 70 (HSP70). The effect of tetramethylpyrazine on streptomycin-induced activation of caspase-3 was evaluated by Western blotting. Co-therapy with tetramethylpyrazine reduced a profound streptomycin-induced auditory threshold shift compared with streptomycin treatment alone (P = .0002 or P = .00008). Tetramethylpyrazine also attenuated the structural disruption in streptomycin-treated outer hair cells and marginal cells of vascular stria by transmission electronic microscopy and scanning electronic microscopy, respectively. Moreover, tetramethylpyrazine decreased the streptomycin-stimulated expressions of HSP70 and caspase-3. The correlation analysis demonstrated that HSP70 expression had a positive correlation with auditory brainstem response thresholds (|R| = 0.6-0.9, P = .0073 or P = .0169). Our data suggest that the protective effect of tetramethylpyrazine on hearing function is associated with the reduction of stress response and inhibition of apoptosis. Tetramethylpyrazine may have therapeutic potential for patients with ototoxicity diseases.	t	\N
25611857	This study reviewed whether advanced age should be a consideration when revision cochlear implantation is warranted. To examine whether age at revision cochlear implantation is related to postrevision speech perception performance. A retrospective analysis was performed in an academic tertiary care center. Participants included 14 younger adults (<65 years) and 15 older adults (≥65 years) who underwent revision cochlear implantation. Revision cochlear implantation. Speech perception performance, as measured with consonant-nucleus-consonant [CNC] words in quiet, at the best prerevision interval as well as the 3- and 6-month postrevision intervals were compared between the 2 cohorts. The CNC word test consists of 10 lists of 50 phonemically balanced monosyllabic words, scored with a range of 0% to 100% correct. Both cohorts experienced a restoration in speech perception scores after revision cochlear implantation compared with their best performance before the revision (mean [SD] CNC word test scores for the younger cohort: 43.9% [25.6%] before revision and 47.7% [21.3%] at 3 months and 47.6% [19.8%] at 6 months after revision; for the older cohort: 36.3% [19.1%] before revision and 35.3% [17.2%] at 3 months and 39.9% [16.3%] at 6 months after revision; F₂,₅₄= 0.93; P = .40). There was no interaction between age at revision surgery and speech perception performance at each assessment interval (F₂,₅₄= 0.51; P = .60). In this study, age at revision cochlear implantation was not related to postrevision speech perception performance. Advanced age should not be considered a contraindication to revision cochlear implantation.	t	\N
25613931	To study electrical stimulation, auditory functionality, and language development in patients with inner ear malformations involving the anterior labyrinth who underwent cochlear implantation. Retrospective case review. Reference hospital for cochlear implantation. Review of 14 cases of severe hearing loss with major (common cavity deformity and cochlear hypoplasia) or minor (e.g., incomplete partition and basal turn aplasia) malformations. After cochlear implantation, data were gathered on the threshold (THR) and maximum comfort level (MCL) of the electrical stimulation and the number of functioning electrodes. Auditory responses to speech (EARS protocol) subtests were used to evaluate auditory functionality and language acquisition at 6, 12, and 24 months post-implantation. Tests used were: LIP profile, MTP (3, 6 and 12 words), OLD (open set test) and CLD (close set test). Results were compared with findings in a control group of 28 cochlear implantation patients without these malformations and with congenital hearing loss. The mean THR was 11.02μC in patients with malformations versus 3.5μC in those without, a significant difference. The THR also significantly differed between groups with major and minor malformations. Fewer functioning electrodes were used in patients with malformations. Auditory functionality scores were best in controls than in patients with malformations, who scored ≤50%, finding the lowest scores in those with major malformations. Patients with inner ear malformations undergoing cochlear implantation require greater stimuli to obtain an auditory response and have worse auditory functionality outcomes; these differences are greater in those with major versus minor malformations Nevertheless, cochlear implantation appears to be beneficial for all patients with these malformations to a greater or lesser extent.	t	\N
25617593	We examined 4- and 6-month-old infants' sensitivity to the perceptual association between pitch and object size. Crossmodal correspondence effects were observed in 6-month-old infants but not in younger infants, suggesting that experience and/or further maturation is needed to fully develop this crossmodal association.	t	\N
25618049	An acoustic survey of secondary schools in England has been undertaken. Room acoustic parameters and background noise levels were measured in 185 unoccupied spaces in 13 schools to provide information on the typical acoustic environment of secondary schools. The unoccupied acoustic and noise data were correlated with various physical characteristics of the spaces. Room height and the amount of glazing were related to the unoccupied reverberation time and therefore need to be controlled to reduce reverberation to suitable levels for teaching and learning. Further analysis of the unoccupied data showed that the introduction of legislation relating to school acoustics in England and Wales in 2003 approximately doubled the number of school spaces complying with current standards. Noise levels were also measured during 274 lessons to examine typical levels generated during teaching activities in secondary schools and to investigate the influence of acoustic design on working noise levels in the classroom. Comparison of unoccupied and occupied data showed that unoccupied acoustic conditions affect the noise levels occurring during lessons. They were also related to the time spent in disruption to the lessons (e.g., students talking or shouting) and so may also have an impact upon student behavior in the classroom.	t	\N
25618071	Listeners can use pitch changes in speech to identify talkers. Individuals exhibit large variability in sensitivity to pitch and in accuracy perceiving talker identity. In particular, people who have musical training or long-term tone language use are found to have enhanced pitch perception. In the present study, the influence of pitch experience on talker identification was investigated as listeners identified talkers in native language as well as non-native languages. Experiment 1 was designed to explore the influence of pitch experience on talker identification in two groups of individuals with potential advantages for pitch processing: musicians and tone language speakers. Experiment 2 further investigated individual differences in pitch processing and the contribution to talker identification by testing a mediation model. Cumulatively, the results suggested that (a) musical training confers an advantage for talker identification, supporting a shared resources hypothesis regarding music and language and (b) linguistic use of lexical tones also increases accuracy in hearing talker identity. Importantly, these two types of hearing experience enhance talker identification by sharpening pitch perception skills in a domain-general manner.	t	\N
25618091	This study reports a finding about vocal expressions of emotion in Mandarin Chinese. Production and perception experiments used the same tone and mixed tone sequences to test whether pitch variation is restricted due to the presence of lexical tones. Results showed that the restriction of pitch variation occurred in all high level tone sequences (tone 1 group) with the expression of happiness but did not happen for other dynamic tone groups. However, perception analysis revealed that all the emotions in every tone group received high identification rates; this indicates that listeners used other cues for encoding happiness in the tone 1 group. This study demonstrates that the restriction of pitch variation does not affect the perception of vocal emotions.	t	\N
25618101	Speech perception studies generally focus on the acoustic information present in the frequency regions below 6 kHz. Recent evidence suggests that there is perceptually relevant information in the higher frequencies, including information affecting speech intelligibility. This experiment examined whether listeners are able to accurately identify a subset of vowels and consonants in CV-context when only high-frequency (above 5 kHz) acoustic information is available (through high-pass filtering and masking of lower frequency energy). The findings reveal that listeners are capable of extracting information from these higher frequency regions to accurately identify certain consonants and vowels.	t	\N
25628152	The aim of the present study was to investigate whether the saliency effect for word beginnings reported in children with dyslexia (Marshall & Van der Lely, 2009) can be found also in typically developing children. Thirty-four typically developing Italian children aged 8-10 years completed two specifically designed tasks: a production task and a perception task. Both tasks used nonwords containing clusters consisting of plosive plus liquid (e.g. pl). Clusters could be either in a stressed or in an unstressed syllable and could be either in initial position (first syllable) or in medial position (second syllable). In the production task, children were asked to repeat the nonwords. In the perception task, the children were asked to discriminate between two nonwords differing in one phoneme belonging to a cluster by reporting whether two repetitions were the same or different. Results from the production task showed that children are more accurate in repeating stressed than unstressed syllables, but there was no difference with respect to position of the cluster. Results from the perception task showed that children performed more accurately when discriminating word initial contrasts than when discriminating word medial contrasts, especially if the cluster was unstressed. Implications of this finding for clinical assessments are discussed.	t	\N
25630393	The objective of this study was to test if stimulating multiple electrodes can improve temporal pitch ranking performance at low and high stimulation rates. Temporal pitch cues are usually based on modifying the stimulation rate of the implant and thereby provide a continuum of pitches on a single electrode up to approximately 300 Hz. Ten cochlear implant subjects were asked to pitch rank stimuli presented with direct electrical stimulation. The pulses were applied on one, three, six, or eleven electrodes. In one of the conditions the current amplitude of each pulse was randomly varied between 0 and 100%. Their frequency ranged from 100 up to 500 pps. Listeners showed the previously reported performance pattern in most conditions with very good performance at the lowest standard rates and deteriorating performance to near chance level at the highest rate tested. Performance with eleven electrodes was significantly better than performance with one electrode at 500 pps. Stimulating on multiple electrodes can improve temporal pitch perception.	t	\N
25634776	To compare some perceptual and acoustic characteristics of the voices of children who use the advanced combination encoder (ACE) or fine structure processing (FSP) speech coding strategies, and to investigate whether these characteristics differ from children with normal hearing. Acoustic analysis of the sustained vowel /a/ was performed using the multi-dimensional voice program (MDVP). Analyses of sequential and spontaneous speech were performed using the real time pitch. Perceptual analyses of these samples were performed using visual-analogic scales of pre-selected parameters. Seventy-six children from three years to five years and 11 months of age participated. Twenty-eight were users of ACE, 23 were users of FSP, and 25 were children with normal hearing. Although both groups with CI presented with some deviated vocal features, the users of ACE presented with voice quality more like children with normal hearing than the users of FSP. Sound processing of ACE appeared to provide better conditions for auditory monitoring of the voice, and consequently, for better control of the voice production. However, these findings need to be further investigated due to the lack of comparative studies published to understand exactly which attributes of sound processing are responsible for differences in performance.	t	\N
25636271	The major purpose of this study was to explore the changes in the local/global gamma-band neural synchronies during target/non-target processing due to task difficulty under an auditory three-stimulus oddball paradigm. Multichannel event-related potentials (ERPs) were recorded from fifteen healthy participants during the oddball task. In addition to the conventional ERP analysis, we investigated the modulations in gamma-band activity (GBA) and inter-regional gamma-band phase synchrony (GBPS) for infrequent target and non-target processing due to task difficulty. The most notable finding was that the difficulty-related changes in inter-regional GBPS (33-35 Hz) at P300 epoch (350-600 ms) completely differed for target and non-target processing. As task difficulty increased, the GBPS significantly reduced for target processing but increased for non-target processing. This result contrasts with the local neural synchrony in gamma-bands, which was not affected by task difficulty. Another major finding was that the spatial patterns of functional connectivity were dissociated for target and non-target processing with regard to the difficult task. The spatial pattern for target processing was compatible with the top-down attention network, whereas that for the non-target corresponded to the bottom-up attention network. Overall, we found that the inter-regional gamma-band neural synchronies during target/non-target processing change significantly with task difficulty and that this change is dissociated between target and non-target processing. Our results indicate that large-scale neural synchrony is more relevant for the difference in information processing between target and non-target stimuli.	t	\N
25638938	When one hears footsteps in the hall, one is able to instantly recognise it as a person: this is an everyday example of auditory biological motion perception. Despite the familiarity of this experience, research into this phenomenon is in its infancy compared with visual biological motion perception. Here, two experiments explored sensitivity to, and recognition of, auditory stimuli of biological and nonbiological origin. We hypothesised that the cadence of a walker gives rise to a temporal pattern of impact sounds that facilitates the recognition of human motion from auditory stimuli alone. First a series of detection tasks compared sensitivity with three carefully matched impact sounds: footsteps, a ball bouncing, and drumbeats. Unexpectedly, participants were no more sensitive to footsteps than to impact sounds of nonbiological origin. In the second experiment participants made discriminations between pairs of the same stimuli, in a series of recognition tasks in which the temporal pattern of impact sounds was manipulated to be either that of a walker or the pattern more typical of the source event (a ball bouncing or a drumbeat). Under these conditions, there was evidence that both temporal and nontemporal cues were important in recognising theses stimuli. It is proposed that the interval between footsteps, which reflects a walker's cadence, is a cue for the recognition of the sounds of a human walking.	t	\N
25646513	Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing.	t	\N
25653354	Perceptual phase entrainment improves speech intelligibility by phase-locking the brain's high-excitability and low-excitability phases to relevant or irrelevant events in the speech input. However, it remains unclear whether phase entrainment to speech can be explained by a passive "following" of rhythmic changes in sound amplitude and spectral content or whether entrainment entails an active tracking of higher-level cues: in everyday speech, rhythmic fluctuations in low-level and high-level features always covary. Here, we resolve this issue by constructing novel speech/noise stimuli with intelligible speech but without systematic changes in sound amplitude and spectral content. The probability of detecting a tone pip, presented to human listeners at random moments during our speech/noise stimuli, was significantly modulated by the rhythmic changes in high-level information. Thus, perception can entrain to the speech rhythm even without concurrent fluctuations in sound amplitude or spectral content. Strikingly, the actual entrainment phase depended on the tone-pip frequency, with tone pips within and beyond the principal frequency range of the speech sound modulated in opposite fashion. This result suggests that only those neural populations processing the actually presented frequencies are set to their high-excitability phase, whereas other populations are entrained to the opposite, low-excitability phase. Furthermore, we show that the perceptual entrainment is strongly reduced when speech intelligibility is abolished by presenting speech/noise stimuli in reverse, indicating that linguistic information plays an important role for the observed perceptual entrainment.	t	\N
25656953	This study investigated the sensitivity of 9-month-old infants to the alignment between prosodic and gesture prominences in pointing-speech combinations. Results revealed that the perception of prominence is multimodal and that infants are aware of the timing of gesture-speech combinations well before they can produce them.	t	\N
25665752	This study compared the timing of appearance of three components of age-related hearing loss that determine the pattern and severity of presbycusis: the functional and structural pathologies of sensory cells and neurons and changes in gap detection (GD), the latter as an indicator of auditory temporal processing. Using UM-HET4 mice, genetically heterogeneous mice derived from four inbred strains, we studied the integrity of inner and outer hair cells by position along the cochlear spiral, inner hair cell-auditory nerve connections, spiral ganglion neurons (SGN), and determined auditory thresholds, as well as pre-pulse and gap inhibition of the acoustic startle reflex (ASR). Comparisons were made between mice of 5-7, 22-24 and 27-29 months of age. There was individual variability among mice in the onset and extent of age-related auditory pathology. At 22-24 months of age a moderate to large loss of outer hair cells was restricted to the apical third of the cochlea and threshold shifts in the auditory brain stem response were minimal. There was also a large and significant loss of inner hair cell-auditory nerve connections and a significant reduction in GD. The expression of Ntf3 in the cochlea was significantly reduced. At 27-29 months of age there was no further change in the mean number of synaptic connections per inner hair cell or in GD, but a moderate to large loss of outer hair cells was found across all cochlear turns as well as significantly increased ABR threshold shifts at 4, 12, 24 and 48 kHz. A statistical analysis of correlations on an individual animal basis revealed that neither the hair cell loss nor the ABR threshold shifts correlated with loss of GD or with the loss of connections, consistent with independent pathological mechanisms.	t	\N
25669257	Individual factors beyond the audiogram, such as age and cognitive abilities, can influence speech intelligibility and speech quality judgments. This paper develops a neural network framework for combining multiple subject factors into a single model that predicts speech intelligibility and quality for a nonlinear hearing-aid processing strategy. The nonlinear processing approach used in the paper is frequency compression, which is intended to improve the audibility of high-frequency speech sounds by shifting them to lower frequency regions where listeners with high-frequency loss have better hearing thresholds. An ensemble averaging approach is used for the neural network to avoid the problems associated with overfitting. Models are developed for two subject groups, one having nearly normal hearing and the other mild-to-moderate sloping losses.	t	\N
25673838	Critical periods are developmental windows during which the stimuli an animal encounters can reshape response properties in the affected system to a profound degree. Despite this window's importance, the neural mechanisms that regulate it are not completely understood. Pioneering studies in visual cortex initially indicated that norepinephrine (NE) permits ocular dominance column plasticity during the critical period, but later research has suggested otherwise. More recent work implicating NE in experience-dependent plasticity in the adult auditory cortex led us to re-examine the role of NE in critical period plasticity. Here, we exposed dopamine β-hydroxylase knock-out (Dbh(-/-)) mice, which lack NE completely from birth, to a biased acoustic environment during the auditory cortical critical period. This manipulation led to a redistribution of best frequencies (BFs) across auditory cortex in our control mice, consistent with prior work. By contrast, Dbh(-/-) mice failed to exhibit the expected redistribution of BFs, even though NE-deficient and NE-competent mice showed comparable auditory cortical organization when reared in a quiet colony environment. These data suggest that while intrinsic tonotopic patterning of auditory cortical circuitry occurs independently from NE, NE is required for critical period plasticity in auditory cortex.	t	\N
25685775	The aim of this research was to analyze temporal auditory processing and phonological awareness in school-age children with benign childhood epilepsy with centrotemporal spikes (BECTS). Patient group (GI) consisted of 13 children diagnosed with BECTS. Control group (GII) consisted of 17 healthy children. After neurological and peripheral audiological assessment, children underwent a behavioral auditory evaluation and phonological awareness assessment. The procedures applied were: Gaps-in-Noise test (GIN), Duration Pattern test, and Phonological Awareness test (PCF). Results were compared between the groups and a correlation analysis was performed between temporal tasks and phonological awareness performance. GII performed significantly better than the children with BECTS (GI) in both GIN and Duration Pattern test (P < 0.001). GI performed significantly worse in all of the 4 categories of phonological awareness assessed: syllabic (P = 0.001), phonemic (P = 0.006), rhyme (P = 0.015) and alliteration (P = 0.010). Statistical analysis showed a significant positive correlation between the phonological awareness assessment and Duration Pattern test (P < 0.001). From the analysis of the results, it was concluded that children with BECTS may have difficulties in temporal resolution, temporal ordering, and phonological awareness skills. A correlation was observed between auditory temporal processing and phonological awareness in the suited sample.	t	\N
25693304	When we interact with objects in our environment, as a general rule we are not aware of the proximal stimulation they provide, but we directly experience the external object. This process of assigning an external cause is known as distal attribution. It is extremely difficult to measure how distal attribution emerges because it arises so early in life and appears to be automatic. Sensory substitution systems give us the possibility to measure the process as it occurs online. With these devices, objects in our environment produce novel proximal stimulation patterns and individuals have to establish the link between the proximal stimulation and the distal object. This review disentangles the contributing factors that allow the nervous system to assign a distal cause, thereby creating the experience of an external world. In particular, it highlights the role of the assumption of a stable world, the role of movement, and finally that of calibration. From the existing sensory substitution literature it appears that distal attribution breaks down when one of these principles is violated and as such the review provides an important piece to the puzzle of distal attribution.	t	\N
25698006	The present study investigated the possibility that the human auditory system demonstrates frequency selectivity to spectro-temporal amplitude modulations. Threshold modulation depth for detecting sinusoidal spectro-temporal modulations was measured using a generalized masked threshold pattern paradigm with narrowband masker modulations. Four target spectro-temporal modulations were examined, differing in their temporal and spectral modulation frequencies: a temporal modulation of -8, 8, or 16 Hz combined with a spectral modulation of 1 cycle/octave and a temporal modulation of 4 Hz combined with a spectral modulation of 0.5 cycles/octave. The temporal center frequencies of the masker modulation ranged from 0.25 to 4 times the target temporal modulation. The spectral masker-modulation center-frequencies were 0, 0.5, 1, 1.5, and 2 times the target spectral modulation. For all target modulations, the pattern of average thresholds for the eight normal-hearing listeners was consistent with the hypothesis of a spectro-temporal modulation filter. Such a pattern of modulation-frequency sensitivity was predicted on the basis of psychoacoustical data for purely temporal amplitude modulations and purely spectral amplitude modulations. An analysis of separability indicates that, for the present data set, selectivity in the spectro-temporal modulation domain can be described by a combination of a purely spectral and a purely temporal modulation filter function.	t	\N
25721795	Music and speech are skills that require high temporal precision of motor output. A key question is how humans achieve this timing precision given the poor temporal resolution of somatosensory feedback, which is classically considered to drive motor learning. We hypothesise that auditory feedback critically contributes to learn timing, and that, similarly to visuo-spatial learning models, learning proceeds by correcting a proportion of perceived timing errors. Thirty-six participants learned to tap a sequence regularly in time. For participants in the synchronous-sound group, a tone was presented simultaneously with every keystroke. For the jittered-sound group, the tone was presented after a random delay of 10-190 ms following the keystroke, thus degrading the temporal information that the sound provided about the movement. For the mute group, no keystroke-triggered sound was presented. In line with the model predictions, participants in the synchronous-sound group were able to improve tapping regularity, whereas the jittered-sound and mute group were not. The improved tapping regularity of the synchronous-sound group also transferred to a novel sequence and was maintained when sound was subsequently removed. The present findings provide evidence that humans engage in auditory feedback error-based learning to improve movement quality (here reduce variability in sequence tapping). We thus elucidate the mechanism by which high temporal precision of movement can be achieved through sound in a way that may not be possible with less temporally precise somatosensory modalities. Furthermore, the finding that sound-supported learning generalises to novel sequences suggests potential rehabilitation applications.	t	\N
25724819	Older adults, even with clinically normal hearing sensitivity, often report difficulty understanding speech in the presence of background noise. Part of this difficulty may be related to age-related degradations in the neural representation of speech sounds, such as formant transitions. Frequency-following responses (FFRs), which are dependent on phase-locked neural activity, were elicited using sounds consisting of linear frequency sweeps, which may be viewed as simple models of formant transitions. Eighteen adults (ten younger, 22-24 years old, and nine older, 51-67 years old) were tested. FFRs were elicited by tonal sweeps in six conditions. Two directions of frequency change, rising or falling, were used for each of three rates of frequency change. Stimulus-to-response cross correlations revealed that older adults had significantly poorer representation of the tonal sweeps, and that FFRs became poorer for faster rates of change. An additional FFR signal-to-noise ratio analysis based on time windows revealed that across the FFR waveforms and rates of frequency change, older adults had smaller (poorer) signal-to-noise ratios. These results indicate that older adults, even with clinically-normal hearing sensitivity, have degraded phase-locked neural representations of dynamic frequency.	t	\N
25726264	Speech is a complex acoustic signal showing a quasiperiodic structure at several timescales. Integrated neural signals recorded in the cortex also show periodicity at different timescales. In this chapter we outline the neural mechanisms that potentially allow the auditory cortex to segment and encode continuous speech. This chapter focuses on how the human auditory cortex uses the temporal structure of the acoustic signal to extract phonemes and syllables, the two major constituents of connected speech. We argue that the quasiperiodic structure of collective neural activity in auditory cortex represents the ideal mechanical infrastructure to fractionate continuous speech into linguistic constituents of variable sizes.	t	\N
25726287	Neural disorders of the auditory nerve are associated with particular disorders of auditory perceptions dependent on processing of acoustic temporal cues. These include: (1) speech perception; (2) localizing a sound's origin in space; and (3) identifying sounds in background noise. Auditory neuropathy (AN) is a consequence of: (1) presynaptic disorders affecting inner hair cell ribbon synapses; (2) postsynaptic disorders of auditory nerve dendrites; and (3) postsynaptic disorders of auditory nerve axons. The etiologies of these disorders are diverse, similar to other cranial or peripheral neuropathies. The pathologies cause attenuated and dyssynchronous auditory nerve discharges. Therapies and management of patients with AN are reviewed.	t	\N
25726290	Neglect is a neurologic disorder, typically associated with lesions of the right hemisphere, in which patients are biased towards their ipsilesional - usually right - side of space while awareness for their contralesional - usually left - side is reduced or absent. Neglect is a multimodal disorder that often includes deficits in the auditory domain. Classically, auditory extinction, in which left-sided sounds that are correctly perceived in isolation are not detected in the presence of synchronous right-sided stimulation, has been considered the primary sign of auditory neglect. However, auditory extinction can also be observed after unilateral auditory cortex lesions and is thus not specific for neglect. Recent research has shown that patients with neglect are also impaired in maintaining sustained attention, on both sides, a fact that is reflected by an impairment of auditory target detection in continuous stimulation conditions. Perhaps the most impressive auditory symptom in full-blown neglect is alloacusis, in which patients mislocalize left-sided sound sources to their right, although even patients with less severe neglect still often show disturbance of auditory spatial perception, most commonly a lateralization bias towards the right. We discuss how these various disorders may be explained by a single model of neglect and review emerging interventions for patient rehabilitation.	t	\N
25730449	To assess whether recombinant growth factor (hGH) therapy has an effect on cochlear implant (CI) performance. Two pediatric CI recipients (S1, S2) who underwent treatment with hGH for short stature were identified for review. S1 has bilateral labyrinthine dysplasia and received implants at ages 10 months (right) and 4 years 3 months (left). S2 was diagnosed with severe to progressive sensorineural hearing loss bilaterally and received a CI at age 9 years 10 months (left). Case series. Cochlear implant, hGH, and speech perception data were collected. Phonetically Balanced Kindergarten (PBK) and Consonant Nucleus Consonant (CNC) word recognition scores were reviewed to assess auditory perception. Electrode impedances, threshold levels, and comfort levels were also reviewed. After 4 months of hGH, word recognition scores for S1 were observed to decrease from 90 to 72% (right) and were stable at 40% (left). Despite troubleshooting, performance continued to decline bilaterally to 52% (right) and 28% (left), and the decision was made to discontinue hGH. One month after cessation of hGH, word recognition scores began improving to 74% (right) and 68% (left). Word recognition scores for S2 were observed to have decreased from 92% the previous year to 82% after taking hGH for 2 months. Given both our previous experience with S1 and discussions with S2's parents, hGH was discontinued after 10 months of therapy. Two months after cessation of hGH, S2's word recognition had improved to 86% (left). Our case studies illustrate that implanted children undergoing treatment with hGH may experience a decrease in speech perception, which recovers after the cessation of treatment. Since hGH use has become more prevalent in recent years, it is important to inquire whether children undergoing, or who have undergone, implantation are receiving hGH so that they may be appropriately monitored.	t	\N
25731581	While potentially improving audibility for listeners with considerable high frequency hearing loss, the effects of implementing nonlinear frequency compression (NFC) for listeners with moderate high frequency hearing loss are unclear. The purpose of this study was to investigate the effects of activating NFC for listeners who are not traditionally considered candidates for this technology. Participants wore study hearing aids with NFC activated for a 3-4 week trial period. After the trial period, they were tested with NFC and with conventional processing on measures of consonant discrimination threshold in quiet, consonant recognition in quiet, sentence recognition in noise, and acceptableness of sound quality of speech and music. Seventeen adult listeners with symmetrical, mild to moderate sensorineural hearing loss participated. Better ear, high frequency pure-tone averages (4, 6, and 8 kHz) were 60 dB HL or better. Activating NFC resulted in lower (better) thresholds for discrimination of /s/, whose spectral center was 9 kHz. There were no other significant effects of NFC compared to conventional processing. These data suggest that the benefits, and detriments, of activating NFC may be limited for this population.	t	\N
25731582	To evaluate wideband amplification and non-linear frequency compression (NLFC) as a means to improve speech recognition for children with mild/moderate hearing loss. Randomized within-subject design with repeated measures across test conditions. Eleven children with mild to moderate hearing loss were evaluated with: (1) Phonak BTE without NLFC, (2) Phonak BTE with NLFC, and (3) Oticon BTE with wideband response extending to 8000 Hz. Use of NLFC provided better detection and recognition of high-frequency stimuli (e.g. /sh/ and /s/). No difference in performance between conditions was observed for speech recognition when measured with the University of Western Ontario (UWO) plurals test and the UWO distinctive features difference test. Finally, there were no differences between conditions on the BKB-SIN test. Children with mild to moderate hearing loss have good access to high-frequency phonemes presented at fixed levels (e.g. 50 to 60 dBA) with both wideband and NLFC technology. Similarly, sentence recognition in noise was similar with wideband and NLFC. Adaptive test procedures that probe performance at lower input levels showed small but significant improvements in the detection and recognition of the phonemes /s/ and /sh/ with NLFC condition when compared to the NLFC Off and wideband conditions.	t	\N
25733362	With the growing number of older adults receiving cochlear implants (CI), there is general agreement that substantial benefits can be gained. Nonetheless, variability in speech perception performance is high, and the relative contribution and interactions among peripheral, central-auditory, and cognitive factors are not fully understood. The goal of the present study was to compare auditory-cognitive processing in older-adult CI recipients with that of older normal-hearing (NH) listeners by means of behavioral and electrophysiologic manifestations of a high-load cognitive task. Auditory event-related potentials (AERPs) were recorded from 9 older postlingually deafened adults with CI (age at CI >60) and 10 age-matched listeners with NH, while performing an auditory Stroop task. Participants were required to classify the speaker's gender (male/female) that produced the words 'mother' or 'father' while ignoring the irrelevant congruent or incongruent word meaning. Older CI and NH listeners exhibited comparable reaction time, performance accuracy, and initial sensory-perceptual processing (i.e. N1 potential). Nonetheless, older CI recipients showed substantially prolonged and less efficient perceptual processing (i.e. P3 potential). Congruency effects manifested in longer reaction time (i.e. Stroop effect), execution time, and P3 latency to incongruent versus congruent stimuli in both groups in a similar fashion; however, markedly prolonged P3 and shortened execution time were evident in older CI recipients. Collectively, older adults (CI and NH) employed a combined perceptual and postperceptual conflict processing strategy; nonetheless, the relative allotment of perceptual resources was substantially enhanced to maintain adequate performance in CI recipients. In sum, the recording of AERPs together with the simultaneously obtained behavioral measures during a Stroop task exposed a differential time course of auditory-cognitive processing in older CI recipients that was not manifested in the behavioral end products of processing. These data may have implications regarding clinical evaluation and rehabilitation procedures that should be tailored specifically for this unique group of patients.	t	\N
25734571	This study assesses attention and response control through visual and auditory stimuli in a primary care pediatric sample. The sample consisted of 191 participants aged between 7 and 13 years old. It was divided into 2 groups: (a) 90 children with ADHD, according to diagnostic (DSM-IV-TR) (APA, 2002) and clinical (ADHD Rating Scale-IV) (DuPaul, Power, Anastopoulos, & Reid, 1998) criteria, and (b) 101 children without a history of ADHD. The aims were: (a) to determine and compare the performance of both groups in attention and response control, (b) to identify attention and response control deficits in the ADHD group. Assessments were carried out using the Integrated Visual and Auditory Continuous Performance Test (IVA/CPT, Sandford & Turner, 2002). Results showed that the ADHD group had visual and auditory attention deficits, F(3, 170) = 14.38; p < .01, deficits in fine motor regulation (Welch´s t-test = 44.768; p < .001) and sensory/motor activity (Welch'st-test = 95.683, p < .001; Welch's t-test = 79.537, p < .001). Both groups exhibited a similar performance in response control, F(3, 170) = .93, p = .43.Children with ADHD showed inattention, mental processing speed deficits, and loss of concentration with visual stimuli. Both groups yielded a better performance in attention with auditory stimuli.	t	\N
25740521	Speech recognition in noise can be challenging for older adults and elicits elevated activity throughout a cingulo-opercular network that is hypothesized to monitor and modify behaviors to optimize performance. A word recognition in noise experiment was used to test the hypothesis that cingulo-opercular engagement provides performance benefit for older adults. Healthy older adults (N = 31; 50-81 years of age; mean pure tone thresholds <32 dB HL from 0.25 to 8 kHz, best ear; species: human) performed word recognition in multitalker babble at 2 signal-to-noise ratios (SNR = +3 or +10 dB) during a sparse sampling fMRI experiment. Elevated cingulo-opercular activity was associated with an increased likelihood of correct recognition on the following trial independently of SNR and performance on the preceding trial. The cingulo-opercular effect increased for participants with the best overall performance. These effects were lower for older adults compared with a younger, normal-hearing adult sample (N = 18). Visual cortex activity also predicted trial-level recognition for the older adults, which resulted from discrete decreases in activity before errors and occurred for the oldest adults with the poorest recognition. Participants demonstrating larger visual cortex effects also had reduced fractional anisotropy in an anterior portion of the left inferior frontal-occipital fasciculus, which projects between frontal and occipital regions where activity predicted word recognition. Together, the results indicate that older adults experience performance benefit from elevated cingulo-opercular activity, but not to the same extent as younger adults, and that declines in attentional control can limit word recognition.	t	\N
25770375	Arthur Lessac developed a voice training approach that concentrated on three energies: structural action, tonal action, and consonant action. In Lessac-Madsen Resonant Voice Therapy (LMRVT), speech-language pathologists help patients achieve a resonant voice through structural posturing and awareness of tonal changes. However, LMRVT many not necessarily include the third component of Lessac's approach: consonant action.This study examines the effect that increased effort on consonant production has on the speaking voice-particularly regarding vocal loudness and projection. Audio samples were collected from eight actor participants who read a monologue using three distinct styles: normal articulation, poor articulation (elicited using a bite block), and overarticulation (elicited using a Lessac-based training intervention). Twenty graduate students of speech-language pathology listened to speech samples from the different conditions and made comparative judgments regarding articulation, loudness, and projection. Group results showed a strong correlation between the articulatory condition and the level of perceived loudness and projection. That is, as precision of articulation increased, the ratings of perceived loudness and projection increased, as well. These findings indicate that articulation treatment may have a positive influence on the perception of vocal loudness and projection. This has implications for future directions in expanding voice therapy modalities.	t	\N
25773636	Most people derive pleasure from music. Neuroimaging studies show that the reward system of the human brain is central to this experience. Specifically, the dorsal and ventral striatum release dopamine when listening to pleasurable music, and activity in these structures also codes the reward value of musical excerpts. Moreover, the striatum interacts with cortical mechanisms involved in perception and valuation of musical stimuli. Recent studies have begun to explore individual differences in the way that this complex system functions. Development of a questionnaire for music reward experiences has allowed the identification of separable factors associated with musical pleasure, described as music-seeking, emotion-evocation, mood regulation, sensorimotor, and social factors. Applying this questionnaire to a large sample uncovered approximately 5% of the population with low sensitivity to musical reward in the absence of generalized anhedonia or depression. Further study of this group revealed that there are individuals who respond normally both behaviorally and psychophysiologically to rewards other than music (e.g., monetary value) but do not experience pleasure from music despite normal music perception ability and preserved ability to identify intended emotions in musical passages. This specific music anhedonia bears further study, as it may shed light on the function and dysfunction of the reward system.	t	\N
25774428	The perception of near-threshold visual stimuli has been shown to depend in part on the phase (i.e., time in the cycle) of ongoing alpha (8-13 Hz) oscillations in the visual cortex relative to the onset of that stimulus. However, it is currently unknown whether the phase of the ongoing alpha activity can be manipulated by top-down factors such as attention or expectancy. Using three variants of a cross-modal attention paradigm with constant predictable stimulus onsets, we examined if cues signaling to attend to either the visual or the auditory domain influenced the phase of alpha oscillations in the associated sensory cortices. Importantly, intermixed in all three experiments, we included trials without a target to estimate the phase at target presentation without contamination from the early evoked responses. For these blank trials, at the time of expected target and distractor onset, we examined (1) the degree of the uniformity in phase angles across trials, (2) differences in phase angle uniformity compared with a pretarget baseline, and (3) phase angle differences between visual and auditory target conditions. Across all three experiments, we found that, although the cues induced a modulation in alpha power in occipital electrodes, neither the visual condition nor the auditory cue condition induced any significant phase-locking across trials during expected target or distractor presentation. These results suggest that, although alpha power can be modulated by top-down factors such as attention and expectation, the phase of the ongoing alpha oscillation is not under such control.	t	\N
25774653	The effect of stimulation history on the perception of a current event can yield two opposite effects, namely: adaptation or hysteresis. The perception of the current event thus goes in the opposite or in the same direction as prior stimulation, respectively. In audiovisual (AV) synchrony perception, adaptation effects have primarily been reported. Here, we tested if perceptual hysteresis could also be observed over adaptation in AV timing perception by varying different experimental conditions. Participants were asked to judge the synchrony of the last (test) stimulus of an AV sequence with either constant or gradually changing AV intervals (constant and dynamic condition, respectively). The onset timing of the test stimulus could be cued or not (prospective vs. retrospective condition, respectively). We observed hysteretic effects for AV synchrony judgments in the retrospective condition that were independent of the constant or dynamic nature of the adapted stimuli; these effects disappeared in the prospective condition. The present findings suggest that knowing when to estimate a stimulus property has a crucial impact on perceptual simultaneity judgments. Our results extend beyond AV timing perception, and have strong implications regarding the comparative study of hysteresis and adaptation phenomena.	t	\N
25781179	Lifestyle including smoking, noise exposure with MP3 player and drinking alcohol are considered as risk factors for affecting hearing synergistically. However, little is known about the association of cigarette smoking with hearing impairment among subjects who carry a lifestyle without using MP3 player and drinking alcohol. We showed here the influence of smoking on hearing among Bangladeshi subjects who maintain a lifestyle devoid of using MP3 player and drinking alcohol. A total of 184 subjects (smokers: 90; non-smokers: 94) were included considering their duration and frequency of smoking for conducting this study. The mean hearing thresholds of non-smoker subjects at 1, 4, 8 and 12 kHz frequencies were 5.63 ± 2.10, 8.56±5.75, 21.06 ± 11.06, 40.79 ± 20.36 decibel (dB), respectively and that of the smokers were 7 ± 3.8, 13.27 ± 8.4, 30.66 ± 12.50 and 56.88 ± 21.58 dB, respectively. The hearing thresholds of the smokers at 4, 8 and 12 kHz frequencies were significantly (p<0.05) higher than those of the non-smokers, while no significant differences were observed at 1 kHz frequency. We also observed no significant difference in auditory thresholds among smoker subgroups based on smoking frequency. In contrast, subjects smoked for longer duration (>5 years) showed higher level of auditory threshold (62.16 ± 19.87 dB) at 12 kHz frequency compared with that (41.52 ± 19.21 dB) of the subjects smoked for 1-5 years and the difference in auditory thresholds was statistically significant (p<0.0002). In this study, the Brinkman Index (BI) of smokers was from 6 to 440 and the adjusted odds ratio showed a positive correlation between hearing loss and smoking when adjusted for age and body mass index (BMI). In addition, age, but not BMI, also played positive role on hearing impairment at all frequencies. Thus, these findings suggested that cigarette smoking affects hearing level at all the frequencies tested but most significantly at extra higher frequencies.	t	\N
25786320	The spatial specificity of auditory approaching and withdrawing aftereffects was investigated in an anechoic chamber. The adapting and testing stimuli were presented from loudspeakers located in front of the subject at the distance of 1.1 m (near) and 4.5 m (far) from the listener's head. Approach and withdrawal of stimuli were simulated by increasing or decreasing the amplitude of the wide-noise impulse sequence. The listeners were required to determine the movement direction of test stimulus following each 5-s adaptation period. The listeners' "withdrawal" responses were used for psychometric functions plotting and for quantitative assessment of auditory aftereffect. The data summarized for all 8 participants indicated that the asymmetry of approaching and withdrawing aftereffects depended on spatial localization of adaptor and test. The asymmetry of aftereffects was largest when adaptor and test were presented from the same loudspeaker (either near or far). Adaptation to the approach induced a directionally dependent displacement of the psychometric functions relative to control condition without adaptation and adaptation to the withdrawal was not. The magnitude of approaching aftereffect was greater when adaptor and test were located in near spatial domain than when they came from far domain. When adaptor and test were presented from the distinct loudspeakers, magnitude approaching aftereffect was decreasing in comparison to the same spatial localization, but after adaptation to withdrawal it was increasing. As a result, the directionally dependent displacements of the psychometric functions relative to control condition were observed after adaptation as to approach and to withdrawal. The discrepancy of the psychometric functions received after adaptation to approach and to withdrawal at near and far spatial domains was greater under the same localization of adaptor and test in comparison to their distinct localization. We assume that the peculiarities of approaching and withdrawing aftereffects observed reflect their spatial specificity. It is possible that spatial peculiarities of approaching and withdrawing aftereffects can be associated with specialized mechanisms for analysis of motion at the different distance from subject.	t	\N
25786957	Performing a secondary task while listening to speech has a detrimental effect on speech processing, but the locus of the disruption within the speech system is poorly understood. Recent research has shown that cognitive load imposed by a concurrent visual task increases dependency on lexical knowledge during speech processing, but it does not affect lexical activation per se. This suggests that "lexical drift" under cognitive load occurs either as a post-lexical bias at the decisional level or as a secondary consequence of reduced perceptual sensitivity. This study aimed to adjudicate between these alternatives using a forced-choice task that required listeners to identify noise-degraded spoken words with or without the addition of a concurrent visual task. Adding cognitive load increased the likelihood that listeners would select a word acoustically similar to the target even though its frequency was lower than that of the target. Thus, there was no evidence that cognitive load led to a high-frequency response bias. Rather, cognitive load seems to disrupt sublexical encoding, possibly by impairing perceptual acuity at the auditory periphery.	t	\N
25788705	Spatial crowding refers to impaired target identification when the target is surrounded by other stimuli in space temporal crowding refers to impaired target identification when the target is surrounded by other stimuli in time previously, when spatial and temporal crowding were measured in the fovea they were interrelated with amblyopic observers but almost absent with normal observers bonneh, sagi, & polat, 2007. In the current study we examined whether reliable temporal crowding can be found for normal observers with peripheral presentation 9° of eccentricity, and whether similar relations between temporal and spatial crowding will emerge to that end, we presented a sequence of three displays separated by a varying interstimulus interval (ISI). Each display included either one letter : experiments 1a ,: 1b ,: 1c or three letters separated by a varying interletter spacing: Experiments 2a ,: 2b). One of these displays included an oriented T. Observers indicated the T's orientation. As expected, we found spatial crowding: accuracy improved as the interletter spacing increased. Critically, we also found temporal crowding: in all experiments accuracy increased as the ISI increased, even when only stimulus-onset asynchronies (SOAs) larger than 150 ms were included, ensuring this effect does not reflect mere ordinary masking. Thus, with peripheral presentation, temporal crowding also emerged for normal observers. However, only a weak interaction between temporal and spatial crowding was found.	t	\N
25798581	Contralateral masking is the phenomenon where a masker presented to one ear affects the ability to detect a signal in the opposite ear. For normal hearing listeners, contralateral masking results in masking patterns that are both sharper and dramatically smaller in magnitude than ipsilateral masking. The goal of this study was to investigate whether medial olivocochlear (MOC) efferents are needed for the sharpness and relatively small magnitude of the contralateral masking function. To do this, bilateral cochlear implant patients were tested because, by directly stimulating the auditory nerve, cochlear implants circumvent the effects of the MOC efferents. The results indicated that, as with normal hearing listeners, the contralateral masking function was sharper than the ipsilateral masking function. However, although there was a reduction in the magnitude of the contralateral masking function compared to the ipsilateral masking function, it was relatively modest. This is in sharp contrast to the results of normal hearing listeners where the magnitude of the contralateral masking function is greatly reduced. These results suggest that MOC function may not play a large role in the sharpness of the contralateral masking function but may play a considerable role in the magnitude of the contralateral masking function.	t	\N
25816820	The Fukuda stepping test is commonly used to assess peripheral vestibular function. It has, however, been suggested that its maximal sensitivity and specificity are 70 per cent and 50 per cent, respectively. This study was undertaken to evaluate environmental factors that may influence the reliability of this assessment and hence to 'sharpen' its use in a clinical setting. Forty-four participants aged between 20 and 43 years were asked to perform the Fukuda stepping test in both a standard clinic room and a soundproofed room under the following conditions in a randomised order: on the floor versus on foam; with and without a sound-localising source; and with and without ear defenders. Significant differences in the extent of rotation were found when comparing the results obtained in several settings, including standing on the floor in a standard room versus a soundproofed room (p = 0.036), and standing on foam in a standard room versus a soundproofed room (p = 0.015). Our results suggest that certain alterations to the test environment may improve the sensitivity of this clinical examination.	t	\N
25832187	Previous studies have shown that discrimination sensitivity in 2AFC tasks depends on the presentation order of the standard and comparison stimulus. The present study examined whether this so-called Type B effect generalizes across different standard magnitudes. Therefore, Experiment 1 employed an auditory duration discrimination task with short (100 ms) and long (1,000 ms) standard durations and a constant interstimulus interval (ISI) of 1,000 ms. For both standard durations, a clear Type B effect emerged. In Experiment 2, discrimination sensitivity was assessed for short (300 ms) and long (1,000 ms) ISIs and a constant standard duration of 100 ms, in order to examine whether the Type B effect diminishes or even reverses when both stimuli are presented in rapid succession, as was suggested by previous studies. In the short, but not the long ISI condition, the Type B effect was virtually eliminated. Taken together, the present experiments suggest that the Type B effect is robust across standard magnitude, but diminishes when the time interval between both stimuli is reduced. This result pattern is discussed within the framework of the Internal Reference Model and the Sensation Weighting Model. It is also demonstrated that both models provide a quantitative account of the present results.	t	\N
25878263	Amplitude modulations are fundamental features of natural signals, including human speech and nonhuman primate vocalizations. Because natural signals frequently occur in the context of other competing signals, we used a forward-masking paradigm to investigate how the modulation context of a prior signal affects cortical responses to subsequent modulated sounds. Psychophysical "modulation masking," in which the presentation of a modulated "masker" signal elevates the threshold for detecting the modulation of a subsequent stimulus, has been interpreted as evidence of a central modulation filterbank and modeled accordingly. Whether cortical modulation tuning is compatible with such models remains unknown. By recording responses to pairs of sinusoidally amplitude modulated (SAM) tones in the auditory cortex of awake squirrel monkeys, we show that the prior presentation of the SAM masker elicited persistent and tuned suppression of the firing rate to subsequent SAM signals. Population averages of these effects are compatible with adaptation in broadly tuned modulation channels. In contrast, modulation context had little effect on the synchrony of the cortical representation of the second SAM stimuli and the tuning of such effects did not match that observed for firing rate. Our results suggest that, although the temporal representation of modulated signals is more robust to changes in stimulus context than representations based on average firing rate, this representation is not fully exploited and psychophysical modulation masking more closely mirrors physiological rate suppression and that rate tuning for a given stimulus feature in a given neuron's signal pathway appears sufficient to engender context-sensitive cortical adaptation.	t	\N
25885195	To verify the effect of long-term use of hearing aids with frequency compression for verbal behavior tests and daily activities. Thirty-two adults, aged between 30 and 60 years old, with moderate to severe sensorineural hearing loss at high frequencies with steeply sloping configuration were divided into two groups: 16 with hearing aids with frequency compression algorithm enabled and 16 not enabled. All participants underwent the detection tests of consonant sounds, monosyllable recognition in quiet environments, identification of fricative monosyllables, and Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire in five times throughout a 12-month trial. Detection of consonant sounds, recognition of monosyllables in quiet environments and identification of fricative monosyllables improved significantly with frequency compression enabled. Participants had their APHAB scores improved whether they were adapted to the frequency compression or not. Frequency compression provides the anticipated improvement in audibility, detection of high-frequency consonant sounds, and recognition of monosyllables.	t	\N
25913551	Since 1972, the World Health Organization (WHO) has declared noise as a pollutant. Over the last decades, the quality of the urban environment has attracted the interest of researchers due to the growing urban sprawl, especially in developing countries. The objective of this study was to evaluate the effects of noise exposure in six urban soundscapes: Areas with high and low levels of noise in scenarios of leisure, work, and home. Cross-sectional study. The study was conducted in two steps: Evaluation of noise levels, with the development of noise maps, and health related inquiries. 180 individuals were interviewed, being 60 in each scenario, divided into 30 exposed to high level of noise and 30 to low level. Chi-Square test and Ordered Logistic Regression Model (P < 0,005). 70% of the interviewees reported noticing some source of noise in the selected scenarios and it was observed an association between exposure and perception of some source of noise (P < 0.001). 41.7% of the interviewees reported some degree of annoyance, being that this was associated with exposure (P < 0.001). There was also an association between exposure in different scenarios and reports of poor quality of sleep (P < 0.001). In the scenarios of work and home, the chance of reporting annoyance increased when compared with the scenario of leisure. We conclude that the use of this sort of assessment may clarify the relationship between urban noise exposure and health.	t	\N
25914528	The possible relationship between audiometric hearing thresholds and cognitive performance on language tests was analyzed in a cross-sectional cohort of older adults aged ≥65 years (N=98) with different degrees of cognitive impairment. Participants were distributed into two groups according to Reisberg's Global Deterioration Scale (GDS): a normal/predementia group (GDS scores 1-3) and a moderate/moderately severe dementia group (GDS scores 4 and 5). Hearing loss (pure-tone audiometry) and receptive and production-based language function (Verbal Fluency Test, Boston Naming Test, and Token Test) were assessed. Results showed that the dementia group achieved significantly lower scores than the predementia group in all language tests. A moderate negative correlation between hearing loss and verbal comprehension (r=-0.298; P<0.003) was observed in the predementia group (r=-0.363; P<0.007). However, no significant relationship between hearing loss and verbal fluency and naming scores was observed, regardless of cognitive impairment. In the predementia group, reduced hearing level partially explains comprehension performance but not language production. In the dementia group, hearing loss cannot be considered as an explanatory factor of poor receptive and production-based language performance. These results are suggestive of cognitive rather than simply auditory problems to explain the language impairment in the elderly.	t	\N
25920851	Broadened auditory filters associated with sensorineural hearing loss have clearly been shown to diminish speech recognition in noise for adults, but far less is known about potential effects for children. This study examined speech recognition in noise for adults and children using simulated auditory filters of different widths. Specifically, 5 groups (20 listeners each) of adults or children (5 and 7 yrs), were asked to recognize sentences in speech-shaped noise. Seven-year-olds listened at 0 dB signal-to-noise ratio (SNR) only; 5-yr-olds listened at +3 or 0 dB SNR; and adults listened at 0 or -3 dB SNR. Sentence materials were processed both to smear the speech spectrum (i.e., simulate broadened filters), and to enhance the spectrum (i.e., simulate narrowed filters). Results showed: (1) Spectral smearing diminished recognition for listeners of all ages; (2) spectral enhancement did not improve recognition, and in fact diminished it somewhat; and (3) interactions were observed between smearing and SNR, but only for adults. That interaction made age effects difficult to gauge. Nonetheless, it was concluded that efforts to diagnose the extent of broadening of auditory filters and to develop techniques to correct this condition could benefit patients with hearing loss, especially children.	t	\N
25994736	A follow-up experiment to those conducted by Brown and Yost [(2011). J. Acoust. Soc. Am. 130, 358-364; (2013). Basic Aspects of Hearing: Physiology and Perception (Springer, London, UK)] examined interaural time difference (ITD) discrimination for a low-frequency target noise band flanked by monotic noise bands that were either lower-frequency than the target band, higher-frequency, or both. The flanking bands were either spectrally contiguous with the target band or spectrally separated. Significant interference in ITD processing occurred in the presence of the high-frequency flanking band. Results are discussed by way of a comparison of the conditions in the present study to those in studies of binaural interference. The possible role of attention is also discussed.	t	\N
25997868	In cochlear implant (CI) recipients with unilateral hearing loss (UHL) and normal hearing (NH) in the contralateral ear, the central auditory system receives signals of different auditory modalities, i.e. electrically via the CI ear as well as acoustically via the NH ear. The present study investigates binaural integration of bimodal stimulation in the central auditory system of 10 CI subjects with UHL by applying a modified version of the Rapidly Alternating Speech Perception (RASP) test to characterise speech recognition ability under monotic and dichotic listening arrangements. Subsequently, the results for each monotic and dichotic test condition were compared to quantify the binaural benefit from CI usage. The study results demonstrate significantly improved speech recognition under dichotic compared to monotic listening conditions, providing evidence that there is binaural integration of acoustically and electrically transmitted speech segments in the central nervous system at brainstem and cortical levels. In contrast to more commonly used tests of binaural integration, such as localisation, the RASP test provides the clinical option to investigate binaural integration involving structures at the cortical level.	t	\N
25998097	Recommendation for cochlear implant (CI) treatment for individuals with severe to profound single-sided deafness (SSD) and asymmetrical hearing loss (AHL) is on the rise. This raises the need for greater consistency in the definition of CI candidacy for these cases and in the assessment methods of patient-related benefits to permit effective comparison and interpretation of the outcomes with both conventional and implantable options across studies. During a dedicated seminar on implant treatment in AHL patients, the panellists of the closing round table reviewed the clinical experience presented with the aim to define clear audiometric characteristics for both AHL and SSD cases, as well as a common data set enabling consistent evaluation of hearing benefits in this population. The panellists agreed on a clear differentiation between AHL and SSD CI candidates, defining average pure-tone thresholds up to 4 kHz for better and poorer ears. Agreement was reached on a minimum set of assessment procedures, and included the necessity of trials with conventional CROS/BICROS hearing aids and bone conduction devices before considering CI treatment. Objective assessment of sound localisation abilities was identified as the most relevant criterion to quantify performance before and after treatment. In parallel, subjective assessment of overall hearing ability was recommended via the Speech, Spatial and Qualities of hearing questionnaire. Longitudinal follow-up of these parameters and the hours of daily use were considered essential to reflect the potential treatment benefits for this population. The consistency in the data collection and its report will further support health authorities in their decision on acceptable gains from available hearing loss treatment options.	t	\N
26017796	To compare the efficacy and feasibility of teleaudiometry with that of sweep audiometry in elementary school children, using pure-tone audiometry as the gold standard. A total of 243 students with a mean age of 8.3 years participated in the study. Of these, 118 were boys, and 125 were girls. The following procedures were performed: teleaudiometry screening with software that evaluates hearing at frequencies of 1,000, 2000 and 4000 Hz at 25 dBHL; sweep audiometry screening in an acoustic booth (20 dBHL at the same frequencies); pure-tone audiometry thresholds in an acoustic booth (frequencies of 500, 1000, 2000 and 4000 Hz); and acoustic immittance measurements. The diagnostic capacities of the teleaudiometry/sweep audiometry screening methods were as follows: sensitivity  ϝ  58%/65%; specificity  ϝ  86%/99%; positive predictive value  ϝ  51%/91%; negative predictive value  ϝ  89%/92%; and accuracy  ϝ  81%/92%. Teleaudiometry and sweep audiometry showed moderate agreement. Furthermore, the use of these methods in series with immittance testing improved the specificity, whereas parallel testing improved the sensitivity. Teleaudiometry was found to be reliable and feasible for screening hearing in school children. Moreover, teleaudiometry is the preferred method for remote areas where specialized personnel and specific equipment are not available, and its use may reduce the costs of hearing screening programs.	t	\N
26025759	Our fMRI study investigates auditory rhyme processing in spoken language to further elucidate the topic of functional lateralization of language processing. During scanning, 14 subjects listened to four different types of versed word strings and subsequently performed either a rhyme or a meter detection task. Our results show lateralization to auditory-related temporal regions in the right hemisphere irrespective of task. As for the left hemisphere we report responses in the supramarginal gyrus as well as in the opercular part of the inferior frontal gyrus modulated by the presence of regular meter and rhyme. The interaction of rhyme and meter was associated with increased involvement of the superior temporal sulcus and the putamen of the right hemisphere. Overall, these findings support the notion of right-hemispheric specialization for suprasegmental analyses during processing of spoken sentences and provide neuroimaging evidence for the influence of metrics on auditory rhyme processing.	t	\N
26055197	The timely diagnosis and treatment of acquired hearing loss in the pediatric population has significant implications for a child's development. Audiological assessment in children, however, carries both technological and logistical challenges. Typically, specialized methods (such as play audiometry) are required to maintain the child's attention and can be resource intensive. These challenges were previously addressed by a novel, calibrated, interactive play audiometer for Apple(®) iOS(®) called "ShoeBOX Audiometry". This device has potential applications for deployment in environments where traditional clinical audiometry is either unavailable or impractical. The objective of this study was to assess the screening capability of the tablet audiometer in an uncontrolled environment using consumer ear-bud headphones. Consecutive patients presenting to the Audiology Clinic at the Children's Hospital of Eastern Ontario (ages 4 and older) were recruited. Participants' hearing was evaluted using the tablet audiometer calibrated to Apple(®) In-Ear headphones. The warble tone thresholds obtained were compared to gold standard measurements taken with a traditional clinical audiometer inside a soundbooth. 80 patients were enrolled. The majority of participants were capable of completing an audiologic assessment using the tablet computer. Due to ambient noise levels outside a soundbooth, thresholds obtained at 500Hz were not consistent with traditional audiometry. Excluding 500Hz threholds, the tablet audiometer demonstrated strong negative predictive value (89.7%) as well as strong sensitivity (91.2%) for hearing loss. Thresholds obtained in an uncontrolled setting are not reflective of diagnostic thresholds due to the uncalibrated nature of the headphones and variability of the setting without a booth. Nevertheless, the tablet audiometer proved to be both a valid and sensitive instrument for unsupervised screening of warble-tone thresholds in children.	t	\N
26065403	To date, there have been less than 30 cases of cochlear implantation (CI) in patients with superficial siderosis (SS) reported in the literature. The primary objective of the current study is to evaluate CI outcomes in six additional patients (seven ears) with SS and sensorineural hearing loss (SNHL) and to perform a systematic review of the literature. Case series and systematic review of the literature. Two tertiary academic CI centers. All patients with SS who underwent CI between 2007 and 2014. Cochlear implantation. Pre- and post-implantation speech perception scores and durability of benefit. A total of seven ears (four males; median age 52 yr) with SS and SNHL met inclusion criteria. All patients developed progressive bilateral SNHL that was no longer amenable to conventional hearing aids. Additional presenting symptoms included vestibulopathy (n = 4), cerebellar ataxia (n = 3), mild dementia (n = 1), and myelopathy (n = 1). All patients underwent uncomplicated CI, and intraoperative device telemetry revealed normal responses in all electrodes. The median postoperative auditory threshold average was 32.5 dB HL (range 16-36 dB) and the median postoperative CNC word score was 51% (range 46-64%). The median duration of follow-up was 15.5 months (range 3-64 mo). All patients demonstrated initial improvement in speech perception testing. Two patients had performance decline and worsening dementia resulting from progressive SS. Cochlear implantation is a viable strategy for auditory rehabilitation in patients with SS and associated SNHL. Most individuals enjoy benefit from CI; however, patients should be counseled regarding the risks of performance decline with progressive SS.	t	\N
26093425	Natural auditory scenes often consist of several sound sources overlapping in time, but separated in space. Yet, location is not fully exploited in auditory grouping: spatially separated sounds can get perceptually fused into a single auditory object and this leads to difficulties in the identification and localization of concurrent sounds. Here, the brain mechanisms responsible for grouping across spatial locations were explored in magnetoencephalography (MEG) recordings. The results show that the cortical representation of a vowel spatially separated into two locations reflects the perceived location of the speech sound rather than the physical locations of the individual components. In other words, the auditory scene is neurally rearranged to bring components into spatial alignment when they were deemed to belong to the same object. This renders the original spatial information unavailable at the level of the auditory cortex and may contribute to difficulties in concurrent sound segregation.	t	\N
26093429	Sound focusing is to create a concentrated acoustic field in the region surrounded by a loudspeaker array. This problem was tackled in the previous research via the Helmholtz integral approach, brightness control, acoustic contrast control, etc. In this paper, the same problem was revisited from the perspective of beamforming. A source array model is reformulated in terms of the steering matrix between the source and the field points, which lends itself to the use of beamforming algorithms such as minimum variance distortionless response (MVDR) and linearly constrained minimum variance (LCMV) originally intended for sensor arrays. The beamforming methods are compared with the conventional methods in terms of beam pattern, directional index, and control effort. Objective tests are conducted to assess the audio quality by using perceptual evaluation of audio quality (PEAQ). Experiments of produced sound field and listening tests are conducted in a listening room, with results processed using analysis of variance and regression analysis. In contrast to the conventional energy-based methods, the results have shown that the proposed methods are phase-sensitive in light of the distortionless constraint in formulating the array filters, which helps enhance audio quality and focusing performance.	t	\N
26093435	Working memory capacity has been linked to performance on many higher cognitive tasks, including the ability to perceive speech in noise. Current efforts to train working memory have demonstrated that working memory performance can be improved, suggesting that working memory training may lead to improved speech perception in noise. A further advantage of working memory training to improve speech perception in noise is that working memory training materials are often simple, such as letters or digits, making them easily translatable across languages. The current effort tested the hypothesis that working memory training would be associated with improved speech perception in noise and that materials would easily translate across languages. Native Mandarin Chinese and native English speakers completed ten days of reversed digit span training. Reading span and speech perception in noise both significantly improved following training, whereas untrained controls showed no gains. These data suggest that working memory training may be used to improve listeners' speech perception in noise and that the materials may be quickly adapted to a wide variety of listeners.	t	\N
26093448	Physiological measures of neural activity in the auditory cortex have revealed plasticity following unilateral deafness. Central projections from the remaining ear reorganize to produce a stronger cortical response than normal. However, little is known about the perceptual consequences of this increase. One possibility is improved sound intensity discrimination. Intensity difference limens were measured in 11 individuals with unilateral deafness that were previously shown to exhibit increased cortical activity to sounds heard by the intact ear. Significantly smaller mean difference limens were observed compared with controls. These results provide evidence of the perceptual consequences of plasticity in humans following unilateral deafness.	t	\N
26107084	To examine the voice and personality characteristics of patients diagnosed with organic dysphonia secondary to vocal fold immobility. The study comprised patients of both genders, attending the Clinic School of Speech Therapy of the Federal University of Paraíba, with otorhinolaryngological diagnosis of vocal fold immobility and speech therapy diagnosis of dysphonia. The self-assessment of voice was measured through a Vocal Screening Protocol and Voice Symptoms Scale (VoiSS), the voice was collected for auditory-perceptive evaluation, and the Factorial Personality Battery (FPB) was used. Descriptive statistical analysis was performed to determine the frequency, mean, and standard deviation of the studied variables. Eight patients participated in the study, of both genders, with average age of 40.4 ± 16.9 years. The more frequent risk factors were the personal ones (4.7 ± 2.1). In the VoiSS, the patients presented a higher average in the limitation score (34.1 ± 15.7). From the auditory-perceptive evaluation, moderate intensity of vocal deviation was obtained, with predominant vocal roughness (57.7 ± 25.2). In the FPB, the patients had an average higher than the cutoff scores in neuroticism (3.8 ± 1.4) and accomplishment (5.2 ± 1.0). The predominant vocal parameter was roughness. The patients referred to a few risk factors that compromise the vocal behavior and presented the neuroticism and realization factors as a highlight in their personality. Thus, individuals with vocal fold immobility show personality characteristics that may be a reflection of their voice disorder, not a factor that determines their dysphonia.	t	\N
26121827	To assess the clinical effeetiveness of prelingually deaf children after cochlear implantation at different ages so as to provide reasonable expectations for the patients and guidance for the clinical treatment. Electronic databases PubMed, YZ365. COM, WANFANG DATA, CMJD, CHKD, CNKI were searched using relevant keywords. Extracted data included author, year of publication, diagnosis, et al. Reported treatment outcomes were clustered into speech discrimination and hearing abilities. Meta-analyses were performed on studies with numerical results using random or fixed effects model. There were eight randomized control studies including 442 patients. Comparing speech perception of prelingually deaf children after cochlear implantation younger than three years old (experimental group) and 3-6 years old (control group), three and six months after operation showed that experimental group performed significantly worse than control group; 12 months after operation showed that experimental group performed significantly better than control group. Comparing hearing abilities, three and six months after operation showed that experimental group performed significantly worse than control group; 12 months after operation showed showed that experimental group performed significantly better than control group. Comparing speech perception of younger or older than 4. 5 years old children showed that after 1.5-2 years of operation children implanted younger than 4.5 years of age performed significantly better than children implanted older than 4.5 years old. Comparing speech perception of 7-12 years old children showed that after 3, 6, 12 months of operation patients of 7-12 years old performed significantly better than those children older than 12 years old. Comparing speech perception of implantation younger or older than 18 years old (7-14 yeas old was group A, > 14-18 yeas old was group B, older than 18 yeas old was group C) showed that after one and four years of operation A > B > C, and there were significant differences among them. Comparing warble tone threshold average (WTA) showed that after one year of operation A < B < C, and there were significant differences among them. However, after four years of operation, there was no significant difference among them. Prelinguistically deafened patients younger than three years old with cochlear implantation, insisting on scienctific rehabilitation training for a long period of time can receive the optimal recovery effect. The older patients are suggested as early as possible receiving cochlear implantation. The longer they are implanted, the better results they will receive. Moreover, the younger age they are implanted, the faster postoperative language progress they will receive. Further controlled studies with longer follow-up periods and more person included may make the effectiveness of cochlear implantaion more reliable.	t	\N
26152053	During the first years of life, sensory modalities communicate with each other. This process is fundamental for the development of unisensory and multisensory skills. The absence of one sensory input impacts on the development of other modalities. Since 2008 we have studied these aspects and developed our cross-sensory calibration theory. This theory emerged from the observation that children start to integrate multisensory information (such as vision and touch) only after 8-10 years of age. Before this age the more accurate sense teaches (calibrates) the others; when one calibrating modality is missing, the other modalities result impaired. Children with visual disability have problems in understanding the haptic or auditory perception of space and children with motor disabilities have problems in understanding the visual dimension of objects. This review presents our recent studies on multisensory integration and cross-sensory calibration in children and adults with and without sensory and motor disabilities. The goal of this review is to show the importance of interaction between sensory systems during the early period of life in order to correct perceptual development to occur.	t	\N
26152058	Echolocation can be used by blind and sighted humans to navigate their environment. The current study investigated the neural activity underlying processing of path direction during walking. Brain activity was measured with fMRI in three blind echolocation experts, and three blind and three sighted novices. During scanning, participants listened to binaural recordings that had been made prior to scanning while echolocation experts had echolocated during walking along a corridor which could continue to the left, right, or straight ahead. Participants also listened to control sounds that contained ambient sounds and clicks, but no echoes. The task was to decide if the corridor in the recording continued to the left, right, or straight ahead, or if they were listening to a control sound. All participants successfully dissociated echo from no echo sounds, however, echolocation experts were superior at direction detection. We found brain activations associated with processing of path direction (contrast: echo vs. no echo) in superior parietal lobule (SPL) and inferior frontal cortex in each group. In sighted novices, additional activation occurred in the inferior parietal lobule (IPL) and middle and superior frontal areas. Within the framework of the dorso-dorsal and ventro-dorsal pathway proposed by Rizzolatti and Matelli (2003), our results suggest that blind participants may automatically assign directional meaning to the echoes, while sighted participants may apply more conscious, high-level spatial processes. High similarity of SPL and IFC activations across all three groups, in combination with previous research, also suggest that all participants recruited a multimodal spatial processing system for action (here: locomotion).	t	\N
26177161	Code-blends (simultaneous words and signs) are a unique characteristic of bimodal bilingual communication. Using fMRI, we investigated code-blend comprehension in hearing native ASL-English bilinguals who made a semantic decision (edible?) about signs, audiovisual words, and semantically equivalent code-blends. English and ASL recruited a similar fronto-temporal network with expected modality differences: stronger activation for English in auditory regions of bilateral superior temporal cortex, and stronger activation for ASL in bilateral occipitotemporal visual regions and left parietal cortex. Code-blend comprehension elicited activity in a combination of these regions, and no cognitive control regions were additionally recruited. Furthermore, code-blends elicited reduced activation relative to ASL presented alone in bilateral prefrontal and visual extrastriate cortices, and relative to English alone in auditory association cortex. Consistent with behavioral facilitation observed during semantic decisions, the findings suggest that redundant semantic content induces more efficient neural processing in language and sensory regions during bimodal language integration.	t	\N
26185045	Discourse structure enables us to generate expectations based upon linguistic material that has already been introduced. The present magnetoencephalography (MEG) study addresses auditory perception of test sentences in which discourse coherence was manipulated by using presuppositions (PSP) that either correspond or fail to correspond to items in preceding context sentences with respect to uniqueness and existence. Context violations yielded delayed auditory M50 and enhanced auditory M200 cross-correlation responses to syllable onsets within an analysis window of 1.5s following the PSP trigger words. Furthermore, discourse incoherence yielded suppression of spectral power within an expanded alpha band ranging from 6 to 16Hz. This effect showed a bimodal temporal distribution, being significant in an early time window of 0.0-0.5s following the PSP trigger and a late interval of 2.0-2.5s. These findings indicate anticipatory top-down mechanisms interacting with various aspects of bottom-up processing during speech perception.	t	\N
26185046	A number of studies have shown that from an early age, bilinguals outperform their monolingual peers on executive control tasks. We previously found that bilingual children and adults also display greater attention to unexpected language switches within speech. Here, we investigated the effect of a bilingual upbringing on speech perception in one language. We recorded monolingual and bilingual toddlers' event-related potentials (ERPs) to spoken words preceded by pictures. Words matching the picture prime elicited an early frontal positivity in bilingual participants only, whereas later ERP amplitudes associated with semantic processing did not differ between groups. These results add to the growing body of evidence that bilingualism increases overall attention during speech perception whilst semantic integration is unaffected.	t	\N
26200250	Event-related brain potentials (ERPs) demonstrate that human auditory cortical responses are sensitive to changes in static pitch as indexed by the pitch onset response (POR), a negativity generated at the initiation of acoustic periodicity. Yet, it is still unclear if this brain signature is sensitive to dynamic, time-varying properties of pitch more characteristic of those found in naturalistic speech and music. Neuroelectric PORs were recorded in response to contrastive pitch patterns differing in their pitch height, time-variance, and directionality (i.e., rise vs. fall). Broadband noise followed by contiguous iterated rippled noise (producing salient pitch sweeps) was used to temporally separate neural activity coding the onset of acoustic energy from the onset of time-varying pitch. Analysis of PORs revealed distinct modulations in response latency that distinguished static from time-varying pitch contours (steady-state<dynamic) and pitch height (high<low). However, PORs were insensitive to the direction of pitch sweeps (rise=fall). Our findings suggest that the POR signature provides a useful neural index of auditory cortical pitch processing for some, but not all pitch-evoking stimuli.	t	\N
26222937	To analyze the occurrence of acoustic reflex and its threshold on newborns using the 226 and 1,000 Hz probes. Thirty-six newborns with "PASS" results in newborn hearing screening and tympanogram with one or two peaks for both probe tones were included. Group I comprised 20 full-term newborns without risk indicator for hearing loss, and Group II comprised 16 newborns with at least one risk indicator. The study about ipsilateral acoustic reflex thresholds was conducted in 500, 1,000, 2,000, and 4,000 Hz. The groups presented the acoustic reflex thresholds between 50 and 100 dB for both probe tones. In the comparison between the probes, there were differences in all frequencies evaluated in Group I, with the lowest threshold mean for the 1,000 Hz probe. In Group II, differences were detected at 2,000 Hz. The mean acoustic reflex thresholds were similar in both groups for the 226 Hz probe. There was a difference for the 1,000 Hz probe in all tested frequencies. The percentage of response was higher in both groups for the 1,000 Hz probe. The kappa test showed extremely poor agreement in the comparison of results between both probes. The occurrence of acoustic reflex was higher in newborns and its thresholds were lower with the 1,000 Hz probe both for healthy newborns and for newborns at risk.	t	\N
26290244	Plasticity in the visual cortex of blind individuals provides a rare window into the mechanisms of cortical specialization. In the absence of visual input, occipital ("visual") brain regions respond to sound and spoken language. Here, we examined the time course and developmental mechanism of this plasticity in blind children. Nineteen blind and 40 sighted children and adolescents (4-17 years old) listened to stories and two auditory control conditions (unfamiliar foreign speech, and music). We find that "visual" cortices of young blind (but not sighted) children respond to sound. Responses to nonlanguage sounds increased between the ages of 4 and 17. By contrast, occipital responses to spoken language were maximal by age 4 and were not related to Braille learning. These findings suggest that occipital plasticity for spoken language is independent of plasticity for Braille and for sound. We conclude that in the absence of visual input, spoken language colonizes the visual system during brain development. Our findings suggest that early in life, human cortex has a remarkably broad computational capacity. The same cortical tissue can take on visual perception and language functions. Studies of plasticity provide key insights into how experience shapes the human brain. The "visual" cortex of adults who are blind from birth responds to touch, sound, and spoken language. To date, all existing studies have been conducted with adults, so little is known about the developmental trajectory of plasticity. We used fMRI to study the emergence of "visual" cortex responses to sound and spoken language in blind children and adolescents. We find that "visual" cortex responses to sound increase between 4 and 17 years of age. By contrast, responses to spoken language are present by 4 years of age and are not related to Braille-learning. These findings suggest that, early in development, human cortex can take on a strikingly wide range of functions.	t	\N
26323201	To determine if differences between dyslexic and typical readers in their reading scores and verbal IQ are evident as early as first grade and whether the trajectory of these differences increases or decreases from childhood to adolescence. The subjects were the 414 participants comprising the Connecticut Longitudinal Study, a sample survey cohort, assessed yearly from 1st to 12th grade on measures of reading and IQ. Statistical analysis employed longitudinal models based on growth curves and multiple groups. As early as first grade, compared with typical readers, dyslexic readers had lower reading scores and verbal IQ, and their trajectories over time never converge with those of typical readers. These data demonstrate that such differences are not so much a function of increasing disparities over time but instead because of differences already present in first grade between typical and dyslexic readers. The achievement gap between typical and dyslexic readers is evident as early as first grade, and this gap persists into adolescence. These findings provide strong evidence and impetus for early identification of and intervention for young children at risk for dyslexia. Implementing effective reading programs as early as kindergarten or even preschool offers the potential to close the achievement gap.	t	\N
26336746	Dynamics of activity in the frequency band of theta waves during of procedures, listening of the acoustic image of the own EEG was investigated. The formation of the acoustic image EEG was performed with a significant reduction of musical properties. It is shown that the increase in activity in the theta range depends on the level of synchronization and consistency of the presentation of the acoustic image own EEG relative to the current bioelectrical activity of the brain. The maximum increase in activity in the theta range was observed with minimum time delay and maximum consistency requirements of sounds with the current EEG. It is concluded that the increase in activity in the range of theta waves in the listening environment acoustic image own EEG is determined by the correlation of sounds with the current bioelectric activity of the brain.	t	\N
26377472	Human cortex is comprised of specialized networks that support functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity offer unique insights into this question. In congenitally blind individuals, "visual" cortex responds to auditory and tactile stimuli. Remarkably, recent evidence suggests that occipital areas participate in language processing. We asked whether in blindness, occipital cortices: (1) develop domain-specific responses to language and (2) respond to a highly specialized aspect of language-syntactic movement. Nineteen congenitally blind and 18 sighted participants took part in two fMRI experiments. We report that in congenitally blind individuals, but not in sighted controls, "visual" cortex is more active during sentence comprehension than during a sequence memory task with nonwords, or a symbolic math task. This suggests that areas of occipital cortex become selective for language, relative to other similar higher-cognitive tasks. Crucially, we find that these occipital areas respond more to sentences with syntactic movement but do not respond to the difficulty of math equations. We conclude that regions within the visual cortex of blind adults are involved in syntactic processing. Our findings suggest that the cognitive function of human cortical areas is largely determined by input during development. Human cortex is made up of specialized regions that perform different functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity show that cortical areas can change function from one sensory modality to another. Here we demonstrate that input during development can alter cortical function even more dramatically. In blindness a subset of "visual" areas becomes specialized for language processing. Crucially, we find that the same "visual" areas respond to a highly specialized and uniquely human aspect of language-syntactic movement. These data suggest that human cortex has broad functional capacity during development, and input plays a major role in determining functional specialization.	t	\N
26380997	The usage of personal listening devices (PLDs) is associated with risks of hearing loss. The aim of this study is to evaluate the effects of music exposure from these devices on high-frequency hearing thresholds of PLD users. A total of 282 young adults were questioned regarding their listening habits and symptoms associated with PLD listening. Their audiogram thresholds were determined at high (3-8 kHz) frequencies and extended high frequencies (EHFs, 9-16 kHz). The preferred listening volumes of PLD users were used to compute their overall 8-h equivalent music exposure levels (LAeq8h). Approximately 80% of the subjects were regular PLD users. Of these, 20.1% had LAeq8h of ≥75 dBA, while 4.4% of them had LAeq8h of ≥85 dBA, which carries a high risk of hearing damage. Compared with those exposed to LAeq8h of <75 dBA, subjects who had LAeq8h of ≥75 dBA reported a significantly higher incidence of tinnitus and difficulty in hearing others immediately after using PLDs. PLD users who were exposed to LAeq8h of ≥75 dBA and had been using their devices for ≥4 years also showed significantly higher mean audiogram thresholds compared with non-users at most EHFs tested. In addition, the thresholds of PLD users at EHFs showed a weak but significant positive correlation with their LAeq8h. The present findings suggest that excessive exposure to music among PLD users may lead to initial effects on their hearing at very high frequencies.	t	\N
26536965	It has been shown that musicians are at risk of noise-induced hearing loss. The aim of the study has been to evaluate the temporary changes of hearing in the case of orchestral musicians after group rehearsals. The study group comprised 18 orchestral musicians, aged 30-58 years old (mean: 40 years old) having 12-40 years (mean: 22 years) of professional experience. The temporary changes in hearing after group rehearsals were determined using transient-evoked otoacoustic emissions (TEOAEs). Noise exposures during group rehearsals were also evaluated. Musicians' hearing threshold levels were higher (worse) than expected for the equivalent non-noise-exposed population. Moreover, the high frequency notched audiograms were observed in some of them. After rehearsals, during which musicians were exposed to orchestral noise at A-weighted equivalent-continuous sound pressure level (normalized to 8-h working day) varied from 75.6-83.1 dB (mean: 79.4 dB). The significant post-exposure reductions of TEOAE amplitudes (approx. 0.7 dB) both for the total response and frequency bands of 2000 and 3000 Hz were noted. However, there were no significant differences between pre- and postexposure reproducibility of TEOAE. Obtained results have confirmed that orchestral musicians are at risk of hearing loss due to their professional activities, even at exposures to orchestral noise less than the limit values for occupational noise.	t	\N
26538659	Deficits in auditory emotion recognition (AER) are a core feature of schizophrenia and a key component of social cognitive impairment. AER deficits are tied behaviorally to impaired ability to interpret tonal ("prosodic") features of speech that normally convey emotion, such as modulations in base pitch (F0M) and pitch variability (F0SD). These modulations can be recreated using synthetic frequency modulated (FM) tones that mimic the prosodic contours of specific emotional stimuli. The present study investigates neural mechanisms underlying impaired AER using a combined event-related potential/resting-state functional connectivity (rsfMRI) approach in 84 schizophrenia/schizoaffective disorder patients and 66 healthy comparison subjects. Mismatch negativity (MMN) to FM tones was assessed in 43 patients/36 controls. rsfMRI between auditory cortex and medial temporal (insula) regions was assessed in 55 patients/51 controls. The relationship between AER, MMN to FM tones, and rsfMRI was assessed in the subset who performed all assessments (14 patients, 21 controls). As predicted, patients showed robust reductions in MMN across FM stimulus type (p = 0.005), particularly to modulations in F0M, along with impairments in AER and FM tone discrimination. MMN source analysis indicated dipoles in both auditory cortex and anterior insula, whereas rsfMRI analyses showed reduced auditory-insula connectivity. MMN to FM tones and functional connectivity together accounted for ∼50% of the variance in AER performance across individuals. These findings demonstrate that impaired preattentive processing of tonal information and reduced auditory-insula connectivity are critical determinants of social cognitive dysfunction in schizophrenia, and thus represent key targets for future research and clinical intervention. Schizophrenia patients show deficits in the ability to infer emotion based upon tone of voice [auditory emotion recognition (AER)] that drive impairments in social cognition and global functional outcome. This study evaluated neural substrates of impaired AER in schizophrenia using a combined event-related potential/resting-state fMRI approach. Patients showed impaired mismatch negativity response to emotionally relevant frequency modulated tones along with impaired functional connectivity between auditory and medial temporal (anterior insula) cortex. These deficits contributed in parallel to impaired AER and accounted for ∼50% of variance in AER performance. Overall, these findings demonstrate the importance of both auditory-level dysfunction and impaired auditory/insula connectivity in the pathophysiology of social cognitive dysfunction in schizophrenia.	t	\N
26562889	Visual search is an essential task for many lifesaving professions; airport security personnel search baggage X-ray images for dangerous items and radiologists examine radiographs for tumors. Accuracy is critical for such searches; however, there are potentially negative influences that can affect performance; for example, the displays can be cluttered and can contain multiple targets. Previous research has demonstrated that clutter can hurt search performance and a second target is less likely to be detected in a multiple-target search after a first target has been found, which raises a concern-how does clutter affect multiple-target search performance? The current study explored clutter in a multiple-target search paradigm, where there could be one or two targets present, and targets appeared in varying levels of clutter. There was a significant interaction between clutter and target number: Increasing levels of clutter did not affect single-target detection but did reduce detection of a second target. Multiple-target search accuracy is known to be sensitive to contextual influences, and the current results reveal a specific effect wherein clutter disproportionally affected multiple-target search accuracy. These results suggest that the detection and processing of a first target might enhance the masking effects of clutter around a second target.	t	\N
26575193	We examined short-term memory for sequences of visual stimuli embedded in varying multisensory contexts. In two experiments, subjects judged the structure of the visual sequences while disregarding concurrent, but task-irrelevant auditory sequences. Stimuli were eight-item sequences in which varying luminances and frequencies were presented concurrently and rapidly (at 8 Hz). Subjects judged whether the final four items in a visual sequence identically replicated the first four items. Luminances and frequencies in each sequence were either perceptually correlated (Congruent) or were unrelated to one another (Incongruent). Experiment 1 showed that, despite encouragement to ignore the auditory stream, subjects' categorization of visual sequences was strongly influenced by the accompanying auditory sequences. Moreover, this influence tracked the similarity between a stimulus's separate audio and visual sequences, demonstrating that task-irrelevant auditory sequences underwent a considerable degree of processing. Using a variant of Hebb's repetition design, Experiment 2 compared musically trained subjects and subjects who had little or no musical training on the same task as used in Experiment 1. Test sequences included some that intermittently and randomly recurred, which produced better performance than sequences that were generated anew for each trial. The auditory component of a recurring audiovisual sequence influenced musically trained subjects more than it did other subjects. This result demonstrates that stimulus-selective, task-irrelevant learning of sequences can occur even when such learning is an incidental by-product of the task being performed.	t	\N
26753216	The stress response has been well documented in past music therapy literature. However, hypometabolism, or the relaxation response, has received much less attention. Music therapists have long utilized various music-assisted relaxation techniques with both live and recorded music to elicit such a response. The ongoing proliferations of relaxation music through commercial media and the dire lack of evidence to support such claims warrant attention from healthcare professionals and music therapists. The purpose of these 3 studies was to investigate the correlational relationships between 12 psychophysical properties of music, preference, familiarity, and degree of perceived relaxation in music. Fourteen music therapists recommended and analyzed 30 selections of relaxation music. A group of 80 healthy adults then rated their familiarity, preference, and degree of perceived relaxation in the music. The analysis provided a detailed description of the intrinsic properties in music that were perceived to be relaxing by listeners. These properties included tempo, mode, harmonic, rhythmic, instrumental, and melodic complexities, timbre, vocalization/lyrics, pitch range, dynamic variations, and contour. In addition, music preference was highly correlated with listeners' perception of relaxation in music for both music therapists and healthy adults. The correlation between familiarity and degree of relaxation reached significance in the healthy adult group. Results from this study provided an in-depth operational definition of the intrinsic parameters in relaxation music and also highlighted the importance of preference and familiarity in eliciting the relaxation response.	t	\N
26891543	PROBLEM/OBJECTIVES: Maxillary constriction and high palatal arch are associated with increased risk of chronic eustachian tube dysfunction and conductive hearing loss (CHL) due to chronic effusion. However, this relationship has not been clearly demonstrated. This study assessed CHL in school children with a narrowed maxilla and deep palatal vault. Thirty-two children with maxillary constriction were randomly selected for the study group and 28 children with normal transverse maxillary development were selected for the control group. Pure-tone audiograms were obtained for all children, and hearing levels and air-bone gaps were measured. Air-bone gap measurements in the control group ranged from 5.50 to 14.50 decibels (dB), and in the study group they were between 5.00 and 24.00 dB. In the study group, 14 (43.8%) children had slight CHL, and the remaining 18 (56.2%) children had normal hearing levels. In the control group, all of the children had normal hearing levels. Hearing levels and air-bone gaps were greater in the study group than the control group. This study showed that children with a narrowed maxilla and deep palatal vault may have slight CHL. Therefore, the onset of CHL should be followed with hearing screening programs.	t	\N
26941686	Actions that produce sounds infuse our daily lives. Some of these sounds are a natural consequence of physical interactions (such as a clang resulting from dropping a pan), but others are artificially designed (such as a beep resulting from a keypress). Although the relationship between actions and sounds has previously been examined, the frame of reference of these associations is still unknown, despite it being a fundamental property of a psychological representation. For example, when an association is created between a keypress and a tone, it is unclear whether the frame of reference is egocentric (gesture-sound association) or exocentric (key-sound association). This question is especially important for artificially created associations, which occur in technology that pairs sounds with actions, such as gestural interfaces, virtual or augmented reality, and simple buttons that produce tones. The frame of reference could directly influence the learnability, the ease of use, the extent of immersion, and many other factors of the interaction. To explore whether action-sound associations are egocentric or exocentric, an experiment was implemented using a computer keyboard's number pad wherein moving a finger from one key to another produced a sound, thus creating an action-sound association. Half of the participants received egocentric instructions to move their finger with a particular gesture. The other half of the participants received exocentric instructions to move their finger to a particular number on the keypad. All participants were performing the same actions, and only the framing of the action varied between conditions by altering task instructions. Participants in the egocentric condition learned the gesture-sound association, as revealed by a priming paradigm. However, the exocentric condition showed no priming effects. This finding suggests that action-sound associations are egocentric in nature. A second part of the same session further confirmed the egocentric nature of these associations by showing no change in the priming effect after moving to a different starting location. Our findings are consistent with an egocentric representation of action-sound associations, which could have implications for applications that utilize these associations.	t	\N
22619989	The paper involves exposure to noise of the State Police officers connected with the use of firearms. The noise generated by these weapons is of short duration and high intensity. The research was carried out during the sessions of firearm training of State Police officers to assess exposure to noise. The values of the various investigations, both audiometric and phonometric, carried out made it possible to demonstrate a significant exposure and a temporary increase in the threshold, above the frequency of 6000 Hz. Even taking account of the abatement from use of headphones, an exposure was demonstrated that was above the statutory limits, as was confirmed by the temporary hearing threshold shift.	t	\N
19616325	A patient with ankylosing spondylitis, migraine, Parkinson syndrome, renal insufficiency and myopathy, received an implantable-cardioverter-defibrillator because of asymptomatic left ventricular hypertrabeculation/noncompaction as primary prophylaxis against sudden cardiac death. Inadvertently the ventricular lead was placed in a cardiac vein, the patient suffered from pericardial effusion and it was impossible to remove the lead. Implantation of an implantable-cardioverter-defibrillator simply upon the presence of LVHT appears not justified and may be more harmful than beneficial. Studies about the risk of SCD in adults with LVHT are necessary and will hopefully clarify if primary prevention of SCD is indicated.	f	\N
19770797	FX06 is a naturally occurring fibrin-derived peptide demonstrated to confer cytoprotection in the setting of primary percutaneous coronary intervention. Because the effect of FX06 on human platelet, coagulation, and fibrinolysis biomarkers (PCFB) is unknown but is important for further clinical development, we evaluated how FX06 affects PCFB. The in vitro effects of the whole-blood pre-incubation with escalating concentrations of FX06 (4, 25, and 75 μg/mL) were assessed in aspirin-naïve healthy volunteers (n = 10), those with multiple risk factors for vascular disease (n = 10), and patients with documented coronary artery disease (n = 10). The last two groups were treated with aspirin (81 mg/daily). Thirty-two variables of PCFB were measured with the vehicle and for each chosen FX06 dose. Pretreatment of blood samples with FX06 resulted in a moderate but significant and mostly dose-dependent increases of platelet aggregation induced by adenosine diphosphate and collagen. Similarly, the closure time was reduced, suggesting share-induced activation, PECAM-1, GP Ib, GP IIb/IIIa activity, and vitronectin receptors, which were also up-regulated. In contrast, P-selectin and GPIIb antigen expression were reduced after FX06. All other PCFB were predominantly unaffected by FX06, with the exception of the increased plasminogen, decreased protein C activity, and activated von Willebrand factor. We conclude that in the therapeutic range, FX06 in vitro mildly affects hemostasis by way of mostly activating platelets. Applying moderate concomitant antiplatelet strategies should be considered for the adequate protection from vascular thrombotic events in patients treated with FX06. Similar ex vivo study in patients receiving aspirin and clopidogrel is warranted.	f	\N
19854042	Upper urinary tract urothelial carcinoma (UUTUC) is relatively rare, occurring in only 5% of all urothelial cancers. It has not been as extensively studied and reviewed as carcinoma of the bladder. UUTUC has a propensity for multifocality, local recurrence, and development of metastases, which argues for an aggressive treatment approach. Open radical nephroureterectomy (ORNU) with removal of an ipsilateral bladder cuff still remains the gold standard treatment for patients with UUTUC and a normal contralateral kidney, which, however, is being challenged by minimally invasive approaches, such as endoscopic and laparoscopic approaches. They are rapidly evolving as reasonable alternatives of care depending on grade and stage of disease. Adjuvant therapy seems to be safe, although its efficacy is debatable. Immunotherapy appears to be most effective in patients with upper-tract carcinoma in situ. Chemotherapy and radiotherapy also show some improvement in recurrence rates, but there have been no randomized, prospective trials. Gene and molecular-targeted therapy is expected. Several controversies remain in our management, including a selection of endoscopic versus laparoscopic approaches, management strategies on the distal ureter, the role of lymphadenectomy, and the value of immunotherapy, chemotherapy, radiotherapy and genetics and molecular markers in UUTUC. Aims of this paper are to critically review the treatment of UUTUC.	f	\N
20049455	Relapsing polychondritis (RP) is a rare disease which presents chondritis in multiple organs. Characteristic features include auricular chondritis, arthritis, nasal chondritis, ocular inflammation, respiratory tract involvement and audiovestibular damage. Fifty percent of cases of RP are associated with inner ear symptoms such as dizziness and hearing loss. We have recently encountered a case of RP in a 34-year-old man who had recurrent chondritis of both auricles and progressive bilateral profound sensorineural hearing loss; he had been treated many times with steroids, immunosuppressants, plasmapheresis treatments. We perfomed a successful cochlear implant surgery on the left ear of this patient. This raises the possibility of using cochlear implants in treating patients with immune-mediated inner ear disease as well as such RP patients.	f	\N
20373123	Juvenile dermatomyositis (JDM) is a rare childhood disease with autoimmune association. Environmental factors are known to trigger JDM in genetically susceptible individuals (Schmieder et al., Dermatol Online 6:3, 2009). Calcinosis is a well-established complication of JDM. Prevalence is higher in children (30-70%; Özkaya et al., Erciyes Med J 30(1):40-43, 2008). Hyperimmunoglobulin E syndrome is a primary immunodeficiency syndrome with multiple recurrent abscess formation and raised serum immunoglobulin E levels. We report a case of JDM with calcinosis cutis universalis with hyperimmunoglobulin E syndrome. With a previous similar case report (Min et al., Korean J Intern Med 14:95-98, 1999), this could well be a new sequence syndrome where abscesses are the trigger for the onset of JDM.	f	\N
20390341	The estrogen signal is mediated by the estrogen receptor (ER). The specific role of ER-beta, a second ER, in breast carcinogenesis is not known. A number of association studies have been carried out to investigate the relationship between polymorphic sites in the ESR2 gene and breast cancer risk, however, the results are inconsistent. We searched PubMed, Medline, and Web of Science database (updated to 10 January 2010) and identified 13 relevant case-control studies, and approximately 28 single-nucleotide polymorphisms (SNPs) and one micro-satellite marker were reported in the literature. The median number of study subjects was 776 (range 158-13,550). Three genetic variants [(CA)n, rs2987983, and rs4986938] showed significant overall associations with breast cancer, and rs4986938 was reported twice. Because rs4986938 and rs1256049 were the most extensively studied polymorphisms, we subsequently conducted a meta-analysis to evaluate their relationship with breast cancer risk (9 studies of 10,837 cases and 16,021 controls for rs4986938; 8 studies of 11,652 cases and 15,726 controls for rs1256049). For rs4986938, the women harboring variant allele seemed to be associated with a decreased risk either in the dominant model [pooled OR = 0.944, 95% confidence interval (95% CI) 0.897-0.993, fixed-effects] or in the co-dominant model (AG vs. GG) (OR = 0.944, 95% CI 0.895-0.997, fixed-effects). rs1256049 was not associated with breast cancer risk in any model. Five studies had investigated the effect of haplotypes in the ESR2 gene on breast cancer risk, and four of them had positive outcomes. In summary, the present systematic review suggests that SNP rs4986938 as well as haplotypes in the ESR2 gene might be associated with breast cancer. The need for additional studies examining these issues seems of vital importance.	f	\N
20434804	The pathophysiology of tinnitus is obscure and its treatment is therefore elusive. Significant progress in this field can only be achieved by determining the mechanisms of tinnitus generation, and thus, histopathologic findings of the cochlea in presbycusis with tinnitus become crucial. We revealed the histopathologic findings of the cochlea in subjects with presbycusis and tinnitus. The subjects were divided into 2 groups, presbycusis with tinnitus (tinnitus) group and presbycusis without tinnitus (control) group, with each group comprising 8 temporal bones from 8 subjects. We quantitatively analyzed the number of spiral ganglion cells, loss of cochlear inner and outer hair cells, and areas of the stria vascularis and spiral ligament. There was a significantly greater loss of outer hair cells in the tinnitus group compared with the control group in the basal and upper middle turns. The stria vascularis was more atrophic in the tinnitus group compared with the control group in the basal turn. Tinnitus is more common in patients with presbycusis who have more severe degeneration of outer hair cells and stria vascularis.	f	\N
20512338	Hoarseness due to left recurrent laryngeal nerve paralysis (LRLN) caused by identifiable cardiovascular disease is described as Ortner's syndrome or cardiovocal syndrome. This was first reported by Ortner in 1897 to describe left recurrent laryngeal nerve palsy secondary to mitral stenosis. This case report describe a patient with giant cell arteritis with initial presentation of Ortner's syndrome.	f	\N
20579773	Oligomeric β-amyloid (Aβ) has recently been linked to synaptic plasticity deficits, which play a major role in progressive cognitive decline in Alzheimer's disease (AD). Here we present evidence that chronic oral administration of carvedilol, a nonselective β-adrenergic receptor blocker, significantly attenuates brain oligomeric β-amyloid content and cognitive deterioration in 2 independent AD mouse models. We found that carvedilol treatment significantly improved neuronal transmission, and that this improvement was associated with the maintenance of number of the less stable "learning" thin spines in the brains of AD mice. Our novel observation that carvedilol interferes with the neuropathologic, biochemical, and electrophysiological mechanisms underlying cognitive deterioration in AD supports the potential development of carvedilol as a treatment for AD.	f	\N
20678147	Psoriasis is today generally considered a systemic disease. Systemic therapies are used frequently. In Germany fumaric acid esters - FAE (Fumaderm(®) ) - are employed in more than 50 % of the patients requiring such therapy. We report for the first time the development of melanoma in two patients during their treatment with FAE. The logical question is - are the tumors coincidental or might they be treatment-related? Further investigations of pathways and immunologic effects as well as careful reports of side effects are necessary to estimate the risks of malignancy of FAE.	f	\N
20696610	This study investigates the relationship between neck muscle coactivation, neck strength and perceived pain and disability in women with neck pain. Surface electromyography (EMG) was acquired from the sternocleidomastoid (SCM) and splenius capitis (SC) muscles of 13 women with chronic neck pain and 10 controls as they performed 1) maximal voluntary contractions (MVC) in flexion, extension and left and right lateral flexion, 2) ramped contractions from 0% to 50% MVC in flexion and extension and 3) circular contractions in the horizontal plane at 15N and 30N force. Higher values of EMG amplitude were observed for the SC (antagonist) during ramped neck flexion and for the SCM during ramped extension in the patient group (P<0.05). The patients displayed reduced values of directional specificity in the surface EMG of the SCM and SC for the circular contractions (P<0.05). The EMG amplitude of SC during cervical flexion was positively correlated with the patients' pain (R² =0.35, P<0.05) and perceived disability (R² 0.53, P<0.01). An inverse correlation was evident between the amount of activation of SC during cervical flexion and strength (R² =0.54, P<0.01). These observations indicate a relationship between alterations in neuromuscular control in patients with neck pain and functional consequences, including impaired motor performance and increased levels of perceived disability.	f	\N
20733020	To report the clinical course, treatment response and prognosis of eight cases which developed acute-onset postoperative endophthalmitis over a 1-month period. 8 patients who were operated on over a period of 1 month and developed acute postoperative endophthalmitis were evaluated. Five of the patients had cataract surgery, one had cataract surgery combined with silicone extraction, and two patients had pars plana vitrectomy (PPV). Clinical patterns were observed, intraocular cultures were obtained, and the source of the organisms causing the epidemic was investigated. All patients had intravitreal antibiotic injections, three had PPV, and in two patients anterior chamber irrigation was performed. Vitreous cultures showed Cellulosimicrobium cellulans in three cases and Stenotrophomonas maltophilia in one case. Four of the cases were culture negative. Stenotrophomonas maltophilia were also isolated from unused bottles of irrigating solutions. The final visual acuity of the patients ranged between HM and 7/10. All three patients with Cellulosimicrobium cellulans had a final visual acuity of ≥ 5/10. The available irrigating solutions were changed, and the endophthalmitis did not recur. The authors are unaware of any previous reports of postoperative endophthalmitis associated with Cellulosimicrobium cellulans. Prompt management with microbiological support, intravitreal antibiotics and PPV when needed were the key to good visual outcomes in this endophthalmitis outbreak.	f	\N
20849277	The ability for public/veterinary health agencies to assess the risks posed by tick-borne pathogens is reliant on an understanding of the main tick vector species. Crucially, the status, distribution, and changing trends in tick distribution and abundance are implicit requirements of any risk assessment; however, this is contingent on the quality of tick distribution data. Since 2005 the Health Protection Agency has promoted an enhanced tick surveillance program. Through engagement with a variety of public and veterinary health agencies and practitioners (e.g., clinicians and veterinarians), wildlife groups (deer society, zoos, animal refuge centers, and academics), and amateur entomologists, >4000 ticks from 900 separate records across Great Britain have been submitted, representing 14 tick species (Ixodes ricinus, Ixodes hexagonus, Ixodes acuminatus, Ixodes arboricola, Ixodes canisuga, Ixodes frontalis, Ixodes lividus, Ixodes trianguliceps, Ixodes ventalloi, Carios vespertilionis, Dermacentor reticulatus, Haemaphysalis punctata, Hyalomma marginatum, and Amblyomma species). The majority of ticks submitted were I. ricinus (81%), followed by I. hexagonus (10%) and I. frontalis (2.5%). Predominant host groups include companion animals (411 records), humans (198 records), wild birds (111 records), and large wild mammals (88 records), with records also from small/medium wild mammals, livestock, the environment and domestic/aviary birds. The scheme has elucidated the detection of two nonnative tick species, the expansion of previously geographically restricted D. reticulatus and produced ground data on the spread of I. ricinus in southwest England. It has also provided a forum for submission of ticks from the concerned public and particularly those infected with Lyme borreliosis, thus raising awareness among public health agencies of the increased peri-urban tick problem in Britain. Our results demonstrate that it is possible to run a cost-effective nationwide surveillance program to successfully monitor endemic tick species, identify subtle changes in their distribution, and detect the arrival and presence of exotic species.	f	\N
20853354	We report our 10-year experience with percutaneous closure of adult congenital and acquired (non-post-infarct) ventricular septal defects (VSDs) using different types of Amplatzer occluder devices. Adult congenital and acquired VSDs may produce significant morbidity and mortality. Furthermore, such VSDs pose a significant surgical challenge. Between February 2000 and August 2009, data were retrospectively reviewed from 28 patients who underwent 29 procedures for percutaneous device closure of hemodynamically significant VSDs. Seventeen had unrepaired congenital VSDs, 10 had post-operative VSDs (5 with residual patch-margin defects, 4 post-aortic valve replacement, 1 post-myomectomy), and one had an acquired traumatic VSD. INDICATIONS FOR CLOSURE INCLUDED: symptoms related to significant shunt (dyspnea on exertion); unexplained deterioration of LV function, and/or LV dilation; recurrent endocarditis, and pulmonary hypertension. Outcome parameters were procedural success, procedure-related complications, evidence of residual shunt by echocardiography, and improvement in the signs/symptoms for which the procedure was performed. The mean follow-up interval was 68 months. Of the 28 patients studied, a single VSD was present in 26 patients, while one patient had two defects, and one patient had one defect on the LV side with three openings at the RV side. The median size of the defects by echocardiography was 6 mm. A device was successfully implanted in 28 of 29 (97%) procedures and 28 of 28 (100%) patients. PROCEDURE-RELATED COMPLICATIONS OCCURRED IN TWO CASES: one involving an access site hematoma not requiring transfusion as well as nonsustained ventricular tachycardia that resolved spontaneously and the other involving acute mitral regurgitation due to inadvertent trapping of the anterior mitral valve leaflet between the left ventricular disk and the septum that was resolved by recapturing of the disk. There was immediate complete closure in 20 patients (71%). In six cases there was trivial residual shunt and in two patients the residual shunt was mild. At the latest follow-up, four of the eight with a residual shunt had no shunt and in the remaining four the residual shunt was trivial. Among symptomatic patients 18 (64%), there was marked improvement in symptoms and for those patients 17 (61%) for whom the procedure was performed to address left ventricular enlargement, there was reduction or stabilization in LV size on serial echoes. Percutaneous closure of VSDs in the adult patient appears to be safe and effective.	f	\N
20853359	A significant proportion (~ 20%) of patients with complex tibial artery occlusions cannot be treated using a conventional antegrade approach. We report our experience using the retrograde approach for the treatment of complex tibial artery occlusive disease using retrograde pedal/tibial access in 13 limbs from 12 patients. Retrograde pedal/tibial access was achieved in all cases (facilitated by surgical cutdown in one case), and procedural success was achieved in 11 of 13 limbs (85%). Based on this experience, a discussion of clinical and technical aspects of the retrograde pedal/tibial approach is provided, and a new classification for tibial artery occlusive disease is proposed.	f	\N
20878712	Endoscopic evaluation plays a pivotal role in the assessment of treatment response in ulcerative colitis (UC). This study aimed to determine the interobserver agreement (IOA) for assessment of mucosal lesions, and to determine lesions predictive of global assessment of endoscopic severity (GAES). Fifty-one UC patients had digital videorecording of their colonoscopic examinations, edited into videoclips representative of five colonic segments (rectum, sigmoid, descending, transverse, ascending/cecum). Seven gastroenterologists specializing in inflammatory bowel disease (IBD) independently and blindly rated individual lesions and endoscopic severity for each segment and globally. Edema, erythema, stricture, loss of haustral folds, rigidity, and pseudopolyps were scored as absent or present while vascular pattern, granularity, ulceration, and bleeding-friability were scored using a predefined severity scale. The GAES was based on a 4-point scale and a 10-cm visual analog scale (VAS). The IOA among raters was estimated using Lin's concordance correlation coefficient (CCC). Strength of agreement was categorized as excellent (0.81-1.00), good (0.61-0.80), moderate (0.41-0.60), and fair (0.21-0.40). Linear regression analysis was used to identify lesions predictive of overall endoscopic severity and develop a scoring system for clinical use. Granularity, vascular pattern, ulceration, bleeding/friability, and pseudopolyps had good IOA in most segments. There was excellent agreement for VAS and good agreement for GAES and the VAS was significantly associated with GAES (P < 0.001). Granularity, vascular pattern, ulceration, and bleeding-friability were significant predictors of overall endoscopic severity. Granularity, vascular pattern, ulceration, and bleeding-friability demonstrated good reproducibility and were predictors of the GAES in UC patients.	f	\N
20881290	Mutations in PITX2 are associated with Axenfeld-Rieger syndrome (ARS), which involves ocular, dental, and umbilical abnormalities. Identification of cis-regulatory elements of PITX2 is important to better understand the mechanisms of disease. Conserved noncoding elements surrounding PITX2/pitx2 were identified and examined through transgenic analysis in zebrafish; expression pattern was studied by in situ hybridization. Patient samples were screened for deletion/duplication of the PITX2 upstream region using arrays and probes. Zebrafish pitx2 demonstrates conserved expression during ocular and craniofacial development. Thirteen conserved noncoding sequences positioned within a gene desert as far as 1.1 Mb upstream of the human PITX2 gene were identified; 11 have enhancer activities consistent with pitx2 expression. Ten elements mediated expression in the developing brain, four regions were active during eye formation, and two sequences were associated with craniofacial expression. One region, CE4, located approximately 111 kb upstream of PITX2, directed a complex pattern including expression in the developing eye and craniofacial region, the classic sites affected in ARS. Screening of ARS patients identified an approximately 7600-kb deletion that began 106 to 108 kb upstream of the PITX2 gene, leaving PITX2 intact while removing regulatory elements CE4 to CE13. These data suggest the presence of a complex distant regulatory matrix within the gene desert located upstream of PITX2 with an essential role in its activity and provides a possible mechanism for the previous reports of ARS in patients with balanced translocations involving the 4q25 region upstream of PITX2 and the current patient with an upstream deletion.	f	\N
20936300	In Huntington's disease (HD) atrophy of the caudate nucleus and putamen has been described many years before clinical manifestation. Volume changes of the pallidum, thalamus, brainstem, accumbens nucleus, hippocampus, and amygdala are less well investigated, or reported with contradicting results. The aim of our study is to provide a more precise view of the specific atrophy of the subcortical grey matter structures in different stages of Huntington's disease, and secondly to investigate how this influences the clinical manifestations. All TRACK-HD subjects underwent standardised T1-weighted 3T MRI scans encompassing 123 manifest HD (stage 1, n = 77; stage 2, n = 46), 120 premanifest HD (close to onset n = 58, far from onset n = 62) and 123 controls. Using FMRIB's FIRST and SIENAX tools the accumbens nucleus, amygdala, brainstem, caudate nucleus, hippocampus, pallidum, putamen, thalamus and whole brain volume were extracted. Results showed that volumes of the caudate nucleus and putamen were reduced in premanifest HD far from predicted onset (>10.8 years). Atrophy of accumbens nucleus and pallidum was apparent in premanifest HD in the close to onset group (0-10.8 years). All other structures were affected to some degree in the manifest group, although brainstem, thalamus and amygdala were relatively spared. The accumbens nucleus, putamen, pallidum and hippocampus had a strong significant correlation with functional and motor scores. We conclude that volume changes may be a sensitive and reliable measure for early disease detection and in this way serve as a biomarker for Huntington's disease. Besides the caudate nucleus and putamen, the pallidum and the accumbens nucleus show great potential in this respect.	f	\N
20938704	We describe an outbreak of Bacillus cereus bacteremia that occurred at Jichi Medical University Hospital in 2006. This study aimed to identify the source of this outbreak and to implement appropriate control measures. We reviewed the charts of patients with blood cultures positive for B. cereus, and investigated B. cereus contamination within the hospital environment. Genetic relationships among B. cereus isolates were analyzed. Eleven patients developed B. cereus bacteremia between January and August 2006. The hospital linens and the washing machine were highly contaminated with B. cereus, which was also isolated from the intravenous fluid. All of the contaminated linens were autoclaved, the washing machine was cleaned with a detergent, and hand hygiene was promoted among the hospital staff. The number of patients per month that developed new B. cereus bacteremia rapidly decreased after implementing these measures. The source of this outbreak was B. cereus contamination of hospital linens, and B. cereus was transmitted from the linens to patients via catheter infection. Our findings demonstrated that bacterial contamination of hospital linens can cause nosocomial bacteremia. Thus, blood cultures that are positive for B. cereus should not be regarded as false positives in the clinical setting.	f	\N
20950346	Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone receptor blockade has been shown to reduce morbidity and mortality in human patients with advanced congestive left ventricular heart failure. This study was designed to assess the efficacy and tolerance of long-term low-dose spironolactone when added to conventional heart failure treatment in dogs with advanced heart failure. Eighteen client-owned dogs with advanced congestive heart failure due to either degenerative valve disease (n=11) or dilated cardiomyopathy (n=7) were included in this prospective, placebo-controlled, double-blinded, randomized clinical study. After initial stabilization including furosemide, angiotensin-converting enzyme inhibitors, pimobendan and digoxin, spironolactone at a median dose of 0.52 mg/kg (range 0.49-0.8 mg/kg) once daily (n=9) or placebo (n=9) was added to the treatment, and the dogs were reassessed 3 and 6 months later. Clinical scoring, echocardiography, electrocardiogram, systolic blood pressure measurement, thoracic radiography, sodium, potassium, urea, creatinine, alanine aminotransferase, aldosterone and aminoterminal atrial natriuretic propeptide were assessed at baseline, 3 and 6 months. Survival times were not significantly different between the two treatment groups. Spironolactone was well tolerated when combined with conventional heart failure treatment.	f	\N
20981578	Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to slow neuronal loss in several brain regions. It is characterised by the presence of cerebral senile plaques comprised of aggregated amyloid-β peptides. Transcriptional regulation of the γ-secretase complex, which cleaves the β-amyloid precursor protein to produce Aβ-peptides, could modulate the pathological phenotype of AD patients. This study investigates whether rosuvastatin, an HMG-CoA reductase inhibitor, modulates the expression of genes involved in the function of the γ-secretase complex, in a human cellular model for Aβ peptide accumulation. In particular, we analysed the effect of the statin combined with apoptotic induction. Experimental apoptosis was induced by thapsigargin treatment, a drug that depletes intracellular calcium stores via inhibition of the calcium ATPase pump. Notably, systemic calcium dysregulation accompanies almost all of the brain pathology processes observed in AD. We found differential transcriptional regulation of some γ-secretase cofactors relative to rosuvastatin treatment, in cells expressing Swedish mutant APP. Interestingly, this statin down-regulated the transcription of some enzyme cofactors, similar to treatment with thapsigargin. However, rosuvastatin neither affected the basal Aβ levels nor counteracted APP processing or Aβ over-production triggered by the thapsigargin. Our results provide evidence that rosuvastatin alters gene expression of the γ-secretase complex without affecting enzyme activity.	f	\N
21040232	Febrile seizures (FSs) relatively represent the most common form of childhood seizures. FSs are not thought of as a true epileptic disease but rather as a special syndrome characterized by its provoking factor (fever) and a typical range of 3 months to 5 years. Although specific genes affecting the majority of FS cases have not been identified yet, several genetic loci for FSs have been reported recently. The aim of this report is to search for the gene responsible for FSs in six affected Tunisian families. A microsatellite marker analysis was performed on the known FS and generalized epilepsy with febrile seizures plus (GEFS+) loci. According to the results obtained by statistical analyses for the six studied families and in agreement with the involvement of SCN1B gene in the GEFS+ syndrome in previous studies, SCN1B on GEFS+1 locus was considered as one of the potential candidate genes and was tested for mutations by direct sequencing. A sequencing analysis of the SCN1B gene revealed a novel mutation (c.374G>T) that changed an arginine residue with leucine at position 125 of the protein. We consider that the variation R125L may affect the protein structure and stability by the loss of hydrogen bonding. Two identified single nucleotide polymorphisms that are located in a neighboring hypothetical polyadenylation were assumed to compose a putative disease-associated haplotype. Our results support that SCN1B is the gene responsible in one amongst the six FS Tunisian families studied and might contribute to the FS susceptibility for the five others.	f	\N
21055462	Environmental factors have a significant impact on biology. Therefore, environmental toxicants through similar mechanisms can modulate biological systems to influence physiology and promote disease states. The majority of environmental toxicants do not have the capacity to modulate DNA sequence, but can alter the epigenome. In the event an environmental toxicant such as an endocrine disruptor modifies the epigenome of a somatic cell, this may promote disease in the individual exposed, but not be transmitted to the next generation. In the event a toxicant modifies the epigenome of the germ line permanently, then the disease promoted can become transgenerationaly transmitted to subsequent progeny. The current review focuses on the ability of environmental factors such as endocrine disruptors to promote transgenerational phenotypes.	f	\N
21073934	Two mouse models, the Coch(G88E/G88E) or "knock-in" and the Coch(-/-) or "knock-out" (Coch null), have been developed to study the human late-onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. This disorder results from missense and in-frame deletion mutations in COCH (coagulation factor C homology), encoding cochlin, the most abundantly detected protein in the inner ear. We have performed hearing and vestibular analyses by auditory brainstem response (ABR) and vestibular evoked potential (VsEP) testing of the Coch(-/-) and Coch(G88E/G88E) mouse models. Both Coch(-/-) and Coch(G88E/G88E) mice show substantially elevated ABRs at 21 months of age, but only at the highest frequency tested for the former and all frequencies for the latter. At 21 months, 9 of 11 Coch(-/-) mice and 4 of 8 Coch(G88E/G88E) mice have absent ABRs. Interestingly Coch(-/+) mice do not show hearing deficits, in contrast to Coch(G88E/+), which demonstrate elevated ABR thresholds similar to homozyotes. These results corroborate the DFNA9 autosomal dominant mode of inheritance, in addition to the observation that haploinsufficiency of Coch does not result in impaired hearing. Vestibular evoked potential (VsEP) thresholds were analyzed using a two factor ANOVA (Age X Genotype). Elevated VsEP thresholds are detected in Coch(-/-) mice at 13 and 21 months, the two ages tested, and as early as seven months in the Coch(G88E/G88E) mice. These results indicate that in both mouse models, vestibular function is compromised before cochlear function. Analysis and comparison of hearing and vestibular function in these two DFNA9 mouse models, where deficits occur at such an advanced age, provide insight into the pathology of DFNA9 and age-related hearing loss and vestibular dysfunction as well as an opportunity to investigate potential interventional therapies.	f	\N
21084426	We performed a three-stage genome-wide association study (GWAS) to identify common Parkinson's disease (PD) risk variants in the European population. The initial genome-wide scan was conducted in a French sample of 1039 cases and 1984 controls, using almost 500 000 single nucleotide polymorphisms (SNPs). Two SNPs at SNCA were found to be associated with PD at the genome-wide significance level (P < 3 × 10(-8)). An additional set of promising and new association signals was identified and submitted for immediate replication in two independent case-control studies of subjects of European descent. We first carried out an in silico replication study using GWAS data from the WTCCC2 PD study sample (1705 cases, 5200 WTCCC controls). Nominally replicated SNPs were further genotyped in a third sample of 1527 cases and 1864 controls from France and Australia. We found converging evidence of association with PD on 12q24 (rs4964469, combined P = 2.4 × 10(-7)) and confirmed the association on 4p15/BST1 (rs4698412, combined P = 1.8 × 10(-6)), previously reported in Japanese data. The 12q24 locus includes RFX4, an isoform of which, named RFX4_v3, encodes brain-specific transcription factors that regulate many genes involved in brain morphogenesis and intracellular calcium homeostasis.	f	\N
21085051	The Centers for Disease Control and Prevention recommend hospitals develop guidelines for the appropriate use of vancomycin as part of comprehensive antimicrobial stewardship. The objective of this study was to evaluate the effectiveness and safety of a guideline to restrict vancomycin use in the neonatal intensive care unit (NICU). A vancomycin use guideline was introduced in 2 tertiary care NICUs with low incidences of methicillin-resistant Staphylococcus aureus infections. We compared all infants >72 hours of age who were evaluated for late-onset infection before and after implementation of this guideline. Vancomycin start rates were reduced from 6.9 to 4.5 per 1000 patient-days (35% reduction; P = 0.01) at Brigham and Women's Hospital, and from 17 to 6.4 per 1000 patient-days (62% reduction; P < 0.0001) at Massachusetts General Hospital. The number of infants exposed to vancomycin decreased from 5.2 to 3.1 per 1000 patient-days (40% reduction; P = 0.008) at Brigham and Women's Hospital, and 10.8 to 5.5 per 1000 patient-days (49% reduction; P = 0.009) at Massachusetts General Hospital. Causes of infection, duration of bacteremia, and incidence of complications or deaths attributable to late-onset infection did not change significantly at either institution. Implementation of a NICU vancomycin use guideline significantly reduced exposure of newborns to vancomycin without adversely affecting short-term patient safety. Further studies are required to evaluate the long-term effect of vancomycin restriction on NICU patient safety and microbial ecology, particularly among institutions with higher rates of methicillin-resistant Staphylococcus aureus infections.	f	\N
21102561	Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the potential to differentiate into all cell lineages, including hepatocytes, in vitro. Induced hepatocytes have a wide range of potential application in biomedical research, drug discovery, and the treatment of liver disease. However, the existing protocols for hepatic differentiation of PSCs are not very efficient. In this study, we developed an efficient method to induce hepatoblasts, which are progenitors of hepatocytes, from human ESCs and iPSCs by overexpression of the HEX gene, which is a homeotic gene and also essential for hepatic differentiation, using a HEX-expressing adenovirus (Ad) vector under serum/feeder cell-free chemically defined conditions. Ad-HEX-transduced cells expressed α-fetoprotein (AFP) at day 9 and then expressed albumin (ALB) at day 12. Furthermore, the Ad-HEX-transduced cells derived from human iPSCs also produced several cytochrome P450 (CYP) isozymes, and these P450 isozymes were capable of converting the substrates to metabolites and responding to the chemical stimulation. Our differentiation protocol using Ad vector-mediated transient HEX transduction under chemically defined conditions efficiently generates hepatoblasts from human ESCs and iPSCs. Thus, our methods would be useful for not only drug screening but also therapeutic applications.	f	\N
21104183	Crohn disease is a chronic granulomatous inflammatory disorder that most commonly affects the gastrointestinal tract, particularly the distal small bowel and colon. While certain extraintestinal manifestations of Crohn disease are relatively common and well-known, others, such as metastatic cutaneous involvement, are quite rare and may be difficult to recognize, particularly in the pediatric population. This case report illustrates the magnetic resonance imaging (MRI) appearance of vulvar region cutaneous Crohn disease in an 11-year-old girl.	f	\N
21106231	The purpose of this study was (1) to investigate the association between BMI self-reported at three time points (during their 20s, 5 years before diagnosis, and post-diagnosis) and mortality among 388 women with newly diagnosed epithelial ovarian cancer and (2) weight change between these 3 time points and mortality. Women completed interview-administered questionnaires on average 9 months post-diagnosis. Women were followed 5 years after diagnosis or until death, whichever came first. Cox proportional hazard regression was used to estimate associations between BMI during the 20s, BMI 5 years prior to diagnosis, BMI post-diagnosis (i.e., at the time of interview) and weight changes between these time points and mortality. The 5-year survival rate was 54% (178 deaths, 146 from ovarian cancer). BMI measured continuously at all three time points was associated with a higher risk of ovarian cancer mortality (P≤0.05). The strongest association was observed with BMI in the 20s and all-cause mortality comparing women with BMI≥25 kg/m(2) to BMI<25 kg/m(2) (HR=1.82; 95% CI, 1.02-3.27; P for trend=0.045). For weight change from the 20s to 5 years prior to diagnosis and ovarian cancer specific mortality, we observed a 68% higher risk of ovarian cancer mortality (HR=1.68; 95% CI, 1.11-2.55; P for trend=0.015, comparing women with <10 lbs weight gain to women with ≥10 lbs weight gain). BMI prior to and after diagnosis and weight gain throughout adulthood is associated with ovarian cancer mortality.	f	\N
21135704	To study the role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis (AP). Bacterial translocation has been implicated in infective complications in AP, which has been shown to be prevented by probiotics. A double-blind, randomized placebo-controlled trial was conducted. Consecutive patients with AP presenting within 72 hours after the onset of abdominal pain or who had been nil orally at the time of presentation for up to 5 days were included in the study. The probiotic group received 4 sachets of Probiotics (2.5 billion bacteria per sachet) whereas the placebo group received 4 sachets of placebo for 7 days. Primary outcome measures were effect on gut permeability [assessed by lactulose/mannitol (L/M) excretion in urine] and endotoxemia assessed by endotoxin-core antibody types IgG and IgM (EndoCab IgG and IgM). Secondary outcome measures were mortality, total hospital/intensive care unit stay, abdominal discomfort, organ failure, C-reactive protein, and prealbumin levels. The study was prematurely stopped after the publication of probiotic prophylaxis in patients with predicted severe acute pancreatitis trial. From March 2007 to May 2008, 50 patients with AP were included in the study (26 in placebo group and 24 in probiotic group). There was no difference after intervention in gut permeability, whereas values of C-reactive protein and immunoglobulins decreased significantly [IgG: 140 (20-920) to 90 (20-600) GGU/mL and IgM: 65 (13-230) to 51 (9-240) GMU/mL] in the probiotic group. No difference was observed in prealbumin values, duration of hospital/intensive care unit stay, and mortality in both the groups. No significant trend was identified for an effect of probiotics on gut permeability or endotoxemia in AP. However, the study was underpowered owing to premature study termination.	f	\N
21172349	Visceral leishmaniasis (VL) is a health issue in Sudan. Our aim was to investigate the involvement of eosinophils and neutrophils in VL by serum and plasma measurements of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) and some key cytokines and chemokines. Blood was collected from 125 VL patients and 181 healthy Sudanese controls from the same rural area. Results showed reduced eosinophil and neutrophil counts in the VL group (P=0.0001 and P=0.002, respectively). Serum-ECP levels were higher in the controls (P<0.0001), while plasma MPO levels were higher in the VL group (P<0.0001). Levels of IL-5, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-17 were increased among the VL group (P<0.0001, P=0.017 and P=0.03, respectively), whereas eotaxin and IL-8 levels were reduced (P<0.0001 and P=0.002, respectively). Positive correlations were found between IL-8 and ECP/MPO (P<0.0001). We conclude that eosinophil and neutrophil turnover and activity are increased in subjects in rural areas of Sudan. In VL the turnover was further increased, but the relatively low secretory activity of eosinophils and neutrophils in VL may relate to the reduced production and availability of the chemokines eotaxin and IL-8. The combined assay of ECP and MPO in serum and plasma provides further insight into the mechanisms of eosinophil and neutrophil involvement in disease and constitutes a novel approach to the study of disease processes.	f	\N
21184197	The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level and whether it might have differential effects on brain function due to the presence of APOE ε 4 allele(s) in HIV-infected patients are unknown. However, APOE ε 4 allele has been associated with greater incidence of HIV-associated dementia and accelerated progression of HIV infection. Here, we show further evidence for the role of APOE ε 4 in promoting cognitive impairment. We measured the APOE levels in the CSF of HIV-infected individuals. HIV+ subjects showed lower CSF APOE proteins than SN controls (-19%, p= 0.03). While SN subjects with or without ε 4 allele showed no difference in CSF APOE levels, ε 4+ HIV+ subjects had similar levels to the SN subjects but higher levels than ε 4- HIV+ subjects (+34%, p= 0.01). Furthermore, while HIV+ subjects with ε 2 or ε 3 allele(s) showed a positive relationship between their CSF APOE levels and cognitive performance on the speed of processing domain (r= +0.35, p= 0.05), ε 4+ HIV+ subjects, in contrast, exhibited a negative relationship such that those with higher levels of CSF APOE(4) performed worse on the HIV Dementia Scale (r= -0.61, p= 0.02), had lower Global Cognitive Scores (r= -0.57, p= 0.03), and had poorer performance on tests involving learning (ε 4 allele x [APOE] interaction, p = 0.01). Our findings also suggest that the relatively higher levels of CSF APOE in ε 4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the ε 4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.	f	\N
21190758	Assuming selective vulnerability of short association U-fibers in early Alzheimer's disease (AD), we quantified demyelination of the surface white matter (dSWM) with magnetization transfer ratio (MTR) in 15 patients (Clinical Dementia Rating Scale [CDR] 0.5-1; Functional Assessment Staging [FAST]: 3-4) compared with 15 controls. MTRs were computed for 39 areas in each hemisphere. We found a bilateral MTR decrease in the temporal, cingulate, parietal, and prefrontal areas. With linear discriminant analysis, we successfully classified all the participants with 3 variates including the cuneus, parahippocampal, and superior temporal regions of the left hemisphere. The pattern of dSWM changed with the age of AD onset. In early onset patients, we found bilateral posterior demyelination spreading to the temporal areas in the left hemisphere. The late onset patients showed a distributed bilateral pattern with the temporal and cingulate areas strongly affected. A correlation with Mini Mental State Examination (MMSE), Lexis, and memory tests revealed the dSWM impact on cognition. A specific landscape of dSWM in early AD shows the potential of MTR imaging as an in vivo biomarker superior to currently used techniques.	f	\N
21211565	Nuclear receptors (NRs) are ligand-activated transcriptional factors that are involved in various physiological, developmental, and toxicological processes. Farnesoid X receptor (FXR) is a NR that belongs to the NR superfamily. The endogenous ligands of FXR are bile acids. FXR is essential in regulating a network of genes involved in maintaining bile acid and lipid homeostasis. It is clear that FXR is critical for liver and intestinal function. In mice FXR deficiency leads to the development of cholestasis, gallstone disease, nonalcoholic steatohepatitis, liver tumor, and colon tumor. Using mouse models where FXR is deleted either in the whole-body, or selectively in hepatocytes or enterocytes, we start to reveal the importance of tissue-specific FXR function in regulating bile acid and lipid homeostasis. However, a great challenge exists for developing tissue-specific FXR modulators to prevent and treat diseases associated with bile acid or lipid disorders. With further understanding of FXR function in both rodents and humans, this nuclear receptor may emerge as a novel target to prevent and treat liver, gastrointestinal and systemic diseases.	f	\N
21220035	We retrospectively compared the outcomes of 225 patients with adult acquired aplastic anemia (AA) who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) from matched related donors (MRDs), and those treated by alloHSCT from alternative donors (ADs). Univariate and multivariate analyses of factors associated with survival were performed. Multivariate analysis showed that age at alloHSCT of ≤ 31 years, MRD, successful engraftment, absence of acute graft-versus-host disease (aGVHD), and platelet engraftment at ≤ 21 days, were independent predictors of longer survival. In addition, time to aGVHD and cumulative nonrelapse mortality (NRM) were better in MRD than in AD recipients. Using propensity score matching (PSM), we performed a case-control study comparing 25 patients in each group who underwent alloHSCT from MRDs and ADs. Pretransplantation clinical factors were well balanced in either group. Median survival time was similar, and no statistically significant difference in transplantation outcomes was apparent when MRD and AD recipients were compared. In conclusion, our results suggest that alloHSCT from an AD should be considered earlier in adult patients with AA who do not have an MRD.	f	\N
21224840	Despite little supporting data, thiopurine use is common in pediatric ulcerative colitis (UC). Our aim was to determine outcome following thiopurine use in a multicenter inception cohort of children diagnosed with UC. Data were obtained from a prospective observational study of newly diagnosed children <16 years of age. Data are recorded at diagnosis, 30 days, and quarterly. Patients are managed by physician dictates not protocol. Disease activity is classified by physician global assessment. The primary outcome was corticosteroid (CS)-free inactive UC at 1 year following thiopurine initiation without the need for rescue therapy (infliximab, calcineurin inhibitors, or colectomy). Of 1,490 patients in our registry, 394 have UC (mean age at diagnosis 11.3±3.7 years); 197 (50%) received thiopurine (49% ≤3 months from diagnosis). Also, 84% were receiving CSs and 60% 5-aminosalicylates at thiopurine start. Of the 197 patients, there was insufficient follow-up (41), previous or concomitant use of infliximab (16), or calcineurin inhibitor (7), leaving 133 patients evaluable at 1 year. Of these, 65 (49%) had CS-free inactive UC without rescue therapy. CS-free inactive disease at 1 year after initiating thiopurine was not affected by starting thiopurine ≤3 months vs. >3 months from diagnosis, gender, age, or concomitant treatment with 5-aminosalicylates. Kaplan-Meier analysis showed that the likelihood of remaining free of rescue therapy in the thiopurine-treated patients was 73% at 1 year. Approximately 50% of children with UC starting thiopurine without previous or concomitant biologic or calcineurin inhibitor therapy have CS-free inactive disease 1 year later without the need for rescue therapy.	f	\N
21240517	We investigated whether there exists a hierarchical vulnerability of subcortical structures with respect to the severity of Alzheimer's disease (AD). A total of 236 subjects (179 with AD and 57 with normal cognition) underwent 1.5-T magnetic resonance (MR) imaging. The volumes of the five subcortical structures (amygdala, thalamus, putamen, globus pallidus, and caudate nucleus) and hippocampus were analyzed using a large deformation diffeomorphic metric mapping algorithm. The volume changes were evaluated according to the Clinical Dementia Rating (CDR). Correlation between the volumes of the subcortical structures and scores of the cognitive domain-specific neuropsychological tests were evaluated. Volume loss of the amygdala occurred even in the very mild stage of AD (CDR 0.5), as did volume loss in the hippocampus. Similar reductions in volume occurred in the thalamus and putamen, however during the mild (CDR 1) and moderate (CDR 2) stages of AD, respectively. The globus pallidus and caudate nucleus remained devoid of changes until the moderate stage of AD (p < 0.01). Volume loss in those subcortical structures correlated with the neuropsychological test scores (p < 0.01). Our results suggest that there is a hierarchical vulnerability in subcortical structures according to the clinical severity of AD and that subcortical volume reductions correlate with cognitive impairment.	f	\N
21242863	A retrospective clinical and radiographic study was performed. The purpose of this study was to compare outcomes of patients with degenerative spondylolisthesis and a preexisting degenerative L5-S1 disc treated with a lumbar floating fusion (LFF) versus lumbosacral fusion (LSF). Fusion for treatment of degenerative spondylolisthesis often ends at the L5 level. These patients usually had a preexisting L5-S1 disc degeneration; however, no literature mentions the role of prophylactic LSF in degenerative spondylolisthesis associated with L5-S1 disc degeneration. A total of 107 patients with a minimum 5-year follow-up who had lumbosacral or LFF with pedicle instrumentation for degenerative spondylolisthesis were included. UCLA (University of California, Los Angeles) classification was used to evaluate the radiographic results of the L5-S1 segment. The Oswestry Disability Index (ODI) and modified Brodsky's criteria were used to evaluate patients' clinical results. The incidence of adjacent segment disease (ASD) (includes radiographic and clinical ASD) of both ends was recorded. There were no statistically significant differences in sex, age distribution, or amount of follow-up between the LFF and LSF groups. The LSF group had a higher percentage of patients that underwent total L5 laminectomy with loss of L5-S1 posterior ligament integrity (LSF = 92% vs. LFF = 67%, P = 0.019). The higher incidence of cephalic ASD in the LSF group was statistically significant (LSF = 25% vs. LFF = 9.7%, P = 0.049). Although no patient in the LSF group developed L5-S1 ASD, need for L5-S1 segment revision surgery was not prevented with LSF. Clinical outcomes on the basis of the success rate (LFF = 85.5% vs.LSF = 70.8%, P = 0.103) and ODI difference (LFF = 28.97 ± 15.82 vs. LSF = 23.04 ± 10.97, P = 0.109), there were no statistically significant difference between these two groups. Posterior instrumentation with posterolateral LFF for the treatment of degenerative spondylolisthesis with concomitant L5-S1 disc degeneration results in a high percentage of satisfactory clinical results. Extended fusion to the sacrum did not provide a better clinical result. LSF could not reduce the incidence of revision surgery at the L5-S1 segment and involved greater incidence of cephalic ASD.	f	\N
21246519	Concurrent inhibition of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) is an active and well tolerated regimen in recurrent head and neck cancer (HNC). In the current phase 1 trial, the authors sought to determine the maximum tolerated dose (MTD) and efficacy of concurrent erlotinib and celecoxib as a radiosensitizing regimen. Fourteen patients with previously irradiated HNC with no distant metastases who required reirradiation were eligible. Treatment consisted of daily erlotinib 150 mg and twice daily celecoxib (escalated from 200 mg to 600 mg using a 3 + 3 design with an expanded cohort at the MTD) starting on Day 1 and was continued during radiation. Daily radiation was started on Day 15, and maintenance erlotinib was recommended. The recommended phase 2 dose of celecoxib was 400 mg. Three dose-limiting toxicities included late in-field orocutaneous fistula (Dose Level 2), osteonecrosis (Dose Level 3), and trismus (Dose Level 3). Acute grade ≥ 3 toxicities were uncommon and included mucositis (21%) and dermatitis (14%). At a median follow-up of 11 months, the 1-year locoregional control, progression-free survival, and overall survival rates were 60%, 37%, and 55%, respectively. Concurrent erlotinib, celecoxib, and reirradiation was a feasible and clinically active regimen in a population of patients with recurrent HNC who had a poor prognosis.	f	\N
21251542	In recent years, a common strategy for the prevention of postsurgical intra-abdominal adhesions has been intrasurgical placement of adhesion barriers into the peritoneal cavity. Osmotic agents, such as various polysaccharides, frequently are used as antiadhesive materials. The effects of these materials on kidney function have not yet been studied. We report a case of an individual with pre-existing chronic kidney disease who developed acute kidney injury after surgical placement of an antiadhesive barrier of macromolecular polysaccharides. A kidney biopsy, performed because of persistent kidney failure, showed tubular cell lesions compatible with osmotic nephrosis lesions. This case suggests that use of polysaccharide-containing antiadhesive barriers can induce severe kidney damage. Such barriers should be used with caution in patients with abnormal kidney function to prevent irreversible damage.	f	\N
21262922	A 2005 report from the Centers for Medicare and Medicaid Services and the Centers for Disease Control Surgical Infection Prevention program indicated that only 41% of prophylactic antibacterials were correctly stopped within 24 h of the end of surgery. Electronic order sets have shown promise as a means of integrating guideline information with electronic order entry systems and facilitating safer, more effective care. The aim was to study the effectiveness of a computer-based antibacterial order set on increasing the proportion of patients who have antibacterial wound prophylaxis discontinued in the appropriate time frame. The authors conducted a quasi-experimental interrupted time-series analysis over an 8-month study period with the implementation of a computer-based order system designed to prevent excessive duration of surgical prophylaxis antibacterials. The primary outcome was the proportion of surgeries with antibacterials discontinued in the appropriate time frame. Additionally, we evaluated the percent of surgeries after implementation of the electronic intervention with chart documentation of infection among surgeries where the prescriber indicated the reason for antibacterial therapy was treatment. The computer-based order intervention significantly improved the proportion of surgeries with timely discontinuation of antibacterials from 38.8% to 55.7% (p < 0.001) in the intervention hospital, while the control hospital remained at 56-57% (p = 0.006 for the difference between treated and control hospitals). In surgeries after intervention implementation where a prescriber indicated the reason for antibacterial therapy was treatment, the prevalence of chart documented infection was only 14%. A computer-based electronic order set intervention increased timely discontinuation of postoperative antibacterials.	f	\N
21278729	Optogenetics is a technique for controlling subpopulations of neurons in the intact brain using light. This technique has the potential to enhance basic systems neuroscience research and to inform the mechanisms and treatment of brain injury and disease. Before launching large-scale primate studies, the method needs to be further characterized and adapted for use in the primate brain. We assessed the safety and efficiency of two viral vector systems (lentivirus and adeno-associated virus), two human promoters (human synapsin (hSyn) and human thymocyte-1 (hThy-1)) and three excitatory and inhibitory mammalian codon-optimized opsins (channelrhodopsin-2, enhanced Natronomonas pharaonis halorhodopsin and the step-function opsin), which we characterized electrophysiologically, histologically and behaviorally in rhesus monkeys (Macaca mulatta). We also introduced a new device for measuring in vivo fluorescence over time, allowing minimally invasive assessment of construct expression in the intact brain. We present a set of optogenetic tools designed for optogenetic experiments in the non-human primate brain.	f	\N
21291294	We have assessed gastroduodenal, endoscopical and histopathological findings in a series of patients with microscopic colitis (MC). We studied 75 patients with MC, 27 with collagenous colitis (CC) and 48 with lymphocytic colitis (LC), and 60 controls. Data of endoscopical findings were collected and biopsies were assessed. Helicobacter pylori infection rate was 15% in MC and 28% in the controls (p = 0.088). Age at diagnosis of MC was higher in H. pylori positive than negative patients (63.4 ± 9.6 vs. 54.4 ± 13.1 years; p = 0.034). Gastric endoscopic erosions were more prevalent in CC than in LC (25.9% vs. 6.2%; p = 0.030) and associated with thick body glands and antral predominance of gastritis in H. pylori positive patients. Rates of focal gastritis (5.6% vs. 6.9%) and lymphocytic gastritis (5.6% vs. 10%) were similar in MC and controls. LC was associated with gastric epithelial lymphocytosis and lymphocytic gastritis. Fifteen patients (20%) had celiac disease. Unlike LC, CC is associated with endoscopic erosions, likely related with the high acid secretion capacity as indicated by the ample body glands and antral predominance of gastritis in H. pylori associated cases of CC. The presence of some divergent gastroduodenal features in LC and CC, and in comparison with those reported in inflammatory bowel disease (IBD), supports the concept that these two conditions differ not only from IBD but also from each other. The findings also suggest the presence of pathogenetic links between colorectal and gastroduodenal abnormalities.	f	\N
21297177	Moderate chronic kidney disease (CKD) (defined by an estimated glomerular filtration rate of 30-60 ml/min) is associated with mild hypertriglyceridemia related to delayed catabolism of triglyceride-rich lipoprotein particles. Altered apolipoprotein C-III (apoC-III) metabolism may contribute to dyslipidemia in CKD. To further characterize the dyslipidemia of CKD, we investigated the kinetics of plasma apoC-III in 7 nonobese, nondiabetic, non-nephrotic CKD subjects and 7 age- and sex-matched healthy controls, using deuterated leucine ([5, 5, 5, ²H₃]leucine), gas chromatography-mass spectrometry, and multicompartmental modeling. Compared with controls, CKD subjects had higher concentrations of plasma and VLDL triglycerides and plasma and VLDL apoC-III (P < 0.05). The increased plasma apoC-III concentration was associated with a decreased apoC-III fractional catabolic rate (FCR) (1.21 ± 0.15 vs. 0.74 ± 0.12 pools/day, P = 0.03). There were no differences between apoC-III production rates of controls and those of CKD subjects. In CKD subjects, plasma apoC-III concentration was significantly and negatively correlated with apoC-III FCR (r = -0.749, P = 0.05) but not with apoC-III production rate. Plasma apoC-III concentration was positively correlated with plasma and VLDL triglycerides and VLDL apoB concentrations and negatively correlated with VLDL apoB FCR (P < 0.05 for all). ApoC-III FCR was negatively correlated with plasma and VLDL triglycerides and VLDL apoB concentration and positively correlated with VLDL apoB FCR (P < 0.05 for all). Altered plasma apoC-III metabolism is a feature of dyslipidemia in moderate CKD. Modification of apoC-III catabolism may be an important therapeutic target for reducing cardiovascular disease risk in moderate CKD.	f	\N
21303529	Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program. Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire. Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase. This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP. ClinicalTrials.gov: NCT00566930.	f	\N
21305298	Spondyloarthritis (SpA) are diseases with increased gut inflammation. To search for (anti-Saccharomyces cerevisiae) ASCA IgA, ASCA IgG, and anti-endomysial antibodies (EmA-IgA) in a cohort of 70 patients with SpA, we found 18.6% (13/70) positive for IgA-ASCA in the SpA group and 3/57 (5.2%) in the control group (P = 0.031). ASCA IgG and EmA-IgA were found at the same frequency in SpA and controls. No relationship of ASCA IgA positivity could be established with disease activity (measured by ESR, C-reactive protein, and BASDAI), presence of uveitis, or peripheral arthritis neither with functional status measured by BASFI. SpA patients present an increase in the IgA-ASCA positivity without any relationship to disease activity, functional index, clinical profile or the presence of HLA-B27. There is no evidence of higher prevalence of EmA-IgA in SpA patients in the studied sample.	f	\N
21307778	Vitamin D deficiency is a global health problem that has various adverse consequences. Vitamin D is mainly synthesized in the skin by sunlight (UV light) irradiation; therefore, vitamin D status is influenced by geographic locations, seasonal changes, and skin pigmentations. The kidney is involved in the biosynthesis of 1,25-dihydroxyvitamin D and the reuptake of filtered 25-hydroxyvitamin D from the proximal tubules, thus, vitamin D deficiency is highly prevalent in patients with kidney disease who have renal insufficiency. There is a growing body of epidemiological and clinical evidence in the literature that links vitamin D deficiency to cardiovascular disease. The discovery of the vitamin D hormone functioning as an endocrine inhibitor of the renin-angiotensin system provides an explanation for this association. This review will discuss the mechanism underlying the connection between vitamin D and cardiovascular disease and its physiological and therapeutic implications.	f	\N
21312278	Abnormal repetitive behaviors have been reported in Parkinson's disease (PD) during dopamine replacement therapy (DRT) and associated with individual predisposing features, including impulsivity. However, impulsivity and compulsive symptoms have never been explored in PD patients before initiation of DRT. We previously reported a 20% of impulse control disorders (ICD) in an Italian cohort. 103 consecutive newly diagnosed drug-naïve PD patients (means: age = 60.5 ± 9.2 years; duration = 15.4 ± 15.3 months) were screened for compulsive sexual behavior, compulsive buying, intermittent explosive disorder (Minnesota Impulsive Disorders Interview, MIDI), and pathological gambling (South Oaks Gambling Screen, SOGS). Barratt Impulsiveness Scale (BIS-11) and Maudsley Obsessional-Compulsive Questionnaire (MOCQ/R) assessed impulsivity, obsessive-compulsive symptoms, respectively. Depression (GDS-15) and general cognitive status were additionally assessed. We also compared ICDs frequency with our healthy controls. 17.5% of PD patients screened positive for at least one ICD at MIDI (17/103) and SOGS (1/103), though none had a disorder based on DSM-IV criteria. These frequencies were similar to healthy controls. There was a trend toward higher scores in BIS-11 attentive-impulsivity subscale (15.2 ± 4.8 vs. 18.7 ± 4.9; P = 0.007) and in MOCQ/R-Doubting subscale (0.67 ± 1.1 vs. 1.5 ± 1.2; P = 0.007) in PD with ICD. We also observed a positive correlation between GDS-15 and BIS-11. Similar to our healthy control population, we found a significant proportion of early PD patients positive for ICDs before starting treatment. We also found a relationship between impulsivity and depression. A detailed behavioral assessment before starting dopaminergic therapy is recommended.	f	\N
21316322	The role of oxidative stress in patients with chronic kidney disease (CKD) as a potential marker of morbidity and mortality remains poorly evaluated. The aim of the present study aims was thus: to determine plasma levels of malondialdehyde (MDA), end product of lipid peroxidation in patients at different CKD stages (predialysis and dialysis); to evaluate the association between plasma MDA levels and vascular disease or overall and cardiovascular mortality. Plasma MDA levels evaluated by HPLC, pulse wave velocity, aortic calcification score were evaluated in 94 CKD patients (67±13 years, 54% males, 29% at CKD stages 2-3, 32% at stages 4-5, 39% at stage 5D) prospectively followed for mortality. We observed that the plasma MDA levels were increased in patient with CKD and augmented progressively with CKD stages. However, we did not find any independent association between plasma levels of MDA and pulse wave velocity, aortic calcification score, or overall and cardiovascular mortality. Our results suggest that plasma MDA is not a useful biomarker in CKD patients.	f	\N
21317510	Many studies document racial variation, gender differences, and socioeconomic status (SES) patterning in cardiovascular disease (CVD) risk factors but few studies have investigated heterogeneity in SES differences by race/ethnicity or gender. Using data from the Multi-Ethnic Study of Atherosclerosis (N=6,814) and stratified regression models, we investigated race/ethnic differences in the SES patterning of diabetes, hypertension, smoking, and body mass index (BMI). Inverse socioeconomic gradients in hypertension, diabetes, smoking, and BMI were observed in White and Black women but associations were weaker or absent in Hispanic and Chinese women (except in the case of diabetes for Hispanic women). Even greater heterogeneity in social patterning of risk factors was observed in men. In White men all four risk factors were inversely associated with socioeconomic position, although often associations were only present or were stronger for education than for income. The inverse socioeconomic patterning was much less consistent in men of other races/ethnic groups, and higher SES was associated with higher BMI in non-White men. These findings have implications for understanding the causes of social patterning, for the analysis of SES adjusted race/ethnic differences, and for the targeting of interventions.	f	\N
21327566	A synergistic effect of alcohol and hypertension has been suggested to increase the risk for stroke. However, the contribution of alcohol-induced hypertension to stroke morbidity and mortality may be greater than observed, because the effects of different drinking patterns have not been separately investigated. Alcohol-induced transient peaks in systolic blood pressure may predispose to stroke. Recent studies have measured time trends of blood pressure elevations in relation to alcohol consumption. They found a significant morning surge in blood pressure, which was related to alcohol intake in a dose-dependent manner and was independent of smoking. Men with a severe form of hypertension showed a 12-fold increased risk for cardiovascular disease mortality associated with heavy binge drinking. Binge drinking is a significant risk factor for stroke. Hypertensive patients should be warned about the risks of alcohol and urged to avoid binge drinking because of an increased risk for all subtypes of stroke.	f	\N
21329838	We sought to study whether patients with right ventricular failure (RVF) secondary to chronic thromboembolic pulmonary hypertension (CTEPH) have reduced left ventricular (LV) mass, and whether LV mass reduction is caused by atrophy. The LV in patients with CTEPH is underfilled (unloaded). LV unloading may cause atrophic remodeling that is associated with diastolic and systolic dysfunction. We studied LV mass using cardiac magnetic resonance imaging (MRI) in 36 consecutive CTEPH patients (before/after pulmonary endarterectomy [PEA]) and 11 healthy volunteers selected to match age and sex of patients. We studied whether LV atrophy is present in monocrotaline (MCT)-injected rats with RVF or controls by measuring myocyte dimensions and performing in situ hybridization. At baseline, CTEPH patients with RVF had significantly lower LV free wall mass indexes than patients without RVF (35 ± 6 g/m(2) vs. 44 ± 7 g/m(2), p = 0.007) or volunteers (42 ± 6 g/m(2), p = 0.006). After PEA, LV free wall mass index increased (from 38 ± 6 g/m(2) to 44 ± 9 g/m(2), p = 0.001), as right ventricular (RV) ejection fraction improved (from 31 ± 8% to 56 ± 12%, p < 0.001). Compared with controls, rats with RVF had reduced LV free wall mass and smaller LV free wall myocytes. Expression of atrial natriuretic peptide was higher, whereas that of α-myosin heavy chain and sarcoplasmic reticulum calcium ATPase-2 were lower in RVF than in controls, both in RV and LV. RVF in patients with CTEPH is associated with reversible reduction in LV free wall mass. In a rat model of RVF, myocyte shrinkage due to atrophic remodeling contributed to reduction in LV free wall mass.	f	\N
21332905	• To describe a multicentre experience with preoperative platinum-based chemotherapy before radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) with loco-regional nodal metastases. • We identified 313 patients from the UTUC Collaboration (over 1200 patients), who underwent RNU with concomitant retroperitoneal lymph node dissection between 1990 and 2007 and met the inclusion criteria for one of three groups. • Group 1 comprised patients who received chemotherapy before RNU because of biopsy-proven loco-regional nodal metastases. • Group 2 consisted of patients who underwent primary RNU and were found to have metastatic nodal disease on final pathological review (node-positive). • Group 3 comprised a comparative cohort of patients treated with primary RNU for invasive or locally advanced (pT2/pT4) node-negative (N0) UTUC. • Groups 1, 2 and 3 included 18, 120 and 175 patients, respectively. The 5-year disease-free survival rates were 49%, 30% and 64%, whereas the 5-year cancer-specific survival rates were 44%, 36% and 69% in groups 1, 2 and 3, respectively. • In group 1, on final pathological evaluation, nine patients were pN0, six patients were pT0 and five patients had pT0N0 disease. Kaplan-Meier survival analyses showed similar recurrence and survival rates in group 1 compared with group 3 (P= 0.14 and P= 0.06, respectively). • Meanwhile, group 2 had significantly lower disease-free and cancer-specific survival rates compared with group 3 (P < 0.001 and P < 0.001, respectively) and compared with group 1 (P= 0.04 and P= 0.06, respectively). • Preoperative chemotherapy followed by aggressive surgical consolidation may yield favourable oncological outcomes in patients with UTUC with loco-regional nodal metastases. • These data support further evaluation of neoadjuvant systemic therapy in patients at risk for locally advanced UTUC.	f	\N
21342667	In Belgium, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the national schedule in 2007. The early impact of PCV7 vaccination on paediatric invasive disease was estimated by comparing pre- and post-vaccination incidence from national surveillance. In children <2 year-olds, vaccine-serotype incidence declined by 96% but non-vaccine-types increased 2-3-fold. Overall invasive disease decreased by 23-46%, depending on adjustment for under-reporting and pre-vaccine trends. Non-vaccine-types 1 and 19A had increased before PCV7 use, suggesting the contribution of other factors. Estimation of PCV7 impact comparing pre- and post-vaccination data should adjust for pre-vaccine trends, and serotype dynamics need further exploration.	f	\N
21349334	The intestinal microbiota is an ecosystem formed by a variety of ecological niches, made of several bacterial species and a very large amount of strains. The microbiota is in close contact with the intestinal mucosa or epithelial interface which is, after the respiratory area, the largest surface of the body, occupying approximately 250-400 m(2). The physiological activities of the microbiota are manifold and are just being unraveled. Based on the observations of the multiple roles played by the microbiota in health and disease, the notion of modifying it with appropriate formulations, i.e. probiotics, is being tested in several settings. This review summarizes the current knowledge on probiotics and discusses both limitations and acquired evidence to support their use in preventive and therapeutic medicine.	f	\N
21350933	This study used data mining techniques to investigate disease forms in various administrative areas and to analyze the differences among various administrative areas in order to further draw up a disease distribution map. It is hoped that may help formulate future public health strategies and to allocate medical resources more appropriately. The major disease forms for residents under the age of 60 were hypertension, hyperglycemia and hyperlipidemia. In regard to the neighboring areas, three neighboring areas, A1, A3, and B9, shared the same disease problems with A4, A5, and B3, while two mountain-area cities, B7 and C10, experienced higher instances of liver function impairment. In terms of the clustering phenomenon among municipally graded administrative areas, the major health problems in Grade A cities were hypertension, hyperglycemia, and hyperlipidemia. The health problems such as liver function impairment and renal dysfunction were more frequently observed in Grade B and Grade C cities.	f	\N
21352090	Autologous chondrocyte implantation (ACI) is considered a promising choice for the treatment of cartilage defects. However, the application of ACI to osteoarthritic patients is, in general, contraindicated. The purpose of this study is to evaluate the efficiency of three-dimensionally structured ACI (3D-ACI; CaReS) in a rat model of knee osteoarthritis (OA). OA-like degenerative changes in the articular cartilage were created by transecting the anterior cruciate ligament (ACLT) in athymic nude rats. Two weeks later, CaReS was transplanted at the cartilage injury sites created by micro-drilling in the patella groove (Chondrocyte-implanted (CI) group: CaReS collagen with human chondrocytes; Collagen group: CaReS collagen without cells; and Sham group: sham operation; n = 15/group). Reverse Transcription Polymerase Chain Reaction (RT-PCR) analysis demonstrated the expression of human-specific type 2 collagen and Sry-type high-mobility-group box 9 (SOX9) in the CI group-not in the other groups-throughout the study period. Double immunohistochemistry for human-specific type 2 collagen and human leukocyte antigen-abacavir (HLA-ABC) at week 4 showed positive staining in the CI group only. Macroscopic assessment showed better repair at the cartilage defect sites in the CI group, compared to the other groups. Histological assessment with toluidine blue staining showed that the thickness of the articular cartilage and semi-quantitative histological scores were higher in the CI group than in the other groups up to week 20. We demonstrate, for the first time, that 3D-ACI is effective in repairing cartilage defects in a rat model of ACLT-induced OA.	f	\N
21354253	Molecular rotors are a form of fluorescent intramolecular charge-transfer complexes that can undergo intramolecular twisting motion upon photoexcitation. Twisted-state formation leads to non-radiative relaxation that competes with fluorescence emission. In bulk solutions, these molecules exhibit a viscosity-dependent quantum yield. On the molecular scale, the fluorescence emission is a function of the local free volume, which in turn is related to the local micro-viscosity. Membrane viscosity, and the inverse; fluidity, are characteristic terms used to describe the ease of movement withing the membrane. Often, changes in membrane viscosity govern intracellular processes and are indicative of a disease state. Molecular rotors have been used to investigate viscosity changes in liposomes and cells, but accuracy is affected by local concentration gradients and sample optical properties. We have developed self-calibrating ratiometric molecular rotors to overcome this challenge and integrated the new molecules into a DLPC liposome model exposed to the membrane-fluidizing agent propanol. We show that the ratiometric emission intensity linearly decreases with the propanol exposure and that the ratiometric intensity is widely independent of the total liposome concentration. Conversely, dye concentration inside liposomes influences the sensitivity of the system. We suggest that the new self-calibrating dyes can be used for real-time viscosity sensing in liposome systems with the advantages of lifetime measurements, but with low-cost steady-state instrumentation.	f	\N
21357888	This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD), which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure), were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils), dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life) and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.	f	\N
21360500	In addition to inducing a self-limited myopathy, statin use is associated with an immune-mediated necrotizing myopathy (IMNM), with autoantibodies that recognize ∼200-kd and ∼100-kd autoantigens. The purpose of this study was to identify these molecules to help clarify the disease mechanism and facilitate diagnosis. The effect of statin treatment on autoantigen expression was addressed by immunoprecipitation using sera from patients. The identity of the ∼100-kd autoantigen was confirmed by immunoprecipitation of in vitro-translated 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) protein. HMGCR expression in muscle was analyzed by immunofluorescence. A cohort of myopathy patients was screened for anti-HMGCR autoantibodies by enzyme-linked immunosorbent assay and genotyped for the rs4149056 C allele, a predictor of self-limited statin myopathy. Statin exposure induced expression of the ∼200-kd/∼100-kd autoantigens in cultured cells. HMGCR was identified as the ∼100-kd autoantigen. Competition experiments demonstrated no distinct autoantibodies recognizing the ∼200-kd protein. In muscle biopsy tissues from anti-HMGCR-positive patients, HMGCR expression was up-regulated in cells expressing neural cell adhesion molecule, a marker of muscle regeneration. Anti-HMGCR autoantibodies were found in 45 of 750 patients presenting to the Johns Hopkins Myositis Center (6%). Among patients ages 50 years and older, 92.3% had taken statins. The prevalence of the rs4149056 C allele was not increased in patients with anti-HMGCR. Statins up-regulate the expression of HMGCR, the major target of autoantibodies in statin-associated IMNM. Regenerating muscle cells express high levels of HMGCR, which may sustain the immune response even after statins are discontinued. These studies demonstrate a mechanistic link between an environmental trigger and the development of sustained autoimmunity. Detection of anti-HMGCR autoantibodies may facilitate diagnosis and direct therapy.	f	\N
21362127	Type 3 von Willebrand disease (VWD) is an autosomal recessive bleeding disorder, characterized by virtually undetectable plasma von Willebrand factor (VWF) and consequently reduced plasma factor VIII levels. Genetic mutations responsible for type 3 VWD are very heterogeneous, scattered throughout the VWF gene and show high variability among different populations. Twenty-five severe VWD patients were studied by direct sequencing of the 51 coding exons of the VWF gene. The total number of VWD type 3 families in Hungary is 24, of which 23 were investigated. Fifteen novel mutations were identified in 31 alleles, five being nonsense mutations (p.Q1238X, p.Q1898X, p.Q1931X, p.S2505X and p.S2568X), four small deletions and insertions resulting in frame shifts (c.1992insC, c.3622delT, c.5315insGA and c.7333delG), one a large partial deletion (delExon1-3) of the 5'-region, four candidate missense mutations (p.C35R, p.R81G, p.C295S, p.C623T) and one a candidate splice site mutation (c.1730-10C>A). Six previously described mutations were detected in 17 alleles, including the repeatedly found c.2435delC, p.R1659X and p.R1853X. Only one patient developed alloantibodies to VWF, carrying a homozygous c.3622delT. We report the genetic background of the entire Hungarian type 3 VWD population. A large novel deletion, most probably due to a founder effect, seems to be unique to Hungarian type 3 VWD patients with high allele frequency. In contrast to previous reports, none of the five patients homozygous for the large partial deletion developed inhibitors to VWF. This discrepancy raises the possibility of selection bias in some of the reports.	f	\N
21363991	Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in Shandong Province, China. In this study, we combined ecologic niche modeling with geographic information systems (GIS) and remote sensing techniques to identify the risk factors and affected areas of hantavirus infections in rodent hosts. Land cover and elevation were found to be closely associated with the presence of hantavirus-infected rodent hosts. The averaged area under the receiver operating characteristic curve was 0.864, implying good performance. The predicted risk maps based on the model were validated both by the hantavirus-infected rodents' distribution and HFRS human case localities with a good fit. These findings have the applications for targeting control and prevention efforts.	f	\N
21397153	Epidermolysis bullosa acquisita (EBA) is the rarest of the autoimmune bullous diseases (AIBD). It is defined as an AIBD secondary to production of antibodies directed against type VII collagen and then binding to anchoring fibrils in the basal membrane zone (BMZ) of the skin and the Malpighian mucosa. To evaluate risk factors, different clinical forms and diagnostic methods, and the efficacy of treatments. The articles were identified by a search of PubMed and Embase from the initial creation of these databases through to March 2009. We selected generalised reviews and meta-analyses, cases involving unusual and/or serious clinical presentations, studies of immunological tests and homogeneous retrospective series regarding therapy. Of the 206 articles analysed, only two were of an adequate level of proof, with four of intermediate level, and all the others of only low level. EBA affects all age groups (from newborn infants to the very elderly) with a slight predominance in female subjects. Diagnosis must be considered in subjects with black skin of African origin. A drug-induced origin of the disease was reported in 11% of cases of IgA-EBA. Classical EBA (30 to 50% of cases), resembles epidermolysis bullosa hereditaria (EBH), with fragile skin, non-inflammatory bullae, dystrophic scars and milia. Numerous atypical and misleading forms exist. Evocative signs are the presence of mucosal lesions and/or scars. The severity of EBA is determined by the extent of cutaneous lesions, and ophthalmological, ENT and/or oesophageal involvement. Crohn's disease is associated in 25% of cases of EBA. Unequivocal diagnosis is provided by direct immunoelectron microscopy (IEM). Therapeutic efficacy has been reported for dapsone, sulphapyridine and colchicine in milder forms, and for cyclosporine, mycophenolate mofetil, rituximab, intravenous immunoglobulins and extracorporeal photochemotherapy in resistant and severe forms. A number of authors have reported inefficacy of systemic corticosteroids, even in high-dose regimens, with the development of corticosteroid dependence in certain cases. In the absence of any therapeutic trials, it is difficult to select optimal treatment; however, the benefit/risk ratio of systemic corticosteroid treatment is unfavourable.	f	\N
21397734	In this paper we introduce a new technical development of branching processes that can potentially model spread of epidemics by including various stages of infection. In fact, we present an epidemic model that the disease spreads from an individual to another one in such a way that the ability of individual u to infect a susceptible individual depends only on how long u has been infected. For analysis of this model, we introduce a new and special model of the Crump-Mode-Jagers branching processes in discrete time and obtain some of its fundamental properties.	f	\N
21404106	To confirm the efficacy and toxicity of Erlotinib in combination with Gemcitabine and Capecitabine when used as a first-line therapy in metastatic/recurrent pancreatic cancer (PC). Locally advanced PC was excluded. Erlotinib was given at a dose of 100 mg daily from D1 to D28. 1000 mg/m(2) of gemcitabine was given on D1,8,15 and 1660 mg/m(2)/day of capecitabine was given from D1 to 21, repeated every 4 weeks. Response was assessed every 8 weeks. A total of 47 patients were enrolled. Response rate and disease control rate was 32.6% (95% CI, 18.6-46.6%) and 83.7% (95% CI, 72.7-94.7%) respectively. The PFS was 6.5 months (95% CI, 3.4-9.7) and OS was 12.0 months (95% CI, 8.6-15.9). The Gr 3/4 toxicities were: neutropenia (6.8%), thrombocytopenia (3.2%), anemia (1.6%). nausea (1.6%), vomiting (1.6%), anorexia (5.3%), rash (2.4%). The EGFR expression was associated with shorter OS and ERCC2 expression was associated with longer PFS and OS. PFS and OS were not different according to K-RAS mutation or polymorphism of RRM1 and CDA. Erlotinib, gemcitabine and capecitabine combination showed promising efficacy and good tolerability in metastatic PC. This efficacy was observed irrespective of K-RAS mutation, and EGFR expression was poor prognostic factor for OS.	f	\N
21415164	Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor-negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase α), ELOVL1 (elongation of very long chain fatty acid-like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element-binding protein cleavage-activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone-responsive protein)] indicated that silencing of multiple lipid metabolism-regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment.	f	\N
21418090	To investigate associations between fasting plasma glucose level and the prevalence of acquired colour vision impairment in type 2 diabetes patients without diabetic retinopathy. Participants in this cross-sectional study of male officials aged 20-60 yr in the Japanese Self Defence Force, underwent colour vision testing, ophthalmic examination, a standardized interview and examination of venous blood samples. Ishihara plates, a Lanthony 15-hue desaturated panel and Standard Pseudoisochromatic Plates Part 2 were used to examine colour vision. The Farnsworth-Munsell 100-hue test was performed to define acquired colour vision impairment. Cardiovascular disease risk factors were determined from serum blood samples, physical records and an interview. We performed logistic regression analysis adjusted for age, diagnosed hypertension, dyslipidaemia, cataract, glaucoma, being overweight, smoking status and alcohol intake. Crude and adjusted odds ratios were calculated for three glucose levels, which included normal fasting glucose, impaired fasting glucose and diabetes. Out of a total of 1042 men enrolled, 872 were eligible for the study, and 31 were diagnosed with acquired colour vision impairment. As compared with the subjects with normal fasting glucose (< 5.6 mmol/l), the crude odds ratio for acquired colour vision impairment was 0.93 (95% CI 0.32-2.74) for the subjects with impaired fasting glucose (5.6-6.9 mmol/l) and 8.07 (95% CI 2.48-26.22) for the patients with type 2 diabetes. The multiple-adjusted odds ratios were 0.77 (95% CI 0.25-2.34) for the subjects with impaired fasting glucose and 5.89 (95% CI 1.55-22.40) for the patients with type 2 diabetes. Our findings suggest that there is a dramatically increased prevalence of acquired colour vision impairment in type 2 diabetes patients without diabetic retinopathy which might be attributable to another pathogenesis associated with diabetic retinopathy.	f	\N
21421095	Appendectomy remains one of the most common emergency surgical procedures encountered throughout the United States. With improvements in diagnostic techniques, the efficiency of diagnosis has increased over the years. However, the entity of negative appendectomies still poses a dilemma because these are associated with unnecessary risks and costs to both patients and institutions. This study was conducted to show current statistics and trends in negative appendectomy rates in the United States. A retrospective analysis was conducted using data from the National Inpatient Sample from 1998 to 2007. Adult patients (>18 y) having undergone appendectomies were identified by the appropriate International Classification of Diseases 9th revision codes. Patients with incidental appendectomy and those with appendiceal pathologies, also identified by relevant International Classification of Diseases 9th revision codes, were excluded. The remaining patients represent those who underwent an appendectomy without appendiceal disease. The patients then were stratified according to sex, women were classified further into younger (18-45 y) and older (>45 y) based on child-bearing age. The primary diagnoses subsequently were categorized by sex to identify the most common conditions mistaken for appendiceal disease in the 2 groups. Between 1998 and 2007, there were 475,651 cases of appendectomy that were isolated. Of these, 56,252 were negative appendectomies (11.83%). There was a consistent decrease in the negative appendectomy rates from 14.7% in 1998 to 8.47% in 2007. Women accounted for 71.6% of cases of negative appendectomy, and men accounted for 28.4%. The mortality rate was 1.07%, men were associated with a higher rate of mortality (1.93% vs .74%; P < .001). Ovarian cyst was the most common diagnosis mistaken for appendicitis in younger women, whereas malignant disease of the ovary was the most common condition mistaken for appendiceal disease in women ages 45 and older. The most common misdiagnosis in men was diverticulitis of the colon. There has been a consistent decline in the rates of negative appendectomy. This trend may be attributed to better diagnostics. Gynecologic conditions involving the ovary are the most common to be misdiagnosed as appendiceal disease in women.	f	\N
21422948	This study was designed to characterize the energy metabolism in the patients with acute-on-chronic liver failure (ACLF). Protein-energy malnutrition usually occurs in the patients with chronic liver disease and is exacerbated during the progression of liver failure. Unfortunately, there is limited study to fully elucidate the energy metabolism in the patients with ACLF. A retrospective cohort was designed with a total of 282 patients (100 patients with ACLF, 100 with liver cirrhosis, and 82 with chronic hepatitis B). Resting energy expenditure and the oxidation rates of glucose, lipid, and protein were assessed by indirect heat measurement using the critical care monitor and desktop analysis system, nutritive metabolic investigation system. Survival rate was estimated with the Kaplan-Meier method. There was no significant difference in resting energy expenditure among the patients with ACLF, the liver cirrhosis, and the chronic hepatitis (1402.05±480.07 kcal/d in patients with ACLF, 1274.27±316.36 kcal/d in patients with liver cirrhosis, and 1396.77±384.80 kcal/d in patients with chronic hepatitis). Respiratory quotient (RQ) was significantly lower in the patients with ACLF than those in the liver cirrhosis and the chronic hepatitis B (P=0.000). In patients with ACLF, RQ of the nonsurvival group was significantly lower than the survival group (P=0.000). It is identified from receiver operating characteristic curve analysis that a RQ cutoff value of 0.83 (area under the receiver operating characteristic curve, 0.760) is favorable to predict good prognosis in patients with liver failure, which has a sensitivity of 73.68%, a specificity of 74.42%, and positive predictive value of 79.2% and negative predictive value of 68.1%. In patients with ACLF, RQ was significantly lower in the nonsurvival group than the survival group, thus suggesting that RQ may be used as an indicator of prognosis of liver failure.	f	\N
21426326	To investigate for the first time the natural history and long-term evolution of "familial cortical tremor, myoclonus, and epilepsy." We evaluated the clinical, electrophysiologic, and treatment data of 14 patients from three families linked to 2p11.1-q12.2. A simplified scale was used to score myoclonus severity. Electroencephalography (EEG) studies were reviewed for the evaluation of background activity, paroxysmal abnormalities, and photoparoxysmal response. Data were organized for age groups. Correlation and logistic regression analysis were performed. Patients' mean age was 47.8 ± 22.0 years (range 20-86 years). Mean age at disease onset was 20.2 ± 7.8 years (range 11-40 years); mean follow-up duration was 14.0 ± 5.8 years (range 7-28 years). Evaluation at different age groups revealed a gradual, progressive worsening of the myoclonus in 10 patients (71.4%). Two subjects aged >80 years showed myoclonus interfering with autonomous walking. Myoclonus severity was correlated with disease duration (p<0.001) and patients' age (p=0.001). Six patients (42.8%) experienced seizures, usually between the second and sixth decades of life. Evaluation of EEG long-term evolution revealed progressive slowing of background activity in parallel with the gradual worsening of myoclonus. In contrast, paroxysmal activity and photosensitivity were particularly evident during the intermediate phases of the disease. In addition, psychiatric and neuropsychological dysfunction occurred in more than one third of the patients. We provide data for a slight age-dependent progression and the presence of neuropsychiatric and neuropsychological dysfunction in this unique syndrome, for which the definition of familial or autosomal dominant cortical tremor, myoclonus, and epilepsy (FCTME/ADCME) seems to be, therefore, more appropriate.	f	\N
21429534	Familial combined hyperlipidemia (FCH) is a genetic model of atherogenic dyslipidemia with insulin resistance and early coronary disease. Our objective was to evaluate the presence of carotid alterations as a marker of systemic atherosclerosis in subjects with FCH and assess the effect of 80 mg of atorvastatin per day in carotid plaque thickness after 2 years. 100 non diabetic subjects with FCH in primary prevention were consecutively included. Clinical and biochemical parameters and carotid ultrasonography were performed. Subjects with carotid plaque started treatment with 80 mg of atorvastatin per day for 2 years. 29% of subjects had carotid plaques. We did not find significant differences in any of the parameters between subjects with presence or absence of carotid plaques. Twenty subjects with carotid plaques accepted/agreed to participate in the interventional study. Two years follow-up showed a significant reduction in LDLc (30%) and carotid plaque thickness (10%). Carotid ultrasonography is useful to detect subclinical atherosclerosis in high risk cardiovascular patients such as subjects with FCH. Treatment with high doses of atorvastatin induces the regression of carotid plaque thickness after 2 years follow-up. Our results suggest that intensive treatment with atorvastatin could be useful to reduce the development of cardiovascular disease in this group of patients.	f	\N
21430371	The aim of this study was to evaluate the impact of clinical variables and biologic features on response rate (RR), overall survival (OS) and progression-free survival (PFS) in 111 patients with de novo diffuse large B cell lymphoma (DLBCL). Fifty-three patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and 58 patients were treated with R-CHOP (rituximab + CHOP). The variables predictive of RR in the CHOP group were B symptoms, age, clinical stage, bone marrow involvement, bulky disease, International Prognostic Index (IPI) and Bcl-2; in the R-CHOP group, these variables were bulky disease, bone marrow involvement, IPI and Ki67 expression >80%. Multivariate analysis showed that in patients treated with CHOP, the independent prognostic factors associated with PFS were age, bulky disease, IPI and Bcl-2 and those associated with OS were performance status, clinical stage, IPI and bone marrow involvement. In contrast, in patients treated with R-CHOP, the variable shown by multivariate analysis to be an independent prognostic factor associated with PFS was bulky disease, whereas Ki67 expression >80% was associated with OS and PFS. Our data show that a high Ki67 expression and bulky disease could represent possible predictive factors of poor prognosis, which would help to identify a high-risk subgroup of newly diagnosed DLBCL.	f	\N
21437774	The enormous abundance of lipid molecules in the central nervous system (CNS) suggests that their role is not limited to be structural and energetic components of cells. Over the last decades, some lipids in the CNS have been identified as intracellular signalers, while others are known to act as neuromodulators of neurotransmission through binding to specific receptors. Neurotransmitters of lipidic nature, currently known as neurolipids, are synthesized during the metabolism of phospholipid precursors present in cell membranes. Therefore, the anatomical identification of each of the different lipid species in human CNS by imaging mass spectrometry (IMS), in association with other biochemical techniques with spatial resolution, can increase our knowledge on the precise metabolic routes that synthesize these neurolipids and their localization. The present study shows the lipid distribution obtained by MALDI-TOF IMS in human frontal cortex, hippocampus, and striatal area, together with functional autoradiography of cannabinoid and LPA receptors. The combined application of these methods to postmortem human brain samples may be envisioned as critical to further understand neurological diseases, in general, and particularly, the neurodegeneration that accompanies Alzheimer's disease.	f	\N
21438696	To test the hypothesis of a significant association between resting heart rate (RHR) and coronary artery calcium (CAC). This is a cross-sectional study of a subset of women enrolled in the estrogen-alone clinical trial of the Women's Health Initiative (WHI). We used a longitudinal study that enrolled 998 postmenopausal women with a history of hysterectomy between the ages of 50 and 59 at enrollment at 40 different clinical centers. RHR was measured at enrollment and throughout the study, and CAC was determined approximately 7 years after the baseline clinic visit. The mean (standard deviation [SD]) age was 55 (2.8) years. With adjustment for age and ethnicity, a 10-unit increment in RHR was significantly associated with CAC (SD 1.18, 95% confidence interval [CI] 1.01-1.38), but this was no longer significant after adjustment for body mass index (BMI), income, education, dyslipidemia, diabetes, smoking, and hypertension (SD 1.06, 95% CI 0.90-1.25). In a fully adjusted multivariable model, however, there was a significant interaction (p=0.03) between baseline RHR and systolic blood pressure (SBP) for the presence of any CAC. Compared to women with an RHR < 80 beats per minute (BPM) and an SBP < 140 mm Hg, those who had an RHR ≥ 80 BPM and an SBP ≥ 140 mm Hg had 2.66-fold higher odds (1.08-6.57) for the presence of any CAC. Compared to those with normal BP and RHR, postmenopausal, hysterectomized women with an elevated SBP and RHR have a significantly higher odds for the presence of calcified coronary artery disease.	f	\N
21438811	Hepatic steatosis, considered the first step in the pathophysiologic continuum of non-alcoholic fatty liver disease, is estimated to afflict 30% of the US population and over 75% of patients with Type 2 diabetes. Given the expected rise in the prevalence of obesity and Type 2 diabetes in the following decades, hepatic steatosis will, if not already, become an epidemic. The consequences of hepatic steatosis are numerous, and range from progression to chronic liver disease, with its associated morbidity and mortality, to worsening insulin resistance and Type 2 diabetes, as well as being an independent contributor to cardiovascular disease. All such consequences are more likely to occur in patients with Type 2 diabetes who are already at high risk of cardiovascular events. In this article we review the evidence behind the available therapeutic options for hepatic steatosis, and identify challenges and unmet needs in the field.	f	\N
21439159	The influence of respiratory infections on asthma has not been fully understood. Acute viral and bacterial infections often lead to exacerbations. Less is known about the role of chronic infections, particularly with atypical pathogens. The aim of this study was to evaluate the impact of Chlamydophila pneumoniae and Mycoplasma pneumoniae infections on the control and severity of asthma. Spirometry, skin-prick tests as well as measurement of immunoglobulin G (IgG), IgM, and IgA against C. pneumoniae and M. pneumoniae (ELISA) were performed in 95 patients with persistent asthma and 58 healthy controls. Additionally, in the selected group of asthmatic patients, presence of C. pneumoniae and M. pneumoniae genetic material was tested in induced sputum (polymerase chain reaction [PCR]). IgA against C. pneumoniae was found in 42 (44.2%) asthmatic patients and 17 (29.3%) controls (p < 0.05). It was found more often in the group with uncontrolled asthma (p = 0.001) as well as in nonatopic asthmatic patients (p < 0.05). IgG was detected in 58 asthmatic patients (61%) and 21 (36.2%) controls, more often in cases of uncontrolled (p < 0.05) and nonatopic asthma patients (p < 0.05). Such correlations were not found in relation to M. pneumoniae infections. C. pneumoniae was detected by means of PCR in respiratory secretions of eight asthmatic patients (40%), and M. pneumoniae was detected in two asthmatic patients (10%). In conclusion, C. pneumoniae infections are more frequent in asthmatic patients compared with healthy individuals and in nonatopic asthmatic patients compared to atopic patients. Chronic infection is associated with poor control of asthma.	f	\N
21443521	The inherited disorders of hemoglobin synthesis are the most common monogenic disorders worldwide. They include thalassemias, hemoglobin variants, and hereditary persistence of fetal hemoglobin. β-thalassemia is the most common monogenic disorder in India. Clinical manifestations of β-thalassemia are extremely variable in severity. The reasons for this heterogeneity are not very well understood. Previous studies have shown that the genetic variants that modulate HbF levels have a very strong impact on ameliorating the clinical phenotype. In the present study, 5570 blood samples from suspected cases were analyzed using HPLC, amplification refractory mutation system-PCR and reverse dot blot techniques. Of 5570 individuals, we found 676 cases of β-thalassemia disease. Molecular analysis revealed the presence of different β-thalassemia mutations in the population under study. Patients with β-thalassemia were classified into mild, moderate, and severe according to severity score based on Hb level, age of onset, age at which patients received their first blood transfusion, degree of growth retardation and splenectomy. Patients with β-thalassemia were analyzed for zinc finger and homeoboxes 2 (ZHX2) G779A polymorphism, and the association between ZHX2 gene polymorphism and severity of β-thalassemia was evaluated. We did not find a significant difference in genotypic and allelic frequency of ZHX2 gene between mild and moderate, mild and severe, and moderate and severe cases. There was no significant difference in high and low percentage of HbF in GG, GA, and AA bearing individuals showing that ZHX2 gene variant has no role in ameliorating the severity of β-thalassemia major in the South Indian population from Andhra Pradesh.	f	\N
21458394	Encapsulating peritoneal sclerosis (EPS) is a rare but life-threatening complication of peritoneal sclerosis (PD). In 2000, the International Society for Peritoneal Dialysis outlined diagnostic guidelines and a clinical definition of EPS. Over the intervening years, new evidence was published and several centers became more experienced managing patients with EPS. Although, further networking was initiated (European EPS Working Group), evidence regarding therapy and diagnosis of EPS is still lacking. Multicenter trials are needed to establish evidence regarding the management of EPS. Risk factors for EPS are identified and patients at risk should be monitored closely. In case of emerging signs of EPS, patients should be referred to an EPS-center before initiation of therapy. Morphology and immunohistochemistry will play a central role in the near future. Nowadays, most pathologists are not sophisticated in the pathology of peritoneal biopsies. Clear histological criteria are warranted. For the outcome of the patient, it is crucial that an EPS experienced surgeon conducts surgery.	f	\N
21463281	Dravet syndrome (DS) is an epileptic encephalopathy related mainly to mutations in the SCN1A gene, encoding for neuronal sodium channels. Patients with DS have a high risk of sudden unexpected death in epilepsy (SUDEP). In this study we investigated whether patients with DS present abnormalities in electrical and autonomic cardiac function. To this aim we assessed ventricular repolarization and heart rate variability (HRV) on standard electrocardiography (ECG) and on 24-h ECG Holter monitoring, respectively, in 20 patients affected by DS (6.8 ± 4 years, 11 female). As age- and sex-matched control groups, we also studied 20 patients with other epileptic syndromes receiving antiepileptic drugs (ES/AED, 6.0 ± 5 years, 12 female), 20 patients with other epileptic syndromes without treatment (ES/no-AED, 6.7 ± 4 years, 10 female), and 20 healthy children (HC, 7.2 ± 5 years, 11 females). Data analysis showed that patients with DS had depressed HRV variables compared to both ES patients (ES/AED and ES/no-AED) and HC control group, whereas no significant differences in HRV variables were found between ES patients (with and without treatment) and HC. There was no significant difference between patients with DS and all the other control groups in RR intervals, QT, and QTc interval analysis. In conclusion, DS patients display an imbalance of cardiac autonomic function toward a relative predominance of adrenergic tone compared to both healthy children and patients with other forms of epilepsy, independent of antiepileptic therapy. Follow-up studies should clarify the clinical significance of this autonomic impairment and whether HRV analysis can be helpful in predicting the risk of sudden death in patients with DS.	f	\N
21463368	Oral lichen planus (OLP) is generally accepted as a chronic and T-cell-mediated autoimmune disease, whose immunopathogenesis may involve antigen presentation, T-cell activation and migration as well as, possibly, tumor necrosis factor-alpha (TNF-α)-induced keratinocytes apoptosis. However, present treatment options for OLP are far from being satisfactory. Recent advances in understanding the pathogenesis of OLP, progress in biologics, and the success of biologic therapies in OLP indicate that biologic agents are facing expanding indications in OLP. In this review, we mainly discuss the role of T cells in the pathogenesis of OLP and several biologic therapies that directly and/or indirectly target T cells to treat OLP.	f	\N
21467169	Purpose. To compare the properties of the visual field index (VFI) to those of mean deviation (MD) in patients with glaucoma. Methods. MD and VFI were calculated in data obtained from an ongoing longitudinal study in which patients with glaucoma (N = 109, 204 eyes) were observed for 9.8 years (median, 21 tests) with static automated perimetry. MD and VFI were compared in one test of each eye, and a subset of 30 tests were selected to compare the VFI with the judgments of eight experts who judged the percentage of the remaining visual field. In series of tests obtained over time, rates of change, statistical significance, evidence of nonlinearity, and variability were compared between both indices. Results. In single tests, MD and VFI were closely related (r = 0.88, P < 0.001). The relationship between both indices appeared linear, except in visual fields with MDs better than -5.0 dB where 29 (22%) of 129 eyes exhibited a ceiling effect (VFI = 100%). Based on this relationship, the predicted VFIs for visual fields with MDs of -5, -10, and -15 dB were 91%, 76%, and 60%, respectively. The percentage of remaining visual field suggested by the VFI exceeded the range of the experts' subjective judgments in 16 (53%) of 30 eyes. In series of tests obtained over time, rates of change with the two indices were closely related (r = 0.79, P < 0.001), and statistically significant reductions over time (P < 0.05) occurred in a similar number of eyes (92 [45%] with MD, and 87 [43%] with VFI). Of the 105 eyes with statistically significant (P < 0.05) negative trend in either MD or VFI, 74 (70%) showed such trends with both indices (κ = 0.69). The variability of MD and VFI increased with damage, and there was no evidence that change over time was more linear with VFI than with MD. Conclusions. The VFI provides a simple and understandable metric of visual field damage, but its estimates of remaining visual field were more optimistic than those of the experts. Rates of change over time with both indices were closely related, but the reliance of the VFI on pattern deviation probability maps caused a ceiling effect that may have reduced its sensitivity to change in eyes with early damage. In this group of patients there was no evidence to suggest that the VFI is either superior or inferior to the MD as a summary measure of visual field damage.	f	\N
21468585	Basic transcription element-binding protein 2 (BTEB2) is a regulator of the proliferation and phenotypic changes of vascular smooth muscle cells (SMCs). The aim of the present study was to determine whether or not BTEB2 knockdown inhibits balloon injury-induced neointimal hyperplasia attributed to the proliferation and phenotypic changes of vascular SMCs. We found that the knockdown of BTEB2 with antisense oligonucleotides (Ad-As-BTEB2) significantly reduced the intima/media ratio compared to uninjured arteries and vessels treated with Ad-LacZ. Knockdown of BTEB2 suppresses the proliferation of cultured vascular SMCs, concurrent with the down-regulation of proliferating cell nuclear antigen, angiotensin II type 1 receptor and platelet-derived growth factor BB. In addition, BTEB2 knockdown caused the up-regulation of the differentiation marker smooth muscle α-actin and down-regulation of the dedifferentiation marker embryonic smooth muscle myosin heavy chain. The present study provides direct evidence that BTEB2 plays a critical role in balloon injury-induced neointimal hyperplasia, which is closely linked to vascular SMC proliferation and phenotypic modulation. This study highlights the fact that BTEB2 may be a potential target for the prevention of restenosis after vascular intervention.	f	\N
21473920	Diffusion imaging of post mortem brains has great potential both as a reference for brain specimens that undergo sectioning, and as a link between in vivo diffusion studies and "gold standard" histology/dissection. While there is a relatively mature literature on post mortem diffusion imaging of animals, human brains have proven more challenging due to their incompatibility with high-performance scanners. This study presents a method for post mortem diffusion imaging of whole, human brains using a clinical 3-Tesla scanner with a 3D segmented EPI spin-echo sequence. Results in eleven brains at 0.94 × 0.94 × 0.94 mm resolution are presented, and in a single brain at 0.73 × 0.73 × 0.73 mm resolution. Region-of-interest analysis of diffusion tensor parameters indicate that these properties are altered compared to in vivo (reduced diffusivity and anisotropy), with significant dependence on post mortem interval (time from death to fixation). Despite these alterations, diffusion tractography of several major tracts is successfully demonstrated at both resolutions. We also report novel findings of cortical anisotropy and partial volume effects.	f	\N
21474147	Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the gold standard surgical treatment for chronic ulcerative colitis. More recently, this procedure is being performed laparoscopically assisted. Postoperatively, small bowel obstruction (SBO) is one of the more common associated complications. However, it is unknown whether the addition of a laparoscopic approach has changed this risk. This study aims to assess and compare the incidence of SBOs after both open and laparoscopic restorative proctocolectomy. All subjects who underwent restorative proctocolectomy from 1998-2008 were identified from a prospective Colorectal Surgery Database. Medical records were reviewed for all cases of SBO, confirmed by a combination of clinical symptoms and radiologic evidence. Comparisons were made between laparoscopic and open approaches. The incidence of SBO was also subdivided into pre-ileostomy takedown, early post-ileostomy takedown (30 d post), and late post-ileostomy takedown (30 d to 1 y post). Several potential risk factors were also evaluated. Statistical analysis was performed utilizing Fisher's exact (for incidence) or t-tests (for means). Significance was defined as P < 0.05 A total of 290 open cases and 100 laparoscopic cases were identified during this time period. The overall incidence of SBO at 1 y post-ileostomy takedown was 14% (n = 42) in the open group and 16% (n = 16) laparoscopic (P = NS). In the pre-ileostomy takedown period the incidence of SBO was 7% (n = 21) open and 13% (n = 13) laparoscopic (P = NS). While in the post-takedown period, the early incidence was 4% (n = 12) open and 1% (n = 1) laparoscopic and late incidence was 3% (n = 9) open and 2% (n = 2) laparoscopic (P = NS). Factors associated with an increased risk of SBO include coronary artery disease, prior appendectomy and W and J pouch configurations. The burden of postoperative small bowel obstruction after restorative proctocolectomy is not changed with a laparoscopic approach. Most cases occur in the early postoperative period, especially prior to ileostomy reversal.	f	\N
21475985	To investigate the nationwide prevalence of hepatitis E virus (HEV) infection and to characterize HEV genomes among Japanese wild boars (Sus scrofa leucomystax), 578 boars captured in 25 prefectures from 2003 to 2010 were studied. Anti-HEV IgG was detected in 8.1%, and HEV RNA in 3.3% of boars. Among the 19 boar HEV isolates obtained from infected boars, 14 isolates (74%) were classified as genotype 3, 4 isolates (21%) as genotype 4, and the remaining isolate (wbJOY_06) was distantly related to all known HEV isolates of genotypes 1-4, differing by 18.4-25.0% and 18.0-24.3% within the 412-nucleotide sequence of ORF1 and ORF2, respectively. A genotype 4 boar HEV isolate (wbJGF_08-1) obtained herein shared 98.6% identity over the entire genome with a human HEV isolate obtained from a patient who developed acute hepatitis after consuming undercooked wild boar meat, suggesting that wild boars are also reservoirs for genotype 4 HEV in humans.	f	\N
21476292	The performance of a latex agglutination test (Mediace TPLA) in the detection of anti-treponemal antibody was evaluated in comparison with chemical luminescence tests (LumipulsII-N and Architect TPAb) in 346 cases. Anti-treponemal antibody was further determined by immunochromatography and immunoblotting tests and additionally evaluated by a serological test for syphilis with lipoidal antigens. The total concordance rate between the latex agglutination test and chemical luminescence tests ranged from 96% to 97%: the positive concordance rate ranged from 96% to 97%, and the negative concordance rate, from 97% to 98%. The latex agglutination test showed two false positive cases, and each chemical luminescence test showed two false positive cases, respectively. In eight cases, only the latex agglutination test showed negative results; all specimens contained anti-treponemal antibodies. However, none of these was considered to be a false positive and each was treated as syphilis based on the results of confirmatory analysis with immunochromatography and immunoblotting tests and a serological test for syphilis. The discordant results in the latex agglutination test and chemical luminescence tests may be caused by the different antigenisity of each test. With detailed analysis of those sera treated as syphilis, each specimen was found to contain various antibodies against syphilitic antigens, suggesting that there was a different specificity of native and recombinant antigens. Based on the present results for the comparison between the latex agglutination test and chemical luminescence tests, it was considered that further investigation is necessary to clarify the anti-treponemal antibody profile of syphilis at the disease stage.	f	\N
21477408	Ideally putative disease-modifying therapies for Alzheimer's disease (AD) should be tested in patients who have minimal morbidity. Current barriers to such trials in early disease include the lack of disease-specific early biomarkers, insensitivity of quantitative cognitive outcome measures, and expensive trial designs requiring large sample sizes and long duration. This paper describes principles and progress towards a novel trial design that overcomes these problems, utilizing wide-scale cognitive performance screening to define pre-trial cognitive decline trajectories which can serve as trial outcome measures to assess AD disease-modifying efficacy. Theoretical principles important for the detection of intra-individual cognitive decline and a practical example are described. Serial evaluations of community-based volunteers demonstrate how a screening tool method to detect subtle cognitive decline can predict in vivo amyloid pathology as a trigger for etiological evaluation. Trajectories of decline appear consistent over at least two years, suggesting they could be used as a trial inclusion criterion and ameliorable outcome measure together with other AD biomarkers. Informative trial durations could be 6-12 months, or extend to incorporate staggered random withdrawal or start designs, with as few as 20 individuals per treatment arm. This trial methodology offers significant advantages over current AD trial designs, including treatment at earlier stages of disease, shorter trial duration, obviation of informed consent difficulties, smaller sample sizes, reduced cost and--given adequate screening programs--sufficient subjects for multiple simultaneous trials. Importantly, it allows the rapid evaluation of putative treatments that may only be efficacious in pre-dementia states.	f	\N
21478119	The impact of drug-eluting stents (DES) has not been extensively investigated in patients with moderate to severe renal dysfunction, as these patients are consistently excluded from randomised studies. We sought to assess prospectively the effectiveness and safety of the new-generation DES in patients with moderate chronic kidney disease (CKD) and an isolated de novo lesion in the proximal segment of the left anterior descending artery (pLAD). We evaluated 400 consecutive patients with a pLAD lesion. There were 96 patients with moderate CKD (estimated glomerular filtration rate 59 ml/min/1.73 m2) and 304 without CKD. Major adverse cardiac events (MACE) were defined as death, non-fatal myocardial infarction and target lesion revascularisation (TLR). Clinical or telephone follow up was performed. There was a significantly higher incidence of mortality in patients with CKD (n=4) as compared with non-CKD (n=2) (4.16% versus 0.65%, respectively, p=0.03). The rate of non-fatal myocardial infarction was similar in the 2 cohorts (p=0.59), as was the TLR rate (p=0.99). Overall, there were no significant differences regarding MACE between the 2 groups of patients (p=0.19) during the 13.62 ± 6.22 month follow-up period. The rate of angiographic stent thrombosis was 2.08% in the CKD group versus 0.98% in the non-CKD group (p=0.59). New generation DES implantation in patients with CKD and a pLAD lesion is effective and safe, with rates of TLR and stent thrombosis comparable to those in patients with normal renal function. However, the higher mortality in patients with CKD needs further evaluation.	f	\N
21481900	Non-Hodgkin lymphomas are common cancers that can develop in the upper aero-digestive tract. We describe a case of a large B-cell palatine lymphoma with spontaneous clinical regression. A 58-year-old female patient presented with a sub-mucosal lesion of the hard palate. CT scan and magnetic resonance imaging revealed a lesion invading the right posterior palatine canal. At the second consultation, 15 days after performing the biopsy, the lesion had disappeared. PET scan proved the absence of lesion. Lymph node biopsy supported the diagnosis of large B-cell lymphoma. Large B-cell lymphoma of the hard palate is a rare disease. Only 27 cases have been described in the international literature. The anatomopathological analysis is often difficult to perform. The final diagnosis is often made by immunochemistry. The usual treatment is R-CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, prednisone combined to rituximab) with a 5-year survival rate at 55%.	f	\N
21484828	Anterior interosseous nerve syndrome (AINS) has not been widely recognized as a possible complication following peripheral catheterization. Herein we present a retrospective review of patients with AINS over the last 5 years. Six cases were identified, 4 associated with catheterization. AINS may be a rare complication of catheterization. Magnetic resonance imaging (MRI) may serve as an adjunct diagnostic modality to conventional electromyography (EMG) and nerve conduction studies, especially in patients who are intolerant of pain.	f	\N
21485204	This paper presents a novel matching method of vessels in 3D reconstruction of heart vessel. The directed binary tree was used to describe the topological structure of heart vessel tree's skeleton. Based on topological property and epipolar property, the branch-points and end-points of each branch level could be automatically matched along the direction of blood stream. Thereupon it is easy to couple the corresponding vessels segments of two angiograms projected in different directions. The 3D heart vessel tree was successfully reconstructed from clinic coronary angiograms, which validates the presented method.	f	\N
21489314	The standard treatment for patients with advanced transitional cell carcinoma of the bladder is platin based chemotherapy. Only approximately 50% of the patients respond to chemotherapy. Therefore, molecular predictive markers for identification of chemotherapy sensitive subgroups of patients are highly needed. We selected the transcription factor TFAP2α from a previously identified gene expression signature for chemotherapy response. TFAP2α expression and localization was assessed by immunohistochemistry using a tissue microarray (TMA) containing 282 bladder cancer tumors from patients with locally advanced (pT2-T4(b) and N(1-3)) or metastatic (M(1)) disease. All patients had received cisplatin containing chemotherapy. Furthermore, QPCR analysis of three TFAP2α isoforms was performed on tumor specimens of advanced muscle invasive bladder cancers (T2-4). Using the bladder cell lines T24 and SW780 the relation of TFAP2α and cisplatin and gemcitabine sensitivity as well as cell proliferation was examined using siRNA directed TFAP2α knockdown. TFAP2α protein expression was analyzed on a TMA with cores from 282 advanced bladder cancer tumors from patients treated with cisplatin based combinational chemotherapy. TFAP2α was identified as a strong independent predictive marker for a good response and survival after cisplatin-containing chemotherapy in patients with advanced bladder cancer. Strong TFAP2α nuclear and cytoplasmic staining predicted good response to chemotherapy in patients with lymph node metastasis, whereas weak TFAP2α nuclear staining predicted good response in patients without lymph node metastasis. In vitro studies showed that siRNA mediated knockdown of TFAP2α increased the proliferation of SW780 cells and rendered the cells less sensitive to cisplatin and gemcitabine. In contrast to that T24 bladder cells with mutated p53 showed to be more drug sensitive upon TFAP2α depletion. High levels of nuclear and cytoplasmic TFAP2α protein were a predictor of increased overall survival and progression free survival in patients with advanced bladder cancer treated with cisplatin based chemotherapy. TFAP2α knockdown increased the proliferation of the SW780 bladder cells and reduced cisplatin and gemcitabine induced cell death. The inverse effect was observed in the TP53 mutated T24 cell line where TFAP2α silencing augmented cisplatin and gemcitabine sensitivity and did not stimulate proliferation.	f	\N
21493631	Data on right ventricle (RV) regional function in adults with interatrial shunt are scarce. The aim of the study was to assess the regional RV deformation in the population of adults with uncorrected atrial left-to-right shunt and to establish a potential relationship between its magnitude and RV regional deformation. We studied 40 adults (30F/10M; mean age 39.2 years) with atrial septal defect (ASD) [average pulmonary-to-systemic blood flow ratio (Qp/Qs) 2.1 ± 0.7]. Standard echocardiographic evaluation was completed with right ventricular dimensions, parameters of its global [tricuspid annular plane systolic excursion (TAPSE), fractional area change, myocardial performance index], and regional [strain/strain rate (ε/SR)] function. Among echocardiographic indices describing RV global function, only TAPSE was increased when compared with healthy subjects. No differences in RV deformation data (ε/SR) between ASD patients and control group were found. Non-linear relationship between the differing Qp/Qs and maximal ε in the mid-segments of the RV free wall was observed. In patients with moderate shunt, maximal ε values were higher when compared with the values obtained in mild and large shunts. Regional RV deformation (ε/SR) does not differ significantly in the group of patients with various degrees of the left-to-right shunts when compared with healthy subjects. However, a non-linear correlation between Qp/Qs and ε could be observed. The affected region of the RV wall is the mid-segment and the highest values of ε were recorded in patients with moderate left-to-right shunts.	f	\N
21493742	The risk of a posttransplant recurrence of secondary glomerulonephritis (GN) is quite variable. Histologic recurrence is frequent in lupus nephritis, but the lesions are rarely severe and usually do not impair the long-term graft outcome. Patients with Henoch-Schonlein nephritis have graft survival similar to that of other renal diseases, although recurrent Henoch-Schonlein nephritis with extensive crescents has a poor prognosis. Amyloid light-chain amyloidosis recurs frequently in renal allografts but it rarely causes graft failure. Amyloidosis secondary to chronic inflammation may also recur, but this is extremely rare in patients with Behcet's disease or in those with familial Mediterranean fever, when the latter are treated with colchicine. Double organ transplantation (liver/kidney; heart/kidney), chemotherapy, and autologous stem cell transplantation may be considered in particular cases of amyloidosis, such as hereditary amyloidosis or multiple myeloma. There is little experience with renal transplantation in light-chain deposition disease, fibrillary/immunotactoid GN, or mixed cryoglobulinemic nephritis but successful cases have been reported. Diabetic nephropathy often recurs but usually only after many years. Recurrence in patients with small vessel vasculitis is unpredictable but can cause graft failure. However, in spite of recurrence, patient and graft survival rates are similar in patients with small vessel vasculitis compared with those with other renal diseases. Many secondary forms of GN no longer represent a potential contraindication to renal transplantation. The main issues in transplantation of patients with secondary GN are the infectious, cardiovascular, or hepatic complications associated with the original disease or its treatment.	f	\N
21496186	Certainty is seen as the 'Holy Grail' of science, despite the fact that all science is based in doubt, and that good scientists always leave a door open for an alternative explanation of their findings. Certainty also is a human desire providing comfort and surety. How can these two notions coexist? The way we perceive is the way we see and understand. Perception, however, is not objective; the way we 'know' what the sensory input we receive means arises from matching it against stored images of prior experiences, or put differently, the way we perceive the world depends on successfully predicting our own sensory status. Only large mismatches create new awareness resulting in new learning. At large we are prisoners of our own making, and awareness of the boundaries of our understanding will help to expand our horizon. The four papers of this edition attempt to expand the boundaries of 'common certainty' in terms of statistical interpretation, management of individual patients, disease management and health policy.	f	\N
21498295	Patients suffering from hereditary hyperlipidemia have a high risk for premature cardiovascular disease and death as a consequence of accelerated atherosclerosis. To prospectively and intra-individually compare image quality and detectability of stenoses in contrast enhanced whole-body MRA (WBMRA) at 1.5 and 3 Tesla (T) in patients with hereditary hyperlipidemia. Twenty-seven patients with hereditary hyperlipidemia received a 1.5 and 3 T gadopentetate dimeglumine contrast-enhanced WBMRA. Twenty-three defined arterial segments were analyzed regarding depiction of target vessels and image quality according to a 5-point-scale ('not evaluable' to 'excellent'). Wilcoxon matched pair test was performed for comparison. Forty-three defined arterial segments were analyzed for the degree of stenosis (0%, 1-49%, 50-99% and 100%) as well as vessel alterations such as aneurysms. Chi-square test was performed for comparison. 1.5 T and 3 T scans yielded WBMRA with diagnostic quality in all patients. In seven of 23 arterial segments (30.4%) image quality was rated significantly higher at 3 T, whereas there was no significant difference in the remaining 16 segments between WBMRA at 1.5 T and 3 T. All relevant stenoses (n = 5), occlusions (n = 6), and aneurysms (n = 3) were evaluated similarly at both field strengths. WBMRA can be performed at 1.5 T and 3 T with diagnostic image quality. Image quality was significantly higher at 3 T than at 1.5 T in only 30.4% of the arterial segments. In order to effectively take advantage of the higher field strength, further optimization of sequence parameters and injection protocols for WBMRA at 3 T is necessary.	f	\N
21503392	The rate of transient dilatation can be determined by exercise testing or pharmacological stress test. It is unknown whether the type of stress has an impact on average transient dilatation index values. To compare average transient dilation index values in 99mTc-sestamibi scintigraphy in patients undergoing treadmill stress test, versus dipyridamole stress test. The secondary purpose was to evaluate the impact on the average index value by demographic characteristics, risk factors for coronary artery disease and severity of ischemia. The cross-sectional study included 200 patients between 40 and 70 years old, with or without risk factors for ischemic heart disease, with or without a previous diagnosis of ischemic heart disease. The separation between groups was sequential. The software 4D-MSPECT calculated the transient dilatation index and provided a scoring system for perfusion analysis. The average transient dilation index value of the group undergoing exercise stress test was 1.06 (±0.23). For the group undergoing the dipyridamole stress test, it was 1.10 (±0.22); (p = 0.200). There was no association between the type of stress and the average transient dilatation index values. An association was found between the average index values and age only for those patients from the exercise test group (p = 0.009). The results of our study demonstrate that the transient dilation index does not differ when patients undergo exercise stress test on a treadmill or pharmacological stress by dipyridamole.	f	\N
21506835	Rapid and reliable detection and identification of coccidian oocysts are essential for animal health and foodborne disease outbreak investigations. Traditional microscopy and morphological techniques can identify large and unique oocysts, but they are often subjective and require parasitological expertise. The objective of this study was to develop a real-time quantitative PCR (qPCR) assay using melting curve analysis (MCA) to detect, differentiate, and identify DNA from coccidian species of animal health, zoonotic, and food safety concern. A universal coccidia primer cocktail was designed and employed to amplify DNA from Cryptosporidium parvum, Toxoplasma gondii, Cyclospora cayetanensis, and several species of Eimeria, Sarcocystis, and Isospora using qPCR with SYBR Green detection. MCA was performed following amplification, and melting temperatures (T(m)) were determined for each species based on multiple replicates. A standard curve was constructed from DNA of serial dilutions of T. gondii oocysts to estimate assay sensitivity. The qPCR assay consistently detected DNA from as few as 10 T. gondii oocysts. T(m) data analysis showed that C. cayetanensis, C. parvum, Cryptosporidium muris, T. gondii, Eimeria bovis, Eimeria acervulina, Isospora suis, and Sarcocystis cruzi could each be identified by unique melting curves and could be differentiated based on T(m). DNA of coccidian oocysts in fecal, food, or clinical diagnostic samples could be sensitively detected, reliably differentiated, and identified using qPCR with MCA. This assay may also be used to detect other life-cycle stages of coccidia in tissues, fluids, and other matrices. MCA studies on multiple isolates of each species will further validate the assay and support its application as a routine parasitology screening tool.	f	\N
21507892	Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare condition defined by eyelid colobomas, cryptophthalmos and anophthalmia/microphthalmia, an aberrant hairline, a bifid or broad nasal tip, and gastrointestinal anomalies such as omphalocele and anal stenosis. Autosomal recessive inheritance had been assumed because of consanguinity in the Oji-Cre population of Manitoba and reports of affected siblings, but no locus or cytogenetic aberration had previously been described. This study shows that MOTA syndrome is caused by mutations in FREM1, a gene previously mutated in bifid nose, renal agenesis, and anorectal malformations (BNAR) syndrome. MOTA syndrome and BNAR syndrome can therefore be considered as part of a phenotypic spectrum that is similar to, but distinct from and less severe than, Fraser syndrome. Re-examination of Frem1(bat/bat) mutant mice found new evidence that Frem1 is involved in anal and craniofacial development, with anal prolapse, eyelid colobomas, telecanthus, a shortened snout and reduced philtral height present in the mutant mice, similar to the human phenotype in MOTA syndrome. The milder phenotypes associated with FREM1 deficiency in humans (MOTA syndrome and BNAR syndrome) compared to that resulting from FRAS1 and FREM2 loss of function (Fraser syndrome) are also consistent with the less severe phenotypes resulting from Frem1 loss of function in mice. Together, Fraser, BNAR and MOTA syndromes constitute a clinically overlapping group of FRAS-FREM complex diseases.	f	\N
21508333	c-Src is a non-receptor tyrosine kinase whose activity is induced by phosphorylation at Y418 and translocation from the cytoplasm to the cell membrane. Increased activity of c-Src has been associated with cell proliferation, matrix adhesion, motility, and apoptosis in tumors. Immunohistochemistry suggested that activated (pY(418))-Src activity is increased in cyst-lining autosomal dominant polycystic kidney disease (ADPKD) epithelial cells in human and mouse ADPKD. Western blot analysis showed that SKI-606 (Wyeth) is a specific inhibitor of pY(418)-Src without demonstrable effects on epidermal growth factor receptor or ErbB2 activity in renal epithelia. In vitro studies on mouse inner medullary collecting duct (mIMCD) cells and human ADPKD cyst-lining epithelial cells showed that SKI-606 inhibited epithelial cell proliferation over a 24-h time frame. In addition, SKI-606 treatment caused a striking statistically significant decrease in adhesion of mIMCD and human ADPKD to extracellular collagen matrix. Retained viability of unattached cells was consistent with a primary effect on epithelial cell anchorage dependence mediated by the loss of extracellular matrix (ECM)-attachment due to α(2)β(1)-integrin function. SKI-606-mediated attenuation of the human ADPKD hyperproliferative and hyper-ECM-adhesive epithelial cell phenotype in vitro was paralleled by retardation of the renal cystic phenotype of Pkd1 orthologous ADPKD heterozygous mice in vivo. This suggests that SKI-606 has dual effects on cystic epithelial cell proliferation and ECM adhesion and may have therapeutic potential for ADPKD patients.	f	\N
21537035	To determine if time to diagnosis is associated with stage of disease at diagnosis or survival among women with symptomatic ovarian cancer. A representative sample of Australian women (n = 1,463) with ovarian cancer diagnosed between 2002 and 2005 who participated in a population-based case-control study were interviewed regarding the events leading to their diagnosis and were observed for mortality for 5 years. Of the 1,318 women (90%) who presented to a medical practitioner with symptoms, 55% presented within 1 month, 70% in less than 2 months, and 92% within 6 months of symptom onset. There were no significant differences in the time from symptom onset to first medical practitioner consultation (P = .19) or symptom onset to diagnosis (P = .64) among women with borderline, early (International Federation of Gynecology and Obstetrics [FIGO] stages I to II) or late (FIGO stages III to IV) disease. There was also no association between time to diagnosis and survival; adjusted hazard ratio for long delay (> 12 months from symptom onset to diagnosis) versus short delay (≤ 1 month) was 0.94 (95% CI, 0.68 to 1.30). Women who had asymptomatic cancers diagnosed incidentally (n = 145) were younger and were more likely to have borderline or stage I disease compared with women who had symptomatic ovarian cancer. The results of this study suggest that, once ovarian cancer is symptomatic, reducing the time to diagnosis would not greatly alter stage of disease at diagnosis or survival.	f	\N
21542809	Endometriosis-associated infertility results in reduced ovarian response, fewer oocytes available for fertilization, compromised oocyte quality and higher miscarriage rates. A consistent proportion of women with endometriosis require in vitro fertilization. We sought to clarify the impact of deep infiltrating pelvic disease on antral follicle count and ovarian response to follicle-stimulating hormone (FSH) stimulation in patients with severe endometriosis. Retrospective cohort study. University hospital. Patients with severe endometriosis (stages III-IV; n=51) were divided into two groups regarding localization of endometriosis during surgical staging: ovarian (n=27) and both ovarian and deep infiltrating disease (n=24). A total of 73 long-protocol ovulation induction cycles with recombinant FSH for an intracytoplasmic sperm injection program were given. On day 3 of the cycle, measurements of FSH and luteinizing hormone and an ultrasound evaluation of antral follicle count were performed. Number of oocytes collected at ovum pick up, number of mature oocytes, number of embryos transferred and clinical pregnancy rate. Ovarian reserve in terms of antral follicle count was damaged in both groups but, if adjusted for age, it was significantly lower in the ovarian and pelvic infiltrating group compared with patients having only ovarian endometriosis. Pelvic deep infiltrating disease significantly impacted on the number of oocytes collected at pick up when adjusted for age. Deep infiltrating pelvic disease can negatively affect ovarian reserve in terms of antral follicle count and number of oocytes retrieved. Mechanisms underlying this phenomenon need to be elucidated.	f	\N
21545837	The proteasome is an enzyme complex responsible for targeted intracellular proteolysis. Alterations in proteasome-mediated protein clearance have been implicated in the pathogenesis of aging, Alzheimer's disease (AD) and Parkinson's disease (PD). In such diseases, proteasome inhibition may contribute to formation of abnormal protein aggregates, which in turn activate intracellular unfolded protein responses that cause oxidative stress and apoptosis. In this study, we investigated the protective effect of Insulin-like Growth Factor-I (IGF-1) for neural SH-SY5Y cells treated with the proteasomal inhibitor, Epoxomicin. In SH-SY5Y cells, Epoxomicin treatment results in accumulation of intracellular ubiquitinated proteins and cytochrome c release from damaged mitochondria, leading to cell death, in Epoxomicin time- and dose-dependent manner. In cells treated with small amounts of IGF-1, the same dosages of Epoxomicin reduced both mitochondrial damage (cytochrome c release) and reduced caspase-3 activation and PARP cleavage, both of which are markers of apoptosis. Notably, however, IGF-1-treated SH-SY5Y cells still contained ubiquitinated protein aggregates. This result indicates that IGF-1 blocks the downstream apoptotic consequences of Epoxomicin treatment leading to decreased proteasome function. Clues as to the mechanism for this protective effect come from (a) increased AKT phosphorylation observed in IGF-1-protected cells, vs. cells exposed to Epoxomicin without IGF-1, and (b) reduction of IGF-1 protection by pretreatment of the cells with LY294002 (an inhibitor of PI3-kinase). Together these findings suggest that activation of PI3/AKT pathways by IGF-1 is involved in IGF-1 neuroprotection against apoptosis following proteasome inhibition.	f	\N
21547907	Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes. Of those, pancreatobiliary and oncocytic types are recently recognized and relatively uncommon, and usually exhibit high-grade dysplasia. The biological properties and molecular characteristics of these two types have not been well documented. The few molecular studies of the oncocytic type showed absence of KRAS mutations commonly seen in the other subtypes, raising the possibility that the oncocytic type is distinct from the other subtypes. Thus, we examined clinicopathological features and molecular alterations of the two subtypes. The study cohort consisted of 12 pancreatobiliary and 18 oncocytic IPMN cases. KRAS, BRAF, and PIK3CA mutations and TP53, SMAD4, and β-catenin expression were analysed, and the results of molecular and clinicopathological profiles were compared between the two subtypes. KRAS mutations were identified in the oncocytic type, but less frequently than the pancreatobiliary type (17% versus 58%, p = 0.048). BRAF mutation was found in a single oncocytic tumour, and no PIK3CA mutations were seen in any of the study cohort. TP53 overexpression was less frequent in the oncocytic type than in the pancreatobiliary type (11% versus 58%, p = 0.013). Invasive components were present in 50% of the oncocytic and 92% of the pancreatobiliary types, with lymph node metastasis more frequently seen in the latter, corresponding to better outcomes in the former (5-year survival rates: 93% versus 32%, p = 0.014). Our demonstration of KRAS and BRAF mutations in the oncocytic-type IPMN supports a role for the activation of the RAS-MAPK pathway in this tumour type. However, the less frequent TP53 overexpression associated with the significantly lower rates of invasion and nodal disease in the oncocytic type correlates with better outcomes compared to the pancreatobiliary type.	f	\N
21565878	Excessive dynamic airway collapse (EDAC) refers to abnormal and exaggerated bulging of the posterior wall within the airway lumen during exhalation. This condition is pathological if the reduced airway lumen is <50% of the normal. It is a relatively new disease entity that is recognised more easily now with the increased use of multi-detector row CT. EDAC is often asymptomatic and diagnosed incidentally. Although the term excessive dynamic airway collapse is often used interchangeably with tracheobronchomalacia, both entities represent morphologically and physiologically distinct processes. Considering the confusion between the two entities, the prevalence of stand-alone EDAC remains unclear. The prevalence of tracheobronchomalacia and EDAC depends upon the patient population, associated comorbidities and underlying aetiologies, diagnostic tools used and criteria used to define the airway collapse. This review defines EDAC and describes its pathophysiology, precipitating factors, associated symptoms and potential treatments.	f	\N
21571478	To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis. Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis. Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity. Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.	f	\N
21572511	The epidemiology of Chagas disease, until recently confined to areas of continental Latin America, has undergone considerable changes in recent decades due to migration to other parts of the world, including Spain. We studied the prevalence of Chagas disease in Latin American patients treated at a health center in Barcelona and evaluated its clinical phase. We make some recommendations for screening for the disease. We performed an observational, cross-sectional prevalence study by means of an immunochromatographic test screening of all continental Latin American patients over the age of 14 years visiting the health centre from October 2007 to October 2009. The diagnosis was confirmed by serological methods: conventional in-house ELISA (cELISA), a commercial kit (rELISA) and ELISA using T cruzi lysate (Ortho-Clinical Diagnostics) (oELISA). Of 766 patients studied, 22 were diagnosed with T. cruzi infection, showing a prevalence of 2.87% (95% CI, 1.6-4.12%). Of the infected patients, 45.45% men and 54.55% women, 21 were from Bolivia, showing a prevalence in the Bolivian subgroup (n=127) of 16.53% (95% CI, 9.6-23.39%). ALL THE INFECTED PATIENTS WERE IN A CHRONIC PHASE OF CHAGAS DISEASE: 81% with the indeterminate form, 9.5% with the cardiac form and 9.5% with the cardiodigestive form. All patients infected with T. cruzi had heard of Chagas disease in their country of origin, 82% knew someone affected, and 77% had a significant history of living in adobe houses in rural areas. We found a high prevalence of T. cruzi infection in immigrants from Bolivia. Detection of T. cruzi-infected persons by screening programs in non-endemic countries would control non-vectorial transmission and would benefit the persons affected, public health and national health systems.	f	\N
21575881	Mesalazine remains the first line treatment for the induction and the maintenance of remission in mild to moderate ulcerative colitis (UC). Its efficacy as a maintenance treatment after a first flare treated with corticosteroids has not been specifically studied. The aims of our work were to study a cohort of UC patients treated with mesalazine after a course of oral systemic corticosteroids and to identify predictive factors of relapse and of colectomy. We studied retrospectively a cohort of 143 UC patients, who never received immunosuppressive drugs, and treated for the first time with oral corticosteroids for a flare. Among patients responding to corticosteroids, we studied the group treated by mesalazine after the flare. Fifty% (n=52) achieved a complete clinical remission with steroid weaning. In this group, 67% (n=35) received oral mesalazine. Seventy-five % of patients treated by mesalazine relapsed (median 29 months, range: 1-156). Fourteen % required a colectomy (median 11 months, range: 1-24). Kaplan Meier curve showed a relapse rate and a colectomy rate over one year of 26% and 11% respectively. In multivariate analysis, male gender and short duration of disease were predictive factors of the time-to-relapse. No factor was predictive of time-to-colectomy. Maintenance efficacy of mesalazine over one year after a first course of corticosteroids for a disease flare is reasonably high. The longer-term relapse rate becomes higher in male patients with a short disease duration. An immunosuppressive treatment could be discussed in case of further relapse despite improved medication-adherence. Medication-adherence should first be assessed and promoted. An immunosuppressive treatment could be discussed in case of further relapse despite improved medication-adherence.	f	\N
21576904	Mutations in IRAK4 have been associated with recurrent Gram-positive infections in children. Given the central role of IRAK4 in innate immunity signaling, we hypothesized that common genetic variants of IRAK4 may be associated with prevalence of Gram-positive infection in critically ill adults. Haplotype clade tag single nucleotide polymorphisms (SNPs) of the IRAK4 gene were selected and genotyped in a cohort of 1,029 critically ill patients with systemic inflammatory response syndrome (SIRS). We found that a haplotype clade tagged by the A allele of the htSNP G29429A (Ala428Thr) was associated with increased relative risk of Gram-positive infection at admission to ICU (RR = 1.2, p < 0.05). Furthermore, the 29429A allele was associated with decreased lymphoblastoid cell response to CpG (as measured by IL-6 production) (raw values ± 95% CI 40.3 ± 32.3 vs. 85.8 ± 29.4 pg/ml; log-transformed values ± 95% CI 1.13 ± 0.37 vs. 1.55 ± 0.18, p < 0.04). We also found that IRAK4-deficient fibroblasts transfected with an IRAK4 expression plasmid containing the 29429A allele produced less IL-6 in response to lipopolysaccharide (p = 0.07). Our data suggest that the IRAK4 haplotype clade marked by 29429A (428Thr) alters susceptibility to Gram-positive bacteria, by decreasing cellular response to TLR ligands.	f	\N
21585286	β-site APP-cleaving enzyme (BACE1) cleaves the wild type (WT) β-site very slowly (k(cat)/K(m): 46.6 m(-1) s(-1)). Therefore we searched for additional β-secretases and identified three cathepsins that split the WT β-site much faster. Human cathepsin S cleaves the WT β-site (k(cat)/K(m): 54 700 m(-1) s(-1)) 1170-fold faster than BACE1 and cathepsins B and L are 440- and 74-fold faster than BACE1, respectively. These cathepsins split two bonds flanking the WT β-site (K-MD-A), where the K-M bond (85%) is cleaved more efficiently than the D-A bond (15%). Cleavage at the major K-M bond yields Aβ (amyloid β-peptide) extended by N-terminal Met that should be removed to generate Aβ initiated by Asp1. The activity of cytosol and microsomal aminopeptidases on relevant peptides revealed rapid removal of N-terminal Met but not N-terminal Asp. Brain aminopeptidases showed similar specificity. Thus, aminopeptidases would convert Aβ extended by Met into regular Aβ (Asp1) found in amyloid plaques. Earlier studies indicate that Aβ is likely produced in the endosome and lysosome system where cathepsins S, B and L are localized and cysteine cathepsin inhibitors reduce the level of Aβ in cells and animals. Taken together, cathepsins S, B and L deserve further evaluation as therapeutic targets to develop disease modifying drugs to treat Alzheimer's disease.	f	\N
21596857	Femoral and lumbar bone mineral densities (BMDs) were measured in 159 adults enrolled in the Leucémies de l'Enfant et de l'Adolescent program, a French prospective multicentric cohort of childhood leukemia survivors. BMDs were expressed as Z-scores, and multivariate linear regression analyses were used to construct association models with potential risk factors. Mean age at evaluation and follow-up was 23 and 14.7 years, respectively. In the whole cohort, mean femoral Z-score was -0.19 ± 0.08. Two factors were associated with lower femoral BMD transplantation (-0.49 ± 0.15 vs -0.04 ± 0.10 in the chemotherapy group; P = .006) and female sex (-0.34 ± 0.10 vs -0.03 ± 0.13; P = .03). Among patients who received a transplant, the only significant risk factor was hypogonadism (-0.88 ± 0.16 vs -0.10 ± 0.23; P = .04). A slight reduction in lumbar BMD (mean Z-score, -0.37 ± 0.08) was detected in the whole cohort without difference between the transplantation and chemotherapy groups. Among patients who received a transplant, younger age at transplantation was correlated with a low lumbar BMD (P = .03). We conclude that adults who had received only chemotherapy for childhood leukemia have a slight reduction in their lumbar BMD and a normal femoral BMD. Patients who received a transplant with gonadal deficiency have a reduced femoral BMD which might increase the fracture risk later in life.	f	\N
21601991	Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Due to either infection or disease activity, elevated levels of inflammatory markers and up-regulation of the autoimmune process can contribute to the development of atherosclerosis in SLE patients. Periodontal diseases are among the most prevalent chronic infections in humans and are characterized by pathogen-induced oral inflammatory disease affecting the supporting tissues of teeth. Several cytokines capable of inducing systemic effects are produced during the course of this infection. The presence of these cytokines can be verified by changes in the levels of C-reactive protein (CRP). Periodontal disease is a well-known risk factor for atherosclerosis. The potential for beneficial prevention of CVD events through the use of periodontal treatment has been previously recommended. This review reinforces the hypothesis that periodontal infection could be a risk factor for CVD in patients diagnosed with SLE, and suggests that by reducing the progression of this oral infection, levels of inflammatory markers common to both diseases (SLE and periodontal disease) would likely decrease.	f	\N
21603646	Miniature pigs are useful model animals for humans because they have similar anatomy and digestive physiology to humans and are easy to breed and handle. In this study, whole blood microarray analyses were conducted to evaluate variations of correlation among individuals and ages using specific pathogen-free (SPF) Clawn miniature pigs. Whole blood RNA is easy to handle compared to isolated white blood cell RNA and can be used for health and disease monitoring and animal control. In addition, whole blood is a heterogeneous mixture of subpopulation cells. Once a great change occurs in composition and expressing condition of subpopulations, their associated change will be reflected on whole blood RNA. From 12 to 30 weeks of age, fractions of lymphocytes, monocytes, neutrophils, eosinophils, and basophils in white blood cells showed insignificant differences with age as a result of ANOVA analysis. This study attempted to identify characteristics of age-related gene expression by taking into account the change in the number of expressed genes by age and similarities of gene expression intensity between individuals. As a result, the number of expressed genes was less in fetal stage and infancy period but increased with age, reaching a steady state of gene expression after 20 weeks of age. Variation in gene expression intensity within the same age was great in fetal stage and infancy period, but converged with age. The variation between 20 and 30 weeks of age was comparable to that among 30 weeks individuals. These results indicate that uniformity of laboratory animals is expected for miniature pigs after 20 weeks of age. Furthermore, a possibility was shown that whole blood RNA analysis is applicable to evaluation of physiological state.	f	\N
21607722	It has been only 5 years since the identification of TDP-43 as the major protein component of the ubiquitinated inclusions in FTLD-U. At that time, there were approximately a dozen papers about TDP-43; today, a "TDP-43" search reveals almost 600 papers. It is now clear that the majority of FTLD cases containing tau- and alpha-synuclein-negative, ubiquitin-positive inclusions (FTLD-U) are FTLD-TDP. The spectrum of TDP-43 proteinopathies includes FTLD-TDP with or without ALS, with or without mutations in GRN, VCP, or TARDBP, with or without chromosome 9p linkage, and sporadic and non-SOD1 familial ALS with or without FTLD-TDP. There are four sub-types of FTLD-TDP, and these correlate with specific clinical and genetic profiles. Sub-types are determined by the presence, predominance, and distribution of the various TDP-43 immunopositive insoluble aggregates-neuronal cytoplasmic inclusions, neuronal intranuclear inclusions, and dystrophic neurites. In this paper, FTLD-TDP pathologic sub-types will be described, and examples of each sub-type will be shown, and implications for future research will be discussed.	f	\N
21609376	Differentiating between benign and malignant causes of obstructive jaundice can be challenging, even with the advanced imaging and endoscopic techniques currently available. In patients with obstructive jaundice, the predictive accuracy of bilirubin levels at presentation was examined in order to determine whether such data could be used to differentiate between malignant and benign disease. A total of 1,026 patients with obstructive jaundice were identified. Patients were divided into benign and malignant groups. The benign patients were subgrouped into those with choledocholithiasis and those with inflammatory strictures of the biliary tree. Bilirubin levels at presentation and other demographic data were obtained from case records. Area under the curve (AUC) values for bilirubin as a predictor of malignancy were highly significant for all benign presentations and for those with benign biliary strictures (AUC: 0.8 for both groups; P < 0.001). A bilirubin level > 100 µmol/l was determined to provide the optimum sensitivity and specificity for malignancy in all patients and in those without choledocholithiasis (71.9% and 86.9%, 71.9% and 88.0%, respectively). The application of a bilirubin level > 250 µmol/l achieved specificities of 97.1% and 98.0% in each subgroup of patients, respectively. In patients with obstructive jaundice, bilirubin levels in isolation represent an important tool for discriminating between benign and malignant underlying causes.	f	\N
21621489	The aim of this study is to develop a standardized LC-MS/MS method for accurate measurement of desmosine (DES) and isodesmosine (IDS) in all body fluids as biomarkers for in vivo degradation of matrix tissue elastin in man and animals. A reproducible three-step analytical procedure: (1) sample hydrolysis in 6N HCl, (2) SPE by a CF1 cartridge with addition of acetylated pyridinoline as internal standard (IS), and (3) LC/MSMS analysis by SRM monitoring of transition ions; DES or IDS (m/z 526-481+397) and IS (m/z 471-128) was developed. The method achieves accurate measurements of DES/IDS in accessible body fluids (i.e. urine, plasma, and sputum). LOQ of DES/IDS in body fluids is 0.1 ng/ml. The % recoveries and reproducibility from urine, plasma, and sputum samples are above 99 ± 8% (n = 3), 94 ± 9% (n = 3) and 87 ± 11% (n = 3), with imprecision 8%, 9% and 10%, respectively. The proposed method was applied to measure DES/IDS in body fluids of patients with chronic obstructive pulmonary disease (COPD) and healthy controls. Total DES/IDS in sputum and plasma is increased over normal controls along with the free DES/IDS in urine in patients. DES/IDS can be used to study the course of COPD and the response to therapy. This practical and reliable LC-MS/MS method is proposed as a standardized method to measure DES and IDS in body fluids. This method can have wide application for investigating diseases which involve elastic tissue degradation.	f	\N
21626540	The Movement Disorder Society (MDS) developed out of a merger with two short-lived organizations, the Movement Disorder Society, primarily organized to develop a journal for the subspecialty, and the International Society of Motor Disturbances, primarily organized to develop international congresses. The formal merger of the Movement Disorder Society and the International Society of Motor Disturbances into the Movement Disorder Society took place at the 2nd International Congress of Movement Disorders in Munich, Germany, in June 1992. Whereas the journal, Movement Disorders, and the annual International Congress of Parkinson's Disease and Movement Disorders remain the anchors of the society, the goals now include the development of regional symposia, regional sections, Web-based educational programs, and outreach efforts to include young investigators, wide international membership, and inclusion of non-neurologists, including basic scientists, neurosurgeons, and nonphysician health professionals. Movement Disorders has a continuingly growing subscribership and rising impact factor.	f	\N
21630606	Renal biopsy is the definitive diagnostic test in patients with renal parenchymal disease. Renal biopsy registry is an important tool which can provide valuable data concerning early and correct epidemiological description and clinical correlations of renal diseases. Records of 326 adult renal biopsies performed at our hospital from January 1991 till the end of December 2006 were retrospectively examined. Overall, secondary glomerular diseases (SGD) were predominant (39.9%), followed by primary glomerular diseases (PGD) (30.4%), vascular diseases (13.2%) and TIN (6.7%). Total sclerosis of the kidney did not allow histopathological diagnosis in 5.8% of all biopsied kidneys. Focal and Segmental Glomerular Sclerosis (FSGS), IgA Nephropathy (IgAGN) and Minimal Change Disease (MCD) and Membranous Glomerulopathy (MGN) were the most common PGD, altogether representing 75.7% of all PGD. FSGS was the most frequent (30.3%), followed by IgAGN (21.2%), MCD (19.1%) and MGN in 15.1%. Vasculitis, HIVAN, diabetic nephropathy and amyloidosis were the most common SGD, altogether representing 90% of all SGD. Immune Mediated Glomerulonephritis (IMGN) were the most frequent (32.3%), followed by HIVAN (16.9%), diabetic nephropathy (14.6%) and amyloidosis (10%). Nephroangiosclerosis (benign and malignant nephroangiosclerosis) was the most frequent vascular nephropathy responsible for 79% of all vascular diseases. Thrombotic microangiopathy was seen in 9.3% and atherothrombotic disease in 7% of all vascular diseases. Concerning tubular diseases, chronic TIN accounted for 63.6% of all tubular diseases, followed by light chain-cast nephropathy (22.7%) and acute TIN (13.6%). Because of lack of material, 3.4% of all biopsies could not be analyzed. These data demonstrate that the distribution of biopsy-proved renal diseases in a Belgian population of the Brussels area is strongly influenced by the indications of renal biopsy. Harmonization of these indications might reflect with more accuracy the actual incidence of different nephropathies in a given population. Nation and worldwide renal biopsy registers are important to follow patterns of renal diseases in different populations. This information is important not only for health organizations in order to plan health budget but also for helping clinicians to provide a better care to patients.	f	\N
21641369	Although very late stent thrombosis occurs several years after implantation of sirolimus-eluting stent (SES), the morphologic changes of the stent beyond 2 years have not yet been systematically studied in living patients. The late vascular response to SES was therefore evaluated by serial angioscopic studies at 2 and 5 years after stent implantation. A total of 17 patients with 17 SES underwent a repeated angioscopy procedure at 2 and 5 years. Neointimal stent coverage (NSC) was classified as follows: grade 0, presence of uncovered struts; grade 1, visible struts through a thin neointima; or grade 2, complete neointimal coverage without visible struts. For each patient, the minimum and maximum NSC grade and the existence of in-stent thrombus were recorded. The minimum and maximum NSC grade did not increase between the 2 and 5 years (0.59 ± 0.51 vs 0.88 ± 0.70, P = .17, and 1.82 ± 0.39 vs 1.94 ± 0.24, P = .30, respectively). The prevalence of patients with uncovered struts did not significantly decrease from 2 to 5 years (41% vs 29%, P = .49). During the follow-up period, 3 of 6 thrombi disappeared, whereas new thrombus formation was found in 3 patients without any clinical symptoms. In-stent thrombus did not decrease (35% vs 35%, P > .99). The current serial angioscopic study suggests that incomplete NSC and the prevalence of latent thrombus within the SES segments did not decrease from 2 to 5 years. The risk of stent thrombosis related to incomplete healing of SES may continue for an extended period.	f	\N
21645024	Retinol-binding protein 4 (RBP4), produced by adipocytes and hepatocytes, contributes to an unfavourable lipid profile and insulin resistance, which can contribute to the development of coronary artery disease (CAD). Recently, several studies have shown that epicardial adipose tissue (EAT) differs from subcutaneous adipose tissue (SAT) and plays a role on the physiopathology of CAD because of its proximity to the coronary arteries. We aimed to study the expression and secretion levels of RBP4 in both fat tissues and explore its possible association with CAD. Fifty-eight patients undergoing heart surgery were included in the study. We analysed RBP4 mRNA expression by real-time PCR, protein expression by Western blot and immunohistochemistry, and secretion of EAT and SAT explants from CAD and non-CAD patients by Enzyme Immunoassay. Retinol-binding protein 4 is expressed at similar levels in EAT and SAT, mainly from adipocytes. Protein levels were higher in EAT from CAD than non-CAD patients (0·63 ± 0·09 arbitrary units (a.u).; n = 10) vs (0·41 ± 0·04 a.u.; n = 13, P = 0·039). In contrast, GLUT4 mRNA levels were lower in EAT from CAD than non-CAD patients (6·55 ± 0·16 a.u.; n = 13) vs (7·21 ± 0·18 a.u.; n = 14, P = 0·012). We also found differential expression in SAT between samples from CAD and non-CAD patients [(6·63 ± 0·16 a.u.; n = 14) vs (7·21 ± 0·14 a.u.; n = 14, P = 0·009)]. Besides, EAT releases higher RBP4 levels than SAT after 3, 6, 24 and 48 h of culture. These levels were independent of CAD but significantly higher in diabetic than nondiabetic patients. Retinol-binding protein 4 levels behave differently in EAT and SAT with respect to CAD. However, both adipose tissues have lower GLUT4 levels in patients with CAD. These findings suggest a differential regulation of RBP4 production in EAT and SAT that may be influenced by local factors.	f	\N
21647871	In this phase 1 trial, the authors evaluated sunitinib combined with radiation therapy (RT) for the treatment of primary or metastatic central nervous system (CNS) malignancies. Eligible patients had CNS malignancies that required a (minimum) 2-week course of RT. Sunitinib (37.5 mg) was administered daily for the duration of RT with optional treatment extension of 1 month. Urine was collected at 3 time points for correlative biomarker studies. The primary endpoint was acute toxicity defined according to Common Toxicity Criteria version 3. Fifteen patients were enrolled (12 with CNS metastasis and 3 with primary tumors). RT doses ranged from 14 Gray (Gy) to 70 Gy (1.8-3.5 Gy per fraction). Acute toxicities included hematologic, nausea, hyperglycemia, fatigue, hypocalcemia, and diarrhea. Six patients (40%) developed grade ≤ 2 toxicities. Grade 3 toxicities occurred in 7 patients (47%) and included hematologic toxicity, fatigue, deep vein thrombosis, dysphasia, hyperglycemia, and hyponatremia. No grade 3 through 5 hypertensive events or intracerebral hemorrhages occurred. Two grade 5 adverse events attributed to disease progression occurred. The median follow-up was 34.2 months. Two patients (13%) achieved a partial response, 9 patients (60%) had stable disease, and 2 patients (13%) patients had progressive disease. The 6-month progression-free survival rate for patients who had brain metastasis was 58%. Grade 3 hematologic toxicity was correlated with greater changes in vascular endothelial growth factor levels changes between baseline and the completion of RT. Continuous 37.5-mg sunitinib combined with RT in patients who had CNS malignancies yielded acceptable toxicities and adverse events. The current results indicated that changes in urine vascular endothelial growth factor levels are associated with hematologic toxicity, and this association should be analyzed in a larger cohort. The feasibility, safety, and early response results warrant a phase 2 trial.	f	\N
21653298	US estimates of the Clostridium difficile infection (CDI) burden have utilized International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Whether ICD-9-CM code rank order affects CDI prevalence estimates is important because the National Hospital Discharge Survey (NHDS) and the Nationwide Inpatient Sample (NIS) have varying limits on the number of ICD-9-CM codes collected. ICD-9-CM codes for CDI (008.45), C. difficile toxin assay results, and dates of admission and discharge were collected from electronic hospital databases for adult patients admitted to 4 hospitals in the United States from July 2000 through June 2006. CDI prevalence per 1000 discharges was calculated and compared for NHDS and NIS limits and toxin assay results from the same hospitals. CDI prevalence estimates were compared using the χ(2) test, and the test of equality was used to compare slopes. CDI prevalence measured by NIS criteria was significantly higher than that measured using NHDS criteria (10.7 cases per 1000 discharges versus 9.4 cases per 1000 discharges; P<.001) in the 4 hospitals. CDI prevalence measured by toxin assay results was 9.4 cases per 1000 discharges (P=.57 versus NHDS). However, the CDI prevalence increased more rapidly over time when measured according to the NHDS criteria than when measured according to toxin assay results (β=1.09 versus 0.84; P=.008). Compared with the NHDS definition, the NIS definition captured 12% more CDI cases and reported significantly higher CDI rates. Rates calculated using toxin assay results were not different from rates calculated using NHDS criteria, but CDI prevalence appeared to increase more rapidly when measured by NHDS criteria than when measured by toxin assay results.	f	\N
21659502	Despite high vaccination coverage rates, there has been a gradual increase in reported pertussis cases. Although whooping cough affects all ages, young infants continue to suffer the greatest pertussis disease burden. Adolescents and adults are the primary source of infection for young babies. In this paper, we report two cases involving the likely transmission of pertussis from mothers to infants in Tunisia.	f	\N
21665106	Radiating leg pain is a common symptom presenting in manual therapy practices. Although this symptom has been reported as a complication of endometriosis, its prevalence and characteristics have not been studied. We surveyed members of a national endometriosis support group with endometriosis using a self-administered, mailed questionnaire. The main outcome measures were the prevalence and characteristics of leg pain. Of 94 respondents, leg pain was reported by 48 women (51%), and was bilateral in 59% of these symptomatic women. The likelihood of experiencing leg pain was related to weight gain since age 18, age, and height. The most common treatments tried included exercise, over-the-counter medications, and massage therapy, all with variable results. These data support leg pain as a prevalent complication of endometriosis, and that the disease may affect multiple peripheral nerves. Manual therapists should remain aware to this possible etiology for radiating pain.	f	\N
21674011	Intestinal luminal microbiota likely contribute to the etiology of necrotizing enterocolitis (NEC), a common disease in preterm infants. Microbiota development, a cascade of initial colonization events leading to the establishment of a diverse commensal microbiota, can now be studied in preterm infants using powerful molecular tools. Starting with the first stool and continuing until discharge, weekly stool specimens were collected prospectively from infants with gestational ages ≤32 completed weeks or birth weights≤1250 g. High throughput 16S rRNA sequencing was used to compare the diversity of microbiota and the prevalence of specific bacterial signatures in nine NEC infants and in nine matched controls. After removal of short and low quality reads we retained a total of 110,021 sequences. Microbiota composition differed in the matched samples collected 1 week but not <72 hours prior to NEC diagnosis. We detected a bloom (34% increase) of Proteobacteria and a decrease (32%) in Firmicutes in NEC cases between the 1 week and <72 hour samples. No significant change was identified in the controls. At both time points, molecular signatures were identified that were increased in NEC cases. One of the bacterial signatures detected more frequently in NEC cases (p<0.01) matched closest to γ-Proteobacteria. Although this sequence grouped to the well-studied Enterobacteriaceae family, it did not match any sequence in Genbank by more than 97%. Our observations suggest that abnormal patterns of microbiota and potentially a novel pathogen contribute to the etiology of NEC.	f	\N
21674889	Awareness of the clinical importance of second-line chemotherapy for incurable gastric cancer has been increasing. To assess the clinical validity of the new concept that second-line chemotherapy following predetermined cycles of first-line chemotherapy would improve survival, we conducted a phase II study. Patients with pathologically proven incurable gastric adenocarcinoma and adequate organ functions were enrolled. S-1 or S-1 plus cisplatin was administered as first-line chemotherapy. The number of cycles of S-1-based chemotherapy was determined to be three as a maximum unless there was disease progression. The treatment was followed by weekly administration of paclitaxel. The primary endpoint was overall survival and the secondary endpoints were progression-free survival and safety. Thirty-seven patients were eligible for enrollment. Twenty-eight patients (76%) underwent the second-line chemotherapy with paclitaxel after completion of S-1-based chemotherapy or disease progression. Treatment-related grade 3 or 4 toxicity was noted in 14 patients during S-1-based chemotherapy, and in 6 patients during paclitaxel treatment. The median survival time was 455 days and the median progression-free survival was 229 days. Sequential set chemotherapy with three cycles of S-1-based chemotherapy followed by weekly paclitaxel is feasible. The survival results are equivalent to those of other current regimens using S-1.	f	\N
21681643	Long-term central venous catheter (CVC) implantation has become more affordable in Taiwan since 1995. Surgical removal of the catheter may be the essential treatment for catheter-related bloodstream infections (CRBSI). The aim of this study was to evaluate the clinical features and microbial isolates in pediatric cancer patients with removal of CVC for CRBSI. The records of positive blood culture from hospitalized pediatric oncology patients between 1995 and 2004 were reviewed. One hundred and forty-three patients implanted with a long-term CVC were further identified. Seventeen catheters in 16 patients developed catheter-related bacteremia that needed catheter removal. The rate of catheter removal was 11.9%. The median device life was 7.7 months. Six catheters were removed within 3 months of insertion. Nine of the 17 catheters were removed from patient younger than 2 years. Eight infections occurred during severe neutropenia, and 6 patients had refractory or relapsed underlying disease. The cultural isolates were Gram-negative bacilli in 7, Gram-positive in 5, fungi in 5, and atypical mycobacterium in 1. The frequency of catheter removal for infection control was significantly higher in the first 5 years (1994-1999) compared to the last 5 years (2000-2004) (30.9 vs. 4.0%, p = 2.3 × 10(-4)). Factors such as microbiological isolates, age of infection, the status of malignancy, and neutropenia are related to catheter outcome. The reduction in patients with positive cultures needing removal of the catheters can be related to improved nursing care and more aggressive antibiotic therapy.	f	\N
21685330	Lymphatic metastasis constitutes a critical route of disease dissemination, which limits the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). As lymphangiogenesis has been implicated in stimulation of lymphatic metastasis by vascular endothelial growth factor-C (VEGF-C) and VEGF-D, we studied the effect of the angioregulatory growth factor angiopoietin-2 (Ang-2) on PDAC progression. Ang-2 was found to be expressed in transformed cells of human PDAC specimens, with corresponding Tie-2 receptors present on blood and lymphatic endothelium. In vitro in PDAC cells, Ang-2 was subject to autocrine/paracrine TGF-β stimulation (2-fold induction, P=0.0106) acting on the -61- to +476-bp element of the human Ang-2 promoter. In turn, Ang-2 regulated the expression of genes involved in cell motility and tumor suppression. Orthotopic PDAC xenografts with forced expression of Ang-2, but not Ang-1, displayed increased blood and lymphatic vessel density, and an enhanced rate of lymphatic metastasis (6.7- to 9.1-fold, P<0.01), which was prevented by sequestration of Ang-2 via coexpression of soluble Tie-2. Notably, elevated circulating Ang-2 in patients with PDAC correlated with the extent of lymphatic metastasis. Furthermore, median survival was reduced from 28.4 to 7.7 mo in patients with circulating Ang-2 ≥ 75th percentile (P=0.0005). These findings indicate that Ang-2 participates in the control of lymphatic metastasis, constitutes a noninvasive prognostic biomarker, and may provide an accessible therapeutic target in PDAC.	f	\N
21689845	To describe the number of urethral dilations, urethrotomies, and urethroplasties performed on men with a diagnosis of urethral stricture disease seeking care in the Veterans Affairs (VA) health care system in southern California and southern Nevada over a 5-year period. To date, few health services research studies have evaluated patterns of care for urethral stricture disease using national datasets. We analyzed stricture treatment for male veterans with an ICD-9 diagnosis code for urethral stricture in the National Patient Care Database (NPCD). Encounters for urethral stricture procedures performed were identified based on the presence of Physicians Current Procedural Terminology Coding System (4th edition, CPT-4) codes for treatments performed during the fiscal years 2002-2006. A total of 1457 men carried a diagnosis of urethral stricture disease during the index time period. Of these, 333 men (23%) underwent 431 procedures. Of the 216 men who underwent urethral dilations, 170 (79%) underwent only 1 procedure and 26 (12%) underwent 2 procedures. Of the 79 men who underwent urethrotomy, 76 (96%) underwent 1 procedure. Sixteen men (5%) underwent a urethroplasty, 8 of whom underwent a perineal urethrostomy. The vast majority of men treated for stricture disease underwent only 1 such procedure over a 5-year time period. Further research is required to investigate whether this is a quality-of-care issue or patients refusing intervention. It is possible that some patients may be temporized for a significant period with dilation/urethrotomy, whereas those with rapid recurrence require early urethroplasty.	f	\N
21690452	Laparoscopy is increasingly used in colon and rectal procedures. However, little is known regarding the incidence of venous thromboembolism (VTE) in laparoscopic colorectal (LC) compared with that in open colorectal (OC) procedures. We aimed to compare the incidences and to highlight the risk factors of developing VTE after LC and OC surgery. Analysis of the Nationwide Inpatient Sample data from 2002 through 2006. National database. Patients who underwent elective LC and OC surgery from 2002 through 2006. Incidence of VTE during initial hospitalization after LC and OC surgery; VTE classified by surgical site, pathology type, and at-risk patient population. Over a 60-month period, 149,304 patients underwent LC or OC resection. Overall, the incidence of VTE was significantly higher in OC cases (2036 of 141,456 [1.44%]) compared with the incidence in LC cases (65 of 7848 [0.83%]) (P < .001). When stratified according to pathologic condition and surgical site, the overall rate of VTE was highest in patients with inflammatory bowel disease and in those undergoing rectal resections. Patients who underwent OC surgery were almost twice as likely to develop VTE compared with patients who underwent LC surgery. We also identified malignancy, obesity, and congestive heart failure as statistically significant (P < .05) risk factors for VTE in OC and LC surgery. On the basis of data from a large clinical data set, the incidence of perioperative VTE is lower after LC than after OC surgery. These findings may help colorectal surgeons use appropriate VTE prophylaxis for patients undergoing colorectal procedures.	f	\N
21699733	Itch sensation is one of the major sensory experiences of human and animals. Recent studies have proposed that gastrin releasing peptide (GRP) is a key neurotransmitter for itch in spinal cord. However, no direct evidence is available to indicate that GRP actually mediate responses between primary afferent fibers and dorsal horn neurons. Here we performed integrative neurobiological experiments to test this question. We found that a small population of rat dorsal horn neurons responded to GRP application with increases in calcium signaling. Whole-cell patch-clamp recordings revealed that a part of superficial dorsal horn neurons responded to GRP application with the increase of action potential firing in adult rats and mice, and these dorsal horn neurons received exclusively primary afferent C-fiber inputs. On the other hands, few A(δ) inputs receiving cells were found to be GRP positive. Finally, we found that evoked sensory responses between primary afferent C fibers and GRP positive superficial dorsal horn neurons are mediated by glutamate but not GRP. CNQX, a blocker of AMPA and kainate (KA) receptors, completely inhibited evoked EPSCs, including in those Fos-GFP positive dorsal horn cells activated by itching. Our findings provide the direct evidence that glutamate is the principal excitatory transmitter between C fibers and GRP positive dorsal horn neurons. Our results will help to understand the neuronal mechanism of itch and aid future treatment for patients with pruritic disease.	f	\N
21699956	The NMDA glutamate hypofunction model of schizophrenia is based in part upon acute effects of NMDA receptor blockade in humans and rodents. Several laboratories have reported glutamate system abnormalities following prenatal exposure to immune challenge, a known environmental risk factor for schizophrenia. Here we report indices of NMDA glutamate receptor hypofunction following prenatal immune activation, as well as the effects of treatment during periadolescence with the atypical antipsychotic medications risperidone and paliperidone. Pregnant Sprague-Dawley rats were injected with polyinosinic:polycytidylic acid (poly I:C) or saline on gestational day 14. Male offspring were treated orally via drinking water with vehicle, risperidone (0.01mg/kg/day), or paliperidone (0.01mg/kg/day) between postnatal days 35 and 56 (periadolescence) and extracellular glutamate levels in the prefrontal cortex were determined by microdialysis at PD 56. Consistent with decreased NMDA receptor function, MK-801-induced increases in extracellular glutamate concentration were markedly blunted following prenatal immune activation. Further suggesting NMDA receptor hypofunction, prefrontal cortex basal extracellular glutamate was significantly elevated (p<0.05) in offspring of poly I:C treated dams. Pretreatment with low dose paliperidone or risperidone (0.01mg/kg/day postnatal days 35-56) normalized prefrontal cortical basal extracellular glutamate (p<0.05 vs. poly I:C vehicle-treatment). Pretreatment with paliperidone and risperidone also prevented the acute MK-801-induced increase in extracellular glutamate. These observations demonstrate decreased NMDA receptor function and elevated extracellular glutamate, two key features of the NMDA glutamate receptor hypofunction model of schizophrenia, during periadolescence following prenatal immune activation. Treatment with the atypical antipsychotic medications paliperidone and risperidone normalized basal extracellular glutamate. Demonstration of glutamatergic abnormalities consistent with the NMDA glutamate receptor hypofunction model of schizophrenia as an early developmental consequence of prenatal immune action provides a model to identify novel early interventions targeting glutamatergic systems which play an important role in both positive and negative symptoms of schizophrenia.	f	\N
21700931	Caloric restriction (CR) confers cardioprotection against ischemia/reperfusion injury. However, the exact mechanism(s) underlying CR-induced cardioprotection remain(s) unknown. Recent evidence indicates that Sirtuins, NAD(+)-dependent deacetylases, regulate various favorable aspects of the CR response. Thus, we hypothesized that deacetylation of specific mitochondrial proteins during CR preserves mitochondrial function and attenuates production of reactive oxygen species during ischemia/reperfusion. The objectives of the present study were (1) to investigate the effect of CR on mitochondrial function and mitochondrial proteome and (2) to investigate what molecular mechanisms mediate CR-induced cardioprotection. Male 26-week-old Fischer344 rats were randomly divided into ad libitum-fed and CR (40% reduction) groups for 6 months. No change was observed in basal mitochondrial function, but CR preserved postischemic mitochondrial respiration and attenuated postischemic mitochondrial H(2)O(2) production. CR decreased the level of acetylated mitochondrial proteins that were associated with enhanced Sirtuin activity in the mitochondrial fraction. We confirmed a significant decrease in the acetylated forms of NDUFS1 and cytochrome bc1 complex Rieske subunit in the CR heart. Low-dose resveratrol treatment mimicked the effect of CR on deacetylating them and attenuated reactive oxygen species production during anoxia/reoxygenation in cultured cardiomyocytes without changing the expression levels of manganese superoxide dismutase. Treatment with nicotinamide completely abrogated the effect of low-dose resveratrol. These results strongly suggest that CR primes mitochondria for stress resistance by deacetylating specific mitochondrial proteins of the electron transport chain. Targeted deacetylation of NDUFS1 and/or Rieske subunit might have potential as a novel therapeutic approach for cardioprotection against ischemia/reperfusion.	f	\N
21703749	Few studies have focused on the full complement of cardiac arrest cases seen in hospital emergency departments (ED). The aims of our study were to describe cardiac arrest visits in the ED by using a nationally representative sample of U.S. adults. ED data from the 2001-2007 National Hospital Ambulatory Medical Care Survey (NHAMCS) were analyzed. Cardiac arrest visits were considered to be those with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 427.5 as the primary diagnosis. From 2001 to 2007, adults in the U.S. made an estimated 600,729,000 ED visits. Of those, 1,001,000 (0.17%) had a primary diagnosis of cardiac arrest. The majority of patients with such visits were dead on arrival or died in the ED (74.0%). The mean age for cardiac arrest visits was 66.7 years (95% confidence interval [CI], 64.6-68.8 years). Women had a lower rate of cardiac arrest visits than men (age-adjusted odds ratio [AOR], 0.6; 95% CI, 0.5-0.8), and the privately insured (AOR, 0.4; 95% CI, 0.2-0.7) and those with government insurance (AOR, 0.5; 95% CI, 0.3-0.9) had a lower proportion of cardiac arrest ED visits than uninsured persons. In addition, increasing age was a significant predictor of cardiac arrest visits. Cardiac arrest visits did not vary significantly by race, geographic region, or metropolitan statistical area. ED visits classified as cardiac arrest represent 1 in 600 visits and these visits differ by age, sex, payment source, and arrival time at the ED.	f	\N
21704888	The safety of long-acting β2 agonists (LABA) for the treatment of persistent asthma remains a topic of ongoing debate. To evaluate the risk of serious asthma-related events among patients treated with formoterol, a meta-analysis of all Novartis-sponsored controlled clinical trials was conducted. Forty-five randomized, placebo- and active-controlled, parallel-group or crossover studies with formoterol were included. Background inhaled corticosteroid (ICS) use was permitted in all studies; however, in only 2 studies was ICS randomized as study medication. Sub-analyses of the pooled data were performed according to age (5-12; 13-18; >18 years), baseline ICS use, and lung function. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated between formoterol (twice-daily), albuterol (salbutamol) 4 times per day (active control), and placebo. Patients were randomized to formoterol (n = 5,367), placebo (n = 2,026), and albuterol (n = 976). Two deaths were reported, 1 each in the formoterol (asthma exacerbation) and the placebo (hemorrhagic pancreatitis) groups. No statistically significant differences in serious asthma exacerbations were observed compared with placebo in adolescents and adults. In children, a higher frequency of hospitalizations was observed among patients treated with formoterol compared with placebo (OR 8.4; 95% CI: 1.1-65.3). A trend toward fewer exacerbations was observed among subjects reporting concomitant ICS use at baseline. This analysis supports current guideline recommendations for the use of LABAs only as add-on therapy to ICS.	f	\N
21706339	The prostate gland is the most common site of neoplastic disorders in men. The pathogenesis of inflammatory cells, prostatic intraepithelial neoplasia (PIN) lesions, and prostate cancer is still under investigation. Inflammatory cells by producing free radicals are considered as major and universal contributors to cancerogenesis. PIN is regarded as a precursor lesion to prostate cancer or a marker signaling the vulnerability of the epithelium to neoplastic transformation [1]. Differentiation markers that are frequently changed in early invasive carcinoma are also changed in PIN lesions. In this study, prostate tissue samples obtained during surgical operation and classified as various disease states (inflammation, PIN lesions, and cancer) were examined. The samples were measured by means of microbeam synchrotron-radiation-induced X-ray emission (micro-SRIXE). Special attention was paid to examine the relationship between the earlier-mentioned disorders and changes in relative concentrations of S, K, Ca, Fe, Cu, and Zn. Applying the image-processing program ImageJ enabled us to select the areas of interest from two-dimensional maps of various prostate samples according to the histopathologist's evaluation. Detailed analysis of micro-SRIXE spectra based on multivariate methods shows significant differences between elemental concentrations in inflammatory cells, PIN lesions, and cancerous tissues, which confirms that this method can be used to distinguish various pathological states in prostate tissues. Information obtained in this way may provide better understanding of the biochemistry of unhealthy prostate tissues, thus opening the way to find new medicines/treatments to prevent or slow down some harmful intracellular processes.	f	\N
21712520	Data have shown that preprocedural statin therapy reduces periprocedural myocardial infarction after percutaneous coronary intervention (PCI). However, whether preprocedural statins improve clinical outcomes in patients with stable coronary artery disease (CAD) has not been established. We aimed to evaluate the clinical effectiveness of preprocedural statin therapy in patients with stable CAD undergoing PCI. We conducted an observational study of 12 980 patients, age >65 years with stable CAD, who underwent PCI from December 1, 2003, to March 31, 2008. Using propensity score-matching analysis, 3098 unique matched pairs (6196 patients) who had similar likelihood of receiving preprocedural statins were identified. Additional analyses adjusting for postprocedural statins as a time-varying variable were performed. The main outcome measure was a composite of death or recurrent acute coronary syndrome. In the propensity-matched cohort, at 90 days, the primary outcome of death and acute coronary syndrome occurred in 5.6% in the preprocedural statin group as compared with 7.4% in the no-pretreatment group (P=0.005). Improved clinical outcomes associated with preprocedural statins were still observed at 2 years (16.7% versus 19.3%, P=0.007). The effectiveness of preprocedural statins was most pronounced at 90 days after PCI (adjusted hazard ratio, 0.80; 95% confidence interval, 0.65 to 0.98) but was no longer significant at 1 year (adjusted hazard ratio, 0.92; 95% confidence interval, 0.79 to 1.07) after accounting for postprocedural statin therapy. Preprocedural statin therapy was associated with significant reduction in the risk of death or recurrent acute coronary syndrome in stable CAD patients after PCI. These findings support the routine use of preprocedural statins for suitable candidates.	f	\N
21722500	To describe the MRI features of gout tophi in the soft-tissues or joints of the limbs by low-field extremity-dedicated MRI. Nine consecutive patients, 8M/1W, affected by chronic tophaceous gout were studied. Mean patients' age was 71.3±11.5 years, mean disease duration 98.1±44.9 months, and mean serum uric acid concentration 9.2±2.8 mg/L. Diagnosis was based on the ACR classification criteria for gout, and by identification of MSU crystals in the tophi and synovial fluid. Conventional radiograms and MRI with an extremity-dedicated system were obtained of the joint areas involved by tophi. At T1 weighted MRI images, all tophi showed a homogeneous intermediate signal intensity, similar to that of muscle. Conversely, in T2 weighted images, a wide spectrum of signal intensity patterns was observed. The pattern of contrast enhancement was variable from intense homogeneous to peripheral and heterogeneous. Capsulo-ligamentous structures were often thickened and degenerated and, on occasion, could be recognised as inhomogeneous, hypointense ribbon-shaped elements in the context of the tophus. In only two cases, tendons were infiltrated by tophaceous matter. Bone marrow oedema (BME) and erosions were seen in 8 out of 10 bones adjacent to tophi. The MRI appearance of gout tophi using an extremity-dedicated machine is similar to that described in the literature using whole body machines. BME adjacent to the tophus was a frequent finding. This technique may occasionally help in the differential diagnosis of nodules and in the follow-up of the disease. It also represents a useful tool to investigate the pathogenesis of gout and to better understand its clinical progression.	f	\N
21726837	Data are lacking on the efficacy and safety of a loading dose (LD) of clopidogrel in elderly patients with acute myocardial infarction (AMI). FAST-MI is a nationwide registry that was carried out over a 1-month period in 2005 and included consecutive patients with AMI admitted to intensive care units <48 hours from symptom onset in 223 participating centers. We assessed the impact of a clopidogrel LD (≥300 mg) compared to a conventional dose (<300 mg) on bleeding, need for blood transfusion, and 30-day and 12-month survivals in 791 elderly patients (≥75 years old, mean age 81 ± 4 years, 48% women, 35% with ST-segment elevation MI) included in this registry. Fifty-nine percent (466 patients) received a clopidogrel LD. Follow-up was >99% complete. Major bleeding and blood transfusions were not significantly different in patients who received a clopidogrel LD (3.2% vs 3.7%, p = 0.72; 5.4% vs 6.2%, p = 0.64, respectively). Early mortality was also not significantly different (10.1 vs 10.8, p = 0.76). Using multivariate analyses, clopidogrel LD did not significantly affect major bleeding or transfusion (odds ratio 1.03, 95% confidence interval 0.49 to 2.17, p = 0.94) and 12-month mortality (hazard ratio 1.00, 95% confidence interval 0.72 to 1.40, p = 0.98). In conclusion, the present data showed that in elderly patients admitted for AMI, use of a LD of clopidogrel compared to a conventional dose was not associated with increased in-hospital bleeding, need for transfusion, or mortality. Large-scale randomized trials are still needed to identify the optimal LD of clopidogrel for elderly patients admitted for AMI.	f	\N
21727012	The lung is the most common site for extrahepatic metastasis from hepatocellular carcinoma (HCC). We previously reported in a series of 20 patients that pulmonary metastasectomy for HCC is feasible in selected patients. The objective of this study was to re-evaluate the long-term outcomes and prognostic factors with an additional 25 patients. We retrospectively analyzed the records of 45 consecutive patients who underwent pulmonary metastasectomy due to HCC at our institution between 1990 and 2010. Thirty-nine patients underwent hepatectomy or liver transplantation, whereas six patients underwent locoregional therapy for primary liver lesions. Twenty-seven patients died during a median 17.6-month follow-up period. The 2-year disease-free survival (DFS) was 19.5%. The 5-year overall survival (OS) was 40.9%. History of recurrence and serum des-gamma-carboxy prothrombin (DCP) level >40 mAU ml(-1) at initial pulmonary resection were unfavorably associated with OS in univariate analysis. Pulmonary metastasectomy for HCC in selected patients resulted in relatively good outcomes with regard to OS. History of recurrence and serum DCP levels were shown to be candidates of prognostic factors for OS.	f	\N
21735745	A 42-year-old Japanese woman was referred to our university hospital due to progressive anemia and bilateral hilar lymphadenopathy with diffuse ground-glass attenuation on chest computed tomography in December 2009. She had suffered from exertional dyspnea and fatigue for several months. Laboratory findings on admission demonstrated leukocytosis (10,950/ul), elevation of C-reactive protein (4.7 mg/dl), IL-6 (19.9 pg/ml), IgG4 (567 mg/dl) and polyclonal hyper gamma-globulinemia. Chest computed tomography represented mediastinal and bilateral hilar lymphadenopathy with diffuse centrilobular fine nodules and intralobular septal thickening. Histopathological findings of the specimens obtained by thoracoscopic lung and mediastinal lymph node biopsies revealed massive infiltration of IgG4-positive plasma cells in lung tissue and lymph nodes. Pathological findings and high levels of C-reactive protein and interleukin-6 suggested a diagnosis of multicentric Castleman's disease (MCD). In addition, pathological findings of peribronchiolar infiltration of IgG4-positive plasma cells and lymphoid follicles with infiltration of IgG4-positive plasma cells with a high level of IgG4 were indicative of the complication of IgG4-related lung disease. Radiological and serological findings improved rapidly soon after the initiation of oral corticosteroid treatment. It was speculated that this case indicated the close relationship between MCD and IgG4-related lung disease.	f	\N
21737965	Bartonella henselae is the causative agent of cat scratch disease (CSD) in humans. Cats are the main reservoir of this bacterium and may infect humans through scratches and bites. The purpose of this study was to determine the B. henselae seroprevalence in cats in Turkey. A total of 298 cats blood samples were collected from six different provinces of Turkey. Sera were tested for the presence of anti-B. henselae IgG antibodies by indirect fluorescent antibody test (IFA). The seroprevalence of B. henselae was 27.9% (83/298) for the cats examined in this study. The seroprevalence of cats by province was significantly higher in Bursa (41.3%), Adana (33.9%), Aydin (27.5%) and Burdur (32.3%) than in Kayseri (17.9%) and Istanbul (12.5%). Statistically significant differences were not observed between cat sexes and living conditions of cats. The results revealed that B. henselae is an important zoonotic pathogen in Turkey.	f	\N
21751546	Intravenous immunoglobulin (IVIG) products are derived from plasma pools of thousands of healthy donors. These immunoglobulin concentrates contain large number of antibodies as well trace levels various other immunologically active molecules. Therapeutic Ig formulations contain intact IgG molecules, with variable amounts of monomeric and dimeric form existing in a dynamic equilibrium. Paradoxically, IgG can exert both pro-and anti-inflammatory activities, depending on its concentration. IVIG have been used for the treatment of primary immunodeficiency disorders for more than 25 years. IVIG products are also effective in the treatment of autoimmune and inflammatory disorders; however, the precise mechanism (s) of action is not known. Clinical and laboratory studies have documented various mechanisms of action of IVIG. The complex network of immunological reactions resulting from the infusion of IVIG includes changes in several cytokines, interactions with dendritic cells, T-and B-cell effects, macrophage effects, mediated by distinct Fc-gamma receptors. IVIG is also a recently recognized modifier of complement activation and injury. The complement--scavenging ability of Ig implies expansion of the use of IVIG to all disease in which generation of complement fragments plays a crucial role in pathogenesis. Recent studies showed that the anti-inflammatory activity of IVIG result from a minor population of the pooled IgG molecules that contains terminal a-2,6 sialic acid linkages on their Fc-linked glycans. This fully processed glycan is found in 1-3% of IgG in IVIG, which may explain the requirement for a high dose of IVIG. Recent data demonstrate, that the anti-inflammatory properties of IVIG can be recapitulated with fully recombinant preparation of appropriately sialylated IgG Fc fragments. This recombinant preparation had a 35 fold enhanced activity and potentially could be used at much lower doses than IVIG preparation in the treatment of autoimmune disorders.	f	\N
21764110	The impact of diffusion-weighted imaging (DWI) and apparent diffusion coefficients (ADCs) of MR imaging on the evaluation of residual Uterine Cervical Carcinoma after Radiation Therapy, in addition to conventional MR images. Fourty-nine women presenting with a uterine cervical cancer were examined with 1.5 T MRI and DWI, 8 (4-20) weeks after treatment. Treatment response was determined based on the histopathological results after therapy and was classified as a complete response (CR) or residual disease (RD). Post-treatment DWI and ADC results were compared. Five (11%) and 44 (89%) patients were considered as having histologically-proven RD or a CR respectively. The mean ADC of cervical tissue for all patients was 1.74±0.324×10(-3) mm(2)/s and the SD was 1.94±1.11×10(-4). The mean ADC was 1.62±0.21×10(-3) mm(2)/s (SD=1.45×10(-4)) for the 5 patients with RD versus 1.76±0.33×10(-3) mm(2)/s (SD=1.99×10(-4)) for the 44 patients with a CR (p=0.09). Using 1.7×10(-3) mm(2)/s as a radiological cut-off value for the ADC, all patients classified as having histologically-proven RD had a mean ADC of ≤1.7×10(-3). In 12 (25%) cases, RD was suspected on T2-weighted MRI images alone. Eight of these cases were considered as false positives compared to the histological results. Their mean ADC was 1.98×10(-3) mm(2)/s and none of them had an ADC of <1.7×10(-3) mm(2)/s. Although our results were not statistically significant, ADC values could potentially be used to predict and monitor the response of uterine cervical cancer.	f	\N
21769106	Strong and unidirectional associations exist between the severity of cardiovascular calcifications and mortality in patients with advanced chronic kidney disease. In the past 10 years, a wealth of experimental and clinical information has been published on the key pathophysiological events that contribute to the development and progression of vascular and soft-tissue calcifications. These processes involve a sensitive balance of calcification inhibition, induction and removal. The traditional view of regarding secondary hyperparathyroidism and elevated calcium × phosphate product as the pivotal risk factors for calcification has been challenged by data demonstrating a role for other, more subtle and complex pathomechanisms. These mechanisms include the loss of endogenous calcification inhibitors, deficient clearance of calcified debris, effects of vitamin K and vitamin D, and the action of calcification inducers as in osteogenic transdifferentiation. In this Review, we describe our current knowledge of the factors involved in the passive and active regulation of extraosseous calcification processes, with an assessment of their importance as targets for future diagnostic and therapeutic interventions.	f	\N
21776811	Tumor characterization employing a voxel-wise analysis of image signal facilitates the determination of the spatial distribution of tumor attributes, and when employed for therapy response assessment offers the promise of greater sensitivity to change than conventional approaches. However, the accuracy of a voxel-wise analysis of change is limited by local registration uncertainties that can disrupt the spatiotemporal correspondence between assessed voxels. We present a method for assessing voxel correspondence strength using a multiresolution local histogram-based measure of image structure similarity. When employed in a longitudinal tumor imaging context, a voxel similarity measure must be robust to intensity variations that can arise from the image acquisition, treatment effects, or changes in underlying disease processes. Consequently, the local histogram-based similarity measure is evaluated for sensitivity to structural change and robustness to intensity variation and is compared against normalized mutual information and normalized cross-correlation. T1-weighted (T1W) magnetic resonance (MR) images of glioblastoma acquired as part of a longitudinal response assessment study are first rigidly registered, and then similarity between spatially corresponding voxels is evaluated using multiresolution local histograms. Region-based and nonuniform intensity changes of varying magnitude as well as deformations to image structure are applied individually and in combination to the test images. Statistical analysis is used to test for interaction effects between the applied perturbations and the value of the local histogram similarity function. Pair-wise voxel similarity maps are computed for pairs of longitudinal clinical MR image volumes and compared with observed patterns of change on conventional imaging. The simulations demonstrated that the local histogram measure was robust to intensity modulations applied to increasing region sizes and exhibited a strong negative correlation with the magnitude of local deformation. No statistically significant interaction effects were observed upon the value of the local histogram similarity function when deformation was applied in conjunction with a nonuniform intensity change. Pair-wise voxel similarity maps were consistent with image change observed on T1W MR imaging and revealed patterns of change not apparent in conventional image sequences. A measure of local histogram image structure similarity can be used to assess the strength of voxel to voxel correspondences independently of intensity nonuniformities. The metric can provide a local estimate of the limits of achievable correspondence underlying the registration and voxel-wise comparison of signal in longitudinal imaging used for assessing tumor response to treatment.	f	\N
21779916	Metastatic pulmonary calcification can be caused by a number of diseases, most common being end-stage renal disease. Most of the patients are asymptomatic, and imaging with computed tomography is useful in making a diagnosis. Demonstration of pulmonary and chest wall vessel calcification is characteristic. We report a case of a 60-year-old patient with chronic renal failure on dialysis, presenting with gradual onset dyspnea, who showed metastatic pulmonary calcification on chest imaging.	f	\N
21784472	Long-term ketamine abuse in humans causes significant lower urinary tract symptoms. However, the etiology of ketamine associated cystitis is still not clear. We created a mouse model of ketamine induced lower urinary tract dysfunction to explore the pathogenesis of this condition. Female C57BL/6 mice randomly distributed into control and ketamine groups received daily intraperitoneal injection of saline and ketamine (100 mg/kg), respectively. Cystometry was done in each group at 4, 8 and 16 weeks. After sacrifice the bladders were harvested for isometric muscle tension recording and immunohistochemical examination. After 8 weeks of treatment body weight growth was significantly decreased in ketamine treated mice. Cystometry revealed a significantly decreased intercontraction interval (mean±SEM 237±9 vs 360±20 seconds, p<0.001) and decreased bladder capacity (0.1±0.004 vs 0.13±0.006 ml, p<0.001) in ketamine vs saline injected mice. Increased adenosine triphosphate evoked detrusor contraction developed in the ketamine group. Immunohistochemical examination revealed increased P2X1 receptor expression in ketamine treated mouse bladders while M2 and M3 receptor expression was unchanged. At 8 weeks mice treated with ketamine showed increased voiding frequency and decreased bladder capacity, the same symptoms that develop in human ketamine abusers. Enhanced noncholinergic contractions and P2X1 receptor expression in the ketamine bladder indicate that dysregulation of purinergic neurotransmission may underlie detrusor overactivity in cases of ketamine induced bladder dysfunction.	f	\N
21785215	Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress. Here, we show that oxidized calmodulin kinase II (ox-CaMKII) is a biomarker for SND in patients and dogs and a disease determinant in mice. In wild-type mice, Ang II infusion caused sinoatrial nodal (SAN) cell oxidation by activating NADPH oxidase, leading to increased ox-CaMKII, SAN cell apoptosis, and SND. p47-/- mice lacking functional NADPH oxidase and mice with myocardial or SAN-targeted CaMKII inhibition were highly resistant to SAN apoptosis and SND, suggesting that ox-CaMKII-triggered SAN cell death contributed to SND. We developed a computational model of the sinoatrial node that showed that a loss of SAN cells below a critical threshold caused SND by preventing normal impulse formation and propagation. These data provide novel molecular and mechanistic information to understand SND and suggest that targeted CaMKII inhibition may be useful for preventing SND in high-risk patients.	f	\N
21791221	This manuscript provides a survey of research findings catered to the development of effective countermeasures against nerve agent poisoning over the past decade. New neuropathophysiological distinctive features as regards organophosphate (OP) intoxication are presented. Such leading neuropathophysiological features include recent data on nerve agent-induced neuropathology, related peripheral or central nervous system inflammation and subsequent angiogenesis process. Hence, leading countermeasures against OP exposure are down-listed in terms of pre-treatment, protection or decontamination and emergency treatments. The final chapter focuses on the description of the self-repair attempt encountered in lesioned rodent brains, up to 3months after soman poisoning. Indeed, an increased proliferation of neuronal progenitors was recently observed in injured brains of mice subjected to soman exposure. Subsequently, the latter experienced a neuronal regeneration in damaged brain regions such as the hippocampus and amygdala. The positive effect of a cytokine treatment on the neuronal regeneration and subsequent cognitive behavioral recovery are also discussed in this review. For the first time, brain cell therapy and neuronal regeneration are considered as a valuable contribution towards delayed treatment against OP intoxication. To date, efficient delayed treatment was lacking in the therapeutic resources administered to patients contaminated by nerve agents.	f	\N
21797955	The outcome of HCC after transplantation (OLT) in children is not well known. Unfavorable features based on adult reports may lead to contraindicate OLT even in children. We reviewed a cohort of children with cirrhosis and HCC to evaluate their outcome after primary transplantation. We considered children with cirrhosis and HCC who had a primary OLT. We retrospectively recorded demographic, medical and surgical features, and MC as predictors of outcome. Among 456 children transplanted in the last 15 yr, 10 (2%), median age at diagnosis 1.8 yr (range 0.5-7.2), had HCC in biliary atresia (3), BSEP deficiency (3), tyrosinemia type 1 (2), complications of choledocal cyst and glycogen storage disease type IV (1 each). At HCC discovery, median AFP was 2322 ng/mL (3-35,000), high or rising in 9/10 patients. Six patients were outside the MC. Median time on the waiting list was 38 days (1-152). Two patients died from early complications of OLT. In the other eight patients, there was no tumor recurrence after a median follow-up of four yr. Children with cirrhosis may develop HCC at a very young age. The outcome appears excellent even outside MC. Primary liver transplantation is advisable for children with cirrhosis, HCC, and no extrahepatic disease.	f	\N
21802018	The cost associated with asthma impairment in children with severe asthma has not been determined. To assess the asthma cost burden in children with severe or difficult-to-treat asthma based on asthma impairment. Children aged 6 to 12 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study with available data at baseline (n = 628), month 12 (n = 385), and month 24 (n = 280) corresponding to the National Heart, Lung, and Blood Institute asthma guidelines' impairment domain were included. Children were categorized as either very poorly controlled (VPC), not well controlled (NWC), or well controlled (WC) and assessed cross-sectionally and longitudinally. Mean total asthma costs based on direct (medication usage, unscheduled office visits, emergency department visits, hospitalizations) and indirect (school/work days lost) asthma costs were assessed. Mean annual total asthma costs were more than twice as high in the VPC group compared with NWC and WC groups (baseline: $7,846, $3,526, $3,766.44, respectively; month 12: $7,326, $2,959, $2,043, respectively; month 24: $8,879, $3,308, $1,861, respectively (all P < .001). Indirect costs accounted for approximately half the total asthma costs for VPC asthma patients at each time point. Significantly lower costs were observed for patients whose impairment status improved or temporarily improved from VPC after baseline. The economic burden of severe or difficult-to-treat asthma in children is associated with VPC asthma and improvement in asthma control and is associated with reducing cost. Further attention to patients with poorly controlled asthma, through better management strategies or more effective medications, may significantly reduce this burden of illness.	f	\N
21803694	The use of experimental model systems has expedited the elucidation of pathogenetic mechanisms of renal developmental disease in humans and the identification of genes that orchestrate developmental programming during nephrogenesis. We conducted studies to evaluate the role of AHR polymorphisms in the disruption of renal developmental programming by benzo(a)pyrene (BaP). We used metanephric cultures of C57BL/6J (C57) mice expressing the Ahr(b-1) allele and B6.D2N-Ahr(d)/J (D2N) mice expressing a mutant allele deficient in ligand binding (Ahr(d)) to investigate molecular mechanisms of renal development. Deficits in fetal programming were evaluated in the offspring of pregnant mice treated with BaP during nephrogenesis. Hydrocarbon challenge of metanephri from C57 mice altered Wilms' tumor suppressor gene (Wt1) mRNA splice variant ratios and reduced mRNAs of the Wt1 transcriptional targets syndecan-1 (Sdc1) paired box gene 2 (Pax2), epidermal growth factor receptor (Egfr), and retinoic acid receptor, alpha (Rarα). These changes correlated with down-regulation of effectors of differentiation [secreted frizzled-related sequence protein 1 (Sfrp1), insulin-like growth factor 1 receptor (Igf1r), wingless-related MMTV-integration site 4 (Wnt4), Lim homeobox protein 1 (Lhx1), E-cadherin]. In contrast, metanephri from D2N mice were spared hydrocarbon-induced changes in Wt1 splice variant ratios and deficits of differentiation. We observed similar patterns of dysmorphogenesis and progressive loss of renal function at postnatal weeks 7 and 52 in the offspring of pregnant C57 but not D2N mice gavaged with 0.1 or 0.5 mg/kg BaP on gestation days 10-13. These findings support a functional link between AHR and WT1 in the regulation of renal morphogenesis and raise important questions about the contribution of human AHR polymorphisms to the fetal origins of adult-onset kidney disease.	f	\N
21804097	Proper understanding of the roles of, and interactions between genetic, lifestyle, environmental and psycho-social factors in determining the risk of development and/or progression of chronic diseases requires access to very large high-quality databases. Because of the financial, technical and time burdens related to developing and maintaining very large studies, the scientific community is increasingly synthesizing data from multiple studies to construct large databases. However, the data items collected by individual studies must be inferentially equivalent to be meaningfully synthesized. The DataSchema and Harmonization Platform for Epidemiological Research (DataSHaPER; http://www.datashaper.org) was developed to enable the rigorous assessment of the inferential equivalence, i.e. the potential for harmonization, of selected information from individual studies. This article examines the value of using the DataSHaPER for retrospective harmonization of established studies. Using the DataSHaPER approach, the potential to generate 148 harmonized variables from the questionnaires and physical measures collected in 53 large population-based studies (6.9 million participants) was assessed. Variable and study characteristics that might influence the potential for data synthesis were also explored. Out of all assessment items evaluated (148 variables for each of the 53 studies), 38% could be harmonized. Certain characteristics of variables (i.e. relative importance, individual targeted, reference period) and of studies (i.e. observational units, data collection start date and mode of questionnaire administration) were associated with the potential for harmonization. For example, for variables deemed to be essential, 62% of assessment items paired could be harmonized. The current article shows that the DataSHaPER provides an effective and flexible approach for the retrospective harmonization of information across studies. To implement data synthesis, some additional scientific, ethico-legal and technical considerations must be addressed. The success of the DataSHaPER as a harmonization approach will depend on its continuing development and on the rigour and extent of its use. The DataSHaPER has the potential to take us closer to a truly collaborative epidemiology and offers the promise of enhanced research potential generated through synthesized databases.	f	\N
21813382	Living donor liver transplantation (LDLT) has recently emerged as an effective therapeutic alternative for patients with end-stage liver disease. In the meantime, the health-related quality of life (HRQoL) of the donors is becoming better appreciated. Here we aimed to review the current literature and summarize the effects of liver donation on the long-term HRQoL of living donors. A literature search of PubMed using "donors", "living donor liver transplantation", "health-related quality of life", and "donation" was performed, and all the information was collected. The varied postoperative outcomes of liver donors are attributive to the different evaluation instruments used. On the whole, donors experienced good long-term physical and mental well-being with a few complaining of compromised quality of life due to mild symptoms or psychiatric problems. The psychosocial dimension has received increasing attention with the vocational, interpersonal and financial impact of liver donation on donors mostly studied. Generally, donors have a good HRQoL after LDLT. Nevertheless, to achieve an ideal donor outcome, further work is necessary to minimize the negative effects as well as to incorporate recent progress in regenerative medicine.	f	\N
21824495	Sandfly fever (SF) is an arthropod-borne disease, which has not yet been reported from Ankara. In the summer of 2007, the disease started to be seen in our region, surprisingly causing severe clinical presentations. This report reviews the clinical and laboratory findings of patients with sandfly virus infection of disease outbreaks in 2008 and 2009. A retrospective single-centre descriptive study was performed. Clinically suspected cases were defined on the basis of epidemiologic history and clinical and laboratory findings. The sera samples of the suspected patients were sent to Germany for diagnostic assistance. 50 patients were included in the study. Fever, headache, photophobia, conjunctivitis, myalgia, arthralgia, nausea, abdominal pain and anorexia were common symptoms. Although the fever lasted only 3-6 days, complete recovery required up to 30 days. Leukopenia, thrombocytopenia and elevated serum aspartate-aminotransferase and alanine-aminotransferase levels were remarkable findings. The viral-load of Sandfly fever Turkey Virus (SFTV) was detected in the serum of acute patients ranged from 3.19×10(6) to 2.79×10(9) viral RNA molecules/ml. As a result we want to underline that the new type of sandfly virus causes a severe clinical picture with elevated liver enzymes and thrombocytopenia, to an extent not described before in the literature, which might be due to the elevated viral-load observed.	f	\N
21832975	In the United States, approximately one in three new human immunodeficiency virus (HIV) infections are transmitted via heterosexual contact. To monitor HIV risk behaviors and HIV prevalence among heterosexuals and other populations, CDC surveys persons in selected metropolitan statistical areas (MSAs), using the National HIV Behavioral Surveillance System (NHBS). This report summarizes data collected from heterosexuals in 24 MSAs with a high prevalence of acquired immunodeficiency syndrome (AIDS) that participated in NHBS during 2006-2007. Of 14,837 heterosexuals aged 18-50 years who were interviewed and tested, 2.0% were HIV infected. HIV prevalence was higher among those with lower socioeconomic status (SES). For example, HIV prevalence was 2.8% among participants with less than a high school education compared with 1.2% among those with more than a high school education, 2.6% among participants who were unemployed compared with 1.0% among those who were employed, and 2.3% among participants with annual household incomes at or below the poverty level compared with 1.0% among those with incomes above the poverty level. This association between HIV prevalence and SES could not be attributed to factors commonly associated with HIV infection risk in heterosexuals, such as using crack cocaine, exchanging sex for things such as money or drugs, or being diagnosed with a sexually transmitted disease (STD). Based on the association observed between HIV prevalence and SES, HIV prevention activities targeted at heterosexuals in urban areas with high AIDS prevalence should be focused on those with lower SES.	f	\N
21835304	A fundamental challenge in analyzing exome-sequence data is distinguishing pathogenic mutations from background polymorphisms. To address this problem in the context of a genetically heterogeneous disease, retinitis pigmentosa (RP), we devised a candidate-gene prioritization strategy called cis-regulatory mapping that utilizes ChIP-seq data for the photoreceptor transcription factor CRX to rank candidate genes. Exome sequencing combined with this approach identified a homozygous nonsense mutation in male germ cell-associated kinase (MAK) in the single affected member of a consanguineous Turkish family with RP. MAK encodes a cilium-associated mitogen-activated protein kinase whose function is conserved from the ciliated alga, Chlamydomonas reinhardtii, to humans. Mutations in MAK orthologs in mice and other model organisms result in abnormally long cilia and, in mice, rapid photoreceptor degeneration. Subsequent sequence analyses of additional individuals with RP identified five probands with missense mutations in MAK. Two of these mutations alter amino acids that are conserved in all known kinases, and an in vitro kinase assay indicates that these mutations result in a loss of kinase activity. Thus, kinase activity appears to be critical for MAK function in humans. This study highlights a previously underappreciated role for CRX as a direct transcriptional regulator of ciliary genes in photoreceptors. In addition, it demonstrates the effectiveness of CRX-based cis-regulatory mapping in prioritizing candidate genes from exome data and suggests that this strategy should be generally applicable to a range of retinal diseases.	f	\N
21846442	Cardiac rhabdomyoma (CR) is the cardiac tumour most commonly diagnosed in utero. Eighty percent of CRs are associated with tuberous sclerosis (TS). TS is a rare multi-system disease, with autosomal dominant genetic transmission. If the parents of an affected child do not have features of TS, then either one parent is mosaic for the TS gene mutation or the affected child is the result of a de novo germline mutation. We present a case of a dizygotic twin pregnancy complicated by CRs in both fetuses at 24 weeks. Twin A died in utero at 28 weeks. Preterm labour and delivery of twin B occurred at 33 weeks. Twin B had multiple small CRs and a large apical CR. At six weeks after delivery, the CRs had disappeared or reduced in size. Regression in the third trimester or postnatally is the natural course of CRs. Molecular testing for TS identified two variants in the TSC2 gene. The parents were clinically unaffected; however, the father was subsequently found on an MRI of the head to have cortical tubers, and he was found to carry the pathogenic TSC2 mutation. Since dizygotic twin pregnancy is akin to two consecutive pregnancies, the etiology in our case is due to one parent having subclinical TS. To the best of our knowledge, this is the first such case to be reported.	f	\N
21852013	We compared the intergenerational variations of the clinical phenotype between 30 patients affected with multiple autoimmune syndrome (MAS) and their affected first- and second-degree relatives. Mean age at onset was always significantly higher in the previous generation than in probands for all the considered diseases.	f	\N
21852664	Observational studies have reported an association between metabolic syndrome (MetS) and microalbuminuria or proteinuria and chronic kidney disease (CKD) with varying risk estimates. We aimed to systematically review the association between MetS, its components, and development of microalbuminuria or proteinuria and CKD. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS AND POPULATION: We searched MEDLINE (1966 to October 2010), SCOPUS, and the Web of Science for prospective cohort confidence interval (CI) studies that reported the development of microalbuminuria or proteinuria and/or CKD in participants with MetS. Risk estimates for eGFR <60 ml/min per 1.73 m(2) were extracted from individual studies and pooled using a random effects model. The results for proteinuria outcomes were not pooled because of the small number of studies. Eleven studies (n = 30,146) were included. MetS was significantly associated with the development of eGFR <60 ml/min per 1.73 m(2) (odds ratio, 1.55; 95% CI, 1.34, 1.80). The strength of this association seemed to increase as the number of components of MetS increased (trend P value = 0.02). In patients with MetS, the odds ratios (95% CI) for development of eGFR <60 ml/min per 1.73 m(2) for individual components of MetS were: elevated blood pressure 1.61 (1.29, 2.01), elevated triglycerides 1.27 (1.11, 1.46), low HDL cholesterol 1.23 (1.12, 1.36), abdominal obesity 1.19 (1.05, 1.34), and impaired fasting glucose 1.14 (1.03, 1.26). Three studies reported an increased risk for development of microalbuminuria or overt proteinuria with MetS. MetS and its components are associated with the development of eGFR <60 ml/min per 1.73 m(2) and microalbuminuria or overt proteinuria.	f	\N
21855111	The EHF (Ets homologous factor) gene was previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared to malignant mesothelioma using gene expression arrays. The objective of this study was to validate this finding at the mRNA level in a larger series. We analyzed the diagnostic role of EHF in 98 ovarian serous carcinoma effusions, 23 malignant mesothelioma specimens (20 effusions, 3 surgical specimens), and 28 primary ovarian serous carcinomas using quantitative real-time polymerase chain reaction. Expression levels of EHF in ovarian carcinoma were additionally investigated for association with clinicopathologic parameters and survival. Quantitative real-time polymerase chain reaction analysis showed significantly higher expression of EHF mRNA in ovarian carcinoma effusions and in primary ovarian carcinoma compared to malignant mesothelioma effusions (P < .001 for both). EHF mRNA expression was additionally higher in primary ovarian carcinomas compared to effusions of this cancer (P < .001). In univariate analysis for all patients with effusions, higher EHF mRNA levels were associated with a trend for shorter progression-free survival (P = .066), which became significant in analysis of 45 patients with primary diagnosis pre-chemotherapy effusions (P = .01). In Cox multivariate analysis, EHF mRNA expression was an independent predictor of poor progression-free survival for all patients and patients with primary diagnosis pre-chemotherapy effusions (P = .033 and P = .009, respectively). EHF mRNA levels differentiate ovarian carcinoma from malignant mesothelioma and may thus be of diagnostic value in this setting. EHF may be a novel prognostic marker in ovarian carcinoma.	f	\N
21872587	Decline in verbal fluency is the most consistent and persistent cognitive impairment documented after deep brain stimulation of the subthalamic nucleus in Parkinson's disease. The mechanisms of this deficit are unclear. We aimed to identify and characterise verbal fluency related processing within the subthalamic nucleus through analysis of local field potentials. Local field potentials were recorded from deep brain stimulation electrodes implanted in the subthalamic nuclei of 8 patients (16 sides) with Parkinson's disease, when patients were on medication. Patients performed phonemic and semantic verbal fluency tasks and a control word repetition task to control for the motor output involved in response generation. Significant increases in local field potential Power (p ≤ 0.05) were seen across a broad gamma frequency band (30-95 Hz) during both verbal fluency tasks, after controlling for motor output. Increases in gamma local field potential Power of +7.5% ± 2.3% (SEM) in the semantic fluency task and +6.9% ± 2.0% in the phonemic fluency task were derived when averaging across all electrode contact pairs. Gamma changes recorded from contacts lying in the left hemisphere (dominant in verbal fluency) correlated with average number of correct responses generated (r=0.81 p=0.015) and measures of 'switching' (r=0.79 p=0.020) particularly strongly in the semantic fluency task. Frequency specific power changes observed during task performance are consistent with involvement of the subthalamic nucleus in switching during verbal fluency. Antagonism of such task-related activity with high frequency stimulation of this nucleus may explain the impairments reported.	f	\N
21876350	We proposed a new method to estimate dry weight (DW) using single frequency bioimpedance. We hypothesized that the change in whole body resistance at 50 kHz (R(50)) was proportional to the ultrafiltration volume (UFV) during a hemodialysis (HD) session. When the targeted resistance estimated in healthy subjects was reached, the patient achieved his/her DW. UFV and R(50) were monitored in 40 HD patients. Another 43 HD patients were stratified into 2 groups to validate this method. The change in whole body resistance was proportional to UFV in each of the 40 HD patients. In the DW(decrease) group, pre-dialysis systolic blood pressure (n = 29, 154.5 ± 22.8 vs. 146.9 ± 22.3, p < 0.05) and antihypertensive medicine (4.7 ± 3.6 vs. 3.3 ± 2.2, p < 0.05) decreased without adverse symptoms change. In the DW(increase) group, the number of adverse symptoms in 1 week (n = 14, 26 vs. 6, p < 0.05) decreased without a change in systolic blood pressure. This method may become a convenient and cheaper way to estimate DW in HD patients.	f	\N
21884641	Breast cancer is a complex and heterogeneous disease. Gene expression profiling has contributed significantly to our understanding of this heterogeneity at a molecular level, refining taxonomy based on simple measures such as histological type, tumour grade, lymph node status and the presence of predictive markers like oestrogen receptor and human epidermal growth factor receptor 2 (HER2) to a more sophisticated classification comprising luminal A, luminal B, basal-like, HER2-positive and normal subgroups. In the laboratory, breast cancer is often modelled using established cell lines. In the present review we discuss some of the issues surrounding the use of breast cancer cell lines as experimental models, in light of these revised clinical classifications, and put forward suggestions for improving their use in translational breast cancer research.	f	\N
21884662	Asthma is a frequent illness in young adults and is characterized by airway hyper responsiveness (AHR) and airway inflammation. Asthma is a complex disease and AHR as well as inflammation may be limited, although characteristic symptoms are present. The clinical experience in asthma treatment is that not all asthmatics have a satisfactory effect of the different drugs. Asthma has been found to develop from one disease to a multifaceted disease with numerous different possibilities. More research is needed in strategic asthma management in the search for tailored treatment strategy.	f	\N
21889188	We report the sixth autopsy case of a patient with aceruloplasminemia. He was the younger brother of the first reported autopsy case of this disease. Among autopsy cases with aceruloplasminemia reported to date, he had the longest duration of neurologic disorders. The neuropathologic findings showed that the basal ganglia and dentate nuclei were most severely affected. The most striking finding in the present case was that marked iron deposition was evident in the cerebral cortex. Many enlarged or deformed astrocytes and globular structures, both of which were heavily iron loaded, were found in the cerebral cortex as well as in the basal ganglia. Pyramidal neurons in his cerebral cortex were fewer in number than observed in the previous reported cases. There was a negative correlation between the number of cortical pyramidal neurons and globular structures. The present case clearly indicates that the neuropathologic process in aceruloplasminemia extends beyond the basal ganglia to the cerebral cortex with time.	f	\N
21889832	Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. Identify predictors of biochemical tumor control and distant metastases-free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. This retrospective analysis comprised 2551 patients with clinical stages T1-T3 PCa. Median follow-up was 8 yr, extending >20 yr. Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels < 70.2 Gy and 70.2-79.2 Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse-free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes. Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high-risk patients; however, an overall survival advantage was not observed.	f	\N
21890816	A multicentre cohort follow-up study of a large number of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma was conducted to elucidate the long-term outcome of the disease after Helicobacter pylori eradication. 420 patients with gastric low-grade MALT lymphoma who had undergone successful H pylori eradication and been followed up for at least 3 years were registered from 21 participating institutes. Responders to treatment were defined as patients whose post-treatment biopsies showed complete histological response (ChR) or probable minimal residual disease (pMRD). Treatment failure was defined as the status of progressive disease or lymphoma relapse after ChR/pMRD. 323 patients (77%) responded to H pylori eradication. A logistic regression analysis showed that absence of H pylori, submucosal invasion determined by endoscopic ultrasonography and t(11;18)/API2-MALT1 were independent predictors of resistance to H pylori eradication. During the follow-up periods ranging from 3.0 to 14.6 years (mean 6.5 years, median 6.04 years), the disease relapsed in 10 of 323 responders (3.1%) while progressive disease was found in 27 of 97 non-responders (27%). Thus, 37 of 420 patients (8.8%) were regarded as treatment failures. Of these 37 patients, transformation into diffuse large B cell lymphoma occurred in nine patients. Among the non-responders and relapsed patients, 17 patients were subjected to a 'watch and wait' strategy while 90 patients underwent second-line treatments including radiotherapy (n=49), chemotherapy (n=26), surgical resection (n=6), chemoradiotherapy (n=5), antibiotic treatment (n=2), rituximab monotherapy (n=1) or endoscopic resection (n=1). Probabilities of freedom from treatment failure, overall survival and event-free survival after 10 years were 90%, 95% and 86%, respectively. Cox multivariate analysis revealed endoscopic non-superficial type to be an independent prognostic factor for adverse freedom from treatment failure, overall survival and event-free survival. The excellent long-term outcome of gastric MALT lymphoma after H pylori eradication was confirmed by this large-scale follow-up study.	f	\N
21896508	The interaction between transcription factor (TF) and transcription factor binding site (TFBS) is essential for gene regulation. Mutation in either the TF or the TFBS may weaken their interaction and thus result in abnormalities. To maintain such vital interaction, a mutation in one of the interacting partners might be compensated by a corresponding mutation in its binding partner during the course of evolution. Confirming this co-evolutionary relationship will guide us in designing protein sequences to target a specific DNA sequence or in predicting TFBS for poorly studied proteins, or even correcting and rescuing disease mutations in clinical applications. Based on six, publicly available, experimentally validated TF-TFBS binding datasets for the basic Helix-Loop-Helix (bHLH) family, Homeo family, High-Mobility Group (HMG) family and Transient Receptor Potential channels (TRP) family, we showed that the evolutions of the TFs and their TFBSs are significantly correlated across eukaryotes. We further developed a mutual information-based method to identify co-evolved protein residues and DNA bases. This research sheds light on the dynamic relationship between TF and TFBS during their evolution. The same principle and strategy can be applied to co-evolutionary studies on protein-DNA interactions in other protein families. All the datasets, scripts and other related files have been made freely available at: http://jjwanglab.org/co-evo. junwen@uw.edu. Supplementary data are available at Bioinformatics online.	f	\N
21904924	The distribution of complement component 4 (C4) gene copy number (GCN) has been validated in European populations. Meanwhile, C4 gene has been identified as a susceptibility gene for systemic lupus erythematosus (SLE). However, the association and the possible phenotype significance remain to be determined intensely in the Chinese population. This study was designed to validate the distribution of C4 GCNs in Chinese Han and the correlation between C4 GCNs and SLE using quantitative real-time polymerase chain reaction in 924 SLE patients and 1,007 controls. The results presented distribution of C4 GCNs in healthy populations and also showed that lower C4 GCN was a risk factor for SLE and higher C4 GCN was a protective factor against the disease susceptibility, which was similar to the report in the Caucasian population. Furthermore, we found the association between C4A GCN and disease subphenotypes of arthritis with SLE. We conclude that the association of C4 GCN with SLE was replicated in Chinese Han population, which highlighted the importance of C4 in SLE pathogenesis of diverse populations.	f	\N
21912125	Women undergoing isolated coronary artery bypass graft (CABG) surgery have been previously shown to be at an independently increased risk for post-operative morbidity and mortality. However, there are considerably less data on whether this trend remains true in patients undergoing concomitant aortic valve replacement (AVR) and CABG surgery. The aim of our study was to investigate this pertinent issue. Data obtained between June 2001 and December 2009 by the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program were retrospectively analysed. Demographic, operative data and post-operative complications were compared between male and female patients using χ(2) and t tests. Long-term survival analysis was performed using Kaplan-Meier survival curves and the log-rank test. Independent risk factors for short- and long-term mortality were identified using binary logistic and Cox regression, respectively. Concomitant AVR and CABG surgery was undertaken in 2,563 patients; 31.8% were female. Female patients were older (mean age 76 vs. 73 years; p < 0.001) and presented more often with hypertension (p < 0.001) but less often with severely impaired ejection fraction (p < 0.001), peripheral vascular disease (p < 0.001) and triple vessel disease (p < 0.001). Women did not demonstrate an increased risk of 30-day mortality (4.8 vs. 3.3%) on univariate (p = 0.069) or multivariate (p = 0.236) analysis. Female gender was independently associated with post-operative myocardial infarction (p = 0.022) and red blood cell transfusion (p < 0.001). There was no difference in long-term survival between men and women on multivariate analysis (p = 0.413). Female gender is not associated with poorer short- or long-term outcomes after concomitant CABG and AVR surgery.	f	\N
21913717	Hepatocellular carcinoma (HCC) is one of the leading causes of mortality from solid organ malignancy worldwide. Because of the complexity of proteins within liver cells and tissues, the discovery of therapeutic targets of HCC has been difficult. To investigate strategies for decreasing the complexity of tissue samples for detecting meaningful protein mediators of HCC, we employed subcellular fractionation combined with 1D-gel electrophoresis and liquid chromatography-tandem mass spectrometry analysis. Moreover, we utilized a statistical method, namely, the Power Law Global Error Model (PLGEM), to distinguish differentially expressed proteins in a duplicate proteomic data set. Mass spectrometric analysis identified 3045 proteins in nontumor and HCC from cytosolic, membrane, nuclear, and cytoskeletal fractions. The final lists of highly differentiated proteins from the targeted fractions were searched for potentially translocated proteins in HCC from soluble compartments to the nuclear or cytoskeletal compartments. This analysis refined our targets of interest to include 21 potential targets of HCC from these fractions. Furthermore, we validated the potential molecular targets of HCC, MATR3, LETM1, ILF2, and IQGAP2 by Western blotting, immunohistochemisty, and immunofluorescent microscopy. Here we demonstrate an efficient strategy of subcellular tissue proteomics toward molecular target discovery of one of the most complicated human disease, HCC.	f	\N
21915990	Investigations of rare cell types in peripheral blood samples, such as tumor, fetal, and endothelial cells, represent an emerging field with several potentially valuable medical applications. Peripheral blood is a particularly attractive body fluid for the detection of rare cells as its collection is minimally invasive and can be repeated throughout the course of the disease. Because the number of rare cells in mononuclear cells can be very low (1 in 10 million), a large number of cells must be quickly screened, which places demanding requirements on the screening technology. While enrichment technology has shown promise in managing metastatic disease, enrichment can cause distortions of cell morphology that limit pathological identification, and the enrichment targeting adds additional constraints that can affect sensitivity. Here, we describe a new approach for detecting rare leukemia cells that does not require prior enrichment. We have developed an immunocytochemical assay for identification of leukemia cells spiked in peripheral blood samples, and a high-speed scanning instrument with high numerical aperture and wide field of view to efficiently locate these cells in large sample sizes. A multiplex immunoassay with four biomarkers was used to uniquely identify the rare cells from leukocytes and labeling artifacts. The cytometer preserves the cell morphology and accurately locates labeled rare cells for subsequent high resolution imaging. The sensitivity and specificity of the approach show promise for detection of a low number of leukemia cells in blood (1 in 10 million nucleated cells). The method enables rapid location of rare circulating cells (25 M cells/min), no specific enrichment step, and excellent imaging of cellular morphology with multiple immunofluorescent markers. The cell imaging is comparable to other imaging approaches such as laser scan cytometry and image flow cytometry, but the cell analysis rate is many orders of magnitude faster making this approach practical for detection of rare cells.	f	\N
21916327	Serum dioxin studies of Vietnam (VN) veterans, military historical records of tactical herbicide use in Vietnam, and the compelling evidence of the photodegradation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aspects of environmental fate and low bioavailability of TCDD are consistent with few, if any, ground troop veterans being exposed to Agent Orange. That conclusion, however, is contrary to the presumption by the Department of Veterans Affairs (DVA) that military service in Vietnam anytime from January 9, 1962 to May 7, 1975 is a proxy for exposure to Agent Orange. The DVA assumption is inconsistent with the scientific principles governing determinations of disease causation. The DVA has nonetheless awarded Agent Orange-related benefits and compensation to an increasing number of VN veterans based on the presumption of exposure and the published findings of the Institute of Medicine that there is sufficient evidence of a "statistical association" (a less stringent standard than "causal relationship") between exposure to tactical herbicides or TCDD and 15 different human diseases. A fairer and more valid approach for VN veterans would have been to enact a program of "Vietnam experience" benefits for those seriously ill, rather than benefits based on the dubious premise of injuries caused by Agent Orange.	f	\N
21917357	To know the relative weight of the diagnosis of detrusor overactivity (DO) in the Urodynamic Units of Spain and relate the prevalence of the overactive bladder (OB) syndrome. An epidemiological, descriptive, retrospective, multicenter, national study conducted according to registered data in 47 Urodynamic Units covering the Spanish geographic area in the different areas of health distributed among the regional communities. These data inform about the health care received by 35% of the Spanish population. Urodynamic diagnoses and related variables, recorded during 2007 and 2008, were collected. A mean of 346.45 (SD=304.03) and 349.72 (SD=296.49) urodynamics studies per care unit were performed in women during 2007 and 2008, respectively and 181.20 (SD=212.71) and 195.68 (SD=257.58) in men. The relative weight of the diagnosis of non-neurogenic DO in women per unit was 31.39% and 35.28%, in 2007 and 2008, and in men was 21.06% and 20.43%. The diagnostic capacity of DO was 19.28 new cases per 100,000 inhabitants/year. The diagnosis of non-neurogenic DO in the woman accounts for one third of all the urodynamic/year diagnoses and more than half of the diagnoses of DO. In men, DO accounts for 25% of the diagnoses, the most frequent one being that associated with benign prostatic hyperplasia, followed by that of neurogenic cause. Approximately half of the DO diagnoses in children correspond to non-neurogenic DO. The differences between the capacity of diagnosis of DO (ratio per 100,000 inhabitants) is far from many of the estimations of the prevalence of OB (relationship %). The doubt may exist about whether part of this quota is secondary and not-idiopathic, given the large difference between the frequency of OB and the capacity of diagnosis of DO.	f	\N
21917441	Idiopathic pulmonary fibrosis (IPF) is a lethal lung disorder of unknown etiology. The disease is likely the result of complex interactions between genetic and environmental factors. Evidence suggests that certain environmental factors, such as cigarette smoking and metal dust exposures, or comorbidities like gastroesophageal reflux, and type 2 diabetes mellitus (DM2) may increase risk to develop IPF. Substantial uncertainty remains, however, regarding these and other putative risk factors for IPF. In this study we performed a case-control analysis including 100 patients with IPF and 263 controls matched for age sex and place of residence. We used a structured questionnaire to identify potential risk factors for IPF, including environmental and occupational exposures as well as the relevance of family history of pulmonary fibrosis. The multivariate analysis revealed that family history of pulmonary fibrosis [OR = 6.1, CI95% 2.3-15.9; p < 0.0001] was strongly associated with increased risk of IPF. Actually, 20% of the cases reported a parent or sibling with pulmonary fibrosis. Gastroesophageal reflux [OR = 2.9, CI: 1.3-6.6; p = 0.007], former cigarette smoking [OR = 2.5, CI: 1.4-4.6, p = 0.003], and past or current occupational exposure to dusts, smokes, gases or chemicals [OR = 2.8, CI: 1.5-5.5; p = 0.002] were also associated with the disease. Despite being a significant risk factor on univariate analysis DM2 was not significant in multivariate analysis. These findings indicate that family history of pulmonary fibrosis is a strong risk factor for IPF. Also, we confirmed that occupational exposures, gastroesophageal reflux and former smoking increase the risk for this disease.	f	\N
21918487	Although the use of embryonic stem cells to treat disease has caused much controversy, one type of stem cell treatment has slowly and steadily shown promise but has not engendered negative ethical media attention: the use of umbilical stem cells. Umbilical cord blood (UCB) contains stem cells that have already successfully treated a variety of diseases, including leukemias, lymphomas, hemoglobinopathies, immunodeficiencies, and disorders of metabolism; ongoing research continues to explore additional diseases for potential treatment. Cord blood can be stored in private banks or public banks. Private cord blood banks save cord blood for use by the family only, at a cost. Public cord blood banks accept donations and the cord blood is then used for the general public and/or research. A review of the literature finds that public banking is the preferred recommendation over private unless there is a known family member with a disease that can currently be treated with cord blood. This article discusses cord blood banking options as well as the ethical issues and barriers facing both healthcare providers and patients when dealing with cord blood banking.	f	\N
21924425	Recent genome-wide association studies (GWAS) have identified associations with myocardial infarction and coronary artery disease (CAD), but the mechanisms underlying these associations remain largely unclear. Carotid intima-media thickness (IMT) is a measure of early arterial remodeling and arteriosclerosis. Therefore, if CAD associated SNPs are also associated with carotid IMT; it suggests that they are acting via the early stages of the atherosclerotic process. In three large community based independent populations (CAPS, KORA and Young Finns) of European ancestry in which common carotid IMT had been measured (total 4961 individuals), we determined whether SNPs that have been associated with CAD in GWAS studies are also associated with carotid IMT. Associations with plaque were not examined. We identified 11 SNPs and one haplotype previously associated with CAD. None of these were associated with common carotid IMT. We found no evidence that SNPs associated with CAD on GWAS are also associated with carotid IMT. This suggests these genetic associations are not acting via early vessel remodeling or early arteriosclerosis.	f	\N
21925097	The aim of this pilot study was to evaluate the feasibility of long-term subcutaneous application of low-dose IL-2 in children with malignancies at very high risk of relapse who underwent highly T cell and B cell depleted HLA-identical (MUD) or full haplotype mismatched related hematopoetic stem cell transplantation. We studied 11 patients with acute leukemias / myelodysplastic syndrome and juvenile myelomonocytic leukemia (active disease and/or second stem cell transplantation, n = 8; ≥CR 2, n = 2) and relapsed or progressive Ewing's sarcoma (n = 2) who received prophylactic IL-2 treatment for a high probability of disease recurrence after allo-HSCT. Toxicities from IL-2 were transient fever, fatigue and local inflammation. In one patient GvHD grade III with no clear association to IL-2 administration occurred. IL-2 administration was started at median day 57 (range 13-154) post-transplant for a mean duration of 28 days (range 15-250). IL-2 administration clearly increased NK cell activity. 3 of 11 patients (ALL, AML, multifocal Ewings sarcoma) survived with a follow-up of ten years. In conclusion, long-term low-dose IL-2 subcutaneous application is feasible in children due to a low side effect profile even after HLA mismatched transplantation and may be a strategy to prevent relapse in pediatric malignancies with extremely high risk of relapse.	f	\N
21926372	Ryanodine receptor 1 (RyR1) is a Ca(2+) release channel located in the sarcoplasmic reticulum membrane of skeletal muscle. More than 200 variants in RyR1 have been identified in DNA from patients with malignant hyperthermia (MH) and congenital myopathies; only 30 have been sufficiently studied so as to be identified as MH-causative mutations. The Ala4894Thr RyR1 variant was found in a Japanese patient with susceptibility to MH, and the Ala4894Pro variant in a rare case of myopathy: congenital neuromuscular disease with uniform type 1 fiber (CNMDU1). We hypothesized that different Ala4894 variants of RyR1 cause different pathophysiological changes that are identifiable by having differing pharmacological sensitivities to RYR1 agonists. Expression vector with a mutation in RYR1 corresponding to the Ala4894Thr, Ala4894Pro, Ala4894Ser, or Ala 4894Gly variant of human RyR1 was transfected into human embryonic kidney 293 cells. At 72 hours after transfection, we determined the intracellular Ca(2+) changes induced by caffeine and 4-chloro-m-cresol (4CmC), in the presence or absence of dantrolene. Ala4894Thr-transfected cells and Ala4894Ser-transfected cells were more sensitive to caffeine than the wild type, and Ala4894Thr-transfected cells were also more sensitive to 4CmC than the wild type, whereas Ala4894Pro-transfected cells had no response to caffeine or 4CmC. Ala4894Gly-transfected cells were significantly less sensitive to caffeine than the wild type. In addition, the responses of Ala4894Thr-transfected cells and Ala4894Ser-transfected cells to caffeine were suppressed by dantrolene. We concluded that different Ala4894 variants of RyR1 lead to different agonist/antagonist sensitivities, which may predict differing RYR1 functionality during excitation-contraction coupling and sensitivity to MH. The hypersensitive Ala4894Thr-RyR1 is associated with MH and the poorly functional Ala4894Pro-RyR1 with CNMDU1.	f	\N
21934067	The role of CRP as a regulator of inflammation is not fully understood. Structural rearrangement in CRP results in expression of potent proinflammatory actions. Proteolysis of CRP yields the C-terminal peptide Lys(201)-Pro-Gln-Leu-Trp-Pro(206). Here, we investigated the impact of this peptide on neutrophil interactions with endothelial cells and platelets, critical inflammatory events triggering acute coronary artery disease. CRP peptide 201-206 induced L-selectin shedding from human neutrophils and inhibited L-selectin-mediated neutrophil adhesion to TNF-α-activated HCAECs under nonstatic conditions. CRP peptide 201-206 also attenuated shear-induced up-regulation of platelet P-selectin expression, platelet capture of neutrophils, and subsequent homotypic neutrophil adhesion in human whole blood. Anti-CD32 but not anti-CD16 or anti-CD64 mAb effectively prevented the inhibitory actions of CRP peptide 201-206. Substitution of Lys(201), Gln(203), or Trp(205) with Ala in CRP peptide 201-206 resulted in loss of the biological activities, whereas peptides in which Pro(202), Leu(204), or Pro(206) was substituted with Ala retained biological activity. We identified amino acid residues involved in CRP peptide 201-206-FcγRII (CD32) interactions, which mediate potent antineutrophil and antiplatelet adhesion actions, and these findings open up new perspectives for limiting inflammation and thrombosis underlying coronary artery disease.	f	\N
21935854	A 65-year-old woman presented with reduced general condition and dyspnoea that was progressive over the last months. Clinical findings revealed an exophthalmus on the right, xanthelasm and mild peripheral oedema. Previously, a pericardiocentesis had been performed due to a large pericardial effusion. A previous CT scan showed a mass attached to the pericardium extending through the atrio-ventricular groove and a thickened aorta. In addition, a retroperitoneal fibrosis and an occlusion of both Aa. iliacae internae were found. The ECG showed sinus rhythm. Laboratory findings demonstrated a microcytic anemia and a renal failure. Chest radiography showed a large cardiac silhouette, while the transthoracic echocardiography revealed a recurrent large pericardial effusion. A PET/CT scan of the chest and abdomen showed a tissue infiltration of the retroperitoneal structures, a mass surrounding the right coronary artery and the right orbita. Finally, a femur biopsy confirmed the diagnosis of Erdheim-Chester disease. With the diagnosis Erdheim-Chester disease we started a high dose immunsuppressive therapy using glucocorticoids and interferon-a. Tumour size slightly decreased during the following 2 months, however the patient developed a severe urosepsis and died from multiorgan failure. We report a case of an Erdheim-Chester disease with cardiovascular involvement primarily diagnosed due to a recurrent large pericardial effusion. In case of cardial tumors with interatrial septum or coronary artery involvement together with cerebral manifestations, an Erdheim-Chester disease should be taken into account.	f	\N
21938677	Cyclosporine A is a potent immunosuppressant used to prevent organ transplant rejection and treat various autoimmune diseases. However, cyclosporine A can also induce gingival overgrowth, which is characterized by increased extracellular matrix due to an altered balance between collagen synthesis and degradation. This study proposed to verify whether trans-glutaminase 2, an enzyme thought to be responsible for the assembly and remodelling of extracellular matrix, plays any role in the pathogenesis of cyclosporine A-induced gingival overgrowth. Cyclosporine A-induced gingival overgrowths were collected from 21 liver transplant patients and case-controlled with 20 non-hyperplastic gingival biopsies from healthy patients who had previous periodontal treatment. In both groups, the presence and tissue distribution of transglutaminase 2 were determined by immunohistochemistry and analyzed in comparison with the tissue morphology and expression of lymphocyte-related antigens (CD3 and CD20) and a vessel-related marker (CD34). Transglutaminase 2 expression showed a significant increase (2.6-fold) in the stromal component of cyclosporine A-treated patients compared with controls (p<0.001), which suggested that transglutaminase 2 had a role in the pathogenesis of the disease. Further studies should investigate the therapeutic effect of anti-transglutaminase 2 drugs (putrescine or 1,4-diamino-butane) in these patients.	f	\N
21946897	Genetic factors may play a role in fibrosis progression in patients with chronic hepatitis C (CHC). A cirrhosis risk score (CRS7) with seven single nucleotide polymorphisms was previously shown to correlate with cirrhosis in patients with CHC. This study aimed to assess the validity of CRS7 as a marker of fibrosis progression and cirrhosis and as a predictor of clinical outcomes in patients with CHC. A total of 938 patients (677 Caucasians, 165 African-Americans, and 96 Hispanic/Other) in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial were studied. CRS7 was categorized a priori as high risk (n=440), medium risk (n=310), or low risk (n=188). Patients were assessed for four possible outcomes: fibrosis progression, cirrhosis, clinical outcomes [decompensation or hepatocellular carcinoma (HCC)], or HCC alone. Twenty-nine percent (142/493) developed an increase in fibrosis score by greater than or equal to 2 points on follow-up biopsies, 58% had cirrhosis on one or more biopsies, 35% developed at least one clinical outcome, and 13% developed HCC. CRS7 (trend test) was associated with risk for fibrosis progression (P=0.04) with adjusted hazard ratio of 1.27 (95% confidence interval: 1.01-1.58) and with cirrhosis (P=0.05) with adjusted odds ratio of 1.19 (1.00-1.41). Rates of HCC and clinical outcomes were increased in patients with higher CRS7 scores, but were not statistically significant (P=0.12 clinical outcomes, and P=0.07 HCC). A single nucleotide polymorphism in AZIN1 was significantly associated with fibrosis progression. CRS7 was validated as a predictor of fibrosis progression and cirrhosis among Hepatitis C Antiviral Long-term Treatment against Cirrhosis patients, who all had advanced fibrosis. CRS7 was not predictive of clinical outcome.	f	\N
21953291	Although tumor reduction via present-day prehepatectomy chemotherapy can render initially unresectable disease potentially resectable, little is known about the effects of such chemotherapy on liver metastases with known attachment to or invasion of major intrahepatic vessels. We histologically assessed the relationships of liver tumors to major intrahepatic vessels after chemotherapy. In 45 patients who underwent chemotherapy and hepatectomy with pretreatment images showing metastases attached to or invading major intrahepatic vessels, 77 metastases showed attachment to or invasion of 96 vessels. Using postchemotherapy imaging, 11 of 77 metastases (14.3%) appeared separated from 12 of 96 major hepatic vessels (12.5%). Among 83 vessels later examined pathologically, 29 showed direct invasion (35%) and 10 showed attachment (12%). Tumors involved another 9 vessels (11%) that were separated surgically from the tumor and preserved during hepatectomy. Tumor attachment that exceeded 25% of vessel circumferences via imaging after chemotherapy was a factor associated with pathological vascular invasion or attachment according to multivariate analysis (relative risk, 8.449; 95% confidence interval, 1.961-36.415; P = .0042). Liver metastasis attachment to or invasion of major intrahepatic vessels is difficult to eradicate even with otherwise effective chemotherapy.	f	\N
21955617	Osteoarthritis (OA) is a degenerative joint disease characterized by progressive loss of articular cartilage, subchondral bone sclerosis, osteophyte formation, and synovial inflammation, causing substantial physical disability, impaired quality of life, and significant health care utilization. Traditionally, non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase (COX)-2 inhibitors, have been used to treat pain and inflammation in OA. Besides its anti-inflammatory properties, evidence is accumulating that celecoxib, one of the selective COX-2 inhibitors, has additional disease-modifying effects. Celecoxib was shown to affect all structures involved in OA pathogenesis: cartilage, bone, and synovium. As well as COX-2 inhibition, evidence indicates that celecoxib also modulates COX-2-independent signal transduction pathways. These findings raise the question of whether celecoxib, and potentially other coxibs, is more than just an anti-inflammatory and analgesic drug. Can celecoxib be considered a disease-modifying osteoarthritic drug? In this review, these direct effects of celecoxib on cartilage, bone, and synoviocytes in OA treatment are discussed.	f	\N
21959310	We report 9 patients with pleural biopsies referred because of concern about infiltration of what appeared to be chest wall fat by pan-keratin-positive spindled cells, a finding that led to a consideration of desmoplastic mesothelioma. All patients showed pleural effusions/pleural thickening on computed tomographic scan. Pleural biopsy showed a greatly thickened and fibrotic paucicellular pleura with circular fat-like spaces and, sometimes, adjacent oblate spaces mostly deep in the fibrotic area. Indistinct, keratin-positive, spindle cells arranged parallel to the pleural surface coursed between these fat-like spaces. S-100 stains were negative around the fat-like spaces. Vimentin stains showed that the spaces did not have a cellular lining of any kind. Sometimes the spaces contained faintly hematoxyphilic material that was Alcian blue positive, and similar material was seen in the fibrotic stroma. Follow-up with periods ranging from 6 to 30 months revealed that 8 cases had stable disease on chest imaging or by clinical findings. One case had slowly progressive pleural thickening. These observations suggest that spaces resembling fat may be encountered in fibrotic pleurae and that horizontally oriented keratin-positive spindled cells between the fat-like spaces deep in the fibrotic portion of a thickened pleura represent a benign finding seen in some cases of organizing pleuritis/fibrothorax. The spaces themselves are probably artifacts derived from the biopsy procedure and/or cutting artifacts. In contrast, in true desmoplastic mesotheliomas there is downward, rather than horizontal, growth of keratin-positive spindled cells running between clearly definable fat cells.	f	\N
21963153	Multimorbidity is increasing in frequency. It can be quantitatively measured and is a major correlate of high use of health services resources of all types, especially over time. The ACG System for characterizing multimorbidity is the only widely used method that is based on combinations of different TYPES of diagnoses over time, rather than the presence or absence of particular conditions or numbers of conditions. It incorporates administrative data (as from claims forms or medical records) on all types of encounters and is not limited to diagnoses captured during hospitalizations or other places of encounter. It can be employed in any one or combination of analytic models, and can incorporate medication use if desired. It is being used in clinical care, management of health services resources, in health services research to control for degree of morbidity, and in understanding morbidity patterns over time. In addition to its research uses, it is being employed in many countries in various applications as a policy to better understand health needs of populations and tailor health services resources to health needs.	f	\N
21970661	Toxoplasma gondii is a major cause of chronic parasitic infection in the world. This protozoan can cause retino-choroiditis in newborns and in adults, both immunocompetent and immunodeficient. This disease tends to be recurrent and can lead to severe visual impairment. The authors review current knowledge on the role of parasite genetics in influencing susceptibility to ocular toxoplasmosis and on the immuno-pathogenesis of this disease.	f	\N
21971930	The development of drug resistance represents a major complication in the effective treatment of breast cancer. Epigenetic therapy, through the use of histone deacetylase inhibitors (HDACi) or demethylation agents, is an emerging area of therapeutic targeting in a number of ontological entities, particularly in the setting of aggressive therapy-resistant disease. Using the well-described HDAC inhibitor trichostatin A (TSA) we demonstrate the suppression of in vitro clonogenicity in the previously described apoptosis-resistant MCF-7TN-R breast carcinoma cell line. Additionally, recent work has demonstrated that these agents can alter the expression profile of microRNA signatures in malignant cells. Using an unbiased microRNA microarray analysis, changes in miRNA expression of MCF-7TN-R cells treated with TSA for 24 h were analyzed. We observed significant up-regulation of 22 miRNAs and down-regulation of 10 miRNAs in response to TSA treatment. Our results demonstrate that the HDACi, TSA, exerts anticancer activity in the apoptosis-resistant MCF-7TN-R breast carcinoma cell line. This activity is correlated with TSA alteration of microRNA expression profiles indicative of a less aggressive phenotype.	f	\N
21973247	Mortality level and cause of death trends are evaluated to chart the epidemiological transition in Fiji. IMPLICATIONS for current health policy are discussed. Published data for infant mortality rate (IMR), life expectancy (LE) and causes of death for 1940-2008 were assessed for quality, and compared with mortality indices generated from recent Ministry of Health death recording. Trends in credible mortality estimates are compared with trends in proportional mortality for cause of death. IMR declined from 60 deaths (per 1,000) in 1945 to below 20 by 2000. IMR for 2006-08 is estimated at 18-20 deaths per 1,000 live births. Excessive LE estimates arise by imputing from the IMR using inappropriate models. LE increased, but has been stable at 64 years for males and 69 years for females since the late 1980s and early 1990s respectively. Proportional mortality from diseases of the circulatory system has increased from around 20% in the 1960s to more than 45%. Extensive variation in published mortality estimates was indentified, including clearly incompatible ranges of IMR and LE. Mortality decline has stagnated. Relatively low IMR and proportional mortality trends suggest this is largely due to chronic diseases (especially cardiovascular) in adults. Reconciliation of mortality data in Fiji to reduce uncertainty is urgently needed. Fiji's health services and donor partners should place continued and increased emphasis on effective control strategies for cardiovascular disease.	f	\N
21978795	Objective of this study was to evaluate the acute cardiovascular and respiratory effects of switching on the deep brain stimulation in the follow up of nine Parkinson's disease patients with subthalamic nucleus stimulation and six cluster headache patients with posterior hypothalamic area stimulation. Systolic and diastolic blood pressure, heart rate, and respiratory rate were monitored continuously during supine rest in both groups. Each patient was assessed in two conditions: resting supine with stimulator off and with stimulator on. In supine resting condition switching on the DBS induced no significant changes (p>0.05) in systolic and diastolic blood pressure as well as in heart rate and respiratory rate, in both groups of patients, either taking 1 min or 10 heartbeats as a sample for analysis. Switching on the DBS does not modify heart rate, blood pressure nor respiratory rate in both Parkinson and cluster headache patients under resting conditions.	f	\N
21985741	Rarely, a patient presents to a surgeon for evaluation of an adrenal incidentaloma where the final pathology is primary malignancy. For primary adrenal lymphoma, fewer than 100 cases have been reported in the literature. We report a case of unilateral primary adrenal aggressive B cell lymphoma discovered incidentally in a 41-year-old female. Preoperative testing demonstrated the 6-cm mass to be biochemically silent. Subsequently, the patient underwent a laparoscopic adrenalectomy. Following pathologic diagnosis of B cell lymphoma, a metastatic workup was negative, and she underwent treatment with systemic chemotherapy. She is currently disease free 6 months postoperatively. Primary adrenal lymphoma should be considered in patients with unilateral adrenal incidentaloma. We believe that adherence to guidelines of resection of incidentalomas allowed for early surgical intervention and possible cure.	f	\N
21986202	Parkinson's disease is a common neurodegenerative disorder characterized by α-synuclein (α-Syn)-containing Lewy body formation and selective loss of dopaminergic neurons in the substantia nigra. We have demonstrated the modulating effect of noopept, a novel proline-containing dipeptide drug with nootropic and neuroprotective properties, on α-Syn oligomerization and fibrillation by using thioflavin T fluorescence, far-UV CD, and atomic force microscopy techniques. Noopept does not bind to a sterically specific site in the α-Syn molecule as revealed by heteronuclear two-dimensional NMR analysis, but due to hydrophobic interactions with toxic amyloid oligomers, it prompts their rapid sequestration into larger fibrillar amyloid aggregates. Consequently, this process rescues the cytotoxic effect of amyloid oligomers on neuroblastoma SH-SY5Y cells as demonstrated by using cell viability assays and fluorescent staining of apoptotic and necrotic cells and by assessing the level of intracellular oxidative stress. The mitigating effect of noopept against amyloid oligomeric cytotoxicity may offer additional benefits to the already well-established therapeutic functions of this new pharmaceutical.	f	\N
21987744	The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections.	f	\N
21994137	Proctitis is a common problem and is most frequently associated with inflammatory bowel diseases. However, the incidence of infectious proctitis appears to be rising, especially in men who have sex with men. This may be due to the rise of people participating in receptive anal sex as well as the increase in sexually transmitted infections. The most frequently reported pathogens include Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, and herpes simplex. Symptoms of infectious proctitis can include rectal blood and mucous discharge, anorectal pain, ulcers, and occasionally lymphadenopathy and fever. History and physical examination are crucial in establishing a diagnosis, supported by endoscopy, histology, serology, culture and PCR. Treatment with antibiotics or antivirals is usually initiated, either empirically or after establishing a diagnosis. Co-infections, HIV testing, and treatment of sexual partners should always be considered.	f	\N
22002662	The destruction of blood-brain barrier (BBB) and blood-nerve barrier (BNB) has been considered to be a key step in the disease process of a number of neurological disorders including cerebral ischemia, Alzheimer's disease, multiple sclerosis, and diabetic neuropathy. Although glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) facilitate neuronal or axonal regeneration in the brain or peripheral nerves, their action in the BBB and BNB remains unclear. The purpose of the present study was to elucidate whether these neurotrophic factors secreted from the brain or peripheral nerve pericytes increase the barrier function of the BBB or BNB, using our newly established human brain microvascular endothelial cell (BMEC) line or peripheral nerve microvascular endothelial cell (PnMEC) line. GDNF increased the expression of claudin-5 and the transendothelial electrical resistance (TEER) of BMECs and PnMECs, whereas BDNF did not have this effect. Furthermore, we herein demonstrate that the GDNF secreted from the brain and peripheral nerve pericytes was one of the key molecules responsible for the up-regulation of claudin-5 expression and the TEER value in the BBB and BNB. These results indicate that the regulation of GDNF secreted from pericytes may therefore be a novel therapeutic strategy to modify the BBB or BNB functions and promote brain or peripheral nerve regeneration.	f	\N
22010196	The eukaryotic cell is organized into membrane-covered compartments that are characterized by specific sets of proteins and biochemically distinct cellular processes. The appropriate subcellular localization of proteins is crucial because it provides the physiological context for their function. In this Commentary, we give a brief overview of the different mechanisms that are involved in protein trafficking and describe how aberrant localization of proteins contributes to the pathogenesis of many human diseases, such as metabolic, cardiovascular and neurodegenerative diseases, as well as cancer. Accordingly, modifying the disease-related subcellular mislocalization of proteins might be an attractive means of therapeutic intervention. In particular, cellular processes that link protein folding and cell signaling, as well as nuclear import and export, to the subcellular localization of proteins have been proposed as targets for therapeutic intervention. We discuss the concepts involved in the therapeutic restoration of disrupted physiological protein localization and therapeutic mislocalization as a strategy to inactivate disease-causing proteins.	f	\N
22011558	Although moderate alcohol drinkers have lower rates of incident coronary artery disease than abstainers, much less is known about the health effects of different patterns of alcohol use in women with established coronary artery disease. In the Determinants of Myocardial Infarction Onset Study, 1,253 women hospitalized for acute myocardial infarction (MI) at 64 centers nationwide from 1989 to 1996 were followed for mortality through December 31, 2007. Of the women, 761 (61%) reported abstention in the year before their MIs, 280 (22%) reported consumption of <1 serving/week, 75 (6%) reported consumption of 1 to 3 servings/week, and 137 (11%) reported consumption of ≥3 servings/week. Using Cox proportional-hazards models, the associations between total weekly volume of consumption, drinking days per week, drinks per drinking day, and beverage type with 10-year mortality were investigated, adjusting for clinical and socioeconomic potential confounders. Compared with abstention, adjusted hazard ratios were 0.66 (95% confidence interval 0.50 to 0.86) for <1 serving/week, 0.65 (95% confidence interval 0.38 to 1.11) for 1 to 3 servings/week, and 0.65 (95% confidence interval 0.38 to 1.11) for ≥3 servings/week (p for trend = 0.008). No differences were found by beverage type, and generally inverse associations of drinking frequency and quantity with mortality were found. In conclusion, in women who survive MI, moderate drinking is associated with a decreased risk for mortality, with no clear differences on the basis of pattern or beverage type. These results suggest that women who survive MI need not abstain from alcohol, but any derived benefit would appear to occur well below currently recommended limits in alcohol consumption.	f	\N
22015458	Cholangitis arising from biliary infection dominates the prognosis in Caroli's disease. To clarify the influences of bacterial infection on the biliary cystogenesis, in vivo and in vitro studies were performed using the polycystic kidney (PCK) rat as an animal model of Caroli's disease. Cholangitis became a frequent histological finding in aged PCK rats, and neovascularization around the bile ducts also increased in aged PCK rats. Immunohistochemistry revealed that expression of vascular endothelial growth factor (VEGF) was increased in PCK rat biliary epithelium. In vitro, PCK cholangiocytes overexpressed VEGF, and the supernatant of cultured PCK cholangiocytes significantly increased the proliferative activity, migration, and tube formation of cultured rat vascular endothelial cells. Stimulation with lipopolysaccharide (LPS) further induced VEGF expression in PCK cholangiocytes, which might be mediated by signaling pathways involving phosphatidylinositol 3-kinase (PI3K)-Akt and c-Jun N-terminal kinase (JNK). Both LPS and VEGF increased cell proliferative activity in PCK cholangiocytes, and siRNA against VEGF significantly reduced LPS-induced cell proliferation. Thus, LPS-induced overexpression of VEGF in the biliary epithelium may lead to hypervascularity around the bile ducts; concurrently, LPS and VEGF act as cell proliferation factors for cholangiocytes. Biliary infection may thus exacerbate biliary cystogenesis in PCK rats.	f	\N
22016594	We investigated the clinical characteristics and prognosis of elderly patients with acute lymphoblastic leukemia (ALL). We reviewed the clinical data, laboratory findings, bone marrow findings, and cytogenetic analysis of elderly patients (≥ 60 years) with ALL, and data of an additional 101 younger adult patients (< 60 years) with ALL were reviewed for comparison. Twenty-six elderly patients (≥ 60 years) and 101 younger adult patients (< 60 years) with ALL were retrospectively enrolled. The median follow-up duration was 6.0 months (range, 0.4 to 113.2) in the elderly patients and 21.7 months (range, 1.0 to 122.7) in the adult patients. In total, 34.6% (9 patients) of the elderly patients and 24.8% (25 patients) of the adult patients had Philadelphia chromosome positive ALL. The overall complete remission (CR) rate was much higher in the younger than in the elderly patients (94.1% vs. 57.7%, p < 0.001). The median overall survival (OS) of the younger patients (< 60 years) was 26.3 months, whereas that of the elderly patients (≥ 60 years) was 10.3 months (p = 0.003). In the elderly patients with ALL, T cell lineage and the presence of lymphadenopathy were significant prognostic factors for OS in a univariate analysis (p = 0.033 and 0.041, respectively). The outcomes of Korean elderly patients with ALL were poor, and the shorter OS was mainly due to the low CR rate. T-cell lineage and the presence of lymphadenopathy were significant prognostic factors in Korean elderly patients with ALL.	f	\N
22017219	Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene. Key symptoms of mania were rated in two sets of medicated bipolar disorder patients (n=171 and n=475) at two specialized outpatient clinics for affective disorders and three regular psychiatric outpatient units in Sweden. The relationships between all manic symptoms according to DSM-IV were entered in a principal component analysis. We used a case-case model to reduce the genetic heterogeneity and tested associations between four factors related to manic symptoms and their association to four single nucleotide polymorphisms in the P2RX7 gene. The combination of the cognitive symptoms, distractibility, talkativeness, and thought disorder was significantly associated with rs1718119 in the P2RX7 gene in Set 1 [odds ratio (OR) = 1.78; p=0.011]. The association was re-tested in the second set (OR = 1.42; p=0.009). In the total sample, the association was even stronger (OR = 1.49; p<0.001). None of the other factors was associated with the P2RX7 gene. Within the first factor, the distractibility symptom accounted for a significant portion of the association to rs1718119 (p=0.016). There is an association between specific symptoms of bipolar disorder and the P2RX7 gene. This finding may open up new approaches to elucidating the neurobiology behind bipolar symptoms.	f	\N
22018216	Although endoscopy and angiography have changed the management of lower gastrointestinal bleeding and the majority of patients respond to conservative treatment 10-20% of cases have no recognizable site of hemorrhage. About 10-30% of all patients will require operative intervation. A very rare case of massive lower gastrointestinal bleeding in a young patient who was found to suffer from two causes of gastrointestinal hemorrhage in the same time is reported. The patient had to undergo surgery for the control of bleeding. A 23 years old male Greek patient presented to the emergency department of our hospital because of three episodes of hematochezia during the last 10 hours. He was admitted to the surgical department for monitoring of his condition. In the next 10 hours the hematochezia continued and the patient although being transfused with three units of packed red blood cells, started to become unstable with his vital signs affected, having also a syncoptic episode. Emergent colonoscopy could not recognize the site of hemorrhage or any other pathology in the colon, but revealed an intestinal lumen full of blood from the anus to the cecum. It was decided that the patient should undergo operation to stop bleeding. An extensive right hemicolectomy was performed. After that the patient remained stable and showed no signs of hemorrage. The histopathological examination of the specimen showed an arteriovenous malformation but also lesions of the mucosa compatible with early inflammatory bowel disease. In young patients with massive lower gastrointestinal bleeding of unknown origin, extensive right hemicolectomy provides a good and safe therapeutic choice that will control hemorrhage in most cases with the advantage of lower mortality and morbidity rates compared to subtotal colectomy. Close monitoring of the patient postoperatively is essential.	f	\N
22023956	Atherosclerotic carotid artery disease remains an important cause of cerebrovascular ischemic disease. We present a patient with residual stenosis of the distal internal carotid artery following carotid endarterectomy that was treated with stenting. The case highlights the potential complimentary benefits of carotid endarterectomy and carotid stenting.	f	\N
22026553	Evidence suggests that occult adenoma remnants are responsible for persistent Cushing's disease (CD) following transsphenoidal surgery (TSS). To optimize the outcome, we have adapted our microsurgical concept. The influence of our surgical strategy on remission rate and pituitary function is presented. 83 patients undergoing TSS for newly diagnosed CD. An enlarged resection was performed in 36 patients. A modified exploration technique with radial incisions was performed in 19 patients in whom an adenoma was not readily detectable. The overall remission rate of primary surgery was 84·3% (70/83). A remission rate of 87·5% (63/72) was achieved in microadenomas. Six patients with microadenomas were re-operated for persistence, and hypercortisolism was corrected in five of them. With re-operation included, the overall remission rate for microadenomas was 94·4%. No procedure-related complications occurred in primary surgery. Of the patients in remission, 72·5% had early postoperative random cortisol levels below 2 μg/dl, 17·4% had cortisol levels between 2 and 5 μg/dl, and 10·1% had cortisol levels >5 μg/dl. 15·2% of the patients with microadenomas developed postoperative partial hypopituitarism and 3% diabetes insipidus. No increased rate of hypopituitarism was found with enlarged adenomectomy compared to selective adenomectomy. Only a slightly higher rate of partial hypopituitarism (23·1%) was found if extensive exploration was required. With our microsurgical concept, a high initial cure rate is achievable with minimal surgical morbidity. Enlarged adenomectomy has no adverse effect on the rate of postoperative hypopituitarism. Early repeat surgery is a successful option if CD persists.	f	\N
22034985	Earlier, we identified proteins connecting different disease proteins in the human protein-protein interaction network and quantified their mediator role. An analysis of the networks of these mediators shows that proteins connecting heart disease and diabetes largely overlap with the ones connecting heart disease and obesity. We quantified their overlap, and based on the identified topological patterns, we inferred the structural disease-relatedness of several proteins. Literature data provide a functional look of them, well supporting our findings. For example, the inferred structurally important role of the PDZ domain-containing protein GIPC1 in diabetes is supported despite the lack of this information in the Online Mendelian Inheritance in Man database. Several key mediator proteins identified here clearly has pleiotropic effects, supported by ample evidence for their general but always of only secondary importance. We suggest that studying central nodes in mediator networks may contribute to better understanding and quantifying pleiotropy. Network analysis provides potentially useful tools here, as well as helps in improving databases.	f	\N
22040839	Coronary artery disease (CAD) is the major cause of morbidity and mortality in type 2 diabetic patients. Severe vitamin D deficiency has been shown to predict cardiovascular mortality in type 2 diabetic patients. We investigated the association among severe vitamin D deficiency, coronary calcium score (CCS), and asymptomatic CAD in type 2 diabetic patients with elevated urinary albumin excretion rate (UAER) >30 mg/24 h. This was a cross-sectional study including 200 type 2 diabetic patients without a history of CAD. Severe vitamin D deficiency was defined as plasma 25-hydroxyvitamin D (p-25[OH]D3) <12.5 nmol/L. Patients with plasma N-terminal pro-brain natriuretic peptide >45.2 ng/L or CCS ≥400 were stratified as being high risk for CAD (n= 133). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109), computed tomography angiography (n = 20), or coronary angiography (CAG; n = 86). Patients' p-25(OH)D3 levels were determined by high-performance liquid chromatography/tandem mass spectrometry. The median (range) vitamin D level was 36.9 (3.8-118.6) nmol/L. The prevalence of severe vitamin D deficiency was 9.5% (19/200). MPI or CAG demonstrated significant CAD in 70 patients (35%). The prevalence of CCS ≥400 was 34% (68/200). Severe vitamin D deficiency was associated with CCS ≥400 (odds ratio [OR] 4.3, 95% CI [1.5-12.1], P = 0.005). This association persisted after adjusting for risk factors (4.6, 1.5-13.9, P = 0.007). Furthermore, severe vitamin D deficiency was associated with asymptomatic CAD (adjusted OR 2.9, 1.02-7.66, P = 0.047). In high-risk type 2 diabetic patients with elevated UAER, low levels of vitamin D are associated with asymptomatic CAD.	f	\N
22047508	Hypertension is a common major risk factor for stroke and coronary heart disease. Little is known about how achievement of financially incentivised and non-incentivised indicators of quality of care varies with deprivation, or about the effect of financial incentives on health inequalities in hypertension. General practices in the UK have received financial incentives for high quality care since 2004. This study set out to assess the variations in achievement of incentivised and non-incentivised quality indicators for hypertension by patient area deprivation, before and after the introduction of financial incentives. Achievement of 14 quality indicators for hypertension in 304 patient participants in 18 general practices in Norfolk, England was assessed one year before (2003) and one year after (2005) the introduction of financial incentives. Four indicators were incentivised and 10 were non-incentivised. Each participant's postcode was linked to an index of multiple deprivation score. The range of achievement of incentivised quality indicators was 65-94% in the least deprived third of participants, and 77-94% in the most deprived third in 2003 and 2005 combined. For non-incentivised indicators, the range was 7-85% in the least deprived and 24-93% in the most deprived third.Achievement of incentivised quality indicators in 2003 and 2005 combined did not vary significantly by area deprivation. Achievement of three of 10 non-incentivised indicators was higher in participants from more deprived postcode areas: providing lifestyle advice (odds ratio 1.34, 95% confidence interval 1.00-1.79), assessment of peripheral vascular disease (1.54, 1.02-2.35) and electrocardiography (1.38, 1.04-1.82). Participants from more deprived areas received at least the same, and sometimes better, quality of care than those from less deprived areas. Quality of care for hypertension in general practice may not follow the inequitable distribution seen with some other conditions.	f	\N
22050270	Vitiligo is a common acquired depigmentation disorder caused by the loss of melanocytes. Despite the numerous treatment modalities available for vitiligo, responses to treatment are still unsatisfactory. For this reason, new treatment modalities and approaches are needed. To investigate the effects of fractional carbon dioxide (CO(2) ) laser therapy followed by systemic narrowband ultraviolet B (NB-UVB) phototherapy on nonsegmental vitiligo (NSV) as a prospective and randomized left-right comparative study. Ten patients with NSV who presented symmetrical vitiligo lesions with no further improvement despite more than 1 year of conventional treatment were enrolled. Two sessions of half-body fractional CO(2) laser therapy were performed at a 2-month interval. NB-UVB phototherapy was then administered to the entire body 5 days after each fractional laser treatment twice a week, increasing the dose incrementally by 15% at each session. Objective clinical assessments were made by two blinded dermatologists using a quartile grading scale, and the patients' overall satisfaction was evaluated using a 10-point visual analogue scale. Two months after the last treatment, mean improvement scores, assessed by physicians, were significantly higher for those treated with half-body fractional CO(2) laser therapy followed by NB-UVB phototherapy, compared with those treated with NB-UVB alone (P=0·034). In addition, according to subjective assessment, the half-body laser treatment followed by NB-UVB showed significantly higher improvements compared with NB-UVB treatment alone (P=0·023). Noticeable adverse events, such as infection, scarring and Koebner phenomenon, were not found in any patient. This study suggests that fractional CO(2) laser therapy followed by NB-UVB phototherapy could be used effectively and safely as an alternative modality for the treatment of refractory vitiligo.	f	\N
22054870	Age-related cognitive decline is likely promoted by accumulated brain injury due to chronic conditions of aging, including neurodegenerative and vascular disease. Because common neuronal mechanisms may mediate the adaptation to diverse cerebral insults, we hypothesized that susceptibility for age-related cognitive decline may be due in part to a shared genetic network. We have therefore performed a genome-wide association study using a quantitative measure of global cognitive decline slope, based on repeated measures of 17 cognitive tests in 749 subjects from the Religious Orders Study. Top results were evaluated in 3 independent replication cohorts, consisting of 2279 additional subjects with repeated cognitive testing. As expected, we find that the Alzheimer's disease (AD) susceptibility locus, APOE, is strongly associated with rate of cognitive decline (P(DISC) = 5.6 × 10(-9); P(JOINT)= 3.7 × 10(-27)). We additionally discover a variant, rs10808746, which shows consistent effects in the replication cohorts and modestly improved evidence of association in the joint analysis (P(DISC) = 6.7 × 10(-5); P(REP) = 9.4 × 10(-3); P(JOINT) = 2.3 × 10(-5)). This variant influences the expression of 2 adjacent genes, PDE7A and MTFR1, which are potential regulators of inflammation and oxidative injury, respectively. Using aggregate measures of genetic risk, we find that known susceptibility loci for cardiovascular disease, type 2 diabetes, and inflammatory diseases are not significantly associated with cognitive decline in our cohort. Our results suggest that intermediate phenotypes, when coupled with larger sample sizes, may be a useful tool to dissect susceptibility loci for age-related cognitive decline and uncover shared molecular pathways with a role in neuronal injury.	f	\N
22054881	Lung cancer is a heterogeneous disease clinically, biologically, histologically, and molecularly. Understanding the molecular causes of this heterogeneity, which might reflect changes occurring in different classes of epithelial cells or different molecular changes occurring in the same target lung epithelial cells, is the focus of current research. Identifying the genes and pathways involved, determining how they relate to the biological behavior of lung cancer, and their utility as diagnostic and therapeutic targets are important basic and translational research issues. This article reviews current information on the key molecular steps in lung cancer pathogenesis, their timing, and clinical implications.	f	\N
22067963	Lewy pathology in Parkinson disease (PD) extends well beyond the CNS, also affecting peripheral autonomic neuronal circuits, especially the enteric nervous system (ENS). The ENS is an integrative neuronal network also referred to as "the brain in the gut" because of its similarities to the CNS. We have recently shown that the ENS can be readily analyzed using routine colonic biopsies. This led us to propose that the ENS could represent a unique window to assess the neuropathology in living patients with PD. In this perspective, we discuss current evidence which indicates that the presence of ENS pathology may by exploited to improve our understanding and management of PD and likely other neurodegenerative disorders.	f	\N
22068070	Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare adrenergically mediated arrhythmogenic disorder classically induced by exercise or emotional stress and found in structurally normal hearts. It is an important cause of cardiac syncope and sudden death in childhood. Catecholaminergic polymorphic ventricular tachycardia is a genetic cardiac channelopathy with known mutations involving genes affecting intracellular calcium regulation. We present a case of a 14-year-old boy who had cardiopulmonary arrest after an emotionally induced episode of CPVT while attempting to invite a girl to the school dance. Review of his presenting cardiac rhythm, induction of concerning ventricular arrhythmias during an exercise stress test, and genetic testing confirmed the diagnosis of CPVT. He recovered fully and was treated with β-blocker therapy and placement of an implantable cardioverter-defibrillator. In this report, we discuss this rare but important entity, including its molecular foundation, clinical presentation, basics of diagnosis, therapeutic options, and implications of genetic testing for family members. We also compare CPVT to other notable cardiomyopathic and channelopathic causes of sudden death in youth including hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, long QT syndrome, short QT syndrome, and Brugada syndrome.	f	\N
22072024	Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include 'off-label' use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors' own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.	f	\N
22072546	Recent genome wide association studies have identified susceptibility loci for adult testicular germ cell tumors (GCT) near KITLG, SPRY4, BAK1, and DMRT1. We evaluated variants in these four genes to determine whether these are also susceptibility loci for pediatric GCTs. DNA was isolated from 52 pediatric GCTs (ages 0-21 years) obtained from the Cooperative Human Tissue Network. Control DNA was isolated from de-identified dried blood spots from 141 white newborns. Genotyping was conducted using TaqMan assays (rs4474514) or by PCR and sequencing (rs4324715, rs210138, and rs755383). Associations between variants and GCT were evaluated using logistic regression with adjustment for sex. We also evaluated whether the associations differed by age at GCT diagnosis (0-9 years, 10-21 years), sex, and tumor location (gonadal, non-gonadal). We observed a significant association for rs210138 (BAK1) and pediatric GCT overall (odds ratio (OR) = 1.80, 95% confidence interval (CI) 1.10-2.95, P = 0.02) with non-significant associations similar in magnitude in both the pediatric (P = 0.09) and adolescent (P = 0.06) age groups. The KITLG (rs4474514) and SPRY4 (rs4324715) variants were significantly associated with GCT only in the adolescent age group (rs4474514: OR = 2.28, 95% CI 1.09-4.79, P = 0.03 and rs4324715: OR = 2.40, 95% CI 1.19-4.83, P = 0.01). Associations were mostly similar when stratified by sex. This is the first study to suggest that these loci may also be important in susceptibility to GCTs in the adolescent (KITLG, SPRY4, and BAK1) and pediatric (BAK1) age groups.	f	\N
22078109	The aim of the present study was to examine abnormalities in the ankle-brachial index (ABI) and related risk factors in patients with type 2 diabetes. Between September 2003 and June 2010, the ABI was determined in 3924 outpatients attending the Diabetes Center of the People's Liberation Army 306th Hospital. In addition, demographic and laboratory data were collected. The risk factors for an abnormal ABI were determined using univariate and stepwise logistic regression analysis. The ABI was normal (0.91-1.3) in 93.1% of patients, low (<0.9) in 5.2%, and high (>1.3) in 1.7%. The prevalence of abnormal lower ABI was greater in elderly (≥ 65 years) patients (12.2%) than in younger (< 65 years) patients (3.6%). Using normal ABI as the reference, low ABI in younger patients was found to be independently associated with HbA1c, the urinary albumin:creatinine ratio, diabetic peripheral neuropathy, diabetic retinopathy, and cerebrovascular disease. A low ABI in elderly patients was found to be independently associated with age, smoking, HbA1c, uric acid, total cholesterol, diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy and cerebrovascular disease. A high ABI in younger patients was associated with being male. The prevalence of an abnormal ABI was high in patients with type 2 diabetes, especially elderly patients. Early identification and intensive treatment are needed to improve the quality of life and overall prognosis of patients with type 2 diabetes.	f	\N
22079056	Cancer represents a complex group of heterogeneous diseases. While many cancers share fundamental biological processes (hallmarks of cancer) necessary for their development and progression, cancers also distinguish themselves by their dependence on distinct oncogenic pathways. Over the last decade, targeted therapies have been introduced to the clinic with variable success. In truth, single targeted therapies may be successful in only a subset of malignancies but insufficient to address malignancies that often rely on multiple pathways, thus evading single targeted agents. Investigators have recently identified potentially functional components of the human genome that were previously thought to have no biological function. This discovery has added to the already established complexity of gene regulation in the pathogenesis of cancer. Non-coding RNAs represent key regulators of gene expression. Improved knowledge of their biogenesis and function may in turn lead to a better understanding of the heterogeneity of malignancies and eventually be leveraged as diagnostic, prognostic and therapeutic targets. MicroRNAs (miRNAs or miRs) for example, have the capacity for the regulation of multiple genes and thus redirection or reprogramming of biological pathways. However, several other members of the non-coding RNA family may be of equal biological relevance. In this review, we provide a perspective on emerging concepts in the clinical application of miRNA and other non-coding RNAs as biomarkers in cancer with an eye on the eventual integration of both miRNA and other non-coding RNA biology into our understanding of cancer pathogenesis and treatment.	f	\N
22082049	A growing number of prognostic indices for chronic obstructive pulmonary disease (COPD) is developed for clinical use. Our aim is to identify, summarize and compare all published prognostic COPD indices, and to discuss their performance, usefulness and implementation in daily practice. We performed a systematic literature search in both Pubmed and Embase up to September 2010. Selection criteria included primary publications of indices developed for stable COPD patients, that predict future outcome by a multidimensional scoring system, developed for and validated with COPD patients only. Two reviewers independently assessed the index quality using a structured screening form for systematically scoring prognostic studies. Of 7,028 articles screened, 13 studies comprising 15 indices were included. Only 1 index had been explored for its application in daily practice. We observed 21 different predictors and 7 prognostic outcomes, the latter reflecting mortality, hospitalization and exacerbation. Consistent strong predictors were FEV1 percentage predicted, age and dyspnoea. The quality of the studies underlying the indices varied between fairly poor and good. Statistical methods to assess the predictive abilities of the indices were heterogenic. They generally revealed moderate to good discrimination, when measured. We focused on prognostic indices for stable disease only and, inevitably, quality judgment was prone to subjectivity. We identified 15 prognostic COPD indices. Although the prognostic performance of some of the indices has been validated, they all lack sufficient evidence for implementation. Whether or not the use of prognostic indices improves COPD disease management or patients' health is currently unknown; impact studies are required to establish this.	f	\N
22082649	INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients.	f	\N
22092655	Immunomodulatory T cells are thought to influence development of allergy and asthma, but early life longitudinal data on their phenotype and function are lacking. As part of the Urban Environment and Childhood Asthma (URECA) study, we investigated the development of immunomodulatory T cell phenotype and function, and characterized their relation to allergic disease progression from birth through to 2 years of age. Immunomodulatory T cell phenotype and function in cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) at 1 and 2 years of age were characterized by analysing CD25(bright) and FoxP3(+) expression, proliferative responses and cytokine production. The relation of immunomodulatory T cell characteristics to allergic sensitization and disease at 1- and 2-years of age was investigated. The proportion of CD4(+)CD25(bright) and CD4(+)CD25(+)FoxP3(+)T cells (n = 114, 83, 82 at birth, 1- and 2-years respectively) increased significantly, whereas there were no significant changes in the suppressive function of CD25(+)T cells (n = 78, 71, 81 at birth, 1- and 2-years respectively). Birth immunomodulatory T cell characteristics were not related to subsequent allergic sensitization or disease. However, increases in the numbers of CD4(+)CD25(bright) cells and their ability to suppress lymphoproliferative responses at 1 year of age were associated with reduced allergic sensitization at 1 (P = 0.03) and 2 (P = 0.02) years of age. Production of the anti-inflammatory cytokine IL-10 by CD25(+)T cells appeared to mediate this protective suppressive function. In contrast, by 2 years of age, we observed the emergence of a positive association of CD4(+)CD25(+) FoxP3(+) T cell numbers with allergic sensitization (P = 0.05) and eczema (P = 0.02). These findings suggest that the relationship between immunomodulatory T cell subsets, allergic sensitization and eczema is developmentally regulated. In the first year of life, CD4(+)CD25(+) IL-10 producing T cells are associated with a reduced incidence of allergic sensitization. Once allergic sensitization or eczema is established, CD4(+)CD25(+)FoxP3(+)T-reg cells expand to potentially counteract the allergic inflammatory response. Understanding the relationship between development of immunoregulatory T cells and early onset atopy could lead to new preventive strategies for allergic diseases.	f	\N
22104022	Bronchiolitis is the most common respiratory disease in children under 2 years-old and a major cause of hospitalization in young children, especially during the winter. To determine the prevalence and etiology of bronchiolitis in south-east of Spain. A prospective study was conducted during the bronchiolitis season (December-April). Children below 18 months-old admitted to the hospital for a first bronchiolitis episode were included. Nasopharyngeal aspirates were analysed by reverse transcription polymerase chain reaction (RT-PCR) respiratory syncytial virus. A total of 235 children were included during this period, and 235 RT-PCR were performed. A total of 287 viruses were detected in nasopharyngeal aspirates from 204 infants. Respiratory syncytial virus was the virus detected more frequently, followed by rhinovirus. Co-infections were found in the 36% of children. Respiratory viruses were detected in most of the children below 18 months-old hospitalised with bronchiolitis, and 36% of them showed a mixed infection.	f	\N
22106694	HLA-DQA1, -DQB1, and -DRB1 gene polymorphism were analyzed to study type 1 DM susceptibility in Malay patients from Southeast Asia (Malaysia and Singapore). Patients showed significant increases in the occurrence of DQA1*0501 (50.7% vs. 20.4%; RR = 3.97; Pc < 0.01), DQB1*0201 (48% vs. 19.1%; RR = 3.86; Pc < 0.05), and DRB1*0301 (38.7 vs. 6.8%; RR = 8.36; 95% Pc < 0.05). Conversely, significant decreases were noted in the occurrence of DQA1*0601 (14.7% vs. 35.2%; RR = 0.33; Pc = 0.008) and DQB1*0601 (4% vs. 23.5%; RR = 0.16; Pc < 0.05) in type 1 DM patients. Using a logistic regression model, we derived a risk prediction model for type 1 DM in our indigenous Malay population based on the identified HLA genotypes. The RR for type 1 DM increases by a factor of 5.68 for every unit increase in the number of DRB1*0301 allele (P < 0.001), and decreases by a factor of 0.18 per unit increase in the number of DQB1*0601 allele (P < 0.001). After adjusting for these two HLA genotypes, DQA1*0501, DQB1*0201 and DQA1*0601 were not statistically significant as risk predictors. The lower incidence of type 1 DM in the Malay population may be contributed by the genotypic combinations of DR and DQ genes as well as the linkage disequilibria between susceptible and protective alleles.	f	\N
22110167	A primary function of B lymphocytes is immunoglobulin production; however, the therapeutic benefit of B cell depletion in autoimmune diseases previously thought to be T cell mediated suggests that some B cells fulfill other roles in autoimmunity. We examined the recently identified human B1 cell population for T cell stimulatory activity. We found two kinds of B1 cells that are distinguished by multiple surface markers and distinct transcriptomic profiles. In both umbilical cord and adult peripheral blood, a CD11b(+) subset constitutes ~1 out of every 8-10 B1 cells, whereas a CD11b(-) subset constitutes the remaining B1 cells. These B1 cell populations differ functionally. CD11b(-) B1 cells spontaneously secrete much more IgM than CD11b(+) B1 cells. In contrast, CD11b(+) B1 cells express more CD86, and more efficiently stimulate allogeneic CD4(+) T cell expansion, than CD11b(-) B1 cells. The frequency of these CD11b(+) B1 cells is markedly elevated in lupus patients. CD11b(+) B1 cells in lupus patients express more CD86 and have increased T cell-stimulating activity in disease. This work distinguishes a novel, T cell-interacting B1 cell population whose abundance and activity may be a reflection of, and a therapeutic target in, autoimmune disease.	f	\N
22112193	Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is one of the most common causes of chronic liver disease, worldwide. Lipoprotein-associated phospholipase A2 (Lp-PLA2) was recently characterized as a novel inflammatory biomarker that is correlated with several components constituting the metabolic syndrome. In this study, we determined the serum levels of Lp-PLA2 in patients with definite nonalcoholic steatohepatitis (NASH, n=25), borderline NASH (n=22), simple fatty liver (n=10), and healthy controls without evidence of liver disease (n=38). The levels of Lp-PLA2 were measured by enzyme-linked immunosorbent assay and compared in the four study groups. Moreover, concentrations of Lp-PLA2 were assessed in relation to the general characteristics of the study participants and the results of liver biopsy. Concentrations of Lp-PLA2 were significantly higher in patients with definite NASH (161.8±0.9 μg/L, P<0.001), borderline NASH (135.4±47.7 μg/L, P=0.001), and simple fatty liver (132.4±46.2 μg/L, P=0.042) compared with healthy controls (86.2±40.7 μg/L). Furthermore, the serum Lp-PLA2 level was strongly associated to histological steatosis scores in patients with NAFLD (β=0.32, t=2.50, P=0.016). Although subject to future confirmation, our data suggest that Lp-PLA2 levels are elevated in NAFLD.	f	\N
22122455	PPAR agonists represent a heterogeneous group of compounds that have been used in the treatment of cardiovascular and metabolic diseases for over thirty years. While the primary indications for PPAR agonist therapy focus on hyperlipidemia and diabetes, there is a growing body of pre-clinical data that suggests they may be beneficial in the treatment of heart failure; a disease marked by abnormal myocardial metabolism, fibrosis and insulin insensitivity. PPAR agonist treatment in numerous animal models of systolic heart failure have demonstrated improvement in cardiac function with decreased fibrosis, improved contractility and endothelial function. However, considerable controversy exists on the cardiac safety profile of PPAR agonists, particularly concern for inducing lipotoxicty and precipitating or worsening heart failure. In addition during pre-clinical testing, many compounds have been associated with increased death and adverse cardiovascular outcomes casting a pall over their future use for treating disorders of myocardial function. This article will review cardiac pathways involved in PPAR activation and their potential regulation of maladaptive pathways involved in heart failure and highlight molecular mechanisms that may contribute to adverse events and raise safety concerns. Specific attention will be focused on PPAR alpha and gamma, subtypes for which commercially available PPAR agonists are currently available.	f	\N
22122790	Atopic dermatitis (AD) is a kind of eczema with an inflammatory, relapsing, non-contagious, and pruritic skin disorder. It is associated with the local infiltration of T helper type 2 (Th2) cells that secrete interleukin (IL)-4 and IL-5. IL-21 is a member of IL-2 family cytokine mainly expressed by activated CD4+ T lymphocytes. Until now, there is no clinical research in the expression of IL-21 in patients with AD. We analyzed serum levels of total immunoglobulin E (IgE), allergen-specific IgE, and cytokines IL-4, IL-5, IFN-γ, IL-17, and IL-21 in AD cases and controls. In addition, cytokine levels in the culture supernatants of peripheral blood mononuclear cells stimulated with anti-CD3 and anti-CD28 Abs, phytohemagglutin (PHA), or pokeweed mitogen (PWM) were measured. We also assessed clinical skin severity by Scoring of Atopic Dermatitis (SCORAD) index. Our results showed that serum total IgE in the case group was significantly higher than that of control group (365.449 ± 52.945 and 39.243 ± 7.605 IU/ml, respectively). Logistic regression analysis system reveals serum levels of IL-21 and IFN-γ are significantly correlated. However, IL-21 and IL-4, IL-21 and IL-5, as well as IL-21 and IL-17 showed no correlation. A significantly decreased level of IL-21 was observed in children suffering with severe AD compared with controls, suggesting that IL-21 may play a role in AD.	f	\N
22124677	Colonic ischemia following colorectal surgery is an unusual and serious complication. As it has been reported that the incidence of colonic ischemia was higher after laparoscopic surgery, the aim of this report was to document the clinical features of postoperative colonic ischemia following colorectal surgery. Among 1,201 surgeries for sigmoid colon and rectal cancer by a single surgeon from 2006 to 2010, 10 cases of postoperative colonic ischemia were retrospectively identified (0.83%). IMA high ligation was routinely made in all surgeries. The clinical findings and laboratory data of these 10 cases were evaluated. Of the 10 patients, 9 were male and 1 was female. The mean age was 66.9 years old. The mean BMI was 23.3. Three patients (30%) had a cardiovascular disease other than hypertension. Eight patients (80%) underwent laparoscopic surgery and two patients (20%) underwent open surgery. Intraoperative bleeding occurred in five patients (50%, mean 435 ml). The average day for occurrence of postoperative colonic ischemia was on the 5th day (range 2nd-10th day). A consistent postoperative fever was found in eight patients (80%). Mortality due to postoperative colonic ischemia was 10%. Postoperative colonic ischemia may be considered one of the more important complications of colorectal resection.	f	\N
22129916	To evaluate the long-term safety and efficacy of etanercept treatment in Polish patients with juvenile idiopathic arthritis (JIA). The study involved patients, fulfilling the JIA criteria of the International League of Associations of Rheumatology (ILAR), who were started on etanercept therapy after methotrexate and other synthetic disease-modifying antirheumatic drugs (DMARDs) had proven ineffective. Patient data were collected in an electronic registry. Disease improvement was assessed based on Giannini's criteria. The statistical analysis involved 188 patients. Significant improvement was observed in all clinical and laboratory parameters after the first month of therapy and was maintained in the following months. ACR Pediatric 30, 50, 70, 90, and 100 improvement was observed in 81.4%, 65.9%, 27.5%, 16.2%, and 15%, respectively, of patients after 3 months and in 94.7%, 88.4%, 62.1%, 34.7%, and 26.3%, respectively, after 24 months of treatment. Throughout the 72-month safety observation period, 1162 adverse events were reported; the exposure-adjusted AE rate was 2.96 per patient per year. In patients with various subtypes of JIA resistant to conventional DMARD treatment, etanercept resulted in significant and long-lasting improvements in disease activity. Combination treatment with etanercept and a DMARD was well tolerated.	f	\N
22133826	The purpose of clinical assessment of atherosclerosis in aorta is to detect early lesions that are associated with a substantial risk of cardiovascular disease, such as stroke, aortic aneurysm and dissection, and to develop a treatment strategy for reduction of the cardiovascular risk. The pulse wave velocity (PWV) and pulse wave analysis (augmentation index : AI) can reveal atherosclerotic functional vascular abnormalities. On the contrary, plain X-rays, ultrasound examination, computed tomography (CT) , and magnetic resonance imaging (MRI) can be employed to easily assess the severity of atherosclerotic vascular damage morphologically. In these examinations, only PWV, as an index of arterial stiffness, can detect early atherosclerotic change in aorta before organic change. So, considering the importance of detecting early lesion, PWV is the most useful examination of atherosclerosis in aorta.	f	\N
22134016	In this review, the pitfalls that still exist with the surgical treatment of endometriosisassociatedpelvic pain have been discussed and the best evidence regarding various aspects of surgical techniques have been reviewed. When laparoscopy is performed to evaluate a woman with pelvic pain symptoms, it is important she be counseled that the primary function of the surgery is to confirm the presence (and allow surgical treatment) of endometriosis, and that it is not the penultimate diagnostic modality for her pelvic pain. There are many etiologies of pelvic pain that present with symptoms resembling those of endometriosis-associated pelvic pain that are not diagnosable with laparoscopy, such as interstitial cystitis and irritable bowel syndrome. It is unfortunate that many women are left with the belief that if a laparoscopy fails to provide a diagnosis of a pain generator, then it means there are no diagnoses other than that the “pain is in her head,” often disparagingly termed “supratentorial” byclinicians. In fact, the pain-related diagnoses that are amenable to and possibly require a laparoscopy are quite limited, a group of diagnoses that this author terms the “dirty dozen” because there are just 12, and only the first 4 have good evidence to clearly associate them with chronic pelvic pain:1. Endometriosis 2. Ovarian remnant syndrome 3. Pelvic inflammatory disease 4. Tuberculous salpingitis 5. Adhesions 6. Benign cystic mesothelioma 7. Postoperative peritoneal cysts 8. Adnexal cysts (nonendometriotic)9. Chronic ectopic pregnancy 10. Endosalpingiosis 11. Residual accessory ovary 12. Hernias: ventral, inguinal, femoral, spigelian.I would argue that diagnostic laparoscopy in modern gynecology has a limited, if any role, and that when laparoscopy is planned for women with chronic pelvic pain, it should be with a very high suspicion of a diagnosis and with plans to treat the disease operatively. In this era, a negative diagnostic laparoscopy should be a rare event.	f	\N
22139583	Omics is the study of proteins, peptides, genes, and metabolites in living organisms. Systems biology aims to understand the system through the study of the relationship between elements such as genes and proteins in biological system. Recently, systems biology emerged as the result of the advanced development of high-throughput analysis technologies such as DNA sequencers, DNA arrays, and mass spectrometry for omics studies. Among a number of analytical tools and technologies, CE and CE coupled to MS are promising and relatively rapidly developing tools with the potential to provide qualitative and quantitative analyses of biological molecules. With an emphasis on CE for systems biology, this review summarizes the method developments and applications of CE for the genomic, transcriptomic, proteomic, and metabolomic studies focusing on the drug discovery and disease diagnosis and therapies since 2009.	f	\N
22145272	The prognosis of multiple myeloma patients has significantly improved since the introduction of the novel agents thalidomide, bortezomib and lenalidomide. We report the data of a medical need programme with lenalidomide plus dexamethasone, conducted in Belgium between August 2007 and March 2008, and including 98 relapsed refractory multiple myeloma patients. In addition to chemotherapy and steroids, all patients had received prior treatment with bortezomib, and 84% of them had been exposed to thalidomide. In 52 patients response data could be retrieved by post-hoc analysis. A partial remission or better was achieved in 52% (49% partial and 3% complete response) of patients, despite a median of 5 previous anti-myeloma treatment lines. Responses were rapid while the majority of patients received lenalidomide with once weekly (also called low-dose) dexamethasone. Treatment with lenalidomide plus dexamethasone did prolong overall survival by nearly half a year in this population with end-stage myeloma. Overall response and quality of response were independent of previous response to thalidomide and bortezomib, although the time to progression tended to be shorter in thalidomide- and bortezomib-refractory patients. It can be concluded that lenalidomide plus dexamethasone is an effective and safe treatment regimen in highly refractory multiple myeloma patients, and that these responses are irrespective of previous exposure or sensitivity to thalidomide and bortezomib.	f	\N
22153142	As important members of the health care team, patients and caregivers must be empowered to recognize their asthma status and to act accordingly. Education about asthma, complications, and successful management of asthma provide the best way to empower children and their caregivers. A Shared Medical Appointment (SMA) is a unique health care delivery approach that integrates disease management and patient education. The SMA described here is a 90-minute group appointment for four to nine patients who share a diagnosis of asthma, bronchospasm, or wheeze and their caregivers. The appointment includes a brief individual examination, health education delivered to the group, and the opportunity for interaction between group members. Because a supporting theoretic framework is not identified in the original design proposals for the SMA model or in the literature on its use, for the purposes of this project, Social Cognitive Theory is identified as the theoretical framework that best explains and reinforces the benefits of the SMA. The theoretic framework is important to direct the development and continued success of this treatment model. This project report describes the first nurse practitioner-led SMA as a tool for improving quality of care and service for children with asthma and their caregivers.	f	\N
22153317	Oral ulcer is the cardinal clinical sign and increased neutrophilic activity is a part of the pathogenesis in Behcet's disease (BD). Saliva, as a part of the innate immune response, contains antimicrobial peptides (AMPs) that are derived from both oral epithelial cells and neutrophils. The aim of this study was to investigate the associations between salivary levels of AMPs HNP 1-3, LL-37 and S100 and disease course in patients with Behcet's disease (BD). Fifty-three patients with BD and 44 healthy controls (HC) were included in the study. Disease severity score reflecting organ involvement was calculated. Salivary HNP 1-3, LL-37 and S100 levels were measured in unstimulated saliva samples by ELISA. Salivary HNP 1-3 and S100 levels in BD patients (2715.2 ± 1333.4 μg/ml and 430.6 ± 203.9 ng/ml) were significantly higher compared to HC (1780.6 ± 933.2 μg/ml and 365.3 ± 84.7 ng/ml) (p = 0.000 and p = 0.004, respectively). Although LL-37 levels were also higher in BD than HC (190.9 ± 189.1 vs 143.1 ± 128.9 ng/ml), no significant difference was observed (p = 0.53). Salivary HNP 1-3 and LL-37 levels were associated with the severity of BD (mild disease: 1975.1 ± 1174.2 μg/ml and 115.9 ± 109.4 ng/ml vs severe disease: 2955.7 ± 1305.6 μg/ml and 215.3 ± 203.8 ng/ml, p=0.020 and p=0.031, respectively). Salivary LL-37 levels also correlated with the number of monthly oral ulcers (r = 0.5 p = 0.000). An increase in salivary HNP 1-3 and S100 levels might be associated with enhanced local and systemic innate responses in BD.	f	\N
22156557	statin drugs may induce skeletal myopathy, but might also have the potential to improve rehabilitation outcomes by improving sarcopenia or by preventing intercurrent illness. We examined the association between statin use and functional outcomes in the rehabilitation of older people. retrospective cohort study using routinely collected clinical data. Admissions to Royal Victoria Hospital, Dundee for inpatient rehabilitation over a 10-year period were identified. Data were available regarding demographics, statin therapy, antiplatelet therapy, admission and discharge Barthel scores, length of stay and comorbid disease. Multivariate analyses were performed to examine the difference between admission and discharge Barthel score in patients taking statins compared with those not taking statins. a total of 3,422 patients were included. Mean age was 81.4 years; 40% were male. Baseline Barthel scores were similar in the statin/non-statin groups, respectively (10.4/20 versus 10.3/20, P = 0.57). Improvement in the Barthel score between admission and discharge was greater in the statin than non-statin group (3.59 versus 4.30 points, P < 0.001) after adjustment for age, sex, baseline Barthel score and comorbid disease. statin use was associated with improved Barthel scores on discharge from rehabilitation. This gain could contribute to improved outcomes as part of the rehabilitation package and requires further prospective investigation.	f	\N
22156787	Spinal muscular atrophy is a relatively stable chronic disease. Patients may gradually experience declines in muscle strength and motor function over time. However, functional progression is difficult to document, and the mechanism remains poorly understood. An 11-year-old girl was diagnosed at 19 months and took a few steps without assistance at 25 months. She was evaluated for 54 months in a prospective multicenter natural history study. Outcome measures were performed serially. From 6 to 7.5 years, motor function improved. From 7.5 to 11 years, motor function declined with increasing growth. Manual muscle testing scores minimally decreased. Motor unit number estimation studies gradually increased over 4.5 years. Compared to the published natural history of spinal muscular atrophy type III, our patient lost motor function over time. However, she walked with assistance 2 years longer than expected. Our report highlights possible precipitating factors that could affect the natural history of spinal muscular atrophy type III.	f	\N
22157156	Rhinitis is a common condition associated with significant under-recognized morbidity and impaired quality of life. The natural history of rhinitis is poorly characterized. Better understanding of its natural history and associated risk factors would improve the ability to effectively manage rhinitis in clinical practice. This review focuses on the current research findings on the natural history of rhinitis and how that is influenced by atopy and sex. Recent work from the Isle of Wight Birth Cohort Study has demonstrated that the prevalence of atopic rhinitis increases steadily in the first 18 years of life in both sexes. However, nonatopic rhinitis behaves differently during adolescence. Its prevalence decreases in boys but continues to increase in girls resulting in a female predominance after puberty. Numerous recent studies have proposed potential roles for sex-related and adipose-related hormonal changes in influencing the course of allergic disease. Further research is needed to establish mechanisms that could underlie such findings. Rhinitis becomes increasingly common through childhood, with prevalence during adolescence being mediated by differential effects of sex and atopy. Mechanisms to explain these findings await elucidation.	f	\N
22174195	Early rheumatoid arthritis (RA) and very early RA are major targets of research and clinical practice. Remission has become a realistic goal in the management of RA, particularly in early disease. The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA classification criteria, the EULAR treatment recommendations for RA, and the EULAR recommendations for the management of early arthritis focus on early disease and translate the knowledge related to early RA into classification and management. Nevertheless, there is a need for further improvement and progress. Results from 6 recent studies are summarized, evaluating the performance of the 2010 ACR/EULAR RA classification criteria. The data show a significant risk of misclassification, and highlight that overdiagnosis and underdiagnosis may become important issues if the criteria recommend synthetic and biological disease-modifying antirheumatic drugs. Therefore, some considerations are presented on how the current problems and limitations could be overcome in clinical practice and future research. A consensus is needed to better define the early phase of RA and differentiate from other early arthritis. The possible effect of misclassification on spontaneous and drug-induced remission of early and very early RA awaits further elucidation. Such research will eventually lead to more reliable diagnostic and classification criteria for new-onset RA.	f	\N
22174210	To compare clinical features of patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) and patients with polymyalgia rheumatica (PMR) and to explore the purported association between RS3PE and malignancy. We did a retrospective chart review of patients with RS3PE and PMR treated in a community-based hospital between January 2000 and December 2009. Outcomes assessed were clinical course of disease and associated malignancies. We identified 28 patients with RS3PE and 123 with pure PMR. All patients with RS3PE fulfilled PMR criteria as well. Age, comorbidity, erythrocyte sedimentation rate, duration and progression of symptoms, treatment response to initial low-dose steroids, and steroid complication rates were similar in both groups. Patients with RS3PE were more likely to be male (79% vs 41%; p = 0.001) and to have a history of smoking (39% vs 15%; p = 0.008) and a higher rate of depression (11% vs 2%; p = 0.044) at diagnosis. Among those with RS3PE, hip pain was less common (39% vs 74%; p = 0.001) than in the PMR group. No patients with RS3PE and 6 patients with pure PMR (4.9%) developed another rheumatological disease during followup. Seven of 9 patients (78%) with concurrent cancer presented slightly more frequently with systemic symptoms compared to patients without cancer (48%; p = 0.098), especially with fatigue (56% vs 22%; p = 0.037) and anorexia (33% vs 9.0%; p = 0.047). Despite rigorous cancer screening in patients with RS3PE, however, the rate of associated malignancy was not statistically different from that of patients with pure PMR [2 (7%) vs 7 (6%), respectively; p = 0.673]. Despite evidence that RS3PE is clinically distinct from PMR, we observed characteristics, treatment response, and outcomes like those expected in pure PMR. Compared to patients with pure PMR, patients with RS3PE are more likely to be male, to be depressed, and to smoke. Contrary to earlier studies, no clear association of RS3PE with malignancy was found despite rigorous cancer screening, although clinicians should be aware that patients with concurrent cancer may manifest more systemic signs and symptoms, as well as steroid resistance.	f	\N
22179327	Population allele frequencies of apolipoprotein E (APOE) vary by geographic region. The purpose of this study is to summarize and evaluate published estimates for the prevalence of APOE e4 carrier status among the population diagnosed with Alzheimer's disease (AD) by geographic region and country. A systematic review of English-language publications from January 1, 1985, through May 31, 2010, was conducted. Studies reporting APOE e4 status for patients diagnosed with AD were included in the analysis; trials and autopsies were excluded. APOE e4 data were pooled, and prevalence and 95% confidence intervals (CIs) were calculated. Pooled estimates for APOE e4 carrier prevalence data were derived from 142 independent samples: 48.7% (95% CI: 46.5-51.0), and from 73 samples for e4/4 (homozygotes): 9.6% (95% CI: 8.4-10.8). The highest estimates were in Northern Europe: 61.3% (95% CI: 55.9-66.7), e4/4 prevalence: 14.1% (95% CI: 12.2-16.0). The lowest estimates were in Asia and Southern Europe. Substantial heterogeneity of these prevalence estimates was observed. APOE e4 genotype prevalence varies among AD patients by region and within each country. Further exploration is warranted to better understand the substantial heterogeneity of these prevalence estimates.	f	\N
22183718	The gut epithelium is a barrier between the 'outside' and 'inside' world. The major function of the epithelium is to absorb nutrients, ions and water, yet it must balance these functions with that of protecting the 'inside' world from potentially harmful toxins, irritants, bacteria and other pathogens that also exist in the gut lumen. The health of an individual depends upon the efficient digestion and absorption of all required nutrients from the diet. This requires sensing of meal components by gut enteroendocrine cells, activation of neural and humoral pathways to regulate gastrointestinal motor, secretory and absorptive functions, and also to regulate food intake and plasma levels of glucose. In this way, there is a balance between the delivery of food and the digestive and absorptive capacity of the intestine. Maintenance of the mucosal barrier likewise requires sensory detection of pathogens, toxins and irritants; breakdown of the epithelial barrier is associated with gut inflammation and may ultimately lead to inflammatory bowel disease. However, disruption of the barrier alone is not sufficient to cause frank inflammatory bowel disease. Several recent studies have provided compelling new evidence to suggest that changes in epithelial barrier function and inflammation are associated with and may even lead to altered regulation of body weight and glucose homeostasis. This article provides a brief review of some recent evidence to support the hypothesis that changes in the gut microbiota and alteration of gut epithelial function will perturb the homeostatic humoral and neural pathways controlling food intake and body weight.	f	\N
22184604	Assessing the medical history of patients before any treatment is an essential aspect of the dentist's responsibility; however, many dental practitioners assume that their patients are systemically healthy so their medical history is often overlooked. The objective of this study was to determine the prevalence of self-reported medical conditions among a sample of dental school patients at the Institute of Dental Sciences, Bareilly (Uttar Pradesh), India. Detailed medical histories were taken from 3,786 new dental patients in an outpatient setting. The demographic data, medical status, and use of medications from the charts were analyzed. Thirty-eight percent of the total patients had a positive finding in their medical history for at least one systemic condition. The most commonly reported systemic condition was hypertension (15.2 percent) followed by diabetes (11.4 percent), and 26 percent of the patients were taking at least one medication daily. The results of this study reflect the medical complexity of the increasingly aging population.	f	\N
22185707	Acute pyelonephritis (APN) requires prompt diagnosis and immediate treatment. To develop a simple score to assist in diagnosing treatment deterioration in patients with serious APN. Using data from a retrospective cohort of 193 patients with APN, we developed scores based on multivariate logistic regression after the jackknife procedure. We validated the scores in a prospective cohort of 40 patients. Nine criteria were independently associated with our investigation: Abscess (adjusted odds ratio [OR], 19.8; 95% confidence interval [95% CI] 4.5-72.1), pyonephrosis with or without stone (18.3; 4.8-70.9), pelvicalyceal air (15.5; 3.2-26.9), poor global excretion of contrast (12.3; 2.9-68.5), tachycardia or hypotension (10.1; 2.5-28.0), obliteration of the renal sinus (9.6; 2.5-45.2), persistent fever or pyuria (9.8; 1.9-25.8), diabetes (9.4; 2.0-31.8), and global renal enlargement (7.5; 2.1-35.8). The APN score was based on these nine criteria. Low-risk and high-risk groups were derived from the score (probability, 3.5% [95% CI 0-7.5] and 67% [51-83]). Application of these criteria to the prospective cohort confirmed the diagnostic accuracy of the score (probability 0% [0-15] and 71% [25-100] in the low-risk and high-risk groups, respectively). This easy-to-calculate score may prove useful for diagnosing patients with serious APN who deteriorate with treatment.	f	\N
22195084	There is increasing interest in leveraging electronic health data across disparate sources for a variety of uses. A fallacy often held by data consumers is that clinical data quality is homogeneous across sources. We examined one attribute of data quality, completeness, in the context of electronic laboratory reporting of notifiable disease information. We evaluated 7.5 million laboratory reports from clinical information systems for their completeness with respect to data needed for public health reporting processes. We also examined the impact of health information exchange (HIE) enhancement methods that attempt to improve completeness. The laboratory data were heterogeneous in their completeness. Fields identifying the patient and test results were usually complete. Fields containing patient demographics, patient contact information, and provider contact information were suboptimal. Data processed by the HIE were often more complete, suggesting that HIEs can support improvements to existing public health reporting processes.	f	\N
22199325	There have been reports suggesting that continuous administration of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is advantageous for patients in which disease progression was observed after the establishment of clinical benefit from EGFR-TKIs. We retrospectively evaluated the clinical course of patients who received continuous administration of EGFR-TKIs after disease progression was detected solely in bone lesions. The medical records of patients administered gefitinib or erlotinib between 2002 and 2010 were reviewed. We evaluated the progression-free survival (PFS) and overall survival (OS) in patients who had bone metastases after the establishment of clinical benefit from EGFR-TKI and who received radiation therapy for the bone lesion and continuous treatment with EGFR-TKI. Ten patients were enrolled in this study. The median PFS and OS were 88 days and 330 days, respectively. Furthermore, a longer duration from the start of first EGFR-TKI to detection of bone metastases (p=0.0049) was identified as being significantly associated with a longer PFS. Our data suggest that continuous administration of EGFR-TKI is a treatment option for patients with bone metastases who previously benefited from therapy with EGFR-TKI.	f	\N
22200856	Caveolin-1 (cav-1) has been implicated in the development of human cancers. However, the distribution of cav-1 in non-small cell lung cancer (NSCLC) and its signiﬁcance require further study. Real-time PCR and Western blot assays were performed to detect cav-1 mRNA and protein levels in tumor tissues (TT) and matched tumor-free tissues (TF). The protein expression in 115 paraffin-embedded blocks was examined by immunohistochemical staining (IHC). Correlations between cav-1 mRNA and protein expression by IHC and clinicopathological features were statistically evaluated. For the 136 patients examined, the levels of cav-1 mRNA and protein expression were significantly lower in lung TT compared to matched TF (P<0.05). High cav-1 expression was detected in 60 of 115 (52.2%) NSCLC tissues and this level was significantly lower than cav-1 expression in non-cancerous lung tissues (15 of 19, 78.9%, P<0.05). Up-regulation of cav-1 mRNA expression in lung adenocarcinoma (AC) (29.7%) was higher than that observed in lung squamous cell carcinoma (SCC) (15.8%). Statistical analysis of the correlation between cav-1 protein expression and clinical features showed a statistical association with poorer N-stage (P=0.032) and higher pathological TNM stage (P=0.012) in lung AC patients, that was not found in lung SCC patients. Moreover, lung AC patients with higher cav-1 expression showed significantly shorter life-spans than those with lower cav-1 expression (P=0.032, log-rank test). The levels of cav-1 mRNA and protein expression were significantly lower in lung cancers when compared to matched TF or non-cancerous lung tissues. The higher protein expression correlated with the advanced pathological stage and shorter survival rates in lung AC patients.	f	\N
22201290	Integrins play myriad and vital roles in development and disease. They connect a cell with its surroundings and transmit chemical and mechanical signals across the plasma membrane to the cell's interior. Dissecting their roles in cell behavior is complicated by their overlapping ligand specificity and shared downstream signaling components. In principle, immobilized synthetic peptides can mimic extracellular matrix proteins by supporting integrin-mediated adhesion, but most short peptide sequences lack selectivity for one integrin over others. In contrast, synthetic integrin antagonists can be highly selective. We hypothesized that this selectivity could be exploited if antagonists, when immobilized, could support cellular adhesion and activate signaling by engaging specific cell-surface integrins. To investigate this possibility, we designed a bifunctional (RGD)-based peptidomimetic for surface presentation. Our conjugate combines a high affinity integrin ligand with a biotin moiety; the former engages the α(v)β(3) integrin, and the latter allows for presentation on streptavidin-coated surfaces. Surfaces decorated with this ligand promote both cellular adhesion and integrin activation. Moreover, the selectivity of these surfaces for the α(v)β(3) integrin can be exploited to capture a subset of cells from a mixed population. We anticipate that surfaces displaying highly selective small molecule ligands can reveal the contributions of specific integrin heterodimers to cell adhesion and signaling.	f	\N
22211766	Retinol binding protein-4 (RBP-4) is a member of adipocytokines, which is potentially associated with fibrosis, vasodilation, and angiogenesis in addition to insulin resistance. To investigate the clinical significance of serum RBP4 levels in patients with systemic sclerosis (SSc), which is a systemic autoimmune disease characterized by fibrosis and vasculopathy. Serum RBP4 levels were determined by enzyme-linked immunosorbent assay in 62 SSc patients and 19 healthy controls. Similar to patients with chronic kidney disease, serum RBP4 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction. Therefore, analyses were carried out by excluding SSc patients with estimated glomerular filtration rate <60 mL/min/1.73 m(2) . Serum RBP4 levels were significantly lower in diffuse cutaneous SSc (dcSSc) than in control subjects [median (25-75 percentile); 25.8 μg/mL (19.6-47.0) vs. 43.1 μg/mL (31.7-53.4), P < 0.05], while there was no significant difference between limited cutaneous SSc (lcSSc) [28.0 μg/mL (25.4-43.3)] and control subjects. In both of dcSSc and lcSSc, patients with Raynaud's phenomenon had RBP4 levels significantly lower than those without. Furthermore, serum RBP4 levels inversely correlated with pulmonary function test results in dcSSc and with right ventricular systolic pressure in lcSSc. CONCLUSION  Decreased RBP4 levels are associated with the prevalence of Raynaud's phenomenon in dcSSc and lcSSc, with the severity of interstitial lung disease in dcSSc, and with the degree of pulmonary vascular involvement in lcSSc, suggesting the possible contribution of RBP4 to the pathological events in this disorder.	f	\N
22215125	Primary hyperoxaluria type I is a rare inherited disease that presents a disturbed metabolism of glyoxylate. Consequently, patients suffer from hyperoxaluria, leading to renal failure and subsequent skeletal calcium oxalate deposition. Areas with high concentrations of calcium oxalate, so-called dense metaphyseal bands, are at risk for pathological fracturing. The primary disease is treated by combined liver-kidney transplantation, although pathological fracturing also occurs in the posttransplant period. In the current case, we present a 3-year-old boy with a pathological fracture of his right femur, 2 years after liver-kidney transplantation. We opted for a conservative regime, leading to good fracture healing. As there are limited data in the literature regarding treatment of fractures in these patients, it is important to notify the outcome of conservative treatment of pathological fractures in patients with primary hyperoxaluria type I.	f	\N
22226887	Cystic fibrosis is a lethal autosomal recessive condition caused by a defect of the transmembrane conductance regulator gene that has a key role in cell homeostasis. A dysfunctional cystic fibrosis transmembrane conductance regulator impairs the efflux of cell anions such as chloride and bicarbonate, and also that of other solutes such as reduced glutathione. This defect produces an increased viscosity of secretions together with other metabolic defects of epithelia that ultimately promote the obstruction and fibrosis of organs. Recurrent pulmonary infections and respiratory dysfunction are main clinical consequences of these pathogenetic events, followed by pancreatic and liver insufficiency, diabetes, protein-energy malnutrition, etc. This complex comorbidity is associated with the extensive injury of different biomolecular targets by reactive oxygen species, which is the biochemical hallmark of oxidative stress. These biological lesions are particularly pronounced in the lung, in which the extent of oxidative markers parallels that of inflammatory markers between chronic events and acute exacerbations along the progression of the disease. Herein, an abnormal flux of reactive oxygen species is present by the sustained activation of neutrophils and other cystic fibrosis-derived defects in the homeostatic processes of pulmonary epithelia and lining fluids. A sub-optimal antioxidant protection is believed to represent a main contributor to oxidative stress and to the poor control of immuno-inflammatory pathways in these patients. Observed defects include an impaired reduced glutathione metabolism and lowered intake and absorption of fat-soluble antioxidants (vitamin E, carotenoids, coenzyme Q-10, some polyunsaturated fatty acids, etc.) and oligoelements (such as Se, Cu and Zn) that are involved in reactive oxygen species detoxification by means of enzymatic defenses. Oral supplements and aerosolized formulations of thiols have been used in the antioxidant therapy of this inherited disease with the main aim of reducing the extent of oxidative lesions and the rate of lung deterioration. Despite positive effects on laboratory end points, poor evidence was obtained on the side of clinical outcome so far. These aspects examined in this critical review of the literature clearly suggest that further and more rigorous trials are needed together with new generations of pharmacological tools to a more effective antioxidant and anti-inflammatory therapy of cystic fibrosis patients. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.	f	\N
22237046	PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism (SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations. PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS)] and in 945 healthy controls. The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P = 0.005, χ(2 )= 7.858, odds ratio (OR) = 1.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, χ(2 )= 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, χ(2 )= 7.258, OR = 1.98), lung involvement (P = 0.0060, χ(2 )= 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, χ(2 )= 16.567, OR = 3.73). The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.	f	\N
22237792	Substantia nigra hyperechogenicity assessed by transcranial sonography is a typical finding in up to 90% of patients with idiopathic Parkinson's disease, although its value as a surrogate marker for disease progression in Parkinson's disease is controversial. (123) I-FP-CIT-single photon emission computed tomography (SPECT) represents an established paraclinical surrogate marker to quantify the nigrostriatal dopaminergic deficit in Parkinson's disease. Whereas most studies found no correlation between extent of substantia nigra echogenicity and the putaminal FP-CIT binding ratio, a more recent analysis reported opposite results. In 92 patients with Parkinson's disease the substantia nigra echogenicity was compared with the putaminal FP-CIT binding ratio using an investigator-independent SPECT analysis protocol and with several clinical parameters. No correlation was found between the substantia nigra hyperechogenicity and the FP-CIT binding ratio or the disease severity. Substantia nigra hyperechogenicity does not reflect the degree of the nigrostriatal degeneration or the clinical state of the disease progression.	f	\N
22239875	Dual-energy x-ray absorptiometry (DEXA) is a safe, noninvasive, inexpensive tool for managing patients with neuromuscular diseases. Regional and whole-body DEXA can be used to guide clinical treatments, such as determining body composition to guide nutritional recommendations, as well as to monitor disease progression by assessing regional and whole-body lean tissue mass. DEXA can also be used as an outcome measure for clinical trials.	f	\N
22239959	An inadequate level of bowel preparation can affect the efficacy and safety of colonoscopy. Although some factors have been associated with outcome, there is no strategy to identify patients at high risk for inadequate preparation. We searched for factors associated with an inadequate level of preparation and tested the validity of a predictive clinical rule based on these factors. We performed a prospective study of 2811 consecutive patients who underwent colonoscopy examinations at 18 medical centers; clinical and demographic data were collected before the colonoscopy. Bowel preparation was classified as adequate or inadequate; 925 patients (33%) were found to have inadequate preparation. Multivariate analysis was used to identify factors associated with inadequate preparation, which were expressed as odds ratio (OR) and used to build a predictive model. Factors associated with inadequate bowel preparation included being overweight (OR, 1.5), male sex (OR, 1.2), a high body mass index (OR, 1.1), older age (OR, 1.01), previous colorectal surgery (OR, 1.6), cirrhosis (OR, 5), Parkinson disease (OR, 3.2), diabetes (OR, 1.8), and positive results in a fecal occult test (OR, 0.6). These factors predicted which patients would have inadequate cleansing with 60% sensitivity, 59% specificity, 41% positive predictive value, and 76% negative predictive value; they had an under the receiver operating characteristic curve value of 0.63. Assuming 100% efficacy of a hypothetical regimen to address patients predicted to be at risk of inadequate preparation, the rate would decrease from 33% to 13%. We identified factors associated with inadequate bowel preparation for colonoscopy and used these to build an accurate predictive model.	f	\N
22241793	Neointimal hyperplasia causes a high rate of hemodialysis synthetic graft failure. Thus, therapies that inhibit neointimal hyperplasia are urgently needed. The Coll-R is a sirolimus-eluting collagen matrix designed for intra-operative perivascular implantation around the graft-venous anastomosis. Sirolimus is an anti-proliferative drug that has proven clinical utility in suppressing neointimal tissue growth in coronary artery disease when delivered locally to the vascular wall by an endovascular drug eluting stent. A cohort of 12 chronic hemodialysis patients underwent surgical placement of 13 polytetrafluoroethylene grafts + Coll-R and were followed for up to 24 months. The primary endpoint was safety (freedom from device related adverse events). Secondary endpoints were pharmacokinetics of sirolimus release, success of Coll-R implantation and primary unassisted graft patency. There were no technical failures, infections, vascular anastomotic or wound-healing problems. Whole blood sirolimus levels rose to a mean peak of 4.8 ng/mL at 6 h and fell to <1 ng/mL at 1 week (n = 5). Twelve and 24-month primary unassisted patencies were 76 and 38%, respectively, and the thrombosis rate was 0.37/patient-year. Perivascular implantation of the Coll-R during graft surgery safely delivered sirolimus to the vascular wall. Systemic sirolimus levels were sub-therapeutic for immunosuppression. This small first-in-human study supports the concept that the Coll-R can safely deliver sirolimus to the graft-venous anastomosis. Safety and patency in this small study were sufficiently encouraging to justify randomized controlled trials to further test the efficacy of the Coll-R.	f	\N
22248333	We assessed HIV prevalence and associated behaviors and risk factors among men who have sex with men (MSM) in Beijing, China. Five hundred MSM were recruited for a biological and behavioral survey using respondent-driven sampling (RDS) in 2009. Serologic specimens were tested for markers of HIV and syphilis infection. A computer-assisted personal interview (CAPI) administered questionnaire gathered information including demographic characteristics, sexual behaviors, HIV testing, and social norms concerning condom use. The adjusted HIV prevalence was 8.0%, syphilis 22.0%. HIV testing and disclosure was low; only 39.3% had HIV tested in the past 12 months, 49.7% knew their own HIV status and 22.8% knew their last male partner's HIV status. HIV infection was associated with syphilis, ever having sex with a woman, not knowing the HIV status of the most recent male partner, and never buying condoms in the past 12 months. Stronger endorsement of positive social norms around condom use strongly and predicted lower prevalence of HIV infection. Compared to surveys of similar design in the recent past, HIV continues to spread rapidly among Beijing's MSM. Our results identify points of intervention that, if addressed in time, may still alter the course of the epidemic including the promotion of HIV testing and partner disclosure, syphilis control and particularly changing social norms around condom use.	f	\N
22249461	Kuru was the first human transmissible spongiform encephalopathy (TSE) or prion disease identified, occurring in the Fore linguistic group of Papua New Guinea. Kuru was a uniformly fatal cerebellar ataxic syndrome, usually followed by choreiform and athetoid movements. Kuru imposed a strong balancing selection on the Fore population, with individuals homozygous for the 129 Met allele of the gene (PRNP) encoding for prion protein (PrP) being the most susceptible. The decline in the incidence of kuru in the Fore has been attributed to the exhaustion of the susceptible genotype and ultimately by discontinuation of exposure via cannibalism. Neuropathologically, kuru-affected brains were characterized by widespread degeneration of neurons, astroglial and microglial proliferation, and the presence of amyloid plaques. These early findings have been confirmed and extended by recent immunohistochemical studies for the detection of the TSE-specific PrP (PrP). Confocal laser microscopy also showed the concentration of glial fibrillary acidic protein-positive astrocytic processes at the plaque periphery. The fine structure of plaques corresponds to that described earlier by light microscopy. The successful experimental transmission of kuru led to the awareness of its similarity to Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease and formed a background against which the recent epidemics of iatrogenic and variant Creutzfeldt-Jakob disease could be studied.	f	\N
22252480	The objective is to evaluate the relationship between cholesterolemia, serum apolipoprotein B (apoB) level and blood pressure in a large sample of general population. The Brisighella Heart Study (BHS) is a prospective, population-based longitudinal epidemiological investigation. For this study, we analysed the data sampled in the 2008 BHS population survey, excluding those participants treated with antihypertensive and/or lipid lowering drugs (N: 2473). In a sex, BMI, smoking habit, physical activity level and serum creatinine adjusted model, low-density lipoprotein-cholesterol (LDL-C) appears to be significantly related to SBP (P < 0.001), DBP (P = 0.026), and pulse pressure (PP) (P < 0.001). In individuals aged less than 52 years, LDL-C was significantly associated to SBP and DBP (P < 0.001), but not PP. In the same model, apoB appears to be mildly but significantly related to SBP (P < 0.001), DBP (P < 0.001), and PP (P < 0.001). In individuals aged less than 52 years, apoB was significantly associated to SBP (P < 0.001), DBP (P < 0.001), and PP (P < 0.001). In individuals aged 52 or more, nor LDL-C neither apoB were significantly associated to blood pressure. Including in the same model LDL-C and apoB, apoB excluded the predicting role of LDL-C as it regards the blood pressure either in the whole population sample and in the younger individuals. On the basis of our observation, either serum LDL-C and apoB are significantly related to the blood pressure level in a large sample of individuals untreated with antihypertensive and lipid-lowering drugs. This association is stronger in younger individuals than in elderly. ApoB seems to be a stronger predictor of either SBP, DBP and PP than LDL-C.	f	\N
22253312	During past decades, twin studies have played an important role in genetic epidemiology studies of complex traits. The strength of twin studies lies in the ability to disentangle genetic and environmental factors that contribute to a phenotype, by comparing genetically identical monozygotic twins to dizygotic twins, who share on average 50% of genetic variants. Twin studies now offer the opportunity to study epigenetic variation across the genome with two aims. First, twin studies can improve our understanding of the factors regulating epigenetic variability by assessing the heritability of epigenetic variants. Secondly, the use of twins in epigenetic research is increasingly recognized as an important approach to help unravel the complexities associated with human development and disease. The strategic use of identical twins discordant for complex disease has revealed the importance of linking epigenetic disruption to the disease-associated risk in humans. Lastly, we also discuss the possibility that epigenetic effects on disease may in part explain some of the missing heritability in genome-wide association studies. The study of human epigenetic factors in twins can inform the role of genetics, as well as in utero and postnatal environments to the establishment, maintenance and functional consequences of human epigenome variation.	f	\N
22257051	Extracellular matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases involved in physiological and pathological processes, through the cleavage of extracellular matrix. MMPs are capable of degrading essentially all matrix components, which is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. The vertebrates MMP family includes at least 26 enzymes (23 have been known in humans) with only MMP-1, 2, and 7 experimentally validated as targets for antitumoral drug design. However, inhibition of MMP-1 has been hypothesized to be the cause of the clinically observed musculoskeletal syndrome when broad spectrum inhibitors are used. On the other hand, MMP-9 is a tricky enzyme, since its inhibition might be useful in treating patients with early-stage cancers, but MMP-9 is an anti-target in patients with advanced disease. So, MMP-9 inhibition should also be prevented. Therefore, selective MMP-2 inhibition arises as a pursued profile for MMP binders. Among them, hydroxamates have been extensively studied as small molecule drug candidates characterized by an effective zinc-binding group plus additional side chains responsible for the selectivity. This article pays particular attention to MMP-2 selectivity on hydroxamate-type inhibitors, especially against MMP-9, and their chemical structure, SAR, general synthetic methods, and molecular modelling studies are here reviewed in order to inspire further design of new effective anticancer agents.	f	\N
22266119	The apicomplexan parasite Plasmodium vivax is responsible for causing more than 70% of human malaria cases in Central and South America, Southeastern Asia and the Indian subcontinent. The rising severity of the disease and the increasing incidences of resistance shown by this parasite towards usual therapeutic regimens have necessitated investigation of putative novel drug targets to combat this disease. The apicoplast, an organelle of procaryotic origin, and its circular genome carrying genes of possible functional importance, are being looked upon as potential drug targets. The genes on this circular genome are believed to be highly conserved among all Plasmodium species. Till date, the plastid genome of P. falciparum, P. berghei and P. chabaudi have been detailed while partial sequences of some genes from other parasites including P. vivax have been studied for identifying evolutionary positions of these parasites. The functional aspects and significance of most of these genes are still hypothetical. In one of our previous reports, we have detailed the complete sequence, as well as structural and functional characteristics of the Elongation factor encoding tufA gene from the plastid genome of P. vivax. We present here the sequences of large and small subunit rRNA (lsu and ssu rRNA) genes, sufB (ORF470) gene, RNA polymerase (rpo B, C) subunit genes and clpC (casienolytic protease) gene from the plastid genome of P. vivax. A comparative analysis of these genes between P. vivax and P. falciparum reveals approximately 5-16% differences. A codon usage analysis of major plastid genes has shown a high frequency of codons rich in A/T at any or all of the three positions in all the species. TTA, AAT, AAA, TAT, and ATA are the major preferred codons. The sequences, functional domains and structural analysis of respective proteins do not show any variations in the active sites. A comparative analysis of these Indian P. vivax plastid genome encoded genes has also been done to understand the evolutionary position of the Indian parasite in comparison to other Plasmodium species.	f	\N
22267663	Oral candidiasis is often accompanied by severe inflammation, resulting in a decline in the quality of life of immunosuppressed individuals and elderly people. To develop a new oral therapeutic option for candidiasis, a nonpathogenic commensal oral probiotic microorganism, Streptococcus salivarius K12, was evaluated for its ability to modulate Candida albicans growth in vitro, and its therapeutic activity in an experimental oral candidiasis model was tested. In vitro inhibition of mycelial growth of C. albicans was determined by plate assay and fluorescence microscopy. Addition of S. salivarius K12 to modified RPMI 1640 culture medium inhibited the adherence of C. albicans to the plastic petri dish in a dose-dependent manner. Preculture of S. salivarius K12 potentiated its inhibitory activity for adherence of C. albicans. Interestingly, S. salivarius K12 was not directly fungicidal but appeared to inhibit Candida adhesion to the substratum by preferentially binding to hyphae rather than yeast. To determine the potentially anti-infective attributes of S. salivarius K12 in oral candidiasis, the probiotic was administered to mice with orally induced candidiasis. Oral treatment with S. salivarius K12 significantly protected the mice from severe candidiasis. These findings suggest that S. salivarius K12 may inhibit the process of invasion of C. albicans into mucous surfaces or its adhesion to denture acrylic resins by mechanisms not associated with the antimicrobial activity of the bacteriocin. S. salivarius K12 may be useful as a probiotic as a protective tool for oral care, especially with regard to candidiasis.	f	\N
22270369	α-Dystroglycan (α-DG) is a membrane-associated glycoprotein that interacts with several extracellular matrix proteins, including laminin and agrin. Aberrant glycosylation of α-DG disrupts its interaction with ligands and causes a certain type of muscular dystrophy commonly referred to as dystroglycanopathy. It has been reported that a unique O-mannosyl tetrasaccharide (Neu5Ac-α2,3-Gal-β1,4-GlcNAc-β1,2-Man) and a phosphodiester-linked modification on O-mannose play important roles in the laminin binding activity of α-DG. In this study, we use several dystroglycanopathy mouse models to demonstrate that, in addition to fukutin and LARGE, FKRP (fukutin-related protein) is also involved in the post-phosphoryl modification of O-mannose on α-DG. Furthermore, we have found that the glycosylation status of α-DG in lung and testis is minimally affected by defects in fukutin, LARGE, or FKRP. α-DG prepared from wild-type lung- or testis-derived cells lacks the post-phosphoryl moiety and shows little laminin-binding activity. These results show that FKRP is involved in post-phosphoryl modification rather than in O-mannosyl tetrasaccharide synthesis. Our data also demonstrate that post-phosphoryl modification not only plays critical roles in the pathogenesis of dystroglycanopathy but also is a key determinant of α-DG functional expression as a laminin receptor in normal tissues and cells.	f	\N
22276367	Evaluation of the fitness of an accused person to participate in legal proceedings is a classic forensic activity. Before the trial, the forensic expert will already assess any preexisting somatic and psychological illnesses and give a written expert opinion describing the condition of the accused at the time of the examination and assessing whether he is fit to stand trial. Nevertheless, decompensation or aggravation of a disease may occur--especially in stress situations as they are to be expected for an accused in the courtroom--so that apart from the current evaluation of the state of health of the accused, emergency treatment may occasionally become necessary in the courtroom. The article tries to answer the question how the expert can meet this challenge.	f	\N
22280950	Endocardial lead-induced tricuspid regurgitation has not been well recognized, either clinically or echocardiographically, and yet it is likely a preventable iatrogenic disease. In severe cases, it can lead to right ventricular failure and require tricuspid valve surgery. This complication will become increasingly important, because the numbers of permanent pacemakers and implantable cardioverter-defibrillators are expected to increase because of the aging population and the expanding capabilities of these devices. Published studies are largely retrospective, and serial studies to assess the time course of the development of tricuspid regurgitation are lacking. The mechanisms and severity of tricuspid regurgitation may not be well evaluated by two-dimensional echocardiography. Real-time three-dimensional echocardiography appears to be a promising technique to evaluate the mechanism of tricuspid regurgitation and may allow the early detection of patients who will develop severe lead-induced tricuspid regurgitation. A better understanding of the mechanism of lead-induced tricuspid regurgitation will be essential to the development of preventive strategies, which can then be tested in future clinical trials.	f	\N
22281228	Progressive multifocal leukoencephalopathy (PML) is a subacute central nervous system infection due to reactivation of the JC virus. Most reported cases occurred in HIV-infected patients (80% of cases), patients with lymphoid malignancies (13%) and transplant recipients taking immunosuppressants (5%). Less often, PML has been described in patients with chronic inflammatory joint diseases associated with autoimmune disorders (lupus, rheumatoid arthritis [RA] and vasculitis) (2%). Magnetic resonance imaging of the brain shows suggestive changes and confirmation of the diagnosis is obtained by performing PCR tests to identify the JC virus in the cerebrospinal fluid or, when necessary, a brain biopsy. No treatments have been proven effective. Most patients experience progressive disease that is fatal within a few months or induces incapacitating neurological impairments. The risk of PML is 0.4/100,000 in patients with RA. In the few case-reports of PML in RA patients, the treatments used included methotrexate (five cases) combined with a biological agent such as infliximab (one case), rituximab (four cases), or leflunomide (two cases including one with concomitant rituximab). PML is an extremely rare but devastating complication. Rituximab therapy is associated with an increased prevalence of PML in RA patients (4/100,000), who should be informed of this risk. In patients with lupus, the risk of PML is higher than in RA (4/100,000) and 40% of cases of PML occur during low-dose glucocorticoid therapy without immunosuppressive therapy.	f	\N
22281918	Sporotrichosis is a subcutaneous fungal infection caused by Sporothrix schenckii and acquired by direct inoculation. Although the majority of cases consist of the classic lymphocutaneous presentation, the frequency of atypical and severe clinical forms of the disease has increased progressively. Systemic and disseminated cutaneous sporotrichosis constitute rare variants and such cases are generally associated with cellular immunodeficiency or debilitated states. The present paper describes the first published case of molluscum-like lesions in disseminated mucocutaneous sporotrichosis. Direct mycological examination and histopathology revealed numerous yeast cells.	f	\N
22283575	Inhaled dry powder mannitol is well established for use in bronchial provocation testing. Inhaled mannitol also increases mucociliary clearance, and therefore could have a role in treating chronic suppurative lung disease. There have been a number of studies in cystic fibrosis and bronchiectasis. An international Phase III trial has just been published that suggests the use of regular inhaled mannitol increases lung function and reduces exacerbation frequency in cystic fibrosis. Inhaled mannitol exerts its effects in a number of ways, most importantly like hypertonic saline, setting up an osmotic gradient so water flows into the airway lumen, increasing mucus hydration and mucociliary clearance. Its formulation as a dry powder makes it quick and convenient to take.	f	\N
22288822	Urinary schistosomiasis is caused by the digenetic trematode Schistosoma haematobium, characterized by accumulation of eggs in the genitourinary tract. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) can play an important role in parasitic infection due to its major role as a negative regulator of T-cell activation and proliferation. This study was performed in patients with schistosomiasis and healthy controls to analyze the allele and genotype frequencies of four CTLA-4 gene polymorphisms. The CTLA-4 gene was amplified using Taqman real-time polymerase chain reaction, and allele and genotypes of 49 patients with schistosomiasis were analyzed using allelic discrimination analysis followed by subsequent direct sequencing. The results were compared with healthy control subjects. The frequencies of CTLA-4 rs733618 A allele at position -1722 (p=0.001), rs11571316 C allele at position -1577 (p<0.001), and rs231775 A allele at position +49 (p=0.002) in the patient group were significantly higher than the control group. The rs733618 AA genotype (p=0.001), rs11571316 CC genotype (p<0.001), and rs231775 AA genotype (p=0.007) were also significantly overrepresented. Meanwhile, rs733618 AG genotype (p=0.001), rs11571316 CT genotype (p=0.02), and rs231775 GG genotype (p=0.029) were significantly decreased in the patients with schistosomiasis, as compared with the controls. No significant difference was observed in both allele and genotype of rs16841252. The results of this study suggest that the rs733618, rs11571316, and rs231775 polymorphisms in the CTLA-4 gene may influence susceptibility to schistosomiasis infection in the Gabonese children.	f	\N
22289889	Accumulating evidence indicates that infiltrating stromal cells contribute directly and indirectly to tumor growth in a wide range of cancers. In follicular lymphoma (FL), malignant B cells are found admixed with heterogeneous lymphoid-like stromal cells within invaded lymph nodes and BM. In addition, mesenchymal stromal cells (MSCs) support in vitro FL B-cell survival, in particular after their engagement toward lymphoid differentiation. We show here that BM-MSCs obtained from patients with FL (FL-MSCs) display a specific gene expression profile compared with MSCs obtained from healthy age-matched donors (HD-MSCs). This FL-MSC signature is significantly enriched for genes associated with a lymphoid-like commitment. Interestingly, CCL2 could be detected at a high level within the FL-cell niche, is up-regulated in HD-MSCs by coculture with malignant B cells, and is overexpressed by FL-MSCs, in agreement with their capacity to recruit monocytes more efficiently than HD-MSCs. Moreover, FL-MSCs and macrophages cooperate to sustain malignant B-cell growth, whereas FL-MSCs drive monocyte differentiation toward a proangiogenic and lipopolysaccharide-unresponsive phenotype close to that of tumor-associated macrophages. Altogether, these results highlight the complex role of FL stromal cells that promote direct tumor B-cell growth and orchestrate FL-cell niche, thus emerging as a potential therapeutic target in this disease.	f	\N
22299123	Abuse of methamphetamine (meth), a potent central nervous system stimulant, has been associated with significant dental disease. Current descriptions of "meth mouth" are limited in their scope and fail to illuminate the potential pathogenic mechanisms of meth for oral disease. The purpose of this pilot study was to characterize the oral health of subjects with a history of meth abuse as compared to nonabusing control subjects. A total of 28 meth abusers and 16 control subjects were enrolled. Interviews and surveys regarding meth abuse, dental history, oral hygiene, and diet were collected. A comprehensive oral cavity examination including salivary characterization was completed. We observed significantly higher rates of decayed surfaces, missing teeth, tooth wear, plaque, and calculus among meth abusers. No significant difference in salivary flow rates were noted, yet results showed significant trends for lower pH and decreased buffering capacity. These findings suggest that salivary quality may play a more important role in meth mouth than previously considered. Salivary analysis may be useful when managing a dental patient with history of methamphetamine abuse.	f	\N
22299530	Traditional forms of treatment of the thyroid diseases: pharmacotherapy, radioiodine therapy and surgery can not always be applied. Intolerance, side effects of antithyroid drugs, low iodine uptake, high risk of surgery or disagreement with the proposed treatment was the reason for seeking alternative healing methods. With the development of interventional radiology, and gained experience in the use of arterial embolization, this method has become possible to use in treatment of thyroid diseases. The essence of this treatment is to shut down blood flow in major arteries of the thyroid by direct injection into the vessel's light of adequate size particles containing polyvinyl alcohol (PVA). The consequence of acute ischemia is septic necrosis of the glandular tissue in a field being supplied by this artery. Further repair processes and fibrosis lead to a reduction of active thyroid hormone synthesis and restriction of thyroid gland. Effects of embolization on angiogenesis, apoptosis and autoimmune reactions contribute to compensation thyroid function and significant reduction a goiter volume in course of Graves' disease. Preoperative selective embolization of a huge goiter or thyroid cancer improves surgery outcomes, reduces the risk of hemorrhage and damage to surrounding tissue. Palliative use of embolization in advanced stages of thyroid cancer reduces symptoms and improves quality of life. Little invasive nature of this procedure, the lack of serious undesirable coincidence makes embolization of thyroid arteries an attractive form of a therapy, which may become a therapeutic option in many difficult clinical situations and improve the clinical effectiveness of treatment of thyroid disease.	f	\N
22299533	Objectification assess the health status of COPD patients poses numerous problems arising from the complexity of both the disease and medical co-operation with the patient. So far, the methods adopted do not correlate with the quality of life. Also, the discrepancy in the evaluation of their symptoms by patients leads to an underestimation of obtained information. Recently proposed a test study of COPD has been validated in many countries and can be implemented into daily practice.	f	\N
22302706	Homozygous germline mutations of the PARK2 gene are responsible for the development of early-onset Parkinson's disease (PD). Homozygous PARK2 mutations have been also detected in lung adenocarcinoma (LADC). However, since heterozygous PARK2 germline mutations are present in a subset of non-PD individuals, the timing for the occurrence of two-hit PARK2 mutations in LADC progression is unclear. Therefore, we comprehensively analyzed mutations, expression and copy number variations of the PARK2 gene in 267 primary LADCs together with the corresponding noncancerous lung cells and 39 LADC cell lines. Heterozygous germline exonic deletions were detected in five patients with LADC, and loss of heterozygosity including the PARK2 locus was detected in 31/267 (11.6%) LADCs. However, homozygous PARK2 inactivation was not detected in any of them, including the five patients with germline mutations. Homozygous PARK2 inactivation was detected in 6/39 (15%) cell lines, two exonic deletions, one exonic duplication, and three point mutations, while heterozygous PARK2 inactivation was detected in two cell lines (both by exonic deletions). These results strongly indicate that somatic PARK2 mutations occur rarely (or do not occur) in LADC development and that germline PARK2 mutations could contribute to LADC progression but not to LADC development.	f	\N
22304951	Coronary computed tomography angiography (CTA) is a highly accurate noninvasive test that is increasingly used in symptomatic patients primarily for the diagnosis of coronary artery disease (CAD). Beyond its proven accuracy, data have now clearly demonstrated the incremental prognostic information available from coronary CTA related to the presence, extent, and severity of obstructive and nonobstructive CAD across a variety of clinical settings and patient populations. Current evidence supports the use of coronary CTA not only for the diagnosis of CAD in appropriately selected symptomatic patients but also to further refine their cardiovascular risk assessment following testing.	f	\N
22306387	Heart disease is one of the leading causes of death in the United States. With the increase in substance abuse, the incidence of acute myocardial infarction (MI) in younger population has been on the rise. Traditionally, cocaine has been blamed for acute MI; however, recently, there have been more incidences of marijuana as an inciting factor. We present a case of marijuana-induced acute MI and discuss the proposed mechanism.	f	\N
22309448	The aetiology of female pattern hair loss (FPHL) is largely unknown. However, it is hypothesized that FPHL and male pattern baldness (AGA) share common susceptibility alleles. The two major susceptibility loci for AGA are the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X-chromosome, and a locus on chromosome 20p11, for which no candidate gene has yet been identified. To examine the role of the AR/EDA2R and 20p11 loci in the development of FPHL using 145 U.K. and 85 German patients with FPHL, 179 U.K. supercontrols and 150 German blood donors. Patients and controls were genotyped for 25 single nucleotide polymorphisms (SNPs) at the AR/EDA2R locus and five SNPs at the 20p11 locus. Analysis of the AR/EDA2R locus revealed no significant association in the German sample. However, a nominally significant association for a single SNP (rs1397631) was found in the U.K. sample. Subgroup analysis of the U.K. patients revealed significant association for seven markers in patients with an early onset (P = 0·047 after adjustment for the testing of multiple SNPs by Monte Carlo simulation). No significant association was obtained for the five 20p11 variants, either in the overall samples or in the analysis of subgroups. The observed association suggests that the AR/EDA2R locus confers susceptibility to early-onset FHPL. Our results do not implicate the 20p11 locus in the aetiology of FPHL.	f	\N
22310615	Due to the severe shortage of deceased donors in Japan, ABO-incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved; the rates of graft survival among these patients are currently similar to those of recipients of ABO-compatible grafts. Our single-center experience describing the immunosuppressive protocols, complications, and grafts survivals is documented in this study. Among 123 patients with end-stage renal disease who underwent living donor kidney transplantation between January 1999 and December 2010, 25 cases were ABO-incompatible grafts. All of these patients were followed until August 2011. Analyzing these patients, we focused on their immunosuppressive protocols, complications, and graft survivals. Patient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and an intractable acute cellular rejection episode, 1 patient an antibody-mediated rejection, and 6 patients had acute cellular rejection episodes. However, there were no severe complications. Although ABO-incompatible kidney transplantation is a high-risk procedure, a short-term graft survival rate of 100% may be expected due to recent significant improvements in desensitization and recipient management.	f	\N
22312826	Combination anti-HIV therapies revolutionized patient life expectancy in the mid-1990's. Afterwards, in the early 2000's, research focused on the adverse effects caused by HIV drugs. Among these, the most serious ones are myocardial infarction at young age, disturbances of kidney function, liver disorders, pancreatitis and osteoporosis. The worsening of prognosis, for instance in respect of cardiac diseases, observed approximately five years ago in patients due to pauses in HIV medication, has changed perspective. Currently it is being discussed whether the overall prognosis will be improved with HIV medication started as early as possible.	f	\N
22318137	Herpes simplex virus 1 (HSV-1) and HSV-2 are medically significant pathogens. The development of an effective HSV vaccine remains a global public health priority. HSV-1 and HSV-2 immunodominant "asymptomatic" antigens (ID-A-Ags), which are strongly recognized by B and T cells from seropositive healthy asymptomatic individuals, may be critical to be included in an effective immunotherapeutic HSV vaccine. In contrast, immunodominant "symptomatic" antigens (ID-S-Ags) may exacerbate herpetic disease and therefore must be excluded from any HSV vaccine. In the present study, proteome microarrays of 88 HSV-1 and 84 HSV-2 open reading frames(ORFs) (ORFomes) were constructed and probed with sera from 32 HSV-1-, 6 HSV-2-, and 5 HSV-1/HSV-2-seropositive individuals and 47 seronegative healthy individuals (negative controls). The proteins detected in both HSV-1 and HSV-2 proteome microarrays were further classified according to their recognition by sera from HSV-seropositive clinically defined symptomatic (n = 10) and asymptomatic (n = 10) individuals. We found that (i) serum antibodies recognized an average of 6 ORFs per seropositive individual; (ii) the antibody responses to HSV antigens were diverse among HSV-1- and HSV-2-seropositive individuals; (iii) panels of 21 and 30 immunodominant antigens (ID-Ags) were identified from the HSV-1 and HSV-2 ORFomes, respectively, as being highly and frequently recognized by serum antibodies from seropositive individuals; and (iv) interestingly, four HSV-1 and HSV-2 cross-reactive asymptomatic ID-A-Ags, US4, US11, UL30, and UL42, were strongly and frequently recognized by sera from 10 of 10 asymptomatic patients but not by sera from 10 of 10 symptomatic patients (P < 0.001). In contrast, sera from symptomatic patients preferentially recognized the US10 ID-S-Ag (P < 0.001). We have identified previously unreported immunodominant HSV antigens, among which were 4 ID-A-Ags and 1 ID-S-Ag. These newly identified ID-A-Ags could lead to the development of an efficient "asymptomatic" vaccine against ocular, orofacial, and genital herpes.	f	\N
22319048	Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.	f	\N
22326991	After age, the second largest risk factor for Alzheimer's disease (AD) is apolipoprotein E (APOE) genotype, where APOE4 is associated with lower apoE protein levels, more severer brain pathology, enhanced inflammation and disease. Small peptides corresponding to the receptor-binding region of apoE mimic the anti-inflammatory activity of the apoE holoprotein. These apoE mimetics greatly improve behavioral outcomes and neuronal survival in head trauma models that display AD pathology and neuronal loss. To determine whether apoE mimetics change behavior, inflammation and pathology in CVND-AD (SwDI-APP/NOS2(-/-)) transgenic mice. Starting at 9 months, apoE peptides were subcutaneously administered 3 times per week for 3 months followed by behavioral, histochemical and biochemical testing. Treatment with apoE mimetics significantly improved behavior while decreasing the inflammatory cytokine IL-6, neurofibrillary tangle-like and amyloid plaque-like structures. Biochemical measures matched the visible pathological results. Treatment with apoE mimetics significantly improved behavior, reduced inflammation and reduced pathology in CVND-AD mice. These improvements are associated with apoE-mimetic-mediated increases in protein phosphatase 2A activity. Testing in additional AD models showed similar benefits, reinforcing this novel mechanism of action of apoE mimetics. These data suggest that the combination of anti-inflammatory and neuroprotective activities of apoE mimetics represents a new generation of potential therapeutics for AD.	f	\N
22333444	To investigate the feasibility and safety of unilateral incision hybrid fixation using pedicle screws and a translaminar screw in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). From January to June 2010, 18 patients with single-level lumbar disc disease were treated with MIS-TLIF under METRx(TM) X-tube. After decompression and fixation using unilateral pedicle screws, a translaminar screw was inserted from the same incision to the other side. The results of perioperative parameters, radiographic images and clinical outcomes were assessed. All patients underwent MIS-TLIF were accomplished unilateral hybrid fixation without any neural complication. The average operative time was (107 ± 19) min, the average operative blood loss was (62 ± 21) ml, and the average postoperative ambulation time was (21 ± 5) h. The average length of translaminar facets screw was (52 ± 2) mm, and the postoperative images showed all screws penetrate through facets joint. During the follow-up the visual analogue scale and Oswestry disability index scores were significant improved compared with preoperative (F = 42.221 - 259.833, P < 0.01). Bilateral hybrid fixation could be completed through unilateral incision by pedicle screws and a translaminar screw in MIS-TLIF, and the advantage including less invasion, quickly recovery, short operative time, and saving fixation cost.	f	\N
22335481	Optical imaging has seen significant developments over the past decade as an investigational tool for in-vivo visualization of cellular and sub-cellular events. With the recent addition of optoacoustic (photoacoustic) methods, in particular multi-spectral opto-acoustic tomography (MSOT), to the already rich armamentarium of photonic methods the capacity of optical molecular imaging across scales has widened significantly. MSOT brings unique features into optical imaging, namely high resolution optical imaging over several millimeters to centimeters of tissue depth and the ability to simultaneously resolve multiple tissue molecules and extrinsically administered optical or optoacoustic agents with physiological or molecular specificity. Here, we discuss the implications of utilizing MSOT in the context of drug discovery and review suitable optoacoustic agents against disease and drug efficacy biomarkers. The combination of existing knowledge on generating optical targeted contrast, with the high resolution deep tissue visualization offered by MSOT, allows for the development of next-generation biological optical imaging and corresponding drug discovery applications.	f	\N
22337313	Rubella virus (RV) usually causes a mild disease. However, infection during the first trimester of pregnancy often leads to severe birth defects known as congenital rubella syndrome (CRS). Although wild-type RVs exist and circulate worldwide, their genotypes remain unknown in many countries. The aim of this study was to identify the molecular characteristics of RVs found in Vietnam during the years 2009-2010 and to provide the first data concerning RV genotypes in this country. Throat swab samples were collected between 2009 and 2010 from four CRS cases and nine rubella infection cases visiting one Children's Hospital and one outpatient clinic in Ho Chi Minh City. The 739-nucleotide coding region of the RV E1 gene recommended by the World Health Organization was amplified by reverse transcriptase PCR, and the resulting DNA fragments were then sequenced. Sequences were assigned to genotypes by phylogenetic analysis with RV reference strains. RV RNA was detected in 11 clinical specimens. Phylogenetic analysis of the sequences showed that all 11 strains belonged to 2B genotype. Several variations in amino acids were found, among which five changes were involved in the B and T cell epitopes. These data indicate that viruses of genotype 2B were circulating in Vietnam. The increasing information about RV genotype in Vietnam should aid in the control of rubella infection and CRS in this country.	f	\N
22339380	Acute pancreatitis is an acute inflammatory condition of the pancreas, which might extend to local and distant extrapancreatic tissues. The global incidence varies between 17.5 and 73.4 cases per 100,000 and the pathogenesis recognizes alcohol exposure and biliary tract disease as the leading causes, ahead of post-endoscopic retrograde cholangiopancreatography, drugs and abdominal trauma. The diagnosis of acute pancreatitis is substantially based on a combination of clinical signs and symptoms, imaging techniques and laboratory investigations. Contrast-enhanced computed tomography is the reference standard for the diagnosis, as well as for establishing disease severity. The assessment of pancreatic enzymes, early released from necrotic tissue, is the cornerstone of laboratory diagnosis in this clinical setting. Although there is no single test that shows optimal diagnostic accuracy, most current guidelines and recommendations indicate that lipase should be preferred over total and pancreatic amylase. Although a definitive diagnostic threshold cannot be identified, cut-offs comprised between ≥ 2 and ≥ 4 times the upper limit of the reference interval are preferable. The combination of amylase and lipase has been discouraged as although it marginally improves the diagnostic efficiency of either marker alone, it increases the cost of investigation. Some interesting biomarkers have been also suggested (e.g., serum and urinary trypsinogen-1, -2 and -3, phospholipase A2, pancreatic elastase, procalcitonin, trypsinogen activated protein, activation peptide of carboxypeptidase B, trypsin-2-alpha1 antitrypsin complex and circulating DNA), but none of them has found widespread application for a variety of reasons, including the inferior diagnostic accuracy when compared with the traditional enzymes, the use of cumbersome techniques, or their recent discovery. The promising results of recent proteomics studies showed that this innovative technique might allow the identification of changes characterizing pancreatic tissue injury, thus highlighting new potential biomarkers of acute pancreatitis.	f	\N
22353988	Several studies have reported that patients with essential tremor (ET) may also have mild cognitive impairment. Event-related potentials (ERPs) involve cognitive processes in the brain. No detailed investigation has been conducted into auditory ERPs (AERPs) to detect the subclinical cognitive dysfunction in patients with ET. Therefore, this study aimed to clarify the usefulness of AERPs in ET-related cognitive impairment. The AERPs were obtained by using an oddball paradigm in 27 patients with ET and 27 age-matched control subjects. The mean latency and amplitude of the ERPs were compared between the two groups. The correlation between disease duration and the mean values of all components of the potentials was assessed. The association between tremor severity and potentials was also evaluated. The patients with ET showed significant prolongation of all components of the ERP latencies at each electrode site. The N200 and P300 amplitudes were reduced in the ET group. Interestingly, the significant prolongation of N100 and N200 latencies correlated with disease duration, and N200 latencies appeared significantly longer in patients with severe tremor. Significant differences were found between the components of the AERPs and tremor severity and disease duration. This finding implies that ERPs may be useful in evaluating the cognitive functions in ET and that those AERP abnormalities may appear before clinical presentation.	f	\N
22356008	A 22 year old female with valvular heart disease, moderate mitral valve insufficiency, moderate aortic insufficiency, extensive aneurysmal dilatation of the entire ascending aorta and arch, and segmental dilatation of descending aorta underwent entire anterior aortic replacement. We performed aortic root and valve replacement with a composite graft, followed by coronary artery reimplantation using the Bentall and De Bono technique. Simultaneously, we carried out a graft replacement of the transverse arch and descending aortic aneurysms with a woven Dacron graft using the Elephant Trunk technique. The goal of this surgery was to correct or optimally treat the multiple sites of aortic disease. To the best of our knowledge, there is no reported case from Pakistan with extensive aortic grafting from root to descending aorta using the Bentall and Elephant Trunk technique simultaneously.	f	\N
22363380	The redox system is an important anti-oxidative system composed of thioredoxin, thioredoxin reductase, and peroxiredoxin (PRx). The fine details of PRx expression and its protective effects in various cells in cardiovascular tissue under oxidative stress created by hydrogen peroxide have not been fully elucidated. Oxidative stress was induced by adding hydrogen peroxide at 0.25 mM for 2 hours to rat neonatal cardiomyocytes (rCMCs), rat vascular smooth muscle cells (rVSMCs), and human umbilical vein endothelial cells (HUVECs). Apoptosis was quantified by flow cytometry and the expression patterns of the six PRx isoforms were evaluated by western blotting in the three cell lines after hydrogen peroxide stimulation. Apoptosis and the cell survival signal pathway were evaluated by PRx1 gene delivery using lentiviral vector in hydrogen peroxide stimulated rCMCs versus green fluorescence protein gene delivery. Hydrogen peroxide induced 25% apoptosis in rCMCs. Furthermore, the PRx1 and 5 isoforms were found to be overexpressed in hydrogen peroxide treated rCMCs, and PRx1 overexpression by gene delivery was found to reduce hydrogen peroxide induced rCMCs apoptosis significantly. In addition, this effect was found to originate from cell survival pathway modification. Hydrogen peroxide induced significant oxidative stress in rCMCs, rVSMCs, and HUVECs, and PRx1 overexpression using a lentiviral vector system significantly reduced hydrogen peroxide induced rCMCs apoptosis by upregulation of cell survival signals and downregulation of apoptotic signals. These findings suggest that PRx1 could be used as a treatment strategy for myocardial salvage in conditions of oxidative stress.	f	\N
22363739	Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia. We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a "mild-to-moderate" pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as "avoidable" mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored. The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.	f	\N
22365640	For an evaluation of the progress achieved in the field of kidney cancer care in the Netherlands in the last decades, we described trends in incidence, treatment, mortality and relative survival. All adult patients newly diagnosed with kidney cancer between 1989 and 2009 (N=32,545) were selected from the Netherlands Cancer Registry. Age-standardised incidence and mortality rates were calculated. Follow-up was completed until January 2010. In order to assess trends estimated annual percentages of change (EAPC) were estimated. The incidence of kidney cancer has been fairly stable between 1989 and 2001 with a European Standardised Rate of approximately 11 per 100,000 person years (PY). Since 2001 the incidence increased to 13 per 100,000 PY in 2009 (EAPC: 2.4%; 95%confidence interval (CI): 1.5 to 3.4%). The mortality rate decreased slightly over time, from 6.2 per 100,000 PY in 1989 to 5.6 in 2010. No changes in treatment were observed, except for the introduction of targeted therapies for stage IV disease, since 2005. The 5-year relative survival improved from 51% in 1989-1994 to 58% in 2005-2009 (EAPC: 0.9%; 95%CI 0.7 to 1.2%). Improvement in survival was especially seen in males, younger age groups and low stages. The incidence of kidney cancer has increased slightly, and survival improved modestly, resulting in a decreasing mortality. A positive effect of the introduction of targeted therapies for metastatic kidney cancer was observed in 1-year relative survival. For progress in kidney cancer care, effective prevention strategies and new therapies remain warranted.	f	\N
22370242	This review describes the features of modern infrared imaging technology and the standardization protocols for thermal imaging in medicine. The technique essentially uses naturally emitted infrared radiation from the skin surface. Recent studies have investigated the influence of equipment and the methods of image recording. The credibility and acceptance of thermal imaging in medicine is subject to critical use of the technology and proper understanding of thermal physiology. Finally, we review established and evolving medical applications for thermal imaging, including inflammatory diseases, complex regional pain syndrome and Raynaud's phenomenon. Recent interest in the potential applications for fever screening is described, and some other areas of medicine where some research papers have included thermal imaging as an assessment modality. In certain applications thermal imaging is shown to provide objective measurement of temperature changes that are clinically significant.	f	\N
22383586	To report the annual incidence of occupational diseases (ODs) in economic sectors in The Netherlands. In a 5-year prospective cohort study (2009-2013), occupational physicians were asked to participate in a sentinel surveillance system for OD notification. The inclusion criteria for participation were (1) covering a population of employees, (2) reporting the economic sectors and the size of their employee population and (3) willingness to report all diagnosed ODs. In this study, an OD was defined as a disease with a specific clinical diagnosis that was predominantly caused by work-related factors. The economic sectors (n=21) were defined according the NACE (Nomenclature des Activités Économiques dans la Communauté Européenne) classification. In a total working population of 514,590 employees, 1782 ODs were reported over 12 months in 2009. The estimated annual incidence for any OD was 346 (95% CI 330 to 362) per 100,000 worker-years. Of all the ODs, mental diseases were reported most frequently (41%), followed by musculoskeletal (39%), hearing (11%), infectious (4%), skin (3%), neurological (2%) and respiratory (2%) diseases. The four economic sectors with the highest annual incidences per 100,000 workers were construction (1127; 95% CI 1002 to 1253), mining and quarrying (888; 95% CI 110 to 1667), water and waste processing (832; 95% CI 518 to 1146) and transport and storage (608; 95% CI 526 to 690). ODs are reported in all economic sectors in The Netherlands. Up to 91% of all ODs are mental, musculoskeletal and hearing diseases. Efforts to increase the effective assessment of ODs and compliance in reporting activities enhance the usability of incidence figures for the government, employers and workers.	f	\N
22394620	The longitudinal degradation mechanism of extracellular matrix (ECM) in the interbertebral disc remains unclear. Our objective was to elucidate catabolic and anabolic gene expression profiles and their balances in intervertebral disc degeneration using a static compression model. Forty-eight 12-week-old male Sprague-Dawley rat tails were instrumented with an Ilizarov-type device with springs and loaded statically at 1.3 MPa for up to 56 days. Experimental loaded and distal-unloaded control discs were harvested and analyzed by real-time reverse transcription-polymerase chain reaction (PCR) messenger RNA quantification for catabolic genes [matrix metalloproteinase (MMP)-1a, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5], anti-catabolic genes [tissue inhibitor of metalloproteinases (TIMP)-1, TIMP-2, and TIMP-3], ECM genes [aggrecan-1, collagen type 1-α1, and collagen type 2-α1], and pro-inflammatory cytokine genes [tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, and IL-6]. Immunohistochemistry for MMP-3, ADAMTS-4, ADAMTS-5, TIMP-1, TIMP-2, and TIMP-3 was performed to assess their protein expression level and distribution. The presence of MMP- and aggrecanase-cleaved aggrecan neoepitopes was similarly investigated to evaluate aggrecanolytic activity. Quantitative PCR demonstrated up-regulation of all MMPs and ADAMTS-4 but not ADAMTS-5. TIMP-1 and TIMP-2 were almost unchanged while TIMP-3 was down-regulated. Down-regulation of aggrecan-1 and collagen type 2-α1 and up-regulation of collagen type 1-α1 were observed. Despite TNF-α elevation, ILs developed little to no up-regulation. Immunohistochemistry showed, in the nucleus pulposus, the percentage of immunopositive cells of MMP-cleaved aggrecan neoepitope increased from 7 through 56 days with increased MMP-3 and decreased TIMP-1 and TIMP-2 immunopositivity. The percentage of immunopositive cells of aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with decreased TIMP-3 immunopositivity. In the annulus fibrosus, MMP-cleaved aggrecan neoepitope presented much the same expression pattern. Aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with increased ADAMTS-4 and ADAMTS-5 immunopositivity. This rat tail sustained static compression model mimics ECM metabolic imbalances of MMPs, aggrecanases, and TIMPs in human degenerative discs. A dominant imbalance of MMP-3/TIMP-1 and TIMP-2 relative to ADAMTS-4 and ADAMTS-5/TIMP-3 signifies an advanced stage of intervertebral disc degeneration.	f	\N
22407767	Cryptic subtelomeric chromosomal aberrations are responsible for 5-10% of moderate/severe and 1% of mild intellectual disability. Unbalanced subtelomeric chromosomal rearrangements result in variable phenotypes which seem to be highly influenced by both the size of the duplication/deletion and the chromosomes involved in the translocation. We report on three related patients with moderate intellectual disability, language delay, hypotonia, facial dysmorphism, cardiac anomalies, scoliosis, and kyphosis in whom a familial (maternal) unbalanced submicroscopic translocation was found by subtelomeric fluorescence in situ hybridization (FISH). This rearrangement resulted in a partial trisomy 10pter and partial monosomy 21qter. The karyotype was 46,XY.ish der(21)t(10;21)(p14;q22.2). Confirmation of a 6.7 Mb size distal duplication of the p15.3-14 region of chromosome 10 and a 5.6 Mb distal deletion of the q22.2-22.3 region of chromosome 21 was obtained by array-CGH. To our best knowledge, such a composition of subtelomeric unbalanced translocations has not yet been published. Detection of this aberration in successive pregnancies of carrier members of the family by prenatal FISH could prevent the recurrence of the disease. Furthermore, detection of the rearrangements and identification of genes located in the chromosomal regions involved might be of interest.	f	\N
22412958	This study identified sex differences in progression of cutaneous melanoma. Of 7,338 patients who were diagnosed as an invasive primary CM without clinically detectable metastases from 1976 to 2008 at the University of Tuebingen in Germany, 1,078 developed subsequent metastases during follow up. The metastatic pathways were defined in these patients and analyzed using the Kaplan-Meier method. Multivariate survival analysis was performed using Cox modeling. In 18.7% of men and 29.2% of women (P<0.001) the first metastasis following diagnosis of primary tumor was locoregional as satellite/in-transit metastasis. The majority of men (54.0%) and women (47.6%, P = 0.035) exhibited direct regional lymph node metastasis. Direct distant metastasis from the stage of the primary tumor was observed in 27.3% of men and 23.2% of women (P = 0.13). Site of first metastasis was the most important prognostic factor of survival after recurrence in multivariate analysis (HR:1.3; 95% CI: 1.0-1.6 for metastasis to the regional lymph nodes vs. satellite/in-transit recurrence, and HR:5.5; 95% CI: 4.2-7.1 for distant metastasis vs. satellite/in-transit recurrence, P<0.001). Median time to distant metastasis was 40.5 months (IQR, 58.75) in women and 33 months (IQR, 44.25) in men (P = 0.002). Five-year survival after distant recurrence probability was 5.2% (95% CI: 1.4-2.5) for men compared with 15.3% (95% CI: 11.1-19.5; P = 0.008) for women. Both, the pattern of metastatic spread with more locoregional metastasis in women, and the time course with retracted metastasis in women contributed to the more favorable outcome of women. Furthermore, the total rate of metastasis is increased in men. Interestingly, there is also a much more favorable long term survival of women after development of distant metastasis. It remains a matter of debate and of future research, whether hormonal or immunologic factors may be responsible for these sex differences.	f	\N
22417127	In approximately 5-8% patients with primary ovarian insufficiency (POI), the disease is caused by an autoimmune process made evident by the appearance of autoantibodies against steroidogenic enzymes (SCA-POI). Anti-müllerian hormone (AMH) is the best marker of the residual follicular pool. To evaluate the rate of loss of the residual follicle pool in women with SCA-POI after clinical diagnosis. One hundred and thirty-two women with POI were tested for 21-hydroxylase autoantibodies, 17α-hydroxylase autoantibodies and P450scc autoantibodies, and 35 patients with SCA-POI were identified. AMH was analysed at the time of the first visit in all women with POI, and in follow-up, serum samples were taken 1-3 years after in 11 women with SCA-POI and detectable AMH. 12/35 (35%) women with SCA-POI had AMH levels within the normal range at the time of first sampling, as compared to 6/97 (6%) with idiopathic POI (P < 0·001). 11/17 (65%) women with SCA-POI with <6 years disease duration had normal serum AMH concentration. A progressive decline in AMH concentration was observed at longitudinal follow-up in all 11 AMH-positive women with SCA-POI, at an estimated average rate of 1·6 μg/l AMH/year (corresponding to an average 57% of preserved follicle pool/previous year) (R(2)  = 0·219, P = 0·028). After 6 years of disease duration, only 1/18 (6%) women with SCA-POI had detectable levels of AMH, similar to women with idiopathic POI (5/78, 6%). Most women with SCA-POI present at clinical diagnosis with a preserved follicle pool that is progressively lost within a few years.	f	\N
22426166	Natural killer (NK) cells are the effector cells of innate immunity that respond to infection and tumor. Interactions between killer cell immunoglobulin like receptors (KIR) and human leukocyte antigen (HLA) class I molecules regulate NK cells responses to eliminate infected and transformed cells. To investigate the impact of KIR genes, HLA ligand genes, and KIR-HLA combinations on susceptibility to tuberculosis (TB) in Lur population of Iran. The genomic DNA of 50 patients with TB from Lorestan province of Iran was genotyped for sixteen KIR genes and their five major HLA class I ligands were determined by a polymerase chain reaction-sequence-specific primers (PCR-SSP) assay. The results were compared with those of 200 healthy unrelated Iranian individuals. In Lur population of Iran, a significant decrease in frequency of KIR3DS1 was found in TB patients compared to control group (24% vs. 44.5%, OR=0.394, CI=0.194-0.798, p=0.013). Also, among the three activating genes that may use HLA class I molecules as their ligands, a significant decrease was shown in frequency of KIR3DS1 with HLA-B Bw4Ile80 ligand in TB patients compared to control group (4% vs. 23%, OR=0.14, CI=0.033-0.596, p=0.004). These findings imply a genetic imbalance between activating and inhibitory KIR genes and KIR-HLA combinations in Lur TB patients. Low level of activating KIR3DS1 and its combination with HLA-B Bw4Ile80 ligand might have an influence on the susceptibility to TB in Lur population of Iran.	f	\N
22433620	The aim of this study was to define body fat percentiles for German children and adolescents aged 3-16 years using the largest German database. The study population included 11,632 girls and 11,604 boys. Data were pooled from: i) Kiel Obesity Prevention Study (KOPS), acquisition period: 1996-2008, n = 12,237; ii) 'Better diet. More exercise. KINDERLEICHT-REGIONS', acquisition period: 2007, n = 9,405; and iii) examination of Jena schoolchildren, acquisition period: 2005, n = 1,594. Body fat mass was measured by bioelectrical impedance analysis using a population-specific algorithm. Data were weighted to achieve a representative sample for Germany. Percentile curves were constructed by the LMS method and proved by Worm plots and Q-statistic. In both genders, the higher body fat percentile curves sloped downwards to age 7 years, whereas the lower percentiles declined up to 8.5 years. Thereafter fat mass remained nearly constant with age in boys and increased in girls. The 10th percentile achieved a minimum of 10-11% body fat in both genders, whereas the 90th percentile curve fluctuated between 29 and 44% in boys or 30-43% in girls. The association between fat mass and blood pressure was too weak to define disease-related cut-offs. These body fat percentiles are suitable reference values for German children and adolescents.	f	\N
22434759	The aim of our study was to evaluate the physical and sedentary activities and energy expenditure (EE) in a group of children affected by non-alcoholic fatty liver disease (NAFLD), compared with normal and obese subjects, using a physical activity questionnaire (PAQ) and a SenseWear armband (SWA). Forty NAFLD (10 females), 41 lean (NRM; 11 females) and 30 obese (OB; 10 females), age- and pubertal stage-matched, children were included. Sedentary activity (PAQ) was similar in NAFLD and NRM but less in OB, while SWA showed that NAFLD spent less time in physical activity and more in sedentary activities compared with NRM, but not with OB. Insulin sensitivity index result is related to active EE (cal kg(-1)  d(-1) ) in NAFLD, while homeostatic model assessment index result was negatively related to total EE in OB. Regular physical activity must be encouraged in all obese children affected by NAFLD or not, and SWA might be a possible valid tool for evaluating actual EE.	f	\N
22458506	The roles of cysteine protease (CP) enzymes in the biochemistry and infectivity of the three trypanosomal parasitic infections, Chagas' disease, leishmaniasis and human African trypanosomiasis, which have been elucidated over the last three decades are summarized. Inhibitors of these enzymes, which act through trapping the active site cysteine with an electrophilic warhead, hold huge potential as therapeutic agents but the promise of these has yet to be realized in clinical studies. The article addresses aspects that ought to be considered in order to develop orally active CP inhibitors that are safe and effective therapies for trypanosomiasis. This article reviews learnings from CP research in the trypanosomal field and recent advances in developing cysteine protease inhibitors (CPIs) of human cathepsin K, a related enzyme. Considerations such as intra- and extracellular localization of the CPs, off-target activities against human cathepsin enzymes, basic versus neutral and potential pro-drug inhibitors are reviewed. A description of odanacatib, a cathepsin K inhibitor currently in late stage development, is made to illustrate the attributes of a clinically viable CPI. The emerging role of CPs in a wide array of parasitic diseases is highlighted with the vision that CP inhibitors could become the 'β-lactams' of anti-parasitic treatments in the coming decades. New CPI research will see the optimization of intra- and extracellular enzyme targeting, reduction of off-target activities and better understanding of pharmacokinetic-pharmacodynamic interactions which will all lead to compounds with much improved efficacy and viability as clinical therapies.	f	\N
22458804	Over the past few years, there has been a rapid rise in the older segments of the world population, which has brought along with it a major health concern: dementia. Alzheimer's disease, considered to be the most common cause of dementia, has become a prospect feared by the elderly. Inflammation of the brain is strongly implicated in Alzheimer's disease which could be enhanced by systemic inflammation. Periodontitis being a chronic inflammatory condition, which can cause systemic inflammation, the question is whether chronic periodontitis can initiate or hasten the rate of progression of Alzheimer's disease in susceptible individuals. In this article, the authors outline the proposed oral systemic link between periodontitis and Alzheimer's disease.	f	\N
22463746	Evaluation of peritoneal involvement in colonic cancer (CC) can be difficult. We studied pT4N0 cancers and their association with pathological prognostic markers, including tumour budding. Tumours were classified as (i) at the peritoneal surface or free in the peritoneal cavity (pT4a subgroup n = 44); (ii) directly invading adjacent organ (pT4b subgroup n = 8); or (iii) showing inflammatory involvement of the peritoneum (pT4I subgroup n = 25). A published pT3N0 cohort was used to compare Stage II subgroups. Standard pathological markers including tumour budding were assessed. Elastin staining was performed in the pT4I subgroup. Seventy-seven Stage II CCs met inclusion criteria. There was no significant difference in survival across subgroups. pT4b tumours were larger than pT4a tumours (P < 0.001). Over-represented features in pT4a versus pT4b tumours were tumour budding (P = 0.02) and infiltrative margin (P = 0.02). Tumour budding did not predict survival. Using multivariate analysis, neural invasion was the only parameter predictive of survival (hazard ratio = 2.8; 95% CI 1.2-6.4; P = 0.02). Stage II pT4I CCs have a similar outcome to T4a/b tumours. Elastin staining is useful in defining this group. Tumour budding may facilitate peritoneal invasion in pT4a tumours, but does not predict outcome in pT4N0 disease. Only neural invasion independently predicted poor outcome.	f	\N
22466542	Most common type of head and neck malignant tumors is squamous cell carcinoma reaching 3% of all human cancers. Oral squamous cell carcinoma (OSCC) has tendency of increasing incidence and mortality worldwide with an overall 5 year survival rate of <60%. In order to explore this disease, different in vivo mouse models have been introduced. In this study we analyzed clinical and morphological characteristics of OSCC in vivo nude mouse model. 80% of mice which were injected with human oral squamous cancer cells developed orthotopic tumors with the mean volume of 146 mm(3), from which 62% exhibited metastatic spread. Morphology of the cancer tissue was characterized with invasive phenotype and inflammation. Proliferation activity rate of orthotopicly grown tumors were 55,7 ± 4,7 mitotic cells/optical field and displayed weakly developed vascular network. OSCC in vivo orthotopic nude mouse model can mimic pathological and clinical picture of the malignant disease and may be effectively used in oncology research.	f	\N
22472026	Patients with Crohn's disease (CD) may need anti-inflammatory drugs for decades. Anti-TNF-α agents have good efficacy and adverse events similar to placebo in randomized controlled trials (RCTs), but there are still questions about long-term safety and efficacy. In this respect, reports from clinical practice may be useful. We currently report on the clinical experience with infliximab and adalimumab in a single-center cohort of patients with CD. Patients with CD treated with infliximab or adalimumab from 2000 to 2010 were reviewed. Patient and disease characteristics at start, reason for discontinuation, and adverse events were recorded retrospectively. Corticosteroid use, the need for hospitalization, and surgeries before and during anti-TNF-α therapy were recorded. Eighty-three patients had received anti-TNF-α treatment against CD, median treatment duration was 11.4 months (0.2-99.5), and follow-up time 59 months (8-135). Eighteen of 43 patients using corticosteroids at treatment start discontinued corticosteroids during TNF-α therapy. Need for hospitalizations (6.13 vs. 3.28 days/year, p < 0.001) and surgeries (0.56 vs. 0.16 operations/year, p < 0.001) were lower during anti-TNF-α therapy than before treatment. Twenty-six percent discontinued therapy due to adverse events and 26% due to lack or loss of response. Two of four deaths observed during follow-up were believed to be related to anti-TNF-α treatment. Anti-TNF-α therapy was beneficial in many patients with CD, but the majority of patients discontinued treatment during follow-up. Reports from clinical experience with anti-TNF-α treatment may be valuable for clinicians treating patients with CD.	f	\N
22483567	Anti tumor necrosis factor alpha (TNFα) agents have become widely used in pediatric inflammatory bowel disease (IBD). So far, only few studies examined the long-term results of anti-TNFα treatment in children with IBD. The long-term outcome of pediatric patients with IBD was assessed retrospectively in a multicenter cohort of children treated with anti-TNFα beyond induction treatment. Short- and long-term response rates, predictors for loss of response, data on growth and laboratory parameters were assessed. 120 patients [101 crohn's disease (CD), 19 ulcerative colitis (UC) or indeterminate colitis (IC)] received either infliximab or adalimumab. The mean age at initiation of anti-TNFα was 13.4 ± 3.9 years and the median duration of anti-TNFα treatment was 15 months (range: 2-90). Overall, 89% of the cohort experienced short-term response following induction. Response was associated with improvement in weight and BMI Z-scores (p<0.001) but not with linear growth. Responders experienced a significant decrease in erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) during treatment (p<0.001). Albumin and hemoglobin both improved but only albumin increased significantly (p<0.001). The cumulative probability of losing response to anti-TNFα treatment was 17%, 38%, and 49% after 1, 3, and 5 years, respectively. Responders had a significantly lower weight and BMI Z-scores at initiation of anti-TNFα treatment in compared to non-responders (p=0.04 and 0.02 respectively). Our long term cohort supports the current evidence on the effectiveness and safety of anti-TNFα treatment in children with IBD. Response to treatment was interestingly associated with lower weight and BMI.	f	\N
22484574	To determine the incidence of radiographic lumbar spondylosis (LS)and lower back pain, and their risk factors in Japan using a large-scale population from the nationwide cohort Research on Osteoarthritis/osteoporosis Against Disability (ROAD) Study. Participants in the ROAD study who had been recruited between 2005 and 2007 were followed up with lumbar spine radiography for 3 years. A total of 2,282 paired radiographs (75% of the original sample) were scored using Kellgren and Lawrence (KL) grades, and the incidence and progression rate of radiographic LS was analyzed. The incidence of lower back pain was also examined. In addition, associations between risk factors and incident and progressive radiographic LS as well as incident lower back pain were tested. Given a 3.3-year follow-up, the incidence of KL≥2 radiographic LS was 50.0% and 34.4% (15.3% and 10.5% per year), while that of KL≥3 LS was 15.3% and 23.7% (4.6% and 7.2% per year) in men and women, respectively. The progression rate of LS was 20.5% and 27.4% (6.2% and 8.3% per year) in men and in women, respectively. In addition, the incidence of lower back pain was 28.3% and 31.2% (8.6% and 9.5% per year) in men and women. Lower back pain was not significantly associated with incident radiographic LS, while a more severe KL grade at baseline was associated with incident lower back pain. The present longitudinal study revealed a high incidence of radiographic LS in Japan.	f	\N
22484921	Sarcoidosis is a multi-systemic disease. A 21-year-old female patient was admitted to our department with lymphadenopathy, B symptoms, erythema nodosum and joint pain. Sarcoidosis showed a very atypical course, lacking any pulmonary symptoms or typical laboratory values. The diagnosis was finally confirmed histologically and thus various differential diagnoses such as microbiological and malignant diseases could be excluded. Oral steroid medication led to remission.	f	\N
22484998	Populations living in poverty in the developing world suffer a heavy burden caused by infectious diseases, most of them zoonoses. The poorer populations also tend to be marginalised from the health sector and so are many of the diseases that affect them. The poor in every society, and particularly in developing countries, bear a disproportionately high share of the disease burden. There is a broad range of viral, bacterial, mycotic, chlamydial, rickettsial and parasitic diseases of global and regional importance given their major impact on the health and socio-economic development of many populations. Endemic infectious diseases, including zoonoses, together with emerging and re-emerging diseases, are mostly shouldered by poor and vulnerable populations. Livestock are important in supporting the livelihoods of poor farmers, consumers and traders throughout the developing world. The animals of poor people are particularly vulnerable to disease because of costs, absence or unsuitability of the animal health sector, etc. The impact of endemic animal diseases are mainly felt at the farm level, while a broader economic impact can occur with these diseases through the restriction of trade in livestock and their products. Addressing comprehensive and sustainable solutions to public health problems created by endemic infections cannot be achieved solely by the public health sector alone. Partnerships with other sectors, particularly agriculture, environment, education, local administration, will be necessary to contain and effectively control zoonotic and foodborne diseases that affect mainly the poor. International organisations could support developing countries by coordinating national intersectoral activities, promoting appropriate technology and public health education, community participation and encouraging decision-makers to commit themselves. This is the only perspective for improved quality of life of poor and marginalised populations.	f	\N
22485050	Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18-55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ≥ 1:32 in initially seronegative; ≥ 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ≥ 98.0% of subjects had rSBA titers ≥ 1:128. Grade 3 solicited AEs were reported in ≤ 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults.   This study is registered at clinicaltrials.gov NCT00453986.	f	\N
22486286	Patients with chronic kidney disease are exposed to oxidative stress (OS) that contributes to deterioration of health. Decrease in renal excretory capacity contributes to the accumulation of pro-oxidative substances that are detrimental not only to kidney but to the whole organism including the cardiovascular system. Components of antioxidant system play an important role in the elimination of the OS. The monitoring of antioxidant levels and products of oxidative damage in these patients and the correct interpretation of relationship between these markers and the function of kidney and other organs may contribute to the more effective treatment and health improvement of the patients.	f	\N
22494938	The whipworms Trichuris trichiura and Trichuris suis in humans and pigs, respectively, are believed to be two different species yet closely related. Morphologically, adult worms, eggs and larvae of the two species are indistinguishable. The aim of this study was to examine the genetic variation of Trichuris sp. mainly recovered from natural infected pigs and humans. Worm material isolated from humans and pigs living in the same geographical region in Uganda were analyzed by PCR, cloning and sequencing. Measurements of morphometric characters were also performed. The analysis of the ITS-2 (internal transcribed spacer) region showed a high genetic variation in the human-derived worms with two sequence types, designated type 1 and type 2, differing with up to 45%, the type 2 being identical to the sequence found in pig-derived worms. A single human-derived worm showed exclusively the type 2-genotype (T. suis-type) and three cases of 'heterozygote' worms in humans were identified. However, the analysis showed that sympatric Trichuris primarily assorted with host origin. Sequence analysis of a part of the genetically conserved β-tubulin gene confirmed two separate populations/species but also showed that the 'heterozygote' worms had a T. suis-like β-tubulin gene. A PCR-RFLP on the ITS-2 region was developed, that could distinguish between worms of the pig, human and 'heterozygote' type. The data suggest that Trichuris in pigs and humans belong to two different populations (i.e. are two different species). However, the data presented also suggest that cross-infections of humans with T. suis takes place. Further studies on sympatric Trichuris populations are highly warranted in order to explore transmission dynamics and unravel the zoonotic potential of T. suis.	f	\N
22498694	Although many of the effects of estrogens on the brain are mediated through estrogen receptors (ERs), there is evidence that neuroprotective activity of estrogens can be mediated by non-ER mechanisms. Herein, we review the substantial evidence that estrogens neuroprotection is in large part non-ER mediated and describe in vitro and in vivo studies that support this conclusion. Also, we described our drug discovery strategy for capitalizing on enhancement in neuroprotection while at the same time, reducing ER binding of a group of synthetic non-feminizing estrogens. Finally, we offer evidence that part of the neuroprotection of these non-feminizing estrogens is due to enhancement in redox potential of the synthesized compounds.	f	\N
22503230	To investigate whether single nucleotide polymorphisms (SNPs) in interleukin (IL)-1β, IL-6, and IL-12β are associated with the susceptibility and severity of contact lens-related keratitis. Retrospective, case control study. One hundred twelve cases of keratitis and 225 controls were recruited from studies conducted at Moorfields Eye Hospital and in Australia during 2003 through 2005. Buccal swab samples were collected on Whatman FTA cards and were mailed by post for analysis. IL-1β (-31), IL-6 (-174, -572, -597), and IL-12B (3'+1158) genotypes were analyzed with pyrosequencing and analyzed using a regression model for susceptibility (sterile, microbial keratitis, controls) and severity. Statistical significance was set at 0.05. The relative risk of developing contact lens-related keratitis and more severe forms of the disease based on allele, genotype, and haplotype associations. Carriers of IL-6 SNPs were more likely to experience moderate and severe events compared with those with nonmutated genotypes (-174 heterozygous: odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-8.3; homozygous: OR, 6.4; 95% CI, 1.4-28.4; -174/-597: OR, 4.1; 95% CI, 1.6-11.0). More severe keratitis and microbial keratitis were less likely to occur in wearers with the nonmutated IL-6 haplotype (severity OR, 0.4 [95% CI, 0.2-0.7]; microbial OR, 0.6 [95% CI, 0.4-0.9]). Wearers carrying an IL-12B SNP had an increased risk of sterile keratitis (OR, 9.7; 95% CI, 1.2-76.9) compared with controls. The IL-6 SNPs are known to reduce protein expression of this cytokine and thus ocular immune defense, and carriers of these SNPs were more likely to experience more severe and microbial keratitis, suggesting that IL-6 decreases the severity and susceptibility of contact lens-related keratitis. Carriers of a functional SNP of IL-12B that is known to increase IL-12 expression and stability are more likely to experience sterile keratitis, suggesting that this is associated with the intense inflammatory reaction that occurs in this condition.	f	\N
22505009	To evaluate inhibin-A immunoreactivity and its utility in the differential diagnosis of nervous system neoplasms and non-neoplastic lesions. An immunohistochemical study of 252 central and peripheral nervous system tumors and 40 non-neoplastic lesions was undertaken. Brain lesions included the basic spectrum of astrocytic, oligodendroglial, and ependymal neoplasms, as well as glioneuronal, pineal parenchymal, choroid plexus, and embryonal. Meningeal neoplasms, basic peripheral nerve tumors, and uncommon sellar lesions were also assessed. Non-neoplastic lesions included demyelinating disease, progressive multifocal leukoencephalopathy, organizing infarct, and reactive gliosis. Diffuse cytoplasmic, membranous, and perinuclear cytoplasmic staining patterns were observed. Significant immunoreactivity was noted in glioblastoma (12 of 20), pleomorphic xanthoastrocytoma (6 of 10), ganglioglioma (8 of 10), meningioma (14 of 20), and hemangioblastoma (10 of 10). Peripheral nerve and sellar tumors as well as non-neoplastic lesions were entirely immunonegative. In our study that investigated the inhibin-A immunoreactivity in a broad spectrum of nervous system lesions, inhibin-A positivity was established in various low-grade and high-grade central nervous system tumors. Thus, inhibin-A is not a specific marker of hemangioblastoma and may be of limited utility in the differential diagnosis of astrocytic and meningothelial neoplasms. Its pathophysiologic role in these various tumors remains to be determined. Further evaluation of the possible significance of staining patterns and degrees of reactivity relative to pathobiology and/or prognosis significance is required.	f	\N
22507833	Osteoporosis, a major health problem among postmenopausal women, is influenced by dietary factors. The purpose of the present study was to evaluate the hypothesis that erythrocyte levels of n-3 polyunsaturated fatty acid (PUFA) and the dietary intake of fish are associated with risk of osteoporosis and correlate with bone mass in postmenopausal Korean women with the disease. Fifty cases and 100 controls were recruited. Osteoporosis was defined according to the International Society for Clinical Densitometry guideline as a score lower than -2.5 SD below the T-score for lumbar vertebrae L₁-L₄, femoral neck or femoral total. The T-score of the femoral neck was positively correlated with erythrocyte levels of n-3 PUFA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the intake of fish, and was negatively correlated with the ratio of n-6/n-3 PUFA after adjusting for age, years after menopause and height. In addition, the risk of osteoporosis was positively associated with erythrocyte levels of saturated fatty acids but negatively associated with EPA + DHA. Erythrocyte levels of n-3 PUFA and the intake of fish were positively correlated with bone mass. In particular, erythrocyte levels of EPA + DHA reduced the risk of osteoporosis in postmenopausal Korean women.	f	\N
22509749	Mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. Limited attention has been given to the role of mast cells in periodontal diseases, and the effects of mast cell degranulation on the chronic stages of non-allergic inflammation, particularly in periodontitis, are not known. The present study analyzes the relationship between the mast cell degranulation and human periodontal disease progression. A total of 50 clinical specimens including moderate periodontitis (n = 17), advanced periodontitis (n = 18), and healthy control tissues (n = 15) were used in this study. All specimens were fixed in 10% buffered formalin and stained with hematoxylin and eosin for histopathology, with toluidine blue for identifying mast cells, and by immunohistochemistry for the expressions of mast cell tryptase in periodontal tissues. The total and degranulated mast cell densities (per high-power field) were quantified in the specimens. Compared with healthy controls, there were significantly increased both total and degranulated mast cell densities in human moderate (P <0.01) and advanced (P <0.01) periodontitis groups by toluidine blue staining, and there were significantly higher densities of both total and degranulated tryptase-positive mast cell subpopulation in the moderate periodontitis group (P <0.01) and even significantly higher subpopulation densities in the advanced periodontitis group by immunohistochemical staining, in which both total and degranulated mast cell densities were significantly higher in the advanced periodontitis group than those in the moderate periodontitis group (P <0.01) by both toluidine blue staining and immunohistochemical staining. There was significantly more severe periodontal inflammatory pathology in the advanced periodontitis group than in the moderate periodontitis group (P <0.01). These findings indicate a significant correlation among tryptase-positive mast cell density, the degree of their degranulation, and the human periodontitis severity, and the results of this study further indicate that mast cell degranulation appears to be associated with human periodontal disease.	f	\N
22511575	We sought to examine the contemporary use of thrombectomy during primary percutaneous coronary intervention (PCI) in the United States. Adjunctive thrombectomy during primary PCI for patients with ST-segment elevation myocardial infarction (STEMI) has demonstrated mixed results. While earlier studies showed either unfavorable or neutral effects with rheolytic thrombectomy, recent clinical trials have shown benefits with manual or rheolytic thrombectomy when compared to PCI alone. We analyzed data from 122,449 patients undergoing primary PCI for STEMI from 1,181 centers reported to the CathPCI Registry® between July 2009 and December 2010. We used logistic regression analysis to examine factors associated with the use of manual and rheolytic thrombectomy. Thrombectomy was performed in 23,195 patients (18.9%): 22,404 (18.3%) had manual thrombectomy and 791 (0.6%) had rheolytic thrombectomy. The use of manual thrombectomy increased over time (P < 0.05). The use of rheolytic thrombectomy did not change. There was significant variation in the use of thrombectomy across hospitals. The strongest predictors of manual versus no thrombectomy included TIMI 0/1 flow (odds ratio 1.69), younger age (OR 0.90 per 10 year increase), saphenous vein graft (OR 2.22), glycoprotein IIb/IIIa inhibitor (OR 1.34), single-vessel disease (OR 1.13), and year of admission (OR 1.20 per year; all P < 0.001). The strongest predictor of manual versus rheolytic thrombectomy was year of admission (OR 1.23, P < 0.001). Our data show that thrombectomy is performed infrequently in the US during primary PCI for STEMI. There is significant variation in the use of thrombectomy across US hospitals.	f	\N
22515999	Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent-onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option.	f	\N
22523117	Podocyturia, i.e. urinary loss of viable podocytes, may serve as a diagnostic tool for pre-eclampsia and as a marker of active renal disease. The current method to detect podocyturia is technically complex, lengthy and requires a high level of expertise for interpretation. The aim of this study was to develop a new technique for the identification of urinary podocytes, based on the detection of podocyte-specific tryptic peptides by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), which will provide an operator-independent and highly reproducible method. The diagnosis of pre-eclampsia was confirmed in the presence of hypertension (>140/90 mmHg) and proteinuria >0.3 g/24 h urine. The diagnosis of HELLP was confirmed based on the accepted clinical criteria of hemolysis, elevated liver enzymes and low platelet count. Random urine samples within 24 h prior to delivery were collected and centrifuged. One half of the sediment was cultured for 24 h to select for viable cells and then stained with a podocin antibody, followed by a secondary fluorescein isothiocyanate-labeled antibody to identify podocytes. The second half of the pellet was solubilized, digested and analyzed by LC-MS/MS using an internal standard. We have recruited 13 patients with pre-eclampsia and 6 patients with pre-eclampsia/HELLP syndrome. The presence of podocytes was confirmed in all patients by the podocyte culture method. In the respective samples, the presence of a podocin-specific tryptic peptide was confirmed with LC-MS/MS technology. The LC-MS/MS method is a reliable technology for the identification of urinary podocytes, based on the presence of podocyte-specific proteins in the urine.	f	\N
22525341	Epoxyeicosatrienoic acids (EETs) are natural angiogenic mediators regulated by soluble epoxide hydrolase (sEH). Inhibitors of sEH can stabilize EETs levels and were reported to reduce atherosclerosis and inhibit myocardial infarction in animal models. In this work, we investigated whether increasing EETs with the sEH inhibitor t-AUCB would increase angiogenesis related function in endothelial progenitor cells (EPCs) from patients with acute myocardial infarction (AMI). EPCs were isolated from 50 AMI patients and 50 healthy subjects (control). EPCs were treated with different concentrations of t-AUCB for 24h with or without peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662. Migration of EPCs was assayed in trans-well chambers. Angiogenesis assays were performed using a Matrigel-Matrix in vitro model. The expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) mRNA and protein in EPCs was measured by real-time PCR or Western blot, respectively. Also, the concentration of EETs in the culture supernatant was detected by ELISA. The activity of EPCs in the AMI patient group was reduced compared to healthy controls. Whereas increasing EET levels with t-AUCB promoted a dose dependent angiogenesis and migration in EPCs from AMI patients. Additionally, the t-AUCB dose dependently increased the expression of the angiogenic factors VEGF and HIF-α. Lastly, we provide evidence that these effects were PPARγ dependent. The results demonstrate that the sEH inhibitor positively modulated the functions of EPCs in patients with AMI through the EETs-PPARγ pathway. The present study suggests the potential utility of sEHi in the therapy of ischemic heart disease.	f	\N
22527997	Early life stress, such as maternal separation, causes adaptive changes in neural mechanisms that have adverse effects on the neuroplasticity of the brain in adulthood. As a consequence, children who are exposed to stress during development may be predisposed to neurodegenerative disorders in adulthood. A possible mechanism for increased vulnerability to neurodegeneration may be dysfunctional mitochondria. Protection from neurotoxins, such as 6-hydroxydopamine (6-OHDA), has been observed following voluntary exercise. The mechanism of this neuroprotection is not understood and mitochondria may play a role. The purpose of this study was to determine the effects of maternal separation and exercise on mitochondrial function in a rat model of Parkinson's disease. Maternally separated (pups separated from the dam for 3 h per day from postnatal day (P) 2-14) and non-separated rats were placed in individual cages with or without attached running wheels for 1 week prior to unilateral infusion of 6-OHDA (5 μg/4 μl, 0.5 μl/min) into the left medial forebrain bundle at P60. After 2 h recovery, rats were returned to their cages and wheel revolutions recorded for a further 2 weeks. On P72, the rats' motor function was assessed using the forelimb akinesia test. On P74, rats were sacrificed for measurement of mitochondrial function. Exercise increased the respiratory control index (RCI) in the non-lesioned hemisphere of 6-OHDA-lesioned rats. This effect was evident in the striatum of non-separated rats and the prefrontal cortex of maternally separated rats. These results suggest that early life stress may reduce the adaptive response to exercise in the striatum, a major target of dopamine neurons, but not the prefrontal cortex in this model of Parkinson's disease.	f	\N
22531706	To identify the underlying mutation and describe the phenotype in a consanguineous Kurdish family with Leber's congenital amaurosis (LCA)/early onset severe retinal dystrophy (EOSRD). Members of the index family were followed up to 22 years by ophthalmological examinations, including best corrected visual acuity (BCVA), Goldmann visual field (GVF), two-color-threshold perimetry (2CTP) and Ganzfeld electroretinogram (ERG), fundus photographs, fundus autofluorescence (FAF), and optical coherence tomography (OCT). After excluding seven of nine known LCA/EOSRD genes in the index patient, linkage analysis was performed in the family using a microarray followed by microsatellite fine mapping and direct sequencing of candidate genes. RD3 was screened by direct sequencing of 85 independent patients with LCA/EOSRD presenting with a BCVA ≥ 1.0 LogMAR before the age of 2 years to assess the prevalence of RD3 mutations in LCA/EOSRD. Since RD3 and RetGC1 have a functional relation, study authors screened for a modifying effect of RD3 mutations in 17 independent patients with mutations in GUCY2D. BCVA was severely reduced from the earliest examinations (as early as 3 months), never exceeding 1.3 LogMAR. The disease presented as cone-rod dystrophy with dystrophic changes in the macula and bone spicules in the periphery on progression. Linkage analysis narrowed the region of interest towards the LCA12 locus. Direct sequencing of RD3 revealed a homozygous nonsense mutation (c.180C > A) in all affected members tested. Screening of additional unrelated LCA/EOSRD patients revealed only polymorphisms in RD3. This is the second family reported so far with mutations in RD3. Mutations in RD3 are a very rare cause of LCA associated with an extremely severe form of retinal dystrophy.	f	\N
22533114	Although the number of tuberculosis cases in the US is at an all-time low, with progressive declines seen for the past 17 years, many goals in the tuberculosis elimination process remain unrealized. This report describes a cluster of four tuberculosis cases in a family, including one case of acquired multidrug resistant tuberculosis. It also underscores some important issues in tuberculosis control today, including significant disparities in the foreign-born population with multidrug resistant tuberculosis as a looming problem, as well as utilization of therapeutic drug level monitoring in complicated cases.	f	\N
22533233	Hen's egg is one of the main causes of food allergy in children. Accidental exposure is common in food-allergic patients. However, the few studies that analyze this problem focus mainly on peanut allergy. We sought to calculate the frequency of accidental exposure reactions in children allergic to hen's egg during a 12-month period, to analyze the clinical characteristics and circumstances surrounding the reactions, and to identify risk factors for the most severe reactions. Ninety-two egg-allergic children (55 boys; median age, 52 months) were included in the study. A systematic questionnaire about accidental exposure was administered. Reactions were classified as mild, moderate, and severe. Egg white-specific immunoglobulin (Ig) E antibody titers were determined. Nineteen (21%) children had 24 reactions in the previous year (42% mild, 50% moderate, and 8% severe). Most reactions took place at home (50%) under routine circumstances (83%). Children with severe or moderate reactions had higher specific IgE levels to egg white (adjusted odds ratio for every 0.1-unit increase in the decimal logarithm, 1.15; 95% CI, 1.03-1.28; P = .008) and lower serum total IgE (adjusted odds ratio for every 1-unit increase in the decimal logarithm, 0.16; 95% CI, 0.05-0.54; P = .001) than those children with mild or no reactions. Reactions to accidental exposure are frequent in children with egg allergy. The proportion of severe or moderate reactions was 58%. The risk factors for such reactions included high titers of specific IgE to egg white and low titers of serum total IgE.	f	\N
22545160	Successful and sustainable intervention against human helminthiases depends on optimal utilisation of available control measures and development of new tools and strategies, as well as an understanding of the evolutionary implications of prolonged intervention on parasite populations and those of their hosts and vectors. This will depend largely on updated knowledge of relevant and fundamental parasite biology. There is a need, therefore, to exploit and apply new knowledge and techniques in order to make significant and novel gains in combating helminthiases and supporting the sustainability of current and successful mass drug administration (MDA) programmes. Among the fields of basic research that are likely to yield improved control tools, the Disease Reference Group on Helminth Infections (DRG4) has identified four broad areas that stand out as central to the development of the next generation of helminth control measures: 1) parasite genetics, genomics, and functional genomics; 2) parasite immunology; 3) (vertebrate) host-parasite interactions and immunopathology; and 4) (invertebrate) host-parasite interactions and transmission biology. The DRG4 was established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR). The Group was given the mandate to undertake a comprehensive review of recent advances in helminthiases research in order to identify notable gaps and highlight priority areas. This paper summarises recent advances and discusses challenges in the investigation of the fundamental biology of those helminth parasites under the DRG4 Group's remit according to the identified priorities, and presents a research and development agenda for basic parasite research and enabling technologies that will help support control and elimination efforts against human helminthiases.	f	\N
22547770	Crizotinib (PF02341066, Xalkori; Pfizer) was recently approved by the U.S. Food and Drug Administration for treatment of ALK-positive non-small cell lung cancer (NSCLC) as defined by a jointly approved diagnostic test using a break-apart fluorescence in situ hybridization assay. The approval was based on dramatic response rates in ALK-positive NSCLC patients of 54% to 61% in phase I and II trials. To date, the overall disease control rates in these trials are close to 90%. Progression-free survival approaches 10 months. This review focuses on the ALK-inhibitory activity of crizotinib in preclinical and clinical trials that led to approval, as well as the diagnostic methods to classify patients with ALK-positive NSCLC. Although these patients represent a small subset of all patients with NSCLC, the rapid time course from identification of this unique target to an approved targeted therapy with striking benefit serves as a paradigm for the development of targeted therapeutics in an era of personalized medicine.	f	\N
22548237	Ochroconis spp. are dematiaceous fungi and have recently become recognized as the cause of human disease. Infections due to members of this genus have primarily occurred in patients with impaired immunity following organ transplantation or chemotherapy for hematologic malignancies. There is no universally agreed upon therapy or duration of treatment, but amphotericin B and/or triazoles are typically employed. We present a case of Ochroconis gallopava infection in a patient with chronic granulomatous disease (CGD). The organism exhibited elevated minimal inhibitory concentrations against itraconazole (0.5 μg/ml) and voriconazole (2 μg/ml) in comparison with results from other studies reported in the literature. This case illustrates the complexities associated with antibiotic susceptibility testing, selection of appropriate drugs, and management in patients with Ochroconis infections. We also review the literature of human infections with Ochroconis to date, and discuss its microbiology to apprise both clinicians and laboratory personnel of this infrequently encountered but potentially aggressive pathogen.	f	\N
22559253	Polyphenols, a ubiquitous group of secondary plant metabolites sharing at least one aromatic ring structure with one or more hydroxyl groups, represent a large group of natural antioxidants abundant in fruits, vegetables, and beverages, such as grape juice, wine, and tea, and are widely considered to contribute to health benefits in humans. However, little is yet known concerning their bioactive forms in vivo and the mechanisms by which they may alter our metabolome, which ultimately contribute toward disease prevention. Here we report a study to determine the metabolic fate of polyphenolic components in a Chinese tea (Pu-erh) in human subjects using a metabonomic profiling approach coupled with multivariate and univariate statistical analysis. Urine samples were collected at 0 h, 1 h, 3 h, 6 h, 9 h, 12 h, and 24 h within the first 24 h and once a day during a 6 week period including a 2 week baseline phase, a 2 week daily Pu-erh tea ingestion phase, and a 2 week "wash-out" phase, and they were analyzed by gas chromatography mass spectrometry and liquid chromatography mass spectrometry. The dynamic concentration profile of bioavailable plant molecules (due to in vivo absorption and the hepatic and gut bacterial metabolism) and the human metabolic response profile were measured and correlated with each other. This study demonstrates that the metabonomic strategy will enable us to integrate the overwhelming amount of metabolic end points as a systems' response to the absorption, metabolism, and disposition of a multicomponent botanical intervention system, leading to a direct elucidation of their mechanisms of action.	f	\N
22571342	In carcinogenesis, methylation of DNA promoter regions results in inactivation of tumor-suppressing genes. MG98 was designed to inhibit DNA methyltransferases enzyme 1 production. This multicenter study explored two schedules of MG98 with Interferon-α-2β to identify schedule and dose for patients with metastatic RCC. Doses of IFN 9 MIU/MG98 125 mg/m(2) for a continuous schedule and IFN 9 MIU/MG98 200 mg/m(2) for an intermittent schedule were considered the MTDs. Treatment resulted in one PR and eight SD. MG98 combined with IFN was safe and resulted in clinical activity.	f	\N
22573749	The increase of severe cases of acute tonsillitis (AT) is presently marked. Severe cases of AT disturb immune and metabolic homoeostasis initiating the development of disease. Therapy optimization is required to select the best treatment. In patients with severe cases of AT of mixed viral/bacterial etiology before the treatment it is revealed the increase of general activity of lactatedehydrigenase (LDH) and increase of the level of cathode "anaerobic" factions LDH4+5 and the decline of concentration ATP in the blood. There was a compensatory rise of level of ADP and АМP. The substantial decline of serum interferon (CIF) activity and diminishing maintenance of α-interferon (α-IFN) and γ-interferon (γ-IFN) in the blood of the patients, that testified to oppressing of interferonogenesis. Treatment of severe cases of AT of mixed viral/bacterial etiology of modern detoxic preparation reamberin and immunoactive preparation cycloferon combination positively influences the studied laboratory indexes. The improvement of power metabolism is marked, that was characterized by normalization of level adenine nucleotides (ATP, АDP, АМP) and general activity of LDH and its izoenzimes spectrum. At the same time the increase of CIF level is set, maintenances α-IFN and γ-IFN in the blood, that testified to the improvement of interferonogenesis. The results demonstrate the therapeutic potential of reamberin and cycloferon combination for treatment of patients with AT of mixed viral/bacterial etiology.	f	\N
22582962	Infants with viral bronchiolitis are often hospitalised with a proportion requiring respiratory support. The aim of this review was to examine the use of nasal prong continuous positive airway pressure (CPAP) as a management strategy for infants with a diagnosis of bronchiolitis, who required stabilisation and transport to a tertiary centre. A retrospective audit of infants with bronchiolitis requiring CPAP during transport between January 2003 and June 2007. Nasal CPAP was initiated in 54 infants with 51 of these (34 ex-preterm, 17 term) subsequently continuing on CPAP during retrieval. Mean CPAP pressure was 7 cmH(2)O. Oxygenation improved between stabilisation and the end of retrieval (P < 0.01). During retrieval, there was no significant increase in transcutaneous CO(2), no infant required endotracheal ventilation and no adverse events were noted. Five infants were intubated within the first 24 h of admission at the receiving hospital. This review demonstrated that use of nasal prong CPAP to transport infants with bronchiolitis was a safe management strategy in those with moderate to severe disease severity.	f	\N
22595407	The authors used multidetector computed tomography (MDCT) to study the relation between culprit plaque characteristics and cardiac troponin T (cTnT) elevation after percutaneous coronary intervention (PCI). Percutaneous coronary intervention is often complicated by post-procedural myocardial necrosis manifested by elevated cardiac biomarkers. Stable angina patients (n = 107) with normal pre-PCI cTnT levels underwent 64-slice MDCT before PCI to evaluate plaque characteristics of culprit lesions. Patients were divided into 2 groups according to presence (group I, n = 36) or absence (group II, n = 71) of post-PCI cTnT elevation ≥3 times the upper limit of normal (0.010 ng/ml) at 24 h after PCI. Computed tomography attenuation values were significantly lower in group I than in group II (43.0 [26.5 to 75.7] HU vs. 94.0 [65.0 to 109.0] HU, p < 0.001). Remodeling index was significantly greater in group I than in group II (1.20 ± 0.18 vs. 1.04 ± 0.15, p < 0.001). Spotty calcification was observed significantly more frequently in group I than in group II (50% vs. 11%, p < 0.001). Multivariate analysis showed presence of positive remodeling (remodeling index >1.05; odds ratio: 4.54; 95% confidence interval: 1.36 to 15.9; p = 0.014) and spotty calcification (odds ratio: 4.27; 95% confidence interval: 1.30 to 14.8; p = 0.016) were statistically significant independent predictors for cTnT elevation. For prediction of cTnT elevation, the presence of all 3 variables (CT attenuation value <55 HU; remodeling index >1.05, and spotty calcification) showed a high positive predictive value of 94%, and their absence showed a high negative predictive value of 90%. MDCT may be useful in detecting which lesions are at high risk for myocardial necrosis after PCI.	f	\N
22610716	A 320-row multidetector CT provides the capability for prospective electrocardiogram (ECG)-gated coronary CT angiography (CTA) and tube current modulated cardiac function assessment (CFA). We assessed and compared the effective radiation dose of these two modes. On a prospective basis, we performed ECG-gated cardiac CT on 119 patients (87 were males). For heart rates (HRs) </=65 beats/min (bpm), we used one-heartbeat acquisition and half-scan reconstruction. HRs from 66 to 79 bpm and >/=80 bpm were scanned with either two or three heartbeats acquisitions, respectively. We used two types of scans. One type was based on a prospective ECG-gated CTA mode and the other using a tube current modulated CFA mode covering an entire R-R interval. The mean BMI of patients was 25.4 (range 18.8-49.3). Fifty-one patients (42.9 %) underwent CFA scanning, while the remaining 68 (57.1 %) had CTA. The majority of patients completed the scan in a single heartbeat (59.7 %). The mean dose of CTA mode at 65-85 % phase window for one and two heartbeats was 3.68 mSv (2.40-7.23) and 8.61 mSv (6.76-10.60), respectively. The mean dose of CFA mode for a single heartbeat measurement with dose modulation (25 % dose for CFA, and 100 % dose during 65-85 % phase window for CTA) was 6.32 mSv (4.69-8.89). CTA with prospective ECG-gating allows for acceptable image quality and radiation dose. HR reduction is mandatory to minimize radiation exposure. Global left ventricle function can be assessed with a single heartbeat within an acceptable radiation dose.	f	\N
22616529	Global climate warming for the last 10 years actualized the problem of mortality rise in some European countries in anomalous summer heat. Russia faced this problem in July-August 2010 when extreme heat entailed a significant elevation of mortality in 31 regions of the country primarily due to coronary heart disease and cerebrovascular diseases. The analysis of foreign researches has shown that old age and living in cities are leading risk factors of deat in anomalous heat. Experience of the European countries and USA evidences that stay in conditioned apartments and early referral for medical assistance are most effective death preventive measures in heat.	f	\N
22621617	Graves' disease (GD) is one of the most common autoimmune thyroid disorders and has a striking characteristic of female preponderance. The main objective of this study was to investigate whether IL12B gene polymorphisms were associated with either GD itself or with gender bias in GD. GD patients (151 males, 97 females) and 211 healthy control subjects without antithyroid autoantibodies or a family history of autoimmune disorders were recruited for this study. The G/C polymorphism (rs6887695) of the IL12B gene was analyzed using the polymerase chain reaction-restriction fragment length polymorphism, and the deletion and insertion polymorphism (rs41292470) in the IL12B promoter was detected after polyacrylamide gel electrophoresis-silver staining method. There was no significant difference between GD patients and normal subjects, and no differences in frequencies of genotypes or alleles of either polymorphism between male and female GD subjects. We conclude that these IL12B gene polymorphisms were not associated with sex bias in GD and do not confer susceptibility to Graves' disease (GD) in the Chinese population.	f	\N
22626277	Inflammation in the ovary, including ovulation and pelvic inflammatory disease, has been proposed to play a role in the pathogenesis of ovarian cancer. Endometriotic lesions trigger a local inflammatory reaction and have been reported to be associated with an increased risk of epithelial ovarian cancer. However, the precise molecular mechanisms of ovarian cancer arising from endometriosis are still to be elucidated. To clarify the involvement of mismatch repair (MMR) abnormalities in the inflammation-associated malignant transformation of endometriosis, the immunohistochemical expression of mismatch repair proteins (human mutL homolog 1 [hMLH1] and human mutS homolog 2 [hMSH2]) was examined in 27 cases of ovarian endometriosis, 25 cases of ovarian carcinoma accompanied by endometriosis, and 39 cases of solitary ovarian carcinoma. In addition, the relationship between mismatch repair abnormalities including the microsatellite instability, PTEN (phosphatase and tensin homolog) mutation, and clinicopathologic parameters was analyzed. The expression of mismatch repair proteins was stepwisely decreased in endometriosis, ovarian carcinoma accompanied by endometriosis, and ovarian carcinoma. Tumors harboring multiple microsatellite instability (high-frequency microsatellite instability [MSI-H]) were detected in 4 (14.8%) of 27 cases of endometriosis and 7 (30.4%) of 23 cases of ovarian carcinomas. The frequency of PTEN mutations was higher in MSI-H cases than in microsatellite instability-stable (MSI-S) cases. In 2 cases of ovarian carcinoma accompanied by endometriosis, the decreased expression of mismatch repair proteins and MSI-H was observed in both the endometriosis and carcinoma lesions. Clinicopathologically, the MSI-H cases were associated with elevated serum levels of C-reactive protein and higher white blood cell counts. These findings suggest that mismatch repair abnormalities might be involved in the malignant transformation of ovarian endometriosis and that inflammation induces mismatch repair abnormalities during ovarian carcinogenesis arising from endometriosis.	f	\N
22639889	Neuronal protein α-synuclein (α-syn) is an essential player in the development of neurodegenerative diseases called synucleinopathies. A spontaneous autosomal recessive rat model for neurodegeneration was developed in our laboratory. These rats demonstrate progressive increases in α-syn in the brain mesencephalon followed by loss of dopaminergic terminals in the basal ganglia (BG) and motor impairments. The severity of pathology is directly related to the overexpression of α-syn and parallel decrease in dopamine (DA) level in the striatum (ST) of affected rats. The neurodegeneration in this model is characterized by the presence of perikarya and neurites Lewis bodies (LB) and diffuse marked accumulation of perikaryal α-syn in the substantia nigra (SN), brain stem (BS), and striatum (ST) along with neuronal loss. Light and ultrastructural analyses revealed that the process of neuronal degeneration is a 'dying back' type. The disease process is accompanied by gliosis and release of inflammatory cytokines. This neurodegeneration is a multisystemic disease and implicate α-syn as a major factor in the pathogenesis of this inherited autosomal recessive animal model. Decrease dopamine (DA) and overexpression of α-syn in the brain mesencephalon may provide a naturally occurring animal model for Parkinson's disease (PD) and other synucleinopathies that reproduces significant pathological, neurochemical, and behavioral features of the human disease.	f	\N
22644412	To evaluate retrospectively whether technical factors of hepatic arterial embolization affect the prognosis of patients with hepatocellular carcinoma (HCC). Inclusion criteria of this study were the following: (1) patients received embolization as the initial treatment during 2003-2004, (2) Child A or B liver profile, (3) five or fewer HCCs with maximum diameter of 7 cm or smaller, and (4) no extrahepatic metastasis. Patient data were gathered from 43 centers. Prognostic factors were evaluated using univariate and multivariate analyses. Eight hundred fifteen patients were enrolled. The 1-, 3-, 5-, and 7-year overall survival rates were 92.0 % (95 % CI 90.1-93.9), 62.9 % (95 % CI 59.3-66.6), 39.0 % (95 % CI 35.1-43.0), and 26.7 % (95 % CI 22.6-30.8) in all patients. Univariate analysis showed a Child-Pugh class-A, alpha-fetoprotein level lower than 100 ng/ml, tumor size of 3 cm or smaller, tumor number of 3 or fewer, one-lobe tumor distribution, nodular tumor type, within the Milan criteria, stage I or II, no portal venous invasion, use of iodized oil, and selective embolization were significantly better prognostic factors. In the multivariate Cox model, the benefit to survival of selective embolization remained significant (hazard ratio 0.68; 95 % CI 0.48-0.97; p = 0.033). Selective embolization contributes to survival in patients with HCCs.	f	\N
22652723	Anemia is a significant cause of morbidity and lowers the quality of life of patients suffering from chronic kidney disease (CKD). Iron deficiency is the most important cause of erythropoietin (EPO) hyporesponsiveness in CKD. EPO administration significantly increases the costs of CKD management. It follows that paramount importance must be given to enhancing responsiveness to EPO thereby ensuring that the patient derives maximum benefit. Intravenous iron (IVI) administration has been used for decades to replenish body iron stores. Multiple preparations of Iron are available in the market. However, IVI administration is fraught with dangers like adverse drug reactions, susceptibility to infection, and, as recently postulated, direct cellular toxicity. Traditional approaches to IVI administration have focused on multiple administrations of lower doses for fear of adverse reactions. However, recent studies have demonstrated that higher doses can be safely administered in a single infusion, thereby reducing hospitalization costs and patient inconvenience. Newer preparations of IVI are relatively safer, easier to administer and efficacious. Preparations like Iron sucrose, ferumoxytol, ferric carboxymaltose and iron isomaltoside do not require test doses and allow higher doses to be administered at a time with cost and effect benefits.	f	\N
22655515	Recently we reported a cytoplasmic sodium overload to cause a severe osmotic oedema in Duchenne muscular dystrophy (DMD). Our results suggested that this dual overload of sodium ions and water precedes the dystrophic process and persists until fatty muscle degeneration is complete. The present paper addresses the questions as to whether these overloads are important for the pathogenesis of the disease, and if so, whether they can be treated. As a first step, we investigated the effects of various diuretic drugs on a cell model of DMD, i.e. rat diaphragm strips previously exposed to amphotericin B. We found that both carbonic anhydrase inhibitors and aldosterone antagonists were able to repolarise depolarised muscle fibres. Since carbonic anhydrase inhibitors are known to have acidifying effects and this might be detrimental to the ventilation of DMD patients, we mainly concentrated on the modern spironolactone derivative, eplerenone. This drug had a very high repolarizing power, the parameter considered by us as being most relevant for a beneficial effect. In a pilot study we administered this drug to a 22-yr-old female DMD patient who was bound to an electric wheelchair and has had no corticosteroid therapy before. Eplerenone decreased both cytoplasmic sodium and water overload and increased muscle strength and mobility. We conclude that eplerenone has beneficial effects on DMD muscle. In our opinion the cytoplasmic oedema is cytotoxic and should be treated before fatty degeneration takes place.	f	\N
22658853	Pulmonary complications associated with Sjögren syndrome (SS) have attracted attention in recent years. Sjögren syndrome has been associated with small cyst formation in salivary glands, thymus, and lungs and has been recently brought to the forefront by radiologists due to high-resolution techniques. However, pathologists are less aware of this finding unless clinico-radiologic-pathologic correlation is sought. Formation of large bullae in SS is a rare complication with potential for confusion with other diseases. Here, we present the clinical, radiologic, and pathologic findings in 3 patients with SS associated with multiple pulmonary cystic lesions. All 3 patients had a variable mixed restrictive and obstructive component of the disease. There was good correlation with the pulmonary function tests (PFTs), high-resolution computed tomographic scan, and morphology with regard to the restrictive component. The small cysts appear to correlate with the extent of obstructive changes on the PFTs. However, the large bullae do not, implying noncommunication with the conducting airways. This noncorrelation between the PFTs and extent of bullous disease with predominant involvement of lower lobes in SS enables distinction from bullous emphysema. The mechanism of bulla formation in SS appears to be different from bullous emphysema. A check valve mechanism has been proposed previously in SS, which does not explain cyst formation in the thymus. Alternately, inflammation may play a role with the key suspects being CD4 T-helper cells and perhaps NK cells. This is the first report of a clinico-radiologic-pathologic correlation with analysis of lymphocyte subsets.	f	\N
22669091	Aim of the study was to analyze outcome in patients who underwent surgery following type A aortic dissections and to evaluate the long-term survival rates in patients 70 years of age and older and those under 70 years of age, and in males as compared to females. Between September 1997 and October 2008, 154 patients were retrospectively enrolled. There were 102 males (66.2%) and 52 females (33.8%) with a mean age of 63.5±12; seven patients (4.5%) were over 80 years of age, 46 (29.8%) were between 70 and 80 years of age and 101 were under 70 years of age at the time of surgery. We compared patients 70 years of age and older with those under 70 years of age, analyzing the early and long-term survival results and postoperative complications. Overall in-hospital mortality was 17.5% and permanent neurological dysfunction occurred in 10 patients (6.5%). Twenty patients (12.9%) died during follow-up. Among the males, the long-term survival rate was 80%, 68% and 51% at 1, 5 and 10 years, respectively. Among the females, survival rate was 84.6%, 72.3% and 47.5% at 1, 5 and 10 years, respectively. Five- and 10-year survival rates were 78.1% and 59.4%, respectively, for patients under 70 years of age, and 50.8% at 5 years and 26.1% at 10 years for those over 70. Patients might not be excluded from surgical intervention for acute type A aortic dissection (ATAAD) only due to age. It is important to consider biological age and the clinical features of the patients at the time of surgery. Age is a relative but not absolute contraindication for surgery in ATAAD. Long-term survival was not statistically different between males and females.	f	\N
22689018	Ampullary and extensive periampullary lesions can be difficult to treat and often require pancreaticoduodenectomy (PD) for complete removal, even if benign. However, PD may be overtreatment for noninvasive lesions, and pancreas-sparing total duodenectomy (PSTD) is an emerging valid surgical option for selected cases. We reviewed patients undergoing PSTD at our institution over 16 months and a comparison group who had undergone PD for benign duodenal disease over the past 15 years. We also reviewed cases in the English-language literature and performed a meta-analysis of those patients who had undergone PSTD. PSTD had been performed in four patients, who had an average hospital length of stay (LOS) of 13 days; two of them experienced complications. None required conversion to PD, experienced a postoperative fistula or endocrine or exocrine insufficiency, or required intensive care. Two of the PSTDs were performed laparoscopically. Open PD for benign duodenal disease was performed in 22 patients, with overall morbidity and pancreas fistula rates of 82 and 27 %, respectively. The meta-analysis found 128 unique cases of PSTD with morbidity and mortality rates of 46.4 and 2.3 %, respectively. Pancreaticobiliary leak was seen in 20 %, with an average LOS of 17 days. Although PSTD can be used to avoid PD and can be performed laparoscopically, it is technically challenging and still associated with morbidity.	f	\N
22691438	To describe the small retinal and systemic vessel involvement in Takayasu's arteritis. We described 3 patients with Takayasu's arteritis and small retinal vessel occlusion seen in our department between 2004 and 2011. We performed an extensive literature review and provided a global analysis of small retinal vessel involvement in Takayasu arteritis (i.e., total number of patients analyzed=9). Seven patients had small retinal artery occlusion, and two had venous involvement. Four cases were inaugural of the disease (44.4%). Takayasu's arteritis was extended (Type V) in the majority of patients presenting with small retinal vessel occlusion (5/9, 55.6%), and 8/9 reported cases (88.9%) presented with involvement of the supra-aortic branches. Immunosuppressive regimen allowed an improvement in 5/9 patients and stabilization in 1/9, but the situation worsened in 3/9 patients. The visual outcome was severe, and 3/9 patients (33.3%) experienced irreversible blindness. Occlusion of small retinal vessels is a rare and severe microcirculatory complication in Takayasu's arteritis, as well as necrotizing cutaneous vasculitis or myocarditis. Small retinal vessel involvement can be inaugural of the disease and seriously impact the visual prognosis in TA patients.	f	\N
22696253	Accumulating evidence demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) may transdifferentiate into cardiomyocytes and replace apoptotic myocardium so as to improve functions of damaged hearts. However, little information is known about molecular mechanisms underlying myogenic conversion of BMSCs. microRNAs as endogenous noncoding small molecules function to inhibit protein translation post-transcriptionally by binding to complementary sequences of targeted mRNAs. Here, we reported that miR-124 was remarkably downregulated during cardiomyocyte differentiation of BMSCs induced by coculture with cardiomyocytes. Forced expression of miR-124 led to a significant downregulation of cardiac-specific markers-ANP, TNT, and α-MHC proteins as well as reduction of cardiac potassium channel currents in cocultured BMSCs. On the contrary, the inhibition of endogenous miR-124 with its antisense oligonucleotide AMO-124 obviously reversed the changes of ANP, TNT, and α-MHC proteins and increased cardiac potassium channel currents. Further study revealed that miR-124 targeted the 3'UTR of STAT3 gene so as to suppress the expression of STAT3 protein but did not affect its mRNA level. STAT3 inhibitors AG490, WP1066, and S3I-201 were shown to attenuate the augmented expression of ANP, TNT, α-MHC, GATA-4 proteins, and mRNAs in cocultured BMSCs with AMO-124 transfection. Moreover, GATA-4 siRNA reduced the expression of ANP, TNT, α-MHC, and GATA-4 proteins but did not impact STAT3 protein in cocultured BMSCs, indicating GATA-4 serves as an effector of STAT3. In summary, we found that miR-124 regulated myogenic differentiation of BMSCs via targeting STAT3 mRNA, which provides new insights into molecular mechanisms of cardiomyogenesis of BMSCs.	f	\N
22697349	α-1 anti-trypsin (AAT) is the most abundant circulating serine protease inhibitor (serpin) and an acute phase reactant. Systemic deficiency in AAT (AATD) due to genetic mutations can result in liver failure and chronic lung disease such as emphysema. Considered the prototypic serpin, the emphysema observed in patients with AATD, consisting of progressive destruction of the alveoli and small airway structures, formed the basis of the protease/anti-protease imbalance theory of chronic obstructive pulmonary disease (COPD). Over the past decade, however, investigations of AATD have described multiple functions of AAT beyond those generally attributed to its antiprotease activity. Evidence now suggests that AAT plays an important role in modulating immunity, inflammation, proteostasis, apoptosis, and possibly cellular senescence programs. When integrated in vivo, these processes contribute to the lung maintenance program which preserves the lung despite a constant bombardment by damage associated molecular patterns (DAMPs) and/or pathogenassociated molecular patterns (PAMPs) initiated by cigarette smoke, pollutants, or infections. In this review, we discuss the clinical aspects of AATD as they pertain to emphysema; including similarities and differences to cigarette smoke-induced emphysema. Examining the lung maintenance program, we next consider the multiple mechanisms of airspace destruction and explore the role AATD contributes. Finally, we consider the data regarding treatment of AATD, including AAT supplementation and its current limitations, and suggest further avenues of research informed by the multiple functions of AAT.	f	\N
22697357	We describe two siblings with epiphora, telecanthus, expressionless face, thick facial skin, bulky nose and profound sensorineural hearing loss. Constellation of these features presented a phenotypic overlap with Blepharo-naso-facial syndrome (BNFS) and Nablus mask-like syndrome (NMLS). They in addition had posterior helical pits. The molecular basis of NMLS is known, while BNFS remains an elusive disorder. We report the first Indian family with features having significant overlap between the two but we attempt to summarize the frequency of reported features and bring out the most consistent features for these two syndromes for the treating clinician.	f	\N
22699458	Innate and adaptive immune responses in neurodegenerative diseases have become recently a focus of research and discussions. Parkinson's disease (PD) is a neurodegenerative disorder without known etiopathogenesis. The past decade has generated evidence for an involvement of the immune system in PD pathogenesis. Both inflammatory and autoimmune mechanisms have been recognized and studies have emphasized the role of activated microglia and T-cell infiltration. In this short review, we focus on dendritic cells, on their role in initiation of autoimmune responses, we discuss aspects of neuroinflammation and autoimmunity in PD, and we report new evidence for the involvement of neuromelanin in these processes.	f	\N
22699661	Hashimoto's thyroiditis as well as lichen planus has been associated to a number of disorders, generally of auto-immune origin. A novel possible association between oral lichen planus (OLP) and Hashimoto's thyroiditis (HT) is here proposed on the basis of a cross-sectional survey. One hundred and five unrelated OLP patients were considered. Diagnosis of HT was based on positive serum anti-TPO, anti-Tg, TSH levels and the typical ultrasound pattern of the thyroid gland. In the present survey, the prevalence of HT in the OLP group was 14.3 % whereas the prevalence of HT-related hypothyroidism in the general population was reported to be equal to 1 %. By Fisher's exact test, it was revealed that the difference between our data and historical prevalence of HT was found statistically significant. Actually, there is no definitive hypothesis that could explain the coexistence of OLP and HT. However, considering the onset timing of HT followed by OLP in 93.3 % of our series, we suspected a causal or predisposing role for HT. Specifically, we believe that in HT patients, circulating thyroid antibodies could contribute to trigger an organ-specific auto-immune response also in the oral mucosa or skin, leading to the development of LP lesions. Because of the large number of cases of asymptomatic chronic auto-immune thyroiditis, it would be useful that women over 40 years of age affected by OLP were screened for thyroid dysfunction, particularly HT.	f	\N
22711587	This study investigated associations between chronic inflammation and coagulation and incident locomotor disability using prospective data from the British Women's Heart and Health Study. Locomotor disability was assessed using self-reported questionnaires in 1999/2000, and 3 and 7 years later. Scores for inflammation and coagulation were obtained from summation of quartile categories of all available biomarkers from blood samples taken at baseline. 534 women developed locomotor disability after 3 years, 260 women after 7 years, while 871 women remained free of locomotor disability over the whole study period. After adjustment for demographic characteristics, lifestyle factors and health conditions, we found associations between inflammation and incident locomotor disability after three (OR per unit increase in score = 1.08, 95 % confidence interval (CI): 1.03, 1.13) and 7 years (OR = 1.10, 95 % CI: 1.03, 1.18) and between coagulation and incident locomotor disability after 3 (OR = 1.06, 95 % CI: 0.98, 1.14) and 7 years (OR = 1.09, 95 % CI: 1.00, 1.18). This corresponds to ORs between 1.8 and 2.4 comparing women with highest to lowest inflammation or coagulation scores. These results support the role of inflammation and coagulation in the development of locomotor disability in elderly women irrespective of their lifestyle factors and underlying age-related chronic diseases.	f	\N
22713729	As science matures, it becomes more mathematical, progressing from enumeration to the use of equations to the formulation of models. Clinical pharmacology has developed to the stage where models play an increasingly important role in predicting and analyzing drug pharmacokinetics and pharmacodynamics, and even in characterizing disease progression and therapeutic response. Useful models have two characteristics that are in ostensible conflict: (i) they must accurately represent the essential features of the underlying system and (ii) the representation must be sufficiently simplified to enable its salient features to be identified and investigated through further experimentation.	f	\N
22726388	Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis. Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein). A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC.	f	\N
22739032	Vascular disease and medical factors are associated with cognitive decline and cardiovascular events. We examined the association between vascular risk factors and events in the Alzheimer's Disease Neuroimaging Initiative cohort. The association between vascular risk factors and cardiovascular events in a cohort of 810 participants, including 400 with mild cognitive impairment, 184 with Alzheimer's, and 226 controls was investigated using a longitudinal hazard model. There were 31 events including 11 strokes, 7 myocardial infarctions, 5 revascularizations, and 8 deaths during an average follow-up of 31 months. Longitudinal cardiovascular event rates were low and similar between diagnostic groups. All baseline vascular risk factors that were expected to be associated with longitudinal cardiovascular events were, or were trending toward, associating with cardiovascular events except atrial fibrillation, depression, and apolipoprotein E genotype. Despite differences in baseline vascular risk factors, longitudinal cardiovascular event rates were similar between diagnostic groups.	f	\N
22740450	Cyclin dependent kinase (CDK) inhibitors, such as flavopiridol, demonstrate significant single-agent activity in chronic lymphocytic leukemia (CLL), but the mechanism of action in these nonproliferating cells is unclear. Here we demonstrate that CLL cells undergo autophagy after treatment with therapeutic agents, including fludarabine, CAL-101, and flavopiridol as well as the endoplasmic reticulum (ER) stress-inducing agent thapsigargin. The addition of chloroquine or siRNA against autophagy components enhanced the cytotoxic effects of flavopiridol and thapsigargin, but not the other agents. Similar to thapsigargin, flavopiridol robustly induces a distinct pattern of ER stress in CLL cells that contributes to cell death through IRE1-mediated activation of ASK1 and possibly downstream caspases. Both autophagy and ER stress were documented in tumor cells from CLL patients receiving flavopiridol. Thus, CLL cells undergo autophagy after multiple stimuli, including therapeutic agents, but only with ER stress mediators and CDK inhibitors is autophagy a mechanism of resistance to cell death. These findings collectively demonstrate, for the first time, a novel mechanism of action (ER stress) and drug resistance (autophagy) for CDK inhibitors, such as flavopiridol in CLL, and provide avenues for new therapeutic combination approaches in this disease.	f	\N
22744150	To provide information about occurrence and patterns of geriatric morbidity and need for long-term care in patients newly diagnosed with dementia compared to controls without dementia. An analysis of administrative data was conducted to compare the geriatric outpatient diagnoses and the patterns of care dependency of 1,848 incident dementia patients and 7,385 matched non-dementia controls older than 65 years in the incidence year. In most cases the geriatric characteristics show an increased (partly statistically significant) prevalence in the group with dementia as compared to controls. Moreover, dementia patients show a higher number of geriatric comorbidities in contrast to non-dementia controls. Furthermore, the percentage of persons with need for long-term care in the dementia-group is significantly higher than for controls (44.4 vs. 12.9 %). Prevention, early recognition or treatment of attendant symptoms are very important in daily clinical and nursing care in patients with dementia to ameliorate the progression of the disease and to improve the patients' quality of life.	f	\N
22744504	Screening for idiopathic scoliosis is not very popular in Poland. Some Polish towns and cities have prevention programmes aimed at discovering spine dysfunctions and disorders in children and adolescents. An assessment of the angle of trunk rotation (ATR) is a reliable, effective and non-invasive action that allows use to determine trunk asymmetry. Since then the scoliometer has spread throughout the United States and other countries, where it is a popular device in the clinical practice of diagnosing scoliosis. 9,500 children aged 7-10 were examined as part of a disease prevention programme entitled "Poznan Chooses Health - Bad Posture Prophylaxis in Class I-IV Primary School Children in Poznan". The analysis included results obtained in 2010 during initial posture assessment in 1000 children, Trunk asymmetry was measured by means of the Bunnell scoliometer. The measurement of the angle of trunk rotation was the spontaneous standing position with use the scoliometer during bending (Adams forward test) at three levels: proximal thoracic, main thoracic and lumbar. For the proximal thoracic section the 0° ATR value was found in 6 children, values of 1°-3° were recorded in 883 children, values of 4°-6° in 108 children, 7° or higher in 3 of the examined children. For the main thoracic section the 0° ATR value was found in 101 children, values of 1°-3° were recorded in 735 children, 4°-6° in 155 children, 7° or higher in 9 of the examined children. For the lumbar section ATR values of 0°, 1°-3°, 4°-6°, and 7° or higher were found, respectively, in 147, 883, 108 and 11 of the examined children.	f	\N
22744756	In newly diagnosed glioblastoma multiforme, surgery, combined radio and chemotherapy, and adjuvant chemotherapy with temozolomide is the standard of care. Therapy for recurrent glioblastoma is less well established and comprises re-operation, re-irradiation, chemotherapy, targeted therapy, inhibition of neoangiogenesis, and others. In this observational study we recorded the efficacy and toxicity of a combination of procarbazine, carmustine, and vincristine (PBV) for 69 patients with recurrent and/or progressive glioblastoma after surgery, concomitant radio and/or chemotherapy, and adjuvant first-line temozolomide therapy. Of 41 patients evaluable for response by MRI, partial response was observed for one, minor response for three, stable disease for at least 6 weeks for ten, and immediate progression for 27. Median PFS was 15 weeks, and PFS-6 was 21 % for 57 patients who could be followed; 12 other patients were lost to follow-up after application of the first PBV cycle. Grade III or IV leucopenia and/or grade III or IV thrombocytopenia were seen in 26 % and 26 % of cycles, respectively. Haematological complications led to interruption of treatment for four (7 %) patients. Non-haematological toxicity was moderate. Salvage PBV therapy in recurrent and/or progressive glioblastoma, pre-treated with temozolomide-based chemotherapy as first-line treatment, is of limited efficacy with a small number of long-term survivors, but is hampered by relevant myelotoxicity.	f	\N
22753355	Hepatic arterial infusional (HAI) chemotherapy combined with systemic chemotherapy is effective palliative therapy for unresectable colorectal cancer liver metastases (CRLM). Some patients considered for HAI have evidence of minimal extrahepatic disease (EHD), and the role of HAI in these situations is unknown. All patients with unresectable CRLM treated with HAI and systemic chemotherapy from 2000 to 2009 were included. Survival of patients who were ultimately proven to have low-volume EHD was compared to those without EHD. Three hundred seventy-three patients were included in this study. Seventy-nine percent of patients were previously treated with chemotherapy. One hundred forty-five patients (39%) ultimately proved to have EHD. Median overall survival from HAI pump placement in patients without EHD was 32 months compared to 16 months for patients with EHD, P < 0.001. Median overall survival from HAI pump placement in patients with a single site of EHD was 18 months compared to 9 months for those with multiple sites of EHD, P = 0.01. In this study of heavily pre-treated patients, overall survival was favorable in patients who proved to have EHD at one site.	f	\N
22761515	To explore areas of consensus and disagreement concerning the interhospital transfer of patients with a clinical diagnosis of ruptured abdominal aortic aneurysm. A three-round Delphi questionnaire approach was used among vascular and endovascular surgery and emergency medicine specialists to explore patient characteristics and clinical management issues for emergency interhospital transfer. Analysis is based on 38 responses to rounds 2 and 3 (19 vascular surgeons, 6 interventional radiologists, 13 emergency care specialists) with agreement reported when 70% of respondents were in agreement. Initially there was agreement that transfer patients should be <85 years of age, either alert or with fluctuating consciousness, with moderate or minimal systemic disease, needing no/some help with daily living. Round 3 clarified that patients requiring inotropes and those institutionalised for mental infirmity should be transferred. Those with cardiac arrest in current episode should not be transferred. There was no agreement as to whether those institutionalised with physical infirmities, unconscious/intubated patients or those with severe systemic disease should be transferred. Speed was accepted as important, with agreement for specialty trainees to arrange transfer if consultants were not on site. Consultant-consultant discussion was recommended for patients with severe systemic disease. CT confirmation of diagnosis was considered unnecessary before transfer but ultrasound assessment was desirable, and transfers should not be delayed by waiting for specific tests. There was no agreement about blood tests and ECG before transfer or whether blood should accompany the patient being transferred. There was no agreement as to whether specific staff/facilities needed to be in place at the specialist hospital. A systolic blood pressure ≥70 mm Hg was sufficient for transfer without the need for intravenous fluids unless deterioration occurred. There is broad agreement about the type of patient who should be eligible for transfer but disagreements about patient management before and during transfer remain.	f	\N
22766701	Cardiovascular disease (CVD) is one of the main causes of mortality in the world representing around 30% of all deaths. It constitutes also an important factor in morbidity and incapacity. There are several related CVD risk factors such as hypertension, metabolic syndrome (MetS) and hypercoagulability. The exact mechanisms that underlie the relation between those factors and CVD are not sufficiently known yet; pathogenic explanations are lacking also for the mechanisms relating metabolic factors to insulin resistance (IR) and the association with the development of atherosclerosis and thrombosis. The possible links between hypertension, hemostasis alterations and MetS are examined in this report.	f	\N
22766888	Metabolic syndrome (MS) is a cluster of risk factors that predispose to major cardiovascular diseases and its complications, determining liver and kidney impairment. In the last decade, the indications to transplantation are increasing, with a linear incidence of the complications of the procedure. MS represents one of the commonest, being in turn may the consequence of the underlying disease that required the transplantation, or the result of the medical treatment, as well as one of the most important factor influencing the morbidity and mortality of the transplanted patients. Due to the growing incidence of the MS in these patients, it is crucial to focus and clarify the leading causes determining the onset of the metabolic disarrangement, its outcome and the hypothetical mechanism through which the clinicians could reduce the impact of the disease. In fact, prevention, early recognition, and treatment of the factor that could predict the onset or progression of the MS after the transplantation may impact long term survival of patients, that is again the scope of the same transplant. This review will update the different mechanisMS of the pathogenesis of MS in this population, the clinical effects of the presence of the MS, observing the risk factors to be treated before and after the transplantation and suggesting the management of the follow-up.	f	\N
22767670	This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of the investigational oral drug MLN8237 (alisertib), a small-molecule Aurora A kinase (AAK) inhibitor, in 87 adult patients with advanced solid tumors. Sequential cohorts of patients received MLN8237 5 to 150 mg orally once daily or twice daily for 7, 14, or 21 days, followed by 14 days' rest per cycle. MLN8237 pharmacokinetics was characterized, and the relative bioavailability of an enteric-coated tablet (ECT) formulation was evaluated in reference to the original powder-in-capsule (PIC) formulation. Pharmacodynamic effects of MLN8237 on inhibition of AAK activity were evaluated in skin biopsies. Tolerability and response to treatment were assessed. Common toxicities included fatigue, nausea, and neutropenia. Plasma exposures increased dose proportionally (5-150 mg/d), and were similar for PIC and ECT. The terminal half-life was 23 hours. At the maximum tolerated dose of 50 mg twice daily on the 7-day schedule, the mitotic index of the skin basal epithelium was increased within 24 hours after MLN8237 administration on days 1 and 7, a finding consistent with AAK inhibition. One (1%) patient achieved a partial response lasting for more than 1 year and received MLN8237 for 51 cycles; 20 (23%) patients achieved stable disease for ≥3 months. This first-in-human trial of MLN8237 showed tolerability and favorable pharmacokinetics in this patient population. The recommended phase II dose of MLN8237 is 50 mg twice daily orally for 7 days in 21-day cycles, which is being evaluated further in the treatment of various solid tumors and hematologic malignancies.	f	\N
22804715	Peripheral arterial disease (PAD) is a chronic, progressive disease with a significant cardiovascular and cerebrovascular risk burden and a considerable impact on functional capacity and quality of life (QoL). Exercise programmes result in significant improvements in walking distances but long-term effects are uncertain. The aim of this study was to assess the one-year effects of participation in a 12-week supervised exercise programme on functional capacity and QoL for PAD patients. Patients were randomly allocated to a control (n = 16) or an exercise (n = 28) group. Data regarding functional capacity (Walking Impairment Questionnaire WIQ), disease-specific QoL (Intermittent Claudication Questionnaire ICQ) and generic QoL (SF-36) were collected at baseline, 12 weeks and 1 year. At 12 weeks, there was a trend towards improved QoL in both groups, with a tendency for greater improvement in the exercise group (p = 0.066) and a trend towards improved functional capacity (WIQ Stair-climbing p = 0.093) in the exercise group. At 1 year, ICQ scores in the exercise group were considerably better than those in the control group (p = 0.058), reflecting improved QoL and maintenance of benefits. Participation in a supervised exercise programme results in improvements in functional capacity and QoL at 1 year post-participation.	f	\N
22819313	Controversy exists regarding the extent of pelvic lymph node dissection (PLND) in radical prostatectomy (RP) for prostate cancer. Impact of the extent of PLND may be determined by the disease risk. The aim of our study was to find the association between the extent of PLND on biochemical progression and disease risk. The study included 360 consecutive patients treated with RP for clinically localized prostate cancer at our department between 2000 and 2003. Patients were randomized to receive extended PLND (n = 180) and standard PLND (n = 180) at RP. Clinical and pathological data were prospectively collected. The patients did not receive any neoadjuvant or adjuvant therapy. The relation of disease risk and the extent of PLND to biochemical progression-free survival (BPFS) were examined. There were no significant differences in age, prostate-specific antigen, and other preoperative features in patients who underwent standard and extended PLND. Mean patient age was 68 y old and median follow-up was 74 mo. BPFS for the standard PLND group and the extended PLND group was 90.1% and 91.3% in low risk disease (log rank P = 0.807), 73.1% and 85.7% in intermediate risk disease (log rank P = 0.042), and 51.1% and 71.4% in high risk disease (log rank P = 0.036), respectively. In multivariate Cox proportional hazard analysis, extended PLND was an independent prognostic factor of biochemical progression-free survival when adjusting for other clinical and pathologic features. In intermediate and high risk patients, extended PLND positively affects BPFS. In low risk patients, extended PLND may be omitted to reduce operation time and complications.	f	\N
22822599	Proctocolectomy and ileoanal anastomosis as a treatment of ulcerative colitis Sphincter-saving proctocolectomy, construction of ileal pouch (J pouch) and associated ileoanal anastomosis constitute an established surgical procedure in the treatment of patients having ulcerative colitis. The procedure has been found to improve the condition: the patient is usually relieved of medications and possible associated adverse effects, the cancer risk associated with the disease is minimized and the quality of life will improve. The most common complication is inflammation of the ileal pouch, developing in half of the patients.	f	\N
22824112	Metabolomics is the systematic study of the unique chemical fingerprints of small molecules or metabolite profiles that are related to a variety of cellular metabolic processes in a cell, organ, or organism. Although messenger RNA gene expression data and proteomic analyses do not tell the whole story of what might be happening in a cell, metabolic profiling provides direct and indirect physiologic insights that can potentially be detectable in a wide range of biospecimens. Although not specific to cardiac conditions, translating metabolomics to cardiovascular biomarkers has followed the traditional path of biomarker discovery from identification and confirmation to clinical validation and bedside testing. With technological advances in metabolomic tools (such as nuclear magnetic resonance spectroscopy and mass spectrometry) and more sophisticated bioinformatics and analytical techniques, the ability to measure low-molecular-weight metabolites in biospecimens provides a unique insight into established and novel metabolic pathways. Systemic metabolomics may provide physiologic understanding of cardiovascular disease states beyond traditional profiling and may involve descriptions of metabolic responses of an individual or population to therapeutic interventions or environmental exposures.	f	\N
22825384	Asthma is an inflammatory disease of the airways. It is suggested by characteristic history of recurrent episodes of wheezing, breathlessness, chest tightness, and/or cough especially at night or in early morning. In asthmatic patients spirometry or pulmonary function tests demonstrate airflow obstruction that improves significantly, defined as both a 12% and 200 ml improvement in either FEV1 in response to inhaled bronchodilator. Measurement of airways responsiveness to methacholine in specialized pulmonary function laboratories may help to diagnose asthma. The goals for successful management of asthma are to achieve and maintain control of symptoms and to prevent asthma exacerbations.	f	\N
22825649	This review summarizes and discusses the role and efficacy of moisturizers, particularly the more recently introduced ceramide-based formulations, in the skin care regimen of patients with both active and quiescent atopic dermatitis (AD). It is now well established that a complex interplay of environmental and genetic factors are responsible for disease onset and chronicity. Indeed, several novel genetic mechanisms have been recently discovered to be associated with AD pathogenesis. Moreover, it is increasingly recognized that the epidermal barrier plays a critical role in the initiation, perpetuation, and exacerbation of AD. The skin of patients with AD harbors several defects in epidermal barrier function, including filaggrin and ceramides. An improved understanding of these etiopathogenic factors has led to the development of topical ceramide-dominant moisturizers to replace the deficient molecules and re-establish the integrity of barrier defenses. Some of these products have demonstrated efficacy in the treatment of adult and childhood AD that are similar to mid-potency topical steroids. More importantly, they have been shown to be safe with very few associated side-effects. We recommend the addition of such new agents as both the first step of treatment and in the maintenance of clinically quiescent skin of patients with AD.	f	\N
22828371	Due to the limited incidence of posttransplant lymphoproliferative disorders (PTLD) in pediatric liver graft recipients, there is a scarcity of data on the characteristics of the disease in this population. We aimed to analyze the special features and behavior of PTLD arising after pediatric liver transplantation. A comprehensive search of the literature was conducted for the available data on PTLD in pediatric liver recipients pediatric PTLD through a search of Pubmed and Google Scholar using appropriate terms. We sought data on liver recipients younger than 18 years of age at the time of transplantation. From 51 reports, 43 fulfilled the inclusion criteria. Overall 250 cases of PTLD (212 pediatric PTLD) were found from 43 reports. Data on pediatric patients was compared to adults. Pediatric PTLD lesions were more likely of the polymorphic type (P=.004) and polyclonal (when age cut-off was defined at 12 years; P=.023). Remission rates, metastasis frequency and organ involvements were not different between the groups (P>.1 for all). Survival analysis showed no disparity between pediatric PTLD and adult patients (P>.1); but when data was reanalyzed for patients surviving at least 4 months post diagnosis, the log rank test showed that pediatric patients have a superior outcome compared to adults (P=.045). Pediatric liver recipients developing PTLD have relatively better disease presentation and behavior than that in adults. Stomach involvement was also more frequently seen in patients younger than 12 years, and should be more intensively evaluated. Future studies with a prospective approach and larger population size are needed for confirming our results.	f	\N
22828643	Several bacteria cause community-acquired invasive bacterial disease in children; many are vaccine preventable. Knowledge of pathogens causing community-acquired invasive bacterial disease is important when selecting antimicrobial therapy and implementing vaccine prevention strategies. We describe bacteriology of community-acquired invasive disease observed among 31,641 blood and sterile fluid cultures from children aged 28 days to 36 months in 3 Latin American countries over 2 years.	f	\N
22830284	Features of spread of cowpox in the contemporary conditions are examined. A decrease of population immunity to pox in the population of Russia caused by cancellation of pox immunization, hidden circulation of cowpox virus in various species of rodents, as well as lack of vigilance to pathogenic orthopoxviurses in healthcare workers were noted to create the real preconditions for the emergence of infection of humans caused by cowpox virus. Thereby presence of means of express laboratory diagnostics of cowpox and means of effective medical protection for the prevention of development of this disease in the population of Russia becomes an actual necessity.	f	\N
22833442	Multiple myeloma is a heterogeneous disease, which is characterized by the occurrence of specific genomic abnormalities that are both of diagnostic and prognostic relevance. Since the detection of these abnormalities through molecular-genetic techniques is hampered by the overall low percentage of plasma cells present in primary bone marrow aspirates, we assessed the efficacy of these techniques in enriched plasma cell fractions from 61 multiple myeloma patients. Using interphase FISH, genomic abnormalities could be detected in 96% of the enriched samples as compared to 61% in the cultured whole bone marrow samples. We also found that microarray-based genomic profiling of enriched plasma samples facilitates the detection of additional, possibly clinically relevant, genomic abnormalities. We conclude that the genomic delineation of enriched plasma cells from multiple myeloma patients results in a significantly increased detection rate of clinically relevant genomic abnormalities. In order to facilitate molecular-genetic data interpretation, we recommend morphological assessment of plasma cell purity after enrichment.	f	\N
22844693	The restorative integral support (RIS) model is a whole person response that assists people to overcome adversity. The adverse childhood experiences (ACE) Study conducted by Kaiser Permanente and the Centers for Disease Control and Prevention shows the association between stressors in childhood and multiple later-life health and social problems. Older adults experiencing co-occurring disorders are an under-served and vulnerable population where gaps in both practice models and research to inform effective service provision exist. The current empirical case study presents Senior Hope as one social service agency employing RIS to intervene on the linkage between ACEs and co-occurring disorders to assist older adults. RIS usefully articulates the way in which Senior Hope is developing ACE-informed programs that mobilize resilience and recovery to help older adults achieve positive mental health outcomes. Implementation and research on the RIS model is recommended to enhance services for groups with ACE characteristics.	f	\N
22847755	Putative animal reservoirs and environmental samples were studied to investigate potential routes of transmission for indigenous hepatitis E virus (HEV) infection in Hokkaido, Japan. A total of 468 liver samples and 954 environmental samples were collected from 2003 to 2011 for this study. Four swine livers (1 %) were positive for HEV RNA; two strains belonged to genotype 3 and the other two strains were genotype 4. Genotype 3 HEV was detected in a sewage sample and a seawater sample. HEV strains derived from swine liver, seawater and raw sewage samples shared 93-100 % sequence similarity with human HEV strains.	f	\N
22849219	This paper examines the State's assumption of medical care for patients with "permanent needs" in 19th century Spain. These patients were the incurably ill, the chronically ill and the elderly. This process is contextualized within the liberal reforms of the Spanish healthcare system in the reign of Isabel 11 (1833-1868). The goal of these reforms was the creation and consolidation of a national health system that would gradually replace the religious health charities. Healthcare reform became necessary due to the increase in migration that started in the 1830's and intensified in the 1850's. Traditional care networks formed by the family, local community and religious charities were no longer available to those who had left their village or town. In addition, many religious charities were bankrupted by the seizure of their properties in a programme of confiscation. Similar healthcare reform processes were taking place in the United Kingdom, France and Germany, among other European countries, and involved significant changes in the lives of patients, who became strictly controlled and medicalised. My aim was to identify changes in the patients' experience of illness through a case study of the living conditions of inmates at the Nuestra Señora del Carmen Hospital for Incurable Men, based in Madrid from 1852 to 1949. This was one of the institutions devoted to caring for patients with "permanent needs" and was under the direct control of the General State Administration.	f	\N
22851496	Nitrotyrosine is a post-translationally modified amino acid with distinctly different properties than tyrosine or any other of the genetically encoded amino acids. Detecting proteins containing nitrotyrosine is the first step towards a better understanding of the role of nitrotyrosine in health and disease. Moreover, quantifying the extent of nitrotyrosine and determining its location in a protein forms the basis for a better understanding of the effect of tyrosine nitration on biological function. Described in this unit is a method to detect tyrosine-nitrated proteins in tissue sections and on western blots after creating a fluorescent complex between aminotyrosine, salicylaldehyde, and Al(3+). In addition, an approach is detailed for labeling aminotyrosine with biotin to enrich peptides from complex samples. Both methods require reduction of nitrotyrosine to aminotyrosine, which can be achieved with sodium dithionite or hemin plus dithiothreitol.	f	\N
22869886	Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored. One hundred sixty-nine children diagnosed with stage 4 NB (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 ± GM-CSF ± 13-cis-retinoic acid (CRA) protocols after achieving first remission (complete remission/very good partial remission). Patients enrolled in regimen A (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT); and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT, whereas 28 of 85 required additional induction therapy and were deemed ultra high risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative reverse transcription polymerase chain reaction. Survival probability was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by multivariate Cox regression model. At 5 years from the start of immunotherapy, progression-free survival (PFS) improved from 44% for HR patients receiving regimen A to 56% and 62% for those receiving regimens B and C, respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated sites. Independent adverse prognostic factors included UHR (PFS) and post-cycle two MRD (PFS and OS), whereas the prognostic factors for improved outcome were missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse antibody response (OS), and regimen C (OS). Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.	f	\N
22870861	Newborn screening for the inborn error of metabolism, classical galactosaemia prevents life-threatening complications in the neonatal period. It does not however influence the development of long-term complications and the complex pathophysiology of this rare disease remains poorly understood. The objective of this study was to report the development of a healthcare database (using Distiller Version 2.1) to review the epidemiology of classical galactosaemia in Ireland since initiation of newborn screening in 1972 and the long-term clinical outcomes of all patients attending the National Centre for Inherited Metabolic Disorders (NCIMD). Since 1982, the average live birth incidence rate of classical galactosaemia in the total Irish population was approximately 1:16,476 births. This reflects a high incidence in the Irish 'Traveller' population, with an estimated birth incidence of 1:33,917 in the non-Traveller Irish population. Despite early initiation of treatment (dietary galactose restriction), the long-term outcomes of classical galactosaemia in the Irish patient population are poor; 30.6 % of patients ≥ 6 yrs have IQs <70, 49.6 % of patients ≥ 2.5 yrs have speech or language impairments and 91.2 % of females ≥ 13 yrs suffer from hypergonadotrophic hypogonadism (HH) possibly leading to decreased fertility. These findings are consistent with the international experience. This emphasizes the requirement for continued clinical research in this complex disorder.	f	\N
22873223	Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice.	f	\N
22882216	The use of monoclonal antibodies in the treatment of malignancy and autoimmune diseases has rapidly expanded in the last decade. Rituximab, a monoclonal antibody to the CD20 antigen on B cells, was first approved by the US FDA in 1997 to treat non-Hodgkin's B-cell lymphoma. It is now used, however, for a variety of diseases in both on- and off-label uses. It was approved by the FDA for use in refractory rheumatoid arthritis in 2007, and in April 2011 it was approved for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitides (including granulomatosis with polyangiitis [Wegener's granulomatosis] and microscopic polyangiitis), based on the promising results of the RAVE trial. Within the field of nephrology, in addition to its use in anti-neutrophil cytoplasmic antibody-associated vasculitides, it is has been used in the treatment of membranous nephropathy, membranoproliferative glomerulonephritis and lupus nephritis.	f	\N
22882559	To test a theoretically and empirically supported model of the relationships among percent truncal fat (truncal obesity); disease severity (carbon monoxide diffusing capacity [DLCO]); symptoms (dyspnea); functional capacity (6-min walk test distance); and functional performance (functional performance index) of elderly people with chronic obstructive pulmonary disease (COPD). A model of functional performance was proposed using a multidimensional framework as expounded by Leidy, and incorporating Wilson and Cleary's model for the relationship between symptoms and functional status. Path analysis was used to examine the relationships among variables. The researchers used a descriptive, cross-sectional design. Subjects were phone screened and completed electrocardiography, physical examination, spirometry testing, and a 4-min walk test as part of initial screening. Enrolled subjects completed a whole-body dual-energy x-ray absorptiometry scan to measure truncal obesity, 6-min walk test, upper body functional performance test, and questionnaires. Subjects were grouped into normal weight, overweight, or obese according to body mass index. The sample consisted of 76 people 55 years of age and older with mild to severe COPD. Percent truncal fat (truncal obesity) did not affect functional performance directly, but did affect it indirectly through dyspnea. The 6-min walk test distance, dyspnea, and DLCO accounted for 29% of the variability in functional performance. We believe that the effectiveness of pulmonary rehabilitation will be enhanced when nurses consider weight loss as a controllable factor for overweight and obese clients. The increasing prevalence of obesity in this population may dictate collaboration between dieticians and pulmonary rehabilitation nurses for effective rehabilitation programs. These findings suggest that percent truncal fat (truncal obesity) may be an indirect factor in the performance of daily activities of people with COPD. We anticipate that clinicians will use knowledge derived from this study to develop interventions to reduce or minimize truncal fat (truncal obesity) and its effects on people with COPD.	f	\N
22883409	To establish a rat model of ulcerative colitis with syndrome of spleen deficiency and dampness stagnancy. Sixty rats were divided into normal control group, ulcerative colitis group, ulcerative colitis with syndrome of spleen deficiency and dampness stagnancy group (model group) and strengthening spleen for resolving dampness group. Ulcerative colitis in rats was induced by enema containing trinitrobenzene sulfonic acid (TNBS) and ethanol. The rats in the model group were suffered from standing in water, limiting sleeping time and abnormal diet based on administration of TNBS and ethanol. The rats in the spleen strengthening and dampness resolving group were gastrically administered with Shenlin Baizhu Powder, a compound traditional Chinese herbal medicine. Symptoms, signs and pathological changes in colon tissue of rats were observed after modeling. The levels of interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α) in serum of rats were measured by enzyme-linked immunosorbent assay. The rats in the model group showed lethargy, poor appetite, loss of energy, diarrhea and bloody stool. Their body weight decreased significantly compared with the normal control group, and similar changes were found in the comparison of food intake, drinking amount, urine amount, stool wet weight and assay of spontaneous activity (P<0.05). When observed under a light microscope, the colon tissues of rats in the model group showed mucosal edema, congestion, inflammatory cell infiltration and ulceration. The degree of colon injury and IL-6, IL-8 and TNF-α levels were significantly increased (P<0.05) as compared to those in the normal control group. The changes mentioned above were improved by Shenlin Baizhu Powder (P<0.05). The rat model of ulcerative colitis with syndrome of spleen deficiency and dampness stagnancy is successfully induced and has the characteristics of ulcerative colitis of humans both in pathological changes and in syndrome.	f	\N
22888223	Membranous nanostructures, such as nanovesicles and nanotubules, are an important pool of biological membranes. Recent results indicate that they constitute cell-cell communication systems and that cancer development is influenced by these systems. Nanovesicles that are pinched off from cancer cells can move within the circulation and interact with distant cells. It has been suggested and indicated by experimental evidence that nanovesicles can induce metastases from the primary tumor in this way. Therefore, it is of importance to understand better the mechanisms of membrane budding and vesiculation. Here, a theoretical description is presented concerning consistently related lateral membrane composition, orientational ordering of membrane constituents, and a stable shape of nanovesicles and nanotubules. It is shown that the character of stable nanostructures reflects the composition of the membrane and the intrinsic shape of its constituents. An extension of the fluid mosaic model of biological membranes is suggested by taking into account curvature-mediated orientational ordering of the membrane constituents on strongly anisotropically curved regions. Based on experimental data for artificial membranes, a possible antimetastatic effect of plasma constituents via mediation of attractive interaction between membranous structures is suggested. This mediated attractive interaction hypothetically suppresses nanovesiculation by causing adhesion of buds to the mother membrane and preventing them from being pinched off from the membrane.	f	\N
22892258	The emergency department (ED) is a common setting for evaluation of patients with urolithiasis based on acute symptoms and a propensity for recurrent disease. We sought to characterize practice patterns in the emergency treatment of stone disease, and to identify potential disparities in care based on non-medical factors. We performed a cross-sectional analysis of ED visits using the National Hospital Ambulatory Medical Care Survey from 2005-2009. Visits with a diagnosis of urolithiasis were identified. The associations between patient, provider and institutional characteristics were analyzed with regard to timing of clinical assessment, use of diagnostic imaging, and use of medical expulsive therapy (MET). The likelihood of a delay in clinical assessment ranged from 30.8%-37.9%. Neither patient nor provider characteristics were associated with a delay in assessment, although urban location (p = 0.004) was more likely, and proprietary ownership was less likely (p = 0.002) to be associated with delay. Factors associated with use of CT included ambulance arrival (p = 0.043), initial ED visit (p = 0.000), and Northeast region (p = 0.030). Patients seen by a resident/intern were more likely to receive MET (p = 0.028). Overall, 10.8% of patients were presenting for follow up treatment, and 7.1% had been seen in the same ED within the last 72 hours. Kidney stones are associated with a high rate of repeated presentations to the ED. Certain non-medical factors did impact details of management. Future efforts should focus on optimizing clinical pathways to improve the efficiency of acute care for kidney stone patients.	f	\N
22910631	Like many intracellular microbes, the protozoan parasite Toxoplasma gondii injects effector proteins into cells it invades. One group of these effector proteins is injected from specialized organelles called the rhoptries, which have previously been described to discharge their contents only during successful invasion of a host cell. In this report, using several reporter systems, we show that in vitro the parasite injects rhoptry proteins into cells it does not productively invade and that the rhoptry effector proteins can manipulate the uninfected cell in a similar manner to infected cells. In addition, as one of the reporter systems uses a rhoptry:Cre recombinase fusion protein, we show that in Cre-reporter mice infected with an encysting Toxoplasma-Cre strain, uninfected-injected cells, which could be derived from aborted invasion or cell-intrinsic killing after invasion, are actually more common than infected-injected cells, especially in the mouse brain, where Toxoplasma encysts and persists. This phenomenon has important implications for how Toxoplasma globally affects its host and opens a new avenue for how other intracellular microbes may similarly manipulate the host environment at large.	f	\N
22911240	In this study, the clinical outcome and prognostic factors of adult medulloblastoma patients receiving multimodal treatment were investigated. The clinical manifestations, treatment variables, and outcome of adult patients with medulloblastoma at our institution between 1983 and 2009 were retrospectively reviewed. A total of 20 adult patients were included (median age 22 years). Craniospinal irradiation (CSI) was given postoperatively. The craniospinal axis received a median of 30 Gy (range 23.4-39.6 Gy) in fractions of 1.6-2 Gy/day, and the tumor was boosted to a total median dose of 50 Gy (range 50-55.25 Gy). The 3-year disease-free survival (DFS) and overall survival (OS) rates for all patients were 45% and 50%, respectively. In univariate analysis, Karnofsky Performance Scale (KPS) > 70, neurologic symptoms duration > 30 days, lateral tumor location, standard risk patients, no hydrocephalus, radiotherapy (RT) treatment field (CSI + brain boost), and CSI dose ≥ 30 Gy were associated with better DFS. Standard-risk patients, RT treatment field (CSI + brain boost), and CSI dose ≥ 30 Gy were also significantly associated with better OS. The combined modality treatment results in a favorable outcome for adult medulloblastoma patients. Further investigation of the prognostic factors, radiation-related factors, and systemic chemotherapy is needed.	f	\N
22917170	Diarrhea is a common clinical feature of inflammatory bowel diseases and may be accompanied by abdominal pain, urgency, and fecal incontinence. The pathophysiology of diarrhea in these diseases is complex, but defective absorption of salt and water by the inflamed bowel is the most important mechanism involved. In addition to inflammation secondary to the disease, diarrhea may arise from a variety of other conditions. It is important to differentiate the pathophysiologic mechanisms involved in the diarrhea in the individual patient to provide the appropriate therapy. This article reviews microscopic colitis, ulcerative colitis, and Crohn's disease, focusing on diarrhea.	f	\N
22924030	Although many parameters were investigated about weaning and mortality in critical patients in intensive units, no studies have yet investigated predictors in prolonged mechanical ventilation (PMV) patients following successful weaning. A cohort of 142 consecutive PMV patients with successful weaning in our respiratory care center was enrolled in this study. Successful weaning is defined as a patient having smooth respiration for more than 5 days after weaning. The results showed as follows: twenty-seven patients (19%) had the reinstitution within 14 days, and 115 patients (81%) had the reinstitution beyond 14 days. Renal disease RIFLE-LE was associated with the reinstitution within 14 days (P = 0.006). One year mortality rates showed significant difference between the two groups (85.2% in the reinstitution within 14 days group versus 53.1% in the reinstitution beyond 14 days; P < 0.001). Kaplan-Meier analysis showed that age ≥70 years (P = 0.04), ESRD (P = 0.02), and the reinstitution within 14 days (P < 0.001) were associated with one-year mortality. Cox proportional hazards regression model showed that only the reinstitution within 14 days was the independent predictor for mortality (P < 0.001). In conclusion, the reinstitution within 14 days was a poor predictor for PMV patients after successful weaning.	f	\N
22931913	Prediction of outcome for melanoma patients with surgically resected macroscopic nodal metastases is very imprecise. We performed a comprehensive clinico-pathologic assessment of fresh-frozen macroscopic nodal metastases and the preceding primary melanoma, somatic mutation profiling, and gene expression profiling to identify determinants of outcome in 79 melanoma patients. In addition to disease stage <II at initial presentation, the following clinical and pathologic factors were independent predictors of improved outcome (odds ratios for survival >4 years, 90% confidence interval): the presence of a nodular component in the primary melanoma (6.8, 0.6-76.0), and small cell size (11.1, 0.8-100.0) or low pigmentation (3.0, 0.8-100.0) in the nodal metastases. Absence of BRAF mutation (20.0, 1.0-1000.0) or NRAS mutation (16.7, 0.6-1000.0) were both favorable prognostic factors. A 46-gene expression signature with strong overrepresentation of immune response genes was predictive of better survival (10.9, 0.4-325.6); in the full cohort, median survival was >100 months in those with the signature, but 10 months in those without. This relationship was validated in two previously published independent stage III melanoma data sets. We conclude that the presence of BRAF mutation, NRAS mutation, and the absence of an immune-related expressed gene profile predict poor outcome in melanoma patients with macroscopic stage III disease.	f	\N
22933250	Renal xenobiotic transporters are important determinants of urinary secretion and reabsorption of chemicals. In addition to glomerular filtration, these processes are key to the overall renal clearance of a diverse array of drugs and toxins. Alterations in kidney transporter levels and function can influence the efficacy and toxicity of chemicals. Studies in experimental animals have revealed distinct patterns of renal transporter expression in response to sex hormones, pregnancy, and growth hormone. Likewise, a number of disease states including diabetes, obesity, and cholestasis alter the expression of kidney transporters. The goal of this review is to provide an overview of the major xenobiotic transporters expressed in the kidneys and an understanding of metabolic conditions and hormonal factors that regulate their expression and function.	f	\N
22933945	The aim of the study was to evaluate the clinical efficacy of superselective intra-arterial targeted neo-adjuvant chemotherapy in the treatment of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) breast cancer. PATIENTS AND METHODS.: A total of 47 triple-negative breast cancer patients (29 at stage II, 13 at stage III and 5 at stage IV) were randomly assigned to two groups: targeted chemotherapy group (n=24) and control group (n=23). Patients in the targeted chemotherapy group received preoperative superselective intra-arterial chemotherapy with CEF regimen (C: cyclophosphamide [600 mg/m(2)]; E: epirubicin [90 mg/m(2)]; F: 5-fluorouracil [600 mg/m(2)]), and those in the control group received routine neoadjuvant chemotherapy with CEF. The duration of the treatment, changes in lesions and the prognosis were determined. The average course of the treatment was 15 days in the targeted chemotherapy group which was significantly shorter than that in the control group (31 days) (P<0.01). The remission rate of lesions was 91.6% in the targeted chemotherapy group and 60.9% in the control group, respectively. Among these patients, 9 died within two years, including 2 (both at IV stage) in the targeted chemotherapy group and 7 (2 at stage II, 4 at stage III and 1 at stage IV) in the control group. As an neoadjuvant therapy, the superselective intra-arterial chemotherapy is effective for triple-negative breast cancer, with advantages of the short treatment course and favourable remission rates as well as prognoses.	f	\N
22934539	The existing literature suggests that theories and models can serve as valuable frameworks for the design and evaluation of health interventions. However, evidence on the use of theories and models in social marketing interventions is sparse. The purpose of this systematic review is to identify to what extent papers about social marketing health interventions report using theory, which theories are most commonly used, and how theory was used. A systematic search was conducted for articles that reported social marketing interventions for the prevention or management of cancer, diabetes, heart disease, HIV, STDs, and tobacco use, and behaviors related to reproductive health, physical activity, nutrition, and smoking cessation. Articles were published in English, after 1990, reported an evaluation, and met the 6 social marketing benchmarks criteria (behavior change, consumer research, segmentation and targeting, exchange, competition and marketing mix). Twenty-four articles, describing 17 interventions, met the inclusion criteria. Of these 17 interventions, 8 reported using theory and 7 stated how it was used. The transtheoretical model/stages of change was used more often than other theories. Findings highlight an ongoing lack of use or underreporting of the use of theory in social marketing campaigns and reinforce the call to action for applying and reporting theory to guide and evaluate interventions.	f	\N
22935019	Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies.	f	\N
22940074	A 33-year-old woman with Wernicke's encephalopathy (WE) due to poor oral intake after allogeneic stem cell transplantation for acute myeloid leukemia showed a sequential development of bilateral gaze-evoked nystagmus (GEN), rightward gaze palsy, and upbeat nystagmus. Initial MRIs obtained when she had GEN only showed a lesion involving the medullary tegmentum, and follow-up MRIs revealed additional lesions in the pontine and midbrain tegmentum along with development of rightward gaze palsy, and finally bilateral medial thalamus lesions in association with upbeat nystagmus. The evolution of abnormal ocular motor findings and serial MRI changes in our patient with WE provide imaging evidence on relative vulnerability of the neural structures, and on the progression of lesions and ocular motor findings in thiamine deficiency.	f	\N
22956992	Cerebral palsy (CP) is an upper motor neuron disease that results in a spectrum of movement disorders. Secondary to the neurological lesion, muscles from patients with CP are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in CP is a response to aberrant complex neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response in CP using transcriptional profiling correlated with functional measures to broadly investigate muscle adaptations leading to mechanical deficits.Biopsies were obtained from both the gracilis and semitendinosus muscles from a cohort of patients with CP (n = 10) and typically developing patients (n = 10) undergoing surgery. Biopsies were obtained to define the unique expression profile of the contractures and passive mechanical testing was conducted to determine stiffness values in previously published work. Affymetrix HG-U133A 2.0 chips (n = 40) generated expression data, which was validated for selected transcripts using quantitative real-time PCR. Chips were clustered based on their expression and those from patients with CP clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n = 1,398). Significantly altered genes were analyzed for over-representation among gene ontologies and muscle specific networks.The majority of altered transcripts were related to increased extracellular matrix expression in CP and a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and development of novel therapies.	f	\N
22958194	Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in haemophilia A. It has been suggested that differences in the distribution of FVIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Data from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and inhibitor risk among individuals of genetically determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and human leucocyte antigen (HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified (N = 49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N = 223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Haplotype 3 was not an independent predictor of inhibitor risk. Furthermore, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual.	f	\N
22964476	Tocopherol, a member of the vitamin E family, consists of four forms designated as α, β, γ, and δ. Several large cancer prevention studies with α-tocopherol have reported no beneficial results, but recent laboratory studies have suggested that δ- and γ-tocopherol may be more effective. In two different animal models of breast cancer, the chemopreventive activities of individual tocopherols were assessed using diets containing 0.3% of tocopherol (α-, δ-, or γ-) or 0.3% of a γ-tocopherol rich mixture (γ-TmT). Although administration of tocopherols did not prevent human epidermal growth factor receptor 2 (HER2/neu)-driven tumorigenesis, δ- and γ-tocopherols inhibited hormone-dependent mammary tumorigenesis in N-methyl-N-nitrosourea (NMU)-treated female Sprague-Dawley rats. NMU-treated rats showed an average tumor burden of 10.6 ± 0.8 g in the control group at 11 weeks, whereas dietary administration of δ- and γ-tocopherols significantly decreased tumor burden to 7.2 ± 0.8 g (P < 0.01) and 7.1 ± 0.7 g (P < 0.01), respectively. Tumor multiplicity was also reduced in δ- and γ-tocopherol treatment groups by 42% (P < 0.001) and 32% (P < 0.01), respectively. In contrast, α-tocopherol did not decrease tumor burden or multiplicity. In mammary tumors, the protein levels of proapoptotic markers (BAX, cleaved caspase-9, cleaved caspase-3, cleaved PARP) were increased, whereas antiapoptotic markers (Bcl-2, XIAP) were inhibited by δ-tocopherol, γ-tocopherol, and γ-TmT. Furthermore, markers of cell proliferation (PCNA, PKCα), survival (PPAR-γ, PTEN, phospho-Akt), and cell cycle (p53, p21) were affected by δ- and γ-tocopherols. Both δ- and γ-tocopherols, but not α-tocopherol, seem to be promising agents for the prevention of hormone-dependent breast cancer.	f	\N
22980951	The role of non-complement activating antibodies (ncAbs) to mismatched donor human leukocyte antigen (HLA) in the pathogenesis of chronic lung rejection is not known. We used a murine model of obliterative airway disease (OAD) induced by Abs to major histocompatibility major histocompatibility complex (MHC) class I and serum from donor-specific Abs developed in human lung transplant (LTx) recipients to test the role of ncAbs in the development of OAD and bronchiolitis obliterans syndrome (BOS). Anti-MHC ncAbs were administered intrabronchially in B.10 mice or in C3 knockout (C3KO) mice. Lungs were analyzed by histopathology. Lymphocytes secreting interleukin (IL)-17, interferon-γ, or IL-10 to collagen V and K-α1 tubulin (Kα1T) were enumerated by enzyme-linked immunospot assay. Serum antibodies to collagen V and Kα1T were determined by enzyme-linked immunosorbent assay. Cytokine and growth factor expression in lungs was determined by real-time polymerase chain reaction. Donor-specific Abs from patients with BOS and control BOS-negative LTx recipients were analyzed by C1q assay. Administration of ncAbs in B.10 mice or C3KO resulted in OAD lesions. There were significant increases in IL-17- and interferon-γ-secreting cells to collagen V and Kα1T, along with serum Abs to these antigens. There was also augmented expression of monocyte chemotactic protein-1, IL-6, IL-1β, vascular endothelial growth factor, transforming growth factor-β, and fibroblastic growth factor in mice administered ncAbs by Day 3. Among 5 LTx recipients with BOS, only 1 had C1q binding donor-specific Abs. Complement activation by Abs to MHC class I is not required for development of OAD and human BOS. Therefore, anti-MHC binding to epithelial and endothelial cells can directly activate pro-fibrotic and pro-inflammatory cascades leading to immune response to self-antigens and chronic rejection.	f	\N
22981307	The "Cohorte Enfant Scanner", a study designed to investigate the risk of radiation-induced cancer after childhood exposure to CT (computed tomography) examinations, used clinical information contained in the "programme de médicalisation des systèmes d'information" (PMSI) database, the French hospital activities national program based upon diagnosis related groups (DRG). However, the quality and adequacy of the data for the specific needs of the study should be verified. The aim of our work was to estimate the percentage of the cohort's children identified in the PMSI database and to develop an algorithm to individualize the children with a cancer or a disease at risk of cancer from medical diagnoses provided by the DRGs database. Of the 1519 children from the "Cohorte Enfant Scanner", who had had a CT scan in the radiology department of a university hospital in 2002, a cross linkage was performed with the DRGs database. All hospitalizations over the period 2002-2009 were taken into account. An algorithm was constructed for the items "cancer" and "disease at risk for cancer" on a sample of 150 children. The algorithm was then tested on the entire population. Overall, 74% of our population was identified in the DRGs database. The algorithm individualized cancer diagnoses with 91% sensitivity (95% confidence interval [95%CI]: 86%; 97%) and 98% specificity (95%CI: 97%; 99%) and 86% positive predictive value (95%CI: 80%; 93%). For the diagnosis of disease at risk for cancer, the sensitivity, specificity and positive predictive value were respectively 91% (95%CI: 84%; 98%), 94% (95%CI: 92%; 95%) and 52% (95%CI: 43%; 61%). The DRG database identified with excellent sensitivity and specificity children with diagnoses of cancer or disease at risk for cancer. Hence, potential confounding factors related to the disease of the child can be taken into account for analyses performed with the cohort.	f	\N
22990715	Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study. Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models. Among DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA(1c) and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline (~0.7% per month). SEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.	f	\N
23005903	A tubo-ovarian abscess (TOA) is a common complication of pelvic inflammatory disease in premenopausal women; however, in virginal females, TOAs are an exceedingly rare occurrence. Within this rare subset of patients, there is almost always an underlying condition, such as vaginal voiding, or a concomitant disease process. A virginal adolescent female with no prior medical history presented with a large pelvic mass which proved to be a TOA. An exploratory laparotomy was eventually required to establish the diagnosis. Open drainage and antibiotic therapy successfully treated the patient. With only the organism, Streptococcus viridians, isolated in her cultures, an etiology of direct ascension from the lower genitourinary tract is implicated. We believe this to be the youngest case of a TOA occurring in a virginal adolescent female without a predisposing condition. A TOA should be considered in the differential diagnosis of pelvic masses in previously healthy pediatric patients regardless of their sexual activity.	f	\N
23008381	Japanese encephalitis (JE) is an epidemic encephalitis characterised by altered sensorium, convulsions, headache, brainstem signs with pyramidal and extrapyramidal features. Immune-mediated manifestation as acute transverse myelitis (ATM) has not been previously reported in JE. We describe a 40-year-old man who presented with an acute onset quadriparesis with urinary retention, which was preceded by fever and headache 3 weeks prior. He had elevated IgM titres against JE virus in serum and cerebrospinal fluid. MRI of cervico-thoracic spine demonstrated signal intensity alterations extending from C1 to D10 spinal segments. The patient was treated with intravenous methyl prednisolone for 5 days. He regained normal power at 6 months follow-up and repeat MRI study demonstrated complete resolution of the lesion. We conclude that in a case of JE, one should be vigilant for early diagnosis of possible complication as ATM, in which an early institution of immunomodulator therapy prevents adverse consequences.	f	\N
23018067	OBJECTIVES. To evaluate attainment of low-density lipoprotein cholesterol goals among hypercholesterolaemic patients undergoing lipid-lowering drug treatment in Hong Kong and to identify potential determinants of treatment outcomes. DESIGN. Cross-sectional observational study. SETTING. A single site in Hong Kong, as part of the CEPHEUS Pan-Asian survey. PATIENTS. Subjects with hypercholesterolaemia aged 18 years or above, who had been on lipid-lowering drug treatment for at least 3 months with no dose adjustment for at least 6 weeks. RESULTS. A total of 561 such patients (mean age, 65.3; standard deviation, 9.7 years) were evaluated. Most had major cardiovascular risk factors; 534 (95.2%) of 561 patients had coronary heart disease and 534 (95.4%) of 560 patients had low-density lipoprotein cholesterol goals set at lower than 70 mg/dL. In all, 465 (82.9%) patients attained their respective low-density lipoprotein cholesterol goals. Among 75 patients who had coronary heart disease or equivalent risk, and multiple risk factors with a 10-year coronary heart disease risk of over 20%, 62 (82.7%) attained their respective low-density lipoprotein cholesterol goals. Significant predictors of low-density lipoprotein cholesterol goal attainment included the patient's baseline lipid profile (total cholesterol and low-density lipoprotein cholesterol levels), blood pressure, and drugs (statin/non-statin) used for treatment. CONCLUSIONS. Hypercholesterolaemic patients undergoing lipid-lowering drug treatment in the present Hong Kong study were able to achieve a very high attainment rate for the low-density lipoprotein cholesterol goal, despite the fact that most of them had major cardiovascular risk factors.	f	\N
23020826	A patient with central nervous system involvement of Behçet's disease was refractory to conventional immunosuppressive therapy and showed secondary failure of the anti-TNF agent infliximab. This presented as a progressive weakness of the legs and reduction in walking distance. The cerebrospinal fluid showed signs of inflammation including a vastly elevated IL-6 concentration. Given this result, the anti-IL-6 receptor antibody tocilizumab was administered and a good improvement of inflammatory parameters and a satisfactory increase of the walking distance were achieved.	f	\N
23028288	The prioritization of candidate disease-causing genes is a fundamental challenge in the post-genomic era. Current state of the art methods exploit a protein-protein interaction (PPI) network for this task. They are based on the observation that genes causing phenotypically-similar diseases tend to lie close to one another in a PPI network. However, to date, these methods have used a static picture of human PPIs, while diseases impact specific tissues in which the PPI networks may be dramatically different. Here, for the first time, we perform a large-scale assessment of the contribution of tissue-specific information to gene prioritization. By integrating tissue-specific gene expression data with PPI information, we construct tissue-specific PPI networks for 60 tissues and investigate their prioritization power. We find that tissue-specific PPI networks considerably improve the prioritization results compared to those obtained using a generic PPI network. Furthermore, they allow predicting novel disease-tissue associations, pointing to sub-clinical tissue effects that may escape early detection.	f	\N
23028439	Several independent studies have supported the association of DYX1C1 with dyslexia, but its role in general reading development remains unclear. Here, we investigated the contribution of this gene to reading, with a focus on orthographic skills, in a sample of 284 unrelated Chinese children aged 5 to 11 years who were participating in the Chinese Longitudinal Study of Reading Development. We tested this association using a quantitative approach for Chinese character reading, Chinese character dictation, orthographic judgment, and visual skills. Significant or marginally significant associations were observed at the marker rs11629841 with children's orthographic judgments at ages 7 and 8 years (all P values<0.020). Significant associations with Chinese character dictation (all P values<0.013) were also observed for this single-nucleotide polymorphism (SNP) at ages 9, 10, and 11 years. Further analyses revealed that the association with orthographic skills was specific to the processing of specific components of characters (P values<0.046). No association was found at either SNP of rs3743205 or rs57809907. Our findings suggest that DYX1C1 influences reading development in the general Chinese population and supports a universal effect of this gene.	f	\N
23049998	Although "uremic fetor" has long been felt to be diagnostic of renal failure, the compounds exhaled in uremia remain largely unknown so far. The present work investigates whether breath analysis by ion mobility spectrometry can be used for the identification of volatile organic compounds retained in uremia. Breath analysis was performed in 28 adults with an eGFR ≥ 60 ml/min per 1.73 m(2), 26 adults with chronic renal failure corresponding to an eGFR of 10-59 ml/min per 1.73 m(2), and 28 adults with end-stage renal disease (ESRD) before and after a hemodialysis session. Breath analysis was performed by ion mobility spectrometryafter gas-chromatographic preseparation. Identification of the compounds of interest was performed by thermal desorption gas chromatography/mass spectrometry. Breath analyses revealed significant differences in the spectra of patients with and without renal failure. Thirteen compounds were chosen for further evaluation. Some compounds including hydroxyacetone, 3-hydroxy-2-butanone and ammonia accumulated with decreasing renal function and were eliminated by dialysis. The concentrations of these compounds allowed a significant differentiation between healthy, chronic renal failure with an eGFR of 10-59 ml/min, and ESRD (p<0.05 each). Other compounds including 4-heptanal, 4-heptanone, and 2-heptanone preferentially or exclusively occurred in patients undergoing hemodialysis. Impairment of renal function induces a characteristic fingerprint of volatile compounds in the breath. The technique of ion mobility spectrometry can be used for the identification of lipophilic uremic retention molecules.	f	\N
23050521	Data from the 2011 Survey of Pathways to Diagnosis and Services The median age when school-aged children with special health care needs (CSHCN) and autism spectrum disorder (ASD) were first identified as having ASD was 5 years. School-aged CSHCN identified as having ASD at a younger age (under age 5 years) were identified most often by generalists and psychologists, while those identified later (aged 5 years and over) were identified primarily by psychologists and psychiatrists. Nine out of 10 school-aged CSHCN with ASD use one or more services to meet their developmental needs. Social skills training and speech or language therapy are the most common, each used by almost three-fifths of these children. More than one-half of school-aged CSHCN with ASD use psychotropic medication.	f	\N
23058984	Mast cells (MCs) are well known for their detrimental effects in the context of allergic disorders. Strategies that limit MC function can therefore have a therapeutic value. Previous studies have shown that siramesine, a sigma-2 receptor agonist originally developed as an anti-depressant, can induce cell death in transformed cells through a mechanism involving lysosomal destabilization. Since MCs are remarkably rich in lysosome-like secretory granules we reasoned that MCs might be sensitive to siramesine. Here we show that murine and human MCs are highly sensitive to siramesine. Cell death was accompanied by secretory granule permeabilization, as shown by reduced acridine orange staining and leakage of granule proteases into the cytosol. Wild type siramesine-treated MCs underwent cell death with typical signs of apoptosis but MCs lacking serglycin, a proteoglycan crucial for promoting the storage of proteases within MC secretory granules, died predominantly by necrosis. A dissection of the underlying mechanism suggested that the necrotic phenotype of serglycin(-/-) cells was linked to defective Poly(ADP-ribose) polymerase-1 degradation. In vivo, siramesine treatment of mice caused a depletion of the MC populations of the peritoneum and skin. The present study shows for the first time that MCs are highly sensitive to apoptosis induced by siramesine and introduces the possibility of using siramesine as a therapeutic agent for treatment of MC-dependent disease.	f	\N
23061325	A paradox exists in health disparities research where African-American cigarette smokers consume fewer cigarettes per day, yet experience higher rates of tobacco-related disease compared to White American smokers. In this study we conducted focus group interviews among alternative high school youth (N = 78; age 18-19 years old) in an urban area in Southwest Texas to investigate if African-American youth smoke cigarettes differently than their White-American and Hispanic-American counterparts. The majority of African-American participants reported inhaling deeper and smoking their cigarettes "to the filter" because of their concern over wasting any part of an expensive cigarette. White and Hispanic respondents most often put out their cigarettes closer to the middle, and did not express concern about wasting cigarettes. The implication from this qualitative study is that because African Americans smoke differently they are exposed to a higher level of harmful particulate per cigarette. Further research on smoking topography is warranted.	f	\N
23063289	A meta-analysis of publicly available gene expression changes in A549 cells upon treatment with anti-cancer drugs is reported. To reduce false positives, both fold-change and significance level cutoffs were used. Simulated datasets and permutation analysis were used to guide choice of ratio cutoff. Of the genes identified, FDXR is the only gene differentially expressed in six of the seven drug treatments. Though FDXR has been reported to be differentially expressed upon treatment with 5-fluorouracil and its expression correlated to long term disease survival, to our knowledge this is a first study implicating a wide effect of anti-cancer drug treatment on FDXR expression. The other genes identified which are differentially expressed in four out of the seven drug treatments are CDKN1A and PARVB which are upregulated and MYC, HBP1, LDLR, SIM2, ALX1 and GPHN which are downregulated.	f	\N
23063663	Liver cancer is one of most deadly cancers worldwide. Hepatocellular carcinoma (HCC) represents a major histological subtype of liver cancers. As cancer is a genetic disease, genetic lesions play a major role in HCC tumorigenesis and progression. Although significant progress has been made to uncover genetic alterations in HCCs, our understanding of genetics involved in the initiation and progression of HCC is far from complete. Next generation sequencing (NGS) has provided a new paradigm in biomedical research to delineate the genetic basis of human diseases. While identification of cancer somatic mutations has been serendipitous, genome sequencing has provided an unbiased approach to systematically catalog somatic mutations and elucidate the mechanisms of tumourigenesis. A number of recently published NGS studies on HCCs have not only confirmed previously known mutations in CTNNB1 and TP53 in HCC, but also identified novel genetic alterations in HCC including mutations in genes involved in epigenetic regulation. WNT, cell cycle and chromatin remodeling pathways have emerged as key oncogenic drivers in HCCs. The frequently altered genes and pathways in HCC reflect classical cancer hallmarks. These findings have started to depict a genetic landscape in HCC and will facilitate development of novel therapeutics for the treatment of this deadly disease.	f	\N
23063979	Vascular calcification is a hallmark of cardiovascular disease. Interleukin-24 (IL-24) has been known to suppress tumor progression in a variety of human cancers. However, the role of IL-24 in the pathophysiology of diseases other than cancer is unclear. We investigated the role of IL-24 in vascular calcification. IL-24 was applied to a β-glycerophosphate (β-GP)-induced rat vascular smooth muscle cell (VSMC) calcification model. In this study, IL-24 significantly inhibited β-GP-induced VSMC calcification, as determined by von Kossa staining and calcium content. The inhibitory effect of IL-24 on VSMC calcification was due to the suppression of β-GP-induced apoptosis and expression of calcification and osteoblastic markers. In addition, IL-24 abrogated β-GP-induced activation of the Wnt/β-catenin pathway, which plays a key role in the pathogenesis of vascular calcification. The specificity of IL-24 for the inhibition of VSMC calcification was confirmed by using a neutralizing antibody to IL-24. Our results suggest that IL-24 inhibits β-GP-induced VSMC calcification by inhibiting apoptosis, the expression of calcification and osteoblastic markers, and the Wnt/ β-catenin pathway. Our study may provide a novel mechanism of action of IL-24 in cardiovascular disease and indicates that IL-24 is a potential therapeutic agent in VSMC calcification.	f	\N
23070622	Multivisceral transplantation includes the simultaneous transplantation of multiple abdominal viscera including the stomach, duodenum, pancreas, and small intestine, with (multivisceral transplant, MVT) or without the liver (modified MVT, MMVT). This study reviews the changing indications and outcomes for this procedure over a 7-year period at a university medical center. This study is a retrospective case review of MVTs performed between 2004 and 2010 at a single center. All cases were either MVT or MMVT and included a simultaneous kidney transplant, if indicated. Graft failure was defined as loss of the graft or complete loss of function. Graft function was monitored by clinical function, laboratory values, and serial endoscopy with biopsy. During the study period, 95 patients received 100 transplants including 84 MVT and 16 MMVT. There were 19 patients who received a simultaneous kidney graft. There were 24 pediatric and 76 adult recipients (range 7 months to 66 years). Indications included intestinal failure alone, intestinal failure with cirrhosis, complete portal mesenteric thrombosis, slow-growing central abdominal tumors, intestinal pseudoobstruction, and frozen abdomen. All patients received antibody-based induction immunosuppression with calcineurin inhibitor-based maintenance immunosuppression. At a median mortality adjusted follow-up of 25 months, 1- and 3-year patient survival is 72 % and 57 %. There was a learning curve with this complex procedure resulting in a 48 % patient survival during the period from 2004 to 2007, followed by a 70 % patient survival during the period from 2008 to 2010. Post-transplant complications included rejection (50 % MMVT and 17 % MVT), infection (>90 % first year), graft versus host disease (13 %), and post-transplant lymphoproliferative disorder (5 %). Indications for MVT and MMVT have broadened to include patients with terminal conditions not amenable to other medical therapies such as slow-growing tumors of the mesenteric root, complete portomesenteric thrombosis, and abdominal catastrophes/frozen abdomen. Outcomes have improved over time with many patients returning to full functional status and enjoying long-term survival.	f	\N
23079185	Elevated serum levels of the proinflammatory cytokine tumor necrosis factor alpha (TNFα) correlate with an increased risk for atherothrombotic events and TNFα is known to induce prothrombotic molecules in endothelial cells. Based on the preexisting evidence for the impact of TNFα in the pathogenesis of autoimmune disorders and their known association with an acquired hypercoagulability, we investigated the effects of TNFα and the role of the TNF receptor subtypes TNFR1 and TNFR2 for arteriolar thrombosis in vivo. Arteriolar thrombosis and platelet-rolling in vivo were investigated in wildtype, TNFR1-/-, TNFR2-/- and TNFR1-/R2-/- C57BL/6 mice using intravital microscopy in the dorsal skinfold chamber microcirculation model. In vitro, expression of prothrombotic molecules was assessed in human endothelial cells by real-time PCR and flow cytometry. In wildtype mice, stimulation with TNFα significantly accelerated thrombotic vessel occlusion in vivo upon ferric chloride injury. Arteriolar thrombosis was much more pronounced in TNFR1-/- animals, where TNFα additionally led to increased platelet-endothelium-interaction. TNFα dependent prothrombotic effects were not observed in TNFR2-/- and TNFR1-/R2- mice. In vitro, stimulation of human platelet rich plasma with TNFα did not influence aggregation properties. In human endothelial cells, TNFα induced superoxide production, p-selectin, tissue factor and PAI-1, and suppressed thrombomodulin, resulting in an accelerated endothelial dependent blood clotting in vitro. Additionally, TNFα caused the release of soluble mediators by endothelial cells which induced prothrombotic and suppressed anticoagulant genes comparable to direct TNFα effects. TNFα accelerates thrombus formation in an in vivo model of arteriolar thrombosis. Its prothrombotic effects in vivo require TNFR2 and are partly compensated by TNFR1. In vitro studies indicate endothelial mechanisms to be responsible for prothrombotic TNFα effects. Our results support a more selective therapeutic approach in anticytokine therapy favouring TNFR2 specific antagonists.	f	\N
23083013	Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease affecting > 10% of children and 1-3% of adults, and can cause significant morbidity. The incidence of AD seems to be increasing. Omalizumab, a monoclonal antibody, has recently been suggested as a potential new systemic treatment for patients with recalcitrant AD with elevated IgE levels, based on its efficacy in treating asthma and allergic rhinitis. We report a study of 10 patients with AD (aged 19-35 years) who received anti-IgE treatment for persistent asthma. All patients, regardless of IgE value, were treated with a fixed schedule of eight cycles of omalizumab 300 mg administered subcutaneously at intervals of 2 weeks. Eczema symptoms were scored at baseline and after 2, 4 and 6 months of treatment. There was a steady improvement in the objective SCORAD (SCORing Atopic Dermatitis), with significantly lower scores observed at the 6-month evaluation. At 2 months after the end of treatment, two patients had a very good result (SCORAD reduction of > 50%), five patients had a satisfactory result (reduction of 25-50%), and three patients had no clinically relevant result (reduction of 25-50%). No patient had worsening of the AD (increase of > 25% in SCORAD), and once a clinical improvement occurred, none of the patients experienced worsening of their eczema symptoms while on omalizumab. With the caveats of the financial expense and unknown long-term risks of malignancy associated with omalizumab, this drug should be considered for treatment-resistant patients with AD, particularly patients with high IgE level whose symptoms are not controlled by routine therapies. Omalizumab has proven useful in treating asthma, but it may also prove valuable for other conditions, such as allergic rhinitis, food allergies, chronic urticaria, and AD, as shown by the present study.	f	\N
23087412	We recently proposed two novel criteria to assess the usefulness of risk prediction models for public health applications. The proportion of cases followed, PCF(p), is the proportion of individuals who will develop disease who are included in the proportion p of individuals in the population at highest risk. The proportion needed to follow-up, PNF(q), is the proportion of the general population at highest risk that one needs to follow in order that a proportion q of those destined to become cases will be followed (Pfeiffer, R.M. and Gail, M.H., 2011. Two criteria for evaluating risk prediction models. Biometrics 67, 1057-1065). Here, we extend these criteria in two ways. First, we introduce two new criteria by integrating PCF and PNF over a range of values of q or p to obtain iPCF, the integrated PCF, and iPNF, the integrated PNF. A key assumption in the previous work was that the risk model is well calibrated. This assumption also underlies novel estimates of iPCF and iPNF based on observed risks in a population alone. The second extension is to propose and study estimates of PCF, PNF, iPCF, and iPNF that are consistent even if the risk models are not well calibrated. These new estimates are obtained from case-control data when the outcome prevalence in the population is known, and from cohort data, with baseline covariates and observed health outcomes. We study the efficiency of the various estimates and propose and compare tests for comparing two risk models, both of which were evaluated in the same validation data.	f	\N
23089926	Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is associated with obesity, dyslipidemias, hypertension (HTN) and type 2 diabetes mellitus (T2DM). LPL gene polymorphisms can be related with the development of cardiovascular risk factors. The present study was conducted to analyze the relationship of the HindIII and S447X polymorphisms in LPL gene with cardiovascular risk factors in Mexican families. The study population comprised ninety members of 30 Mexican families, in which an index case had obesity, were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical parameters. Screening for both polymorphisms was made by PCR-RFLPs. In the parents, both polymorphisms were in Hardy-Weinberg's equilibrium. We found that the genotype T/T of HindIII was associated with diastolic blood pressure ≥ 85 mmHg (OR=1.1; p=0.011), whereas the genotype C/C of S447X was associated with systolic blood pressure ≥ 130 mmHg (OR=1.2; p<0.001), diastolic blood pressure ≥ 85 mmHg (OR = 1.3; p< 0.001), T2DM (OR=1.3; p< 0.001) and with increase of total cholesterol (β =23.6 mg/mL; p=0.03). These data suggest that the HindIII and S447X LPL gene polymorphisms can confer susceptibility for the development of hypertension and T2DM in Mexican families.	f	\N
23092312	Many coronary heart disease (CHD) events occur in individuals classified as intermediate risk by commonly used assessment tools. Over half the individuals presenting with a severe cardiac event, such as myocardial infarction (MI), have at most one risk factor as included in the widely used Framingham risk assessment. Individuals classified as intermediate risk, who are actually at high risk, may not receive guideline recommended treatments. A clinically useful method for accurately predicting 5-year CHD risk among intermediate risk patients remains an unmet medical need. This study sought to develop a CHD Risk Assessment (CHDRA) model that improves 5-year risk stratification among intermediate risk individuals. Assay panels for biomarkers associated with atherosclerosis biology (inflammation, angiogenesis, apoptosis, chemotaxis, etc.) were optimized for measuring baseline serum samples from 1084 initially CHD-free Marshfield Clinic Personalized Medicine Research Project (PMRP) individuals. A multivariable Cox regression model was fit using the most powerful risk predictors within the clinical and protein variables identified by repeated cross-validation. The resulting CHDRA algorithm was validated in a Multiple-Ethnic Study of Atherosclerosis (MESA) case-cohort sample. A CHDRA algorithm of age, sex, diabetes, and family history of MI, combined with serum levels of seven biomarkers (CTACK, Eotaxin, Fas Ligand, HGF, IL-16, MCP-3, and sFas) yielded a clinical net reclassification index of 42.7% (p < 0.001) for MESA patients with a recalibrated Framingham 5-year intermediate risk level. Across all patients, the model predicted acute coronary events (hazard ratio = 2.17, p < 0.001), and remained an independent predictor after Framingham risk factor adjustments. These include the slightly different event definition with the MESA samples and inability to include PMRP fatal CHD events. A novel risk score of serum protein levels plus clinical risk factors, developed and validated in independent cohorts, demonstrated clinical utility for assessing the true risk of CHD events in intermediate risk patients. Improved accuracy in cardiovascular risk classification could lead to improved preventive care and fewer deaths.	f	\N
23097963	This work, partial pressure of the respiratory gases in the capillary blood (pH, PaO2, PaCO2) was studied, following the protective action of the beta2-drenergic stimulator-Hexoprenaline and alpha2-adrenergic blocker-Tolazoline in the bronchoconstriction caused by a beta-blocker-Propranolol. in patients with increased bronchial reactibility. pH, oxygen partial pressure (PaO2), dioxide carbon partial pressure (PaCO2) in the arterial blood, with the assistance of the analyzer IL, following some minutes of sample taking were defined in all patients. As a standard to verify the accuracy of the measurement, ampoule solutions of pH, PaO2 and PaCO2 were utilized (Acidobasel, Berlin). Following the inhalation of the beta-blocker-Propranolol (20 mg/ml-aerosol), there was an evident decrease (p < 0.05) of pO2 and a non-significant increase (p > 0.1) of pCO2. Beta2-adrenergcic stimulator-Hexoprenaline (2 inh x 0.2 mg), shows an protective effect in the decrease of pO2 (p < 0.05) following the bronchoconstriction being provoked by Propranolol. Alpha2-adrenergic blocker-Tolazoline (20 mg/ml-aerosol), has not shown a protective action in the bronchoconstriction caused with propranolol, therefore significant decrease (p < 0.05) of pO2 and a non-significant increase (p > 0.1) of pCO2 appeared. This shows that stimulation of beta2-adrenergic receptor has protective action in changes of the respiratory gases. Meantime, blocker of the alpha2-adrenergic receptor (Tolazoline) has not shown a protective action in changes of the respiratory gases.	f	\N
23101267	CD200 and its receptor were recognized as having the multiple immunoregulatory functions. Their immunoregulatory, suppressive, and tolerogenic potentials could be very effectively exploited in the treatment of many diseases, e.g. Alzheimer disease, rheumatoid arthritis, and allergy to name only some. Many research projects are aimed to develop clinically valuable methods being based on the structure and function of these paired molecules. In this review, we would like to introduce CD200/CD200R functions in a clinical context.	f	\N
23114434	Surveillance of nosocomial infections is meanwhile a cornerstone of infection prevention activities in hospitals. The objective of this article is to compare healthcare-associated infection rates in intensive care patients, neonatal intensive care patients and operated patients (ICU-KISS, OP-KISS, NEO-KISS) of the German nosocomial infection surveillance system (KISS) with the corresponding data of the US American National Healthcare Safety Network (NHSN) and the European Centre for Disease Prevention and Control (ECDC). In general, the methodological differences among the three surveillance systems are minor but there are some exceptions. Therefore, differences between countries have to be interpreted very carefully as they may be due to differences in diagnostics, patient mix, types of interventions, length of stay, selection of participating hospitals, post-discharge surveillance activities and interpretation of case definitions. Organizational aspects, such as mandatory participation with public disclosure on infection rates may also have an impact.	f	\N
23117745	Arterial calcification is the result of the same highly organized processes as seen in bone, which rely on a delicate balance between osteoblasts and osteoclasts. Although previously understood as passive precipitation, evidence has accumulated to suggest that arterial calcification is the result of organized, regulated processes bearing many similarities to osteogenesis in bone, including the presence of subpopulations of arterial wall cells that retain osteoblastic lineage potential. These cells have the potential to form mineralized nodules and express osteoblast markers, including bone morphogenetic protein-2, osteocalcin, osteopontin, and alkaline phosphatase. By contrast, osteoclast-like cells mediate the catabolic process of mineral resorption. Recent data shows that cells positive for tartrate-resistant acid phosphatase, a major marker for osteoclasts, have been histologically identified in atherosclerotic lesions and are referred to as osteoclast-like cells. Evidence has accumulated to suggest that initial arterial calcification through passive precipitation of calcium phosphate initiates balanced mineralization regulated by osteoclast-like and osteoblast-like cells. Subsequently, various pathogenic conditions may trigger an imbalance between osteoblastogenesis and osteoclastogenesis, leading to either calcification in stenotic/occlusive disease or destruction of the extracellular matrix in aneurysmal disease. Further elucidation of these newly emerging concepts could lead to a novel therapeutic approach to arterial stenotic/occlusive disease and/or abdominal aortic aneurysm.	f	\N
23126056	Amyloidosis is a clinical entity that results from deposition of an extracellular protein material that causes disruption in normal architecture and impairs function of multiple organs and tissues. Secondary amyloidosis (AA) is a rare but serious complication that appears in the context of cancer, chronic inflammation, and chronic infectious disease, including rheumatoid arthritis. Renal failure is the most common clinical presentation of AA, ranging from nephrotic syndrome and impaired renal function to renal failure, with a potential for high morbidity. We present a case of a 52-year-old female patient diagnosed with rheumatoid arthritis at age 27. She was hospitalized due to worsening clinical condition. Physical examination revealed marked peripheral edema in both lower extremities. Laboratory tests showed an increase of inflammatory reactants, anemia, electrolyte disbalance, and severe hypoalbuminemia and hypoproteinemia. She had proteinuria 15.4 g/24 h and renal function estimated by creatinine clearance was 78 mL/min, within the second degree of chronic kidney disease. Renal biopsy was performed for evaluation of renal insufficiency with nephrotic range proteinuria. Congo red staining showed the presence of characteristic amyloid deposits that immunoreacted with the antibody against amyloid A protein, thus confirming the diagnosis of secondary amyloidosis.	f	\N
23132831	Development of effective therapeutic strategies to eliminate cancer stem cells, which play a major role in drug resistance and disease recurrence, is critical to improve cancer treatment outcomes. Our study showed that glioblastoma stem cells (GSCs) exhibited low mitochondrial respiration and high glycolytic activity. These GSCs were highly resistant to standard drugs such as carmustine and temozolomide (TMZ), but showed high sensitivity to a glycolytic inhibitor 3-bromo-2-oxopropionate-1-propyl ester (3-BrOP), especially under hypoxic conditions. We further showed that combination of 3-BrOP with carmustine but not with TMZ achieved a striking synergistic effect and effectively killed GSCs through a rapid depletion of cellular ATP and inhibition of carmustine-induced DNA repair. This drug combination significantly impaired the sphere-forming ability of GSCs in vitro and tumor formation in vivo, leading to increase in the overall survival of mice bearing orthotopic inoculation of GSCs. Further mechanistic study showed that 3-BrOP and carmustine inhibited glyceraldehyde-3-phosphate dehydrogenase and caused a severe energy crisis in GSCs. Our study suggests that GSCs are highly glycolytic and that certain drug combination strategies can be used to effectively overcome their drug resistance based on their metabolic properties.	f	\N
23133607	Functional genetic variations play important roles in shaping phenotypic differences among individuals through affecting gene expression, and thus, very likely to influence disease susceptibility, such as cancer susceptibility. One critical question in this era of post-genome wide association studies (GWAS) is how to assess the functional significance of the genetic variations identified from GWAS. In the current study, with lymphoblastoid cell lines (LCLs) from 74 non-related women with familial ovarian cancer and 47 unrelated controls matched on gender and race, we explored the associations between seven ovarian cancer risk variants identified from GWAS (rs3814113 on 9p22.2, rs2072590 on 2q31, rs2665390 on 3q25, rs10088218, rs1516982, rs10098821 on 8q24.21, and rs2363956 on 19p13) and whole genome mRNA expression profiles. We observed 95 significant trans-associations at a permutation level of 0.001. Compared to the other risk variants, rs10088218, rs1516982, and rs10098821 on 8q24.21 had the greatest number of significant associations (25, 16, and 38, respectively). Two possible cis-associations were observed between rs10098821 and c-Myc, and rs2072590 and HS.565379 (Permutated P = 0.0198 and 0.0399, respectively). Pathway enrichment analysis showed that several key biological pathways, such as cell cycle (P = 2.59×10(-06)), etc, were significantly overrepresented. Further characterization of significant associations between mRNAs and risk alleles might facilitate understanding the functions of GWAS discovered risk alleles in the genetic etiology of ovarian cancer.	f	\N
23136226	A combination of bortezomib (1.3 mg/m(2)), melphalan (5 mg/m(2)), and dexamethasone (40 mg) (BMD), with all three drugs given as a contemporary intravenous administration, was retrospectively evaluated. Fifty previously treated (median 2 previous lines) patients with myeloma (33 relapsed and 17 refractory) were assessed. The first 19 patients were treated with a twice-a-week (days 1, 4, 8, 11, 'base' schedule) administration while, in the remaining 31 patients, the three drugs were administered once a week (days 1, 8, 15, 22, 'weekly' schedule). Side-effects were predictable and manageable, with prominent haematological toxicity, and a better toxic profile in 'weekly' schedule (36% versus 66% in 'base' schedule). The overall response rate was 62%. After median follow-up of 24.5 months (range 2.7-50 months), the median progression-free survival (PFS) was 21.6 with no difference between the two schedules and the median overall survival (OS) was 33.8 months. Independently from the adopted schedule, we found that also in a cohort of relapsed/refractory patients achieving at least partial remission improved PFS (35.2 versus 9 months) and OS (unreached median versus 18 months). Taken together, our observations suggest that BMD is an effective regimen in advanced myeloma patients with acceptable toxicity.	f	\N
23137772	Molecular cytogenetic evaluation of human osteosarcoma (OS) has revealed the characteristically high degree of genomic reorganization that is the hallmark of this cancer. The extent of genomic disorder in OS has hindered identification of the genomic aberrations driving disease progression. With pathophysiological similarities to its human counterpart, canine OS represents an ideal model for comparison of conserved regions of genomic instability that may be disease-associated rather than genomic passengers. This study used high-resolution oligonucleotide array comparative genomic hybridization and a variety of informatics tools to aid in the identification of disease-associated genome-wide DNA copy number aberrations in canine and human OS. Our findings support and build upon the high level of cytogenetic complexity, through the identification of shared regions of microaberration (<500 kb) and functional analysis of possible orthologous OS-associated genes to pinpoint the cellular processes most commonly affected by aberration in human and canine OS. Aberrant regions contained previously reported genes such as CDC5L, MYC, RUNX2, and CDKN2A/CDKN2B, while expanding the gene of interest list to include ADAM15, CTC1, MEN1, CDK7, and others. Such regions of instability may thus have functional significance in the etiology of OS, the most common primary bone tumor in both species.	f	\N
23143555	The objective of the study is to investigate the mechanisms of cyclophosphamide sequential therapy for patient with primary Sjögren's syndrome-associated interstitial lung disease (PSS-ILD). This was a retrospective review of 15 patients (2005-2008) with PSS-ILD who underwent cyclophosphamide sequential therapy. Peripheral blood and bronchoalveolar lavage (BALF) were obtained before and 3, 6, 12 and 24 months after the treatment. The TNF-α and TGF-β1 mRNA levels in peripheral blood were measured using reverse transcription polymerase chain reaction. Serum and BALF TNF-α, TGF-β1 and MMP-9 levels were measured using sandwich enzyme-linked immunosorbent assay. The average levels of serum TNF-α (0.39 ± 0.22) and TGF-β1 (0.31 ± 0.18) mRNA in patients with PSS-ILD were higher compared with that in patients with PSS without ILD. TNF-α level (0.23 ± 0.19) was significantly decreased 3 months after cyclophosphamide treatment (t = 2.533, p < 0.05), and TGF-β1 (0.31 ± 0.18) level markedly decreased after 6 months of treatment (t = 2.617, p < 0.05). The levels of serum TNF-α (11.2 ± 2.6) μg/L, TGF-β1 (72 ± 19) μg/L and MMP-9 (38 ± 9) μg/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-β1 (36 ± 12) μg/L level decreased significantly after 3 months of treatment (t = 2.526, p < 0.05), and TNF-α level (7.1 ± 1.3) μg/L markedly decreased after 6 months of therapy (t = 2.578, p < 0.05). MMP-9 level (18 ± 4) μg/L decreased significantly after 12-month treatment (t = 2.329, p < 0.05). The levels of BALF TNF-α (17.1 ± 3.5) μg/L, TGF-β1 (36 ± 17) μg/L and MMP-9 (27 ± 10) μg/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-β1 (21 ± 14) μg/L level decreased significantly after 3-month treatment, and TNF-α level (9.4 ± 1.7) μg/L was decreased after 6 months of cyclophosphamide treatment that may be associated with its inhabitation on production of TNF-α, TGF-β1 and MMP-9.	f	\N
23144854	The Glutathione S-transferase P1 (GSTP1) polymorphism have been considered a risk modifier for developing head and neck cancer (HNC) in many studies; however, the results of such studies are inconsistent. The aim of this study was to evaluate the possible association between the GSTP1 Ile105Val polymorphism and risk of HNC. We performed a search in the relevant electronic database and a meta-analysis based on 28 published case-control studies that included 6,404 cases and 6,523 controls. To take into account the possibility of heterogeneity across the studies, a Chi-square based I(2)-statistic test was performed. Crude pooled odds ratios (ORs) with 95% confidence intervals (CIs) were assessed using both fixed-effects and random-effects models. The results of this meta-analysis showed that the GSTP1 Ile105Val polymorphism was not significantly associated with risk of HNC in the overall study population (pooled OR 1.00, 95% CI 0.92-1.09) or in subgroup analyses stratified by ethnicity, sample size, tumor site or publication year. Moreover, substantial evidence of heterogeneity among the studies was observed. Publication year was identified as the main cause of heterogeneity. This meta-analysis does not support a significant association between the GSTP1 Ile105Val polymorphism and risk of HNC.	f	\N
23145068	Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9-15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4).In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation.	f	\N
23146629	We report a 14-year-old-boy with markedly elevated serum creatine kinase (CK) levels, in whom massive triglyceride storage was found in peripheral blood leukocytes and in muscle biopsy. Sequencing PNPLA2, the gene encoding the adipose triglyceride lipase (ATGL) and responsible for the neutral lipid storage disease with myopathy (NLSDM), we identified two heterozygous mutations, including a previously reported nonsense and a novel missense mutation in the patatin domain of the gene. Lipid storage myopathy can be clinically silent in childhood and presenting only with hyperCKemia.	f	\N
23154328	Trismus is a common problem among oral cancer patients. This report aimed to study the inciting factors of trismus and to find out the rationale of trismus release. Between 1996 and 2008, 61 oral cancer patients with retrievable records of interincisor distance (IID) were analyzed by retrospective chart review. The IID decreased from 31.4 (12.4) to 24.9 (12.0) mm in 36 patients undergoing cancer ablation only (P = 0.001). Other variables prompting trismus include buccal cancer (P = 0.017), radiotherapy (P = 0.008), and recurrence (P = 0.001). In contrast, the IID improved from 11.7 (7.1) to 22.7 (11.9) mm in 25 patients receiving cancer ablative and trismus releasing surgeries (P = 0.000). The improvement fared better in individuals with IID less than 15 mm than the others (P = 0.037). In conclusion, involvement of buccal region, ablative surgery, radiotherapy, and recurrence are provocative factors of trismus. Patients with IID less than 15 mm will benefit from releasing surgery significantly. Others may better be handled with conservative managements firstly, and enrolled as candidates of surgical release only until the patients entertained a 28-month period of disease-free interval, by which time the risk of recurrence would be markedly reduced.	f	\N
23159635	Activin, a member of the transforming growth factor-β family, has been known to be a growth and differentiating factor. Despite its pluripotent effects, the roles of activin signaling in prostate cancer pathogenesis are still unclear. In this study, we established several cell lines that express a constitutive active form of activin type IB receptor (ActRIBCA) in human prostate cancer cells, ALVA41 (ALVA-ActRIBCA). There was no apparent change in the proliferation of ALVA-ActRIBCA cells in vitro; however, their migratory ability was significantly enhanced. In a xenograft model, histological analysis revealed that the expression of Snail, a cell-adhesion-suppressing transcription factor, was dramatically increased in ALVA-ActRIBCA tumors, indicating epithelial mesenchymal transition (EMT). Finally, mice bearing ALVA-ActRIBCA cells developed multiple lymph node metastases. In this study, we demonstrated that ActRIBCA signaling can promote cell migration in prostate cancer cells via a network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancers.	f	\N
23167225	In this study, we hypothesized that subclinical impairment of left ventricular (LV) mechanical function in bicuspid aortic valve (BAV) patients is independent of valvular hemodynamics represented by valvuloarterial impedance and aortic elastic characteristics. Therefore, we aimed to test left ventricular mechanics in cases of isolated non-stenotic BAV with non-dilated aorta. Thirty-three patients with isolated BAV exhibiting non-dilated aorta, and 25 age-and gender-matched healthy subjects were included in the study. Patients with aortic valve velocity > 1.5 m/s and mild-to-moderate aortic regurgitation or ascending aorta diameter > 3.5 cm were excluded from the study. Aortic elasticity parameters and valvulo-arterial impedance were calculated. Strain measurements were reported as the peak longitudinal strain (LS) for four chamber (4C), long axis (LAX) and two chamber (2C) views. Strain rate (Sr) measurements were reported as the peak systolic strain rate (Sr-sm), early diastolic strain rate (Sr-em) and late diastolic strain rate (Sr-am) for 4C, LAX and 2C views. Systolic and diastolic diameters of the ascending aorta, aortic elastic properties (aortic strain, aortic distensibility, aortic stiffness and aortic elastic modulus), and valvulo-arterial impedances were found to be comparable between the BAV and control groups. BAV group was observed to have statistically significantly lower 4C (18.9 +/- 1.7 vs. 17.8 +/- 1.5, p = 0.02), LAX (19.7 +/- 1.7 vs. 17.7 +/- 1.3, p = 0.001) and 2C (20.1 +/- 1.8 vs. 17.7 +/- 1.2, p < 0.001) peak longitudinal strain values compared with the control group. Moreover, LV-GS values were found to be significantly lower in the BAV group than in the control group (19.6 +/- 1.1 vs. 17.7 +/- 0.9, p < 0.001). However, there was no statistically significant difference between the groups in terms of Sr-sm, Sr-em ve Sr-am values in the 4C, LAX, and 2C views. BAV might affect LV systolic functions, assessed by 2D strain imaging, in a fashion independent from the valvular dynamics and aortic elasticity. This might show that BAV is not only a valvular disease, but possibly a ventricular disease as well.	f	\N
23168153	Allergic rhinitis (AR) is a highly prevalent allergic disease and also counts among the 10 most frequent reasons for medical consultation. Its impact on quality of life (QoL) and work productivity has been established but comparisons with other diseases are rare in the literature. The aim of this study was to evaluate the impact of AR in health-related QoL (HRQoL) and work productivity in primary care patients, compared with other prevalent diseases such as hypertension, diabetes mellitus (DM) type II, and symptomatic depression. Six hundred sixteen patients were included in a multicenter cross-sectional observational study. A generic HRQoL questionnaire, 36-item Short Form, and a specific questionnaire, "Work Productivity and Activity Impairment" were handed out to measure QoL and work productivity impact of the diseases. To assess clinical severity with a comparable scale between diseases Clinical Global Impression (CGI) had been used. Symptomatic depression was found to produce the greatest impairment on work productivity with a decrease of 59.5%, with significant differences compared with AR, hypertension, and DM type II (p < 0.05). Symptomatic depression was found to produce the highest negative impact on daily activities with a statistically significant reduction of 59.4% (p < 0.05) compared with AR (26.6% decrease), hypertension (8.8% decrease), and DM (16.7% decrease) patients. Differences between AR and DM or hypertension were also significant (p < 0.05). Restriction on daily activities for AR was 27.8%, which is significantly higher (p < 0.05) than hypertension (19.8% decrease) but not DM (25.7% decrease). Depression had the highest impairment on daily activities (59.4%), compared with the remaining three groups (p < 0.05). AR impairs work productivity in a greater magnitude than hypertension and DM type II.	f	\N
23174870	Head and neck cancer is the fifth most common type of cancer worldwide. The objective of this study was to evaluate the clinical and epidemiological parameters in a head and neck surgery service. Cross-sectional study using patients' records, developed in otolaryngology and head and neck department of a university hospital in the northwest of the state of São Paulo. A total of 995 patients in the head and neck surgery service between January 2000 and May 2010 were evaluated. The variables analyzed included: age, gender, skin color, tobacco and alcohol consumption, primary site, staging and histological tumor type, treatment and number of deaths. The disease was more frequent among men (79.70%), smokers (75.15%) and alcohol abusers (58.25%). The most representative sites were oral cavity (29.65%) and larynx (24.12%) for the primary site; squamous cell carcinoma (84.92%) was the most frequent histological type, and surgery (29.04%) and radiotherapy (14.19%) were the most common treatments. The cancer that affects patients assisted by the head and neck surgery service occurs mainly men, smokers and alcohol abusers, and the oral cavity and larynx are the sites with the highest incidence. The high rate of patients with stages III and IV indicates late diagnosis by the treatment centers, which reflects the need for prevention education campaigns for early diagnosis of the disease.	f	\N
23178050	Antidepressants might increase compliance with cardiovascular disease risk reduction interventions. However, antidepressants have been linked to deleterious metabolic effects. In the present multicenter study, we sought to determine whether patients who take antidepressants derive the expected benefits from cardiac rehabilitation in terms of improvements in multiple atherosclerotic risk factors. A cohort of 26,957 patients who had completed a baseline assessment before participating in an exercise-based cardiac rehabilitation program constituted the study population. The patients were stratified into 3 cohorts (i.e., nondepressed, depressed unmedicated, and depressed medicated) at baseline according to a self-reported history of depression and the current use of antidepressants. Risk factors were assessed at baseline and after ∼12 weeks of program participation. A self-reported history of depression was present at baseline in 5,172 patients (19.2%). Of these patients, 2,147 (41.5%) were taking antidepressants. Patients in the nondepressed cohort (49.4% completion) were more likely (p <0.001) to complete the exit assessment than patients in the depressed unmedicated (44.5% completion) or depressed medicated (43.5% completion) cohorts. Patients in all 3 cohorts who completed the exit assessment showed significant improvement in multiple risk factors. Moreover, the magnitude of improvement in blood pressure, serum lipids and lipoproteins, fasting glucose, weight, and body mass index was similar (p >0.05) in patients taking antidepressants and those who were not. In conclusion, our study is the first to show that antidepressants do not offset the average magnitude of improvement in multiple atherosclerotic risk factors that occurs with completion of a cardiac rehabilitation program.	f	\N
23179223	Exposomic studies of the rapidly changing environment of the Three Gorges Reservoir (TGR) after its impounding is elaborated as a novel field of human and environmental research. Molecular exposomics is focused on the measure of all exposures to molecules and especially persistent organic pollutants-like compounds are of emerging interest due to their lifetime existence in the environment and humans. Theoretical considerations in general and particular for the TGR are deduced and presented using quantitative approaches for this research field. Since exposomics is strongly time-dependent, a theory is presented to link extension of exposure, time, and related effects. Similarity to the first law of thermodynamics is outlined. On top of this, the integrated use of biomarkers is presented employing chemical analysis for biomarkers of exposure and effects, biomarkers in vivo, in vitro approaches and the link between chemical mixtures, and the onset of disease and lethality. Besides real organisms, also virtual organisms are favored to act as well-defined sub-compartments such as fat of biota and with respect to time of exposure. Exposomics is the perspective of risk evaluation and chronic exposures in the running century. It needs novel theories, approaches, and integrated action between medical and environmental disciplines. The existing knowledge about molecular stressors has to be assembled and put into a context especially with respect not only to time resp. lifetime exposure of humans but also eco-toxicological findings by using highly conserved phylogenetic mechanisms to enable links between human and risks of environmental biota. The TGR is a good example not only to employ biomonitoring of real but also virtual organisms due to the lack of established ecotopes in this changing environment so far. Progress in understanding long-term risks requires a proper theory as well as novel tools such as virtual organisms. On top, multidisciplinary approaches and the utilization of existing knowledge about the exposure of the environment and humans have to be merged and directed into mutual concepts. Effect-oriented and chemical analysis must be designed time-oriented to determine lifetime exposures of mankind and nature. Perspectively, a first attempt about exposomic theory and concepts is proposed and has to be developed experimentally further enclosing virtual besides of real organisms and compartments. Environmental and human exposomics have to be considered as a unified global issue in order to effectively utilize their mutual existing knowledge most effectively. The TGR is a challenging model system aiming this objective.	f	\N
23179576	In this study of 100,949 new users of oral bisphosphonates age ≥ 35 years, "early quitters" were found to differ from others with poor refill compliance in terms of socioeconomic, demographic, and treatment-related characteristics. New risk factors for poor compliance and persistence were identified. Poor compliance with anti-osteoporotic therapy is an on-going worldwide challenge. In this study, we hypothesized that "early quitters" differ in socioeconomics, demographics, co-medications, and comorbid conditions from other patients with low compliance. The study was a register-based nationwide cohort study of anti-osteoporotic therapy comprising 100,949 men and women. Statistical analysis including backward stepwise logistic regression analysis was used to explain causes of treatment failure and Kaplan-Meier survival analysis to estimate persistence of treatment. It was noted that 56.6 % of the patients were persistent and compliant, 4.7 % of the patients were persistent but "low compliant" while 38.7 % of the patients were "early quitters". "Early quitters" were found to differ in socioeconomics from "low compliant" patients. Differences concerning increased risk of "early quitters" were associated with high household income, subjects' age 71.9-79 years, living in the countryside or village, prior treatment with analgesics and anti-parkinson drugs, and dementia. Differences concerning decreased risk of "early quitters" were associated with male, living in an apartment, children living at home, living close to a university hospital, anti-osteoporotic therapy other than alendronate, number of drugs especially above three, pulmonary disease, collagen disease. The results suggest a need for improved support for patients to facilitate the interpretation of the disease and the perception of the benefits and risks of treatment-to reduce the risk of "early quitters". We were able to identify new risk groups that may be candidates for targeted actions.	f	\N
23198711	To examine the long-term relationships between costs, utilization, and patient-centered medical home (PCMH) clinical practice systems. Clinical practice systems were evaluated at baseline by the Physician Practice Connections-Research Survey (PPC-RS). Annual costs and utilization of a retrospectively constructed cohort of 58,391 persons receiving primary care at 1 of 22 medical groups over a 5-year period (2005-2009) were compared. Multivariate regressions adjusting for patient demographics, health status, and autoregressive errors compared PPC-RS scores and study outcomes for the entire cohort and 3 subcohorts defined by medical complexity (medication count 0-2 [n = 29,657], 2-6 [n = 19,505], >7 [n = 9229]). Outcomes (adjusted to 2005 dollars) were total costs, outpatient costs, inpatient costs, inpatient days, and emergency department (ED) use. For the entire cohort, a 10% increase in PPC-RS scores was associated with 3.9 (medication count: 0-2), 6 (3-6), and 11.6 (>7) fewer ED visits per 1000 in 2005; and 5.1, 7.6, and 13.6 fewer ED visits in 2009. That 10% increase was not associated with the 0-2 medication subcohort's total (-$22/person in 2005; $184/person in 2009), outpatient (-$11/person in 2005; $42/person in 2009), or inpatient ($26/person in 2005; $29/person in 2009) costs. However, it was associated with significantly decreased total (-$446/person in 2005; -$184/person in 2009) and outpatient (-$241/person in 2005; -$54/person in 2009) costs for the most medically complex subcohort (>7 medications). Association of PCMH clinical practice systems with reduced costs appears limited to the most medically complex patients.	f	\N
23199744	Due to their unique electric, magnetic, and optical properties, engineered nanostructures have been applied to provide diagnostic, therapeutic, as well as prognostic information about the status of disease. In this study, we report a multifunctional nanoprobe based on PEGylated Gd(2)O(3):Yb(3+), Er(3+) nanorods (denoted as PEG-UCNPs) for in vivo up-conversion luminescence (UCL), T(1)-enhanced magnetic resonance (MR), and X-ray computed tomography (CT) multi-modality imaging. A facile and large-scale hydrothermal system combining the merits of an in situ thermal decomposition method and a surface-modified approach is introduced to construct high-quality PEG-UCNPs. By grafting PEG molecules on the surface of PEG-UCNPs, the nanostructures possess excellent stability against in vivo environment and hold long blood circulation time. Cell-cytotoxicity assay, hemolyticity, as well as post-injection histology, hematology, and inflammation analysis further demonstrate their non-cytotoxic character and indicate further in vivo application. In detail, the capability of PEG-UCNPs as high-performance contrast agents for UCL/MR/CT imaging is evaluated successfully through small-animal experiments. Additionally, pharmacokinetics, biodistribution, and clearance route are studied after intravenous injection in a mouse model, reflecting their overall safety.	f	\N
23208668	The surgical lesion of different brain structures has been used as a treatment for Parkinson's disease (PD) for several decades. More recently, the favored therapeutic approach has involved the administration of levodopa and the use of DBS. These two major therapeutic advances have greatly modified both the clinical condition of patients and the history of the disease. With the introduction of L-dopa in 1967, patients could regain mobility, because their akinesia, tremor, and rigidity were greatly improved, with consequent significant improvement in quality of life and increased life expectancy. However, after the so-called "honeymoon" period in which the disease seemed to be controlled, motor fluctuations and L-dopa-induced dyskinesias mitigated the initial enthusiasm. In the 1990s, unilateral pallidotomy and DBS of the globus palllidus internus and STN reduced these motor fluctuations and dyskinesias remarkably, thereby inaugurating a new era in the surgical treatment of PD. Short- and medium-term follow-up studies of patients who underwent surgery have documented sustained, significant motor benefits. However, given the progressive nature of PD and the purely symptomatic effects of pallidotomy and DBS, the long-term clinical evolution of these surgical patients currently seems to be associated with a new PD phenotype, mainly characterized by axial motor problems and cognitive impairment. Here, we analyze the long-term clinical outcomes of surgical PD patients with at least 5-year follow-up, focusing on the long-term motor symptoms that were initially responsive to surgery.	f	\N
23216270	Although associations between autoimmune disorders (AIs) and the development of myeloid neoplasms have been described, the pathologic features and natural history of these malignancies have not been well characterized. We evaluated whether patients with AIs with acute myeloid leukemia (AML) were similar in nature to patients traditionally considered to have therapy-related AML (t-AML). Twenty-three patients with AML with a documented prior AI were included in our analysis. Median age at AML diagnosis was 59 years (range 32-78 years), and four patients were men (17%). Median latency between AI diagnosis and AML was 7.0 years. Ten patients (43%) had normal cytogenetics and six patients (26%) had favorable risk disease. In patients older than 65, all four patients had a normal karyotype. Median follow-up for all patients was 19.8 months (range 1.8-100.4 months), with 12 patients alive at last follow-up and median overall survival for all patients of 68.1 months. The encouraging survival data lend support to the notion that AML in patients with AIs appears to have characteristics and outcome more analogous to de novo than t-AML.	f	\N
23217354	MicroRNAs are endogenously expressed small noncoding RNAs that regulate gene expression at the post-transcriptional level. MicroRNAs have emerged as key regulators of several physiological and pathophysiological processes in the cardiovascular system. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the development of atherosclerosis and cardiovascular disease, including change in endothelial function, vascular smooth muscle cell proliferation and migration, macrophage function, and foam cell formation. In this review, we summarize the recent data showing the roles of microRNAs in cell studies, studies on atherosclerotic mice, and human studies.	f	\N
23219418	The appearance of liver metastases during the follow-up of a patient with a skin melanoma has classically been considered a sign of a very poor prognosis. There are limited therapeutic options, since these lesions are non-resectable and form part of a disseminated disease in several organs. In certain cases, in those where the disease is restricted to the liver or accompanied by a resectable extra-hepatic disease, hepatectomy can be useful, obtaining acceptable survivals of about 25% at 5 years, although hepatic or skin recurrence is usually early. The limited number of patient cases published, the absence of randomised studies, and the heterogeneity of the series, makes it difficult to reach conclusions to be able to recommend which patients may benefit from liver resection, with an acceptable level of scientific evidence, and thus define its real usefulness. There are also no action plans defined as to when and what type of adjuvant therapy we should use.	f	\N
23222568	The rarity of conjunctival melanoma has impeded progress in the management of patients with this cancer; however, much progress has occurred in recent years. Primary acquired melanosis is now differentiated histologically into hypermelanosis and conjunctival melanocytic intra-epithelial neoplasia, for which an objective reproducible scoring system has been developed. Mapping and clinical staging of conjunctival disease has improved. Adjunctive radiotherapy and topical chemotherapy have made tumour control more successful, with reduced morbidity. Genetic analyses have identified BRAF and other mutations, which may predict responsiveness to new chemotherapeutic agents, for example Vemurafenib, should metastatic disease develop. Multicentre studies are under way to enhance survival prediction by integrating clinical stage of disease with histological grade of malignancy and genetic abnormalities. Such improved prognostication would not only be more relevant to individual patients, but would also provide greater opportunities for basic science research.	f	\N
23222982	The study aimed to assess the efficacy of the adopted principles of the treatment of lung abscess without sequestration on the example of 2397 patients. Treatment led to the complete recovery in 1731 (72,2%) patients. The 614 (25,6%) patients showed the chronization of the process and 52 (2,2%) died. The surgical treatment of lung abscess without sequestration (performed in cases of uneffective conservative treatment) led to the complete recovery on 45.7% more often and the chronization of the process was registered on 26.8% more seldom, whereas the lethality rate was higher than by conservative treatment on 8%.	f	\N
23226290	MiRNAs are key regulators of tumorigenesis that are aberrantly expressed in the circulation and tissue of patients with cancer. The aim of this study was to determine whether miRNA dysregulation in the circulation reflected similar changes in tumour tissue. Athymic nude mice (n = 20) received either a mammary fat pad (n = 8, MFP), or subcutaneous (n = 7, SC) injection of MDA-MB-231 cells. Controls received no tumour cells (n = 5). Tumour volume was monitored weekly and blood sampling performed at weeks 1, 3 and 6 following tumour induction (total n = 60). Animals were sacrificed at week 6 and tumour tissue (n = 15), lungs (n = 20) and enlarged lymph nodes (n = 3) harvested. MicroRNAs were extracted from all samples (n = 98) and relative expression quantified using RQ-PCR. MiR-221 expression was significantly increased in tumour compared to healthy tissue (p<0.001). MiR-10b expression was significantly higher in MFP compared to SC tumours (p<0.05), with the highest levels detected in diseased lymph nodes (p<0.05). MiR-10b was undetectable in the circulation, with no significant change in circulating miR-221 expression detected during disease progression. MiR-195 and miR-497 were significantly decreased in tumour tissue (p<0.05), and also in the circulation of animals 3 weeks following tumour induction (p<0.05). At both tissue and circulating level, a positive correlation was observed between miR-497 and miR-195 (r = 0.61, p<0.001; r = 0.41, p<0.01 respectively). This study highlights the distinct roles of miRNAs in circulation and tissue. It also implicates miRNAs in disease dissemination and progression, which may be important in systemic therapy and biomarker development.	f	\N
23227561	We reviewed the tuberculosis (TB) surveillance database to determine the mode of detection, delays in achieving a TB diagnosis, and patients' occupational status upon registration. Of the 23,261 TB patients who were newly notified in 2010, 81.7% were diagnosed at medical institutions. Of these, 12.0% were diagnosed during hospitalisation with a disease other than TB, and 9.9% were diagnosed during outpatient visits with diseases other than TB. The overall proportion of TB cases detected by contact examination was only 2.8%, but this mode of detection was higher (56.1%) among younger TB patients aged 0-14 years. Of the 18,328 pulmonary TB patients, 27.3% had only respiratory symptoms, 31.0% had both respiratory and other symptoms, and 16.4% had only non-respiratory symptoms. Approximately one-quarter of elderly patients aged > or = 80 years with symptomatic pulmonary TB had only non-respiratory symptoms. pulmonary TB tended to have long total delays (the amount of time between the onset of symptoms and diagnosis). Among elderly patients, patient delays tended to be short, whereas doctor delays tended to be long. Of the 2,785 female pulmonary TB patients aged 20-59 years, 14.5% were medical workers and 10.4% of these were nurses.	f	\N
23251076	NK cells exhibit the highest cytotoxic capacity within the immune system. Alteration of their number or functionality may have a deep impact on overall immunity. This is of particular relevance in aging where the elderly population becomes more susceptible to infection, cancer, autoimmune diseases, and neurodegenerative diseases amongst others. As the fraction of elderly increases worldwide, it becomes urgent to better understand the aging of the immune system to prevent and cure the elderly population. For this, a better understanding of the function and phenotype of the different immune cells and their subsets is necessary. We review here NK cell functions and phenotype in healthy aging as well as in various age-associated diseases.	f	\N
23254356	Similar to T-helper (Th) cells, CD8(+) T cells also differentiate into distinct subpopulations. However, the existence of IL-9-producing CD8(+) T (Tc9) cells has not been elucidated so far. We show that murine CD8(+) T cells activated in the presence of IL-4 plus TGF-β develop into transient IL-9 producers characterized by specific IFN-γ and IL-10 expression patterns as well as by low cytotoxic function along with diminished expression of the CTL-associated transcription factors T-bet and Eomesodermin. Similarly to the CD4(+) counterpart, Tc9 cells required for their differentiation STAT6 and IRF4. Tc9 cells deficient for these master regulators displayed increased levels of Foxp3 that in turn suppressed IL-9 production. In an allergic airway disease model, Tc9 cells promoted the onset of airway inflammation, mediated by subpathogenic numbers of Th2 cells. This support was specific for Tc9 cells because CTLs failed to exert this function. We detected increased Tc9 frequency in the periphery in mice and humans with atopic dermatitis, a Th2-associated skin disease that often precedes asthma. Thus, our data point to the existence of Tc9 cells and to their supportive function in Th2-dependent airway inflammation, suggesting that these cells might be a therapeutic target in allergic disorders.	f	\N
23254704	Organ transplantation and other major surgeries are impacted by ischemia-reperfusion injury (IRI). Mesenchymal stromal cells (MSCs) recently became an attractive alternative therapeutic tool to combat IRI. The present review highlights the effects of MSCs in the preclinical animal models of IRI and clinical trials, and explains their potential modes of action based on the pathophysiological IRI cascade. The application of MSCs in animal models of IRI show anti-inflammatory and anti-apoptotic effects, particularly for damage to the kidneys, heart and lungs. The mechanism of MSC action remains unclear, but may involve paracrine factors which could include the transfer of microvesicles, RNA or mitochondria. Although few clinical trials have reached completion, adverse effects appear minimal. MSCs show promise in protecting against IRI-induced damage. They appear to help recovery mainly by affecting the levels of inflammation and apoptosis during the organ repair process. In addition, they may mediate immunomodulatory effects on the innate and adaptive immune processes triggered during reperfusion and reduce fibrosis. Success in preclinical animal models has led to the initiation of ongoing clinical trials.	f	\N
23265076	Diabetes is an important contributor to the burden of disease in South Africa and prevalence rates as high as 33% have been recorded in Cape Town. Previous studies show that quality of care and health outcomes are poor. The development of an effective education programme should impact on self-care, lifestyle change and adherence to medication; and lead to better control of diabetes, fewer complications and better quality of life. Pragmatic cluster randomized controlled trialParticipants: Type 2 diabetic patients attending 45 public sector community health centres in Cape TownInterventions: The intervention group will receive 4 sessions of group diabetes education delivered by a health promotion officer in a guiding style. The control group will receive usual care which consists of ad hoc advice during consultations and occasional educational talks in the waiting room. To evaluate the effectiveness of the group diabetes education programmeOutcomes: diabetes self-care activities, 5% weight loss, 1% reduction in HbA1c. self-efficacy, locus of control, mean blood pressure, mean weight loss, mean waist circumference, mean HbA1c, mean total cholesterol, quality of lifeRandomisation: Computer generated random numbersBlinding: Patients, health promoters and research assistants could not be blinded to the health centre's allocationNumbers randomized: Seventeen health centres (34 in total) will be randomly assigned to either control or intervention groups. A sample size of 1360 patients in 34 clusters of 40 patients will give a power of 80% to detect the primary outcomes with 5% precision. Altogether 720 patients were recruited in the intervention arm and 850 in the control arm giving a total of 1570. The study will inform policy makers and managers of the district health system, particularly in low to middle income countries, if this programme can be implemented more widely. Pan African Clinical Trial Registry PACTR201205000380384.	f	\N
23268170	Kawasaki disease is a common paediatric vasculitide. It is usually diagnosed by its classical constellation of mucocutaneous signs. Recurrent Kawasaki disease is a rare phenomenon that occurs in approximately 3% of all patients diagnosed with Kawasaki disease. Its presentation is usually similar to the first episode of Kawasaki disease, and early diagnosis with prompt treatment is key in preventing associated cardiovascular morbidities. Recurrent Kawasaki disease is not well reported, and atypical presentations have not been previously reported in medical literature. Here, we report the case of a young girl with recurrent Kawasaki disease who presented atypically with acute airway obstruction secondary to retropharyngeal phlegmon.	f	\N
23275389	To determine the longitudinal effects of TNF inhibitors on BMD and radiographic progression in patients with AS and to assess independent factors associated with increased BMD in the lumbar spine. Sixty-three patients with AS were included. Twenty-six patients were treated with TNF inhibitors and 37 were not. BMD in the lumbar spine and right femur was measured by DXA at baseline and 1 and 2 years later. Lumbar spine radiography was performed at baseline and after 2 years. Radiographic progression was scored using the Stoke AS Spinal Score (SASSS) and the modified SASSS. Univariate and multivariate linear regression analyses were performed to identify factors independently associated with spinal BMD increase. BMD in the lumbar spine and total proximal femur of patients receiving TNF inhibitors increased consistently over 2 years compared with that in patients not receiving TNF inhibitors (P < 0.01 and P = 0.02), and treated patients showed increased SASSS scores (P = 0.05); however, syndesmophyte development was no different between the two groups. There was a significant difference in the change of SASSS in patients treated with both TNF inhibitors and bisphosphonates compared with those treated with TNF inhibitors alone (P < 0.01). TNF inhibitor therapy and the increase in SASSS were independently associated with increased lumbar spine BMD (P = 0.009 and P < 0.001). TNF inhibitors appear to be associated with increased SASSS scores and improvements in BMD. Further prospective studies with larger subject numbers are needed to validate this paradoxical role of TNF inhibitors.	f	\N
23278140	In contrast to adolescent acne, infantile acne (IA) is a rare condition with only a limited body of available literature. In this descriptive, retrospective study, we reviewed six cases from 2002 to 2010 treated with oral isotretinoin. The average age of onset was 6.16 months (range 0-21 mos). Consistent with the previous, limited literature, we found predominantly boys are affected, a predilection for the cheeks, and a polymorphic inflammatory morphology. Two patients had a family history of acne. All cases were successfully and safely treated with oral isotretinoin. The suggested treatment of childhood acne is similar to that of adolescents (graded according to the severity of the skin disease and risk of scarring). Oral isotretinoin appears to be an effective and safe treatment for severe IA.	f	\N
23280098	Influenza A viruses circulating in pigs in Brazil are still not characterized, and only limited data are available about swine influenza epidemiology in the country. Therefore, we characterized the hemagglutinin (HA) and neuraminidase (NA) genes of influenza viruses isolated from Brazilian pigs. We also evaluated one case of probable swine-to-human transmission. Twenty influenza viruses isolated from pigs during 2009-2010 in five Brazilian states (Minas Gerais, Sao Paulo, Parana, Rio Grande do Sul, and Mato Grosso) were used. One human isolate, from a technician who became ill after visiting a swineherd going through a respiratory disease outbreak, was also used in the study. Phylogenetic analysis for the HA and NA genes and hemagglutinin amino acid sequence alignment were performed. All isolates clustered with pandemic H1N1 2009 (pH1N1) viruses and appeared to have a common ancestor. Genetic diversity was higher in the HA than in the NA gene, and the amino acid substitution S203T in one of HA's antigenic sites was found in most of the samples. The human isolate was more related to swine isolates from the same herd visited by the technician than to other human isolates, suggesting swine-to-human transmission. Our results show that pH1N1 was disseminated and the predominant subtype in Brazilian pigs in 2009-2010.	f	\N
23284040	Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is one of the two established Hodgkin lymphoma (HL) subtypes. The risk factors of NLPHL are largely unknown. In general, genetic factors are known to have a modest effect on the risk of HL; however, familial risk in NLPHL has not been previously examined. We conducted a population-based study by using the Finnish registries and evaluated the familial risk in NLPHL. We launched a population-based search to identify patients with NLPHL and their relatives by examining the records of the Finnish Cancer Registry, established in 1953, and the official Finnish population registries. We collected a data set of 692 patients with NLPHL, identified their 4,280 first-degree relatives, and calculated the registry-based standardized incidence ratios (SIRs) for different cancers in the first-degree relatives. In addition, the primary tumor biopsies of HL-affected relatives were collected when possible, the HL diagnoses were re-reviewed by a hematopathologist, and the SIR for NLPHL was calculated on the basis of confirmed NLPHL diagnoses. On the basis of confirmed NLPHL diagnoses, the SIR for NLPHL was 19 (95% CI, 8.8 to 36) in the first-degree relatives. The risk was most prominent in female relatives of young patients. The registry-based SIR for classical HL was 5.3 (95% CI, 3.0 to 8.8), and for non-Hodgkin lymphoma, it was 1.9 (95% CI, 1.3 to 2.6). Our results implicate an unexpectedly high familial component in the development of NLPHL. Research is warranted to identify the putative genetic and environmental factors underlying this finding and to develop strategies for better management of patients with NLPHL and their relatives.	f	\N
23293016	Kawasaki disease (KD) is a systemic inflammatory illness of childhood that particularly affects the coronary arteries. It can lead to coronary artery aneurysms, myocardial infarction, and sudden death. Clinical and epidemiologic data support an infectious cause, and the etiology remains unknown, but recent data support infection with a 'new' virus. Genetic factors influence KD susceptibility; the incidence is 10-fold higher in children of Asian when compared with Caucasian ethnicity. Recent research has identified genes affecting immune response that are associated with KD susceptibility and outcome. A re-examination of the pathologic features of KD has yielded a three process model of KD vasculopathy, providing a framework for understanding the KD arterial immune response and the damage it inflicts and for identifying new therapeutic targets for KD patients with coronary artery abnormalities. The researcher is faced with many challenges in determining the pathogenesis of KD. A systems biology approach incorporating genomics, proteomics, transcriptomics, and microbial bioinformatics analysis of high-throughput sequence data from KD tissues could provide the keys to unlocking the mysteries of this potentially fatal illness of childhood.	f	\N
23295556	To describe the course and management of a protracted outbreak after intercontinental transfer of 2 patients colonized with multidrug-resistant Acinetobacter baumannii (MDRAB). An 18-month outbreak investigation. An 860-bed university hospital in France. Case patients (ie, carriers) were those colonized or infected with an MDRAB isolate. During the epidemic period, all intensive care unit (ICU) patients and contacts of carriers who were transferred to wards were screened for MDRAB carriage. Contact precautions, environmental screening, and auditing of healthcare worker (HCW) practices were implemented; rooms were cleaned with hydrogen peroxide mist disinfection. One ICU, in which most of the cases occurred, was closed on 4 occasions for thorough cleaning and disinfection. The 2 index case patients were identified as 2 patients who carried the same MDRAB strain and who were admitted to the hospital after repatriation from Tahiti 5 months apart. During an 18-month period, a total of 84 secondary cases occurred. Reintroduction of MDRAB into the ICUs occurred from patients previously colonized or from healthcare personnel. Termination of the outbreak was only achieved when all carriers from wards or the ICU were cohorted to an isolation unit with dedicated healthcare personnel. Intercontinental transfer of carriers of MDRAB can result in extensive outbreaks and serious disruption of the hospital's organization. Transmission from carriers most likely occurred via the hands of HCWs, poor cleaning protocols, airborne spread, and contaminated water from sink traps. This protracted outbreak was controlled only after implementation of an extensive control program and eventual cohorting of all carriers in an isolation unit with dedicated healthcare personnel.	f	\N
23296696	Previously, most dengue cases in Singapore were hospitalized despite low incidence of dengue hemorrhagic fever (DHF) or death. To minimize hospitalization, the Communicable Disease Centre at Tan Tock Seng Hospital (TTSH) in Singapore implemented new admission criteria which included clinical, laboratory, and DHF predictive parameters in 2007. All laboratory-confirmed dengue patients seen at TTSH during 2006-2008 were retrospectively reviewed for clinical data. Disease outcome and clinical parameters were compared over the 3 years. There was a 33.0% mean decrease in inpatients after the new criteria were implemented compared with the period before (p < 0.001). The proportion of inpatients with DHF increased significantly from 31.7% in 2006 to 34.4% in 2008 (p = 0.008); 68 DHF cases were managed safely on an outpatient basis after compared with none before implementation. DHF inpatients had more serious signs such as clinical fluid accumulation (15.5% vs 2.9% of outpatients), while most DHF outpatients had hypoproteinemia (92.7% vs 81.3% of inpatients). The eight intensive care unit admissions and five deaths during this time period all occurred among inpatients. The new criteria resulted in a median cost saving of US$1.4 million to patients in 2008. The new dengue admission criteria were effective in sustainably reducing length of hospitalization, yielding considerable cost savings. A minority of DHF patients with mild symptoms recovered uneventfully through outpatient management.	f	\N
23301916	Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia and immune deficiency. WAS gene mutations impair WAS protein function which cause WAS. The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may have similar but less severe symptoms those are also caused by mutations of the same gene. We present two cases of WAS in neonates with WAS gene mutations. Early genetic diagnosis can help to the treatment and prevention this disease.	f	\N
23313927	Mexican Americans are the fastest aging segment of the U.S. population, yet little scientific literature exists regarding the Alzheimer's disease (AD) among this segment of the population. The extant literature suggests that biomarkers of AD will vary according to race/ethnicity though no prior work has explicitly studied this possibility. The aim of this study was to create a serum-based biomarker profile of AD among Mexican American. Data were analyzed from 363 Mexican American participants (49 AD and 314 normal controls) enrolled in the Texas Alzheimer's Research & Care Consortium (TARCC). Non-fasting serum samples were analyzed using a luminex-based multi-plex platform. A biomarker profile was generated using random forest analyses. The biomarker profile of AD among Mexican Americans was different from prior work from non-Hispanic populations with regards to the variable importance plots. In fact, many of the top markers were related to metabolic factors (e.g., FABP, GLP-1, CD40, pancreatic polypeptide, insulin-like-growth factor, and insulin). The biomarker profile was a significant classifier of AD status yielding an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.77, 0.92, and 0.64, respectively. Combining biomarkers with clinical variables yielded a better balance of sensitivity and specificity. The biomarker profile for AD among Mexican American cases is significantly different from that previously identified among non-Hispanic cases from many large-scale studies. This is the first study to explicitly examine and provide support for blood-based biomarkers of AD among Mexican Americans. Areas for future research are highlighted.	f	\N
23316660	Polyarteritis nodosa (PAN) is a multi-system disease, characterized by necrotizing vasculitis of medium-sized arteries that may affect any organ system. Cutaneous PAN is the cutaneous limited form of PAN. It affects 10% of all cases of PAN and usually demonstrates a benign and chronic course. We hereby describe a 47-year-old female with diabetes mellitus who presented with painful ulcers on both legs. The clinical and histological findings were consistent with PAN. A thorough investigation ruled out systemic PAN and cutaneous PAN was determined. Despite intensive therapies including corticosteroids and azathioprine, marked progression of the ulcers was noted and large areas of necrosis appeared. The patient underwent above-knee amputation of both legs and eventually died in less than three years. Although cutaneous PAN is known to have a benign and chronic course, we have presented an unusual progressive and severe course that resulted in the death of the patient.	f	\N
23324593	An under-appreciated clue about pathogenesis in Parkinson disease (PD) is the distribution of pathology in the early and middle stages of the disease. This pathological 'roadmap' shows that in addition to dopaminergic neurons in the substantia nigra pars compacta (SNc), a significant number of other central and peripheral neuronal populations exhibit Lewy pathology, phenotypic dysregulation or frank degeneration in PD patients. This spatially distributed, at-risk population of neurons shares a number of features, including autonomously generated activity, broad action potentials, low intrinsic calcium buffering capacity and long, poorly myelinated, highly branched axons. Many, and perhaps all, of these traits add to the metabolic burden in these neurons, suggesting that mitochondrial deficits could drive pathogenesis in PD-in agreement with a large segment of the literature. What is less clear is how this neuronal phenotype might shape the susceptibility to proteostatic dysfunction or to the spread of α-synuclein fibrils deposited in the extracellular space. The review explores the literature on these issues and their translational implications.	f	\N
23327371	Over the past few decades a large number of new and emerging infectious diseases have been recognised in humans, partly because of improved diagnostic technologies and increased awareness and also, partly because of dynamic ecological changes between human hosts and their exposure to animals and the environment (Coker et al. 2011). Some 177 new pathogenic organisms have been recognised to be 'emerging', that is, have newly arisen or been newly introduced into human populations; almost three quarters of these, 130 (73%), have come from zoonotic origins (Cascio et al. 2011; Cutler, Fooks &amp; Van Der Poel 2010; Taylor, Latham &amp; Woolhouse 2001; Woolhouse &amp; Gowtage-Sequeria 2005). One of the most prevalent and important human infectious disease is influenza, a disease responsible globally for a quarter million deaths annually. In the USA alone the toll from influenza is estimated at 36 000 deaths and 226 000 hospitalisations, and it ranks as the most important cause of vaccine preventable mortality in that country (CDC 2010). The epidemiological behaviour of human influenza clearly defines it as an emerging infectious disease and the recent understanding of its zoonotic origins has contributed much to the understanding of its behaviour in humans (Fauci 2006).	f	\N
23330027	Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) constitute important public health problems in developing countries. Children with ARF and RHD seen at Children's Hospital-Sudan from May 2008-2009 were examined clinically and by echocardiography. Blood cytokines (interleukin 10 (IL10), Tumor necrosis factor alpha (TNF- alpha) and interferon gamma (IFN-gamma) were done. Thirty six children were enrolled; 63% had established RHD, and 37% ARF. Mitral regurgitation (MR) was the most common lesion (94%).Ninety five percent of the valve lesions were severe. The serum interleukin IL10 level ranged between 3-6 pg/ml. TNF alpha levels were 9- 100 pg/ml in 12 patients (40%), 101-1000 pg/ml in 10 patients (33%), more than 1000 in 8 patients (26%). The level of IFN gamma ranged between 2-7 pg/m in all patients except 2 (84 and 135 pg/ml). RHD is manifested with severe valvular lesions and a high TNF alpha indicating and ongoing inflammation.	f	\N
23330952	The authors present 1-year results in 60 patients with cervical radiculopathy due to spondylosis and stenosis that was treated with a bilateral percutaneous facet implant. The implant consists of a screw and washer that distracts and immobilizes the cervical facet for root decompression and fusion. Clinical and radiological results are analyzed. Between 2009 and 2011, 60 patients were treated with the DTRAX Facet System in a multicenter prospective single-arm study. All patients had symptomatic clinical radiculopathy, and conservative management had failed. The majority of patients had multilevel radiographically confirmed disease. Only patients with single-level radiculopathy confirmed by history, physical examination, and in some cases confirmatory nerve blocks were included. Patients were assessed preoperatively with Neck Disability Index, visual analog scale, quality of life questionnaire (Short Form-12 version 2), CT scans, MRI, and dynamic radiographs. Surgery was percutaneous posterior bilateral facet implants consisting of a screw and expandable washer and iliac crest bone aspirate. Patients underwent postoperative assessments at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year with validated outcome questionnaires. Alterations of segmental and overall cervical lordosis, foraminal dimensions, device retention and fusion criteria were assessed for up to 1 year with CT reconstructions and radiographs. Fusion criteria were defined as bridging trabecular bone between the facets, translational motion < 2 mm, and angular motion < 5°. All patients were followed to 1 year postoperatively. Ages in this cohort ranged from 40 to 75 years, with a mean of 53 years. Forty-two patients were treated at C5-6, 8 at C6-7, 7 at C4-5, and 3 at C3-4. Fifty-six had bilateral implants; 4 had unilateral implants due to intraoperative facet fracture (2 patients) and inability to access the facet (2 patients). The Neck Disability Index, Short Form-12 version 2, and visual analog scale scores were significantly improved at 2 weeks and remained significantly improved up to 1 year. At the treated level, 93% had intrafacet bridging trabecular bone on CT scans, translational motion was < 2 mm in 100% and angular movement was < 5° in 83% at the 1-year follow-up. There was no significant change in overall cervical lordosis. There was a 1.6° loss of segmental lordosis at the treated level at 1 year that was significant. Foraminal width, volume, and posterior disc height was significantly increased at 6 months and returned to baseline levels at 1 year. There was no significant decrease in foraminal width and height at adjacent levels. There were no reoperations or surgery- or device-related complications, including implant failure or retained hardware. Results indicate that the DTRAX Facet System is safe and effective for treatment of cervical radiculopathy.	f	\N
23336917	The use of ventricular assist devices in patients with complex congenital heart disease has not been well described. We present a case of successful ventricular assist device support in a 38-year-old man with congenitally corrected transposition of the great arteries and severe secondary pulmonary hypertension.	f	\N
23338998	The aim of this study was to verify if genetic factors influence the short- and long-term therapeutic responses to oestroprogestagen (OP) therapy, implemented in girls with functional hypothalamic amenorrhoea (FHA) in order to improve their bone mineral density (BMD). The study included 78 FHA girls who underwent a four-year sequential OP therapy with 17-beta oestradiol and didrogesterone. Changes in the lumbar spine BMD were determined at the end of the therapy and six years after its discontinuation, and analysed in regards to PvuII and XbaI polymorphisms of oestrogen receptor-alpha gene, BsmI polymorphism of vitamin D3 receptor gene, and Sp1 polymorphism of the type-1 collagen gene. After four years of OP therapy, a significant increase in BMD was documented in the studied group. Follow-up densitometry performed six years after completing the therapy revealed a significant decrease in BMD level; nonetheless, the values of this parameter were still significantly higher compared to pretreatment level. Neither the particular polymorphisms nor their combinations influenced the relative change in BMD at the end of the therapy and after a six-year follow-up. Variability of genes involved in oestrogen, vitamin D3 and collagen metabolism does not influence the short- and long-term results of OP therapy in girls with FHA.	f	\N
23344286	Preeclampsia complicates approximately 3-5% of pregnancies and remains one of the major causes of maternal and neonatal morbidity. It shares pathogenic similarities with adult cardiovascular disease as well as many risk factors. Attempts at prevention of preeclampsia using various supplements and classes of medications have failed or had limited success, and they were not convincing enough to lead to widespread adoption of any particular strategy. Contrary to the experience with preeclampsia, prevention of cardiovascular mortality and other cardiovascular events in nonpregnant patients using 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, or statins, is widely accepted. Pravastatin and other statins have been shown to reverse various pathophysiologic pathways associated with preeclampsia, such as angiogenic imbalance, endothelial injury, inflammation, and oxidative stress. These beneficial effects are likely to contribute substantially to preventing preeclampsia and provide biological plausibility for the use of pravastatin in this setting. Pravastatin has favorable safety and pharmacokinetic profiles. In addition, animal studies and human pregnancy exposure data do not support teratogenicity claims for pravastatin. Therefore, the Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric--Fetal Pharmacology Research Units Network started a pilot trial to collect maternal--fetal safety data and to evaluate pravastatin pharmacokinetics when used as a prophylactic daily treatment in high-risk pregnant women (identifier NCT01717586, clinicaltrials.gov).	f	\N
23346802	The purpose of this article was to describe the phenomena related to the mechanisms regulating alterations of vascular blood flow in ophthalmic and retrobulbar circulation. In this review, various indirect and direct methods of evaluating retinal blood flow have been discussed. Laser, contrast and ultrasonographic techniques, including color Doppler ultrasonography, electroretinography, electroencephalography, calorimetric investigations, with the radiographic entities and registering changes in tunica vasculosa circulation were described. Additionally, radiographic investigations, isometric measurements and studies with the use of pharmacological agents, evaluation of partial pressure of oxygen or carbon dioxide in both inhaled and exhaled air, and in daylight as well as in darkness were presented. Although there are many control methods of regulating mechanisms of bulbar circulation, none of those techniques used presently and in the past is ideal, hence the only investigations widely applied for this purpose have been both Doppler ultrasonography and laser methods. In the review influence of myogenic and neurogenic mechanisms on blood flow in eyeball was described. Moreover, the part of vessels coarcting and dilating substances in these hemodynamic phenomena has been included. In the course of various ophthalmic disease entities of vascular origin, different substances take part in general and local regulation of ocular and retrobulbar circulation, whose action mechanism might be the cause of hemodynamic disorders. Color Doppler ultrasonography remains one of the more frequently used methods which could indirectly register alterations of vascular blood flow in retrobulbar arteries.	f	\N
23347399	Methcathinone abuse is a new cause of manganism. The psychostimulant is prepared from pseudoephedrine using potassium permanganate as an oxidant. We describe the clinical, biological, neuroimaging characteristics and follow-up results in a large Estonian cohort of intravenous methcathinone users. During 2006-2012 we studied 38 methcathinone abusers with a mean age of 33 years. Subjects were rated by the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (HY), and Schwab and England (SE) rating scales. Twenty-four cases were reassessed 9-70 (20 ± 15) months after the initial evaluation. Manganese (Mn) in plasma and hair was analysed by inductively coupled plasma-atom emission spectrometry. Magnetic resonance imaging (MRI) was performed in 11, and single-photon emission computed tomography (SPECT) with iodobenzamide (IBZM) in eight subjects. The average total UPDRS score was 43 ± 21. The most severely affected domains in UPDRS Part III were speech and postural stability, the least affected domain was resting tremor. At follow-up there was worsening of HY and SE rating scales. Subjects had a higher mean level of Mn in hair (2.9 ± 3.8 ppm) than controls (0.82 ± 1.02 ppm), P = 0.02. Plasma Mn concentrations were higher (11.5 ± 6.2 ppb) in active than in former users (5.6 ± 1.8 ppb), P = 0.006. Active methcathinone users had increased MRI T1-signal intensity in the globus pallidus, substantia nigra and periaquaductal gray matter. IBZM-SPECT showed normal symmetric tracer uptake in striatum. Methcathinone abusers develop a distinctive hypokinetic syndrome. Though the biomarkers of Mn exposure are characteristic only of recent abuse, the syndrome is not reversible.	f	\N
23347458	We compared values of baseline serum cystatin C (SCysC), serum creatinine (SCr), and measured glomerular filtration rate (mGFR) for predicting end-stage renal disease (ESRD) in patients with type 2 diabetes and elevated albuminuria. Observational longitudinal study. Pima Indians with type 2 diabetes and elevated albumin-creatinine ratio (ACR ≥30 mg/g). Baseline SCysC, SCr, and mGFR. Individuals were followed up from their first examination with diabetes and ACR ≥30 mg/g until December 2010, onset of ESRD, or death, whichever came first. Incidence rates adjusted for age and sex were computed by Mantel-Haenszel stratification. The abilities of SCysC, SCr, and mGFR values to predict ESRD were compared with receiver operating characteristic curves. Of 234 Pima Indians with a mean age of 42.8 years who were followed up for a median of 10.7 (range, 0.6-21.3) years, 68 (29%) developed ESRD. The incidence of ESRD was significantly higher in patients in the lowest versus highest tertile of 1/SCysC (incidence rate ratio, 2.43; 95% CI, 1.31-4.50). By contrast, mGFR and 1/SCr had J-shaped associations with ESRD. In unadjusted analyses, 1/SCysC had the highest area under the receiver operating characteristic curve (AUROC; 0.719 ± 0.035) and mGFR had the lowest (0.585 ± 0.042; P < 0.001); the AUROC for 1/SCr was intermediate (0.672 ± 0.040; P = 0.1 and P = 0.03 vs 1/SCysC and mGFR, respectively). In analyses adjusted for age, sex, diabetes duration, height, weight, hemoglobin A1c level, and ACR, 1/SCysC had the highest AUROC (0.845 ± 0.026). Models with mGFR or 1/SCr alone had similar AUROCs (P = 0.9) and both were lower than the model with 1/SCysC alone (P = 0.02 and P = 0.03, respectively). The predictive values of the filtration markers are limited to the extent that their precision is based on a single measurement. SCysC level was a better predictor of ESRD than mGFR or SCr level in Pima Indians with type 2 diabetes and elevated albuminuria.	f	\N
23354259	The surgical treatment of acute colonic diverticulitis is associated with significant morbidity and mortality. However, patient and operative characteristics associated with mortality in this patient population are unclear. We hypothesize that demographic and perioperative variables can be used to predict postoperative mortality.The purpose of this study was to identify perioperative variables predictive of postoperative mortality after emergent surgery for acute diverticulitis. Patients with diverticulitis undergoing colostomy and/or partial colectomy with or without primary anastomosis were retrieved from the American College of Surgeons National Surgical Quality Improvement Program database for years 2005 to 2008 inclusive. Only patients undergoing emergent surgery for acute diverticulitis were included. Univariate analyses were performed to compare demographic characteristics, preoperative laboratory values, comorbidities, and intraoperative variables. Variables with a significant (p < 0.10) difference between survivors and nonsurvivors were included in a stepwise logistic regression model to determine predictors of 30-day mortality. Concordance indices (c indices) for postoperative mortality were calculated using 2005 to 2008 data to determine predictive accuracy and validated on 2009 data. A total of 2,214 patients met inclusion criteria. Mean age was 61 years, and 50% of patients were male. Thirty-day mortality was 5.1%. Nine preoperative variables were significantly associated with postoperative mortality on multivariable analysis. The c index of this nine-variable model was 0.901. Renal dysfunction, hypoalbuminemia, American Society of Anesthesiologists class, and age were chosen to create a simpler model, with a c index of 0.886 for 2005 to 2008 data and 0.893 for 2009 data. Four readily available perioperative variables can be used to predict 30-day mortality after emergent surgery for acute diverticulitis. Prognostic study, level II.	f	\N
23379818	MicroRNAs (miRNAs) are small noncoding RNAs that not only regulate gene expression during normal development but can also be active players in several diseases. To date, several studies have demonstrated a possible role for specific miRNAs in the regulation of pulmonary vascular homeostasis suggesting that novel therapeutic agents which target these modulators of gene expression could serve to treat pulmonary arterial hypertension (PAH). The characterization of miRNA-mediated gene modulation in the pulmonary circulation is expanding very rapidly. This review summarizes current relevant findings on the role of miRNAs in the pathogenesis of PAH and expands on the potential use of agents that target these molecules as future disease-modifying therapies. Further understanding of miRNA biology and function in the pulmonary circulation will serve to further enhance our understanding of their contribution to the pathogenesis of PAH. The implementation of a systems biology approach will help accelerate the discovery of miRNAs that influence angiogenesis and cellular responses to vascular injury. Experimental characterization of these miRNAs using in vitro and in vivo methods will be required to validate the biological roles of these miRNAs prior to the consideration of their use as therapeutic targets in future clinical trials.	f	\N
23382786	CXCR4 is a G-protein-coupled receptor involved in a number of physiological processes in the hematopoietic and immune systems. The SDF-1/CXCR4 axis is significantly associated with several diseases, such as HIV, cancer, WHIM syndrome, rheumatoid arthritis, pulmonary fibrosis and lupus. For example, CXCR4 is one of the major co-receptors for HIV entry into target cells, while in cancer it plays an important role in tumor cell metastasis. Several promising CXCR4 antagonists have been developed to block SDF-1/CXCR4 interactions that are currently under different stages of development. The first in class CXCR4 antagonist, plerixafor, was approved by the FDA in 2008 for the mobilization of hematopoietic stem cells and several other drugs are currently in clinical trials for cancer, HIV, and WHIM syndrome. While the long-term safety data for the first generation CXCR4 antagonists are not yet available, several new compounds are under preclinical development in an attempt to provide safer and more efficient treatment options for HIV and cancer patients.	f	\N
23389330	Childhood tuberculosis (TB) accounts for a significant proportion of the global tuberculosis disease burden. However, current and previous efforts to develop better diagnostic, therapeutic, and preventive interventions have focused on TB in adults, and childhood TB has been relatively neglected. The purpose of this review is to provide an update on the diagnostic and therapeutic recommendations for childhood TB with an emphasis on intrathoracic disease. The literature from a range of sources was reviewed and synthesized to provide an overview of the contemporary approaches for the diagnosis and treatment of childhood TB. This review summarizes the clinical, radiological, bacteriological, and immunological approaches to diagnose TB infection and disease in children. In addition, we summarize the updated guidelines for the treatment of TB in children. The development of better diagnostic and therapeutic methods for childhood TB remains a significant challenge. As the strategies for diagnosis and treatment of childhood TB continue to improve and the knowledge base increases, the implementation of these strategies will be crucial.	f	\N
23393912	The most common autosomal form of Chronic Granulomatous Disease, p47-phox deficient CGD, generally features a GT (deltaGT) deletion in the GTGT sequence at the start of exon 2 on the NCF-1 gene. This consistency is due to the coexistence of and the recombination between 2 homologous pseudogenes (psi s) and NCF-1. The GTGT: deltaGT ratio mirrors the NCF-I: NCF-1 psi ratio and is 2:4 in normal individuals. To determine the molecular basis of the Autosomal-CGD in a family with 2 children, a male and female, affected by the disease. The female patient suffered recurrent infection, retinitis pigmentosa and discoid lupus. Chemiluminescence (CL) was used to study the respiratory burst, while genetic analysis was done by RT-PCR, PCR, deltaGT and the 20bp gene scans. The CL response of the patient was profoundly low. The patient's p47-phox band was absent in the RT-PCR for NADPH-oxidase component mRNAs. The deltaGT scan showed that the patient's GTGT: deltaGT ratio was 0:6, the parents' and the younger brother's was 1:5 and the younger sister's was 2:4. Examination of other NCF-1/ NCF-1 psi s differences showed that the father had a compound deltaGT allele ie. deltaGT-20bp, inherited by the patient, and that both parents had compound GTGT alleles with a single 30bp segment in intron 1. The patient was a classic, homozygous deltaGT p47-phox deficient CGD with one allele harbouring a compound deltaGT-20bp gene. The deltaGT and 20bp gene scans offer a relatively simple and efficient means of defining a p47-phox deficient CGD patient.	f	\N
23394360	Acute kidney injury (AKI) is common in hospitalized human immunodeficiency virus (HIV)-infected patients and is associated with hospital mortality. We aimed to evaluate the impact of AKI on long-term mortality of hospitalized HIV-infected patients. Retrospective analysis of a cohort of 433 hospitalized HIV-infected patients who were discharged alive from the hospital. AKI was defined according to 'Risk Injury Failure Loss of kidney function End-stage kidney disease' creatinine criteria, as an increase of baseline serum creatinine (SCr) X 1.5 or in patients with baseline SCr > 4 mg/dL if there was an acute rise in SCr of at least 0.5 mg/dL. Cumulative mortality curves were determined by the Kaplan-Meier method, and log-rank test was employed to analyze statistically significant differences between curves. Cox regression method was used to determine independent predictors of mortality. Risk factors were assessed with univariate analysis, and variables that were statistically significant (P < 0.05) in the univariate analysis were included in the multivariate analysis. Sixty-four patients (14.8%) had AKI. Median follow-up was 37 months. At follow-up 81 patients (18.7%) died. At 1, 2 and 5 years of follow-up, the cumulative probability of death of patients with AKI was 21.2, 25 and 31.3%, respectively, as compared with 10, 13.3 and 16.5% in patients without AKI (log-rank, P = 0.011). In multivariate analysis AKI was associated with increased mortality (adjusted HR 1.7, 95% CI 1.1-3; P = 0.049). AKI was independently associated with long-term mortality of hospitalized HIV-infected patients.	f	\N
23394995	Maintenance of an adequate and properly regulated immune system is essential for health and well-being. Components in food may modulate immune responses in a positive way (immunonutrition), and some of these components are present in kiwifruit. Kiwifruit contains vitamin C, carotenoids, polyphenols, and dietary fiber, and these are all potentially beneficial to the immune system. Research that has contributed to our understanding of the beneficial effects that kiwifruit may have on immune responses spans from in vitro studies using cell lines and human blood cells, to using animal models targeting both mucosal and systemic immunity. Some limited human intervention trials have been undertaken and are described, in which kiwifruit has been shown to influence a number of biomarkers of oxidative stress and beneficial immune responses, to reduce the incidence and severity of symptoms of upper respiratory tract infections and potentially be more beneficial than supplementation with vitamin C alone.	f	\N
23395237	To investigate the expression and possible roles of Twist1 and Y-box-binding protein-1 (YB-1) in bladder cancer tissue. Twist1 belongs to the family of basic helix-loop-helix transcription factors. A functional link between Twist1 and YB-1 has recently been determined to play an important role in bladder cancer cell lines. Frozen samples from 75 patients with bladder cancer were analyzed by quantitative real-time polymerase chain reaction (PCR). Formalin-fixed and paraffin-embedded tissues from 53 patients with bladder cancer were examined by immunohistochemistry. Twist1 transcript levels were positively correlated with YB-1 transcript levels (coefficient of correlation = 0.42, P<0.001), tumor grade (low grade vs. high grade; P<0.001), invasiveness (non-muscle-invasive bladder cancer vs. muscle invasive bladder cancer; P = 0.0018), and metastasis (meta- vs. meta+; P<0.001). YB-1 transcript level was also correlated with grade (P = 0.029) and invasiveness (P = 0.006). By immunohistochemistry, Twist1 expression was also correlated with YB-1 expression (P<0.001). Further, both Twist1 and YB-1 expression were positively correlated with invasiveness (P = 0.007 and P = 0.002, respectively). Patients with high Twist1 expression and high YB-1 expression had lower overall survival rates, compared with patients with low expression (log-rank test, P = 0.040 and P<0.001, respectively). These results suggest a functional link between Twist1 and YB-1, and they indicate that Twist1 and YB-1 promote bladder cancer progression.	f	\N
23396208	Regulatory T (Treg) cells suppress autoimmune disease, and impaired Treg cell function is associated with rheumatoid arthritis. Here we demonstrate that forkhead box P3 (FOXP3) transcriptional activity and, consequently, Treg cell suppressive function are regulated by phosphorylation at Ser418 in the C-terminal DNA-binding domain. In rheumatoid arthritis-derived Treg cells, the Ser418 site was specifically dephosphorylated by protein phosphatase 1 (PP1), whose expression and enzymatic activity were induced in the inflamed synovium by tumor necrosis factor α (TNF-α), leading to impaired Treg cell function. Moreover, TNF-α-induced Treg cell dysfunction correlated with increased numbers of interleukin-17 (IL-17)(+) and interferon-γ (IFN-γ)(+)CD4(+) T cells within the inflamed synovium in rheumatoid arthritis. Treatment with a TNF-α-specific antibody restored Treg cell function in subjects with rheumatoid arthritis, which was associated with decreased PP1 expression and increased FOXP3 phosphorylation in Treg cells. Thus, TNF-α controls the balance between Treg cells and pathogenic TH17 and TH1 cells in the synovium of individuals with rheumatoid arthritis through FOXP3 dephosphorylation.	f	\N
23399616	Tyrosine kinase inhibitors (TKIs) are increasingly common treatments for cancer; however, their effective use is hampered by unwanted side effects. One of the most common of these is TKI-induced diarrhea, although so far very little is known about its mechanisms and the best management approaches. As such, this review will briefly cover the extent of the problem, models for researching the problem and touch on future directions for management approaches to the problem. As there is a paucity of knowledge regarding the mechanisms of TKI-induced diarrhea in humans, this review will discuss the rodent models that have been used in the investigation of TKI-induced gut injury. This will be put into context with the pharmacological targets of TKIs and how this new information might help to better tailor treatment and management of patients on these drugs. The recognition of TKI-induced diarrhea as a significant treatment side effect has prompted efforts into uncovering the pathogenesis of this complication. This will enable future patients to be better managed throughout their treatment with these highly effective cancer drugs.	f	\N
23399972	Blood pressure (BP) is characterized by marked short-term fluctuations occurring within a 24 h period (beat-to-beat, minute-to-minute, hour-to-hour, and day-to-night changes) and also by long-term fluctuations occurring over more-prolonged periods of time (days, weeks, months, seasons, and even years). Rather than representing 'background noise' or a randomly occurring phenomenon, these variations have been shown to be the result of complex interactions between extrinsic environmental and behavioural factors and intrinsic cardiovascular regulatory mechanisms. Although the adverse cardiovascular consequences of hypertension largely depend on absolute BP values, evidence from observational studies and post-hoc analyses of data from clinical trials have indicated that these outcomes might also depend on increased BP variability (BPV). Increased short-term and long-term BPV are associated with the development, progression, and severity of cardiac, vascular, and renal damage and with an increased risk of cardiovascular events and mortality. Of particular interest are the findings from post-hoc analyses of large intervention trials in hypertension, showing that within-patient visit-to-visit BPV is strongly prognostic for cardiovascular morbidity and mortality. This result has prompted discussion on whether antihypertensive treatment should be targeted not only towards reducing mean BP levels but also to stabilizing BPV with the aim of achieving consistent BP control over time, which might favour cardiovascular protection.	f	\N
23404743	In 2010, guidelines published by the National Institute for Clinical Excellence (NICE) suggested a change in the way patients with stable chest pain of suspected cardiac origin were investigated. These guidelines removed exercise treadmill testing from routine use and introduced cardiac CT to regular use. To investigate whether these guidelines had improved our service provision by reducing the number of further investigations required to make a diagnosis, and to see if our costs had increased now that the less expensive exercise treadmill tests were not recommended. Clinic letters were used to assess patients pretest likelihood of coronary artery disease for two six-month cohorts of consecutive patients seen in the rapid access chest pain clinic (January-June 2010 and July-December 2011) using NICE published methodology, and to ascertain which investigations patients had. Using NICE modelled costs, we generated comparative hypothetical costs for each cohort and an average cost per patient. In the January-June 2010 cohort, 435 patients with chest pain were seen, and in July-December 2011, 334 patients were seen. In the pre-NICE guidelines cohort, 23% of patients required two investigations as compared with 11.4% in the post-NICE guidelines cohort, with no patient requiring three investigations as compared with 3% in the original cohort. There was no significant increase in costs per patient in the post-NICE guidance group. Implementing NICE guidance reduced the number of investigations needed per patient, and did not prove more expensive for our department in the short term.	f	\N
23406712	The Centers for Medicare and Medicaid Services (CMS) require high-risk (HR) criteria for carotid artery stenting (CAS) reimbursement. The impact of these criteria on outcomes after carotid endarterectomy (CEA) and CAS remains uncertain. Additionally, if these HR criteria are associated with more adverse events after CAS, then existing comparative effectiveness analysis of CEA vs CAS may be biased. We sought to elucidate this using data from the SVS Vascular Registry. We analyzed 10,107 patients undergoing CEA (6370) and CAS (3737), stratified by CMS HR criteria. The primary endpoint was composite death, stroke, and myocardial infarction (MI) (major adverse cardiovascular event [MACE]) at 30 days. We compared baseline characteristics and outcomes using univariate and multivariable analyses. CAS patients were more likely to have preoperative stroke (26% vs 21%) or transient ischemic attack (23% vs 19%) than CEA. Although age ≥ 80 years was similar, CAS patients were more likely to have all other HR criteria. For CEA, HR patients had higher MACEs than normal risk in both symptomatic (7.3% vs 4.6%; P < .01) and asymptomatic patients (5% vs 2.2%; P < .0001). For CAS, HR status was not associated with a significant increase in MACE for symptomatic (9.1% vs 6.2%; P = .24) or asymptomatic patients (5.4% vs 4.2%; P = .61). All CAS patients had MACE rates similar to HR CEA. After multivariable risk adjustment, CAS had higher rates than CEA for MACE (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0-1.5), death (OR, 1.5; 95% CI, 1.0-2.2), and stroke (OR, 1.3; 95% CI,1.0-1.7), whereas there was no difference in MI (OR, 0.8; 95% CI, 0.6-1.3). Among CEA patients, age ≥ 80 (OR, 1.4; 95% CI, 1.02-1.8), congestive heart failure (OR, 1.7; 95% CI, 1.03-2.8), EF <30% (OR, 3.5; 95% CI, 1.6-7.7), angina (OR, 3.9; 95% CI, 1.6-9.9), contralateral occlusion (OR, 3.2; 95% CI, 2.1-4.7), and high anatomic lesion (OR, 2.7; 95% CI, 1.33-5.6) predicted MACE. Among CAS patients, recent MI (OR, 3.2; 95% CI, 1.5-7.0) was predictive, and radiation (OR, 0.6; 95% CI, 0.4-0.8) and restenosis (OR, 0.5; 95% CI, 0.3-0.96) were protective for MACE. Although CMS HR criteria can successfully discriminate a group of patients at HR for adverse events after CEA, certain CMS HR criteria are more important than others. However, CEA appears safer for the majority of patients with carotid disease. Among patients undergoing CAS, non-HR status may be limited to restenosis and radiation.	f	\N
23408511	Intellectual disability is a condition characterized by significant limitations in cognitive abilities and social/behavioral adaptive skills and is an important reason for pediatric, neurologic, and genetic referrals. Approximately 10% of protein-encoding genes on the X chromosome are implicated in intellectual disability, and the corresponding intellectual disability is termed X-linked ID (XLID). Although few mutations and a small number of families have been identified and XLID is rare, collectively the impact of XLID is significant because patients usually are unable to fully participate in society. To reveal the molecular mechanisms of various intellectual disabilities and to suggest small molecules which by binding to the malfunctioning protein can reduce unwanted effects. Using various in silico methods we reveal the molecular mechanism of XLID in cases involving proteins with known 3D structure. The 3D structures were used to predict the effect of disease-causing missense mutations on the folding free energy, conformational dynamics, hydrogen bond network and, if appropriate, protein-protein binding free energy. It is shown that the vast majority of XLID mutation sites are outside the active pocket and are accessible from the water phase, thus providing the opportunity to alter their effect by binding appropriate small molecules in the vicinity of the mutation site. This observation is used to demonstrate, computationally and experimentally, that a particular condition, Snyder-Robinson syndrome caused by the G56S spermine synthase mutation, might be ameliorated by small molecule binding.	f	\N
23409482	Although cutaneous amebiasis (CA) is a rare disease, it is a public health concern worldwide, particularly in developing nations. It gains importance because of its severe clinical course, which can be confused with other disorders. Therefore, knowledge of its clinical features, histopathology, and pathogenesis is essential. We present a retrospective analysis over 50 years of 26 patients with CA who were diagnosed and treated at 2 Mexican institutions. Our main focus was to draw clinical information to identify mechanisms by which amebae reach the skin, occurring in a relatively small percentage of infected individuals. The recorded data included age and sex of the patients, form of presentation, any associated illnesses and/or factors, and methods for diagnosis. Histologic slides were reviewed in all cases; cytologic preparations also were available for 6 cases. Most patients were male (overall male to female ratio, 1.9 to 1). The disease always presented as painful ulcers containing varying amounts of amebae microscopically; the amebae were fairly easy to identify with routine stains, particularly when examination of tissue or smears was prepared from the edges of the ulcer instead of the necrotic centers. Erythrophagocytosis by the trophozoites was found and represented an unequivocal sign of its pathogenicity. We review the 2 mechanisms by which the organisms reach the skin. Most cases resolve with the use of specific antiamebic drugs; however, if left untreated, progression is rapid and unrelenting, sometimes with massive destruction of skin and subcutaneous tissues. Therefore, CA is a particularly virulent form of amebiasis.	f	\N
23412808	The use of natural remedies and pharmacological mineral supplements for liver disease treatment has a long history. In present study, the levels of selenium (Se) and zinc (Zn) were determined in biological samples (serum and whole blood) of female hepatitis C patients (n = 132), age ranged 30-45 years, before and after 30 days treatment with herbal/pharmaceutical supplements. For comparative study, 128 age-matched female subjects, residing in the same residential areas and have socioeconomic status, were selected as referents. The Se and Zn in supplements, blood, and sera were determined by atomic absorption spectrometry. It was observed that Zn and Se in blood and serum samples of viral hepatitis C (HCV) patients were reduced in the range of 28.6-39 % and 24-36 %, respectively, as compared to those of referents. After herbal/pharmaceutical supplementations, 20.6-25.0 and 9.15-13.2 % of Zn and 10.6-12.1 and 19.6-21.4 % of Se were enhanced in sera and blood samples of HCV patients, respectively. The resulted data indicated that the levels of Se and Zn in addition to some biochemical parameters were improved in HCV patients after herbal/pharmaceutical supplementation. The effects of both supplements were not significantly different (p > 0.05).	f	\N
23412860	We report 20 infants aged between 1 month and 6 months found to have subdural bleeding and also multiple unexplained fractures in a pattern similar to that described earlier as temporary brittle bone disease. Child abuse seemed unlikely as a cause of the fractures as in no case was there clinical evidence of injury commensurate with the fracturing, as some patients had fractures while in hospital and as metaphyseal lesions, when present, were often symmetrical in distribution. Abuse seemed unlikely to have been the cause of the subdural bleeding in several patients; three had clear histories of accidental injury and five had evidence that the initial bleeding was likely to have taken place at birth. Abuse also seemed unlikely as the cause of the syndrome; the nine patients who were returned to their parents had no subsequent allegations of abuse with a mean follow-up period of 15.8 years. The finding of hypermobile joints in the parents of eight of the children is an additional pointer to a natural cause for this condition. The cause of this combination of fractures and subdural bleeding is not yet clear but it is important to be aware that it can result from natural disease.	f	\N
23423257	Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitides characterized by small-to-medium-sized blood vessel vasculitis and the presence of ANCA. Although our understanding of the causes of AAV remains limited, new information supporting an autoimmune basis is emerging. This review highlights recent progresses in etiology, pathogenesis, classification, and treatment. A genome-wide association study has confirmed a role for genetic susceptibility in AAV, and links between environmental factors and AAV induction through abnormal neutrophil extracellular traps has been demonstrated. Ongoing international consensus initiatives have revised approaches to the classification of vasculitis that has been enhanced by the analysis of large-scale prospective clinical data sets. New autoantibodies to human lysosome-associated membrane protein-2 antibody, moesin, and plasminogen have been detected in AAV sera and a prognostic classification of renal biopsies developed. Clinical trial networks have extended the evidence base for the treatment of AAV, and rituximab has emerged as an alternative to cyclophosphamide for remission induction. Long-term outcomes following current treatment strategies have been determined and increased risks for cardiovascular and malignant disease reported.	f	\N
23425809	Liver diseases are responsible for metabolic disturbances and the loss of muscle mass and function. This study aims to correlate maximal oxygen uptake (VO2max) with the Model for End Stage Liver Disease (MELD) severity score and associate VO2max with mortality in patients with alcoholic cirrhosis. This prospective study included 27 patients who had a diagnosis of alcoholic liver cirrhosis. All subjects were followed for 3 years and performed an exercise test to determine VO2max. The study included 18 men and 9 women. We observed a strong inverse correlation between VO2max and MELD (r=-0.91, p<0.001). In a survival analysis, individuals who had a VO2max less than 14mL/kg showed 60% mortality when compared with those who had a VO2max greater than 14mL/kg (p<0.0001; OR: 3.29; 95% CI: 1.44-5.25). The VO2max is directly associated with the survival of patients with alcoholic cirrhosis and demonstrates a strong inverse correlation with the MELD severity score.	f	\N
23440103	We hereby report two patients with parathyroid carcinoma presenting extremely high calcium and PTH levels, severe bone disease, and palpable neck mass at diagnosis. They both underwent parathyroidectomy, and one of them evolved to lung metastasis. Important hypocalcemia was observed after surgery in both: after parathyroidectomy in one patient, and only after surgical removal of the metastasis in the other. Both required intravenous calcium replacement, thus revealing hungry bone syndrome (HBS). HBS usually reflects rapid mineralization after correction of hyperparathyroidism. The more severe the bone disease before surgery, the more prone the patient is to HBS after surgery. Despite being an unfavorable outcome, HBS state suggests that surgical removal of hypersecretory parathyroid tissue was accomplished. In this study, HBS was observed in both patients, who presented severe bone disease prior to surgery. HBS would be expected post-operatively in successful parathyroid carcinoma removal.	f	\N
23442763	The relationship between cytomegalovirus (CMV) infection and mortality among immunocompetent individuals is uncertain. We aimed to examine whether seropositivity for CMV and the level of CMV immunoglobulin G (IgG) antibody are associated with all-cause and cause-specific mortality. We used data from a random sample of 13 090 participants aged 40-79 years at recruitment in 1993-1997 to the European Prospective Investigation of Cancer-Norfolk population-based cohort study. We measured baseline IgG antibody levels against CMV. Death certificates were obtained for all participants who died before 31 March 2011. Codes for the underlying cause of death were used to investigate cause-specific mortality. A total of 2514 deaths occurred during a mean follow-up of 14.3 years (SD, 3.3 years). Compared to seronegative participants (age- and sex-adjusted mortality rate, 12.4 [95% confidence interval {CI}, 11.3-13.2] per 1000 person-years at risk), rates increased across thirds of IgG antibody levels (score test of trend P < .0001). CMV seropositivity (prevalence 59%) was associated with increased all-cause mortality (age- and sex-adjusted hazard ratio [HR], 1.16 [95% CI, 1.07-1.26]), similarly in men and women (P for interaction = .52). The association persisted after additionally adjusting for measures of socioeconomic status and possible confounders. Cause-specific analyses suggested that increased mortality from cardiovascular disease (HR, 1.06 [95% CI, .91-1.24]), cancer (HR, 1.13 [95% CI, .98-1.31]), and other causes (HR, 1.23 [95% CI, 1.04-1.47) all appeared to contribute to the overall associations. Seropositivity and higher IgG antibody levels against CMV are associated with increased mortality and after adjustment for a range of potential confounders in the general population.	f	\N
23443955	Radioiodine (RAI) is used in the treatment of hyperthyroidism and differentiated thyroid cancer. Radioiodine therapy is associated with dry eyes and some side effects are seen especially due to beta rays. In this study, the functional and cytological status of lacrimal glands after RAI therapy was evaluated. Twenty-five patients with a mean age of 55.16 years with planned low-dose RAI therapy were evaluated. Just before and 6 months after the treatment, the lacrimal glands were evaluated with tear break-up time (BUT), Schirmer's test, impression cytology and "Ocular Surface Disease Index (OSDI)" questionnaire. The mean value of Schirmer's test was 16.20 ± 3.61 pre-treatment and 11.28 ± 4.39 post-treatment for the right eye, and 15.76 ± 3.27 and 10.60 ± 4.42 for the left eye, respectively. The mean value of Schirmer's test decreased significantly post-treatment in both eyes (p = 0.0001). The BUT score also decreased significantly post-treatment (p = 0.001). The mean value of OSDI score was 27.5 ± 8.02 pre-treatment and 46.36 ± 10.27 post-treatment. The mean value of OSDI score increased post-treatment (p = 0.0001). The impression scores also increased post-treatment in both eyes (p = 0.0001). Even low-dose (≤30 mci) RAI treatment affects lacrimal gland functions. Low-dose RAI causes a decrease in the value of Schirmer's test and the BUT test, and an increase in the value of OSDI score and impression scores.	f	\N
23444587	In this paper, we explore the benefits of storytelling in health communication and, in particular, immunization education. During the mid-20th century polio epidemic, both personal stories and scientific information abounded in the media. However, as rates of vaccine-preventable diseases declined, narratives about the dangers of such diseases faded as did the public fear of them. Meanwhile, anti-vaccine advocates flooded the media and Internet with stories of injured children and tied those injuries, such as autism, to vaccines. Medical experts often counter anti-vaccine concerns with scientific information which can fail to persuade parents. Furthermore, evidence suggests that many people misunderstand quantitative information resulting in a misinterpretation of risk. Compared to scientific information, stories relate life lessons and values. They are effective because they are memorable and relatable. Evidence also suggests that storytelling can effectively improve health knowledge and behaviors. Inspired by In Harm's Way--True Stories of Uninsured Texas Children by the Children's Defense Fund and Faces of Influenza by the American Lung Association, we published Vaccine-Preventable Disease: The Forgotten Story, a collection of photographs and personal stories of families affected by vaccine-preventable diseases. We have found that the stories included in our booklet capture all the benefits of storytelling. Given the many benefits of storytelling, providers should strive to include stories along with medical facts in their daily practice.	f	\N
23446227	Neuroendocrine tumors (NET) are malignant solid tumors that arise in hormone-secreting tissue of the diffuse neuroendocrine system or endocrine glands. Although traditionally understood to be a rare disease, the incidence and prevalence of NET have increased greatly in the past 3 decades. However, during this time, progress in diagnosis and outcome of NET has generally been modest. In order to achieve improved outcome in NET, a better understanding of NET biology combined with more reliable serum markers and better techniques to identify tumor localization and small lesions are needed. Although some NET biomarkers exist, sensitive and specific markers that predict tumor growth and behavior are generally lacking. In addition, the integration of new molecular imaging technologies in patient diagnosis and follow-up has the potential to enhance care. To discuss developments and issues required to improve diagnostics and management of NET patients, with specific focus on the latest advances in molecular imaging and biomarker science, 17 global leaders in the fields of NET, molecular imaging and biomarker technology gathered to participate in a 2-day meeting hosted by Prof. Kjell Öberg at the University of Uppsala in Sweden. During this time, findings were presented regarding methods with potential prognostic and treatment applications in NET or other types of cancers. This paper describes the symposium presentations and resulting discussions.	f	\N
23447119	Erdheim-Chester disease (ECD) is a rare, non-Langerhans form of histiocytosis of unknown origin with distinct clinicopathologic and radiographic features. Reports detailing the cytology of ECD are rare. We describe a case of ECD with pericardial effusion. Cytologic examination revealed a hypercellular specimen composed of clusters and singly dispersed foamy macrophages with round nuclei and inconspicuous nucleoli, admixed with lymphocytes, eosinophils, and Touton-type multinucleated giant cells. Immunostains for CD68 were strongly positive in the foamy macrophages while S100 and CD1a were negative. The presence of foamy histiocytes, multinucleated giant cells, lymphocytes and eosinophils are also features of other systemic histiocytic disorders, including Langerhans cell histiocytosis (LCH), Rosai-Dorfman disease (RDD) and sarcoidosis. To the best of out knowledge, this is the first report describing the cytological features of ECD in a pericardial effusion.	f	\N
23449087	Single cell genomics has made increasingly significant contributions to our understanding of the role that somatic genome variations play in human neuronal diversity and brain diseases. Studying intercellular genome and epigenome variations has provided new clues to the delineation of molecular mechanisms that regulate development, function and plasticity of the human central nervous system (CNS). It has been shown that changes of genomic content and epigenetic profiling at single cell level are involved in the pathogenesis of neuropsychiatric diseases (schizophrenia, mental retardation (intellectual/leaning disability), autism, Alzheimer's disease etc.). Additionally, several brain diseases were found to be associated with genome and chromosome instability (copy number variations, aneuploidy) variably affecting cell populations of the human CNS. The present review focuses on the latest advances of single cell genomics, which have led to a better understanding of molecular mechanisms of neuronal diversity and neuropsychiatric diseases, in the light of dynamically developing fields of systems biology and "omics".	f	\N
23451796	Lowering blood glucose with insulin therapy towards beneficial target levels while also avoiding hypoglycaemia is a challenging task. An important confounding factor, which might be under-appreciated in this scenario, is that of variable glucose readings causing difficulties with dose adjustment. Furthermore, this glucose variability is, to some extent, a reflection of variability in the glucose-lowering action of the insulin therapy itself. Not only is glucose variability a major confounding factor in disease management but it is possibly also of direct prognostic consequence and is increasingly recognized as an informative measurement in diabetes management. The scope for insulin-induced glucose variability is particularly great with basal insulins because of their prolonged absorption from high-dose depots. Pharmacodynamic (PD) variability manifests as both fluctuations in the level of glucose-lowering effect over time, and as inconsistencies in the response from one injection to another. Well-controlled pharmacokinetic (PK)/PD studies using repeated isoglycaemic clamp methodology clearly how that many injected basal insulin products have high variable absorption with correspondingly variable action. Incomplete resuspension and precipitation appear to be important issues with regard to unpredictability in this action, while an inadequate duration of action relative to the dosing interval results in a fluctuating action profile. There are some ultra-long-acting basal insulins with novel protraction mechanisms currently in clinical development for which clamp studies show markedly improved PK/PD profiles.	f	\N
23456185	The temporal lobe is of importance for visuospatial orientation. Intracranial arachnoid cysts have a predilection for the temporal fossa, and might therefore affect visuospatial orientation. The aim was to find out whether temporal cysts affect maze learning and if surgical cyst decompression improves maze performance. Forty-five patients with a temporal arachnoid cyst and 17 control patients with cervical disc disease were tested in a labyrinth route in the hospital corridors the day before surgery and at least 3 months postoperatively. Thirty-five cyst patients (78 %) experienced postoperative improvement of their preoperative complaints. The cyst patients spent significantly longer time than the controls navigating through the maze in the preoperative test, 161 s and 127 s, respectively, but there was no difference in number of errors between the two groups. However, the cyst patients improved significantly in the postoperative test, both with regards to number of errors they made and time spent, contrary to the control patients, whose postoperative performance equalled that of the preoperative test. For the cyst patients, postoperative improvement in the labyrinth test correlated with the clinical outcome-but not the neuroradiological outcome-after the operation. Thus, temporal arachnoid cysts may affect visuospatial orientation and learning in a reversible manner.	f	\N
23459906	this paper reports the results of a nursing-administered theory-based intervention, the "Moving Heart Program", based on the implementation intention theory and pointed at improving physical activity adherence among coronary heart disease outpatients in Brazil. this experimental study applied assessments at baseline, 1 and 2 months after baseline. The Consolidated Standards of Reporting Trials statement was followed. Participants were randomly assigned to intervention, comprising action and coping plans on how to deal with anticipated barriers (n=69), or a standard-care control group (n=67). participants submitted to the intervention showed significant higher levels of physical activity 2 months after baseline and were significantly more active than the control group. the results indicate that the intervention is feasible for patients with coronary heart disease and can be a useful tool to facilitate intended lifestyle changes. This study brings relevant contributions to the Nursing field and other health-related areas, once the intervention presents low cost to health services and can be applied in cardiac rehabilitation programs, showing significant benefits to participants.	f	\N
23462063	To assess the effectiveness of flow reversal as an alternative means of cerebral protection by using transcranial Doppler recordings and diffusion-weighted imaging (DWI) as surrogate markers of brain injury. Eighteen patients with symptomatic carotid artery disease were recruited. Magnetic resonance imaging was performed before the intervention and at 3 and 24 hours and 30 days after the intervention to detect new ischemic lesions with DWI. Transcranial Doppler recordings were made during the procedure to assess for microembolic signals (MESs). Data were compared against data from a historical control cohort of patients who underwent CAS placement with or without filter protection (n = 15 each) under the same protocol in a different study. There were fewer periprocedural new lesions on DWI in the reverse-flow cohort compared with the historical control cohort with filter protection (P = .084). Reverse flow revealed significantly fewer MESs during the whole procedure compared with the filter-protected group (P = .01) but not the unprotected group (P = .55). There was a marked decrease in MES counts for reverse flow protection during the embologenic stages of the procedure (P = .004). Use of the reverse flow device was associated with fewer overall lesions on DWI and proportionately fewer positive scans compared with the use of filter-type devices (P = .08, not significant). Transcranial Doppler recordings demonstrated a significant reduction in embolization to the brain during carotid artery stent placement with the use of reverse-flow cerebral protection.	f	\N
23462484	Patients suffering from Parkinson's disease (PD) frequently experience painful sensations that may be due to central modification of nociception in PD. We compared pain thresholds and cerebral activity in nociceptive areas using Positron Emission Tomography (PET) during nociceptive stimulation before (OFF condition) and after (ON condition) levodopa challenge between nine PD patients with and nine PD patients without neuropathic pain. Pain thresholds were determined using a cold pressor test in the two conditions. We used H2(15)O PET to study the regional cerebral blood flow changes in subjects while they received alternate randomized noxious and innocuous cold stimuli during OFF and ON periods. Pain thresholds were not significantly different between PD patients with and without pain in either condition (OFF and ON). In both groups of PD patients, levodopa significantly raised pain threshold (F1,16 = 26.71; p < 0.0001) with a mean variation of -2.7 (±2.3 °C). In the OFF condition, PD patients with pain had a lower pain activation in the right prefrontal cortex and posterior insula and a higher pain activation in the right anterior cingulate cortex (BA32/8) than pain-free patients. Levodopa significantly reduced pain-induced-activation in the right insula and in the anterior cingulate cortex in both groups. Levodopa decreased nociceptive perception in both PD patients with and without pain. In PD patients with neuropathic pain the medial affective pathway was preferentially recruited whereas pain-free PD patients exhibited a greater activation in lateral discriminative nociceptive areas.	f	\N
23462618	The objective of this study was to compare the toxicological effects of different source-related ambient PM10 samples in regard to their chemical composition. In this context we investigated airborne PM from different sites in Aachen, Germany. For the toxicological investigation human alveolar epithelial cells (A549) and murine macrophages (RAW264.7) were exposed from 0 to 96 h to increasing PM concentrations (0-100 μg/ml) followed by analyses of cell viability, pro-inflammatory and oxidative stress responses. The chemical analysis of these particles indicated the presence of 21 elements, water-soluble ions and PAHs. The toxicological investigations of the PM10 samples demonstrated a concentration- and time-dependent decrease in cell viability and an increase in pro-inflammatory and oxidative stress markers.	f	\N
23470563	The IGF-I receptor (IGF-IR) has an important role in malignant disease and is the target of several drugs presently in clinical trials. Gene therapy has been explored as cancer treatment, mainly for delivery of genes that induce cell death or enhance the immunological response to cancer. Previously, we have shown that the implantation of autologous bone-marrow stromal cells producing a soluble form of IGF-IR (sIGFIR) inhibited experimental liver metastasis of several tumor types in mice. Here, we evaluated the utility of adenovirus-based gene delivery for generating therapeutically effective plasma levels of this decoy. We constructed a third generation gutless adenovirus expressing sIGFIR and found that HEK-293 cells transduced by this, but not control adenoviruses, secreted soluble receptor protein that blocked IGF-I-induced tumor cell migration, proliferation and survival in vitro. Following virus injection in vivo, viral DNA was detectable by PCR in several host organs, particularly the liver, and this resulted in the production of measurable sIGFIR plasma levels for up to 21 days post injection. In mice producing virus-encoded sIGFIR, experimental liver metastasis was inhibited, indicating that sIGFIR levels were therapeutically effective. The results show that adenovirus-based delivery of inhibitory soluble proteins can provide an effective anticancer strategy.	f	\N
23475581	Tissue oxidative stress is a common hallmark of atherosclerosis and non-alcoholic steatohepatitis (NASH), 2 conditions linked epidemiologically and pathophysiologically. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of inducible antioxidant responses, that can attenuate cellular injury from oxidative stress induced by obesity and other redox insults. Nrf2 expression and activation is reduced in mouse and human vessels that harbor accelerated atherosclerosis and in livers with histologic criteria of NASH. Systemic antioxidants have thus been attractive therapeutic targets, but clinical trials have been largely unsuccessful in improving cardiovascular health. Macrophage-selective Nrf2 activation may, however, provide an approach to reduce vascular and hepatocyte injury without the complications of systemic antioxidants, since macrophages play key roles in the development and progression of both atherosclerosis and NASH. In this article, we review the common mechanisms of oxidative stress and inflammation in atherosclerosis and NASH, and discuss the role of Nrf2 in vascular and hepatocyte protection.	f	\N
23478151	Primary carcinoid tumors of the kidney are very rare, malignant tumors consisting of neuroendocrine cells. The pathogenesis of renal carcinoid is unclear because neuroendocrine cells are not normally found in adult renal parenchyma. Electron microscopy, immunohistochemistry, octreotide scan, positron emission tomography along with conventional radiographic imaging techniques are used in diagnosis and follow-up. Presenting symptoms usually include flank pain and haematuria. Early stage disease is treated with surgery only. However, randomized trials are lacking because of the very low number of reported cases. Thus, the role of debulking surgery, chemotherapy, radiotherapy, octreotide and targeted therapy in the management of advanced disease remains an open question. In this article the clinicopathologic features and prognosis of this very rare disease along with treatment outcomes of the reported cases are reviewed. In addition, we report a new case of a metastatic primary renal atypical carcinoid tumor treated with octreotide therapy.	f	\N
23479135	Platinum-based chemotherapy is the most common treatment for patients with advanced non-small cell lung cancer (NSCLC). Genetic polymorphisms in the base excision repair (BER) pathway are suspected to influence the response of patients to this type of therapy. In this study, we investigated whether nonsynonymous single nucleotide polymorphisms (SNPs) in the BER pathway were associated with the response, progression-free survival (PFS) and overall survival (OS) of NSCLC patients following platinum-based chemotherapy. We used TaqMan to genotype four SNPs (APE1 Asp148Glu, PARP1 Va1762Ala, XRCC1 Arg194Trp and XRCC1 Arg399Gln) in 147 patients with advanced NSCLC who had undergone routine platinum-based chemotherapy. Logistic regression analysis showed that subjects with the XRCC1-399 A allele had a significantly better response to platinum-based chemotherapy than those with the XRCC1-399 GG genotype (AA/AG vs. GG: adjusted OR = 2.35, 95 % CI = 1.11-5.00). Furthermore, multivariate Cox proportional hazard regression analysis showed that the PARP1-762 CC genotype was a significantly unfavorable prognostic factor for PFS (CC vs. CT/TT: adjusted HR = 1.90, 95 % CI = 1.02-3.52). In contrast, the APE1-148 GG genotype was a significantly protective prognostic factor for OS (GG vs. TT: adjusted HR = 0.33, 95 % CI = 0.12-0.92). We found that XRCC1 Arg399Gln, PARP1 Va1762Ala and APE1 Asp148Glu SNPs in the BER pathway may influence the prognosis of advanced NSCLC patients following platinum-based chemotherapy.	f	\N
23484318	To increase the death rate of fatal anaphylaxis in guinea pigs and the detectahie level of the tryptase of mast cell in hlood serum. Seventy-four guinea pigs were randomly divided into five groups: original model group, original model control group, improved model group, improved model control group, improved model with non-anaphylaxis group. Using mixed human serum as the allergen, the way of injection, sensitization and induction were improved. ELISA was used to detect the serum mast cell tryptase and total IgE in guinea pigs of each group. The death rate of fatal anaphylaxis in original model group was 54.2% with the different degree of hemopericardium. The severe pericardial tamponade appeared in 9 guinea pigs in original model group and original model control group. The death rate of fatal anaphylaxis in improved model group was 75% without pericardial tamponade. The concentration of the serum total IgE showed no statistically difference hetween original model group and original model control group (P > 0.05), hut the serum mast cell tryptase level was higher in the original model group than that in the original model control group (P > 0.05). The concentration of the serum total IgE and the serum mast cell tryptase level were significantly higher in improved model group than that in the improved model control group (P < 0.05). The death rate of the improved model significantly increases, which can provide effective animal model for the study of serum total IgE and mast cell tryptase.	f	\N
23484512	An increasing number of people with mild cognitive impairment (MCI) visits a memory clinic to find out whether their symptoms indicate Alzheimer's disease (AD). Markers in cerebrospinal fluid are increasingly used for the diagnosis of Alzheimer's disease. In the short term, CSF biomarkers are more accurate in ruling out progression to AD-type dementia than demonstrating progression. The predictive value of the CSF biomarkers increases with longer-duration follow-up and declines with age. The added value of CSF biomarkers is not yet clear in MCI patients in whom extensive clinical, neuropsychological examination or imaging have already been performed.	f	\N
23485507	An optimal prostate biopsy in clinical practice is based on a balance among adequate detection of clinically significant prostate cancers (sensitivity), assuredness regarding the accuracy of negative sampling (negative predictive value), limited detection of clinically insignificant cancers and good concordance with whole gland surgical pathology results to allow accurate risk stratification and disease localization for treatment selection. Inherent within this optimization is variation of the core number, location, labeling and processing for pathological evaluation. To date, there is no consensus in this regard. The purpose of this review is to 1) define the optimal number and location of biopsy cores during primary prostate biopsy among men with suspected prostate cancer, 2) define the optimal method of labeling prostate biopsy cores for pathological processing which will provide relevant and necessary clinical information for all potential clinical scenarios, and 3) determine the maximal number of prostate biopsy cores allowable within a specimen jar which would not preclude accurate histological evaluation of the tissue. A bibliographic search using PubMed® covering the period up to July 2012 yielded approximately 550 articles. Articles were reviewed and categorized based on which of the 3 objectives of this review was addressed. Data were extracted, analyzed and summarized. Recommendations are provided based on this literature review and our clinical experience. The use of 10 to 12-core extended sampling protocols increases cancer detection rates compared to traditional sextant sampling methods and reduces the likelihood of repeat biopsy by increasing negative predictive value, ultimately allowing more accurate risk stratification without increasing the likelihood of detecting insignificant cancers. As the number of cores increases above 12, the increase in diagnostic yield becomes marginal. Only limited evidence supports the use of initial biopsy schemes involving more than 12 cores or saturation. Apical and laterally directed sampling of the peripheral zone increases cancer detection rate, reduces the need for repeat biopsies and predicts pathological features on prostatectomy while transition zone biopsies do not. There are little data to suggest that knowing the exact site of an individual positive biopsy core provides meaningful clinical information. However, determining laterality of cancer on biopsy may be helpful for predicting sites of extracapsular extension and therapeutic planning. Placement of multiple biopsy cores in a single container (greater than 2) appears to compromise pathological evaluation, which can reduce cancer detection rate and increase the likelihood of equivocal diagnoses. A 12-core systematic biopsy that incorporates apical and far-lateral cores in the template distribution allows maximal cancer detection, avoids repeat biopsy, and provides information adequate for identifying men who need therapy and planning that therapy while minimizing the detection of occult, indolent prostate cancers. This literature review does not provide compelling evidence that individual site specific labeling of cores benefits clinical decision making regarding the management of prostate cancer. Based on the available literature, we recommend packaging no more than 2 cores in each jar to avoid reduction of the cancer detection rate through inadequate tissue sampling.	f	\N
23494361	Disseminated intravascular coagulation (DIC) is a life-threatening complication, and its control is essential for therapeutic success. Recombinant human soluble thrombomodulin alfa (rTM) is a novel therapeutic agent for DIC. The efficacy of rTM in the treatment of DIC is reportedly superior to that of conventional anti-DIC treatments, such as unfractionated heparin or low molecular weight heparin, but hemorrhagic events occasionally interfere with the therapeutic benefits of rTM. We assessed the clinical features of 20 consecutive patients who were given rTM for DIC associated with various hematologic disorders. Eight patients achieved remission of both primary disease and DIC, eight died due to progression of the primary disease, and four died of various hemorrhagic complications. Assessment of 16 biomarkers for coagulation showed that the four patients who died of hemorrhagic complications despite remission of their primary disease showed lower ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin Type 1 motif, member 13) plasma activity than other patients (P = 0.016). The optimal cut-off level of ADAMTS-13 for predicting risk of hemorrhagic complications was 42 % (P = 0.007). Plasma ADAMTS-13 activity determined at diagnosis of DIC may help predict the risk of hemorrhagic events during and/or following DIC treatment with hematologic disorders.	f	\N
23494513	The use of self-expandable metal stents (SEMS) for the treatment of malignant colorectal obstruction is increasing. However, results of risk factors for its complications are inconsistent. This study aimed to examine the clinical effectiveness of the procedure as well as the complications and risk factors associated with the complications. Medical records of patients with malignant colorectal obstruction who underwent endoscopic placement of covered or uncovered SEMS were reviewed retrospectively. The procedure was performed by two endoscopists with experience in pancreatobiliary endoscopy. A total of 152 patients were included (102 men; mean age, 70 ± 12.5 years). The procedure was performed for palliative management in 83 patients and performed as a bridge to surgery in 69 patients. There were 111 uncovered stents and 41 covered stents. The technical success rate was 100% and the clinical success rate 94.1%. Overall complications were observed in 49 patients (32.2%) during the follow-up period (median, 98 days; interquartile range, 19-302 days). Obstruction (17.1%), migration (7.9%), perforation (5.2%), bleeding (1.3%), and tenesmus (0.7%) were the causes of the complications. Stage IV disease, carcinomatosis peritonei, complete obstruction of the colon, palliative intention, and covered stents increased the complications based on the univariate analysis. Multivariate analysis revealed that complete obstruction of the colon and covered stents were significantly independent risk factors for complications. In the palliative group, Kaplan-Meier analysis showed significantly shorter median duration to the onset of complications in the covered stent group than in the uncovered stent group. Although SEMS in patients with malignant colorectal obstruction is effective both as palliative therapy and as a bridge to surgery, one-third of patients experienced complications. Severity of obstruction and stent type can influence outcomes.	f	\N
23510013	Children with disabilities are two to three times more likely to become overweight or obese than typically developing children. Children with spina bifida (SB) are at particular risk, yet obesity prevalence and weight management with this population are under-researched. This retrospective chart review explored how weight is assessed and discussed in a children's SB outpatient clinic. Height/weight data were extracted from records of children aged 2-18 with a diagnosis of SB attending an outpatient clinic at least once between June 2009-2011. Body mass index was calculated and classified using Centers for Disease Control and Prevention cut-offs. Notes around weight, diet and physical/sedentary activities were transcribed verbatim and analysed using descriptive thematic analysis. Of 180 eligible patients identified, only 63 records had sufficient data to calculate BMI; 15 patients were overweight (23.81%) and 11 obese (17.46%). Weight and physical activity discussions were typically related to function (e.g. mobility, pain). Diet discussions focused on bowel and bladder function and dietary challenges. Anthropometrics were infrequently recorded, leaving an incomplete picture of weight status in children with SB and suggesting that weight is not prioritised. Bowel/bladder function was highlighted over other benefits of a healthy body weight, indicating that health promotion opportunities are being missed. Implications for Rehabilitation It is important to assess, categorise and record anthropometric data for children and youth with spina bifida as they may be at particular risk of excess weight. Information around weight categorisation should be discussed openly and non-judgmentally with children and their families. Health promotion opportunities may be missed by focusing solely on symptom management or function. Healthcare professionals should emphasise the broad benefits of healthy eating and physical activity, offering strategies to enable the child to incorporate healthy lifestyle behaviours appropriate to their level of ability.	f	\N
23511908	Corticostriatal projections are essential components of forebrain circuits and are widely involved in motivated behaviour. These axonal projections are formed by two distinct classes of cortical neurons, intratelencephalic (IT) and pyramidal tract (PT) neurons. Convergent evidence points to IT versus PT differentiation of the corticostriatal system at all levels of functional organization, from cellular signalling mechanisms to circuit topology. There is also growing evidence for IT/PT imbalance as an aetiological factor in neurodevelopmental, neuropsychiatric and movement disorders - autism, amyotrophic lateral sclerosis, obsessive-compulsive disorder, schizophrenia, Huntington's and Parkinson's diseases and major depression are highlighted here.	f	\N
23515578	Disturbances in proteostasis are observed in many neurodegenerative diseases. This leads to activation of protein quality control to restore proteostasis, with a key role for the removal of aberrant proteins by proteolysis. The unfolded protein response (UPR) is a protein quality control mechanism of the endoplasmic reticulum (ER) that is activated in several neurodegenerative diseases. Recently we showed that the major proteolytic pathway during UPR activation is via the autophagy/lysosomal system. Here we investigate UPR induction if the other major proteolytic pathway of the ER -ER associated degradation (ERAD)-is inhibited. Surprisingly, impairment of ERAD results in decreased UPR activation and protects against ER stress toxicity. Autophagy induction is not affected under these conditions, however, a striking relocalization of the lysosomes is observed. Our data suggest that a protective UPR-modulating mechanism is activated if ERAD is inhibited, which involves lysosomes. Our data provide insight in the cross-talk between proteolytic pathways involved in ER proteostasis. This has implications for neurodegenerative diseases like Alzheimer's disease where disturbed ER proteostasis and proteolytic impairment are early phenomena in the pathology.	f	\N
23523498	Unicompartmental knee arthroplasty (UKA) is a less invasive treatment for medial gonarthrosis. However, registry data have demonstrated higher revision and early failure rates. The purpose of this study is to report the early survivorship and failure modes in a series of 1000 consecutive medial mobile bearing UKA. UKA patients with a minimum of 2 year follow-up or those meeting the study endpoint (UKA failure or death) were included. Demographic variables, pre and post-operative clinical variables, and mode of failure were analyzed. Eight hundred and thirty-nine knees were included in the analysis. Forty revisions were performed at an average of 23.1 months (range, 2.3-74.2) following UKA for a survivorship of 95.2%. Indications for revision were aseptic loosening (15), tibial collapse (7), mobile bearing dislocation (2), persistent pain (12), progression of disease (2), infection (1), and tibiofemoral instability (1). These results are from a single center and may not be comparable to those of larger reports such as national registries.	f	\N
23526950	Transformation is a complex process, involving many changes in the cell. In this work, we investigated the transcriptional changes that arose during the development of squamous cell carcinoma (SCC) in mice. Using microarray analysis, we looked at gene expression during different stages in cancer progression in 31 mice. By analyzing tumor progression in each mouse separately, we were able to define the global changes that were common to all 31 mice, as well as significant changes that occurred in fewer individuals. We found that different genes can contribute to the tumorigenic process in different mice, and that there are many ways to acquire the malignant properties defined by Hanahan and Weinberg as "hallmarks of cancer". Eventually, however, all these changes lead to a very similar cancerous phenotype. The finding that gene expression is strongly heterogeneous in tumors that were induced by a standardized protocol in closely related mice underscores the need for molecular characterization of human tumors and personalized therapy.	f	\N
23528171	Surgical resection of lung metastases of epithelial and mesenchymal tumors has an irreplaceable position in the complex treatment of advanced stages of these malignancies. Among the most significant prognostic factors affecting longterm survival of these patients are: parameter of complete resection, number and size of metastases, histological type of primary tumor, lymph node involvement, DFI (Disease Free Interval) and biological aggressiveness of the tumor or TDT (Tumor Doubling Time). retrospective analysis of patients with lung metastases of epithelial and mesenchymal tumors operated on at the I. Department of Surgery from 2005 to 2011. The authors present a set of 50 patients and evaluation of their age, gender, type of primary tumor, number of metastases, occurrence of bilateral metastases, repeat metastasectomies, duration of DFI, type of operation and selected approach and performance of mediastinal lymphadenectomy. The probability of five-year survival, relationship between survival on DFI, difference in survival between metastases of colorectal cancer versus renal cancer and the influence of repeated metastasectomies and number of metastases on survival were statistically analyzed. Sixty operations were performed on a set of 50 patients (average age 61.2 years). Forty-two procedures were performed by thoracotomic approach. A solitary metastasis was discovered in 43 patients; in 8 patients, more than 3 metastases were resected. Repeated metastasectomies were performed 10 times. Mediastinal lymphadenectomy was performed in 21 cases. The most frequent procedure was extraanatomic resection (28×). Fourteen patients had DFI < 12 months, 19 patients had DFI 12-36 months and 17 patients had DFI > 36 months. Average survival was 66.9 months; the probability of five-year survival was 0.549 (54.9%). A relationship between DFI and survival was not discovered. There was no statistically significant difference in survival after metastasectomy for colorectal cancer and renal cancer. A relationship between survival interval and number of metastases and repeated metastasectomies was not discovered. Surgical resection of lung metastases plays an important role in multidisciplinary care, assuming a precise selection of patients indicated for this treatment. When properly adhering to the indication criteria, very positive results of long-term survival may be expected.	f	\N
23537409	Nitric oxide (NO) is involved in the regulation of several physiological processes such as vascular homeostasis. Exogenous NO supply offers major therapeutic interest, especially in the treatment of coronary artery disease, ischemic syndromes and other cardiovascular pathologies. Nevertheless, the administration of NO itself is limited by its short half-life. NO prodrugs have been marketed for decades, e.g. organic nitrates for angina pectoris. These prodrugs display undeniable advantages such as angina crisis relief and preconditioning effect. Nevertheless, they suffer from several drawbacks: toxicity, tolerance, endothelial dysfunction exacerbation. These negative effects are related to massive production of reactive species derived from oxygen or nitrogen, which trigger oxidative and nitrosative stress. New NO donors are under development to overcome those disadvantages, among which the S-nitrosothiols family seems especially promising.	f	\N
23539255	Laparoscopy-assisted total gastrectomy (LATG) has been used more frequently despite the associated technical difficulty and concerns over oncological safety. This study was undertaken to compare the short- and long-term surgical outcomes following either LATG or open total gastrectomy (OTG) for gastric cancer. A total of 120 LATG and 228 OTG were retrospectively matched with respect to sex, age (±5 years), and pathological tumor-node-metastasis stage for comparison of the clinical outcomes. The total complication rate among 120 LATG and 228 OTG was 18.3 % (22/120) and 16.2 % (37/228), respectively. The most common complication after LATG was anastomotic-related complication (6.7 %); five anastomotic leakages (4.2 %) and three anastomotic strictures were reported (2.5 %). That after OTG was wound complication (3.5 %), including seroma or infection. Matched patients analysis: Time to first gas passing and time to the resumption of a soft diet were significantly shorter in the LATG group than in the OTG group. The postoperative hospital stay of LATG was shorter in the LATG group (9.3 ± 4.2 days) than in the OTG group (11.7 ± 7.3 days; p = 0.057). Among matched patients, there was no significant difference between complication rate (24 vs. 32 %; p = 0.504) or leakage rate (6 vs. 4 %). During median follow-up of 50 (range, 10-92) months, there was no significant difference in the disease-free survival rate between the matched groups, respectively (94.5 vs. 87.1 %: p = 0.148). As for patients with TNM stage I gastric cancer, the disease-free survival rate (100 vs. 90.9 %; p = 0.5) and the cumulative survival rate (91.5 vs. 95.2 %; p = 0.618) did not differ significantly between the LATG and OTG groups. LATG for gastric cancer has the advantage over an OTG in terms of better short-term outcomes and similar long-term outcome. LATG is an acceptable alternative to OTG for the treatment of gastric cancer.	f	\N
23541879	This consensus document was prepared by an expert panel of the Grupo de Estudio de Sida (GESIDA [Spanish AIDS Study Group]) and the Plan Nacional sobre el Sida (PNS [Spanish National AIDS Plan]). The document updates current guidelines on the treatment of tuberculosis (TB) in HIV-infected individuals contained in the guidelines on the treatment of opportunistic infections published by GESIDA and PNS in 2008. The document aims to facilitate the management and treatment of HIV-infected patients with TB in Spain, and includes specific sections and recommendations on the treatment of drug-sensitive TB, multidrug-resistant TB, and extensively drug-resistant TB, in this population. The consensus guidelines also make recommendations on the treatment of HIV-infected patients with TB in special situations, such as chronic liver disease, pregnancy, kidney failure, and transplantation. Recommendations are made on the timing and initial regimens of antiretroviral therapy in patients with TB, and on immune reconstitution syndrome in HIV-infected patients with TB who are receiving antiretroviral therapy. The document does not cover the diagnosis of TB, diagnosis/treatment of latent TB, or treatment of TB in children. The quality of the evidence was evaluated and the recommendations graded using the approach of the Grading of Recommendations Assessment, Development and Evaluation Working Group.	f	\N
23542225	BM failure (BMF) is a major and frequent complication of dyskeratosis congenita (DKC). Allogeneic hematopoietic SCT (allo-HSCT) represents the only curative treatment for BMF associated with this condition. Transplant-related morbidity/mortality is common especially after myeloablative conditioning regimens. Herein, we report nine cases of patients with DKC who received an allo-SCT at five different member centers within the Eastern Mediterranean Blood and Marrow Transplantation Registry. Between October 1992 and February 2011, nine DKC patients (male, 7 and female, 2), with a median age at transplantation of 19.1 (4.9-31.1) years, underwent an allo-HSCT from HLA-matched, morphologically normal-related donors (100%). Preparative regimens varied according to different centers, but was reduced intensity conditioning (RIC) in eight patients. Graft source was unstimulated BM in five cases (56%) and G-CSF-mobilized PBSCs in four (44%) cases. The median stem cell dose was 6.79 (2.06-12.4) × 10(6) cells/kg body weight. GVHD prophylaxis consisted of CsA in all nine cases; MTX or mycophenolate mofetil were added in five (56%) and two (22%) cases, respectively. Anti-thymocyte globulin was administered at various doses and scheduled in four (44%) cases. Median time-to-neutrophil engraftment was 21 (17-27) days. In one case, late graft failure was noted at 10.4 months post allo-HSCT. Only one patient developed grade II acute GVHD (11%). Extensive chronic GVHD was reported in one case, whereas limited chronic GVHD occurred in another four cases. At a median follow-up of 61 (0.8-212) months, seven (78%) patients were still alive and transfusion independent. One patient died of metastatic gastric adenocarcinoma and graft failure was the cause of death in another patient. This study suggests that RIC preparative regimens are successful in inducing hematopoietic cell engraftment in patients with BMF from DKC. Owing to the limited sample size, the use of registry data and heterogeneity of preparative as well as GVHD prophylaxis regimens reported in this series, we are unable to recommend a particular regimen to be considered as the standard for patients with this disease.	f	\N
23544766	To evaluate chemotherapy regimen utilization in patients with non-small cell lung cancer (NSCLC) treated in US community oncology practices, to examine the relationship between evidence-based guideline adherence and the follow-up monitoring period (FUMP) over 1.5 years, and to understand the relative costs of commonly administered chemotherapy regimens. Retrospective data analysis. Using a large US medical oncology clinical database derived from a proprietary web-based drug dispensing technology, we identified adult patients with NSCLC who started adjuvant therapy for early-stage disease or first-line therapy for advanced and metastatic disease from July 1, 2009, through June 30, 2010. Adjuvant or first-line regimen utilization and the FUMP within 1.5 years were analyzed with respect to national evidence-based guideline adherence. Costs for commonly administered regimens based on 2010 Medicare reimbursement were compared. A total of 3505 patient treatment regimens were included in this study. Rates of guideline adherence were 75.0% and 61.3% for the first-line and the adjuvant treatment groups, respectively (P < .0001). Treatment with guidelinebased regimens correlated with a significantly longer FUMP in the first-line treatment groupcompared with non-guideline-based regimens (P = .005). Regimen costs for the top 11 regimens in the adjuvant and first-line treatment settings varied greatly. Low-cost regimens were prescribed more commonly. Rates of guideline adherence were significantly higher in the first-line than in the adjuvant NSCLC treatment group. First-line treatment with guideline-based regimens correlated with an extended FUMP for advanced NSCLC patients.	f	\N
23544828	Osteoporosis is a systemic disease that affects millions of people worldwide. It is estimated that 50% of women and approximately 20% of men more than 50 years of age will sustain a fragility fracture. The cause of nonunion in patients with osteoporosis is likely multifactorial, and includes age-related changes in fracture repair as well as challenges in achieving stable internal fixation. This article discusses fracture healing in patients with osteoporosis and the principles of fixation. Pharmacotherapy for the patient with osteoporosis is also discussed.	f	\N
23547660	Tiotropium bromide is an effective therapy for COPD patients. Comparing across programs tiotropium Respimat Soft Mist inhaler was at least as efficacious as tiotropium HandiHaler, however, concerns have been raised about tiotropium's safety when given via Respimat. The TIOSPIR trial (NCT01126437) compares the safety and efficacy of tiotropium Respimat 5 μg once daily (marketed) and 2.5 μg once daily (investigational) with tiotropium HandiHaler 18 μ once daily (marketed). The hypotheses to be tested are 1). that tiotropium Respimat 5 μg once daily and Respimat 2.5 μg once daily are non-inferior to HandiHaler in terms of all-cause mortality, and 2). that tiotropium Respimat 5 μg once daily is superior to HandiHaler in terms of time to first exacerbation. A spirometry substudy evaluates the bronchodilator efficacy. The trial is a randomized, double-blind, double dummy, event-driven, parallel group study. Participants can use any background treatment for COPD except inhaled anticholinergic agents. The study encompasses a wide range of COPD patients, e.g. patients with stable cardiac diseases including arrhythmia can be included. Clinical sites are international and include both primary care as well as specialists. To date, over 17,000 participants have been randomized from over 1200 sites in 50 countries with an anticipated treatment duration of 2-3 years. TIOSPIR will provide precise estimates of the relative safety and efficacy of the Respimat and HandiHaler formulations of tiotropium, assess potential dose-dependence of important outcomes and provide information on the clinical epidemiology of COPD in a large international patient cohort.	f	\N
23549020	Metastatic prostate carcinoma commonly involves bones and extrapelvic lymph nodes, with occasional visceral deposits. Central nervous system involvement is unusual and particularly the occurrence of leptomeningeal metastasis (LM) is extremely rare, with few cases described in the medical literature. The clinical presentation is characterized by multifocal neurological deficit and the prognosis is generally dismal, with survival ranging between 3 and 6 months. We report on a patient affected by LM due to prostate cancer who was treated with a combined-modality approach consisting of sequential chemotherapy and radiotherapy. A 70-year-old man was referred to our group for cognitive mental disorder, left-sided frontal headache and nausea; the patient had a previous history of metastatic prostate cancer. LM was diagnosed neuroradiologically with brain MRI and evidence of a detectable level of PSA in the cerebrospinal fluid. He was treated with docetaxel and prednisone for 3 cycles followed by external beam radiotherapy (EBRT) to the whole brain to a total dose of 30 Gy in 10 fractions with a simultaneous integrated boost to the macroscopic disease (total dose of 35 Gy in 10 fractions). No acute toxicity was observed. A substantial clinical response was obtained after EBRT with neurological improvement and radiologically stable disease at post-treatment imaging until 10 weeks after radiation. The patient died of sudden general condition deterioration 3 months after EBRT. Since LM derived from prostate cancer is likely to become a more common clinical event, such patients would need to be included in clinical trials evaluating new therapeutic approaches, considering that the current treatment strategies have been shown to be rather ineffective.	f	\N
23549631	The prognosis of thrombotic thrombocytopenic purpura (TTP) has considerably improved since the introduction of plasma exchange (PEX) therapy. However, unresponsive thrombotic thrombocytopenic purpura (Un-TTP) still carries high morbidity and mortality rates, indicating a need for early specific treatments. In a retrospective study including consecutive adults with TTP admitted between January 1997 and January 2011 in a teaching hospital intensive care unit (ICU), our objective here is to identify early clinical and laboratory features predicting Un-TTP. Patients who responded to plasma exchange and steroids (N = 49) were compared with patients with unresponsive TTP defined as requirement for other treatments, protracted course, or death (N = 37, 43 %). Hospital mortality was 24.3 % in the Un-TTP group. Variables associated with Un-TTP on univariate logistic regression were older age, cardiac involvement, neurological involvement, higher anti-a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS13) immunoglobulin G (IgG) titer, lower platelet counts starting on day 2, higher Sequential Organ Failure Assessment (SOFA) scores starting on day 3, need for higher plasma volumes to obtain remission, and greater use of adjuvant treatments and life-sustaining interventions. Multivariate logistic regression identified four factors independently associated with Un-TTP: age over 60 years [odds ratio (OR) 7.90; 95 % confidence interval (95 % CI) 1.06-78.34], cardiac (OR 5.17; 95 % CI 1.63-16.39) or neurological (OR 8.04; 95 % CI 1.27-51.03) manifestations at diagnosis, and day 2 platelet count less than 15 G/l (OR 3.88; 95 % CI 1.30-11.62). Therapeutic intensification starting on day 3 or even earlier in patients with the independent risk factors for unresponsive TTP identified in our study deserves evaluation in a multicenter prospective study.	f	\N
23554958	Intracranial Artery Stenosis (ICAS) is one of the most common causes of ischemic stroke in Asia. Previous studies have shown the number of ideal cardiovascular health (CVH) metrics was associated with lower risk of stroke. This study aimed to investigate the relationship between ideal CVH metrics and prevalence of ICAS. A random sample of 5,412 participants (selected from Kailuan Study as a reference population) aged 40 years or older (40.10% women), free of stroke, transient ischemic attack, and coronary disease, were enrolled in the Asymptomatic Polyvascular Abnormalities Community study from 2010 to 2011. We collected information on the seven CVH metrics (including smoking, body mass index, dietary intake, physical activity, blood pressure, total cholesterol and fasting blood glucose); and assessed ICAS by transcranial Doppler. The relationship between the ideal CVH metrics and prevalence of ICAS was analyzed using the multivariate logistic regression. After adjusting for age, sex, and other potential confounders, the adjusted odds ratios(95% confidence interval) for ICAS were 0.76(0.58-0.99), 0.55(0.43-0.72), 0.49(0.37-0.65), 0.43(0.31-0.61), and 0.36(0.22-0.62), respectively, for those having 2, 3, 4, 5, and 6-7 ideal CVH metrics compared with those having 0-1 ideal metric(p-trend<0.0001). Similar inverse associations were observed in different age and gender groups (all p-trends<0.05). We found a clear gradient relationship between the number of ideal CVH metrics and lower prevalence of ICAS in a Chinese population, which supports the importance of ideal health behaviors and factors in the prevention of ICAS.	f	\N
23557197	Human leukocyte antigen matching at allelic resolution is proven clinically significant in hematopoietic stem cell transplantation, lowering the risk of graft-versus-host disease and mortality. However, due to the ever growing HLA allele database, tissue typing laboratories face substantial challenges. In light of the complexity and the high degree of allelic diversity, it has become increasingly difficult to define the classical transplantation antigens at high-resolution by using well-tried methods. Thus, next-generation sequencing is entering into diagnostic laboratories at the perfect time and serving as a promising tool to overcome intrinsic HLA typing problems. Therefore, we have developed and validated a scalable automated HLA class I and class II typing approach suitable for diagnostic use. A validation panel of 173 clinical and proficiency testing samples was analysed, demonstrating 100% concordance to the reference method. From a total of 1,273 loci we were able to generate 1,241 (97.3%) initial successful typings. The mean ambiguity reduction for the analysed loci was 93.5%. Allele assignment including intronic sequences showed an improved resolution (99.2%) of non-expressed HLA alleles. We provide a powerful HLA typing protocol offering a short turnaround time of only two days, a fully integrated workflow and most importantly a high degree of typing reliability. The presented automated assay is flexible and can be scaled by specific primer compilations and the use of different 454 sequencing systems. The workflow was successfully validated according to the policies of the European Federation for Immunogenetics. Next-generation sequencing seems to become one of the new methods in the field of Histocompatibility.	f	\N
23557266	Adhesion molecules play a key role in the pathogenetic mechanisms of inflammatory bowel disease (IBD), both in Crohn's disease (CD) and ulcerative colitis (UC). In the last decade, some progress has been made in understanding their key role in leukocyte trafficking control in terms of basic research, but evidence of clinical efficacy is lacking. In the last 2 years, new molecules directed against integrins and integrin receptors have been developed and investigated in clinical trials, showing that anti-α4β7 integrin agents can be effective and safe for the induction and maintenance of remission in active CD and UC. Preliminary data show that anti-MAdCAM, anti-β7 and anti-integrin receptor agents are not all effective in IBD. Such results open new perspectives on clinical management of IBD, and new directions in understanding the role of adhesion molecules and leukocyte recruitment both in CD and UC.	f	\N
23578358	Angiogenic stimulation is a promising new strategy for treating patients with arteriosclerotic coronary artery disease. This strategy aims to ameliorate cardiac function by improving myocardial perfusion and lowering the risk of myocardial infarction. However, angiogenesis may contribute to the growth of atherosclerotic lesions. Atherogenesis is also a potential side effect of angiogenic therapy. Early clinical trials were performed using fibroblast growth factor 2 (FGF2) protein, which enhances the formation of new collateral vessels to reduce ischaemic symptoms. Conversely, angiogenic stimulation by FGF2 is a dilemma because it could cause negative angiogenic effects, such as atherosclerosis. Thus far, clinical trials in patients with recombinant FGF2 protein therapy have not yet yielded undisputable beneficial effects. Future trials should determine whether an improvement can be obtained in patients with coronary artery disease using a combination of FGF2 and other growth factors or a combination of the FGF2 gene and stem cell therapy. This review summarises the multiple roles of FGF2 in the progression of atherosclerosis, its effect on pro-angiogenesis and improvement of cardiac function in coronary artery disease, and the potentially unfavourable effect of angiogenesis on the prevention and treatment of atherogenesis.	f	\N
23581956	To review cases of nosocomial influenza and compare the epidemiology, clinical characteristics and outcomes with community-acquired cases. Prospective case series of adults hospitalised with influenza during April - November of 2010 and 2011 using a hospital-based sentinel surveillance system. A nosocomial case was defined as polymerase chain reaction-confirmed influenza where symptom onset was more than 2 15s after admission or, if this was not known, where the date of the positive test was more than 7 15s after admission. Demographic, clinical and outcome measures for patients with nosocomial influenza compared with patients admitted with community-acquired influenza. In 2010-2011, 598 cases of influenza were detected, of which 26 (4.3%) were nosocomial. All patients with nosocomial influenza had chronic comorbidities, compared with 71.7% of patients (410/572) with community-acquired influenza (P = 0.001). Similar proportions of community-acquired (32.5%) and nosocomial (36.4%) cases occurred in patients vaccinated in the current season. Clinical findings at time of enrollment did not differ between the two groups, with similar rates of fever, cough, chest pain and dyspnoea. Compared with community-acquired cases, a higher proportion of patients with nosocomial influenza received neuraminidase inhibitors within 2 15s of symptom onset (38.5% v 15.9%; P = 0.003). Admission to intensive care took place in 21.3% and 23.1% of community-acquired and nosocomial cases, respectively. One death from nosocomial influenza occurred in a patient with end-stage respiratory disease. Nosocomial influenza is uncommon but may be associated with severe disease. It may be partially preventable as patients frequently have comorbidities for which influenza vaccination is recommended. Patients, particularly those at high risk of complications, and their contacts (including health care workers) should be vaccinated to prevent severe disease.	f	\N
23591331	Self-expandable metal stents (SEMSs) are used to relieve malignant biliary obstruction. To compare outcomes between covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (USEMSs) in malignant biliary obstruction. Retrospective cohort study. Tertiary cancer center. Patients with malignant biliary obstruction. Placement of CSEMS or USEMS. Time to recurrent biliary obstruction (TRO), overall survival (OS), and adverse events. From January 2000 to June 2011, 749 patients received SEMSs: 171 CSEMSs and 578 USEMSs. At 1 year, there was no significant difference in the percentage of patients with recurrent obstruction (CSEMSs, 35% vs USEMSs, 38%) and survival (CSEMSs, 45% vs USEMSs, 49%). There was no significant difference in the median OS (CSEMSs, 10.4 months vs USEMSs, 11.8 months; P = .84) and the median TRO (CSEMSs, 15.4 months vs USEMSs, 26.3 months; P = .61). The adverse event rate was 27.5% for the CSEMS group and 27.7% for the USEMS group. Although tumor ingrowth with recurrent obstruction was more common in the USEMS group (76% vs 9%, P < .001), stent migration (36% vs 2%, P < .001) and acute pancreatitis (6% vs 1%, P < .001) were more common in the CSEMS group. Retrospective study. There was no significant difference in the patency rate or overall survival between CSEMSs and USEMSs for malignant distal biliary strictures. The CSEMS group had a significantly higher rate of migration and pancreatitis than the USEMS group. No significant SEMS-related adverse events were observed in patients undergoing neoadjuvant chemoradiation or surgical resection.	f	\N
23594492	To detect fully penetrant rare recessive variants that could constitute Mendelian subentities of complex diseases, we propose a novel strategy, the HBD-GWAS strategy, which can be applied to genome-wide association study (GWAS) data. This strategy first involves the identification of inbred individuals among cases using the genome-wide SNP data and then focuses on these inbred affected individuals and searches for genomic regions of shared homozygosity by descent that could harbor rare recessive disease-causing variants. In this second step, analogous to homozygosity mapping, a heterogeneity lod-score, HFLOD, is computed to quantify the evidence of linkage provided by the data. In this paper, we evaluate this strategy theoretically under different scenarios and compare its performances with those of linkage analysis using affected sib-pair (ASP) data. If cases affected by these Mendelian subentities are not enriched in the sample of cases, the HBD-GWAS strategy has almost no power to detect them, unless they explain an important part of the disease prevalence. The HBD-GWAS strategy outperforms the ASP linkage strategy only in a very limited number of situations where there exists a strong allelic heterogeneity. When several rare recessive variants within the same gene are involved, the ASP design indeed often fails to detect the gene, whereas, by focusing on inbred individuals using the HBD-GWAS strategy, the gene might be detected provided very large samples of cases are available.	f	\N
23594728	The presence of baseline proteinuria predicts the outcome in patients with chronic kidney disease and in the general population, independent of renal function. However, the predictive value of proteinuria during an episode of acute illness has not been reported yet. Therefore, we investigated the incidence and predictive value of proteinuria in patients with community-acquired pneumonia. An analysis of prospectively collected data, obtained from patients >18 years of age, was performed. Patients were hospitalized with community-acquired pneumonia in two hospitals in the Netherlands and participated in two consecutive clinical trials. A total protein/creatinine (P/C) ratio was measured in a urine sample from the day of admission. Patients were categorized in quartiles of P/C ratio. Primary outcome was length of hospital stay. 198/319 patients (62%) had a P/C ratio >23 mg/mmol creatinine. In multivariate analysis, proteinuria turned out to be an independent predictor for length of stay and admission to the intensive care unit. The incidence of proteinuria during pneumonia is high and proteinuria is an independent predictor for length of hospital stay and admission to the intensive care unit. Proteinuria is a cheap and easily accessible marker for outcome and might be used to assess the severity of pneumonia.	f	\N
23602249	Obesity is associated with elevated risk of heart disease. A solid understanding of the safety and potential adverse effects of high-fat, low-carbohydrate diet (HFLCD) similar to that used by humans for weight loss on the heart is crucial. High fat intake is known to promote increases in reactive oxygen species and mitochondrial damage. We hypothesized that there would be adverse effects of HFLCD on myocardial ischemia/reperfusion injury through enhancing oxidative stress injury and impairing mitochondrial biogenesis in a nongenetic, diet-induced rat model of obesity. To test the hypothesis, 250-g male Sprague-Dawley rats were fed an obesity-promoting diet for 7 weeks to induce obesity, then switched to HFLCD or a low-fat control diet for 2 weeks. Isolated hearts underwent global low flow ischemia for 60 minutes and reperfusion for 60 minutes. High-fat, low-carbohydrate diet resulted in greater weight gain and lower myocardial glycogen, plasma adiponectin, and insulin. Myocardial antioxidant gene transcript and protein expression of superoxide dismutase and catalase were reduced in HFLCD, along with increased oxidative gene NADPH oxidase-4 transcript and xanthine oxidase activity, and a 37% increase in nitrated protein (nitrotyrosine) in HFLCD hearts. The cardiac expression of key mitochondrial regulatory factors such as nuclear respiratory factor-1 and transcription factor A-mitochondrial were inhibited and myocardial mitochondrial DNA copy number decreased. The cardiac expression of adiponectin and its receptors was down-regulated in HFLCD. High-fat, low-carbohydrate diet impaired recovery of left ventricular rate-pressure product after ischemia/reperfusion and led to 3.5-fold increased injury as measured by lactate dehydrogenase release. In conclusion, HFLCD leads to increased ischemic myocardial injury and impaired recovery of function after reperfusion and was associated with attenuation of mitochondrial biogenesis and enhanced oxidative stress in obese rats. These findings may have important implications for diet selection in obese patients with ischemic heart disease.	f	\N
23607333	Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of -308 G < A tumour necrosis factor (TNF)-α, -174 G > C interleukin (IL)-6 and -1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case-control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-α/IL-10 combinations, it was observed that low TNF-α plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-α producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16-4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19-12·23; P = 0·02). In this study, the combination of low TNF-α plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients.	f	\N
23613224	High-intensity interval training (HIT) as exercise therapy is gradually implemented in cardiac rehabilitation as the cardiovascular benefits from exercise is intensity dependent. However, in previous studies, HIT has been performed with strict supervision. The aim of the study was to assess the feasibility and effectiveness of different modes of HIT in cardiac rehabilitation. a randomized clinical study. Ninety participants with coronary artery disease (80 men/10 women, mean age 57 ± 8 years) were randomly assigned to one of three exercise modes: group exercise (GE), treadmill exercise (TE), or home-based exercise (HE). HIT was performed twice a week for 12 weeks with an exercise intensity of 85-95% of peak heart rate. The primary outcome measure was change in peak oxygen uptake (peak VO2). Eighty-three participants (92%) completed the intervention without any severe adverse events. Peak VO2 increased from 34.7 ± 7.3 to 39.0 ± 8.0 ml/kg/min, 32.7 ± 6.5 to 36.0 ± 6.2 ml/kg/min, and 34.4 ± 4.8 to 37.2 ± 5.2 ml/kg/min in TE, GE, and HE, respectively. Mean group difference for TE vs. HE was 1.6 ml/kg/min (95% confidence interval, CI, 0.7 to 3.1, p = 0.02), TE vs. GE 1.1 ml/kg/min (95% CI-0.5 to 2.5, p = 0.27), and GE vs. HE 0.6 ml/kg/min (95% CI -1.0 to 2.1, p = 1). However, on-treatment analysis showed no significant difference between groups. HIT was efficiently performed in three settings of cardiac rehabilitation, with respect to target exercise intensity, exercise attendance, and increase in peak VO2. Exercise mode was not essential for exercise capacity.	f	\N
23613636	To investigate the significance of Twist2 for colorectal cancer (CRC). In this study, 93 CRC patients were included who received curative surgery in Eastern Hepatobiliary Surgery Hospital from January 1999 to December 2010. Records of patients' clinicopathological characteristics and follow up data were reviewed. Formalin-fixed, paraffin-embedded tissue blocks were used to observe the protein expression of Twist2 and E-cadherin by immunohistochemistry. Two independent pathologists who were blinded to the clinical information performed semiquantitative scoring of immunostaining. A total score of 3-6 (sum of extent + intensity) was considered as Twist2-positive expression. The expression of E-cadherin was divided into two levels (preserved and reduced). An exploratory statistical analysis was conducted to determine the association between Twist2 expression and clinicopathological parameters, as well as E-cadherin expression. Furthermore, the variables associated with prognosis were analyzed by Cox's proportional hazards model. Kaplan-Meier analysis was used to plot survival curves according to different expression levels of Twist2. Twist2-positive expression was observed in 66 (71.0%) samples and mainly located in the cytoplasm. Forty-three (46.2%) samples showed reduced expression of E-cadherin. There were no significant correlations between Twist2 expression and any of the clinicopathological parameters. However, Twist2-positive expression was significantly associated with reduced expression of E-cadherin (P = 0.040). Multivariate analysis revealed that bad M-stage [hazard ratio (HR) = 7.694, 95%CI: 2.927-20.224, P < 0.001] and Twist2-positive (HR = 5.744, 95%CI: 1.347-24.298, P = 0.018) were the independent risk factors for poor overall survival (OS), while Twist2-positive (HR = 3.264, 95%CI: 1.455-7.375, P = 0.004), bad N-stage (HR = 2.149, 95%CI: 1.226-3.767, P = 0.008) and bad M-stage (HR = 10.907, 95%CI: 4.937-24.096, P < 0.001) were independently associated with poor disease-free survival (DFS). Survival curves showed a definite trend for Twist2-negative patients to have longer OS and DFS than Twist2-negative patients, not only overall, but also for patients in different stages, especially for DFS of patients in stage III (P = 0.033) and IV (P = 0.026). Our data suggests, for the first time, that Twist2 is a valuable prognostic biomarker for CRC, particularly for patients in stage III and IV.	f	\N
23617953	By definition, a generic product is considered interchangeable with the innovator brand product. Controversy exists about interchangeability, and attention is predominantly directed to contaminants. In particular for chronic, degenerative conditions such as in Parkinson's disease (PD) generic substitution remains debated among physicians, patients and pharmacists. The objective of this study was to compare the pharmaceutical quality of seven generic levodopa/benserazide hydrochloride combination products marketed in Germany with the original product (Madopar® / Prolopa® 125, Roche, Switzerland) in order to evaluate the potential impact of Madopar® generics versus branded products for PD patients and clinicians. Madopar® / Prolopa® 125 tablets and capsules were used as reference material. The generic products tested (all 100 mg/25 mg formulations) included four tablet and three capsule formulations. Colour, appearance of powder (capsules), disintegration and dissolution, mass of tablets and fill mass of capsules, content, identity and amounts of impurities were assessed along with standard physical and chemical laboratory tests developed and routinely practiced at Roche facilities. Results were compared to the original "shelf-life" specifications in use by Roche. Each of the seven generic products had one or two parameters outside the specifications. Deviations for the active ingredients ranged from +8.4% (benserazide) to -7.6% (levodopa) in two tablet formulations. Degradation products were measured in marked excess (+26.5%) in one capsule formulation. Disintegration time and dissolution for levodopa and benserazide hydrochloride at 30 min were within specifications for all seven generic samples analysed, however with some outliers. Deviations for the active ingredients may go unnoticed by a new user of the generic product, but may entail clinical consequences when switching from original to generic during a long-term therapy. Degradation products may pose a safety concern. Our results should prompt caution when prescribing a generic of Madopar®/Prolopa®, and also invite to further investigations in view of a more comprehensive approach, both pharmaceutical and clinical.	f	\N
23620363	The number of missense mutations being identified in cancer genomes has greatly increased as a consequence of technological advances and the reduced cost of whole-genome/whole-exome sequencing methods. However, a high proportion of the amino acid substitutions detected in cancer genomes have little or no effect on tumour progression (passenger mutations). Therefore, accurate automated methods capable of discriminating between driver (cancer-promoting) and passenger mutations are becoming increasingly important. In our previous work, we developed the Functional Analysis through Hidden Markov Models (FATHMM) software and, using a model weighted for inherited disease mutations, observed improved performances over alternative computational prediction algorithms. Here, we describe an adaptation of our original algorithm that incorporates a cancer-specific model to potentiate the functional analysis of driver mutations. The performance of our algorithm was evaluated using two separate benchmarks. In our analysis, we observed improved performances when distinguishing between driver mutations and other germ line variants (both disease-causing and putatively neutral mutations). In addition, when discriminating between somatic driver and passenger mutations, we observed performances comparable with the leading computational prediction algorithms: SPF-Cancer and TransFIC. A web-based implementation of our cancer-specific model, including a downloadable stand-alone package, is available at http://fathmm.biocompute.org.uk.	f	\N
23620431	To report the findings of en face adaptive optics (AO) near infrared (NIR) reflectance fundus flood imaging in eyes with geographic atrophy (GA). Observational clinical study of AO NIR fundus imaging was performed in 12 eyes of nine patients with GA, and in seven controls using a flood illumination camera operating at 840 nm, in addition to routine clinical examination. To document short term and midterm changes, AO imaging sessions were repeated in four patients (mean interval between sessions 21 days; median follow up 6 months). As compared with scanning laser ophthalmoscope imaging, AO NIR imaging improved the resolution of the changes affecting the RPE. Multiple hyporeflective clumps were seen within and around GA areas. Time-lapse imaging revealed micrometric-scale details of the emergence and progression of areas of atrophy as well as the complex kinetics of some hyporeflective clumps. Such dynamic changes were observed within as well as outside atrophic areas. in eyes affected by GA, AO nir imaging allows high resolution documentation of the extent of RPE damage. this also revealed that a complex, dynamic process of redistribution of hyporeflective clumps throughout the posterior pole precedes and accompanies the emergence and progression of atrophy. therefore, these clumps are probably also a biomarker of rpe damage. AO NIR imaging may, therefore, be of interest to detect the earliest stages, to document the retinal pathology and to monitor the progression oF GA. (ClinicalTrials.gov number, NCT01546181.).	f	\N
23625177	Expression and function of the immunoregulatory molecule HLA-E was investigated in patients with relapsing-remitting (RR) multiple sclerosis (MS). Serum and cerebrospinal fluid (CSF) soluble (s)HLA-E and -G levels were measured by ELISA in 80 RRMS patients. Controls were patients with other inflammatory neurological disorders (OIND, n = 81) and noninflammatory neurological disorders (NIND, n = 86). Serum sHLA-E concentrations were higher in RRMS than in NIND patients only. CSF sHLA-E concentrations were higher in RRMS than controls. Increased CSF sHLA-E levels were detected in MRI inactive and clinically stable RRMS patients. sHLA-E intrathecal synthesis (ITS) was higher in RRMS than controls, and the number of patients with sHLA-E ITS above cut-off was higher i) in MS than controls, and ii) in clinically stable than clinically active MS patients. sHLA-E CSF levels and ITS correlated with i) the same sHLA-G parameters, and ii) disease duration. HLA-E expression and co-expression with CD markers were investigated in MS plaques from three different cases by immunohistochemistry and confocal microscopy, respectively. Infiltrating T lymphocytes and macrophages, as well as resident microglial cells and astrocytes expressed HLA-E. CSF samples from MS patients were finally tested for inhibitory activity of in vitro CTL and NK cell mediated cytotoxicity. sHLA-E⁺ were more effective than sHLA-E⁻ CSF samples in such inhibition. Maximum inhibition was achieved with sHLA-E⁺/sHLA-G⁺ CSF samples In conclusion, increased sHLA-E CSF levels may play an immunomodulatory role in MS, contributing to the inhibition of intrathecal inflammatory response. The potential of sHLA-E as biomarker of MS activity warrants further investigation.	f	\N
23628099	The apex is a particular region of the prostate in its surgical dissection and pathological analysis. We sought to evaluate the prognostic value of the apical localization of prostate tumors. From 1988 to 2010, data pre- (age, clinical stage, preoperative PSA, biopsy Gleason score) and postoperative (prostate weight, pathologic stage TNM 2010, Gleason score, margin status) of 2765 total prostatectomies were collected prospectively. These data were compared according to existence or absence of tumor at the apex. The prognostic impact of tumor at the apex on biochemical recurrence-free survival (PSA>0.2 ng/mL) has been studied in univariate and multivariate models. One thousand eight hundred seventeen tumors had a location at the apex (65.7%). In univariate analysis, there was a significant difference in the clinical stage, the biopsy and pathological Gleason score, the result of curage, the pathological stage and the margin status between apical tumors and others. With a mean decline of 34.6 months, 502 patients had a biochemical recurrence (18.1%). Disease-free survival at 10 years was 60.7% for tumor at the apex versus 65.9% in other cases. The location at the apex was significantly associated with biochemical recurrence on univariate analysis (P=0.01). After adjustment for clinical and pathological stage, PSA level, Gleason score and surgical margins, the apex was not anymore a pejorative independent predictor (P=0.0087). The existence of tumor in the prostatic apex was associated with more aggressive tumoral criteria and was an independent and pejorative predictor of biochemical recurrence-free survival at 10 years in univariate analysis. The apical localization could be an additional argument in the decision of adjuvant therapy after prostatectomy.	f	\N
23638302	Immune cells called mast cells can hinder rather than help the body's response to dengue virus, which suggests that mast cell products could be used as biomarkers to identify severe forms of the disease.	f	\N
23644526	Vertebral metastases affect 20 to 50% of cancer patients and represent a major turning point in the disease from the functional impact they generate. Early treatment is mandatory to prevent or treat any neurological compression. Due to the high variability of clinical and radiological presentations, best care requires a multidisciplinary team, involving oncologists, radiation oncologists, interventional radiologists and spine surgeons. Recent advances in radiotherapy and interventional radiology have offered various efficient therapeutic solutions with relatively low morbidity rate in the management of symptomatic spine metastases. However, surgery remains the standard treatment for patients with rapidly progressive spinal cord compression or significant osteolytic lesion leading to a high risk of fracture. However, conventional surgical strategies are associated with significant morbidity and contraindicated in patients in poor general condition. In addition, postoperative complications are likely to affect patient's quality of life and delay the initiation of anticancer therapies. In order to reduce iatrogenic lesions, new "minimally invasive" techniques were developed to achieve immediate stabilisation and decompression while reducing the morbidity of the approach. We aim to inform the reader of the existence of these techniques so that each patient can benefit from treatment best suited to their situation.	f	\N
23645623	Weight gain increases the prevalence of obesity, a risk factor for cardiovascular disease. Nevertheless, unintentional weight loss can be a harbinger of health problems. The Atherosclerosis Risk in Communities Study (1987-2009) included 15,792 US adults aged 45-64 years at baseline and was used to compare associations of long-term (30 years) and short-term (3 years) weight change with the risks of coronary heart disease (CHD) and ischemic stroke. Age-, gender-, and race-standardized incidence rates were 4.9 (95% confidence interval (CI): 4.6, 5.2) per 1,000 person-years for CHD and 2.5 (95% CI: 2.3, 2.8) per 1,000 person-years for stroke. After controlling for baseline body mass index and other covariates, long-term weight gain (since age 25 years) of more than 2.7% was associated with elevated CHD risk, and any long-term weight gain was associated with increased stroke risk. Among middle-aged adults, short-term (3-year) weight loss of more than 3% was associated with elevated immediate CHD risk (hazard ratio = 1.46, 95% CI: 1.18, 1.81) and stroke risk (hazard ratio = 1.45, 95% CI: 1.10, 1.92). Risk tended to be larger in adults whose weight loss did not occur through dieting. Avoidance of weight gain between early and middle adulthood can reduce risks of CHD and stroke, but short-term, unintentional weight loss in middle adulthood may be an indicator of immediate elevated risk that has not previously been well recognized.	f	\N
23649916	CD146 is an adhesion molecule localized at endothelial cell junctions and facilitates cell-cell interactions. The circulating soluble form (sCD146) lacks both the intracellular and the transmembrane domains. In this study we show that CD146 expression was significantly decreased in the lung tissue of smokers with chronic obstructive pulmonary disease (COPD) and also in rats exposed to second-hand smoke (SHS). Concurrently, levels of sCD146 were increased in both the plasma and bronchoalveolar lavage fluid (BALF) of COPD patients as well as in BALF from rats exposed to SHS. Decreased or abolished CD146 protein expression in rat pulmonary micro- and macrovascular endothelial cells was found after treatment with cigarette smoke extract (CSE), proinflammatory cytokine interleukin 18 (IL-18) or after silencing CD146 expression with siRNA. The decrease in CD146 protein was accompanied by increased endothelial monolayer permeability and enhanced macrophage infiltration in vitro. In CD146 knockout (KO) mice, distinct perivascular oedema was seen and increased numbers of inflammatory cells, along with increased protein levels in BALF. Increased sCD146 was found in BALF and plasma from patients with COPD. The circulating plasma levels of sCD146 correlated positively with the presence of anti-endothelial cell antibodies (AECAs). sCD146 in combination with AECAs may be useful markers for early detection of COPD. Our study indicates that loss of CD146 function damages pulmonary endothelial integrity. This damage may represent part of the pathophysiological processes that are involved in the basic aetiology of COPD/emphysema.	f	\N
23653428	Colistin is increasingly used as the last-resort treatment option against infections caused by multidrug-resistant (MDR) Gram-negative pathogens, but its nephrotoxicity is of concern, especially in severely ill patients. The aim of this study was to analyze the toxicity of colistin therapy in adults and children with hematological malignancies (HM) and hematopoietic stem cell transplantation (HSCT) recipients. Data on HSCT recipients and HM patients, treated with intravenous colistin (2.5-5 mg/kg/day in children and 3-6 million international units (IU) in adults, adjusted to renal function) during the period 2008-2011 in our center, were retrospectively collected and analyzed. Nephrotoxicity was defined according to the RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease). Twenty-nine children and adults received 38 courses of intravenous colistin (2.5-5 mg/kg/day in children and 3-6 × 10(6) IU in adults, adjusted to renal function) [allogeneic HSCT (22 courses) and HM (16 courses)] for 3-28 days (median 10 days) for empirical therapy for nosocomial clinical sepsis (28) or local infection (6), and bacteremia with MDR Gram-negative rods (4). Nephrotoxicity was observed at the end of 4 (10.5%) courses. In 32 (84%) courses, nephrotoxic medications were concomitantly administered. Two patients had convulsions, probably unrelated to colistin. Seven patients (18%) died while on colistin therapy. No death was attributed to an adverse effect of colistin. Treatment with intravenous colistin, with dosage adjusted to renal function, was relatively safe for HM/HSCT patients, even with concomitantly administered nephrotoxic medications. Concern about nephrotoxicity should not justify a delay in initiating empirical colistin treatment in situations where infection with MDR Gram-negative rods is likely.	f	\N
23658247	The implementation of national estimated glomerular filatration rate reporting and the inclusion of renal-specific indicators in a primary care pay for performance (P4P) system since April 2006 has promoted identification and better management of risk factors related to chronic kidney disease (CKD). In the UK, the P4P framework is known as the Quality and Outcomes Framework (QOF). One of the key targets for intervention in primary care was hypertension. It is clear that hypertension is a major predictor of development and progression of CKD; thus, targeting better blood pressure control is likely to have a positive impact on outcomes in CKD. The aim of this study was to evaluate the effectiveness of renal indicators outlined in P4P on the management of hypertension in primary care. To estimate the cost implications of the resulting changes in prescribing patterns of antihypertensive medication following introduction of such indicators. We performed a prospective cohort study using a large primary care database. This cohort was taken from a database collated as part of a clinical decision support system used to assist the management of CKD in primary care. We investigated a total population of 90 250 individuals on general practitioner (GP) registers with a valid serum creatinine estimation in the 6-year study period. A total of 10 040 patients had confirmed stage 3-5 CKD in the 2 years pre-QOF and formed the study cohort. Patients were studied over three time periods, pre-QOF (1 April 2004 to 31 March 2006), 2 years post-QOF (1 April 2006 to 31 March 2008) and finally the two subsequent years (1 April 2008 to 31 March 2010). The mean systolic and diastolic blood pressures (BP) together with antihypertensive medication were analysed over the three time periods. Cost calculation was based on 2009 British National Formulary list prices for antihypertensives. The mean age of the cohort at the start of the study period was 64.8 years, 55% were female. In those patients with stage 3-5 CKD 83.9% were hypertensive, defined by a pre-P4P BP of >140/85 or currently taking antihypertensive medication. The proportion of patients with CKD 3-5 attaining the BP target of 145/80 increased from 41.5% in the pre-QOF period to 50.0% in the post-QOF period. This increase was even more marked for those with hypertension in the pre-QOF period (28.8-45.1%). In the hypertensive patients, mean BP fell from 146/79 mmHg to 140/76 in the first 2 years post-P4P [P < 0.01, analysis of variance (ANOVA)]. This BP reduction was sustained in the last 2 years of the study, 139/75 (P < 0.01, ANOVA). The proportion of hypertensive patients taking angiotensin-converting enzyme inhibitors or angiotensin blockers increased, this was also sustained in the third time period. An increase in the prescribing of diuretics, calcium channel blockers and β-blockers was also observed. The additional cost of increased prescribing was calculated to be €25.00 per hypertensive patient based on GP prescription data. Population BP control has improved since the introduction of P4P renal indicators, and this improvement has been sustained. This was associated with a significant increase in the use of antihypertensive medication, resulting in increased prescription cost. Longer-term follow-up will establish whether or not this translates to improved outcomes in terms of progression of CKD, cardiovascular disease and patient mortality.	f	\N
23662931	An intradural somatic-to-autonomic anastomosis, or Xiao procedure, has been described to create a "skin-CNS-bladder" reflex that improves bladder and bowel function in patients with neurogenic bladder and bowel dysfunction. The authors present their experience with a 10-year-old boy with chronic neurogenic bladder and bowel dysfunction related to spinal cord injury who underwent the Xiao procedure. After undergoing a left L-5 ventral root to left S2-3 intradural anastomosis, the patient reported that his bladder and bowel dysfunction improved between 6 and 12 months. Two years after the procedure, however, he reported that there was no change in his bladder or bowel dysfunction as compared with his condition prior to the procedure. Frequent, systematic multidisciplinary evaluations produced conflicting data. Electrophysiological and histological evaluation of the previously performed anastomosis during surgical reexploration 3 years after the Xiao procedure revealed that the anastomosis was in anatomical continuity but neuroma formation had prevented reinnervation. Nerve action potentials were not demonstrable across the anastomosis, and stimulation of the nerve above and below the anastomosis created no bladder or perineal contractions. This is the first clinical report on the outcome of the Xiao procedure in a child with spinal cord injury outside of China. It is impossible to draw broad conclusions about the efficacy of the procedure based on a single patient with no demonstrable benefit. However, future studies should carefully interpret transient improvements in bladder function, urodynamic findings, and the patient's ability to void in response to scratching after the Xiao procedure. The authors' experience with the featured patient, in whom reinnervation could not be demonstrated, suggests that such changes could be related to factors other than the establishment of a skin-CNS-bladder reflex as a result of a somatic-to-autonomic anastomosis.	f	\N
23664519	In the field of emerging innovative therapies, such as thrombopoietin mimetics, the question of who needs splenectomy remains highly relevant. Removal of the spleen is an accepted and potentially curative treatment of immune thrombocytopenia (ITP) after decades with a favorable economical-effect ratio but with relevant morbidity particularly in the young patients. ITP is rare and splenectomy is performed in a minority of children, which makes its research almost impossible, resulting in a poor standardization of the procedure. Hence, in children, recommendation and decision for splenectomy is individually based and rests on expert opinions. Furthermore, local practice and availability of health products affect the frequency of splenectomy. Current guidelines agree on one point: splenectomy should be postponed for at least 12 months after the initial diagnosis of ITP, due to the high probability of improvement or even spontaneous remission. However, evidence-based data are lacking and splenectomy remains controversial. This article reviews the current literature and delineates controversies and complexities of splenectomy in children with ITP. There is an urgent need for consensus of this procedure in pediatric patients.	f	\N
23668671	Recent genome-wide association studies have identified multiple loci associated with BMI or the waist:hip ratio (WHR). However, evidence on gene-lifestyle interactions is still scarce, and investigation of the effects of well-documented dietary and other lifestyle data is warranted to assess whether genetic risk can be modified by lifestyle. We assessed whether previously established BMI and WHR genetic variants associate with obesity and weight change in the Finnish Diabetes Prevention Study, and whether the associations are modified by dietary factors or physical activity. Individuals (n 459) completed a 3 d food record and were genotyped for twenty-six BMI- and fourteen WHR-related variants. The effects of the variants individually and in combination were investigated in relation to obesity and to 1- and 3-year weight change by calculating genetic risk scores (GRS). The GRS were separately calculated for BMI and the WHR by summing the increasing alleles weighted by their published effect sizes. At baseline, the GRS were not associated with total intakes of energy, macronutrients or fibre. The mean 1- and 3-year weight changes were not affected by the BMI or WHR GRS. During the 3-year follow-up, a trend for higher BMI by the GRS was detected especially in those who reported a diet low in fibre (P for interaction=0·065). Based on the present findings, it appears unlikely that obesity-predisposing variants substantially modify the effect of lifestyle modification on the success of weight reduction in the long term. In addition, these findings suggest that the association between the BMI-related genetic variants and obesity could be modulated by the diet.	f	\N
23669496	We evaluated the prevalence of chronotropic incompetence (CI), a marker of autonomic dysfunction, and its prognostic value in patients with chronic obstructive pulmonary disease (COPD). We performed a retrospective analysis of 449 patients with severe COPD who underwent a cardiopulmonary exercise test, after excluding patients with lung volume reduction surgery, left ventricular dysfunction and those not in sinus rhythm. CI was defined as percent predicted heart rate reserve (%HRR). Events were defined as death or lung transplant during a median follow-up of 68 months. Median age was 61 years; median percent predicted forced expiratory volume in one second (%FEV1) of 25% and median %HRR of 33%. The hazard ratio for an event in the lowest quartile of %HRR, taking the highest quartile as reference, was of 3.2 (95% confidence interval: 2.1-4.8; p<0.001). In a multivariate regression model, %HRR was an independent predictor of events. In conclusion, CI was an independent and powerful outcome predictor in patients with severe COPD.	f	\N
23669598	Although human papillomavirus (HPV) infections have been causally linked to oral cavity squamous cell carcinoma (OSCC), the potential role of low-risk HPV (LR-HPV) types in the pathogenesis of this malignancy remains unclear. We sought to investigate the distribution of HPV genotypes and their prognostic significance in OSCC patients treated by radical surgery, either with or without adjuvant therapy. We studied two non-overlapping OSCC cohorts for the periods 2005-2006 (2005 cohort, n = 204) and 2010-2011 (2010 cohort, n = 206). Paraffin-embedded tissue blocks were collected, and the HPV genotype was determined using PCR plus HPV blot tests. The primary study endpoint was the prevalence of HPV genotypes. The secondary endpoints were the 2-year therapeutic outcomes. The overall prevalence of HPV infections did not differ significantly in the two study cohorts. However, the prevalence of LR-HPV was significantly higher in the 2010 cohort than in the 2005 cohort (p = 0.002). The overall prevalence of HPV infections was not significantly associated with the 2-year outcomes. However, multivariate analysis demonstrated that LR-HPV infection was a predictor of poor 2-year disease-free survival (p = 0.036, hazard ratio [HR] = 3.1), disease-specific survival (p = 0.014, HR = 3.8), and overall survival (p = 0.016, HR = 3.2) in the subgroups of OSCC patients with poor differentiation, pN2 lymph node metastases, or extracapsular spread (n = 150). LR-HPV infections may have an important role in determining the clinical outcomes of certain OSCC patients bearing specific risk factors.	f	\N
23670309	It is a matter of debate whether increased brain iron levels are the cause or only the consequence of neurodegenerative process in degenerative parkinsonism. The aim of this study is to characterize disease-related changes in volumes and iron-related R2 values of basal ganglia and thalamus. 13 patients with progressive supranuclear palsy (PSP), 15 with a parkinsonian variant of multiple system atrophy (MSA-p), 29 with Parkinson's disease (PD), and 21 age-matched controls underwent 3-Tesla MRI. The R2 values and volumes were calculated for the selected subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) using an automated region-based analysis. Voxel-based analysis was also performed to visualize a topographical correlation of R2 value and volume. The PSP group had significantly higher R2 values in globus pallidus and caudate nucleus (p < 0.05), whereas the MSA-p group had higher R2 values in putamen (p < 0.001) than PD and controls. The globus pallidus in PSP and the putamen in MSA-p were the most significant areas of atrophy to differentiate PSP, MSA-p and PD (AUC = 0.856, 0.832, respectively, p < 0.001). The R2 values in both structures increased in parallel with the extent of atrophy. They were negatively correlated with volumes in putamen (r = -0.777, p < 0.001) and globus pallidus (r = -0.409, p = 0.025) of MSA-p, and globus pallidus (r = -0.4, p = 0.043) of PSP. Voxel-based analysis identified higher R2 values in more severely atrophic sub-regions in these structures. We observed topographical differences of iron deposition as well as atrophy between MSA-p and PSP. Increased iron levels were related to the structural atrophy in basal ganglia. Our results imply that iron accumulation is likely an epiphenomenon of the degenerative process.	f	\N
23682773	Some studies have shown differences in specific cognitive ability domains between the sexes at 60 years-of-age. However is important to analyze whether the rate of cognitive decline is also similar between the sexes after this age. The present study examined previously published literature to investigate whether cognitive decline is distinct between men and women after the age of 60 years. A systematic review was carried out with the PubMed, LILACS and PsycINFO databases (2001-2011) using the following search terms: aging, aged, cognitive function, mild cognitive impairment, mental health and cognition. We analyzed longitudinal research that used neuropsychological tests for evaluating cognitive function, showed results separated by sex and that excluded participants with dementia. Elderly women showed better performance in tests of episodic memory, whereas elderly men had a better visuospatial ability. Only one study detected distinct rates of cognitive decline in specific tests between the sexes. Despite differences observed in some domains, most of the studies showed that this rate is similar between the sexes until the age of 80 years. It is unclear whether sex influences the rate of cognitive decline after the age of 80 years. The present review observed that sex does not determine the rate of cognitive decline between 60 and 80 years-of-age. The contextual and cultural factors that involve men and women might determine a distinct decline between them, rather than sex alone.	f	\N
23683938	The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than LDL cholesterol (LDLC), total LDL particles and usual measurement of oxidized LDL. The association between LAB and intima-media thickness (IMT) of carotid artery was investigated by ultrasound in US and Japan men. Participants were 297 US Caucasian and 310 Japanese men, aged 40-49 years without past history of cardiovascular disease. Serum LAB levels were measured by ELISAs with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody. Serum LAB levels [median (interquartile range), μg/L] were 1321 (936, 1730) in US Caucasians and 940 (688, 1259) in Japanese. For Caucasian men, average IMT was higher in higher LAB quartile, which was 0.653, 0.667, 0.688, and 0.702 mm, respectively (p for trend = 0.02). Linear regression analysis showed serum LAB was significantly associated with IMT after adjustment for LDLC or total LDL particles in addition to other traditional or novel risk factors for atherosclerosis such as C-reactive protein. However, there was no significant relationship between LAB and IMT in Japanese men. Serum LAB, a new candidate biomarker for residual risk, was associated with an increased carotid IMT in US Caucasian men independently of various risk factors; however, ethnic difference should be clarified in the future.	f	\N
23685553	Current guidelines do not support the use of genetic profiles in risk assessment of coronary heart disease (CHD). However, new single nucleotide polymorphisms associated with CHD and intermediate cardiovascular traits have recently been discovered. We aimed to compare several multilocus genetic risk score (MGRS) in terms of association with CHD and to evaluate clinical use. We investigated 6 Swedish prospective cohort studies with 10 612 participants free of CHD at baseline. We developed 1 overall MGRS based on 395 single nucleotide polymorphisms reported as being associated with cardiovascular traits, 1 CHD-specific MGRS, including 46 single nucleotide polymorphisms, and 6 trait-specific MGRS for each established CHD risk factors. Both the overall and the CHD-specific MGRS were significantly associated with CHD risk (781 incident events; hazard ratios for fourth versus first quartile, 1.54 and 1.52; P<0.001) and improved risk classification beyond established risk factors (net reclassification improvement, 4.2% and 4.9%; P=0.006 and 0.017). Discrimination improvement was modest (C-index improvement, 0.004). A polygene MGRS performed worse than the CHD-specific MGRS. We estimate that 1 additional CHD event for every 318 people screened at intermediate risk could be saved by measuring the CHD-specific genetic score in addition to the established risk factors. Our results indicate that genetic information could be of some clinical value for prediction of CHD, although further studies are needed to address aspects, such as feasibility, ethics, and cost efficiency of genetic profiling in the primary prevention setting.	f	\N
23685743	We evaluate sex-based differences in the effectiveness of early cardiac computed tomographic angiography (CCTA) and standard emergency department (ED) evaluation in patients with acute chest pain. In the Rule-Out Myocardial Infarction With Computer-Assisted Tomography (ROMICAT)-II multicenter, controlled trial, we randomized 1000 patients (47% women) 40 to 74 years of age with symptoms suggestive of acute coronary syndrome to an early CCTA or standard ED evaluation. In this prespecified analysis, women in the CCTA arm had a greater reduction in length of stay, lower hospital admission rates, and lesser increased cumulative radiation dose than men in a comparison of ED strategies (P for interaction ≤0.02). Although women had lower acute coronary syndrome rates than men (3% versus 12%; P<0.0001), sex differences in length of stay persisted after adjustment for baseline differences, including acute coronary syndrome rate (P for interaction <0.03). Length of stay was similar between sexes with normal CCTA findings (P=0.11). There was no missed acute coronary syndrome for either sex. No difference was observed in major adverse cardiac events between sexes and ED strategies (P for interaction =0.39). Women had more normal CCTA examinations than men (58% versus 37%; P<0.0001), less obstructive coronary disease by CCTA (5% versus 17%; P=0.0001), but similar normalcy rates for functional testing (P=0.65). Men in the CCTA arm had the highest rate of invasive coronary angiography (18%), whereas women had comparable low 5% rates regardless of ED strategy. This trial provides data supporting an early CCTA strategy as an attractive option in women presenting to the ED with symptoms suggestive of acute coronary syndrome. The findings may be explained by lower CAD prevalence and severity in women than men. http://www.clinicaltrials.gov. Unique identifier: NCT01084239.	f	\N
23689410	Coronary heart disease and ischemic stroke are frequent coexistent conditions that share risk factors and pose major burdens to global health. Even though a clear relation has been established between extracranial internal carotid artery atherosclerosis and symptomatic or asymptomatic coronary heart disease, there is a gap in knowledge about the association between intracranial atherosclerosis and coronary heart disease. Intracranial atherosclerosis is associated with high risks of stroke recurrence and vascular death. More research and clinical trials are needed to answer whether early diagnosis of asymptomatic coronary heart disease and aggressive treatment can decrease the risk of vascular death in patients with ischemic stroke caused by intracranial atherosclerosis.	f	\N
23698559	Animal models will be critical for preclinical evaluations of novel HIV eradication and/or functional cure strategies in the setting of suppressive combination antiretroviral therapy (cART). Here, the strengths, limitations, and challenges of recent efforts to develop nonhuman primate (NHP) models of cART-mediated suppression for use in studies of persistent virus and curative approaches are discussed. Several combinations of NHP species and viruses that recapitulate key aspects of human HIV infection have been adapted for cART-mediated suppression studies. Different cART regimens incorporating drugs targeting multiple different steps of the viral replication cycle have provided varying levels of virologic suppression, dependent in part upon the host species, virus, drug regimen and timing, and virologic monitoring assay sensitivity. New, increasingly sensitive virologic monitoring approaches for measurements of plasma viral RNA, cell-associated and tissue-associated viral RNA and DNA, and the replication-competent residual viral pool in the setting of cART in NHP models are being developed to allow for the assessment of persistent virus on cART and to evaluate the impact of viral induction/eradication strategies in vivo. Given the vagaries of each specific virus and host species, and cART regimen, each model will require further development and analysis to determine their appropriate application for addressing specific experimental questions.	f	\N
23700280	Lymphoma-associated hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal disease. Differences between B cell and T cell lymphoma-associated HLH remain unclear, specifically clinical characteristics and survival. We retrospectively analyzed 30 lymphoma-associated HLH patients from July 2004 to October 2012. Patients were divided into B cell (n = 13) and T cell (n = 17) lymphoma groups. Patients' age, performance status, presence of Epstein-Barr virus infection, international prognostic index, presence of disseminated intravascular coagulopathy, serum triglyceride, fibrinogen, and lactate dehydrogenase levels were not significantly different between B cell and T cell lymphoma groups. HLH was an indicator for treatment resistance in patients with B cell (p = 0.048), but not T cell (p = 0.217), lymphoma. Patients in the T cell lymphoma group, however, had higher serum ferritin levels than patients in the B cell lymphoma group (11,525.6 versus 3,790.6 ng/mL; p = 0.043). The median survival time for patients in the B cell and T cell lymphoma groups was 330 and 96 days, respectively. Although the difference was not statistically significant (p = 0.273), our results suggested a trend toward a better overall survival time in patients with B cell lymphoma. This survival advantage could be at least partially due to use of rituximab (p = 0.045) for the treatment of patients with B cell lymphoma. Our results also suggested that allogeneic hematopoietic stem cell transplantation could possibly provide survival benefits to T cell lymphoma-associated HLH by graft-versus-lymphoma effect.	f	\N
23701659	Reduced endogenous pain inhibition, as part of the degenerative process, is presumed to be the mechanism underlying the common presence of pain in patients with Parkinson's disease (PD). The present study aimed to assess an endogenous pain inhibitory system in PD using the conditioned pain modulation paradigm. Twenty-six predominantly unilateral PD patients and 19 controls underwent psychophysical pain assessment before and after patients' morning dopaminergic medication. An unexpected increase in several parameters of pain perception for PD patients was found after dopaminergic medication (e.g. for 49°C noxious heat stimulation an increase from 70.6 ± 4.0 to 77.6 ± 4.0 on the numerical pain scale, P < 0.001). This increase was seen in patients with predominantly left-sided PD, regardless of the stimulated side (for 49°C noxious heat stimulation, predominantly left-sided PD patients, pain perception increased from 73.5 ± 6.8 to 85.0 ± 6.8, P < 0.001, whereas predominantly right-sided PD patients did not show a significant increase, 68.3 ± 6.8 to 70.4 ± 6.5, P = 0.777). Baseline efficiency of conditioned pain modulation inversely correlated with age at disease onset (r = -0.522; P = 0.009) and disease severity (Unified PD Rating Scale, r = 0.447; P = 0.032) but did not differ between patients and controls. Increased sensory response causing hyperalgesia occurs after dopaminergic medication in patients with predominantly left-sided PD.	f	\N
23704428	Human monocytic ehrlichiosis (HME) is a tick-born disease that presents predominantly as a mild to moderate acute illness. Severe life-threatening disease has been reported with a case death rate of approximately 3%, often in immunosuppressed persons. A delay in therapy initiation has been proven to increase the morbidity of the disease. We report a case of an elderly immunocompetent man with severe HME disease and multiorgan failure to emphasise on the severity of this disease in the elderly, as well as the importance of early therapy for overall favourable prognosis.	f	\N
23706729	The health of the tens of millions of street children globally is understudied. We undertook a systematic review of the existing quantitative literature regarding the health status of street children and youth in low- and middle-income countries to summarize available knowledge, identify underexplored areas of research, and inform the future research agenda regarding the health of this population. A total of 108 articles met our inclusion criteria. Demographic data and structural factors associated with street life are summarized. Although data in specific regions or diseases are sparse, the literature review illustrates that youth's survival behaviors and the exposures associated with poor shelter have resulted in disproportionate morbidity in the areas of infectious illness, psychiatric disease, reproductive health, and perhaps to a lesser extent, growth. Vast areas of health that may disproportionately affect street children in childhood or later on as adults have not been investigated, including chronic diseases and cognitive deficits. Studies of specific diseases or conditions vary considerably by region. Strengths and limitations of the literature are discussed and principles for future research in this area are proposed.	f	\N
23709100	This multicenter analysis evaluated patient outcome and clinical pathologic features of thymic epithelial tumors after complete surgical resection and adjuvant treatment. Histologic classification and clinical staging were performed according to WHO classification and Masaoka staging system, respectively. We analyzed 62 patients, 20 (32%) of whom had myasthenia at diagnosis. Clinical and pathologic staging was as follows: 31 (50%) and 30 (48%) patients had stage I disease, 19 (30%) and 22 (35%) stage II, 5 (8%) and 3 (6%) stage III, 2 (4%) and 2 (3%) stage IVa, and 5 (8%) and 5 (8%) stage IVb, respectively. Histologic examination revealed 11 (19%) type A tumors, 19 (30%) type AB tumors, 7 (12%) type B1 tumors, 11 (17%) type B2 tumors, 11 (17%) type B3 tumors, and 3 (5%) type C tumors. Adjuvant therapies comprised chemotherapy in 3 (5%) patients and radiotherapy in 16 (26%) patients. Median follow-up was 71 months (range 1-145). DFS and OS at 48, 60, and 72 months were 89 and 89%, 86 and 97%, and 95% and 92%, respectively. Myasthenia at the onset of disease (P=0.18 for DFS; P=0.97) and tumor size>5 cm (P=0.94 for DFS; P=0.56) were not prognostic factors. TETs are rare and indolent tumors. Complete surgical resection followed by adjuvant therapies, such as chemotherapy and/or radiotherapy, in patients at risk of recurrence show very good DFS and OS results, even in cases with radically resected pleural-pulmonary metastases.	f	\N
23712633	Ticagrelor, a recently approved platelet antagonist indicated for the reduction of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS), has been reported to cause dyspnea in more than 13% of patients. Dyspnea is not a clinically relevant adverse event with other medications indicated for ACS. One suggested mechanism of ticagrelor-induced dyspnea involves an increase in systemic adenosine concentrations through adenosine deaminase inhibition. Dyspnea, a subjective finding resulting from physiologic and sensory mechanisms, may be a consequence of increased systemic adenosine concentrations, leading to amplified and prolonged receptor activity. Current literature suggests, however, that pulmonary status is not compromised, with no reduction of efficacy seen in patients with ticagrelor-induced dyspnea, thus allowing clinicians to continue therapy without reservation. Still, patients with a history of asthma and chronic obstructive pulmonary disease may be more susceptible to ticagrelor-induced dyspnea, potentially leading to nonadherence and exacerbations of morbidity. Therefore, it is paramount that health care providers continually monitor these patients with the aims of maintaining medication therapy adherence and providing relevant options if dyspnea becomes intolerable.	f	\N
23723040	We previously identified a four-generation family with medullary thyroid cancer (MTC) and a germline p.Y791F RET mutation whose cancer lacked a strong genotype-phenotype correlation. The entire gene coding region of the RET gene should be sequenced when genotype-phenotype discrepancies are observed in patients with multiple endocrine neoplasia type 2 (MEN 2), even if a RET hotspot mutation has been identified. A new genetic test was performed in the index case of this family with the p.Y791F RET germline mutation. The entire coding region of the RET gene was investigated by direct sequencing of PCR products. Once a mutation was identified, the target exon was sequenced in all at-risk relatives. An additional p.C634Y germline mutation in the RET gene was identified in the reported family. The double mutation occurred in cis and segregated with the phenotype. Through the Brazilian Genetic Screening Program developed at our institution, we additionally report the combination of these two mutations (p.C634Y/p.Y791F) in the RET gene in four other unrelated families. The overall penetrance of MTC and pheochromocytoma in patients with the p.C634Y/p.Y791F mutations was 79% and 13%, respectively. Our data emphasises that a comprehensive analysis of the RET gene may reveal multiple germline mutations in MEN 2 patients who exhibit an atypical clinical course of the disease.	f	\N
23725082	To examine the effect of hypertensive disease of pregnancy (HDP) on the development of respiratory distress syndrome (RDS) in preterm neonates. A retrospective cohort study. All neonatal intensive care units in New South Wales and the Australian Capital Territory. A total of 18,845 preterm neonates aged between 24 and 36 weeks gestation admitted to the units from 1998 to 2006 were included for study purpose. Exclusion criteria were multiple pregnancies, chorioamnionitis, antepartum hemorrhage and neonates who developed respiratory diagnoses other than RDS. Effect of HDP on the development of RDS was measured. A total of 1093 neonates from hypertensive and 2274 from normotensive pregnancies with complete datasets were included. The association between HDP and the development of RDS was modified by gestational age (HDP-by-gestational age interaction p value <0.0001). Therefore the cohort was divided into extreme (24-28 weeks gestation, n = 752), severe (29-32 weeks gestation, n = 1448) and moderate (33-36 weeks gestation, n = 1167) preterm groups. HDP was associated with a decreased risk of RDS in the moderate preterm group (OR: 0.68; 95% CI: 0.48-0.98, p = 0.04) and a non-significant change in risk for the severe preterm group. Almost all neonates in the extreme preterm group experienced RDS. HDP is associated with a lower risk of developing RDS in moderate preterm neonates. This could have clinical implications in terms of risk stratification for this group of neonates.	f	\N
23726393	The balance of risk and benefit from early neurosurgical intervention for conscious patients with superficial lobar intracerebral haemorrhage of 10-100 mL and no intraventricular haemorrhage admitted within 48 h of ictus is unclear. We therefore tested the hypothesis that early surgery compared with initial conservative treatment could improve outcome in these patients. In this international, parallel-group trial undertaken in 78 centres in 27 countries, we compared early surgical haematoma evacuation within 12 h of randomisation plus medical treatment with initial medical treatment alone (later evacuation was allowed if judged necessary). An automatic telephone and internet-based randomisation service was used to assign patients to surgery and initial conservative treatment in a 1:1 ratio. The trial was not masked. The primary outcome was a prognosis-based dichotomised (favourable or unfavourable) outcome of the 8 point Extended Glasgow Outcome Scale (GOSE) obtained by questionnaires posted to patients at 6 months. Analysis was by intention to treat. This trial is registered, number ISRCTN22153967. 307 of 601 patients were randomly assigned to early surgery and 294 to initial conservative treatment; 298 and 291 were followed up at 6 months, respectively; and 297 and 286 were included in the analysis, respectively. 174 (59%) of 297 patients in the early surgery group had an unfavourable outcome versus 178 (62%) of 286 patients in the initial conservative treatment group (absolute difference 3·7% [95% CI -4·3 to 11·6], odds ratio 0·86 [0·62 to 1·20]; p=0·367). The STICH II results confirm that early surgery does not increase the rate of death or disability at 6 months and might have a small but clinically relevant survival advantage for patients with spontaneous superficial intracerebral haemorrhage without intraventricular haemorrhage. UK Medical Research Council.	f	\N
23731266	Existing nutritional guidelines suggest that protein requirements of adults with stage five chronic kidney disease undergoing haemodialysis (HD) or peritoneal dialysis (PD) are increased as a result of protein losses during dialysis. The present review aimed to update previous guidance and develop evidence-based practice guidelines on the protein requirements of adults undergoing maintenance dialysis. Following a PICO approach (Participants or Population, Intervention or Exposure, Comparison and Outcome), four research questions were formulated to investigate the total protein requirement and protein quality required by adults undergoing HD and PD. A comprehensive, systematic review was undertaken using the databases Medline, EMBASE and the Cochrane Library from 2005 to September 2009 for HD studies and from 1997 to September 2009 for PD studies. The literature search yielded 2931 studies, which were assessed for inclusion. Following appraisal, 19 studies in HD and 18 studies in PD met the inclusion criteria and were systematically reviewed. Limited good quality evidence supports the recommendations that: (i) adults undergoing maintenance HD require a minimum protein intake of 1.1 g kg(-1) ideal body weight (IBW) per day; and (ii) adults undergoing maintenance PD require a minimum protein intake of 1.0-1.2 kg(-1) IBW per day, in conjunction with an adequate energy intake. There were no studies that addressed the quality of protein for either HD or PD. Evidence suggests that nutritional status may be maintained with lower protein intakes than previously recommended. However, the evidence base is limited and further randomised controlled trials are required to establish the optimal protein intake for dialysis patients.	f	\N
23742957	To determine the prevalence and persistence of new-onset clinical remission in rheumatoid arthritis (RA) patients. The Consortium of Rheumatology Researchers of North America (CORRONA) cohort was used to examine the prevalence of remission and associated comorbidities and RA therapies according to the 2011 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) remission criteria. Factors influencing the likelihood of remaining in remission were identified by logistic regression with generalized estimating equations. Analysis of variance and Tukey's test were used to determine differences in disability according to whether RA patients had been in remission or only low disease activity (LDA). A total of 2105 individuals met ACR/EULAR remission criteria at the most recent visit within CORRONA, yielding an 8% point prevalence of remission. Patients with certain comorbidities (e.g., heart failure) were significantly less likely to achieve or remain in remission compared to those without these conditions (p < 0.001 for each). Among prednisone users, the prevalence of remission was 1-6% (depending on dose) higher compared to those not on prednisone (10%). More than 50% of patients who had consistently been in remission for ≥1 year were able to remain in remission over the next year. Patients consistently in remission had less disability than patients who achieved LDA or who fluctuated between remission and LDA. Patients consistently in remission for at least 1 year had a high likelihood to remain in remission. These individuals might be considered the most likely candidates for de-escalation or withdrawal of RA treatments.	f	\N
23745323	The GOLD 2011 recommendations for chronic obstructive pulmonary disease (COPD) introduce a new classification system to optimize treatment in individual patients. Except for FEV,, this classification incorporates breathlessness measurement using modified medical research council questionnaire (mMRC) or the COPD assessment Test (CAT) and the number of exacerbations. The aim of our study was to compare the GOLD 2010 and GOLD 2011 COPD. The study group consisted of 143 patients. Based on the post-bronchodilator FEV, only, as recommended in the GOLD 2010 report, there were 24 patients in stage I, 57patients in II, 43 in Ill and 19 in IV, respectively. In all patients, the number of exacerbations per year was noted and dyspnea was assessed with the modified MRC scale. The patients were subsequently graded to group A,B,C,D as proposed in the combined COPD assessment in GOLD 2011. Grading of 51 (35,7%) patients according to the GOLD 2011 criteria was difficult; there were 22 patients in GOLD stage I/II with > or =2 exacerbations per year and 29 patients in GOLD stage Ill/IV with < 2 exacerbations per year. They were grading to more risk group. The new classification according to GOLD 2011 lets on optimizations of the treatment, in most cases of COPD patients but in clinical practice, there may be problems with the classification of the patients with severe airway obstruction without frequent exacerbations and especially those with mild/moderate airflow limitation and frequent exacerbations.	f	\N
23750230	All non-human great apes are endangered in the wild, and it is therefore important to gain an understanding of their demography and genetic diversity. Whole genome assembly projects have provided an invaluable foundation for understanding genetics in all four genera, but to date genetic studies of multiple individuals within great ape species have largely been confined to mitochondrial DNA and a small number of other loci. Here, we present a genome-wide survey of genetic variation in gorillas using a reduced representation sequencing approach, focusing on the two lowland subspecies. We identify 3,006,670 polymorphic sites in 14 individuals: 12 western lowland gorillas (Gorilla gorilla gorilla) and 2 eastern lowland gorillas (Gorilla beringei graueri). We find that the two species are genetically distinct, based on levels of heterozygosity and patterns of allele sharing. Focusing on the western lowland population, we observe evidence for population substructure, and a deficit of rare genetic variants suggesting a recent episode of population contraction. In western lowland gorillas, there is an elevation of variation towards telomeres and centromeres on the chromosomal scale. On a finer scale, we find substantial variation in genetic diversity, including a marked reduction close to the major histocompatibility locus, perhaps indicative of recent strong selection there. These findings suggest that despite their maintaining an overall level of genetic diversity equal to or greater than that of humans, population decline, perhaps associated with disease, has been a significant factor in recent and long-term pressures on wild gorilla populations.	f	\N
23752073	Several studies have indicated that plasma citrulline levels reflect the extent of mucosal injury of the small intestine. This study was performed to determine whether plasma citrulline levels correlate with the disease activity in pediatric patients with Crohn disease (CD). A total of 63 CD and 23 ulcerative colitis (UC) patients were included in this study. Disease severity was assessed by pediatric CD activity index (PCDAI), pediatric UC activity index, simplified endoscopic activity score for CD, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The correlations among these variables and plasma citrulline levels were evaluated. We performed subgroup analysis whether correlations between plasma citrulline levels and disease activity depend on small bowel involvement in patients with CD. The plasma citrulline levels correlated negatively with CRP (r = -0.332, P = 0.008), ESR (r = -0.290, P = 0.022), and PCDAI (r = -0.424, P = 0.001) in patients with CD. The plasma citrulline levels were significantly lower in patients with jejunal involvement than in those without (P = 0.027). In subgroup analysis, patients with CD with jejunal involvement showed significantly negative correlations of plasma citrulline levels with CRP (r = -0.628, P = 0.016) and PCDAI (r = -0.632, P = 0.015); however, patients with CD without jejunal involvement revealed no correlations of plasma citrulline levels with CRP and PCDAI. There were no significant correlations between plasma citrulline levels and simplified endoscopic activity score for CD. There were no significant correlations of plasma citrulline levels with CRP, ESR, and pediatric UC activity index in patients with UC. Plasma citrulline levels correlated with disease severity as measured by PCDAI, CRP, and ESR in pediatric patients with CD with jejunal involvement.	f	\N
23756272	To assess the effectiveness of a multidisciplinary team approach to reduce severe maternal morbidity in women with invasive placenta previa. We conducted a prospective study of 33 women with placenta previa and increta-percreta (diagnosed by ultrasound and/or magnetic resonance imaging) delivering at Mount Sinai Hospital, Toronto, following the introduction in January 2008 of a team-based approach to women with this condition. We included women who delivered by June 2012. We reviewed antenatal outpatient and inpatient records for use of six pre-defined team components by the attending staff obstetrician: (1) antenatal maternal-fetal medicine consultation, (2) surgical gynaecology consultation, (3) antenatal MRI, (4) interventional radiology consultation and preoperative placement of balloon catheters in the anterior divisions of the internal iliac arteries, (5) pre-planned surgical date, and (6) surgery performed by members of the invasive placenta surgical team. Antenatal course, delivery, and postpartum details were recorded to derive a five-point composite severe maternal morbidity score based on the presence or absence of: (1) ICU admission following delivery, (2) transfusion > 2 units of blood, (3) general anaesthesia start or conversion, (4) operating time in highest quartile (> 125 minutes), and (5) significant postoperative complications (readmission, prolonged postpartum stay, and/or pulmonary embolism). All 33 women survived during this time period. Two thirds (22/33) had either five or six of the six components of multidisciplinary care. Increasing use of multidisciplinary team components was associated with a significant reduction in composite morbidity (R2 = 0.228, P = 0.005). Team-based assessment and management of women with invasive placenta previa is likely to improve maternal outcomes and should be encouraged on a regional basis.	f	\N
23774792	Both genetic inactivation and pharmacological inhibition of the cholesteryl ester synthetic enzyme acyl-CoA:cholesterol acyltransferase 1 (ACAT1) have shown benefit in mouse models of Alzheimer's disease (AD). In this study, we aimed to test the potential therapeutic applications of adeno-associated virus (AAV)-mediated Acat1 gene knockdown in AD mice. We constructed recombinant AAVs expressing artificial microRNA (miRNA) sequences, which targeted Acat1 for knockdown. We demonstrated that our AAVs could infect cultured mouse neurons and glia and effectively knockdown ACAT activity in vitro. We next delivered the AAVs to mouse brains neurosurgically, and demonstrated that Acat1-targeting AAVs could express viral proteins and effectively diminish ACAT activity in vivo, without inducing appreciable inflammation. We delivered the AAVs to the brains of 10-month-old AD mice and analyzed the effects on the AD phenotype at 12 months of age. Acat1-targeting AAV delivered to the brains of AD mice decreased the levels of brain amyloid-β and full-length human amyloid precursor protein (hAPP), to levels similar to complete genetic ablation of Acat1. This study provides support for the potential therapeutic use of Acat1 knockdown gene therapy in AD.	f	\N
23782739	Shewanella spp. is infrequently recovered from clinical specimens. Following two outbreaks of food poisoning, eight Shewanella spp. strains were obtained from the fecal specimens of patients, food and food processing-related materials. Tetrodotoxin (TTX) was identified in the culture supernatants of these strains, and the toxin's biological activity was detected using a mouse bioassay. This study suggested that Shewanella strains can colonize and survive in human intestines. The study also raises the issues of the accumulation of TTX produced by Shewanella in food and the possible role of TTX-producing Shewanella in food poisoning.	f	\N
23793899	Middle East Respiratory Syndrome coronavirus (MERS CoV) came to attention as an emerging pathogen causing severe respiratory illness in patients from the Middle East in September 2012. As of 14 June 2013, 58 human cases of MERS CoV infection have been confirmed, including 33 deaths (case fatality rate of 57%). MERS CoV is a beta-coronavirus, in the same family as SARS-CoV, and shares a probable origin from bats. No animal reservoir or intermediates have been definitely implicated in transmission. Limited human-to-human transmission has occurred within several clusters, as individuals without a recent travel history have become infected after exposure to an ill returned traveler.	f	\N
23811578	Acute thallium poisoning rarely occurs but is a serious and even fatal medical condition. Currently, patients with acute thallium poisoning are usually treated with Prussian blue and blood purification therapy. However, there are few studies about these treatments for acute thallium poisoning. Nine patients with acute thallium poisoning from 1 family were treated successfully with Prussian blue and different types of blood purification therapies and analyzed. Prussian blue combined with sequential hemodialysis, hemoperfusion and/or continuous veno-venous hemofiltration were effective for the treatment of patients with acute thallium poisoning, even after delayed diagnosis. Blood purification therapies help in the clearance of thallium in those with acute thallium poisoning. Prussian blue treatment may do the benefit during this process.	f	\N
23815257	A hallmark of acute inflammation involves the recruitment of polymorphonuclear leukocytes (neutrophils) to infected or injured tissues. The processes underlying this recruitment are complex, and include multiple mechanisms of intercellular communication between neutrophils and the inflamed tissue. In recent studies of the systemic and pulmonary vasculature, interest has increased in novel forms of intercellular communication, such as microparticle exchange and gap junctional intercellular communication. To understand the roles of these novel forms of communication in the onset, progression, and resolution of inflammatory lung injury (such as acute respiratory distress syndrome), we review the literature concerning the contributions of microparticle exchange and gap junctional intercellular communication to neutrophil-alveolar crosstalk during pulmonary inflammation. By focusing on these cell-cell communications, we aim to demonstrate significant gaps of knowledge and identify areas of considerable need for further investigations of the processes of acute lung inflammation.	f	\N
23817139	Animal models of chronic kidney disease (CKD) approximate the human condition and are keys to understanding its pathogenesis and to developing rational treatment strategies. The ethical use of animals requires a detailed understanding of the strengths and limitations of each species and the disease model, and the way in which findings can be translated from animals to humans. While not perfect, the careful use of animal experiments offers the opportunity to examine individual mechanisms in an accelerated time frame.	f	\N
23830210	Postoperative chylothorax is a frequently encountered pathology occurring in up to 4% of patients undergoing surgery for repair of congenital heart disease. Symptomatic thrombosis is associated with chylothorax and may contribute to its severity and duration. Furthermore, vessel thrombosis resulting in persistent vessel occlusion may impede future treatments, diagnostic studies and cardio-surgical interventions. The objective of this study was to determine the incidence of upper system thrombosis in pediatric congenital heart patients with confirmed chylothorax with ultrasound screening of all patients diagnosed with chylothorax. All pediatric patients with confirmed with chylothorax underwent doppler ultrasound of the upper venous system as per hospital standard. This retrospective cohort study enrolled all children between February 1, 2010-August 2012, post cardiac surgery with confirmed chylothorax to determine the incidence of all thrombosis. There were 1396 children who underwent 1396 cardiac surgical procedures during the study time with 760 undergoing cardiopulmonary bypass. Development of chylothorax occurred in 54 of 1396, 3.9% (95%CI 3.0;5.0) procedures in all children. In those children with chylothorax, 28 of 54 episodes, 51.8% (95%CI 38.9;64.6) had confirmed VTE. The 51.8% incidence in this study demonstrates a 2.6 fold increase in risk of thrombosis compared to 20% in children with heart disease and central venous lines and may result in serious clinical consequences. The contribution of upper venous system thrombosis to chylothorax is unknown. Often, clinical suspicion of chylothorax exists, however the lack of a standardized approach to objective diagnosis results in delayed confirmation. Approaches to therapy either treatment of confirmed thrombosis or prevention of thrombosis in patients with chylothorax require formal evaluation. Future studies are urgently needed.	f	\N
23832758	Kallikrein 6 (KLK6) is a secreted serine protease preferentially expressed by oligodendroglia in CNS white matter. Elevated levels of KLK6 occur in actively demyelinating multiple sclerosis (MS) lesions and in cases of spinal cord injury (SCI), stroke, and glioblastoma. Taken with recent evidence establishing KLK6 as a CNS-endogenous activator of protease-activated receptors (PARs), we hypothesized that KLK6 activates a subset of PARs to regulate oligodendrocyte physiology and potentially pathophysiology. Here, primary oligodendrocyte cultures derived from wild type or PAR1-deficient mice and the murine oligodendrocyte cell line, Oli-neu, were used to demonstrate that Klk6 (rodent form) mediates loss of oligodendrocyte processes and impedes morphological differentiation of oligodendrocyte progenitor cells (OPCs) in a PAR1-dependent fashion. Comparable gliopathy was also elicited by the canonical PAR1 agonist, thrombin, as well as PAR1-activating peptides (PAR1-APs). Klk6 also exacerbated ATP-mediated oligodendrogliopathy in vitro, pointing to a potential role in augmenting excitotoxicity. In addition, Klk6 suppressed the expression of proteolipid protein (PLP) RNA in cultured oligodendrocytes by a mechanism involving PAR1-mediated Erk1/2 signaling. Microinjection of PAR1 agonists, including Klk6 or PAR1-APs, into the dorsal column white matter of PAR1(+/+) but not PAR1(-/-) mice promoted vacuolating myelopathy and a loss of immunoreactivity for myelin basic protein (MBP) and CC-1(+) oligodendrocytes. These results demonstrate a functional role for Klk6-PAR1 signaling in oligodendroglial pathophysiology and suggest that antagonists of PAR1 or its protease agonists may represent new modalities to moderate demyelination and to promote myelin regeneration in cases of CNS white matter injury or disease.	f	\N
23838529	Classical multiple sclerosis (CMS) and neuromyelitis optica spectrum disorders (NMOSD) are distinct central nervous system inflammatory demyelinating disorders (CNS IDD). Early diagnosis of CNS IDD is important as appropriate immunotherapies to optimize prognosis. We studied the diagnoses of CNS IDD among Hong Kong Chinese in a hospital-based setting. Consecutive Chinese patients who presented to our hospital with clinically isolated syndrome and subsequently diagnosed to have CNS IDD from 1980 to 2010 were reviewed. Patients with known diagnosis of CNS IDD referred for further care were excluded. Serial sera were assayed for aquaporin-4 autoantibodies (AQP4 Ab), at least 3 assays within 2-5years. A total of 210 patients diagnosed to have CNS IDD with disease duration of at least 2years were studied. Among 198 patients with serial sera available, 40 (20.2%, 20 had NMO and 20 other NMOSD) were AQP4 Ab-positive. Four patients who were AQP4 Ab-negative on the initial assay converted to AQP4 Ab-positive on repeated assays. The diagnoses of 210 patients were CMS in 88 (41.9%), NMOSD 47 (22.4%, 27 NMO, 20 other NMOSD), single attack of myelitis 23 (11.0%), single attack of optic neuritis 21 (10.0%), relapsing myelitis 10 (4.8%), acute disseminated encephalomyelitis (ADEM) 9 (4.3%), relapsing optic neuritis in 6 (2.9%), opticospinal multiple sclerosis 3 (1.4%) and single attack of brainstem encephalitis 3 (1.4%). Compared to CMS, NMOSD patients had older onset age, lower frequencies of brain MRI abnormalities and CSF OCB, higher frequency of LETM, higher CNS inflammation attack frequency in the first 2years, worse clinical outcome with higher EDSS score and mortality rate. This hospital-based study suggests that CMS (41.9%) and NMOSD (22.4%) are the most common CNS IDD among Hong Kong Chinese. NMOSD has worse clinical outcome than CMS. Detection of AQP4 Ab facilitates early diagnosis and prompts immunotherapies of NMOSD.	f	\N
23846297	Decoy receptor 3 (DcR3) is abundantly expressed in human tumors and protects cells from a wide range of apoptotic stimuli. In this study, we demonstrate that DcR3 is overexpressed in pancreatic carcinoma cells, and that the pancreatic carcinoma cell lines, Panc-1 and SW1990, are resistant to Fas ligand (FasL)-mediated apoptosis. To further define the function of DcR3 in cell growth and apoptosis, we used small interfering RNA (siRNA) to knockdown the expression of the DcR3 gene in Panc-1 and SW1990 cells. Our results revealed that the silencing of DcR3 expression enhanced the inhibitory effects of FasL and reduced the capabiltiy of the cells for proliferation and colony formation in vitro. In addition, the downregulation of DcR3 modulated the cell apoptotic regulators, Fas-associated death domain (FADD), caspase‑3 and caspase‑8, thus triggering cell apoptosis. Furthermore, the knockdown of DcR3 inhibited the growth of Panc-1 tumor xenografts. Taken together, our findings indicate that DcR3 is important in cancer progression and may be a used as a potential therapeutic target for the gene therapy of pancreatic carcinoma.	f	\N
23849416	Abiraterone, an androgen synthesis inhibitor, has been successfully used in the treatment of castration-resistant prostate cancer (CRPC) for 2 yr. Enzalutamide is a second-generation nonsteroidal antiandrogen that has recently been approved for the same indication. This is the first study to evaluate the effectiveness of enzalutamide after failure of abiraterone. Thirty-five patients were identified as having received sequential therapy with abiraterone followed by enzalutamide. All patients had undergone prior docetaxel chemotherapy, and no patient had received ketoconazole. Posttreatment changes in prostate-specific antigen (PSA) were used to determine the activity of enzalutamide in patients who had received prior abiraterone. The median duration of abiraterone treatment was 9.0 mo (range: 2.0-19.0 mo). Of the 35 patients, 16 (45.7%) achieved a >50% decline in PSA, and 14 (40%) had a rising PSA as the best response. The median duration of subsequent enzalutamide treatment was 4.9 mo (Kaplan-Meier estimate; 95% confidence interval [CI], 2.4-7.4). Seven of 16 CRPC patients who were initially abiraterone-sensitive (43.8%) and 3 of 19 CRPC patients who were initially abiraterone-insensitive (15.8%) showed a >50% PSA decline while taking enzalutamide. Of the 35 patients, 17 (48.6%) were primarily enzalutamide-resistant and showed a rising PSA as the best response. Median time to progression was 4.0 mo (95% CI, 2.0-6.0) for 18 of 35 patients with at least one declining PSA value while taking enzalutamide (51.4%). Of the 17 patients who were assessable radiologically, only 1 (2.9%) attained a confirmed partial response. Small sample size was the major limitation. Enzalutamide treatment achieved only a modest response rate in patients progressing after abiraterone. Although cross-resistance between abiraterone and enzalutamide was a common phenomenon, it was not inevitable, and a small but significant number of patients showed significant benefit from sequential treatment.	f	\N
23850538	A few years ago, Anisakis infection was almost unknown. Since the first observation in the Netherlands in 1960, several cases of gastrointestinal infections due to a zoonosis sustained by this nematode have been described in countries in which the consumption of raw or uncooked fish (e.g., marinated or salted) is common. Japan alone accounts for 90% of all cases of anisakiasis described in the literature because of the widespread use of raw fish in traditional Japanese cuisine, with sushi and sashimi. Nonetheless, other cases have been reported in Europe, North and South America, and Asia. In Italy, this zoonosis is rare and mostly transmitted by the ingestion of marinated anchovies in coastal areas, or fashion foods (sushi, sashimi, etc.) in inland areas. Once eaten, this parasite can cause an acute form of disease characterized by severe abdominal pain, and for this reason many patients receive the final diagnosis only on obtaining the surgical specimen. Since conservative medical treatment for acute anisakiasis relies on endoscopic removal of the nematode from the gastrointestinal wall if performed within 12h from the ingestion of contaminated fish, it should be compulsory to consider this parasitosis in the accident and emergency department. Here we describe two cases of infection by Anisakis simplex due to ingestion of marinated anchovies in a coastal area of the Tyrrhenian Sea and discuss the types and varieties of Anisakis infection in humans.	f	\N
23861956	Severe stress experienced in early life may have long-term effects on adult physiological and psychological health and well-being. We studied physical and psychosocial functioning in late adulthood in subjects separated temporarily from their parents in childhood during World War II. The 1803 participants belong to the Helsinki Birth Cohort Study, born 1934-44. Of them, 267 (14.8%) had been evacuated abroad in childhood during WWII and the remaining subjects served as controls. Physical and psychosocial functioning was assessed with the Short Form 36 scale (SF-36) between 2001 and 2004. A test for trends was based on linear regression. All analyses were adjusted for age at clinical examination, social class in childhood and adulthood, smoking, alcohol intake, physical activity, body mass index, cardiovascular disease and diabetes. Physical functioning in late adulthood was lower among the separated men compared to non-separated men (b = -0.40, 95% confidence interval [95% CI]: -0.71 to -0.08). Those men separated in school age (>7 years) and who were separated for a duration over 2 years had the highest risk for lower physical functioning (b = -0.89, 95% CI: -1.58 to -0.20) and (b = -0.65, 95% CI: -1.25 to -0.05), respectively). Men separated for a duration over 2 years also had lower psychosocial functioning (b = -0.70, 95% CI: -1.35 to -0.06). These differences in physical and psychosocial functioning were not observed among women. Early life stress may increase the risk for impaired physical functioning in late adulthood among men. Timing and duration of the separation influenced the physical and psychosocial functioning in late adulthood.	f	\N
23866601	The lecture considers a number of molecular and cellular mechanisms underlying the structural and functional rearrangement and development of renal and cardiac fibrosis in chronic kidney disease (CKD). It details the key component of disadaptative organ remodeling (the formation of myofibroblasts via epithelial-mesenchymal and endothelial-mesenchymal transdifferentiation) and the role of leading angiofibrogenic mediators (angiotensin II, transforming growth factor-beta type 1, a plasminogen activator inhibitor type 1, etc.) in the regulation of these processes. Investigation of the molecular and cellular bases of organ fibrosis, including the factors of dysregulated activation, differentiation and survival of microfibroblasts, makes it possible to specify the mechanisms of action of traditional nephro- and cardioprotective agents, to offer a possibility for a goal-oriented (target) effect on individual fibrogenic components, and to expand the arsenal of medications suppressing renal and cardiac remodeling.	f	\N
23868901	Dabigatran is an oral direct thrombin inhibitor widely used to prevent and treat various thromboembolic complications. An advantage of this agent over other anticoagulants is that routine laboratory monitoring and related dose adjustments are considered unnecessary. A major disadvantage is the absence of a reliable means of reversing its anticoagulant effect. After U.S. Food and Drug Administration approval, recently emerged data suggest a higher bleeding risk with dabigatran, especially in the elderly. Clinicians are thus faced with caring for patients with serious bleeding events without readily available tests to measure drug levels or the anticoagulant effects of dabigatran and without effective antidotes to rapidly reverse the anticoagulant effect. On the basis of dabigatran's pharmacokinetic profile, hemodialysis and continuous renal replacement therapy have been used to remove dabigatran with the hope, still unproven, that this would rapidly reverse the anticoagulant effect and reduce bleeding in patients with normal and those with reduced kidney function. However, the best clinical approach to the patient with serious bleeding is not known, and the risks of placing a hemodialysis catheter in an anticoagulated patient can be substantial. This article reviews this issue, addressing clinical indications, drug pharmacokinetics, clinical and laboratory monitoring tests, and dialytic and nondialytic approaches to reduce bleeding in dabigatran-treated patients.	f	\N
23871729	Acute ischemic stroke is a major cerebrovascular disease with potential morbidity and mortality. Despite the availability of thrombolytic therapy in some centers, risk factor modification and rehabilitation therapy are the mainstays of stroke management. There is supporting evidence that Ginkgo biloba may afford neuroprotection and improve the outcomes of patients with acute ischemic stroke. In a double-blind, placebo-controlled, randomized controlled trial, we assessed the efficacy of G biloba on functional outcome in patients with acute stroke. The National Institutes of Heath Stroke Scale (NIHSS) was used to measure functional outcome. A total of 102 patients with acute ischemic stroke were studied. All patients received either G biloba or placebo tablets for 4 months. This trial was registered to the Iranian Registry of Clinical Trials (www.irct.ir; trial IRCT138804212150N1). There were 52 patients who received G biloba and 50 patients who were in the placebo group. Age, sex distribution, previous medical condition, and laboratory data did not have any significant difference between the 2 groups (P>.05). The mean difference of 4-month follow-up NIHSS scores and NIHSS scores at admission was 4.7±2.7 and 4.1±3.0 in the G biloba and placebo groups, respectively (P>.05). The primary outcome-a 50% reduction in the 4-month follow-up NIHSS score compared to the baseline NIHSS score-was reached in 17 patients (58.6%) and 5 patients (18.5%) in the G biloba and placebo groups, respectively (P<.05). The risk ratio and number needed to treat were 3.16 (confidence interval 1.35-7.39) and 2.50 (confidence interval 1.58-5.90), respectively. In addition, multivariate regression adjusted for age and sex revealed a significant NIHSS decline in the G biloba group compared to the placebo group (P<.05). Our data suggest that G biloba may have protective effects in ischemic stroke. Therefore, the administration of G biloba is recommended after acute ischemic stroke.	f	\N
23872666	Sequences of human endogenous retroviruses (HERVs) are members of the long terminal repeat (LTR) retrotransposon family. Although the expression of HERV has long been a topic of investigation, HERV-insertion polymorphisms are not well known, and a genetic association between HERV-insertion polymorphisms and cancer has never been reported. To identify novel HERV loci in the genome from cancer tissues, we carried out the inverse PCR method targeting a conserved LTR region of HML-2, which is the most recently acquired HERV group. Novel two insertions, HML-2_sLTR(1p13.2) and HML-2_sLTR(19q12), were identified as insertionally polymorphic solo LTRs. Furthermore, a significant prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in female never-smoking patients aged 60 years and over who had lung adenocarcinoma [versus the other genotyping; odds ratio (OR): 1.97; 95% confidence interval (CI): 1.01-3.81]. In another cohort consisting of female never-smoking patients with lung adenocarcinoma, a prevalence of HML-2_sLTR(1p13.2) homozygosity tended to be high in patients aged 60 years and over (versus the other genotyping; OR: 2.03; 95% CI: 0.96-4.29), whereas a low prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in patients <60 years old (versus the other genotyping; OR: 0.31; 95% CI: 0.11-0.94). Our results suggest that HML-2_sLTR(1p13.2) is involved with the susceptibility to lung adenocarcinoma in female never-smokers in an age-dependent manner and that other HERV polymorphisms related to human diseases might remain to be identified in the human genome.	f	\N
23874931	The HIV-1 characteristics associated with mother to child transmission (MTCT) are still poorly understood and if known would indicate where intervention strategies should be targeted. In contrast to horizontally infected individuals, exposed infants possess inherited antibodies (Abs) from their mother with the potential to protect against infection. We investigated the HIV-1 gp160 envelope proteins from seven transmitting mothers (TM) whose children were infected either during gestation or soon after delivery and from four non-transmitting mothers (NTM) with similar viral loads and CD4 counts. Using pseudo-typed viruses we tested gp160 envelope glycoproteins for TZM-bl infectivity, CD4 and CCR5 interactions, DC-SIGN capture and transfer and neutralization with an array of common neutralizing Abs (NAbs) (2F5, 2G12, 4E10 and b12) as well as mother and infant plasma. We found no viral correlates associated with HIV-1 MTCT nor did we find differences in neutralization with the panel of NAbs. We did, however, find that TM possessed significantly higher plasma neutralization capacities than NTM (P = 0.002). Furthermore, we found that in utero (IU) TM had a higher neutralization capacity than mothers transmitting either peri - partum (PP) or via breastfeeding (BF) (P = 0.002). Plasma from children infected IU neutralized viruses carrying autologous gp160 viral envelopes as well as those from their corresponding mothers whilst plasma from children infected PP and/or BF demonstrated poor neutralizing capacity. Our results demonstrate heightened autologous NAb responses against gp120/gp41 can associate with a greater risk of HIV-1 MTCT and more specifically in those infants infected IU. Although the number of HIV-1 transmitting pairs is low our results indicate that autologous NAb responses in mothers and infants do not protect against MTCT and may in fact be detrimental when considering IU HIV-1 transmissions.	f	\N
23876833	Tyrosine kinase inhibitors treatment in responding chronic myeloid leukaemia (CML) patients is generally continued indefinitely. In this randomised phase II trial, we investigated whether CML patients in molecular response(4.5) (MR(4.5), quantitative reverse-transcription polymerase chain reaction (RQ-PCR)) after previous combination therapy with imatinib and cytarabine may discontinue imatinib treatment safely. Thirty-three patients from the HOVON 51 study with an MR(4.5) for at least 2 years who were still on imatinib treatment were randomised between continuation of imatinib (arm A, n=18) or discontinuation of imatinib (arm B, n=15). After a median follow up of 36 months since randomisation, 3 patients (17%) in arm A and 10 patients (67%) in arm B had a molecular relapse. All 3 relapsing patients in arm A had also stopped imatinib after randomisation. All but one relapsing patient relapsed within 7 months after discontinuation of imatinib. The molecular relapse rate at 12 and 24 months after randomisation was 0% and 6% (arm A) and 53% and 67% (arm B) respectively. As-treated analysis revealed 56% and 61% relapses at 1 and 2 years since cessation in patients who discontinued imatinib, in contrast to 0% of patients who continued imatinib. All evaluable patients remained sensitive to imatinib after reinitiation and regained a molecular response. Our data suggest that discontinuation of imatinib is safe in patients with durable MR(4.5).	f	\N
23877014	This study aimed to evaluate the efficacy of radiation therapy for pelvic lymph node metastasis from uterine cervical cancer and identify an optimal radiation regimen. A total of 111 metastatic pelvic lymph nodes, ranging from 11 to 56 mm (median, 25 mm) on CT/MRI, in 62 patients with uterine cervical cancer were treated initially with curative radiation therapy, with 46 patients receiving concurrent chemotherapy. Total radiation doses ranged from 45 to 61.2 Gy (median, 50.4 Gy) in 1.8-2 Gy (median, 1.8 Gy) fractions. At a median follow-up of 33 months, 46 of the 62 patients survived. Only 2 irradiated lymph nodes, 24 and 28 mm in diameter, in 1 patient progressed after irradiation alone with 50.4 Gy in 1.8 Gy fractions. All 33 metastatic lymph nodes ≥ 30 mm in diameter were controlled by irradiation at a median dose of 55.8 Gy. The 3-year lymph node-progression free rates were 98.2% in all 62 patients and 98.0% in all 111 metastatic lymph nodes. Except for transient hematologic reactions, 2 patients developed grade ≥ 3 therapy-related toxicities, 1 with an ulcer and the other with perforation of the sigmoid colon. In addition, 2 patients experienced ileus after irradiation. Radiation therapy effectively controlled pelvic lymph node metastases in patients with uterine cervical cancer, with most nodes <24 mm in diameter controlled by total doses of 50.4 Gy in 1.8 Gy fractions and larger nodes controlled by 55.8 Gy, particularly with concurrent chemotherapy. Higher doses to metastatic lymph nodes may increase intestinal toxicities.	f	\N
23880785	The most abundant urinary protein, Tamm-Horsfall protein, later renamed uromodulin, is expressed exclusively by the thick ascending limb cells of the kidney and released into urine from the apical cell membrane. Uromodulin is believed to protect against urinary tract infections and stones, but its other physiologic functions have remained obscure until recently. Renewed interest in uromodulin has been brought about by the identification of uromodulin mutations as causes of a discrete group of diseases that are distinct from nephronophthisis. The three overlapping clinical uromodulin-associated kidney diseases (UAKD) are medullary cystic disease type 2, familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Previously thought of as "adult diseases", it is now recognized that they may also present in childhood and even in infancy. Common characteristics of all three diseases are autosomal dominant inheritance, unremarkable urine sediment and slow progression to end-stage renal disease (ESRD). They are frequently associated with hyperuricemia and gout. These diseases appear to result from failure of the mutant uromodulin to be incorporated into the apical cilium, thereby placing UAKD in the category of "ciliopathies". In addition to causing specific UAKD, certain uromodulin gene polymorphisms have been linked to ESRD in general, suggesting that uromodulin plays a modulatory role in kidney disease progression.	f	\N
23886073	Influenza A and B viruses form different genera, which were originally distinguished by antigenic differences in their nucleoproteins and matrix 1 proteins. Cross-protection between these two genera has not been observed in animal experiments, which is consistent with the low homology in viral proteins common to both viruses except for one of three polymerase proteins, polymerase basic 1 (PB1). Recently, however, antibody and CD4+ T cell epitopes conserved between the two genera were identified in humans. A protective antibody epitope was located in the stalk region of the surface glycoprotein, hemagglutinin, and a CD4+ T cell epitope was located in the fusion peptide of the hemagglutinin. The fusion peptide was also found to contain antibody epitopes in humans and animals. A short stretch of well-conserved peptide was also identified in the other surface glycoprotein, neuraminidase, and antibodies binding to this peptide were generated by peptide immunization in rabbits. Although PB1, the only protein which has relatively high overall sequence homology between influenza A and B viruses, is not considered an immunodominant protein in the T cell responses to influenza A virus infection, amino acid sequence comparisons show that a considerable number of previously identified T cell epitopes in the PB1 of influenza A viruses are conserved in the PB1 of influenza B viruses. These data indicate that B and T cell cross-reactivity exists between influenza A and B viruses, which may have modulatory effects on the disease process and recovery. Although the antibody titers and the specific T cell frequencies induced by natural infection or standard vaccination may not be high enough to provide cross protection in humans, it might be possible to develop immunization strategies to induce these cross-reactive responses more efficiently.	f	\N
23894446	A prostacyclin analogue, ONO-1301, is reported to upregulate beneficial proteins, including stromal cell derived factor-1 (SDF-1). We hypothesized that the sustained-release delivery of ONO-1301 would enhance SDF-1 expression in the acute myocardial infarction (MI) heart and induce bone marrow cells (BMCs) to home to the myocardium, leading to improved cardiac function in mice. ONO-1301 significantly upregulated SDF-1 secretion by fibroblasts. BMC migration was greater to ONO-1301-stimulated than unstimulated conditioned medium. This increase was diminished by treating the BMCs with a CXCR4-neutralizing antibody or CXCR4 antagonist (AMD3100). Atelocollagen sheets containing a sustained-release form of ONO-1301 (n = 33) or ONO-1301-free vehicle (n = 48) were implanted on the left ventricular (LV) anterior wall immediately after permanent left-anterior descending artery occlusion in C57BL6/N mice (male, 8-weeks-old). The SDF-1 expression in the infarct border zone was significantly elevated for 1 month in the ONO-1301-treated group. BMC accumulation in the infarcted hearts, detected by in vivo imaging after intravenous injection of labeled BMCs, was enhanced in the ONO-1301-treated hearts. This increase was inhibited by AMD3100. The accumulated BMCs differentiated into capillary structures. The survival rates and cardiac function were significantly improved in the ONO-1301-treated group (fractional area change 23±1%; n = 22) compared to the vehicle group (19±1%; n = 20; P = 0.004). LV anterior wall thinning, expansion of infarction, and fibrosis were lower in the ONO-1301-treated group. Sustained-release delivery of ONO-1301 promoted BMC recruitment to the acute MI heart via SDF-1/CXCR4 signaling and restored cardiac performance, suggesting a novel mechanism for ONO-1301-mediated acute-MI heart repair.	f	\N
23899604	In the mammalian nervous system, axons are commonly surrounded by myelin, a lipid-rich sheath that is essential for precise and rapid conduction of nerve impulses. In the peripheral nervous system (PNS), myelin sheaths are formed by Schwann cells which wrap around individual axons. While the tyrosine kinase receptors ERBB2 and ERBB3 are established mediators of peripheral myelination, less is known about the functions of the related epidermal growth factor receptor (EGFR) in the regulation of PNS myelination. Here, we report a peripheral neurodegenerative disease caused by increased EGFR activation. Specifically, we characterize a symmetric and distally pronounced, late-onset muscular atrophy in transgenic mice overexpressing the EGFR ligand epigen. Histological examination revealed a demyelinating neuropathy and axon degeneration, and molecular analysis of signaling pathways showed reduced protein kinase B (PKB, AKT) activation in the nerves of Epigen-tg mice, indicating that the muscular phenotype is secondary to PNS demyelination and axon degeneration. Crossing of Epigen-tg mice into an EGFR-deficient background revealed the pathology to be completely EGFR-dependent. This mouse line provides a new model for studying molecular events associated with early stages of peripheral neuropathies, an essential prerequisite for the development of successful therapeutic interventions.	f	\N
23902839	To explore the value of sentinel lymph nodes (SLN) metastasis status in predicting the presence of residual disease in non-sentinel lymph nodes (nSLN) and the feasibility of avoiding or reducing the scope of axillary lymph node dissection (ALND) for patients with single positive SLN. A retrospective study was conducted for 2265 patients with invasive breast carcinomas undergoing sentinel lymph nodes biopsy (SLNB) at Shandong Cancer Hospital between November 1999 and December 2011. And 1228 patients with axillary dissection were screened and divided into 5 groups of (-), (1/n), (1/1), (n/N), (n/n) (n ≥ 2, N ≥ 3, N > n) according to the status of SLN metastasis. The nSLN metastasis rate of SLN(-), (1/n), (1/1), (n/N) and (n/n) groups was 11.8%(73/618), 25.2%(65/258), 49.6%(67/135), 48.4%(60/124)and 65.6%(61/93)respectively. A comparison of SLN(-), (1/n), (1/1), (n/N), and (n/n) groups of nSLN metastasis showed a significant difference (P = 0.000). The differences of nSLN metastasis between SLN(-) and other groups (including 1/n, 1/1, n/N, n/n group) were significant (P = 0.000). This difference was also significant between SLN (1/n) and other positive groups (include 1/1, n/N, n/n group) (P = 0.000), but not significant between SLN(1/1), (n/N) and (n/n) groups (P = 0.842, 0.017, 0.042 respectively, Chi-square segmentation). No significant difference existed between axillary lymph node metastasis on Level II and III of SLN 1/n group and SLN(-) group (P = 0.012, 0.570,χ(2) segmentation). The status of SLN metastasis is one of influencing factors for the nSLN metastasis of patients with invasive breast cancer. The possibility of non-sentinel lymph node involvement for patients with single SLN metastasis was smaller than that of other SLN-positive patients. It is safe for some SLN 1/n patients to undergo low lymph node dissection. But ALND is not avoided for patients with single positive SLN (SLN 1/n n ≥ 2). Their clinicopathological variables should be also considered.	f	\N
23905909	Peripheral arterial diseases associated with an increased risk of death in kidney transplant patients. Natriuretic peptide has anti-atherosclerotic effects. We sought to evaluate the relation between ankle-brachial index and fasting serum long-acting natriuretic peptide concentrations in kidney transplant patients. Fasting blood samples were obtained from 69 kidney transplant patients. Serum long-acting natriuretic peptide concentrations were measured using a commercially available enzyme immunoassay kit. Left or right ankle-brachial index values that were < 0.9 were included in the low ankle-brachial index group. Fifteen patients (21.7%) were enrolled in the low ankle-brachial index group. Increased waist circumference (P = .013), higher serum total cholesterol levels (P = .019), higher triglyceride levels (P = .002), and decreased serum long-acting natriuretic peptide concentrations (P = .006) were noted in the low ankle-brachial index group. Univariate linear regression analysis indicated that the left/right ankle-brachial index values of the subjects were negatively correlated with serum triglycerides (P = .008 or P < .001) and fasting glucose levels (P = .034 or P = .012), but were positively correlated with long-acting natriuretic peptide concentrations (P = .011 or P = .011). Multivariate forward stepwise linear regression analyses of the significant variables revealed that serum triglycerides and long-acting natriuretic peptide levels were independent predictors of the left/right ankle-brachial index values of kidney transplant patients. Serum long-acting natriuretic peptide concentrations correlate positively with ankle-brachial index values among the kidney transplant patients.	f	\N
23908572	To evaluate the clinical usefulness of binocular multifocal electroretinography (mfERG) by comparing results with conventional monocular mfERG in patients with monocular macular disease. mfERG testing was conducted on 32 patients with monocular macular disease and 30 normal subjects. An initial mfERG was simultaneously recorded from both eyes with two recording electrodes under binocular stimulation. A second mfERG was subsequently recorded with conventional monocular stimulation. Amplitudes and implicit times of each ring response of the binocular and monocular recordings were compared. Ring ratios of the binocular and monocular recording were also compared. In the macular disease group, there were no statistical differences in amplitude or implicit time for each of the five concentric rings between the monocular and binocular recordings. However, with binocular simulation, the ring ratios (ring 1 / ring 4, ring 1 / ring 5) were significantly reduced in the affected eye. In the normal control group, there were no statistical differences in any parameters between the monocular and binocular recordings. Binocular mfERG could be a good alternative to the conventional monocular test. In addition, given that the test needs stable fixation of the affected eye during the binocular test, the reliability of the test results could be improved, especially for patients with monocular macular disease.	f	\N
23934213	Human Nijmegen breakage syndrome, caused by the hypomorphic mutation of Nbn gene, is a hereditary instability disease, characterized by chromosomal instability, immunodeficiency, radiosensitivity, cancer predisposition and microcephaly. To study the roles of Nbn protein in microcephaly, Nbn gene was specifically deleted in the central nervous system of mice by nestin-Cre targeting gene system (Frappart et al. in Nat Med 11:538-544, 2005). Strikingly, newborn Nbn-deficient mice exhibit the evident microcephalic cerebellum, which contributes to severe ataxia and balance deficiency. In this study, we first report that PI3K/AKT/mTOR signaling pathway that performs neurotrophic-protecting role in neuronal growth is significantly inhibited in newborn Nbn-deficient cortex and cerebellum. In addition, JNK signaling and ATR signaling are likely to converge to regulate the cerebellar apoptosis of newborn Nbn-deficient mice.	f	\N
23935207	This Phase II trial was designed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy in patients with poor-risk rectal cancer. Patients with magnetic resonance imaging-defined poor-risk rectal cancer received neoadjuvant oxaliplatin and capecitabine and bevacizumab followed by total mesorectal excision or more extensive surgery. Between February 2010 and December 2011, 32 patients were enrolled in this study. The completion rate of the scheduled chemotherapy was 91%. Reasons for withdrawal were refusal to continue therapy in two patients and disease progression in one, with two of these three patients not undergoing surgery. Among the 29 patients who completed the scheduled chemotherapy, one refused surgery within 8 weeks after the completion of chemotherapy, which was the period stipulated by the protocol, and another had rectal perforation, requiring urgent laparotomy. As a result, the completion rate of this experimental treatment was 84%. Of the 30 patients who underwent surgery, the R0 resection rate was 90% and a postoperative complication occurred in 43%. A pathological complete response was observed in 13% and good tumor regression was exhibited in 37%. Neoadjuvant oxaliplatin and capecitabine plus bevacizumab for poor-risk rectal cancer caused a high rate of anastomotic leakage and experienced a case with perforation during chemotherapy, both of which were bevacizumab-related toxicity. Although the short-term results with the completion rate of 84.4% and the pathological complete response rate of 13.3% were satisfactory, we have to reconsider the necessity of bevacizumab in neoadjuvant chemotherapy (UMIN number, 000003507).	f	\N
23955530	Type 1 diabetes (T1D) is one of the most common chronic diseases with childhood onset, and the disease incidence has increased two to fivefold over the past half century by as yet unknown means. T1D occurs when the body's immune system turns against itself, destroying in a very specific and targeted way-the pancreatic β-cells. T1D results from poorly defined interactions between susceptibility genes and environmental determinants. In contrast to the rapid progress in finding T1D genes, identification and confirmation of environmental determinants remain a formidable challenge. This review article will give an overview of ongoing prospective cohort studies aiming to identify the environmental trigger(s) causing T1D.	f	\N
23956301	Human papillomavirus 16 (HPV16) infection causes 50 % or more of cervical cancers in women. The HPV16 E7 oncogene is continuously expressed in infected epithelium with its oncogenicity linked to cervical cancer. The E7 protein is an ideal target in control of HPV infection through T-cell-mediated immunity. Using HPV16 E7-transgenic mouse keratinocytes (KCs-E7) to investigate T-cell-mediated immune responses, we have shown previously that HPV16-encoded E7 protein inhibits IFN-γ-mediated enhancement of MHC class I antigen processing and T-cell-induced target cell lysis. In this study, we found that HPV16 E7 suppresses IFN-γ-induced phosphorylation of STAT1((Tyr701)), leading to the blockade of interferon regulatory factor-1 (IRF-1) and transporter associated antigen processing subunit 1 (TAP-1) expression in KCs-E7. The results of a (51)Cr release assay demonstrated that IFN-γ-treated KCs-E7 escaped from CTL recognition because HPV16 E7 downregulated MHC class I antigen presentation on KCs. Restoration of IRF-1 expression in KCs-E7 overcame the inhibitory effect of E7 protein on IFN-γ-mediated CTL lysis and MHC class I antigen presentation on KCs. Our results suggest that HPV16 E7 interferes with the IFN-γ-mediated JAK1/JAK2/STAT1/IRF-1 signal transduction pathway and reduces the efficiency of peptide loading and MHC class I antigen presentation on KCs-E7. These results may reveal a new mechanism whereby HPV16 escapes from immune surveillance in vivo.	f	\N
23962064	Understanding how alveoli and the underlying capillary network develop and how these mechanisms are disrupted in disease states is critical for developing effective therapies for lung regeneration. Recent evidence suggests that lung angiogenesis promotes lung development and repair. Vascular endothelial growth factor (VEGF) preserves lung angiogenesis and alveolarization in experimental O2-induced arrested alveolar growth in newborn rats, but combined VEGF+angiopoietin 1 treatment is necessary to correct VEGF-induced vessel leakiness. Hypoxia-inducible factors (HIFs) are transcription factors that activate multiple O2-sensitive genes, including those encoding for angiogenic growth factors, but their role during postnatal lung growth is incompletely understood. By inducing the expression of a range of angiogenic factors in a coordinated fashion, HIF may orchestrate efficient and safe angiogenesis superior to VEGF. We hypothesized that HIF inhibition impairs alveolarization and that HIF activation regenerates irreversible O2-induced arrested alveolar growth. HIF inhibition by intratracheal dominant-negative adenovirus (dnHIF-1α)-mediated gene transfer or chetomin decreased lung HIF-1α, HIF-2α, and VEGF expression and led to air space enlargement and arrested lung vascular growth. In experimental O2-induced arrested alveolar growth in newborn rats, the characteristic features of air space enlargement and loss of lung capillaries were associated with decreased lung HIF-1α and HIF-2α expression. Intratracheal administration of Ad.HIF-1α restored HIF-1α, endothelial nitric oxide synthase, VEGF, VEGFR2, and Tie2 expression and preserved and rescued alveolar growth and lung capillary formation in this model. HIFs promote normal alveolar development and may be useful targets for alveolar regeneration.	f	\N
23962825	G protein-mediated signal transduction is essential for the regulation of cardiovascular function, including heart rate, growth, contraction, and vascular tone. Regulators of G protein Signaling (RGS proteins) fine-tune G protein-coupled receptor-induced signaling by regulating its magnitude and duration through direct interaction with the α subunits of heterotrimeric G proteins. Changes in the RGS protein expression and/or function in the heart often lead to pathophysiological changes and are associated with cardiac disease in animals and humans, including hypertrophy, fibrosis development, heart failure, and arrhythmias. This article focuses on Regulator of G protein Signaling 2 (RGS2), which is widely expressed in many tissues and is highly regulated in its expression and function. Most information to date has been obtained in biochemical, cellular, and animal studies, but data from humans is emerging. We review recent advances on the functional role of cardiovascular RGS2 and the mechanisms that determine its signaling selectivity, expression, and functionality. We highlight key unanswered questions and discuss the potential of RGS2 as a therapeutic target.	f	\N
23968196	Actinic prurigo (AP) is an idiopathic photodermatosis that usually onsets during childhood and predominates in women. It is characterized by the symmetrical involvement of sun-exposed areas of the skin, lips, and conjunctiva. This study aimed to analyze the risk factors associated with AP using a case-control design. All patients diagnosed with AP during 1990-2006 at Dr. Manuel Gea González General Hospital in Mexico City were included. Respective controls were recruited. Race, demographic, geographic, socioeconomic, environmental, clinical, and nutritional risk factors were assessed. A total of 132 persons were enrolled. These included 44 cases and two control groups comprising, respectively, dermatology and non-dermatology outpatients without AP or any autoimmune disease. Distribution by gender, age, place of birth, place of residence, and economic status did not differ significantly among the three groups. A total of 256 variables were analyzed. Only 19 variables were found to be statistically significant (P < 0.05). These were: use of a boiler; use of firewood; car ownership; use of earthenware; mixed material housing; socioeconomic level 1; sun exposure; use of soap; lemon consumption; use of moisturizing hair cream; living with pets in the house; living with farm animals; age; having a family member with AP; having had surgery; having had trauma; having been hospitalized; use of oral medication; and use of herbal medication. Of 40 macro- and micronutrients analyzed, 11 were found to have statistically significant effects (P < 0.05). Multiple epidemiologic, geographic, clinical, and immunologic factors are involved in the etiology of AP. This study proposes a clear line for research directed at specific risk factors that refer to an individual's clinical, allergic, health, and socioeconomic status. Further study should also investigate the etiologic role of diet in AP and the molecular mechanisms behind the development of AP to establish whether AP is caused by exposure to polycyclic aromatic hydrocarbons.	f	\N
23982030	To determine the rate of unplanned PICU readmissions, examine the characteristics of index admissions associated with readmission, and compare outcomes of readmissions versus index admissions. Retrospective cohort analysis. Ninety North American PICUs that participated in the Virtual Pediatric Intensive Care Unit Systems. One hundred five thousand four hundred thirty-seven admissions between July 2009 and March 2011. None. Unplanned PICU readmission within 48 hours of index discharge was the primary outcome. Summary statistics, bivariate analyses, and mixed-effects logistic regression model with random effects for each hospital were performed.There were 1,161 readmissions (1.2%). The readmission rate varied among PICUs (0-3.3%), and acute respiratory (56%), infectious (35%), neurological (28%), and cardiovascular (20%) diagnoses were often present on readmission. Readmission risk increased in patients with two or more complex chronic conditions (adjusted odds ratio, 1.72; p < 0.001), unscheduled index admission (adjusted odds ratio, 1.37; p < 0.001), and transfer to an intermediate unit (adjusted odds ratio, 1.29; p = 0.004, compared with ward). Trauma patients had a decreased risk of readmission (adjusted odds ratio, 0.67; p = 0.003). Gender, race, insurance, age more than 6 months, perioperative status, and nighttime transfer were not associated with readmission. Compared with index admissions, readmissions had longer median PICU length of stay (3.1 vs 1.7 d, p < 0.001) and higher mortality (4% vs 2.5%, p = 0.002). Unplanned PICU readmissions were relatively uncommon, but were associated with worse outcomes. Several patient and admission characteristics were associated with readmission. These data help identify high-risk patient groups and inform risk-adjustment for standardized readmission rates.	f	\N
23983044	To determine the differences in carotid intima-media thickness (CIMT) between patients with psoriatic diseases with and without metabolic syndrome. Eligible patients from the Cardiometabolic Outcome Measures in Psoriatic Arthritis Study database, which is comprised of both psoriasis and psoriatic arthritis (PsA) patients enrolled at 2 academic medical centers, were included. Detailed cardiovascular (CV) risk factors, including metabolic syndrome profiles, medication use, disease activity, and CIMT, were examined. A total of 343 patients with psoriatic disease were evaluated (42.28% with psoriasis and 57.72% with PsA). PsA patients were significantly older, with longer disease duration and higher blood pressure, body mass index, and C-reactive protein (CRP) level. PsA patients took more disease-modifying antirheumatic drugs (DMARDs) and corticosteroids and underwent more CV procedures. There were no differences in prior CV events, family history of CV risk, and Framingham/Adult Treatment Panel III Risk Score. PsA patients had a higher risk of metabolic syndrome (univariate odds ratio [OR] 1.78 [95% confidence interval (95% CI) 1.08-2.95], P = 0.025). Even after adjusting for age, CRP level, and diastolic blood pressure, PsA patients not taking DMARDs were twice as likely to have metabolic syndrome compared to psoriasis patients (adjusted OR 2.09 [95% CI 0.78-5.59], P = 0.049). PsA patients with metabolic syndrome had the thickest CIMT compared to any other group (P < 0.001). PsA patients had an increased prevalence of metabolic syndrome with significantly greater CIMT measurements compared to patients with psoriasis. Furthermore, PsA patients with metabolic syndrome had the greatest CIMT measurements compared to PsA patients without metabolic syndrome and psoriasis patients with or without metabolic syndrome. Incremental increases in inflammatory pathways in PsA may contribute to a higher CV risk as compared to psoriasis patients.	f	\N
23987905	This study evaluated effectiveness of three different surgical strategies for treating ascending aorta aneurysm, with or without involvement of the aortic root, associated with bicuspid aortic valve (BAV). Between 2005 and 2011, 150 consecutive patients underwent a Bentall operation in the presence of ascending aorta and aortic root dilation exceeding 45 mm in diameter and malfunctioning BAV (n = 46, group 1); separate aortic valve and ascending aorta replacement in presence of ascending aorta dilation exceeding 45 mm, aortic root of less than 45 mm, and malfunctioning BAV (n = 77, group 2); or ascending aorta replacement, with or without BAV repair, in the presence of ascending aorta dilation exceeding 45 mm, aortic root of less than 45 mm, and normally functioning or mildly insufficient BAV (n = 27, group 3). Compared with groups 2 and 3, group 1 patients were younger and affected by more severe BAV insufficiency and worse left ventricular function. In groups 1, 2, and 3, respectively, operative mortality was 2.1%, 1.3%, and 0%, and 5-year survival was 94% ± 4%, 92% ± 3.4%, and 100%. At 5 years, no patient in any group required reoperation on the ascending aorta or experienced aortic complications. In groups 2 and 3, root dimensions did not increase and were also significantly smaller compared with preoperative measurements (p < 0.05). Aortic regurgitation grade in group 3 (0.5 ± 0.8/4+) did not increase compared with the preoperative grade (0.8 ± 0.9/4+). At midterm follow-up, the Bentall operation remains associated with optimal results for the treatment of BAV, despite a worse preoperative presentation. In presence of a mildly diseased or normal aortic root and normal BAV function at the time of operation, less invasive surgical procedures, BAV-sparing, or repair procedures, appear to offer gratifying results.	f	\N
23993863	Despite extensive study, few therapeutic targets have been identified for glioblastoma (GBM). Here we show that patient-derived glioma sphere cultures (GSCs) that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics. Moreover, we found that a subset of the PN GSCs undergoes differentiation to a MES state in a TNF-α/NF-κB-dependent manner with an associated enrichment of CD44 subpopulations and radioresistant phenotypes. We present data to suggest that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process. We further show that the MES signature, CD44 expression, and NF-κB activation correlate with poor radiation response and shorter survival in patients with GBM.	f	\N
24010694	Lenalidomide is an immunomodulatory drug approved by the AEMPS and the EMA, in combination with dexamethasone, for the treatment of multiple myeloma in adult patients who have received at least one prior therapy. Moreover, it has recently been approved for the treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate. It has also shown to be active in other hematologic and no hematologic diseases. Growing evidence of its use entails a challenge when situating the drug in a cost-effective way to treat these diseases. On this article we review the available evidence on the use of lenalidomide in the second line treatment of patients with chronic lymphocytic leukemia, primary amyloidosis and primary myelofibrosis, and in the first line treatment of patients with myelodysplastic syndrome, and also the evidence of other immunomodulators. Different clinical practice guidelines and scientific evidence portals consider lenalidomide a valid alternative in the first-line treatment of patients with myelodysplastic syndromes, specially those with the deletion of 5q, and in second line for patients with chronic lymphocytic leukemia. However, the available evidence of lenalidomide in the treatment of patients with primary amyloidosis and primary myelofibrosis is limited, ant thus is not considered as the first choice treatment. In any case, the treatment of choice should consider the safety profile in each patient, the previous treatments that has received and the own therapeutic protocols of each center.	f	\N
24016609	Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. This retrospective study investigated ROP, including incidence, demographic information,risk factors, treatments, and refractive outcomes, in southern Taiwan over a 10-year period. The authors retrieved the National Cheng Kung University Hospital database between the years 2000 and 2009 for newborns with a gestational age less than 32 weeks and/or with a birth weight less than 1500 g who had been screened for ROP. We recorded sex, birth weight, gestational age, in-hospital versus out-of-hospital birth, paternal and maternal ages, whether there were multiple gestations, parity, Apgar scores, length of hospital stay, risk factors, presence and severity of ROP and whether it was treated, and refraction at the last visit. Regression analyses were performed to identify risk factors for ROP. A total of 503 live births were included. ROP was identified in 190 (37.8%) and met criteria for treatment in 59 (11.7%).ROP was diagnosed as stage 1, 2, 3, 4, and 5 in 61 (12.1%), 36 (7.2%), 81 (16.1%), 11 (2.2%), and 1 (0.2%) infant, respectively. Lower birth weight and younger gestational age were risk factors for greater severity of ROP (p < 0.001). Of the 167 with extremely low birth weight (<1000 g), 118 (70.7%) had ROP and 49 (29.3%) required treatment. On univariate analysis, low birth weight, younger gestational age, and risk factors such as respiratory distress syndrome, chronic lung disease, patent ductus arteriosus, surfactant usage, indomethacin usage, sepsis, upper gastrointestinal bleeding, blood transfusion, and necrotizing enterocolitis were associated with ROP. Multivariate logistic regression analysis showed that only lower birth weight was a significant and independent risk factor for ROP. Myopia (76%)and anisometropia (28%)were common in advanced ROP. Low birth weight is a major risk factor for ROP. Infants with extremely low birth weight had a higher risk of severe ROP. Common ocular sequelae of advanced ROP were myopia and anisometropia.	f	\N
24021446	We present two young patients with morphea or localized scleroderma undergoing systemic treatment, who developed papular lesions on pre-existing sclerotic plaques. Histology was compatible with a papular presentation of morphea and other entities in the differential diagnosis were ruled out. We believe this is a very uncommon presentation of activity in lesions of morphea and should be made known to clinicians so that activity and progression of the disease can be recognized and treated to avoid complications.	f	\N
24032423	Spinocerebellar ataxia type 1 (SCA1) is a hereditary, progressive and fatal movement disorder that primarily affects the cerebellum. Non-invasive imaging markers to detect early disease in SCA1 will facilitate testing and implementation of potential therapies. We have previously demonstrated the sensitivity of neurochemical levels measured by (1) H magnetic resonance spectroscopy (MRS) to progressive neurodegeneration using a transgenic mouse model of SCA1. In order to investigate very early neurochemical changes related to neurodegeneration, here we utilized a knock-in mouse model, the Sca1(154Q/2Q) line, which displays milder cerebellar pathology than the transgenic model. We measured cerebellar neurochemical profiles of Sca1(154Q/2Q) mice and wild-type littermates using 9.4T MRS at ages 6, 12, 24, and 39 weeks and assessed the cerebellar pathology of a subset of the mice at each time point. The Sca1(154Q/2Q) mice displayed very mild cerebellar pathology even at 39 weeks, however, were distinguished from wild types by MRS starting at 6 weeks. Taurine and total choline levels were significantly lower at all ages and glutamine and total creatine levels were higher starting at 12 weeks in Sca1(154Q/2Q) mice than controls, demonstrating the sensitivity of neurochemical levels to neurodegeneration related changes in the absence of overt pathology. We measured cerebellar neurochemical alterations in a knock-in mouse model of spinocerebellar ataxia type 1, a hereditary movement disorder, using ultra-high field magnetic resonance spectroscopy (MRS). Very early neurochemical alterations were detectable prior to overt pathology in the volume-of-interest for MRS. Alterations were indicative of osmolytic changes and of disturbances in membrane phospholipid and energy metabolism.	f	\N
24039761	Pig is an important agricultural animal for meat production and provides a valuable model for many human diseases. Functional studies have demonstrated that microRNAs (miRNAs) play critical roles in almost all aspects of skeletal muscle development and disease pathogenesis. To investigate the miRNAs involved in regulating different periods of skeletal muscle development, we herein performed a comprehensive research for porcine microRNAome (miRNAome) during 10 skeletal muscle developmental stages including 35, 49, 63, 77, 91 dpc (days post coitum) and 2, 28, 90, 120, 180 dpn (days postnatal) using Solexa sequencing technology. Our results extend the repertoire of pig miRNAome to 247 known miRNAs processed from 210 pre-miRNAs and 297 candidate novel miRNAs through comparison with known miRNAs in the miRBase. Expression analysis of the 15 most abundant miRNAs in every library indicated that functional miRNAome may be smaller and tend to be highly expressed. A series of muscle-related miRNAs summarized in our study present different patterns between myofibers formation phase and muscle maturation phase, providing valuable reference for investigation of functional miRNAs during skeletal muscle development. Analysis of temporal profiles of miRNA expression identifies 18 novel candidate myogenic miRNAs in pig, which might provide new insight into regulation mechanism mediated by miRNAs underlying muscle development.	f	\N
24050030	To evaluate serum and peritoneal concentrations of amyloid protein A in women with endometriosis and to compare them with those of women without endometriosis. A prospective study evaluated 76 women suspected of having pelvic endometriosis. Fifty-seven women (group A) were confirmed by videolaparoscopy and had their serum and peritoneal amyloid A concentrations measured by ELISA. The average levels from group A were compared to those obtained in group B. Group B was composed of 13 women without endometriosis, submitted to elective laparoscopy for tubal ligation. Peritoneal amyloid A concentrations in group A (310.3 +/- 97.8 ng/mL) were higher than those of group B (53.4 +/- 58.2 ng/mL); p = 0.0. However, serum concentrations in groups A (14.01 +/- 32.3 ng/mL) and B (9.5 +/- 15.9 ng/mL) did not differ significantly; p = 0.35. The peritoneal amyloid A protein concentration in pelvic endometriosis was higher when compared to normal controls, corroborating the inflammatory nature of the disease. This finding suggests that the procedure of evaluating the peritoneal amyloid A concentration in endometriosis merits further investigation.	f	\N
24052521	Resistin, which is derived from the gene of RSTN, belongs to a family of cysteine-rich secretory proteins called resistin-like molecules (RELMs). Increased serum resistin levels are associated with coronary artery disease (CAD) and the risk of cardiovascular death. Patients (n = 214) with an initial diagnosis of stable angina pectoris, unstable angina pectoris, and myocardial infarction without ST-segment elevation and referred to catheter laboratory for coronary angiography were enrolled in the study. We aimed to investigate the relationship between increased serum resistin level and CAD. The severity of CAD was calculated by the Gensini scoring system. In conclusion, we established a significant correlation between serum resistin levels and CAD (P = .010). Also, serum resistin levels correlated with the Gensini score that represents the severity of CAD angiographically (P = .010).	f	\N
24063011	Aspergillus fumigatus is a ubiquitously present respiratory pathogen. The outcome of a pulmonary disease may vary significantly with fungal viability and host immune status. Our objective in this study was (1) to assess the ability of inhaled irradiation-killed or live A. fumigatus spores to induce allergic pulmonary disease and (2) to assess the extent to which inhaled dead or live A. fumigatus spores influence pulmonary symptoms in a previously established allergic state. Our newly developed fungal delivery apparatus allowed us to recapitulate human exposure through repeated inhalation of dry fungal spores in an animal model. We found that live A. fumigatus spore inhalation led to a significantly increased humoral response, pulmonary inflammation, and airway remodeling in naïve mice and is more likely to induce allergic asthma symptoms than the dead spores. In contrast, in allergic mice, inhalation of dead and live conidia recruited neutrophils and induced goblet cell metaplasia. This data suggests that asthma symptoms might be exacerbated by the inhalation of live or dead spores in individuals with established allergy to fungal antigens, although the extent of symptoms was less with dead spores. These results are likely to be important while considering fungal exposure assessment methods and for making informed therapeutic decisions for mold-associated diseases.	f	\N
24064013	Since the publication of the first reports on the efficiency of colchicine in familial Mediterranean fever (FMF), very few randomised studies have investigated issues related to its long-term use. Thus, different approaches taken by physicians involved in FMF care, are exclusively empiric, emulative, and based on case-reports or case-series. Problems such as colchicine intolerance and colchicine resistance have not been solved yet. This paper aims to evaluate trends in colchicine therapy among physicians taking care of FMF patients around the world. We conducted a survey by sending questionnaires to FMF research and treatment centres in Europe and Asia. Many issues (such as dosages, schedules, side effects, interactions, efficacy and toxicity monitoring, definition of colchicine intolerance, colchicine resistance and responsiveness, etc) have been investigated. When more than 70% of physicians responded giving similar answers to an item, the response was considered as a 'trend'. A comparison between answers of physicians from FMF-prevalent and non-prevalent countries was also made. Thirty-five physicians from 11 countries filled the questionnaires, taking care of a total of more than 15000 FMF patients (pts). Different approaches were evident among the various physicians. Statistically significant different approaches between physicians from FMF-prevalent countries with respect to those from non-prevalent countries were found in items like colchicine during pregnancy, severity score and blood tests for disease monitoring. No consensus was found regarding the definition of colchicine resistance. The current study demonstrated significant variations in the strategy of colchicine therapy for FMF around the world and re-emphasised the need for standardised definitions of colchicine resistance and colchicine intolerance.	f	\N
24072601	Increasing evidence suggests low disease activity or remission is achievable in rheumatoid arthritis (RA). Using a treat to target strategy (T2T) has been shown to achieve these targets of remission or low disease activity in RA. In order to successfully treat to target, rheumatologists need reliable measures of disease activity to switch and/or escalate therapy to achieve or maintain therapeutic targets. Multiple disease-activity measures have been developed for both research and clinical practice. For clinical practice, the American College of Rheumatology (ACR) has recommended the PAS, PAS II, RAPID 3, CDAI, DAS 28, and SDAI for measuring disease activity in rheumatoid arthritis. Each of these measures has strengths and limitations, but they all accurately reflect disease activity, discriminate well between disease states, and are feasible to perform in the clinical setting. Implementation in the clinical setting can be optimized through leveraging technology and systems redesign. Tools such as web-based and smartphone applications have been developed to increase the ease with which these measures can be deployed. Disease-activity measurement in rheumatoid arthritis is included in the rheumatoid arthritis quality measures group in the Centers for Medicare and Medicaid Services' incentive-based Physician Quality Reporting System.	f	\N
24098438	Seminoma is one of the most common Testicular Germ Cell Tumours that originates during embryonic development due to an alteration of the local niche that in turn results in a delayed or blocked differentiation of Primordial Germ Cells. The block of differentiation is actually a common way to develop cancer disease as postulated by the "embryonic rest theory of cancer". In agreement with this theory different studies have demonstrated that embryonic cues display the capacity of reprogramming aggressive cancer cells towards a less aggressive phenotype. Herein we investigate the ability of a culture medium added with 10% egg albumen (EW, Egg White) to modulate seminoma cell phenotype and behaviour, by ensuring a proper set of morphogenetic signals. We chose to use the TCam-2 seminoma cell line that has been established as the only available cell line, obtained from a primary testicular seminoma. EW is able to: 1) modify TCam-2 cell spreading rate and cell-substrate adhesion without affecting proliferation and survival indexes; 2) modulate TCam-2 actin distribution pattern increasing cortical localization of actin filaments; 3) increase TCam-2 cell-cell junction capability; 4) decrease both chemo-sensitive and collective TCam-2 migratory behaviour. According to these observations morphometric fractal analysis revealed the ability of EW to increase Circularity and Solidity parameters and, consequently, to decrease Fractal dimension. Prompted by these observations we hypothesize that EW treatment could rescue, at least in part, the neoplastic-metastatic behaviour of seminoma cells.	f	\N
24102319	Transient receptor potential (TRP) channels are important mediators of sensory signals with marked effects on cellular functions and signalling pathways. Indeed, mutations in genes encoding TRP channels are the cause of several inherited diseases in humans (the so-called 'TRP channelopathies') that affect the cardiovascular, renal, skeletal and nervous systems. TRP channels are also promising targets for drug discovery. The initial focus of research was on TRP channels that are expressed on nociceptive neurons. Indeed, a number of potent, small-molecule TRPV1, TRPV3 and TRPA1 antagonists have already entered clinical trials as novel analgesic agents. There has been a recent upsurge in the amount of work that expands TRP channel drug discovery efforts into new disease areas such as asthma, cancer, anxiety, cardiac hypertrophy, as well as obesity and metabolic disorders. A better understanding of TRP channel functions in health and disease should lead to the discovery of first-in-class drugs for these intractable diseases. With this review, we hope to capture the current state of this rapidly expanding and changing field.	f	\N
24107731	The metabolic dysfunction accompanying the polycystic ovary syndrome (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD). Although menopause per se may be an additional risk factor of CVD, the association between PCOS in postmenopausal women and cardiovascular risk has not been adequately investigated. We aimed to evaluate the effect of PCOS on markers of subclinical atherosclerosis in nondiabetic postmenopausal women. This cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS phenotype was defined if three of the following were present: insulin resistance, current hyperandrogenism or history of clinical androgen excess, history of infertility, central obesity and history of irregular menses. Traditional CVD risk factors, as well as indices of arterial structure (intima-media thickness, atheromatous plaques presence) and function [flow-mediated dilation, pulse wave velocity (PWV), augmentation index] were compared between women with a PCOS phenotype and the rest of the sample, who served as controls. Women with the PCOS phenotype (N=43) had higher SBP and triglycerides and lower high-density lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed significantly between PCOS cases and controls (9.46±1.74 vs. 8.60±1.51 m/s, P=0.001, univariate). Multivariate regression analysis showed that the PCOS phenotype, age and SBP were the only independent predictors of PWV. Arterial stiffness is increased in asymptomatic, nondiabetic women with a putative PCOS phenotype, independently of age, BMI or blood pressure. This might present one mechanism through which PCOS increases the risk of CVD and hypertension later in life.	f	\N
24108471	Brain vasculature is uniquely programmed to protect central nervous system tissues and respond to their metabolic demands. These functions are subverted during the development of primary and metastatic brain tumors, resulting in vascular perturbations that are thought to contribute to progression and comorbidities of the underlying disease, including thrombosis and hemorrhage. Chronic activation of the coagulation system is particularly obvious in glioblastoma multiforme (GBM), where intratumoral vasoocclusive thrombosis may contribute to hypoxia, pseudopalisading necrosis, and angiogenesis. GBM is also associated with spontaneous or iatrogenic bleeding, and the emission of circulating procoagulants implicated in the unusually high risk of peripheral venous thromboembolism. Tissue factor (TF) expression is elevated in several types of brain tumors, including adult and pediatric GBM, as is the production of TF-containing microparticles (TF-MPs). Both TF expression and its vesicular emission are regulated by tumor microenvironment (e.g., hypoxia), in concert with activated oncogenic and growth factor pathways (RAS, EGFR, MET), as well as the loss of tumor suppressor gene activity (PTEN). Discovery of distinct oncogenic networks led to recognition of unique molecular subtypes within brain tumors, of which GBM (proneural, neural, classical, and mesenchymal), and medulloblastoma (SHH, WNT, group 3, and group 4) exhibit subtype-specific composition of the tumor coagulome. It remains to be established whether mechanisms of thrombosis and biological effects of coagulation in brain tumors are also subtype specific. In this regard, TF pathway represents a paradigm, and its impact on tumor dormancy, inflammation, angiogenesis, formation of cancer stem cell niches, and dissemination is a subject of considerable interest. However, establishing the extent to which TF and TF-MPs contribute to pathogenesis and thromboembolic disease in the context of primary and secondary brain tumors may require molecular stratification of patient populations. We suggest that a better understanding of these molecular linkages may pave the way to a more effective (targeted) therapy, prophylaxis, adjunctive use of anticoagulants, and other agents able to modulate interactions between brain tumors and the coagulation system.	f	\N
24124671	To explore the exercise characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH). From November 2010 to September 2012 , 76 consecutive IPAH patients and 24 healthy controls from Fuwai Cardiovascular Hospital were enrolled to undergo cardiopulmonary exercise testing. The exercise parameters were compared. Correlations among peak oxygen consumption, anaerobic threshold, peak oxygen pulse, New York Heart Association (NYHA) class, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6 MWD) and cardiac index are analyzed in IPAH. There were 21 males and 55 females in IPAH and 8 males and 16 females in controls. Their mean ages were (31.5 ± 10.6) and (35.5 ± 6.4) years respectively. Significant differences (P = 0.000) existed between two groups in peak oxygen consumption ((12.7 ± 3.3) vs (25.6 ± 5.8) ml·min(-1)·kg(-1)), anaerobic threshold ((9.8 ± 2.5) vs (16.7 ± 3.9) ml·min(-1)·kg(-1)), peak oxygen pulse ((5.3 ± 1.6) vs (9.9 ± 2.5) ml/bpm) and ventilator efficiency (slope of minute ventilation in relation to CO2 produced) ((42.6 ± 2.0) vs (25.5 ± 3.5)). In IPAH, peak oxygen consumption was significantly correlated with NYHA class (r = -0.509, P = 0.000), 6 MWD (r = 0.443, P = 0.002) and NT-proBNP levels (r = -0.423, P = 0.011). And anaerobic threshold was significantly correlated with NYHA class (r = -0.362, P = 0.002), 6MWD (r = 0.343, P = 0.004) and NT-proBNP levels (r = -0.275, P = 0.017). Peak oxygen pulse and ventilator efficiency were both correlated well with total pulmonary vascular resistance. Partial correlation analysis demonstrated that there were significant correlations among peak oxygen consumption, anaerobic threshold, NYHA class, NT-proBNP levels and 6MWD after adjusting for age, gender and weight. Peak oxygen consumption and anaerobic threshold decrease ventilator efficiency in IPAH patients. Cardiopulmonary exercise testing is an invasive tool of assessing safely the function of IPAH patients.	f	\N
24127735	Knee osteoarthritis (OA) is a major cause of pain, functional limitation, and reduced quality-of-life, particularly in older adults. This study evaluated the 'real world' NSAID-sparing effect of glucosamine (specifically Structoflex®) in patients with knee OA compared with a control population of patients who did not receive a slow-acting symptomatic anti-osteoarthritis agent. This analysis was conducted over a 1-year follow-up period. Data were sourced from the French Disease Analyzer (IMS Lifelink EMR™) database. The primary measure was the NSAID-sparing effect produced by Structoflex® compared with a matched control group. Secondary measures included an evaluation of the change in the number of general practitioner visits and use of other medicinal products related to knee OA. A total of 11,772 patients (67.66% female) were included in the analysis (436 and 11,336 patients in the Structoflex® and control groups, respectively). Most patients were aged 50-65 years (58.72%); 19.5% of patients were aged >76 years. At study inclusion, 51.61% of patients had experienced OA for <1 year. Prior to starting Structoflex®, 51.61% of patients had received an NSAID prescription. Significantly more patients who were receiving an NSAID at the time of starting Structoflex® discontinued their NSAID treatment during the follow-up period compared with patients in the control group (32% vs 23%; p = 0.0452). During the 1-year follow-up period, the total mean duration of NSAID prescription (30.39 ± 38.64 days vs 37.82 ± 54.62 days; p = 0.0109) and the mean number of days (calculated using Defined Daily Dose) on NSAID (45.12 ± 49.03 days vs 53.00 ± 71.14 days; p = 0.0333) was significantly lower in Structoflex®-treated patients compared with control group patients. This large 'real world' analysis demonstrated a significant NSAID-sparing effect of glucosamine in patients with knee OA.	f	\N
24138892	I shall discuss the work of researchers at Harvard Medical School who came together in the early 1990s. Scattered across various Harvard-affiliated hospitals and research centers, these individuals were unified by their interest in ocular neovascularization. Together and separately, they investigated models of ocular neovascularization, exploring tumor angiogenesis in eye development and disease.	f	\N
24141443	To validate the Clinical Gait and Balance Scale (GABS) for a Brazilian population of patients with Parkinson's disease (PD) and to compare it to the Berg Balance Scale (BBS). One hundred and seven PD patients were evaluated by shortened UPDRS motor scale (sUPDRSm), Hoehn and Yahr (HY), Schwab and England scale (SE), Falls Efficacy Scale International (FES-I), Freezing of Gait Questionnaire (FOG-Q), BBS and GABS. The internal consistency of the GABS was 0.94, the intra-rater and inter-rater reliability were 0.94 and 0.98 respectively. The area under the receiver operating characteristic (ROC) curve was 0.72, with a sensitivity of 0.75 and specificity of 0.6, to discriminate patients with a history of falls in the last twelve months, for a cut-off score of 13 points. Our study shows that the Brazilian version of the GABS is a reliable and valid instrument to assess gait and balance in PD.	f	\N
24144148	Pompe disease is a rare, progressive and often fatal neuromuscular disorder. It is caused by a deficiency of the lysosomal alpha-glucosidase. Among glycogen storage disorders, it is one of the most common. Its clinical manifestations can start at any moment of life, with a very variable symptomatology. In this article, we show an extended revision of the literature in regards to the main medical aspects of Pompe disease: etiology, psychopathology, epidemiology, clinical variants, pathological diagnosis, and enzyme replacement therapy. With this information, we created a diagnostic and therapeutic guide, which is addressed to specialists and to first-level physicians, in order to let them identify both the classic and the late forms of this disease. We describe as well the best, timely, multidisciplinary treatment in use. Also, we show some suggestions to the proper functioning of health institutions, and routes to diagnosis. We conclude that Pompe disease may be properly diagnosed and treated if health care professionals follow the internationally approved recommendations.	f	\N
24151631	Cystic echinococcosis (CE) is a chronic, clinically complex, and neglected disease. Its prevalence in Italy, a country of medium to high endemicity, remains poorly defined, as notification has long ceased to be mandatory. We set up a retrospective cohort study involving all CE patients followed at our institute between January 2005 and December 2012. Demographical and clinical features were recorded and analyzed. CE was found in 28 patients (64.3%), mostly Italians from the central regions (50%), followed by subjects from the islands (33.3%) and Southern Italy (16.7%). Their median age was 45 years (IQR: 38.5-66.5), with Eastern Europeans being significantly younger (28 years, IQR: 19-39) than other patients (P ≤ 0.0001). A total of 149 cysts, mostly with hepatic localization (96%), were described. Based on the WHO classification, the cysts were mainly small (80.5%) and active (CE1 (73.8%); CE2 (7.4%)). Active cysts were more common in Eastern Europeans (85.7%) than Italians (66.7%). Our data confirm CE occurrence in Italy. We emphasize the importance to have a national CE registry, opportunely recently introduced. This is essential to assess CE prevalence in this country, implement appropriate control measures, and improve patient management.	f	\N
24152546	Pre-diagnosis oophorectomy and estrogen therapy could impact mortality due to breast cancer and cardiovascular disease (CVD) among breast cancer survivors. Elective bilateral oophorectomy at the time of hysterectomy for benign conditions is not uncommon among US women. We examined the association between pre-diagnosis total abdominal hysterectomy with bilateral salpingooophorectomy (TAHBSO) and both overall and cause-specific mortality in the Collaborative Breast Cancer Studies cohort. Medical history and prior estrogen use were collected during standardized telephone interviews. Vital status, including date and cause of death, was obtained by linkage with the National Death Index. Multivariate hazard ratios (HR) and 95% confidence intervals (CI) for cause-specific mortality were calculated using Cox proportional hazards regression. Seventeen percent (N = 1,778) of breast cancer survivors (mean age at diagnosis = 63.5) reported pre-diagnosis TAHBSO. During follow-up (mean = 9.5 years), 2,856 deaths occurred, including 1,060 breast cancer deaths and 459 CVD deaths. Breast cancer deaths occurred a median of 5.1 years after diagnosis; CVD deaths occurred further from diagnosis (median = 9.7 years). Women who reported pre-diagnosis TAHBSO had a 16% decrease in all-cause mortality (HR = 0.84; 95% CI: 0.76, 0.92) compared to those with an intact uterus and ovaries. This overall decrease reflected a 27% lower breast cancer mortality among women who never used postmenopausal hormones (HR = 0.73; CI: 0.55, 0.96) and 43% lower CVD risk among women who reported using estrogen (HR = 0.57; CI: 0.39, 0.83) after TAHBSO. Information on prior TAHBSO and estrogen use can inform risk of death fromboth breast cancer and cardiovascular disease among breast cancer survivors.	f	\N
24152582	The Ca(2+) channel-binding domain 3 (CBD3) peptide, derived from the collapsin response mediator protein 2 (CRMP-2), is a recently discovered voltage-gated Ca(2+) channel (VGCC) blocker with a preference for CaV2.2. Rodent administration of CBD3 conjugated to cell penetrating motif TAT (TAT-CBD3) has been shown to reduce pain behavior in inflammatory and neuropathic pain models. However, TAT-CBD3 analgesia has limitations, including short half-life, lack of cellular specificity and undesired potential off-site effects. We hypothesized that these issues could be addressed by expressing CBD3 encoded by high-expression vectors in primary sensory neurons. We constructed an adeno-associated viral (AAV) vector expressing recombinant fluorescent CBD3 peptide and injected it into lumbar dorsal root ganglia (DRGs) of rats before spared nerve injury (SNI). We show that selective expression of enhanced green fluorescent protein (EGFP)-CBD3 in lumbar 4 (L4) and L5 DRG neurons and their axonal projections results in effective attenuation of nerve injury-induced neuropathic pain in the SNI model. We conclude that AAV-encoded CBD3 delivered to peripheral sensory neurons through DRG injection may be a valuable approach for exploring the role of presynaptic VGCCs and long-term modulation of neurotransmission, and may also be considered for development as a gene therapy strategy to treat chronic neuropathic pain.	f	\N
24157515	While undernutrition and infectious diseases are still persistent in developing countries, overweight, obesity, and associated comorbidities have become more prevalent. Uganda, a developing sub-Saharan African country, is currently experiencing the public health paradox of undernutrition and overnutrition. We utilized the 2011 Uganda Demographic and Health Survey (DHS) to examine risk factors and hot spots for underweight, overweight, and obesity among adult females (N = 2,420) and their children (N = 1,099) using ordinary least squares and multinomial logit regression and the ArcGIS Getis-Ord Gi* statistic. Overweight and obese women were significantly more likely to have overweight children, and overweight was correlated with being in the highest wealth class (OR = 2.94, 95% CI = 1.99-4.35), and residing in an urban (OR = 1.76, 95% CI = 1.34-2.29) but not a conflict prone (OR = 0.48, 95% CI = 0.29-0.78) area. Underweight clustered significantly in the Northern and Northeastern regions, while overweight females and children clustered in the Southeast. We demonstrate that the DHS can be used to assess geographic clustering and burden of disease, thereby allowing for targeted programs and policies. Further, we pinpoint specific regions and population groups in Uganda for targeted preventive measures and treatment to reduce the burden of overweight and chronic diseases in Uganda.	f	\N
24169298	Morbidity and mortality from preventable, noncommunicable chronic disease (NCD) threatens the health of our populations and our economies. The accumulation of vast amounts of scientific knowledge has done little to change this. New and innovative thinking is essential to foster new creative approaches that leverage and integrate evidence through the support of big data, technology, and design thinking. The purpose of this paper is to summarize the results of a consensus meeting on NCD prevention sponsored by the International Olympic Committee (IOC) in April 2013. Within the context of advocacy for multifaceted systems change, the IOC's focus is to create solutions that gain traction within health care systems. The group of participants attending the meeting achieved consensus on a strategy for the prevention and management of chronic disease that includes the following: 1. Focus on behavioral change as the core component of all clinical programs for the prevention and management of chronic disease. 2. Establish actual centers to design, implement, study, and improve preventive programs for chronic disease. 3. Use human-centered design (HCD) in the creation of prevention programs with an inclination to action, rapid prototyping and multiple iterations. 4. Extend the knowledge and skills of Sports and Exercise Medicine (SEM) professionals to build new programs for the prevention and treatment of chronic disease focused on physical activity, diet, and lifestyle. 5. Mobilize resources and leverage networks to scale and distribute programs of prevention. True innovation lies in the ability to align thinking around these core strategies to ensure successful implementation of NCD prevention and management programs within health care. The IOC and SEM community are in an ideal position to lead this disruptive change. The outcome of the consensus meeting was the creation of the IOC Non-Communicable Diseases ad hoc Working Group charged with the responsibility of moving this agenda forward.	f	\N
24171516	The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era. We treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus rituximab. Patients with a response were randomly assigned to receive three additional cycles of induction chemotherapy (control group) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation (transplantation group). The primary efficacy end points were 2-year progression-free survival and overall survival. Of 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression-free survival rates of 69 and 55%, respectively (hazard ratio in the control group vs. the transplantation group, 1.72; 95% confidence interval [CI], 1.18 to 2.51; P=0.005). Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71%, respectively (hazard ratio, 1.26; 95% CI, 0.82 to 1.94; P=0.30). Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P=0.04 for interaction) and overall survival (P=0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82% in the transplantation group and 64% in the control group. Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy. Overall survival after transplantation was not improved, probably because of the effectiveness of salvage transplantation. (Funded by the National Cancer Institute, Department of Health and Human Services, and others; SWOG-9704 ClinicalTrials.gov number, NCT00004031.).	f	\N
24172078	Many symptomatic patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) are denied surgery and have a grim prognosis with medical management. Between 2003 and 2012, among 550 patients with severe isolated AS and preserved LVEF on transthoracic echocardiography, 241 did not undergo aortic valve replacement (mean age, 83.2±7.6 years; 54% female; aortic valve area index, 0.40±0.13cm(2)/m(2); mean LVEF, 64.8±7.6%) and 67% presented with cardiac symptoms. At a mean follow-up of 25.5±25.1 months, 134 patients (56%) had died. Survival at 1, 5 and 9.5 years was 71%, 28% at 12%, respectively. Median survival was 36.3 months (95% confidence interval [CI]: 27.2-42.4 months). In unadjusted analyses, age, heart failure, hypertension, renal insufficiency, left atrial size, pulmonary artery systolic pressure (PASP), relative wall thickness and LV mass/LV end diastolic volume ratio were associated with mortality. On multivariate analysis adjusted for all significant univariate predictors, age ≥78 years, history of hypertension, left atrial diameter ≥40mm and PASP ≥42mmHg gave a joint area under the curve of 0.80 (95% CI: 0.73-0.86) for mortality. In medically treated patients with severe isolated AS and preserved LVEF, older age, history of hypertension, and echo-Doppler variables reflecting LV diastolic dysfunction are independent predictors of death.	f	\N
24203705	Microbial genome sequencing is one of the longest-standing areas of biological database development, but high-throughput, low-cost technologies have increased its throughput to an unprecedented number of new genomes per year. Several thousand microbial genomes are now available, necessitating new approaches to organizing information on gene function, phylogeny and microbial taxonomy to facilitate downstream biological interpretation. MetaRef, available at http://metaref.org, is a novel online resource systematically cataloguing a comprehensive pan-genome of all microbial clades with sequenced isolates. It organizes currently available draft and finished bacterial and archaeal genomes into quality-controlled clades, reports all core and pan gene families at multiple levels in the resulting taxonomy, and it annotates families' conservation, phylogeny and consensus functional information. MetaRef also provides a comprehensive non-redundant reference gene catalogue for metagenomic studies, including the abundance and prevalence of all gene families in the >700 shotgun metagenomic samples of the Human Microbiome Project. This constitutes a systematic mapping of clade-specific microbial functions within the healthy human microbiome across multiple body sites and can be used as reference for identifying potential functional biomarkers in disease-associate microbiomes. MetaRef provides all information both as an online browsable resource and as downloadable sequences and tabular data files that can be used for subsequent offline studies.	f	\N
24206993	Ulnar impaction syndrome generally occurs with positive ulnar variance. The solution to the problem is to unload the ulnocarpal joint. Effective surgical options include diaphyseal ulnar shortening osteotomy, open wafer osteotomy, and arthroscopic wafer osteotomy. Recently, Slade and Gillon described an open procedure of ulnar shortening in the osteochondral region of the ulnar head. The procedure minimizes the risk of hemarthrosis and does not require hardware removal, which are problems with other surgical options. This article introduces a new arthroscopic technique of distal metaphyseal ulnar shortening osteotomy for ulnar impaction syndrome. This technique offers the advantages of minimizing surgical injury to the dorsal capsule of the distal radoulnar joint and so protects its stability.	f	\N
24211848	Crimean-Congo hemorrhagic fever virus (CCHFV) etiology was detected in a family cluster (nine cases, including two deaths) in the village of Karyana, Amreli District, and also a fatal case in the village of Undra, Patan District, in Gujarat State, India. Anti-CCHFV IgG antibodies were detected in domestic animals from Karyana and adjoining villages. Hyalomma ticks from households were found to be positive for CCHF viral RNA. This confirms the emergence of CCHFV in new areas and the wide spread of this disease in Gujarat State.	f	\N
24218343	Regional body-fat distribution is one of the key variables that explains the metabolic heterogeneity of obesity and its related cardiovascular risks. According to the ectopy concept, the inability of subcutaneous adipose tissue to store surplus triglycerides may lead to the development of fat in ectopic sites, such as the heart. Epicardial adipose tissue is a metabolically active endocrine organ that produces numerous factors that can modulate cardiac structure and function. The development of in vivo noninvasive imaging has made it possible to quantify its thickness and volume with increasing accuracy. In this review, we discuss the local interaction and cross-talk between epicardial fat and neighboring structures, such as coronary arteries and myocardium, and its relevance to cardiac diseases, such as coronary-artery disease or atrial fibrillation. Beneficial and harmful effects of epicardial adipose tissue are described and analyzed. What leads to an imbalance between protective and deleterious actions has to be further explored. We believe that epicardial fat, which has been neglected for years, plays a key role in cardiovascular disease pathophysiology and represents a "new world" exploration for therapeutic targets, which will be addressed in future clinical and research studies. Elucidating the mechanisms that drive the deposition or mobilization of cardiac adiposity between other ectopic-fat stores needs to be accomplished within the next few years.	f	\N
24223459	We evaluated whether the methylenetetrahydrofolate reductase (MTHFR) 677C>T marker influences the risk and severity of Alzheimer's disease (AD) and whether AD is associated with homocysteine, vitamin B12, and cholesterol levels in Egypt. Forty-three Alzheimer's cases and 32 non-AD controls were genotyped for the 677C>T polymorphism. Clinical characteristics and levels of homocysteine, vitamin B12, and cholesterol were assessed. No significant differences in the frequencies of the MTHFR alleles or genotypes between AD cases and controls (P = 0.14) were identified. The 677T mutant allele was significantly overrepresented in AD cases compared to controls (OR = 2.22; P = 0.03). The 677T/T frequency was three times higher in AD patients than in controls, which could increase plasma homocysteine levels. Severe cases of AD were the most frequent in patients with the T/T genotype (11.6%). The effect of the MTHFR polymorphism on the risk of AD may be independent of homocysteine, vitamin B12, or even cholesterol levels. The MTHFR 677C>T polymorphism--especially the presence of one copy of the T allele--appears to confer a potential risk for the development of AD. The T/T genotype may contribute to hypercysteinemia as a sensitive marker.	f	\N
24226095	Sterol 12α-hydroxylase (CYP8B1) is required for cholic acid synthesis and plays a critical role in intestinal cholesterol absorption and pathogenesis of cholesterol gallstone, dyslipidemia, and diabetes. In this study we investigated the underlying mechanism of fasting induction and circadian rhythm of CYP8B1 by a cholesterol-activated nuclear receptor and core clock gene retinoic acid-related orphan receptor α (RORα). Fasting stimulated, whereas restricted-feeding reduced expression of CYP8B1 mRNA and protein. However, fasting and feeding had little effect on the diurnal rhythm of RORα mRNA expression, but fasting increased RORα protein levels by cAMP-activated protein kinase A-mediated phosphorylation and stabilization of the protein. Adenovirus-mediated gene transduction of RORα to mice strongly induced CYP8B1 expression, and increased liver cholesterol and 12α-hydroxylated bile acids in the bile acid pool and serum. A reporter assay identified a functional RORα response element in the CYP8B1 promoter. RORα recruited cAMP response element-binding protein-binding protein (CBP) to stimulate histone acetylation on the CYP8B1 gene promoter. In conclusion, RORα is a key regulator of diurnal rhythm and fasting induction of CYP8B1, which regulates bile acid composition and serum and liver cholesterol levels. Antagonizing RORα activity may be a therapeutic strategy for treating inflammatory diseases such as non-alcoholic fatty liver disease and type 2 diabetes.	f	\N
24226419	IL-32 is a pro-inflammatory cytokine expressed by activated natural killer cells, T cells, keratinocytes, and fibroblasts. In this study, we examined the role of IL-32 in cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF) and Sézary syndrome (SS). IL-32 mRNA expression levels in lesional skin of MF patch, plaque, and tumor were increased compared with those of normal skin, which positively correlated with CCL17 and CCL18 mRNA expression levels. Serum IL-32 levels positively correlated with disease activity within each patient. Immunostaining showed that keratinocytes expressed IL-32 in the lesional skin of MF patch and plaque, whereas in MF tumor, atypical T cells in the dermis strongly expressed IL-32. We also showed that IL-32 dose-dependently accelerated the proliferation of MF and SS cell lines in vitro, which was inhibited by blocking mitogen-activated protein kinase and NF-κB-mediated signaling. The addition of anti-IL-32 antibodies in culture decreased the proliferation of SS cells and the viability of MF cells, suggesting that IL-32 serves as an autocrine growth factor. In conclusion, our results suggest that IL-32 has a role in the formation and maintenance of CTCL lesions, providing a possible therapeutic target for patients with this disease.	f	\N
24240787	To assess the efficacy of pirfenidone in patients with advanced-stage idiopathic pulmonary fibrosis (IPF), we conducted a retrospective study of patients who received pirfenidone therapy. In addition, the combined effects of inhaled N-acetylcysteine (NAC) and pirfenidone were evaluated. Eligible patients had a clinical and radiologic diagnosis of advanced-stage IPF (stages of severity III&IV). Patients who exhibited a relative decline in forced vital capacity (FVC) of 10% or more within the preceding six (±2) months were enrolled. The outcome was evaluated from the date of the 6-month follow-up PFT. Relative declines in FVC of more than 10% were defined as progressive disease (ineffective group), while those less than 10% were defined as stable disease (effective group). The clinical features were compared between the two groups. We also compared the efficacy of the combined therapy with inhaled NAC and pirfenidone (n=11) with that of pirfenidone alone (n=7). Eighteen patients 59-82 years of age with IPF who received pirfenidone therapy were reviewed. Pirfenidone stabilized declines in FVC by 10% at six months in eight of the 18 cases (44%). The median changes in FVC at six months were +120 mL in the effective group and -590 mL in the ineffective group. The number of NAC users was significantly higher in the effective group (7/8=87.5%) than in the ineffective group (3/10=30%) (p=0.02). Furthermore, the use of combined NAC therapy was correlated with a favorable outcome. The median change in FVC at six months was 0 mL in the NAC group and -290 mL in the non-NAC group. The median survival period was 557 ± 66 days in the NAC group and 196 ± 57 days in the non-NAC group (p=0.03). Among the advanced-stage IPF patients with a more progressive status, pirfenidone decreased the rate of decline in FVC. In addition, patients treated with pirfenidone combined with NAC therapy exhibited favorable outcomes. Additional studies are needed to confirm the efficacy of this combined therapy for IPF.	f	\N
24246538	The use of "chimney" stents to augment the proximal landing zone for endovascular aneurysm repair has been increasingly reported. Despite mounting enthusiasm for this technique, the durability of this type of repair and capability to preserve perfusion to target branches remains a paramount concern. Here, we report management of a patient presenting with acute bilateral renal chimney stent thrombosis and a type Ia endoleak.	f	\N
24252129	Favre-Racouchot syndrome (FRS) is both disfiguring and difficult to treat. Available medical and surgical therapies are of variable efficacy. Most treatments do not achieve complete resolution and do not show maintenance of therapeutic response. To assess the response to a novel two-step treatment using the CO2 laser in patients with FRS. Seven patients with FRS were treated with the CO2 laser in resurfacing mode with manual expression of comedones under infiltrative local anaesthesia. The procedure was completed in one treatment session lasting 30 min and the wound was left to heal by secondary intention. A topical antibiotic was applied to treated areas, which were covered with a nonadherent dressing. All patients were assessed 3 months postoperatively by the operating laser surgeon and a visual assessment of clinical response to treatment in comparison with pretreatment photographs was made. Patient satisfaction was also recorded. All patients achieved complete resolution of FRS. The follow-up duration for our cohort ranged from 8 months to 3 years. Two patients required further treatment within a 2-3-year period from initial treatment. Disease relapse was noted over 1 year after the primary treatment; both these cases were smokers and repeat treatment with similar laser parameters maintained reproducible results. Our longest disease-free follow-up duration was 3 years postprimary treatment. The laser surgeons and patients reported high levels of therapeutic benefit and satisfaction with the results. This two-step treatment of FRS (CO2 laser resurfacing and manual pressure-induced expression of comedones) is an effective and durable treatment for FRS with an excellent cosmetic outcome. Long-term follow-up beyond 3 years is planned to determine whether later recurrence occurs with this technique.	f	\N
24263779	Over recent decades, the prevalence of high blood pressure (BP) has increased among children. Several risk factors are involved in the genesis of high BP during childhood, and their early identification can prevent the development of that disease. To assess the prevalence of high BP and associated factors in children. Cross-sectional, population-based study, carried out at the household. This study included 276 two- to five-year-old children in the city of Goiânia, state of Goiás, and assessed their BP, sociodemographic characteristics, birth weight, high BP family history, passive smoking, maternal breastfeeding, dietary habits, sedentary lifestyle and nutritional status. Poisson regression was used to assess the association between risk factors and high BP. Their mean age was 3.1 ± 0.79 years, and high BP and overweight were observed in 19.9% and 11.2% of the children, respectively. Direct association of high BP was identified with age [prevalence ratio (PR) = 2.3; 95%CI: 1.2 - 4.8; p = 0.017] and overweight (PR = 2.0; 95%CI: 1.2 - 3.6; p = 0.014). No other variable associated with high BP. The prevalence of high BP in children was high. Overweight and younger children had greater prevalence of high BP.	f	\N
24264509	According to 1981-2009 data, homicide accounts for 16,000-26,000 deaths annually in the United States and ranks within the top four leading causes of death among U.S. residents aged 1-40 years. Homicide can have profound long-term emotional consequences on families and friends of victims and on witnesses to the violence, as well as cause excessive economic costs to residents of affected communities. For years, homicide rates have been substantially higher among certain populations. Previous reports have found that homicides are higher among males, adolescents and young adults, and certain racial/ethnic groups, such as non-Hispanic blacks, non-Hispanic American Indian/Alaska Natives (AI/ANs), and Hispanics. The 2011 CDC Health Disparities and Inequalities Report (CHDIR) described similar findings for the year 2007. For example, the 2011 report showed that the 2007 homicide rate was highest among non-Hispanic blacks (23.1 deaths per 100,000), followed by AI/ANs (7.8 deaths per 100,000), Hispanics (7.6 deaths per 100,000), non-Hispanic whites (2.7 deaths per 100,000), and Asian/Pacific Islanders (A/PIs) (2.4 deaths per 100,000). In addition, non-Hispanic black men aged 20-24 years were at greatest risk for homicide in 2007, with a rate that exceeded 100 deaths per 100,000 population. Other studies have reported that community factors such as poverty and economic inequality and individual factors such as unemployment and involvement in criminal activities can play a substantial role in these persistent disparities in homicide rates. Public health strategies are needed in communities at high risk for homicide to prevent violence and save lives.	f	\N
24269993	To report on unexpected findings in 4 patients with chronic paraplegia who underwent the laparoscopic implantation of neuroprosthesis procedure in the pelvic lumbosacral nerves. Observational case series. Tertiary referral unit specialized in advanced gynecological surgery and neuropelveology. Three patients with incomplete American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade B (n=2) and AIS grade C (n=1) spinal cord injury (SCI) and 1 patient with flaccid complete chronic SCI (AIS grade A) (n=1). Functional electrical stimulation (FES)-assisted locomotor training and continuous low-frequency pelvic-lumbosacral neuromodulation. Change in ASIA Lower Extremity Motor Scores, ASIA sensory scores for light touch and pinprick sensation, and Walking Index for Spinal Cord Injury scores. All 4 patients developed progressive recovery of some sensory and voluntary motor functions below the lesions. Three are currently capable of voluntary weight-bearing standing and walking a few meters with a walker without FES. The first patient with the longest follow-up is even capable of electrically assisted standing/walking with 2 crutches without braces or assistance for a distance of about 900 meters, and of weight-bearing standing and walking for 30 meters with a walker without stimulation. We report unexpected sensory and locomotor recovery in 4 people with paraplegia with SCI. Our findings suggest that FES-assisted locomotor training with continuous low-frequency pelvic nerve stimulation in patients with SCI may induce changes that affect the central pattern generator and allow supra- and infraspinal inputs to engage residual spinal pathways.	f	\N
24274981	DMD gene which is composed of 79 exons is the largest known gene located on X chromosome (Xp21). Point mutations in the dystrophin gene are responsible for 30-35% of cases with DMD/BMD. Mutation analysis of all the exons of the DMD gene is costly in developing countries, therefore, a few of the exons are selected to be analyzed routinely in clinical laboratories. In this study, direct sequencing was used for detection of point mutations in 10 exons of dystrophin gene in patients affected with DMD without detectable large rearrangements. Freely available programs were used to predict the damaging effects of the mutations. Point mutations were successfully detected in three patients. Three novel mutations, two missense mutations located on nonconservative domains and a single nucleotide deletion, were detected. Missense mutations were predicted to change splicing efficiency. Detection of point mutations by DNA analysis followed by prediction of the pathogenecity by using bioinformatic tool might be an asset to provide proper diagnosis or genetic counseling to patients and their family.	f	\N
24276026	Early detection and improved (neo)-adjuvant treatment has extended survival of breast cancer over the last decades. It remains controversial whether a survival benefit is achieved once metastases have occurred. This study investigates survival trends in metastatic breast cancer (MBC) looking at the distribution of prognostic factors and the time period of the diagnosis of the primary and metastatic disease. In this retrospective study, 1635 patients, diagnosed with MBC and treated at three German cancer centers, were included. For the survival analysis, patients were grouped into three time periods [1980-1994 (a), 1995-1999 (b) and 2000-2009 (c)], which were chosen according to the availability of new antineoplastic drugs for the treatment of MBC. Additionally, patients were divided into three risk groups using the simultaneously published prognostic score. The analysis of overall survival according to the date of primary diagnosis demonstrated a significant decline compared with the reference (a): (a versus b) hazard ratio (HR) = 1.37; P < 0.001; (a versus c) HR = 2.45; P < 0.001. Considering the time of first occurrence of metastasis, survival remains unchanged over the three periods (a versus b): HR = 0.94 P = 0.436; (a versus c): HR = 0.95; P = 0.435. However, a significant shift towards more unfavorable risk factors was seen. Although survival in MBC remains unchanged over time, patients developing metastatic disease have a more aggressive disease that is presumably compensated by more effective treatment. This alteration of tumor biology in MBC may be explained by a negative selection of patients with adverse risk profiles due to the advantages of the adjuvant therapy.	f	\N
24280762	Helicobacter pylori infections can induce pathologies ranging from chronic gastritis, peptic ulceration to gastric cancer. Bacterial isolates harbor numerous well-known adhesins, vacuolating cytotoxin VacA, protease HtrA, urease, peptidoglycan, and type IV secretion systems (T4SS). It appears that H. pylori targets more than 40 known host protein receptors on epithelial or immune cells. A series of T4SS components such as CagL, CagI, CagY, and CagA can bind to the integrin α 5β 1 receptor. Other targeted membrane-based receptors include the integrins αvβ 3, αvβ 5, and β 2 (CD18), RPTP-α/β, GP130, E-cadherin, fibronectin, laminin, CD46, CD74, ICAM1/LFA1, T-cell receptor, Toll-like receptors, and receptor tyrosine kinases EGFR, ErbB2, ErbB3, and c-Met. In addition, H. pylori is able to activate the intracellular receptors NOD1, NOD2, and NLRP3 with important roles in innate immunity. Here we review the interplay of various bacterial factors with host protein receptors. The contribution of these interactions to signal transduction and pathogenesis is discussed.	f	\N
24281461	Pediatric-onset Crohn disease is more aggressive than adult-onset disease, has high rates of resistance to existing drugs, and can lead to permanent impairments. Few trials have evaluated new drugs for refractory Crohn disease in children. To determine whether thalidomide is effective in inducing remission in refractory pediatric Crohn disease. Multicenter, double-blind, placebo-controlled, randomized clinical trial of 56 children with active Crohn disease despite immunosuppressive treatment, conducted August 2008-September 2012 in 6 pediatric tertiary care centers in Italy. Thalidomide, 1.5 to 2.5 mg/kg per day, or placebo once daily for 8 weeks. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks. Primary outcomes were clinical remission at week 8, measured by Pediatric Crohn Disease Activity Index (PCDAI) score and reduction in PCDAI by ≥25% or ≥75% at weeks 4 and 8. Primary outcomes during the open-label follow-up were clinical remission and 75% response. Twenty-eight children were randomized to thalidomide and 26 to placebo. Clinical remission was achieved by significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26 [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2-12.5]; P = .01; number needed to treat [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs 3/26 [11.5%]; RR, 4.0 [95% CI, 1.2-12.5]; NNT = 2.86; P = .01; and 25% response, 18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI, 1.1-3.9]; NNT = 2.99; P = .01). Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%) subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4-14.1]; NNT = 2.45; P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved clinical remission, and 32 of 49 (65.3%) achieved 75% response. Mean duration of clinical remission in the thalidomide group was 181.1 weeks (95% CI, 144.53-217.76) vs 6.3 weeks (95% CI, 3.51-9.15) in the placebo group (P < .001). Cumulative incidence of severe adverse events was 2.1 per 1000 patient-weeks, with peripheral neuropathy the most frequent severe adverse event. In children and adolescents with refractory Crohn disease, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and longer-term maintenance of remission in an open-label follow-up. These findings require replication to definitively determine clinical utility of this treatment. clinicaltrials.gov Identifier: NCT00720538.	f	\N
24284613	The aim of this review was to identify, evaluate and summarize all relevant studies reporting on the clinical response to gluten challenge by adult or pediatric patients with suspected or diagnosed coeliac disease (CD) on a gluten-free diet. We evaluated the effect of gluten challenge on changes in symptoms, intestinal mucosa histology, and serum antibodies. A systematic electronic search was performed for studies published as of 1966 using PubMed and Scopus databases. In the reviewed studies, doses ranged from 0.2 to 30 g/day of wheat gluten or comprised a gluten-containing diet. The onset of symptoms upon gluten intake varied largely from days to months and did not parallel serum antibody or histological changes. Within 3 months of gluten challenge, 70%-100% of pediatric CD patients became positive for AGA-IgA and EMA-IgA antibodies and 50%-70% for AGA-IgG. A limited number of trials suggest that no more than half of adult patients developed positive AGA-IgA, EMA-IgA, tTG-IgA or DGP-IgA/IgG titers. Approximately 50%-100% of pediatric and adult patients experienced mucosal relapse of gluten provocation within 3 months, which was preceded by increased mucosal intra-epithelial lymphocytes within several days of challenge. A 3-month high-dose gluten challenge should be suitable to diagnose the majority of CD patients. In some cases prolonged challenge may be needed to verify diagnosis. Combination testing for antibodies and mucosal histology may fasten the diagnosis.	f	\N
24286024	Brain changes reminiscent of Alzheimer disease (AD) have been previously reported in a substantial portion of elderly cognitive healthy (HC) subjects. The major aim was to evaluate the accuracy of MRI assessed regional gray matter (GM) volume, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and neuropsychological test scores to identify those HC subjects who subsequently convert to mild cognitive impairment (MCI) or AD dementia. We obtained in 54 healthy control (HC) subjects a priori defined region of interest (ROI) values of medial temporal and parietal FDG-PET and medial temporal GM volume. In logistic regression analyses, these ROI values were tested together with neuropsychological test scores (free recall, trail making test B (TMT-B)) as predictors of HC conversion during a clinical follow-up between 3 and 4 years. In voxel-based analyses, FDG-PET and MRI GM maps were compared between HC converters and HC non-converters. Out of the 54 HC subjects, 11 subjects converted to MCI or AD dementia. Lower FDG-PET ROI values were associated with higher likelihood of conversion (p = 0.004), with the area under the curve (AUC) yielding 82.0% (95% CI = (95.5%, 68.5%)). The GM volume ROI was not a significant predictor (p = 0.07). TMT-B but not the free recall tests were a significant predictor (AUC = 71% (95% CI = 50.4%, 91.7%)). For the combination of FDG-PET and TMT-B, the AUC was 93.4% (sensitivity = 82%, specificity = 93%). Voxel-based group comparison showed reduced FDG-PET metabolism within the temporo-parietal and prefrontal cortex in HC converters. In conclusion, medial temporal and-parietal FDG-PET and executive function show a clinically acceptable accuracy for predicting clinical progression in elderly HC subjects.	f	\N
24286594	Optimal management of colon cancer (CC) requires detailed assessment of extent of disease. This study prospectively investigates the diagnostic accuracy of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) for staging and detection of recurrence in primary CC. PET/CT for preoperative staging was performed in 66 prospectively included patients with primary CC. Diagnostic accuracy for PET/CT and CT was analyzed. In addition to routine follow up, 42 stages I-III CC patients had postoperative PET/CT examinations every 6 months for 2 years. Serological levels of tissue inhibitor of metalloproteinase-1 (TIMP-1), carcinoembryonic antigen, and liberated domain I of urokinase plasminogen activator receptor were analyzed. Accuracy for tumor, nodal, and metastases staging by PET/CT were 82% (95% confidence interval [CI]: 70; 91), 66% (CI: 51; 78), and 89% (CI: 79; 96); for CT the accuracy was 77% (CI: 64; 87), 60% (CI: 46; 73), and 69% (CI: 57; 80). Cumulative relapse incidences for stages I-III CC at 6, 12, 18, and 24 months were 7.1% (CI: 0; 15); 14.3% (CI: 4; 25); 19% (CI: 7; 31), and 21.4% (CI: 9; 34). PET/CT diagnosed all relapses detected during the first 2 years. High preoperative TIMP-1 levels were associated with significant hazards toward risk of recurrence and shorter overall survival. This study indicates PET/CT as a valuable tool for staging and follow up in CC. TIMP-1 provided prognostic information potentially useful in selection of patients for intensive follow up.	f	\N
24292183	Pulmonary arterial hypertension (PAH) is a rare, progressive, and fetal disease. The five-year survival rate after diagnosis is ～50%. In Japan, PAH is listed in the Specified Rare and Intractable Diseases. Pulmonary vascular remodeling and sustained pulmonary vasoconstriction are the major causes for the elevated pulmonary vascular resistance (PVR) in PAH. The pathogenic mechanisms involved in the pulmonary vascular abnormalities in PAH remain unclear. Sustained vasoconstriction and vascular remodeling owing to proliferation of pulmonary arterial smooth muscle cells (PASMCs) are key pathogenic events that lead to early morbidity and mortality. These events have been closely linked to Ca(2+) mobilization and signaling in PASMCs. An increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) in PASMCs is an important stimulus for pulmonary vasoconstriction and cell proliferation which subsequently cause pulmonary vascular wall thickening followed by the increase in PVR. Increased resting [Ca(2+)]cyt and enhanced Ca(2+) influx have been implicated in PASMCs from PAH patients, but precise therapeutic targets to interrupt these signal pathways have not been identified. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), a G protein-coupled receptor (GPCR), is upregulated in PASMCs from patients with idiopathic pulmonary arterial hypertension (IPAH). In addition, blockage of the CaSR with an antagonist (NPS2143) prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The functionally upregulated CaSR in PASMCs is a novel pathogenic mechanism contributing to the augmented Ca(2+) signaling and excessive cell proliferation in IPAH. Targeting CaSR in PASMCs may help develop novel therapeutic approach for PAH.	f	\N
24298283	In January 2012, Boström and colleagues identified a new muscle tissue secreted peptide, which they named irisin, to highlight its role as a messenger that comes from skeletal muscle to other parts of the body. Irisin is a cleaved and secreted fragment of FNDC5 (also known as FRCP2 and PeP), a member of fibronectin type III repeat containing gene family. Major interest in this protein arose because of its great therapeutic potential in diabetes and perhaps also therapy for obesity. Here we review the most important aspects of irisin's action and discuss its involvement in energy and metabolic homeostasis and whether the beneficial effects of exercise in these disease states could be mediated by this protein. In addition the effects of irisin at the central nervous system (CNS) are highlighted. It is concluded that although current and upcoming research on irisin is very promising it is still necessary to deepen in several aspects in order to clarify its full potential as a meaningful drug target in human disease states.	f	\N
24299152	Patients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE. Fibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38) previous VD and from matched healthy controls (n = 68) were analyzed for the presence of complexes formed between contact system enzymes and antithrombin (AT) or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory parameters. Fibrin clots elicited FXII activation and acted as co-factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa-C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa-AT was elevated in the SLE patients with a history of VD, while the corresponding levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated strongly with platelet parameters. The odds ratio for VD among the SLE patients was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa-C1INH and increased levels of FXIIa-AT. Activation of FXII is elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered levels of FXIIa-serpin complexes, supporting that the contact system is involved in this disease. FXIIa-serpin complexes are strongly associated with previous VD in SLE patients, suggesting that these complexes are potential biomarkers for monitoring and assessing the risk of thrombotic events in SLE.	f	\N
24305931	Intense postoperative monitoring has resulted in increasing detection of patients with recurrent papillary thyroid cancer (PTC). Our goals included quantifying successful reoperation, and analyzing surgical complications and reasons for relapse. From 1999 to 2008, a total of 410 patients underwent reoperation for PTC relapse. We analyzed post-reoperative disease outcomes, reasons for relapse, and complications. Bilateral reoperative thyroidectomy was performed in 13 (3 %) patients; lobectomy, 34 (8 %); central neck (VI) soft tissue local recurrence excision, 47 (11.5 %); bilateral VI node dissection, 107 (26 %); unilateral VI dissection, 112 (27 %); levels II-V dissection, 93 (23 %); levels III-V, 86 (21 %); lateral single- or two-compartment dissection, 51 (12 %); and node picking, 20 (5 %) of level VI and 53 (13 %) lateral neck. Complications occurred in 6 %; including hypoparathyroidism, 3 %; unintentional recurrent laryngeal nerve (RLN) paralysis, 3 %; phrenic nerve injury, 0.5 %; spinal accessory nerve injury, 0.5 %; and chyle leak in 1.6 %. Of 380 (93 %) patients with follow-up (mean 5.2 years); 274 (72 %) patients are alive with no structural evidence of disease, 38 % developed disease relapse (mean 2.1 years), 42 (11 %) died from PTC, and 55 (14 %) are alive with disease. The reason for relapse was a false negative pre-reoperative ultrasound (US) in 18 (5 %), nodal recurrence in the operative field in 37 (10 %), a combination of these two reasons in 10 (3 %), and disease virulence (local or systemic recurrence) in 81 (21 %). Although 72 % of patients were rendered structurally disease free after reoperation, nearly 40 % suffered additional relapse. Improved surgical technique or preoperative localization might positively affect 15-20 %; at least 20 % reflect the biologic aggressiveness of the disease.	f	\N
24319959	To study the clinical characteristics of pediatric Kawasaki disease complicating mycoplasma pneumoniae pneumonia. Retrospective analysis was conducted on 11 children who had been diagnosed with Kawasaki disease with Mycoplasma pneumoniae pneumonia. The 11 cases presented with varying degrees of fever, conjunctival congestion, skin rashes, lymphadenectasis, distal extremities lesions, heart and lung lesions. 8 of them were standartly treated with azithromycin, while 3 of them were treatad with azithromycin and erythromycin. 2 patients with pleural effusion complicated by lobar pneumonia consolidation were treated with gamma globulin combined aspirin. All of the 11 patients were healed. Infections are common at the diagonosis of KD. Reasonable examination and antibiotics is useful to cure KD with MPP.	f	\N
24321203	Data from surveillance networks help epidemiologists and public health officials detect emerging diseases, conduct outbreak investigations, manage epidemics, and better understand the mechanics of a particular disease. Surveillance networks are used to determine outbreak intensity (i.e., disease burden) and outbreak timing (i.e., the start, peak, and end of the epidemic), as well as outbreak location. Networks can be tuned to preferentially perform these tasks. Given that resources are limited, careful site selection can save costs while minimizing performance loss. We study three different site placement algorithms: two algorithms based on the maximal coverage model and one based on the K-median model. The maximal coverage model chooses sites that maximize the total number of people within a specified distance of a site. The K-median model minimizes the sum of the distances from each individual to the individual's nearest site. Using a ground truth dataset consisting of two million de-identified Medicaid billing records representing eight complete influenza seasons and an evaluation function based on the Huff spatial interaction model, we empirically compare networks against the existing Iowa Department of Public Health influenza-like illness network by simulating the spread of influenza across the state of Iowa. We show that it is possible to design a network that achieves outbreak intensity performance identical to the status quo network using two fewer sites. We also show that if outbreak timing detection is of primary interest, it is actually possible to create a network that matches the existing network's performance using 59% fewer sites. By simulating the spread of influenza across the state of Iowa, we show that our methods are capable of designing networks that perform better than the status quo in terms of both outbreak intensity and timing. Additionally, our results suggest that network size may only play a minimal role in outbreak timing detection. Finally, we show that it may be possible to reduce the size of a surveillance system without affecting the quality of surveillance information produced.	f	\N
24326825	Lymph node metastasis (LNm), local recurrence (LR), and second primary tumor (SPT) after primary surgery for oral squamous cell carcinoma (OSCC) have been considered poor prognostic entities in terms of survival rate. The purpose of this study was to identify the clinicopathologic parameters significantly related to LNm, LR, and SPT. Records from 180 patients who underwent radical surgery for OSCC were retrospectively reviewed. Perineural invasion was significantly related to LNm (18% vs 8%) and LR (15% vs 5%), while the status of the surgical margin (10% in case of clear margins, 18% close margins, and 24% involved margins), namely epithelial precursor lesions (43%) was an independent factor influencing SPT. Perineural invasion proved a good prognostic factor for early events, either LNm or LR, while a surgical margin width less than 5 mm or with epithelial precursor lesions may be considered a risk factor for late events such as SPT.	f	\N
24342581	To evaluate the efficacy of plasma-rich growth factor (PRGF) in improving socket healing after tooth extraction in diabetic patients. This was a split-mouth study in which each patient also served as the control: the study socket was treated with PRGF, whereas the control socket underwent natural healing. The outcome variables were the Healing Index, residual socket volume, visual analog scale score, postsurgical complications, and outcome of a patient questionnaire. The investigation considered the impact of hyperglycemia, glycated hemoglobin, End Organ Disease Score, and smoking habits. Follow-up included 4 postextraction checkups over a 21-day period. Pairs of correlated continuous variables were analyzed with the Wilcoxon test, independent continuous variables with the Mann-Whitney test, and categorical variables with the χ(2) test or Fisher test. From January 2012 to December 2012, 34 patients affected by insulin-dependent diabetes mellitus underwent contemporary bilateral extractions of homologous teeth. The treatment-versus-control postoperative comparison showed that PRGF resulted in significantly smaller residual socket volumes and better Healing Indices from days 3 to 14. The patients' questionnaire outcomes were unanimously in favor of PRGF treatment. The small sample of patients with glycemia values of at least 240 mg/dL showed worse Healing Index and minor socket decreases. PRGF application after extraction improved the healing process in diabetic patients by accelerating socket closure (epithelialization) and tissue maturation, proving the association between PRGF use and improved wound healing in diabetic patients.	f	\N
24349495	Panton-Valentine leukocidin (PVL; gene designation lukF/S-PV) is likely an important virulence factor for Staphylococcus aureus (S. aureus), as qualitative expression of the protein correlates with severity for specific clinical presentations, including skin and soft tissue infections (SSTIs). Development of genetic approaches for risk-assessment of patients with S. aureus infections may prove clinically useful, and whether lukF/S-PV gene expression correlates with specific clinical presentations for S. aureus has been largely unexplored. In the present study, we quantified lukS-PV mRNA among 96 S. aureus isolates to determine whether expression levels correlated with specific clinical presentations in adults and children. Expression level of lukS-PV mRNA among isolates from skin and soft tissue infections (SSTIs) was significantly greater than among isolates from blood stream infection (BSIs), and expression level of lukS-PV mRNA among BSI isolates from children was significantly greater than for BSI isolates among adults. Moreover, expression level of lukS-PV mRNA among community-acquired (CA) isolates was significantly greater than for hospital-acquired (HA) isolates. These data justify additional studies to determine the potential clinical utility for lukS-PV mRNA quantification as a predictive tool for severity of S. aureus infection.	f	\N
24352112	This report contains CDC guidance that augments the 2011 recommendations of the Advisory Committee on Immunization Practices (ACIP) for evaluating hepatitis B protection among health-care personnel (HCP) and administering post-exposure prophylaxis. Explicit guidance is provided for persons working, training, or volunteering in health-care settings who have documented hepatitis B (HepB) vaccination years before hire or matriculation (e.g., when HepB vaccination was received as part of routine infant [recommended since 1991] or catch-up adolescent [recommended since 1995] vaccination). In the United States, 2,890 cases of acute hepatitis B were reported to CDC in 2011, and an estimated 18,800 new cases of hepatitis B occurred after accounting for underreporting of cases and asymptomatic infection. Although the rate of acute hepatitis B virus (HBV) infections have declined approximately 89% during 1990-2011, from 8.5 to 0.9 cases per 100,000 population in the United States, the risk for occupationally acquired HBV among HCP persists, largely from exposures to patients with chronic HBV infection. ACIP recommends HepB vaccination for unvaccinated or incompletely vaccinated HCP with reasonably anticipated risk for blood or body fluid exposure. ACIP also recommends that vaccinated HCP receive postvaccination serologic testing (antibody to hepatitis B surface antigen [anti-HBs]) 1-2 months after the final dose of vaccine is administered (CDC. Immunization of health-care personnel: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2011;60 [No. RR-7]). Increasing numbers of HCP have received routine HepB vaccination either as infants (recommended since 1991) or as catch-up vaccination (recommended since 1995) in adolescence. HepB vaccination results in protective anti-HBs responses among approximately 95% of healthy-term infants. Certain institutions test vaccinated HCP by measuring anti-HBs upon hire or matriculation, even when anti-HBs testing occurs greater than 2 months after vaccination. This guidance can assist clinicians, occupational health and student health providers, infection-control specialists, hospital and health-care training program administrators, and others in selection of an approach for assessing HBV protection for vaccinated HCP. This report emphasizes the importance of administering HepB vaccination for all HCP, provides explicit guidance for evaluating hepatitis B protection among previously vaccinated HCP (particularly those who were vaccinated in infancy or adolescence), and clarifies recommendations for postexposure management of HCP exposed to blood or body fluids.	f	\N
24355565	The pancreas consists of two major divisions, the exocrine and the endocrine pancreas. Recent data from our laboratory have shown that the functions of the two divisions are under modulatory regulation by separate neurocircuits that originate in the dorsal motor nucleus of the vagus (DMV). Metabotropic glutamate receptors (mGluRs) are expressed throughout the central nervous system and have been implicated in the modulation of synaptic transmission. mGluRs consist of three groups of receptors, which can be distinguished based on their pharmacological properties and second messenger systems. Group I mGluRs predominantly increase, whereas group II and III mGluRs decrease synaptic transmission. Group II and group III mGluRs are present on excitatory and inhibitory synaptic terminals impinging on pancreas-projecting DMV neurons. We have shown that group II mGluRs regulate both exocrine pancreatic secretions and insulin release, whereas group III mGluRs only regulate insulin release. Several mGluR agonists and antagonists have been shown to have clinical uses for disorders accompanied by abnormal synaptic transmission, including anxiety and Parkinson's disease. Moreover, a negative allosteric modulator of Group I mGluRs is effective in alleviating symptoms of gastro-esophageal reflux disease (GERD). Since the role of the three mGluR groups in mediating different gastrointestinal (GI) functions appears to be highly specific, the use of agonists or antagonists directed at a single receptor group could potentially provide highly selective targets for the treatment of GI disorders including GERD, functional dyspepsia and acute pancreatitis.	f	\N
24361034	The integration of body, mind, and spirit has become a key dimension of health education and disease prevention and treatment; however, our health care system remains primarily disease centered. Finding simple steps to help each of us find our own balance can improve our lives, our work, and our relationships. On the basis of interviews with health care experts at the leading edge of the new model of medicine, this article identifies simple tools to improve the health of patients and caregivers.	f	\N
24362818	Follicular lymphoma is an incurable malignancy, with transformation to an aggressive subtype representing a critical event during disease progression. Here we performed whole-genome or whole-exome sequencing on 10 follicular lymphoma-transformed follicular lymphoma pairs followed by deep sequencing of 28 genes in an extension cohort, and we report the key events and evolutionary processes governing tumor initiation and transformation. Tumor evolution occurred through either a 'rich' or 'sparse' ancestral common progenitor clone (CPC). We identified recurrent mutations in linker histone, JAK-STAT signaling, NF-κB signaling and B cell developmental genes. Longitudinal analyses identified early driver mutations in chromatin regulator genes (CREBBP, EZH2 and KMT2D (MLL2)), whereas mutations in EBF1 and regulators of NF-κB signaling (MYD88 and TNFAIP3) were gained at transformation. Collectively, this study provides new insights into the genetic basis of follicular lymphoma and the clonal dynamics of transformation and suggests that personalizing therapies to target key genetic alterations in the CPC represents an attractive therapeutic strategy.	f	\N
24368549	Hugh Henry Bentall, the inventor of the surgical procedure that enabled concomitant replacement of the aortic valve and ascending aorta, died on September 2012 at the age of 92. He was the first Professor of Cardiothoracic Surgery in the United Kingdom, at the Hammersmith Hospital, and carried out the first open-heart operations with a heart-lung machine in London in 1953. Besides cardiac surgery, he paid particular attention to cardiac anatomy and embryology, which he enriched even following retirement. He leaves three sons and a daughter.	f	\N
24369205	Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en-bloc removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation, and re-implantation back in the body. We report our preliminary experience of using ECI for management of MBT. From year 2009 to 2010, 14 patients with primary MBT were enrolled into this study. The eligibility criteria included histopathological proof of malignancy, no evidence of distant metastases, and suitability for limb preservation therapy. Surgery was performed about 4 weeks after completion of neoadjuvant chemotherapy. The affected bone segment was resected, irradiated extracorporeally with a dose of 50 Gy and reimplanted. Local control, complications and short-term survival were studied. Functional outcome was assessed by Musculoskeletal Tumor Society (MSTS) scoring system. There were 10 males and four females with median age of 14 years. Histopthologically, nine patients had osteosarcoma (OS) and five had Ewing's sarcoma family of tumors (ESFT). Distribution of primary site was as follows: Femur eight patients, tibia five patients and humerus one patient. At a median follow-up was 22 months, three patients (two OS, one ESFT) had local recurrence. Two patients (14%) developed wound infection in the perioperative period. The 2 year local recurrence free survival was 73% and mean MSTS score was 88. Results of our study suggest that ECI is technically feasible in the management of MBT and provides decent local control and short-term survival rates.	f	\N
24377187	Optimal nutrition, immunological state and psychological condition play an important role in the process of chronic wound healing. Infections caused by pathogens resistant to commonly used antibiotics additionally complicate and disturb regeneration of wounds. As part of the treatment, modern wound dressings are used, for example designed on the basis of alginates, dextranomers, hydrogels, hydrofiber, polyurethanes foams, hydrocolloids and liquids for wound debridement such us 0.9% NaCl, the PWE liquid, Ringer's liquid, octenidine. Owing to their features, treatment in accordance with TIME concept could be realized, because they provide moisture wound bed, protection against contamination, gas exchange, protection of wound edges and infection control. Repairing process in chronic wounds is dependent on blood flow in tissues, which may be insufficient. The result is a permanent hypoxia. Natural occurring antioxidants are becoming more crucial in chronic wound treatment. They decrease oxygen radical concentration, increase angiogenesis, reduce inflammatory response, stimulate fibroblasts and keratinocytes proliferation, possess antibacterial properties against chemotherapeutic resistant strains. There are a lot of antioxidants in honey, papaya fruit (Carrica papaia L.), transgenic flax (Linum usitatissimum), and in orange oil (Citrus sinensis), stem of acanthus (Acanthus ebracteatus), leafs of tea (Camellia sinensis). Application of biologically active, natural derived compounds is nowadays a direction of intense in vitro and in vivo research focused on the chronic wound treatment. Results suggest beneficial influence of antioxidant on wound repairing process. Clinical research are needed to state effective influence of natural compound in the chronic wound treatment.	f	\N
24382893	Pathological inflammation and autoimmune disease frequently involve elevated neutrophil activity in the absence of infectious agents. Tumor necrosis factor-α (TNF-α) contributes to many of the problems associated with autoimmune diseases. We investigated the ability of serum α-1 antitrypsin (AAT) to control TNF-α biosynthesis and signaling in neutrophils and assessed whether AAT deficiency (AATD) is a TNF-α-related disease. In vitro studies demonstrate that serum AAT coordinates TNF-α intracellular signaling and neutrophil degranulation of tertiary and secondary granules via modulation of ligand-receptor interactions. AATD patients homozygous for the Z allele were characterized by increased activation of the TNF-α system, as demonstrated by increased membrane TNF-α levels and increased plasma concentrations of TNF receptor 1 and neutrophil-released secondary and tertiary granule proteins. The incidence of autoantibodies directed against degranulated lactoferrin and surface protein accessible to these antibodies was increased in ZZ-AATD, leading to an enhanced rate of neutrophil reactive oxygen species production. Treatment of ZZ-AATD individuals with AAT augmentation therapy resulted in decreased membrane TNF-α expression and plasma levels of granule antigenic proteins and immunoglobulin G class autoantibodies. These results provide a mechanism by which AAT augmentation therapy affects TNF-α signaling in the circulating neutrophil, indicating promising potential of this therapy for other TNF-α-related diseases.	f	\N
24390521	Patients with atrial fibrillation (AF) have an increased risk of congestive heart failure (CHF) as well as ischemic stroke. The aim of this study was to investigate the clinical predictors of CHF in patients with non-valvular AF (NVAF). Three hundred and forty-seven patients (derivation cohort) with NVAF were retrospectively evaluated between 2004 and 2005. The associations between potential risk factors and CHF were tested using a Cox proportional hazards analysis, and a risk score for predicting CHF was created. The model was then validated in 161 patients (validation cohort) enrolled between 2008 and 2010. During the follow-up period, 41 patients in the derivation cohort developed CHF requiring hospitalization due to New York Heart Association (NYHA) class III or IV disease. Four independent risk factors were identified, each of which was assigned a number of points as follows: Age ≥72 years (1 point), heart rate ≥80 bpm (1 point), hypertension (1 point), and a previous history of congestive heart failure (2 points). The patients were grouped into one of three risk categories according to the calculated risk score (ARC2H score): low risk (0 points), intermediate risk (1-3 points) and high risk (4-5 points). In the derivation cohort, the annual rates of CHF in these risk categories were 0%, 2.5% and 18% per year respectively. In the validation cohort, the corresponding rates were 0.8%, 8% and 35% per year respectively. A simple clinical risk score, the ARC2H score, was developed to predict CHF in patients with NVAF and validated in an independent cohort.	f	\N
24395633	Although Hodgkin's lymphoma (HL) was one of the first human cancers to be cured by chemotherapy, no new agents other than brentuximab vedotin (Adcetris®, CD 30 directed antibody drug conjugate) have received US Food and Drug Administration (FDA) approval for HL since 1977. Subsets of young adult patients with HL continue to relapse, even after stem cell transplantation, warranting new approaches. Against this background, we report a dramatic response in a young patient with advanced HL refractory to the standard treatment who responded to the combination of a pan-histone deacetylase inhibitor (vorinostat, suberoylanilide hydroxamic acid, SAHA) and mammalian target of rapamycin (mTOR) inhibitor therapy (sirolimus,rapamume). In-depth immunohistochemical and morphoproteomic analyses of this exceptional responder to targeted therapy have yielded potential insights into the biology of advanced HL. The PI3K/AKT/mTOR pathway is a commonly activated pathway in multiple tumor types including HL. The patient was treated using therapy based on mechanistic in vitro data demonstrating that combined histone deacetylase (HDAC) and mTOR inhibition act together on this pathway, resulting in inhibition of reciprocal feedback networks, leading to better anti-proliferative activity. The in vivo response signature from this patient's tissue sample sheds light on immune dysregulation in HL. We describe the response signature achieved from targeting immune dysregulation in addition to targeting the key oncogenic PI3K/AKT/mTOR pathway. We also expand on the role of rapamycin analogs in oncology. This study supports a role for an immune-type pathogenesis that is amenable to immune modulating targeted therapy in refractory HL. We report an exceptional responder to molecularly targeted and immune modulator therapy in advanced Hodgkin's lymphoma. The morphoproteomic/morphometric findings in this "unusual responder" patient's relapsed HL that correlate best, as a response signature with the subsequent clinical remission following rapamycin (sirolimus) and vorinostat (SAHA) therapies, center on an immune dysregulation involving an imbalance between effector and functional T regulatory cells in addition to targeting the mTOR pathway. This underscores the need for an approach illustrated in our study--namely of focusing on pathogenetic mechanisms and combinatorial therapies that target both the pathogenesis and adaptive responses to contemplated therapies.	f	\N
24395648	Information on the chimpanzee nasopharygeal colonization in captive sanctuaries and in the wild is rare. This study was undertaken to establish the nasopharygeal colonization and potential bacterial pathogens in sanctuary chimpanzees as a basis for improving chimpanzee and employee health. Nasopharygeal colonization of 39 healthy chimpanzees were analyzed by microbiological cultivation method and polymerase chain reaction (PCR) targeting the bacterial 16S rRNA gene. We report four major phyla dominated by Proteobacteria (50%), Fermicutes (35.7%), Bacteriodes (7.1%), and Cynobacteria (7.1%) in healthy semi-captive chimpanzees. Further classification based on 7-base oligomers revealed the following genera: Streptococcus, Veillonella, Neisseria, Prevotella, Kingella and unclassified Cynobacteria, Actinobacillus, Bacteriodes and Pasteurellaceae. On microbiological cultivation we were able to identify and characterize some of the bacteria to species level as Klebsiella pneumonie and Pseudomonas aeruginosa being dominant bacteria with 54.7% and 50% colonization, respectively. Of these, Streptococcus, Neisseria, Klebsiella, and Haemophillus have representatives known to potentially cause severe respiratory disease. Our data present important information on chimpanzee nasopharygeal colonization as a guide to understanding disease processes and pharmaceutical therapies required for improving the health of chimpanzees. The results from this study will guide the processes to improve procedures for routine management of sanctuary chimpanzees and use it as a basis for evaluation of future reintroduction possibilities.	f	\N
24418861	Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma and is mostly represented by the embryonal (ERMS) and alveolar (ARMS) histotypes. Whereas ERMS shows variable genetic alterations including TP53, RB1, and RAS mutations, ARMS carries a gene fusion between PAX3 or PAX7 and FOXO1. Epithelioid RMS is a morphologic variant of RMS recently described in adults. Five cases of epithelioid RMS were identified after histologic review of 85 cases of ARMS enrolled in Italian therapeutic protocols. Immunostaining analyses (muscle-specific actin, desmin, myogenin, AP-2β, EMA, cytokeratins, INI-1) and reverse transcription polymerase chain reaction assays to detect MyoD1, myogenin, and PAX3/7-FOXO1 transcripts were performed. In 4 cases DNA sequencing of TP53 was performed; and RB1 allelic imbalance and homozygous deletion were analyzed by quantitative real-time polymerase chain reaction. Histologically, epithelioid RMS displayed sheets of large cells without rhabdomyoblastic differentiation or anaplasia in 3 and prominent rhabdoid cells in 2; necrosis was evident in 4, often with a geographic pattern. Immunostainings for INI, desmin, myogenin (scattered cells in 4, diffuse in 1) were positive in all; EMA and MNF116 were positive in 2; AP-2β was negative. PAX3/7-FOXO1 transcripts were absent. In all cases RB1 was wild type, and a TP53 mutation at R273H codon was found in 1. All patients are in complete remission, with a median follow-up of 6 years. Epithelioid RMS may occur in children and is probably related to ERMS, as suggested by lack of fusion transcripts, weak staining for myogenin, negative AP-2β, evidence of TP53 mutation (although only in 1 case), and a favorable clinical course.	f	\N
24424075	Hyperphosphataemia, a common biochemical abnormality in chronic kidney disease, poses significant management challenges. This study aims to determine whether the reasons for this are multifactorial; including poor dietary knowledge, poor adherence to a low phosphate diet and phosphate-binding medications and the impact of age on these parameters. In order to compare serum phosphate and other associated parameters to the UK Renal Association Clinical Practice Guidelines 2010 an audit and service evaluation questionnaire was carried out in May 2011 on 130 haemodialysis outpatients attending the Plymouth Dialysis Unit. Fifty-three percent of patients had serum phosphate within the target range of 1.1-1.7 mmol/l, 77% and 85% had serum calcium and parathyroid hormone within target ranges, respectively. Younger patients (18-45 years) were significantly less likely to have serum phosphate within range χ(2) (2, n=124)=18.77, P<0.001. Despite better knowledge of their own phosphate levels (P=0.005), phosphorus-rich foods (P<0.001), symptoms of hyperphosphataemia (P<0.001) and increased use of Renal Patient View (P=0.002), <65 years old had significantly higher phosphate levels than those >65 years (P<0.001). No significant associations were found between phosphate control and the following factors: gender, timing of dialysis shift, years on dialysis or dialysis adequacy. In this population, despite better knowledge, younger patients have worse phosphate control than older patients. Using the same dietary education techniques may not be suitable for all ages, more innovative approaches supported by skilled health professionals are needed to motivate and engage with younger patients to promote self-management and adherence.	f	\N
24424629	To evaluate the long-term efficacy of pain reduction by two dose fractionation schedules used for low-dose radiotherapy of painful elbow syndrome. Between February 2006 and February 2010, 199 evaluable patients were recruited for this prospective trial. All patients received low-dose orthovoltage radiotherapy. One course consisted of 6 fractions in 3 weeks. In the case of insufficient pain remission after 6 weeks, a second course was administered. Patients were randomly assigned to one of two groups to receive single doses of either 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before radiotherapy, as well as immediately after (early response), 6 weeks after (delayed response) and approximately 3 years after (long-term response) completion of radiotherapy using a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS). Median follow-up was 35 months (range 9-57 months). The overall early, delayed and long-term response rates for all patients were 80, 90 and 94 %, respectively. The mean VAS scores before treatment and those for early, delayed and long-term response in the 0.5- and 1.0-Gy groups were 59.6 ± 20.2 and 55.7 ± 18.0 (p = 0.46); 32.1 ± 24.5 and 34.4 ± 22.5 (p = 0.26); 27.0 ± 27.7 and 23.5 ± 21.6 (p = 0.82) and 10.7 ± 15.0 and 21.5 ± 26.9 (p = 0.12), respectively. The mean CPS values before treatment and those for early, delayed and long-term response were 8.7 ± 2.9 and 8.1 ± 3.1 (p = 0.21); 4.5 ± 3.2 and 5.0 ± 3.4 (p = 0.51); 3.9 ± 3.6 and 2.8 ± 2.8 (p = 0.19) and 1.5 ± 2.3 and 2.4 ± 3.5 (p = 0.27), respectively. No significant differences in the quality of the long-term response were found between the 0.5- and 1.0-Gy arms (p = 0.28). Low-dose radiotherapy is an effective treatment for the management of benign painful elbow syndrome. For radiation protection reasons, the dose for a radiotherapy series should not exceed 3.0 Gy.	f	\N
24436152	L-Asparaginase is an integral component of standard chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL). Clinical hypersensitivity, a common reason for treatment discontinuation, has been reported in 10-30% of patients receiving Escherichia coli-derived asparaginase. After hypersensitivity, E. coli-derived asparaginase should be discontinued and an alternative asparaginase preparation, such as asparaginase Erwinia chrysanthemi, may be initiated. We conducted a compassionate-use study to collect additional safety information on asparaginase Erwinia chrysanthemi and to support FDA approval of the product. Patients with ALL or lymphoblastic lymphoma (LBL; N = 1368) who developed a hypersensitivity reaction (grade ≥2) to an E. coli-derived asparaginase participated in this trial. The recommended asparaginase Erwinia chrysanthemi dose was 25,000 IU/m(2) three days per week (Monday/Wednesday/Friday) for two consecutive weeks for each missed pegylated E. coli-derived asparaginase dose and 25,000 IU/m(2) for each missed nonpegylated asparaginase dose for the completion of their planned asparaginase treatment. Adverse event reports and/or case report forms were completed for 940 patients. The most common adverse event (AE) was hypersensitivity (13.6%). Eighteen patients (1.9%) died during the study. Most patients (77.6%) completed their planned asparaginase treatment with asparaginase Erwinia chrysanthemi. There was no apparent difference in the incidence of the most commonly reported AEs with asparaginase treatment by age, administration, or disease state. This study further established the safety profile of asparaginase Erwinia chrysanthemi in patients with ALL or LBL who had a hypersensitivity reaction to an E. coli-derived asparaginase.	f	\N
24437400	The development of culture-independent techniques has revolutionized our understanding of how our human cells interact with the even greater number of microbial inhabitants of our bodies. As part of this revolution, data are increasingly challenging the old dogma that in health, the lung mucosa is sterile. To understand how the lung microbiome may play a role in human health, we identified five major questions for lung microbiome research: (1) Is the lung sterile? (2) Is there a unique core microbiome in the lung? (3) How dynamic are the microbial populations? (4) How do pulmonary immune responses affect microbiome composition? and (5) Are the lungs influenced by the intestinal immune responses to the gut microbiome? From birth, we are exposed to continuous microbial challenges that shape our microbiome. In our changing environment, perturbation of the gut microbiome affects both human health and disease. With widespread antibiotic use, the ancient microbes that formerly resided within us are being lost, for example, Helicobacter pylori in the stomach. Animal models show that antibiotic exposure in early life has developmental consequences. Considering the potential effects of this altered microbiome on pulmonary responses will be critical for future investigations.	f	\N
24446993	With an estimated 12.1% of children aged 2-5 years already obese, prevention efforts must target our youngest children. One of the best places to reach young children for such efforts is the early care and education setting (ECE). More than 11 million U.S. children spend an average of 30 hours per week in ECE facilities. Increased attention at the national, state, and community level on the ECE setting for early obesity prevention efforts has sparked a range of innovative efforts. To assist these efforts, CDC developed a technical assistance and training framework - the Spectrum of Opportunities for Obesity Prevention in the ECE setting - which also served as the organizing framework for the Weight of the Nation ECE track. Participants highlighted their efforts at national, state, and local levels pursuing opportunities on the Spectrum, the standards and best practices that had been the emphasis of their efforts, and common steps for developing, implementing, and evaluating initiatives. Strong leadership and collaboration among a broad group of stakeholders; systematic assessment of needs, opportunities and resources; funding sources; and training and professional development were reported to be integral for successful implementation of standards and best practices, and sustainability.	f	\N
24447640	Fungal endophthalmitis is a rare but serious infection. In March 2012, several cases of probable and laboratory-confirmed fungal endophthalmitis occurring after invasive ocular procedures were reported nationwide. We identified 47 cases in 9 states: 21 patients had been exposed to the intraocular dye Brilliant Blue G (BBG) during retinal surgery, and the other 26 had received an intravitreal injection containing triamcinolone acetonide. Both drugs were produced by Franck's Compounding Lab (Ocala, FL, USA). Fusarium incarnatum-equiseti species complex mold was identified in specimens from BBG-exposed case-patients and an unopened BBG vial. Bipolaris hawaiiensis mold was identified in specimens from triamcinolone-exposed case-patients. Exposure to either product was the only factor associated with case status. Of 40 case-patients for whom data were available, 39 (98%) lost vision. These concurrent outbreaks, associated with 1 compounding pharmacy, resulted in a product recall. Ensuring safety and integrity of compounded medications is critical for preventing further outbreaks associated with compounded products.	f	\N
24449063	Psychotic symptoms have previously been reported following right hemisphere brain injury. We sought to identify the specific neuroanatomical basis of delusions following stroke by studying a series of patients with post-stroke psychosis. Lesion overlap analysis was conducted on three individuals with delusions following right hemisphere stroke. These cases were compared with a control group of patients with similar anatomical damage. The main outcome measures were presence of delusions and presence of behavioural susceptibility. The right inferior frontal gyrus and underlying white matter, including the superior longitudinal fasciculus and anterior corona radiata, were involved in all three cases. All three had a preexisting untreated psychiatric disorder. In contrast, only one of nine control cases with equivalent lesions had evidence of previous psychiatric disorder (p = 0.0182, Fisher's exact test), and this was being treated at the time of stroke. We provide clinical evidence from patients with structural brain lesions implicating damage to the right inferior frontal lobe in the generation of persistent psychosis following stroke. We suggest that preexisting psychiatric disease provided a behavioural susceptibility to develop delusions in these individuals.	f	\N
24449064	The logopenic variant of primary progressive aphasia (lvPPA) strongly associates with Alzheimer's disease, but can also associate with frontotemporal lobar degeneration. We aimed to assess the frequency of lvPPA in patients with speech and language disorders without β-amyloid deposition, and to perform detailed neuroimaging and genetic testing in such lvPPA patients. Seventy-six patients with a neurodegenerative speech and language disorder and Pittsburgh compound B (PiB) PET imaging demonstrating no β-amyloid deposition were analyzed. Six lvPPA patients (8 %) were identified. All six underwent progranulin (GRN) gene testing. Structural abnormality index maps and Cortex ID analysis were utilized to assess individual patterns of grey matter atrophy on MRI and hypometabolism on 18-F fluorodeoxyglucose (FDG) PET. Statistical parametric mapping was used to perform MRI and FDG-PET group comparisons between those with (GRN-positive) and without (GRN-negative) progranulin mutations. All six lvPPA patients showed left temporoparietal atrophy and hypometabolism. Three patients (50 %) were GRN-positive. Speech, language, and neurological and neuropsychological profiles did not differ between GRN-positive and negative patients, although GRN-positive patients had family histories, were on average 8 years younger, and had lower PiB-PET ratios. All six patients showed similar patterns of atrophy and hypometabolism, although, as a group, GRN-positive patients had more severe abnormalities, particularly in anteromedial temporal lobes. Logopenic PPA accounts for a small minority of neurodegenerative speech and language disorders not associated with β-amyloid deposition. Identification of such patients, however, should prompt testing for GRN mutations, since GRN-positive patients do not have distinctive features, yet account for 50 % of this patient population.	f	\N
24449169	Low-frequency, bilateral stimulation of the subthalamic nucleus can improve axial symptoms of advanced Parkinson's disease (PD), but it is not particularly effective for segmental symptoms. The optimal contacts for low-frequency (60 Hz) and high-frequency (130 Hz) single monopolar stimulation were determined. Then, in a randomized, double-blind, prospective crossover manner, 60-Hz and 130-Hz stimulations via the respective optimal contacts were compared for immediate efficacy in improving the motor function of patients with PD. The optimal contacts for 60-Hz stimulation were situated more ventrally than those for 130-Hz stimulation (P = 0.038). Under the respective optimal, single monopolar stimulation, 60 Hz provided superior efficacy over 130 Hz in improving the total Unified Parkinson's Disease Rating Scale motor score (P < 0.001) and the akinesia (P = 0.011) and axial motor signs (P = 0.012) subscores without compromising the therapeutic effect on tremor and rigidity. Low-frequency stimulation via the optimal contacts is effective in improving overall motor function of patients with PD.	f	\N
24450996	Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. Our results demonstrate that vaccinating children 2-17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany.	f	\N
24459296	Huntington disease (HD) is a debilitating neurodegenerative disease characterized by the loss of motor control and cognitive ability that ultimately leads to death. It is caused by the expansion of a polyglutamine tract in the huntingtin (HTT) protein, which leads to aggregation of the protein and eventually cellular death. Both the wild-type and mutant form of the protein are highly regulated by post-translational modifications including proteolysis, palmitoylation and phosphorylation. We now demonstrate the existence of a new post-translational modification of HTT: the addition of the 14 carbon fatty acid myristate to a glycine residue exposed on a caspase-3-cleaved fragment (post-translational myristoylation) and that myristoylation of this fragment is altered in a physiologically relevant model of mutant HTT. Myristoylated HTT553-585-EGFP, but not its non-myristoylated variant, initially localized to the ER, induced the formation of autophagosomes and accumulated in abnormally large autophagolysosomal/lysosomal structures in a variety of cell types, including neuronal cell lines under nutrient-rich conditions. Our results suggest that accumulation of myristoylated HTT553-586 in cells may alter the rate of production of autophagosomes and/or their clearance through the heterotypic autophagosomal/lysosomal fusion process. Overall, our novel observations establish a role for the post-translational myristoylation of a caspase-3-cleaved fragment of HTT, highly similar to the Barkor/ATG14L autophagosome-targeting sequence domain thought to sense, maintain and/or promote membrane curvature in the regulation of autophagy. Abnormal processing or production of this myristoylated HTT fragment might be involved in the pathophysiology of HD.	f	\N
24460750	In patients with essential thrombocythemia (ET), vascular complications contribute to both morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score of thrombosis for ET (IPSET-thrombosis) was recently developed. We hereby presented an external validation and analysis of this model in a large Cohort of Chinese Patients. We retrospectively evaluated the characteristics and risk factors for thrombosis in 970 Chinese patients with ET and estimated the clinical implications of the IPSET-thrombosis model. The median follow-up was 49 months (range, 0-360). Chinese ET patients had similar clinical characteristics as Caucasian patients. Similar to the IPSET-thrombosis study, our multivariate analysis revealed age >60 (HR = 1.949), previous thrombosis (HR = 2.484), JAK2V617F mutation (HR = 1.719), and cardiovascular risk factors (HR = 1.877) as independent risk factors for thrombosis. We confirmed that the above risk factors in IPSET-thrombosis, when compared with traditional risk factors (e.g., age ≥60 and previous thrombotic events), were more predictive of thrombotic events (C-index 0.714 vs. 0.647). Classification by IPSET-thrombosis risk groups revealed different cumulative thrombosis-free survival (P < 0.001). For treatment, patients in the intermediate- and high-risk group derived clinical benefit from cytoreductive agents (P < 0.05), but those in the low-risk group did not (P = 0.446). The lower risk of thrombosis on cytoreductive therapy was related to decrease in leukocyte count during the disease course. We validate the reproducibility of IPSET-thrombosis in Chinese ET patients and provide key clinical implications.	f	\N
24467498	alcohol use disorders are associated with a greater incidence of certain comorbidities in patients with celiac disease. Currently there is no available information about the impact that these disorders may have on length of hospital stays, overexpenditures during hospital stays, and excess mortality in these patients. a case-control study was conducted with a selection of patients 18 years and older hospitalized during 2008-2010 in 87 hospitals in Spain. Estimations of excess length of stays, costs, and attributable mortality were calculated using a multivariate analysis of covariance, which included age, gender, hospital group, alcohol use disorders, tobacco related disease and 30 other comorbidities. patients who had both celiac disease and alcohol use disorders had an increased length of hospital stay, an average of 3.1 days longer in women, and 1.7 days longer in men. Excess costs per stay ranged from 838.7 euros in female patients, to 389.1 euros in male patients. Excess attributable mortality was 15.1 % in women, 12.2 % in men. apart from a gluten-free diet and other medical measures, the prevention of alcohol abuse is indicated in these patients. Patients hospitalized who present these disorders should receive specialized attention after leaving the hospital. Early detection and treatment should be used to prevent the appearance of organic lesions and should not be solely focused on male patients.	f	\N
24469423	The molecular epidemiology of group B Streptococcus (GBS) in Ireland was investigated. Invasive (n = 132) and non-invasive (n = 45) isolates, collected in 2007-2011, were analysed by multilocus locus sequence typing, capsular polysaccharide (CPS) serotyping, profiling of surface proteins, pilus islands (PI), and antimicrobial susceptibility. Isolates grouped into 45 sequence types and five main clonal complexes (CC). CC1, CC17 and CC23 represented 67.2 % of isolates and the most prevalent serotypes Ia, III and V. Serotype and surface protein genes were largely predictive of CC. Accordingly, CPS V/alp3, CPS Ib/CPS II/bca + bac, and CPS Ia/eps predominated in CC1, CC12 and CC23, respectively, and CPS III/rib in CC17 and CC19. Supporting their vaccine potential, all isolates harboured at least one PI, of which the PI-1 + PI-2a combination was most prevalent. Macrolide resistance was found in 18.6 % of isolates. erm(B) and the globally disseminated CC1/CPS V were the most common resistance mechanism and CC/CPS type, respectively. CC17, significantly associated with neonatal disease, was also prevalent in pregnant adults, but was underrepresented among non-pregnant adults. Two of 46 CC17 isolates (typically CPS III) were CPS IV. Sequence analysis confirmed capsular switching and their relatedness to CC17/CPS IV strains recently characterized in France. CPS IV, detected only in invasive isolates (6.8 %), was most prevalent in adults (12 %) and showed an increase in prevalence to that reported (1.4 %) for invasive isolates in Ireland 1997-1999. Increases in serotype IV and evidence of capsular switching in CC17 highlights the importance of ongoing surveillance of GBS and may have implications for vaccine development strategies.	f	\N
24478094	Evidence from clinical trials of malaria vaccine candidates suggests that both cell-mediated and humoral immunity to pre-erythrocytic parasite stages can provide protection against infection. Novel pre-erythrocytic antibody (Ab) targets could be key to improving vaccine formulations, which are currently based on targeting antigens such as the circumsporozoite protein (CSP). However, methods to assess the effects of sporozoite-specific Abs on pre-erythrocytic infection in vivo remain underdeveloped. Here, we combined passive transfer of monoclonal Abs (MAbs) or immune serum with a luciferase-expressing Plasmodium yoelii sporozoite challenge to assess Ab-mediated inhibition of liver infection in mice. Passive transfer of a P. yoelii CSP MAb showed inhibition of liver infection when mice were challenged with sporozoites either intravenously or by infectious mosquito bite. However, inhibition was most potent for the mosquito bite challenge, leading to a more significant reduction of liver-stage burden and even a lack of progression to blood-stage parasitemia. This suggests that Abs provide effective protection against a natural infection. Inhibition of liver infection was also achieved by passive transfer of immune serum from whole-parasite-immunized mice. Furthermore, we demonstrated that passive transfer of a MAb against P. falciparum CSP inhibited liver-stage infection in a humanized mouse/P. falciparum challenge model. Together, these models constitute unique and sensitive in vivo methods to assess serum-transferable protection against Plasmodium sporozoite challenge.	f	\N
24501382	It has been established that bimanual coordination with augmented feedback (FB) versus no augmented feedback (NFB) is associated with activity in different brain regions. It is unclear however, whether this distinction remains after practice comprising both these conditions. Functional magnetic resonance imaging was used in humans to compare visual FB versus NFB conditions for a bimanual tracking task, and their differential evolution across learning. Scanning occurred before (Pre) and after 2 weeks (Post) of mixed FB and NFB training using an event-related design, allowing differentiation between the planning and execution phase of the task. Activations at the whole-brain level initially differed for FB versus NFB movements but this differentiation diminished with training for the movement execution phase. Specifically, in right dorsal premotor cortex and right dorsolateral prefrontal cortex activation increased for NFB and decreased for FB trials to converge toward the end of practice. This suggests that learning led to a decreased need to adjust the ongoing movement on the basis of FB, whereas online monitoring became more pronounced in NFB trials as discrepancies between the required and the produced motor output were detected more accurately after training, due to a generic internal reference of correctness supporting movement control under varying conditions.	f	\N
24505382	Public health surveillance systems provide valuable data for reliable predication of future epidemic events. This paper describes a study that used nine types of infectious disease data collected through a national public health surveillance system in mainland China to evaluate and compare the performances of four time series methods, namely, two decomposition methods (regression and exponential smoothing), autoregressive integrated moving average (ARIMA) and support vector machine (SVM). The data obtained from 2005 to 2011 and in 2012 were used as modeling and forecasting samples, respectively. The performances were evaluated based on three metrics: mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE). The accuracy of the statistical models in forecasting future epidemic disease proved their effectiveness in epidemiological surveillance. Although the comparisons found that no single method is completely superior to the others, the present study indeed highlighted that the SVMs outperforms the ARIMA model and decomposition methods in most cases.	f	\N
24507376	Human infections with different avian influenza viruses--eg, H5N1, H9N2, and H7N9--have raised concerns about pandemic potential worldwide. We report the first human infection with a novel reassortant avian influenza A H10N8 virus. We obtained and analysed clinical, epidemiological, and virological data from a patient from Nanchang City, China. Tracheal aspirate specimens were tested for influenza virus and other possible pathogens by RT-PCR, viral culture, and sequence analyses. A maximum likelihood phylogenetic tree was constructed. A woman aged 73 years presented with fever and was admitted to hospital on Nov 30, 2013. She developed multiple organ failure and died 9 days after illness onset. A novel reassortant avian influenza A H10N8 virus was isolated from the tracheal aspirate specimen obtained from the patient 7 days after onset of illness. Sequence analyses revealed that all the genes of the virus were of avian origin, with six internal genes from avian influenza A H9N2 viruses. The aminoacid motif GlnSerGly at residues 226-228 of the haemagglutinin protein indicated avian-like receptor binding preference. A mixture of glutamic acid and lysine at residue 627 in PB2 protein--which is associated with mammalian adaptation--was detected in the original tracheal aspirate samples. The virus was sensitive to neuraminidase inhibitors. Sputum and blood cultures and deep sequencing analysis indicated no co-infection with bacteria or fungi. Epidemiological investigation established that the patient had visited a live poultry market 4 days before illness onset. The novel reassortant H10N8 virus obtained is distinct from previously reported H10N8 viruses. The virus caused human infection and could have been associated with the death of a patient. Emergency Research Project on human infection with avian influenza H7N9 virus, the National Basic Research Program of China, and the National Mega-projects for Infectious Diseases.	f	\N
24508287	Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue receptor and is closely associated with chronic heart failure (CHF). We undertook this study to investigate the relevance of ghrelin in CHF prognosis. A total of 145 in-patients with CHF in NYHA class II, III or IV despite optimized therapy were prospectively included in the study, grouped according to NYHA class and compared with 55 healthy control subjects. Ghrelin and N-terminal pro-B-type natriuretic peptide (Nt pro-BNP) were measured in plasma by ELISA. Echocardiographic information was also measured, including left atrial dimension, left ventricular end-diastolic diameter, LV volume and left ventricular ejection fraction (LVEF). Patients were followed for 2 years or until major adverse cardiac events. Plasma ghrelin levels were significantly lower in patients with CHF than in control subjects (p = 0.014). In addition, plasma ghrelin levels differed significantly with the severity of CHF. Notably, survival analysis showed that high ghrelin levels were an indicator of a favorable prognosis for CHF. Our results also showed that ghrelin correlated inversely with plasma Nt pro-BNP levels (r = -0.562, p <0.001) and positively with LVEF (r = 0.620, p <0.001) in patients with CHF. Furthermore, multivariate analysis showed that ghrelin levels were independently associated with adverse cardiac events (hazard ratio: 0.72; 95% CI: 0.64-0.81, p = 0.03). Ghrelin is a new biomarker of CHF severity as well as a new prognostic predictor for patients with CHF. Future experimental and clinical studies are warranted to evaluate ghrelin as a novel prognostic tool and for its therapeutic potential in patients with CHF.	f	\N
24512284	To perform psychometric testing an owner self-administered questionnaire, the Canine Orthopedic Index (COI), designed to assess outcome in dogs with orthopedic disease. Original study. Owners (n = 20) of dogs with osteoarthritis (OA) for item (question) pretesting, and 80 owners of dogs with OA for reliability and validity testing. Standard methodology for the stepwise development and testing of instruments designed to assess subjective states was followed. Items generated in previous studies were pretested for readability, ambiguity, and inter-item correlations; poorly performing items were removed; and the reduced set of items subjected to factor analysis, reliability, and validity testing. Four factors were identified and named on the basis of the items contained in them: "Stiffness," "Gait," "Function," and "Quality of Life." Cronbach's α ranged from 0.76 to 0.86, suggesting the items in each factor could be assessed as a group to compute factor scores (i.e., stiffness, gait, function, and quality of life scores). The test-retest analysis revealed κ values from 0.68 to 0.80. Overall, the scores amongst the 4 factors correlated moderately well (r = 0.52-0.58), with a mild correlation (r = 0.35) between gait and function scores. The COI is a psychometrically sound owner completed instrument that can assess 4 domains in dogs with OA: Stiffness, Gait, Function, and Quality of Life.	f	\N
24513795	Blood sample and placenta were taken from a 37-week pregnant woman; serologic results indicated acute toxoplasmosis. Placenta was inoculated into mice. Seropositive mice were sacrificed and tissue cysts from brain were inoculated into new mice. Specific DNA was detected by PCR, and the isolate was characterized as Type II by nPCR-RFLP for nSAG2, SAG3, BTUB, GRA6, c29-2, c22-8, L358, PK1 and Apico markers. This is the first isolation and molecular characterization of Toxoplasma gondii from humans in Argentina.	f	\N
24517642	Salvage liver transplantation (SLT) is an attractive sequential strategy which combines liver resection (LR) for hepatocellular carcinoma (HCC), followed by liver transplant (LT) in the event of HCC recurrence or progressive liver deterioration. To compare the long-term results of SLT with primary liver transplant (PLT). Between 2000 and 2011, 125 patients (72 transplantable) underwent LR and 226 underwent LT in our unit. The outcome of SLT was analysed in a two-step fashion: firstly, SLT (n = 28) was compared with PLT (n = 198), secondly an intention-to-treat analysis was performed on all transplantable HCC patients who underwent LR (LRT group = 72) compared to PLT (n = 198). The five-year overall survival (OS) was 65.4% vs. 49.2% (P = 0.63), and disease-free survival (DFS) was 89.7% vs. 80.6% (P = 0.31) for PLT and SLT respectively. Predictive factors for DFS after LT included HCC total diameter [hazard ratio (HR) 1.29 P = 0.003], alpha-foetoprotein (HR 1.002 P < 0.001) and number of HCC nodules (HR 1.317 P = 0.035), whereas viral hepatitis C positivity (HR 1.911 P = 0.03) and outside Up-to-seven criteria (HR 2.652 P < 0.001) were negative independent prediction factors of OS. Intention-to-treat analysis showed that OS at 5 years was improved in PLT vs. LRT (LRT n = 72 including SLT plus LR group) and was 69.4% vs. 42.2% (P < 0.004), with an additional increase in DFS (89.2% vs. 54.5% respectively P < 0.001). Salvage liver transplantation is a safe treatment strategy, as it does not impair long-term survival. At intention-to-treat analysis, PLT showed improved survival compared with LRT.	f	\N
24519340	Mental health is a human right and fundamental to good personal health. Developing, planning, and implementing mental health programs is a key part of health policies worldwide. This paper uses the perspective of "mental health mainstreaming" to define mental health and explore its relationship with mental illness and psychiatric disease. Further, we apply this perspective to Taiwan's three-tiered community mental illness prevention strategy as a reference for mental health promotion and rehabilitation programs in hopes that all healthcare providers help facilitate holistic community health.	f	\N
24524071	Heat shock protein 72 (Hsp72) exhibits a protective role during times of increased risk of pathogenic challenge and/or tissue damage. The aim of the study was to ascertain Hsp72 protective effect differences between animal and human studies in sepsis using a hypothetical "comparative study" model. Forty-one in vivo (56.1%), in vitro (17.1%), or combined (26.8%) animal and 14 in vivo (2) or in vitro (12) human Hsp72 studies (P < 0.0001) were enrolled in the analysis. Of the 14 human studies, 50% showed a protective Hsp72 effect compared to 95.8% protection shown in septic animal studies (P < 0.0001). Only human studies reported Hsp72-associated mortality (21.4%) or infection (7.1%) or reported results (14.3%) to be nonprotective (P < 0.001). In animal models, any Hsp72 induction method tried increased intracellular Hsp72 (100%), compared to 57.1% of human studies (P < 0.02), reduced proinflammatory cytokines (28/29), and enhanced survival (18/18). Animal studies show a clear Hsp72 protective effect in sepsis. Human studies are inconclusive, showing either protection or a possible relation to mortality and infections. This might be due to the fact that using evermore purified target cell populations in animal models, a lot of clinical information regarding the net response that occurs in sepsis is missing.	f	\N
24529770	When tried in court, mothers accused of neonaticide may claim that the umbilical cord just broke during birth and the newborn child bled to death accordingly. To evaluate the possibility of a breakage of the umbilical cord is the goal of this work. Therefore 25 umbilical cords from neonates of both sexes born at term were stretched using an electrically operated material testing machine and the energy necessary to break them was measured. This experimental set-up equals a static strain, not a dynamic one. The maximum force endured (F max) ranged from 37.24 N to 150.04 N. The average force endured was 79.87 N with a standard deviation of 27.39. The elongation at break varied from 13.24% to a maximum of 119.93%. We found no relationship between the force endured and any of the following parameters: birth weight, pH of the venous umbilical blood, diameter of cord, free length under testing, duration of pregnancy or the mother's age. We performed a literature research and tried to define the circumstances in which a break is more likely to occur, these being malformations, entanglement or disease, e.g. inflammation.	f	\N
24550581	Levosimendan is a calcium sensitizer drug which has been used in cardiac surgery for the prevention of postoperative low cardiac output syndrome (LCOS) and in difficult weaning from cardiopulmonary bypass (CPB). This study aims to evaluate perioperative hemodynamic effects of levosimendan pretreatment in patients for off-pump coronary artery bypass graft (OPCABG) surgery with low left ventricular ejection fractions (LVEF < 30%). Fifty patients undergoing OPCABG surgery with low LVEF (<30%) were enrolled in the study. Patients were randomly divided in two groups: Levosimendan pretreatment (Group L) and placebo pretreatment (Group C) of 25 each. Group L, patients received levosimendan infusion 200 μg/kg over 24 h and in Group C Patients received placebo. The clinical parameters measured before and after the drug administration up to 48 h were heart rate (HR; for the hour after drug infusion), cardiac index (CI), and pulmonary capillary wedge pressure (PCWP). The requirement of inotropes, intraaortic balloon pump (IABP), CPB, intensive care unit (ICU) stay, and hospital stay were also measured. The patients in group L exhibited higher CI and PCWP during operative in early postoperative period as compared to control group C. Group L also had a less requirement for inotropes, CPB support and IABP with shorter ICU stay as well as hospital stay. Levosimendan pretreatment (24 h infusion) in patient for OPCABG with poor LVEF shows better outcomes and hemodynamics in terms of inotropes, CPB and IABP requirements. It also reduces ICU stay.	f	\N
24554437	The ER is the largest cellular compartment and a major storage site for lipids and ions. In recent years, much attention has focused on contacts between the ER and other organelles, and one particularly intimate relationship is that between the ER and the endosomal system. ER-endosome contacts intensify when endosomes mature, and the ER participates in endosomal processes, such as the termination of surface receptor signaling, multi-vesicular body formation, and transport and fusion events. Cholesterol and Ca(2+) are transferred between the ER and endosomes, possibly acting as messengers for ER-endosome crosstalk. Here, we summarize different types of ER-endosomal communication and discuss membrane contact sites that might facilitate this crosstalk. We review the protein pairs that interact at the ER-endosome interface and find that many of these have a role in cholesterol exchange. We also summarize Ca(2+) exchange between the ER and endosomes, and hypothesize that ER-endosome contacts integrate several cellular functions to guide endosomal maturation. We post the hypothesis that failure in ER-endosome contacts is an unrecognized but important contributor to diseases, such as Niemann-Pick type C disease, Alzheimer's disease and amyotrophic lateral sclerosis.	f	\N
24555602	This article will describe the elements of performing a thorough venous ultrasound evaluation of the lower extremity in patients with manifestations of chronic venous disorder. The emphasis will be on the evaluation of superficial venous reflux. Only the specific aspects of the evaluation of the deep system pertaining to chronic venous disease will be discussed. Duplex ultrasound requires the examiner to solve a puzzle to explain the patient's clinical manifestations. Patients who have been treated with surgery, thermal ablation, or ultrasound-guided sclerotherapy will require duplex ultrasound after treatment to identify complications, gauge the extent of treatment success, and evaluate the cause for any recurrence.	f	\N
24557586	The survival of patients with axial skeletal or pelvic osteosarcoma (OS) remains poor, and the management of these patients is challenging. The object of this study is a cohort of unselected patients aged < 19 years with primary high-grade pelvic/axial OS. Patients were treated with high-dose methotrexate, doxorubicin, cisplatin, ifosfamide followed or preceded by local treatment (surgery and/or radiotherapy). Twenty patients aged 3-19 years were treated. Eight patients had pelvic OS, 8 axial OS and 4 mandible/maxilla OS. All patients received chemotherapy, after which necrosis was evaluable in 9 patients (≥ 90% in 3). Sixteen patients underwent surgery. Radiotherapy was administered to 8 patients (total dose 34-60 Gy). The median follow-up was 35 months (8-276), and the 5-year disease-free survival and overall survival rates were 37 and 40%, respectively. Six patients were alive at the time of this report: 2 with pelvic OS (both responded well to chemotherapy, one underwent hemipelvectomy and the other had non-radical surgery plus radiotherapy); 1 with axial and multicentric OS (with a good histological response and radical surgery); 3 with mandible/maxilla OS. Two patients died of secondary tumors (one bone and one breast cancer). It is worth noting that 4 patients had a p53 mutation: 1 is alive, 2 died of their OS, 1 of breast cancer. Adequacy of local treatment and pathological response influenced the prognosis for axial OS, which remained dismal. A high incidence of p53 mutation emerged in our series of patients.	f	\N
24560191	In this issue of Immunity, Funabiki et al. (2014) have identified in mice a mutation of the IFIH1 gene, encoding the viral receptor MDA5 that causes constitutive IFN production and fatal autoimmune disease. The authors show that the autoimmune disease-associated variant of human MDA5 is permanently switched on.	f	\N
24566636	In the current open society and with the growth of human rights, people are more and more concerned about the privacy of their information and other important data. This study makes use of electrocardiography (ECG) data in order to protect individual information. An ECG signal can not only be used to analyze disease, but also to provide crucial biometric information for identification and authentication. In this study, we propose a new idea of integrating electrocardiogram watermarking and compression approach, which has never been researched before. ECG watermarking can ensure the confidentiality and reliability of a user's data while reducing the amount of data. In the evaluation, we apply the embedding capacity, bit error rate (BER), signal-to-noise ratio (SNR), compression ratio (CR), and compressed-signal to noise ratio (CNR) methods to assess the proposed algorithm. After comprehensive evaluation the final results show that our algorithm is robust and feasible.	f	\N
24568610	The generation of induced pluripotent stem cells (iPSCs) from somatic cells by expressing ectopic reprogramming transcriptional factors such as Oct3/4, Sox2, Klf4, c-Myc, and Nanog is one of the cutting-edge discoveries in stem cell and cancer research. This discovery has raised several safety issues regarding the use of iPSC technology for human disease research. Tumorigenesis is the major obstacle observed for iPSC-mediated transplantation therapy. Recently, a new method to generate human iPSCs either by a chemical method or by direct delivery of reprogramming factors has become a promising approach for future customized cell therapy of human disorders. These reprogramming transcriptional factors play critical roles in diverse cellular functions such as transactivation, cellular proliferation, differentiation, apoptosis, and tumorigenesis. Posttranslational modifications (PTMs) (phosphorylation, ubiquitination, acetylation, sumoylation, and so on) of these proteins act as a regulatory signal to control protein activity, expression, and stability in a wide variety of cellular processes. We attempt to summarize the accumulated evidence to address the role of PTMs of Oct3/4, Sox2, Klf4, c-Myc, and Nanog in regulating their biological functions. This review allows us to understand the importance of PTMs and their application in developing an efficient and safe reprogramming method without cancer development for cell therapy. Finally, we discuss the importance of PTMs of reprogramming factors in tumor pathogenesis.	f	\N
24574413	Interferons (IFNs) are cytokines produced by host cells in response to the infection with pathogens. By binding to the corresponding receptors, IFNs trigger different pathways to block intracellular replication and growth of pathogens and to impede the infection of surrounding cells. Due to their key role in host defense against viral infections, as well as for clinical therapies, the IFN responses and regulation mechanisms are well studied. However, studies of type I IFNs have mainly focused on alpha interferon (IFN-α) and IFN-β subtypes. Knowledge of IFN-κ and IFN-ω is limited. Moreover, most studies are performed in humans or mouse models but not in the original host of zoonotic pathogens. Bats are important reservoirs and transmitters of zoonotic viruses such as lyssaviruses. A few studies have shown an antiviral activity of IFNs in fruit bats. However, the function of type I IFNs against lyssaviruses in bats has not been studied yet. Here, IFN-κ and IFN-ω genes from the European serotine bat, Eptesicus serotinus, were cloned and functionally characterized. E. serotinus IFN-κ and IFN-ω genes are intronless and well conserved between microchiropteran species. The promoter regions of both genes contain essential regulatory elements for transcription factors. In vitro studies indicated a strong activation of IFN signaling by recombinant IFN-ω, whereas IFN-κ displayed weaker activation. Noticeably, both IFNs inhibit to different extents the replication of different lyssaviruses in susceptible bat cell lines. The present study provides functional data on the innate host defense against lyssaviruses in endangered European bats. We describe here for the first time the molecular and functional characterization of two type I interferons (IFN-κ and -ω) from European serotine bat (Eptesicus serotinus). The importance of this study is mainly based on the fact that very limited information about the early innate immune response against bat lyssaviruses in their natural host serotine bats is yet available. Generally, whereas the antiviral activity of other type I interferons is well studied, the functional involvement of IFN-κ and -ω has not yet been investigated.	f	\N
24579399	Patients with chronic kidney disease (CKD) who are treated with dialysis have impaired physical functioning that is associated with poor outcomes. Gait speed is an important measure of mobility that predicts adverse events and mortality in older people. Gait speed is low in patients with CKD, and those treated with hemodialysis average below cut-points known to indicate increased risk of reduced survival and adverse health events. Measurement of gait speed in patients with CKD may be valuable in identifying those at risk for adverse events, including disability and mortality.	f	\N
24583421	Magnetic resonance imaging has been shown to be a powerful tool for diagnosing multiple sclerosis (MS) and evaluating surrogate markers of the disease activity. However, biomarkers may provide more accurate information regarding ongoing immune responses leading to demyelination and treatment effects in MS patients. Although serum biomarkers are easily accessible, they do not provide clear-cut results, whereas cerebrospinal fluid (CSF) biomarkers provide unequivocal information, although samples cannot be repeatedly obtained. For diagnosis, the presence of oligoclonal IgG bands remains important. In addition, measuring the levels of adhesion molecules, matrix metalloproteinase-9 and complement regulator factor H in the serum and evaluating the proportion of Th1/Th2 cells in the blood may be clinically feasible for monitoring the disease activity. In CSF samples, increased IL-8, IL-12, IL-17, CCL3, CCL5 and CXCL10 levels indicate active disease, and the flow cytometry findings of CSF cells can be used to detect increases in Th1 and CD4(+)CD25(+) cells during relapse. Biomarkers closely linked to the disease activity may be informative of the pathogenesis of MS, while those associated with tissue damage or repair may be targets of new treatment strategies. Establishing the latter will be a primary point of research in the near future.	f	\N
24583589	A 76-year-old woman was admitted to our hospital because of convulsions that developed after a 1-month history of progressive right-leg palsy. MRI showed thickening of the meninges with gadolinium enhancement in the left parietal lobe and it revealed pia-subarachnoid space pattern. A lumbar puncture was performed, and cerebrospinal fluid analysis revealed no abnormality. Her serum adenosine deaminase level was elevated (28.7 IU/l). The results of serum cultures were normal. To differentially diagnose collagen disease, infection, malignancy, and inflammation of uncommon causes, we conducted brain and meningeal biopsies on the 15th hospital day. Histopathological examination of the brain tissue showed mainly necrosis and inflammation. There was severe pachymeningeal thickening without necrosis. Although it was difficult to reach a definitive diagnosis, a tissue sample taken from under the leptomeninges tested positive for mycobacterium on Ziehl-Neelsen staining. The results of polymerase chain reaction for mycobacterium were negative in the meningeal tissue. The patient received anti-tuberculous drugs, anti-nontuberculous mycobacteriosis drugs, and corticosteroids to treat Mycobacterium tuberculosis and nontuberculous mycobacterium. After starting treatment, the findings on magnetic resonance imaging improved dramatically, and no convulsions occurred during hospitalization. She was discharged on the 153rd hospital day without any neurological deficit. Because previous studies have reported that isolated mycobacterium meningitis is a diagnostically challenging condition, brain and meningeal biopsies should be considered in patients with gadolinium enhancement in the meninges.	f	\N
24585436	The development of fully automated and high-throughput systems for proteomics is now in demand because of the need to generate new protein-based disease biomarkers. Unfortunately, it is difficult to identify protein biomarkers that are low abundant when in the presence of highly abundant proteins, especially in complex biological samples such as serum, cell lysates, and other biological fluids. Membrane proteins, which are in many cases of low abundance compared to the cytosolic proteins, have various functions and can provide insight into the state of a disease and serve as targets for new drugs making them attractive biomarker candidates. Traditionally, proteins are identified through the use of gel electrophoretic techniques, which are not always suitable for particular protein samples such as membrane proteins. Microfluidics offers the potential as a fully automated platform for the efficient and high-throughput analysis of complex samples, such as membrane proteins, and do so with performance metrics that exceed their bench-top counterparts. In recent years, there have been various improvements to microfluidics and their use for proteomic analysis as reported in the literature. Consequently, this review presents an overview of the traditional proteomic-processing pipelines for membrane proteins and insights into new technological developments with a focus on the applicability of microfluidics for the analysis of membrane proteins. Sample preparation techniques will be discussed in detail and novel interfacing strategies as it relates to MS will be highlighted. Lastly, some general conclusions and future perspectives are presented.	f	\N
24588669	Tumour hypoxia is increasingly recognized as a major deleterious factor in cancer therapies, as it compromises treatment and drives malignant progression. This review seeks to clarify the oxygen levels that are pertinent to this issue. It is argued that normoxia (20% oxygen) is an extremely poor comparator for "physoxia", i.e. the much lower levels of oxygen universally found in normal tissues, which averages about 5% oxygen, and ranges from about 3% to 7.4%. Importantly, it should be recognized that the median oxygenation in untreated tumours is significantly much lower, falling between approximately 0.3% and 4.2% oxygen, with most tumours exhibiting median oxygen levels <2%. This is partially dependent on the tissue of origin, and it is notable that many prostate and pancreatic tumours are profoundly hypoxic. In addition, therapy can induce even further, often unrecognized, changes in tumour oxygenation that may vary longitudinally, increasing or decreasing during treatment in ways that are not always predictable. Studies that fail to take cognizance of the actual physiological levels of oxygen in tissues (approximately 5%) and tumours (approximately 1%) may fail to identify the real circumstances driving tumour response to treatment and/or malignant progression. This can be of particular importance in genetic studies in vitro when comparison to human tumours is required.	f	\N
24590608	Iron is an essential mineral in many proteins and enzymes in human physiology, with limited means of iron elimination to maintain iron balance. Iron accrual incurs various pathological mechanisms linked to cardiovascular disease. In atherosclerosis, iron catalyzes the creation of reactive oxygen free radicals that contribute to lipid modification, which is essential to atheroma formation. Inflammation further fuels iron-related pathologic processes associated with plaque progression. Given iron's role in atherosclerosis development, in vivo detection techniques sensitive iron are needed for translational studies targeting iron for earlier diagnosis and treatment. Magnetic resonance imaging is uniquely able to quantify iron in human tissues noninvasively and without ionizing radiation, offering appealing for longitudinal and interventional studies. Particularly intriguing is iron's complementary biology vs. calcium, which is readily detectable by computed tomography. This review summarizes the role of iron in atherosclerosis with considerable implications for novel diagnostic and therapeutic approaches.	f	\N
24603533	Telomere biology is frequently associated with disease evolution in human cancer and dysfunctional telomeres have been demonstrated to contribute to genetic instability. In BCR-ABL(+) chronic myeloid leukemia (CML), accelerated telomere shortening has been shown to correlate with leukemia progression, risk score and response to treatment. Here, we demonstrate that proliferation of murine CML-like bone marrow cells strongly depends on telomere maintenance. CML-like cells of telomerase knockout mice with critically short telomeres (CML-iG4) are growth retarded and proliferation is terminally stalled by a robust senescent cell cycle arrest. In sharp contrast, CML-like cells with pre-shortened, but not critically short telomere lengths (CML-G2) grew most rapidly and were found to express a specific 'telomere-associated secretory phenotype', comprising secretion of chemokines, interleukins and other growth factors, thereby potentiating oncogene-driven growth. Moreover, conditioned supernatant of CML-G2 cells markedly enhanced proliferation of CML-WT and pre-senescent CML-iG4 cells. Strikingly, a similar inflammatory mRNA expression pattern was found with disease progression from chronic phase to accelerated phase in CML patients. These findings demonstrate that telomere-induced senescence needs to be bypassed by leukemic cells in order to progress to blast crisis and provide a novel mechanism by which telomere shortening may contribute to disease evolution in CML.	f	\N
24610167	The aim of this study was to evaluate the diagnostic accuracy of postnatal multidetector computed tomography (MDCT) compared with prenatal ultrasound (US), surgical findings, and histology, in 33 patients with congenital cystic lung disease. Thirty-three patients, 17 males and 16 females, were evaluated by MDCT. Twenty-seven of these patients underwent prenatal US between week 18 and 22, and between week 32 and 35 of gestation. Lung lobectomy, segmentectomy, atypical resection, lesion resection were performed in 31 patients and surgical specimens were analysed. Prenatal US and MDCT correctly diagnosed 76.9 and 94 % of the lesions, respectively. Disagreement occurred in six lesions with prenatal US and in two lesions with MDCT. No statistically significant differences were observed between the two techniques (P = 0.122). As most surgeons consider the surgical resection of these lesions mandatory, our study underscores the essential role of imaging, in particular CT, in providing invaluable preoperative information on congenital cystic lung diseases recognised in uterus.	f	\N
24611185	To investigate factors associated with 30-day perioperative complications (POC) after aorto-iliac (AI) stenting, and to compare follow-up cardiovascular prognosis between patients with and without POC. This was a retrospective multicenter study. We used a multicenter database of 2012 consecutive patients who successfully underwent AI stenting for peripheral arterial disease in 18 centers in Japan from January 2005 to December 2009 to analyze independent predictors of POC and impact of POC on prognosis by logistic regression and a Cox proportional hazard regression model, respectively. Mean age was 71 ± 9 years (median: 72 years; range: 37-98 years), and 1,636 patients (81%) were men. POC occurred in 126 patients (6.3%). In multivariate logistic regression analysis, old age (≥80 years), critical limb ischemia (CLI), and Trans Atlantic Inter-Societal Consensus (TASC) II class C/D were independently associated with POC with adjusted odds ratios and 95% confidence intervals (CI) of 1.9 (1.3-2.9), 2.3 (1.5-3.4), and 2.4 (1.6-3.4), respectively. Out of 2012 patients, 1995 were followed up for more than 30 days (mean: 2.6 ± 1.5 years; range: 2-2,393 days). In a Cox hazard regression model adjusted for baseline clinical characteristics, POC was positively and independently associated with follow-up major adverse cardiac events (adjusted hazard ratio [HR]: 1.9; 95% CI: 1.3-2.8; p = .002), but not with major adverse limb events and target lesion revascularization (adjusted HR: 1.4; 95% CI: 0.7-2.7; p = .25; and adjusted HR: 1.2; 95% CI 0.6-2.6; p = .568), respectively. Age >80 years, CLI, and TASC C/D lesion were positively associated with POC after AI stenting. Occurrence of POC appears to adversely affect follow-up cardiovascular, but not limb and vessel prognosis.	f	\N
24614649	The microsatellite instability (MSI) pathway is one of the important mutational pathways that play a critical role in colorectal carcinogenesis. About 15% of colorectal cancers (CRCs) are characterized by MSI. MSI tumors usually arise because of a genetic defect in mismatch repair (MMR) genes, one of the main DNA-repairing systems. MMR is a highly conserved biological pathway that plays a key role in maintaining genomic stability by correcting the base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Mutations in at least five pivotal genes of MMR, namely, in those encoding mutS homolog 2 (MSH2), mutL homolog 1 (MLH1), mutS homolog 6 (MSH6), postmeiotic segregation increased 1 (PMS1), and postmeiotic segregation, increased 2 (PMS2) have been found in CRC, highlighting the importance of understanding the basic structure and functions of the essential molecules that make up the MMR system. In this review, we have attempted to focus on this aspect, that is, the role that MMR molecules play in CRC carcinogenesis.	f	\N
24617559	Exaggerated postprandial lipemia has been reported after spinal cord injury (SCI). We examined metabolite and accompanying pro-inflammatory biomarker responses to repeat feeding of typical high-fat meals in individuals with chronic paraplegia. Descriptive trial. Metabolites (triglycerides, glucose, and insulin) and inflammatory biomarkers (interleukin-6 and high-sensitivity C-reactive protein (hsCRP)) were measured under fasting conditions in 11 recreationally active individuals with chronic (>1 year) paraplegia. Subjects received high-fat meals at time point 0 and again at minute 240. Antecubital venous blood was obtained at time points -30 (fasting), 0 (first meal), 30, 60, 90, 120, 240 (second meal), 360, and 480 minutes. Correlations were examined among the study variables. Exploratory subgroup analysis was performed for subjects with levels of postprandial glucose greater than >200 mg/dl. Triglycerides showed a significant rise 4 hours after eating. Basal inflammatory markers were elevated, and did not undergo additional change during the testing. Additionally, subjects with excessive postprandial glucose responses showed higher hsCRP levels than those having typical glucose responses both for fasting (11.8 ± 6.5 vs. 2.9 ± 2.7 mg/l, P = 0.064) and postprandial (11.1 ± 4.9 vs. 3.7 ± 3.8 mg/l, P = 0.018) values. Despite elevations in metabolic response markers, inflammatory markers did not change significantly after consumption of population-representative (i.e. hypercaloric) mixed-nutrient meals. Levels of fasting CRP in the high-risk range are consistent with other reports in persons with SCI and continue to pose concern for their cardiovascular disease risk. The possible association between postprandial metabolic responses and inflammatory states warrants further investigation to identify individual component risks for this secondary health hazard.	f	\N
24619118	The northward spread of leishmaniasis from Mediterranean to Continental Europe affects our area where it is typically associated with Leishmania infantum infection. In this study a 22-year survey was performed in patients (including both patients with and without history of travel through endemic areas other than Italy) attending the University Hospital of Parma, Northern Italy, in order to make a contribution to describe the cases of the visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) diagnosed in this area. One hundred fifty-six samples from 134 patients with clinical suspicion of leishmaniasis (96 suspected of having VL, 37 CL and one both VL and CL) were analyzed in our laboratory during 1992-2013 by microscopy, culture and, from 2005, also by real-time PCR. Leishmania spp. were detected in 23 samples of 15 patients (seven with VL and eight with CL), representing an infection rate of 11.2%. The figure of the cases of leishmaniasis herein reported, even if not comparable to that described for Italian areas other than Parma, underlines that suitable tools are mandatory for correct diagnosis. Moreover, the severity of this disease, particularly VL with its documented northward spread, requires physicians of continental Europe to increase their attention about the possibility of suspecting leishmaniasis in patients reporting related signs and symptoms and/or risk factors.	f	\N
24626438	Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited. Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome. In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.	f	\N
24628295	Imatinib (Glivec(®)/Gleevec(®)) has shown long-term efficacy and safety in randomized trials. No large-scale studies have prospectively assessed the benefit-risk profile of an imatinib copy drug. We prospectively evaluated the response of patients with chronic myeloid leukemia in chronic phase in one institution. Patients with a complete hematologic response (n = 126) switched from branded imatinib to an imatinib copy drug. Subsequently, all patients switched back to the branded imatinib. Many patients in this study had a loss of hematologic response and tolerability issues with the imatinib copy drug. Hematologic response and tolerability improved upon retreatment with branded Glivec.	f	\N
24628740	Pentraxin 3 (PTX3) is probably a specific marker of vascular inflammation. However, associations of PTX3 with cardiovascular disease (CVD) risk have not been well studied in healthy adults or multi-ethnic populations. We examined associations of PTX3 with CVD risk factors, measures of subclinical CVD, coronary artery calcification (CAC) and CVD events in the Multi-Ethnic Study of Atherosclerosis. Two thousand eight hundred and thirty-eight participants free of prevalent CVD with measurements of PTX3 were included in the present study. After adjustment for age, sex, and ethnicity, PTX3 was positively associated with age, obesity, insulin, systolic blood pressure, C-reactive protein (CRP), and carotid intima-media thickness (all P < 0.045). A one standard deviation increase in PTX3 level (1.62 ng mL(-1) ) was associated with the presence of CAC in fully adjusted models including multiple CVD risk factors (relative risk of 1.05; 95% confidence interval [CI] 1.01-1.08). In fully adjusted models, a standard deviation higher level of PTX3 was associated with an increased risk of myocardial infarction (hazard ratio [HR] 1.51; 95% [CI] 1.16-1.97), combined CVD events (HR 1.23; 95% [CI] 1.05-1.45), and combined CHD events (HR 1.33; 95% [CI] 1.10-1.60), but not stroke, CVD-related mortality, or all-cause death. In these apparently healthy adults, PTX3 was associated with CVD risk factors, subclinical CVD, CAC and incident coronary heart disease events independently of CRP and CVD risk factors. These results support the hypothesis that PTX3 reflects different aspects of inflammation than CRP, and may provide additional insights into the development and progression of atherosclerosis.	f	\N
24631511	The aim of this study was to report the frequency, patient and lesion-related characteristics, and outcomes of subclinical, nonculprit plaque ruptures in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Plaque rupture and subsequent thrombosis is the most common cause of acute coronary syndrome (ACS). Secondary, subclinical, nonculprit plaque ruptures have been seen in both stable patients and patients with ACS; however, reports of the natural history of these secondary plaque ruptures are limited. After successful stenting in 697 patients with ACS, 3-vessel grayscale and intravascular ultrasound virtual histology (IVUS-VH) was performed in the proximal-mid segments of all 3 coronary arteries as part of a prospective multicenter study. Among 660 patients with complete IVUS data, 128 plaque ruptures were identified in 105 nonculprit lesions in 100 arteries from 93 patients (14.1%). Although the minimum lumen area (MLA) was similar, the plaque burden was significantly greater in nonculprit lesions with a plaque rupture compared with nonculprit lesions without a plaque rupture (66.0% [95% confidence interval: 64.5% to 67.4%] vs. 56.0% [95% confidence interval: 55.6% to 56.4%]; p < 0.0001). IVUS-VH analysis revealed that a nonculprit lesion with a plaque rupture was more often classified as a fibroatheroma than a nonculprit lesion without a plaque rupture (77.1% vs. 51.4%; p < 0.0001). Independent predictors of a plaque rupture were lesion length (per 10 mm; odds ratio: 1.30; p < 0.0001), plaque burden at the MLA site (per 10%; odds ratio: 2.56; p < 0.0001), vessel area at the MLA site (per 1 mm(2); odds ratio: 1.13; p < 0.0001), and VH-thin-cap fibroatheroma (odds ratio: 1.80; p = 0.016). During 3 years of follow-up, the incidence of overall major adverse cardiac events did not differ significantly between the patients with and patients without subclinical, nonculprit plaque ruptures. Secondary, nonculprit plaque ruptures were seen in 14% of patients with ACS and were associated with a fibroatheroma phenotype with a residual necrotic core but not with adverse outcomes if patients were treated with optimal medical therapy as part of a multicenter study. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree [PROSPECT]; NCT00180466).	f	\N
24634197	The redox-active transition metal copper is an essential trace element for growth and development and serves as a structural or catalytic cofactor for many enzymes in a range of physiological processes. Mammalian copper homeostasis is tightly regulated, and an imbalance in copper metabolism is implicated in various pathological disorders. Radioactive copper isotopes, in particular (64) Cu (t1/2  = 12.7 h) and (67) Cu (t1/2  = 62.01 h), have made important contributions to the understanding of copper metabolism in health and disease. This review gives a brief account of how radiolabelled copper(II) salts and bioreductive copper complexes have been used to trace copper uptake, transport and efflux in vitro and in vivo. Recently, positron emission tomography (PET) has emerged as a noninvasive tool to image copper metabolism in living subjects and (64) Cu-PET is investigated for the study of copper-related neurological disorders, genetic diseases and cancer.	f	\N
24642005	Every year about 2500 patients in Sweden undergo surgery due to heart valve disease. A mechanical heart valve prosthesis causes risk of thromboembolic stroke or thrombus formation in the valve while anticoagulant treatment increases the risk of bleeding. Treatment quality with warfarin is crucial for patients with mechanical valve prostheses. It has previously been shown that poorly controlled warfarin treatment increases mortality in this patient group. TTR (Time in Therapeutic Range) on warfarin has been shown to affect the risk of complications in atrial fibrillation, but has not been studied in patients with mechanical heart valves. Our aim is to evaluate the impact of TTR on the risk of complications in this patient group. A non-randomized, prospective study of 534 adults with mechanical heart valve prostheses from Malmö and Sundsvall registered in the Swedish National Quality Registry Auricula between 01.01.2008 and 31.12.2011. Quartiles regarding individual TTR levels were compared regarding risk of complications. The risk of complications was significantly higher at lower TTR levels for all complications (p=0.005), bleeding (p=0.01) and death (p=0.018) but not for thromboembolism. In multivariate analysis the risk was significantly increased at lower TTR levels for bleeding and all complications but not for death or thromboembolism. Patients with a lower warfarin treatment quality measured by TTR have a higher risk of complications such as severe bleeding or death. A TTR of 83% or higher at the individual level should be obtained for best outcome.	f	\N
24653575	There are various models of health care, such as the epidemiological, psychosocial, sociological, economic, systemic of Neuman, cognitive medicine or ecological, ayurvedic, supraparadigmatic among others. All of them are seeking to combine one or more elements to integrate a model of health care. The article presents a systemic approach to health care with complementary medicines such as rehabilitative acupuncture, homeopathy and chiropractic through the application of a method of holistic care and integrated approach. There was a participatory action research in January 2012 to January 2013, with a comprehensive approach in 64 patients using the clinical method. We included the environmental aspects, biological, emotional, and behavioral to identify, recognize and integrate the form of manifestation of the disease. Later, it was ordered in a coherent way the etiologic factors, precipitating factors and identified the vulnerability of the patients as well as the structural alterations, classifying them in immediate, mediate and late. Referred to the three disciplines: rehabilitative acupuncture, homeopathy and chiropractic to be seen doing references and against-references between them, evaluating the current state of health and each meeting by noting the clinical and behavioral changes submitted and thus the area of attention to which would be forwarded to continue their treatment. 64 patients rotated by the 3 areas taking an average of 30 meetings with rehabilitative acupuncture, 12 with homeopathy and 10 with chiropractic. The changes were submitted clinical attitudinal, behavioral, clinical and organic. The model of care was multifaceted and interdisciplinary with a therapeutic approach of individualization and a holistic view to carry out a comprehensive diagnosis and provide quality health care to the population.	f	\N
24654676	To identify the frequency of disc hyperfluorescence, and to use optical coherence tomography to look for vitreopapillary traction as a possible underlying cause. Eight patients with presumed Fuchs uveitis syndrome were included. A complete ocular examination, fundus fluorescein angiography, and spectral-domain optical coherence tomography for optic nerve head were performed. There were 4 males and 4 female patients, and the mean age at diagnosis was 41.7 years. The most common ocular symptom was floaters (5/9). The range of initial visual acuity was 6/5-6/12. The most frequent clinical sign was inflammatory cells in the anterior chamber (9/9). Fundus fluorescein angiography showed disc hyperfluorescence in all but 1 patient. Optical coherence tomography did not show evidence of vitreopapillary traction in all eyes but one eye. We think that the high frequency of disc hyperfluorescence on fundus fluorescein angiography is an indication of an inflammatory process rather than a mechanical one.	f	\N
24655021	Gliomas are highly vascular and rich in VEGF, which promotes angiogenesis. Bevacizumab is a monoclonal antibody against VEGF, inhibiting angiogenesis by preventing receptor activation. Early Phase II clinical trials using bevacizumab in both newly diagnosed and recurrent high-grade gliomas (HGG) showed promising results, but these have not been confirmed in recent Phase III trials. This review is an update including recently reported Phase II and III study results. This is a review of clinical trials investigating bevacizumab in newly diagnosed and recurrent HGG with a focus on outcome results. A future perspective about the expected future role of bevacizumab is given. Bevacizumab efficacy, safety and tolerability, the combination of radiation and bevacizumab, as well as the use of bevacizumab to treat pseudoprogression are discussed. Further criteria of response evaluation needed to be adjusted in the age of antiangiogenic therapy are also discussed. Bevacizumab has been shown to be safe and tolerable in HGG. In the recurrent disease setting, bevacizumab might offer clinical benefits and is currently approved as a single agent for this indication. Although clinical trials demonstrate a prolonged progression-free survival (PFS) in bevacizumab-treated HGG, a benefit on overall survival has not been demonstrated. Research so far shows that bevacizumab appears to prolong PFS in newly diagnosed glioblastoma. Available data do not demonstrate a survival benefit in newly diagnosed patients. In the recurrent setting, there is no adequately powered randomized clinical trial to address whether there is a PFS or survival benefit with bevacizumab. Bevacizumab has also been introduced into other settings in neuro-oncology, including concurrent administration with re-irradiation for recurrent HGG.	f	\N
24659875	Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide, and alterations of glucose metabolism have reached pandemic proportions in western countries. However, the frequent coexistence between these two conditions is more than simply coincidental, since HCV can induce insulin resistance through several mechanisms. Indeed, the virus interferes with insulin signaling both directly and indirectly, inducing the production of pro-inflammatory cytokines. Furthermore, the entire viral life cycle has strict interconnections with lipid metabolism, and HCV is responsible for a "viral" steatosis which is frequently superimposed to a "metabolic" one. Several evidences suggest that HCV-induced metabolic disorders contribute both to the evolution of liver fibrosis and, likely, to the progression of the other disorders which are typically associated with altered metabolism, in particular atherosclerosis. In the present review, we will examine in depth the links between HCV infection and insulin resistance, liver steatosis and diabetes, and analyze the impact of these interactions on the progression of liver fibrosis and atherosclerosis. Special attention will be focused on the highly debated topic of the relationship between HCV infection and cardiovascular disease. The available clinical literature on this item will be broadly reviewed and all the mechanisms possibly implied will be discussed.	f	\N
24669569	Nasopharyngeal carcinoma (NPC) has the propensity to develop distant metastases at a high rate and with poor prognosis. The metastatic sites are usually multifocal and involve the bones, lungs, liver and distant lymph nodes. The management of metastatic disease is essenti- ally palliative and is based on radiochemotherapy. A 50-year old man with a huge hematoma in the liver derived from a diagnosed NPC was treated with intermittent drainage of the hepatic hematoma for abdominal decompression, and the cavity was packed with omentum. In addition, 2 suspected metastatic lesions were excised. Neoadjuvant radiochemotherapy followed by concurrent chemotherapy was administered. After surgical treatment of the huge hematoma, the suspect sites in the liver were diagnosed as metastatic carcinoma, similar to the primary tumor. Several months later, bone metastatic lesions in the vertebra and oss iliaca dextra were detected due to distant metastasis. Treatment of metastatic NPC is essentially palliative and survival is usually poor.	f	\N
24670466	To evaluate the feasibility of monitoring clopidogrel resistance with flow cytometric analysis of platelet vasodilator stimulated phosphoprotein (VASP) phosphorylation. Twenty patients with coronary heart disease (CHD) and 17 healthy volunteers were examined for platelet aggregation rate and phosphorylation of VASP (calculated as platelet reactivity index, PRI) using traditional optical nephelometry and flow cytometry before and after concurrent therapy of clopidogrel and aspirin. No significant differences were found in PRI between CHD group and healthy control group [(89.45∓5.22)% vs (86.58∓4.35)%] before treatment. The PRI in CHD group was significantly lowered after treatment to (67.66∓19.77)% (P<0.05). Clopidogrel resistance was found in 6 (30%) cases in CHD group by flow cytometric analysis, which showed a higher sensitivity than optical nephelometry (10%). Flow cytometric analysis of VASP phosphorylation is a more reliable test to specifically evaluate clopidogrel resistance.	f	\N
24670932	The second leading cause of cancer-related deaths (both genders combined) in the United States is colorectal cancer (CRC). This emphasizes the need to develop both effective therapies for CRC patients and pre-clinical models mimicking human disease that carry translational potential in drug-development. Notably, at present there are no in situ models of CRC metastasis to lung. In our azoxymethane-induced colon tumorigenesis study in A/J mice assessing grape seed extract (GSE) efficacy, during necropsy we also found multiple lung nodules suggestive of colon tumor metastasis to lung that were significantly inhibited in GSE fed group. Both histopathological and molecular studies were performed to characterize and establish the origin of these lesions in lung. Histologically these nodules were determined as adenocarcinoma of mucin origin. Molecular analyses by immunohistochemistry (IHC) and RT-PCR revealed strong protein and transcript levels of colon specific markers CDX2 and CK20 in these lung nodules compared to uninvolved control lung tissue. Vis-à-vis, these nodules also showed minimally expressed lung specific biomarkers, specifically surfactant D and TTF-1, in IHC analysis. Additionally, 0.25% GSE supplementation in diet (w/w) decreased the incidence of these lung nodules by 53% and their total number by 66%. Together, the characterization of this unique in situ mouse model of CRC metastasis to lung provides translational opportunities in developing effective therapies to clinically manage and treat CRC at the advanced stage. Moreover, GSE efficacy in inhibiting CRC metastasis to lung in this model further supports its translational potential in controlling CRC growth, progression and metastasis in patients.	f	\N
24671083	Determining the composition and function of subgingival dental plaque is crucial to understanding human periodontal health and disease, but it is challenging because of the complexity of the interactions between human microbiomes and human body. Here, we examined the phylogenetic and functional gene differences between periodontal and healthy individuals using MiSeq sequencing of 16S rRNA gene amplicons and a specific functional gene array (a combination of GeoChip 4.0 for biogeochemical processes and HuMiChip 1.0 for human microbiomes). Our analyses indicated that the phylogenetic and functional gene structure of the oral microbiomes were distinctly different between periodontal and healthy groups. Also, 16S rRNA gene sequencing analysis indicated that 39 genera were significantly different between healthy and periodontitis groups, and Fusobacterium, Porphyromonas, Treponema, Filifactor, Eubacterium, Tannerella, Hallella, Parvimonas, Peptostreptococcus and Catonella showed higher relative abundances in the periodontitis group. In addition, functional gene array data showed that a lower gene number but higher signal intensity of major genes existed in periodontitis, and a variety of genes involved in virulence factors, amino acid metabolism and glycosaminoglycan and pyrimidine degradation were enriched in periodontitis, suggesting their potential importance in periodontal pathogenesis. However, the genes involved in amino acid synthesis and pyrimidine synthesis exhibited a significantly lower relative abundance compared with healthy group. Overall, this study provides new insights into our understanding of phylogenetic and functional gene structure of subgingival microbial communities of periodontal patients and their importance in pathogenesis of periodontitis.	f	\N
24674299	Erdheim-Chester disease is a rare systemic disease. The diagnosis is difficult due to significant clinical and morphological polymorphism. Orbital involvement is rare, but constitutes a classic means of detection. We report the case of a 60-year-old man, who consulted for evaluation of bilateral retro-orbital tumors. These tumors had been discovered on head CT two years previously during work-up of proptosis. Two biopsies were performed. The first one revealed polymorphous inflammatory tissue. The second one revealed intense granulomatous reaction, rich in non-specific foamy histiocytes. Thoracic-abdominal-pelvic CT scan detected peri-aortic and retroperitoneal infiltration. The association of these signs pointed to a diagnosis of Erdheim-Chester disease, confirmed by the re-examination of the histological samples. Erdheim-Chester disease is a rare non-Langerhans histiocytosis with a specific tropism for perivascular and fatty connective tissue. The cause is not known. The diagnosis of this systemic disease is histological. In the case of bilateral intra-orbital tumors, the diagnosis of Erdheim-Chester disease must be considered.	f	\N
24674770	Excessive daytime sleepiness (EDS) is common in Parkinson's Disease (PD). Actigraphy uses periods of immobility as surrogate markers of nighttime sleep but there are no examples of its use in assessing EDS of PD. A commercial wrist worn system for measuring bradykinesia and dyskinesia also detects 2 min periods of immobility, which have a 85.2% concordance with the detection of sleep by ambulatory daytime polysomnography, (p < 0.0001 Chi Squared). High Epworth Sleepiness Scores (ESS) were associated with a proportion of time immobile (PTI) (p = 0.01 Mann-Whitney U). The median PTI between 0900 and 1800 h w in 30 age matched control subjects was 2%, representing 10 min and PTI at or above the 75th percentile (5% or 27 min) was taken as a high level. PD patients had higher PTI (median 4.8%) than controls (p < 0.0001, Mann-Whitney U). PD subjects with a high PTI had more bradykinesia, less dyskinesia and higher PDQ39 scores than those with low PTI. There was no relationship between PTI and dose or type of PD medications. However, in 53% of subjects, PTI increased in the 30-60 min after levodopa confirming that in some subjects levodopa results in increased sleepiness. In summary, immobility is a surrogate marker of daytime sleep in PD, confirmed by correlation with PSG and ESS. PD subjects measured this way are more likely to be sleepy and sleepy PD subjects are more likely to be bradykinetic and have a higher PDQ39. Levodopa leads to an increase in sleepiness in more than half of subjects post dosing.	f	\N
24677192	Donor factors influence hepatitis C virus (HCV) disease severity in liver transplant (LT) recipients. Living donors, because they are typically young and have short cold ischemic times, may be advantageous for HCV-infected patients. Among HCV-infected patients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) surviving >90 days and followed for a median 4.7 years, advanced fibrosis (Ishak stage ≥3) and graft loss were determined. The 5-year cumulative risk of advanced fibrosis was 44% and 37% in living donor LT (LDLT) and deceased donor LT (DDLT) patients (P = 0.16), respectively. Aspartate aminotransferase (AST) activity at LT (hazard ratio [HR] = 1.38 for doubling of AST, P = 0.005) and biliary strictures (HR = 2.68, P = 0.0001) were associated with advanced fibrosis, but LDLT was not (HR = 1.11, 95% confidence interval [CI] 0.73-1.69, P = 0.63). The 5-year unadjusted patient and graft survival probabilities were 79% and 78% in LDLT, and 77% and 75% in DDLT (P = 0.43 and 0.32), with 27% and 20% of LDLT and DDLT graft losses due to HCV (P = 0.45). Biliary strictures (HR = 2.25, P = 0.0006), creatinine at LT (HR = 1.74 for doubling of creatinine, P = 0.0004), and AST at LT (HR = 1.36 for doubling of AST, P = 0.004) were associated with graft loss, but LDLT was not (HR = 0.76, 95% CI: 0.49-1.18, P = 0.23). Donor type does not affect the probability of advanced fibrosis or patient and graft survival in HCV-infected recipients. Thus, while LDLT offers the advantage of shorter wait times, there is no apparent benefit for HCV disease progression. Biliary strictures have a negative effect on HCV fibrosis severity and graft survival, and a high AST at LT may be an important predictor of fibrosis risk post-LT.	f	\N
24684672	Rheumatoid arthritis (RA) is an autoimmune disease of unknown cause and a chronic and progressive inflammatory disorder ensuing in genetically predisposed subjects, characterized by synovitis causing joint destruction, as well as inflammation in body organ systems, leading to anatomical alteration and functional disability. Immune competent cells, deregulated synoviocytes and cytokines play a key role in the pathophysiological mechanisms. The immune system function shows time-related variations related to the influence of the neuroendocrine system and driven by the circadian clock circuitry. Immune processes and symptom intensity in RA are characterized by oscillations during the day following a pattern of circadian rhythmicity. A cross-talk between inflammatory and circadian pathways is involved in RA pathogenesis and underlies the mutual actions of disruption of the circadian clock circuitry on immune system function as well as of inflammation on the function of the biological clock. Modulation of molecular processes and humoral factors mediating in RA the interplay between the biological clock and the immune response and underlying the rhythmic fluctuations of pathogenic processes and symptomatology could represent a promising therapeutic strategy in the future.	f	\N
24685603	The effects of thymidylate synthase (TS) polymorphisms on susceptibility to colorectal cancer (CRC) have been investigated in many studies, but the results remain conflicting rather than conclusive. To resolve these conflicts, we performed a quantitative synthesis of the evidence on the association between these two polymorphisms and CRC risk. All eligible case-control studies published up to September 2013 were identified by searching PubMed, Web of Science and CNKI. Effect sizes of odds ratio (OR) and 95% confidence interval (95% CI) were calculated by using a fixed- or random-effect model. A total of 11 case-control studies were included, including 10 studies (3324 cases and 4622 controls) for TSER polymorphism and 9 studies (3223 cases and 3886 controls) for TS1494del6 polymorphism. Overall, no significant association between the TS polymorphisms and CRC risk was found. In the subgroup analysis by ethnicity, a significantly association were found among Caucasian populations for TSER polymorphism; but for TS1494del6 polymorphism, no significantly association was observed in both Asian and Caucasian populations. When stratifying by source of controls, we found there was a statistically significant association between TSER polymorphism and risk of CRC in the population-based population; however, we detected no association in both population-based and hospital-based populations for TS1494del6 polymorphism. This meta-analysis suggests that the TSER polymorphism in TS gene but not TS1494del6 polymorphism might be a protective factor for CRC among Caucasian populations.	f	\N
24713244	To study the expression and clinicopathologic significance of cancer stem cell markers CD44v6 and CD24 in ovarian serous carcinoma tissues. One hundred and two cases of ovarian carcinoma diagnosed during the period from June, 2001 to December, 2010 were retrieved from archival files. The histology slides were reviewed and a two-tier system for grading of ovarian serous carcinoma was applied. The expression of CD44v6 and CD24 was detected by immunohistochemistry using EnVision method. The relationship between CD44v6/CD24 expression and various clinicopathologic parameters was analyzed. There were 46.1% (47/102) and 59.8% (61/102) cases expressing CD44v6 and CD24, respectively. Both CD44v6 and CD24 expression showed positive correlation with higher histopathologic grade (P = 0.003 and P < 0.05, respectively). CD24 expression also correlated with the presence of lymph node metastasis (P < 0.05). There was no statistically significant relationship between the expression of these two markers (χ(2) = 0.394, P = 0.530). The age of the patients, histopathologic grade, clinical stage and nodal status correlated with progression-free survival time (P < 0.05). CD44v6 expression and histopathologic grade correlated with the overall survival time (P < 0.05). Patient age was an independent poor prognostic factor by multivariate analysis. CD44v6 expression, age older than 50 years, high clinical stage and presence of lymph node metastasis are associated with poor prognosis in patients with ovarian serous carcinoma. The two-tier system for grading of ovarian serous carcinoma is useful in predicting survival; and high tumor grade represents an important poor prognostic indicator for ovarian serous carcinoma.	f	\N
24713591	High-density-lipoprotein cholesterol (HDL-C) has been identified in population studies as an independent inverse predictor of cardiovascular events. Although the causal nature of this association has been questioned, HDL and its major protein, apolipoprotein (apo)A1, have been shown to prevent and reverse atherosclerosis in animal models. In addition, HDL and apoA1 have several putatively atheroprotective functions, such as the ability to promote efflux of cholesterol from macrophages in the artery wall, inhibit vascular inflammation, and enhance endothelial function. Therefore, HDL-C and apoA1 have been investigated as therapeutic targets for coronary heart disease. However, recent clinical trials with drugs that raise HDL-C, such as niacin and inhibitors of cholesteryl ester transfer protein, have been disappointing. Here, we review the current state of the science regarding HDL as a therapeutic target.	f	\N
24715127	The objective of this study was to evaluate the 25-year outcome of patients with primary Sjögren's syndrome (pSS). One hundred and fifty-two patients diagnosed with pSS (American-European classification criteria) were retrospectively and descriptively analysed (1986-2011). Of all 152 patients, 55.9% were alive, 18.4% had died and 25.7% discontinued follow-up (mostly due to old age). Malignancy affected 28.3% and non-Hodgkin's lymphoma (NHL) affected 10.5%. The adjusted risk for development of NHL was an odds ratio (OR) of 10.5 (95% confidence interval [CI]: 3.05-36.42) in patients with vasculitis (p<0.001), and OR 3.4 (95% CI 1.05-11.2) in the presence of glandular complications (parotid swelling, lymphadenopathy) (p < 0.041). Seventy-five patients (49.3%) developed other autoimmune diseases (autoimmune thyroid disease [15.8%], pulmonary fibrosis [7.2%] and vasculitis [10.5%]). Although the course of pSS is relatively benign, over 25 years patients experience more clinical complications than previously described. In addition, vasculitis and glandular manifestations were significant predictors for NHL.	f	\N
24720286	There is currently no cure for metastatic castration-resistant prostate cancer (CRPC). Chemoresistance and metastatic disease remain the main causes of treatment failure and mortality in CaP patients. Although several advances have been made in the control of CRPC with some newly developed drugs, there is still an urgent need to investigate the mechanisms and pathways of prostate cancer (CaP) metastasis and chemoresistance, identify useful therapeutic targets, develop novel treatment approaches, improve current therapeutic modalities and increase patients' survival. Cancer stem cells (CSCs), a minority population of cancer cells characterised by self-renewal and tumor initiation, have gained intense attention as they not only play a crucial role in cancer recurrence but also contribute substantially to chemoresistance. As such, a number of mechanisms in chemoresistance have been identified to be associated with CSCs. Therefore, a thorough and integral understanding of these mechanisms can identify novel biomarkers and develop innovative therapeutic strategies for CaP treatment. Our recent data have demonstrated CSCs are associated with CaP chemosensitivity. In this review, we discuss the roles of putative CSC markers in CaP chemoresistance and elucidate several CSC-associated signaling pathways such as PI3K/Akt/mTOR, Wnt/β-catenin and Notch pathways in the regulation of CaP chemoresistance. Moreover, we will summarize emerging and innovative approaches for the treatment of CRPC and address the challenging CRPC that is driven by CSCs. Understanding the link between CSCs and metastatic CRPC will facilitate the development of novel therapeutic approaches to overcome chemoresistance and improve the clinical outcomes of CaP patients.	f	\N
24723322	The mitochondrial toxin 3-nitropropionic acid (3-NP) is an irreversible inhibitor of respiratory chain complex II. Chronic systemic administration of 3-NP to mice, rats, and non-human primates leads to preferential degeneration of the striatum, and produces motor and cognitive symptoms that are highly reminiscent of Huntington's disease (HD). HD is caused by a dominant inherited expansion of CAG repeats in the Huntington gene. Thus, many aspects of HD cannot be mimicked by 3-NP. However, recent research shows that mitochondrial defects and oxidative stress may play a key role in HD pathogenesis, further supporting the potential utility of the 3-NP model of striatal degeneration. First, a basic protocol to produce acute striatal lesions in rats using repeated intraperitoneal injection of 3-NP is described. Second, a more complex protocol that takes advantage of the use of osmotic minipumps to steadily release 3-NP leading to consistent lesions and motor symptoms in Lewis rats is presented. Curr. Protoc. Neurosci. 67:9.48.1-9.48.14. © 2014 by John Wiley & Sons, Inc.	f	\N
24725410	Maintenance of a constant cell volume in response to extracellular or intracellular osmotic changes is critical for cellular homeostasis. Activation of a ubiquitous volume-regulated anion channel (VRAC) plays a key role in this process; however, its molecular identity in vertebrates remains unknown. Here, we used a cell-based fluorescence assay and performed a genome-wide RNAi screen to find components of VRAC. We identified SWELL1 (LRRC8A), a member of a four-transmembrane protein family with unknown function, as essential for hypotonicity-induced iodide influx. SWELL1 is localized to the plasma membrane, and its knockdown dramatically reduces endogenous VRAC currents and regulatory cell volume decrease in various cell types. Furthermore, point mutations in SWELL1 cause a significant change in VRAC anion selectivity, demonstrating that SWELL1 is an essential VRAC component. These findings enable further molecular characterization of the VRAC channel complex and genetic studies for understanding the function of VRAC in normal physiology and disease.	f	\N
24726273	Central obesity represents the major factor responsible for NAFLD, but several immunological and endocrinological mechanisms are involved in fatty infiltration in the liver, inflammation and fibrosis. Gut microbiota and genetic factors were recently indicated as major players in liver injury. Loss of weight and physical activity represent till now the cornerstone of treatment, but they are very difficult to obtain and to maintain. Several pharamocotherapeutic approaches including insulin sensitizers, omega-3 fatty acids and vitamin E have been extensively studied in randomized trials, but final conclusions still could not be formulated. Therefore, new treatments based on pathogenetic mechanisms leading to NAFLD are under evaluation to establish the effective pharmacological therapy of this disorder.	f	\N
24734429	In 2013 the main efforts of the Medical Service were aimed at the following tasks: optimization of management system of military medical service, improvement of medical evacuation system, medical service security for military contingents, assigned according to territory principle to military-medical facilities of the Ministry of Defence of the Russian Federation, implementation of innovations at all stages of medical evacuation in peace- and wartime, security of combat and mobilization readiness of regulatory bodies of the Medical Service, medical military units and military medical facilities, medical service of troops battle training, improvement of material and technical resources, security of regular pharmacy and equipment supply, activation of research work in the Medical Service interests. Lines of military medicine development in 2014 are: transfer of treatment facilities that are not used by the Ministry of Defence into the Federal Biomedical Agency till the end of 2014, prevention of pneumonia and meningitis in military personnel, improvement of early diagnosis system, medical service for military contingents according to territory principle, improvement of diagnostic and treatment work in military-medical units and subunits and military-medical facilities by means of development of material and technical resources, monitor the implementation of innovative diagnostic and treatment technologies, completion of construction projects of central military hospitals and etc.	f	\N
24744504	Consumption of tomato fruits, like those of many other plant species that are part of the human diet, is considered to be associated with several positive effects on health. Indeed, tomato fruits are an important source of bioactive compounds with known beneficial effects including vitamins, antioxidants, and anticancer substances. In particular, antioxidant metabolites are a group of vitamins, carotenoids, phenolic compounds, and phenolic acid that can provide effective protection by neutralizing free radicals, which are unstable molecules linked to the development of a number of degenerative diseases and conditions. In this review, we will summarize the recent progress on tomatoes nutritional importance and mechanisms of action of different phytochemicals against inflammation processes and prevention of chronic noncommunicable diseases (e.g., obesity, diabetes, coronary heart disease, and hypertension). In addition, we will summarize the significant progress recently made to improve the nutritional quality of tomato fruits through metabolic engineering and/or breeding.	f	\N
24748016	Food allergy is a common condition that plays an important role in the pathogenicity and maintenance of atopic dermatitis (AD), however, must be carefully investigated before imposing a restrictive diet. The aim of this study was to evaluate the sensitivity to foods in patients with AD, correlating it with the severity of the disease and other possible associated factors. One hundred and eleven children (6-180 months of age) with AD were evaluated and later followed up at the Allergy and Clinical Immunology Division, Department of Pediatrics at FMABC. The serum concentrations of specific IgE to cow's milk (CM), egg, soy, wheat, corn, peanut and fish were measured using an enzymatic fluorescence method (ImmunoCAP™). In order to identify the clinical reactivity, the open oral provocation test was performed when specific IgE was positive to CM, egg and wheat and in all those who related symptoms after the intake of such foods regardless of the presence or absence of sensitization. In total, 40.5 % of the studied population was sensitized to at least one food allergen, especially those between 73 and 180 months of age. There was a higher prevalence of sensitization in children with more severe AD, and foods like CM, egg and wheat were the most involved, but with low clinical reactivity. We observed increased severity of AD in cases that initiated symptoms earlier and who had shorter duration of exclusive breastfeeding as well as a linear increase in sensitization in the most serious cases. Serum-specific immunoglobulin E was the only factor associated with the relationship that showed sensitization. The occurrence of sensitization to foods was frequent, mainly in the age group of 6-9 years and in patients with severe AD; however, the validation of the clinical reactivity was negative in most of the provocations performed, which agrees with the need to prove the same before the imposition of restrictive diets, often unnecessary and complex.	f	\N
24748137	This report describes the case of a 44-year-old Caucasian woman of Northern European descent with a medical history of pyoderma gangrenosum, chronic abdominal pain and erythema nodosum which required intermittent use of high-dose steroids that failed to improve her symptoms. The patient was initially diagnosed with Crohn's disease and most recently with sclerosing mesenteritis. She presented to the hospital with worsening abdominal pain. She was found to have recurrent painful aphthous oral, genital and perianal ulcers and a clinical diagnosis of Behçet's disease was made. Her hospitalisation was complicated by haemoptysis, and bronchoscopy revealed alveolar haemorrhage. Treatment was initiated with three days of pulse intravenous solumedrol 1 g/day and cyclophosphamide at 700 mg/m(2). The case had a favourable outcome despite the initial diagnostic challenges. This report emphasises that systemic diseases, including Behçet's disease, can have variable presentations and can be frequently misdiagnosed.	f	\N
24751894	Both the diagnosis and treatment of Mycoplasma pneumoniae infections in children are currently facing two main challenges: a relatively high carriage in asymptomatic children, and a worldwide increase in macrolide-resistant M. pneumoniae (MRMP). This review focuses on the scientific and clinical implications of these crucial issues. Recent studies have indicated that the prevalence of M. pneumoniae in the upper respiratory tract is similar among asymptomatic, healthy children and children with a symptomatic respiratory tract infection, and that current diagnostic procedures for M. pneumoniae are unable to differentiate between bacterial carriage and infection. It is therefore possible that the burden of M. pneumoniae-associated disease is overestimated. Another phenomenon that has an important impact on the treatment of M. pneumoniae infections is the rapid worldwide emergence of MRMP isolates. The current diagnostic procedures for M. pneumoniae cannot discern between bacterial carriage and infection in a clinically relevant time frame. It is therefore imperative that these procedures be modified such as to unambiguously detect symptomatic M. pneumoniae infections. Moreover, the emergence of MRMP necessitates the application of methods to detect macrolide resistance as well as the implementation of restrictive policies regarding the use of macrolides.	f	\N
24763465	Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity. As the population ages and the prevalence of AF continues to rise, the socioeconomic consequences of AF will become increasingly burdensome. Although there are well-defined clinical risk factors for AF, a significant heritable component is also recognized. To identify the molecular basis for the heritability of AF, investigators have used a combination of classical Mendelian genetics, candidate gene screening, and genome-wide association studies. However, these avenues have, as yet, failed to define the majority of the heritability of AF. The goal of this review is to describe the results from both candidate gene and genome-wide studies, as well as to outline potential future avenues for creating a more complete understanding of AF genetics. Ultimately, a more comprehensive view of the genetic underpinnings for AF will lead to the identification of novel molecular pathways and improved risk prediction of this complex arrhythmia.	f	\N
24782446	We aimed to evaluate whether a recent knee injury was associated with accelerated knee osteoarthritis (OA) progression. In the Osteoarthritis Initiative, we studied participants free of knee OA on their baseline radiographs (Kellgren/Lawrence [K/L] <2). We compared 3 groups as follows: 1) individuals with accelerated progression of knee OA: defined as having at least 1 knee that progressed to end-stage knee OA (K/L grade 3 or 4) within 48 months, 2) common knee OA progression: at least 1 knee increased in radiographic scoring within 48 months (excluding those defined as accelerated knee OA), and 3) no knee OA: no change in K/L grade in either knee. At baseline, participants were asked if their knees had ever been injured, and at each annual visit they were asked about injuries during the prior 12 months. We used multinomial logistic regressions to determine whether a new knee injury was associated with the outcome of accelerated knee OA or common knee OA progression, after adjusting for age, sex, body mass index, static knee malalignment, and systolic blood pressure. A knee injury during the total observation period was associated with accelerated knee OA progression (n = 54; odds ratio [OR] 3.14) but not common knee OA progression (n = 187; OR 1.08). Furthermore, a more recent knee injury (within a year of the outcome) was associated with accelerated (OR 8.46) and common knee OA progression (OR 3.12). Recent knee injuries are associated with accelerated knee OA. Most concerning is that certain injuries may be associated with a rapid cascade toward joint failure in less than 1 year.	f	\N
24783461	Patients with established rheumatoid arthritis (RA) have a higher cardiovascular morbidity and mortality in comparison with the general population. It is considered to be an independent risk factor for cardiovascular disease. The purpose of this article is to describe the mechanisms responsible for accelerated atherogenesis in RA patients and to give an overview of the effects of different RA therapies (methotrexate, TNF antagonists and other biologicals).	f	\N
24800540	To analyze the clinical features and treatment of tuberculous otitis media and mastoiditis. Thirteen patients with tuberculous otitis media and mastoiditis were retrospectively analyzed and the related literatures were reviewed. One case was treated by surgery only, and anti-tuberculosis treatment was given to another one patient, and surgical removal of disease lesions in combination with anti-tuberculosis treatment were given to 12 patients. One patient received surgery only was found to recur after follow-up for seven months. The patient did not recur after seven months' follow-up after antituberculosis therapy,and other patients did not recur. Although the regular anti-tuberculosis chemotherapy treatment was the main treatment for tuberculous otitis and mastoiditis, surgical treatment was helpful to achieved more rapid healing of the ear.	f	\N
24804836	Non-melanoma skin cancers (NMSCs) are among the most common human malignancies. Current methods for their prevention include avoidance of natural and artificial sources of UV radiation and using photoprotective clothing and sunscreens. However, these methods have proven to be inadequate in stemming the rise in skin cancer incidence over the past several years. There is accumulating evidence that cyclooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis, may be involved in the pathogenesis of NMSC. In preclinical studies, animals genetically deficient in the COX-2 enzyme or that have been treated with pharmacological inhibitors of COX-2 develop significantly fewer tumors when subjected to a UV-induced skin carcinogenesis protocol compared with control mice. Several epidemiological studies in humans support the concept that this enzyme is intimately involved in UV-induced skin cancer development, and UV radiation is known to augment COX-2 expression in human skin. Recent studies suggest that drugs that block COX-2 expression may prevent the development of NMSCs. Thus, pharmacologic agents that inhibit the enzyme COX-2 may be effective chemopreventive agents for NMSCs.	f	\N
24806099	The use of liver retransplantation (ReLT) for hepatitis C virus (HCV) recurrence is controversial because of subsequent viral recurrence after ReLT. Case-control analysis between patients undergoing ReLT for HCV reinfection between 1993 and 2012 (ReLT group: 26 patients) and patients undergoing liver transplantation (LT) for HCV infection immediately before and after each ReLT (LT group: 52 patients). ReLT group had worse hepatocellular function, higher preoperative viral load, higher transfusion requirements, and increased number of postoperative complications than LT group. ReLT patients showed a trend toward worse graft survival compared with LT (five-yr graft survival: 42.3% vs. 64.3%, p = 0.145), but the rate of severe HCV recurrence and infection-free survival (IFS) was similar. The use of donors older than 60 yr led to a lower IFS and graft survival in both groups. Early severe HCV infection rate was similar in both groups, but it affected prognosis in ReLT more markedly than in LT (three-yr graft survival: 0% vs. 66.7%, p = 0.003). ReLT for HCV reinfection has acceptable results when strict selection policies of donor and recipient are applied. However, early severe recurrence more markedly impairs prognosis in ReLT patients than in LT.	f	\N
24820120	Regardless of whether alone or in combination, cecal ligation and puncture (CLP) is the most commonly used model to emulate human polymicrobial sepsis. Numerous CLP studies have shown that female mice survive better than males. In adult mice, this effect may be partly due to the unequal cecum mass (larger in males), as cecum ligation is frequently not size standardized. Comparing two ligation approaches, we investigated whether cecum size influences gender-specific outcome differences. 15-month-old (middle-aged) female and male CD-1 mice underwent sublethal trauma/hemorrhage followed by CLP 48 h later. The evaluation of cecum size (in centimeters) and filling (score) was immediately followed by two ligation protocols: (1) ileocecal ligation (IC-L; n = 28/each gender) below the ileocecal valve, and (2) apex ligation (AP-L; n = 31 males, n = 24 females) 2 cm from the apex ceci - all followed by an identical double puncture and 10-day monitoring. Cecum length (3.4 cm in males vs. 2.65 cm in females) and filling (2.5 score points in males vs. 1.7 in females; both p < 0.05) were always greater in male than female mice (27 vs. 44%, respectively). Compared to AP-L, the 10-day CLP mortality was higher with IC-L (86% in males and 61% in females), and this exacerbation was similar in both genders (by 21% in male and 23% in female mice). Finally, the intergender comparison demonstrated that female mice displayed a significant and similar survival advantage regardless of the ligation approach: the difference reached 25% with IC-L and 24% with AP-L. Standardization by AP-L did not eliminate the gender-specific difference in mortality due to posttraumatic sepsis. The greater cecum length/filling in middle-aged male mice was not responsible for their inferior survival compared to females.	f	\N
24821164	Nephronophthisis is an autosomal recessive disease that leads to end-stage renal disease. These days, molecular genetic analysis is used pre-emptively for making a definitive diagnosis in patients who have clinical and radiological data suggestive of the disease. Herein, we are reporting a 12-year-old girl who was genetically diagnosed to have juvenile nephronophthisis, which explained the mystery of the chronic kidney disease in her four affected siblings.	f	\N
24821649	Hepatocellular carcinoma (HCC) is associated with a poor prognosis because of a lack of effective treatment options. The objective of this study was to examine a new strategy for HCC treatment, namely the use of poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor (ABT-888) together with Temozolomide (TMZ) incorporated onto magnetic nanoparticles. Magnetic Fe3 O4 /Fe cores were encapsulated within a silica shell to facilitate the simultaneous incorporation of ABT-888 and TMZ. In vitro tests were performed with HepG2, Hep3B and PLC-PRF-5 liver tumoural cell lines and with WRL-68 liver non-tumoural cells. The magnetic nanocarriers were loaded simultaneously with ABT-888 and TMZ. High stability and extended release were achieved in culture medium. Confocal microscopy images showed that drug-loaded particles were uptaken and accumulated into the cytoplasm of liver tumoural cells, inducing the following effects: G2/M cell cycle arrest (P < 0.05), accumulation of DNA damage (P < 0.05), mitochondrial depolarization (P < 0.01), reduction in BCL-xL, FOS, JUND gene expression (P < 0.05), PARP-1 fragmentation, Caspase-3 activation and apoptotic cell death (P < 0.05). Interestingly, drugs loaded onto nanoparticles exhibited better efficiency than free drugs (cell death triggered by drug delivery nanosystem: 53.5% vs. 34.5% by free drugs, P = 0.01). These magnetic nanocompounds are able to incorporate both drugs simultaneously, enter the tumour cells and release them. ABT-888/TMZ/NPs decrease the transcription of key genes involved in tumour survival and induce apoptotic cell death in a more effective manner than is achieved by free drugs.	f	\N
24821915	Only a small fraction of individuals exposed to Mycobacterium tuberculosis develop clinical tuberculosis (TB). Over the past century, epidemiological studies have shown that human genetic factors contribute significantly to this interindividual variability, and molecular progress has been made over the past decade for at least two of the three key TB-related phenotypes: (i) a major locus controlling resistance to infection with M. tuberculosis has been identified, and (ii) proof of principle that severe TB of childhood can result from single-gene inborn errors of interferon-γ immunity has been provided; genetic association studies with pulmonary TB in adulthood have met with more limited success. Future genetic studies of these three phenotypes could consider subgroups of subjects defined on the basis of individual (e.g. age at TB onset) or environmental (e.g. pathogen strain) factors. Progress may also be facilitated by further methodological advances in human genetics. Identification of the human genetic variants controlling the various stages and forms of TB is critical for understanding TB pathogenesis. These findings should have major implications for TB control, in the definition of improved prevention strategies, the optimization of vaccines and clinical trials and the development of novel treatments aiming to restore deficient immune responses.	f	\N
24843888	The adaptive function of melanin located in the integument is well known. Although pigments are also deposited in various internal organs, their function is unclear. A review of the literature revealed that 'internal melanin' protects against parasites, pollutants, low temperature, oxidative stress, hypoxemia and UV light, and is involved in the development and function of organs. Importantly, several studies have shown that the amount of melanin deposited on the external body surface is correlated with the amount located inside the body. This finding raises the possibility that internal melanin plays more important physiological roles in dark than light-colored individuals. Internal melanin and coloration may therefore not evolve independently. This further emphasizes the major role played by indirect selection in evolutionary processes.	f	\N
24845215	Over 5100 colorectal cancers (CRCs) are diagnosed in the United Kingdom in 85 years and older age group per year but little is known of cancer progression in this group. We assessed clinical, pathological and molecular features of CRC with early and late mortality in such patients. Data were analysed in relation to early mortality and long-term survival in 90 consecutive patients with CRC aged 85 years or older in a single hospital. Patients not undergoing operation, those with an ASA score of III or greater and those with advanced tumour stage were more likely to die within 30 days. Regression analysis showed that 30 day mortality was independently related to failure to undergo resection (odds ratio (O.R.), 10.0; 95% confidence interval [C.I.], 1.7-58.2; p=0.01) and an ASA score of III or greater (O.R. 13.0; 95% C.I., 1.4-12.6; p=0.03). All cause three and five year survival were 47% and 23% respectively for patients who are alive 30 days after diagnosis. Three and five year relative survivals were 64% and 54%, respectively. Long-term outcome was independently related to tumour stage (relative risk [R.R.], 2; 95% C.I., 1.3-3.1; p=0.001), presence of co-morbid diseases (R.R., 2.8; 95% C.I., 1.3-6.0; p=0.007) and lipid peroxidation status (R.R., 2.9; 95% C.I., 1.1-7.5; p=0.025). An active multidisciplinary approach to the care of patients with CRC at the upper extreme of life is reasonable. It also seems sensible to individualise care based upon the extent of disease at diagnosis and the presence of co-morbid conditions. Further studies to examine the role of lipid peroxidation are warranted.	f	\N
24850149	Inflammasomes are specialized signaling platforms critical for the regulation of innate immune and inflammatory responses. Various NLR family members (i.e., NLRP1, NLRP3, and IPAF) as well as the PYHIN family member AIM2 can form inflammasome complexes. These multi-protein complexes activate inflammatory caspases (i.e., caspase-1) which in turn catalyze the maturation of select pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. Activation of the NLRP3 inflammasome typically requires two initiating signals. Toll-like receptor (TLR) and NOD-like receptor (NLR) agonists activate the transcription of pro-inflammatory cytokine genes through an NF-κB-dependent priming signal. Following exposure to extracellular ATP, stimulation of the P2X purinoreceptor-7 (P2X7R), which results in K(+) efflux, is required as a second signal for NLRP3 inflammasome formation. Alternative models for NLRP3 activation involve lysosomal destabilization and phagocytic NADPH oxidase and/or mitochondria-dependent reactive oxygen species (ROS) production. In this review we examine regulatory mechanisms that activate the NLRP3 inflammasome pathway. Furthermore, we discuss the potential roles of NLRP3 in metabolic and cognitive diseases, including obesity, type 2 diabetes mellitus, Alzheimer's disease, and major depressive disorder. Novel therapeutics involving inflammasome activation may result in possible clinical applications in the near future.	f	\N
24851665	Self-efficacy, a central construct in health interventions, has been measured in various contexts. The absence of any published meta-review of self-efficacy instrumentation led to the current meta-synthesis that reports and evaluates the instrumentation processes. A systematic search resulted in 39 self-efficacy instrumentation studies, which were evaluated for the aspects of conceptual bases, health contexts, operational definition, instrumentation procedures, reliability and scale length, and item content. Primarily based in Bandura's social cognitive theory, these studies reported self-efficacy instrumentation for developing new scales and modifying/validating measures for illness management, healthy behavior adoption/maintenance, disease/risk prevention, and aging management. Trait-like, specific-domain, and situation approaches were used for generating item content. Problems in some studies include non-efficacy items, a lack of systematic instrumentation procedures, item content too general for specific-domain self-efficacy, and measurement inefficiency. The piecemeal fashion of self-efficacy instrumentation has resulted in incomparable self-efficacy measures of similar domains of health functioning. A trans-domain framework, thus, is warranted. Suggestions are provided for solving other problems in self-efficacy instrumentation.	f	\N
24852869	The ABC-02 trial has defined the standard therapy for patients with advanced biliary tract cancer (ABC); however, outcome in an unselected patient population in the UK has not been described. We aimed to investigate the outcome of a series of patients with ABC from two large UK cancer networks. We retrospectively reviewed all cases of ABC presenting to two UK cancer networks over a nine-year period. Overall survival (OS) and factors influencing OS were assessed. Four hundred and two patients were available for analysis. The median OS was 6.2 months. On univariate analysis, age ≥70 years (P = 0.047), advanced disease stage (P <0.001), gall bladder primary (P = 0.033), poor performance status (P <0.001) and lack of chemotherapy (P <0.001) were associated with worse outcome. Survival was superior in the 36.4% of patients who received palliative chemotherapy (12.5 vs 4.3 months; P <0.001). On multivariate analysis of patients who had chemotherapy, those who did not receive fluoropyrimidine-based regimens (HR = 5.12; P = 0.022) or gemcitabine-based regimens (HR = 5.01; P = 0.021) had a higher mortality, whereas the effect of platinum-containing regimens was of borderline significance (HR = 2.23; P = 0.086). Sites, age, and multi-agent regimens were not significant. This is one of the largest retrospective studies reporting outcome of palliative chemotherapy for ABC. It confirms the benefit of palliative chemotherapy in an unselected group of patients. Fluoropyrimidine-based regimens appear to be as effective as gemcitabine-based treatments.	f	\N
24853219	Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of many cancers, and the cutaneous toxicity profile associated with these agents has become prominent. In fact, dermatologic side effects have also been reported with other targeted agents, including both BRAF and mTOR inhibitors. During her presentation at the NCCN 19th Annual Conference, Dr. Barbara Burtness reviewed the array of skin complications caused by many targeted therapies, focusing on the more common culprits, the role of prophylactic versus reactive management strategies, the need to be attentive to potential infections, the importance of mastering local measures to improve quality of life and cosmetic issues, the therapeutic mainstays (oral and topical antibiotics and topical steroids), and the preference of improving these cutaneous complications over suspending anticancer treatment.	f	\N
24861877	Vitamin D deficiency has been associated with hypertension, diabetes mellitus, and incident stroke. Little is known about the association between vitamin D and subclinical cerebrovascular disease. To examine the relationship of 25-hydroxyvitamin D (25[OH]D) levels with cerebrovascular abnormalities as assessed on brain magnetic resonance imaging (MRI) among participants of the Atherosclerosis Risk in Communities (ARIC) Brain MRI study. Participants were white and black adults aged 55 to 72 years with no history of clinical stroke who underwent a cerebral MRI at ARIC visit 3 (n = 1622) and a second cerebral MRI approximately 10 years later (n = 888). The 25(OH)D level was measured by mass spectrometry at visit 3, with levels adjusted for calendar month and categorized using race-specific quartiles. The cross-sectional and prospective associations of 25(OH)D levels with white matter hyperintensities (WMHs) and MRI-defined infarcts were investigated using multivariable regression models. The mean age of the participants was 62 years, 59.6% were women, and 48.6% were black. Lower 25(OH)D levels were not significantly associated with WMH score of severity, prevalent high-grade WMH score (≥3), or prevalent infarcts in cross-sectional, multivariable-adjusted models (all P > .05). Similarly, no significant prospective associations were found for lower 25(OH)D levels with change in WMH volume, incident high WMH score (≥3), or incident infarcts on the follow-up MRI, which occurred approximately 10 years later. A single measure of 25(OH)D was not cross-sectionally associated with WMH grade or prevalent subclinical infarcts and was not prospectively associated with WMH progression or subclinical brain infarcts seen on serial cerebral MRIs obtained approximately 10 years apart. These findings do not support optimizing vitamin D levels for brain health.	f	\N
24871260	A major symptom of hand-arm vibration syndrome is a secondary Raynaud's phenomenon-vibration white finger (VWF)-which results from a vasospasm of the digital arteries caused by work with vibration devices leading to occupational disease. Pharmacotherapy of VWF is often ineffective or has adverse effects. The aim of this work was to verify the influence of inhalation of partially ionized oxygen (O2•-) on peripheral blood vessels in the hands of patients with VWF. Ninety one (91)patients with VWF underwent four-finger adsorption plethysmography, and the pulse wave amplitude was recorded expressed in numeric parameters-called the native record. Next, a cold water test was conducted following with second plethysmography. The patients were divided in to the three groups. First and second inhaled 20-min of ionized oxygen O2•- or oxygen O2 respectively. Thirth group was control without treatment. All three groups a follow-up third plethysmography-the post-therapy record. Changes in the pulse wave amplitudes were evaluated. Inpatients group inhaling O2•- a modest increase of pulse wave amplitude was observed compared to the native record; patients inhaling medical oxygen O2 and the control showed a undesirable decline of pulse wave amplitude in VWF fingers. Strong vasodilatation were more frequent in the group inhaling O2•- compare to O2 (p < 0.05). Peripheral vasodilatation achieved by inhalation of O2•- could be used for VWF treatment without undesirable side effect in hospital as well as at home environment.	f	\N
24872268	Excessive postoperative hemorrhage in cardiac surgery is a serious complication associated with adverse postoperative events. Also, its associated risk of re-exploration, places a high demand on hospital resources in terms of transfusion needs, ventilatory support requirements, intensive care support, and manpower requirements. To determine predictors of 24-hour drain volume (pleural and mediastinal) after coronary artery bypass graft (CABG), in order to focus on preventive measures for patients with identified risk factors. Fifty-four consecutive adult patients who had CABG at the Madras Medical Mission, Chennai, India in July 2008 were retrospectively studied. In order to determine risk factors for excessive post-operative bleeding, 11 pre-operative, and 13 operative and 2 post-operative variables were analyzed using univariate analysis and multiple linear regression. Cardiopulmonary bypass was used for all the patients and anti-fibrinolytic in 13 (22.8%). No mortality was recorded. Mean 24-hour post-operative drain volume was 458 ± 270 ml (range 90-1230). Re-exploration for bleeding was required in 2 (3.5%) patients. Predictors of 24-hour drain volume were heparin therapy before commencement of CPB (p=0.024), intra-operative transfusion of fresh frozen plasma (p=0.010), and pre-operative serum ALT value (p=0.047). The strongest predictor was intra-operative transfusion of platelets (p=0.005). To guard against excessive post-operative haemorrhage after CABG, pre-operative stabilisation and correction of coagulation should be achieved. Also the administration of heparin intra-operatively should be individualized and not only based on dose per body weight.	f	\N
24875660	Peritoneal dialysis (PD) continues to be underutilized in the United States, even though it is less expensive, provides better quality of life and has better outcomes compared with hemodialysis. The reasons for low utilization of PD are influenced by complex psychosocial and economic factors, lack of physician training, physician bias and inadequate pre-end-stage renal disease care and education to the patients. Providing quality pre-end-stage renal disease education to patients and families and improving education and training of physician in PD, so that they become comfortable with the therapy, are of paramount importance to increase PD growth. Minimizing episodes of PD-related infections and noninfectious complications, preserving peritoneal membrane using more biocompatible solutions and drugs, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and careful management of volume status can reduce the loss of PD patients to hemodialysis. Timely surgical interventions can prevent the malfunction and loss of PD catheters. Consolidating smaller PD facilities in a given geographical area into a single large PD center can further improve PD outcomes and PD growth. Finally, with the introduction of bundled payment for dialysis services, PD may emerge as a cost-effective therapy and rekindle interest in the dialysis community to consider PD as a better renal replacement therapy option.	f	\N
24877851	This was a systematic review of the literature to determine which compression method is superior in promoting ulcer healing and reducing recurrence in patients with lower extremity venous ulcer disease. We conducted a comprehensive search of multiple databases for randomized and nonrandomized comparative studies from 1990 to December 2013. We identified 36 studies and two Cochrane systematic reviews. Many studies had moderate risk of bias. We found no overall difference between compression stockings vs compression bandages with respect to ulcer healing, time to ulcer healing, or ulcer recurrence outcomes. When we compared stockings vs short stretch bandages, stockings were superior with respect to ulcer healing. However, stockings compared with four-layer systems showed no difference in ulcer healing outcomes. When four-layer systems were compared with compression with less than four layers, there was also no significant difference in ulcer healing outcomes. Similarly, short stretch bandages were not superior to long stretch bandages with respect to ulcer healing, time to ulcer healing, or ulcer recurrence. One Cochrane review presented many additional comparisons and reported increased wound healing with compression compared with no compression, with multicomponent systems over single component systems, and compression systems with an elastic component over no elastic component. Another Cochrane review demonstrated a reduction in recurrence with compression in patients with healed ulcers. At least moderate-quality evidence supports compression over no compression, multicomponent systems over single component systems, and systems with an elastic component over those without. We did not find significant differences with respect to ulcer healing outcomes for other comparisons. Low-quality evidence supports the effect of compression on ulcer recurrence.	f	\N
24878150	To explore barriers and facilitators to implementing and sustaining Healthy Choices, a 3-year multicomponent obesity prevention intervention implemented in middle schools in Massachusetts. Using purposive sampling, 56 in-depth interviews were conducted with middle school employees representing different positions (administrators, teachers, food service personnel, and employees serving as intervention coordinators). Interviews were recorded and transcribed. Emergent themes were identified using thematic analyses. State-mandated testing, budget limitations, and time constraints were viewed as implementation barriers, whereas staff buy-in, external support, and technical assistance were seen as facilitating implementation. Respondents thought that intervention sustainability depended on external funding and expert assistance. Results confirm the importance of gaining faculty and staff support. Schools implementing large-scale interventions should consider developing sustainable partnerships with organizations that can provide resources and ongoing training. Sustainability of complex interventions may depend on state-level strategies that provide resources for implementation and technical assistance.	f	\N
24882305	Loeys-Dietz syndrome (LDS) is a recently recognized connective tissue disorder caused by mutations of the transforming growth factor (TGF)-β receptors. It is an autosomal dominant syndrome characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. We treated an 18-year-old woman with a 100-mm-diameter aortic root aneurysm and severe aortic valve regurgitation. She underwent urgent aortic root replacement and bioprosthetic valve implantation. LDS was diagnosed by postoperative genetic screening results. Histopathologic examination of the aortic wall showed diffuse degeneration and elastin fragmentation in the media.	f	\N
24895051	Haploidentical stem cell transplantation (haploSCT) offers an alternative treatment option for advanced leukemia patients lacking a HLA-compatible donor. Transfer of NK cells represents a promising therapeutic option in combination with SCT, as NK cells can promote graft versus leukemia with low risk of GVH disease. In this study, we show results from a phase I/II trial in which 24 acute myeloid leukemia patients underwent haploSCT in combination with early transfer of unmodified NK cells and observed a promising 2-year overall survival rate of 37%. By performing immunomonitoring and subsequent principal component analysis, we tracked donor NK-cell dynamics in the patients and distinguished between NK cells reconstituting from CD34(+) precursors, giving rise over time to a continuum of multiple differentiation stages, and adoptively transferred NK cells. Transferred NK cells displayed a mature phenotype and proliferated in vivo during the early days after haploSCT even in the absence of exogenous IL-2 administration. Moreover, we identified the NK-cell phenotype associated with in vivo expansion. Thus, our study indicates a promising path for adoptive transfer of unmodified NK cells in the treatment of high-risk acute myeloid leukemia.	f	\N
24896322	The design of antioxidant pharmaceuticals is a major challenge for the treatment of many clinical conditions and in aging. Free radical damage (FRD) is primarily catalysed by iron catalytic centers. Most of the natural and synthetic antioxidants are ineffective in inhibiting FRD because of the achievement of low concentrations at the affected tissues. Despite that many chelators inhibit FRD in vitro and in vivo, only Deferiprone (L1) has been shown to be effective and safe in the reversal of oxidative stress related tissue damage in iron overload and other conditions such as cardiomyopathy, acute kidney disease, Friedreich ataxia etc. Deferiprone, other chelators and their combinations could be used as main, adjuvant and alternative therapies in untreated conditions eg forms of cancer, Alzheimer's and Parkinson's diseases. Therapeutic targeting in each case requires specific chelator selection based on structure/activity correlation and consideration of other parameters eg ADMET. The ability of L1 to reach extracellular and intracellular compartments of almost all tissues including the brain is a major advantage for further development and use in many clinical conditions.	f	\N
24896980	Abnormally aggregated tau is the hallmark pathology of tauopathy neurodegenerative disorders and is a target for development of both diagnostic tools and therapeutic strategies across the tauopathy disease spectrum. Development of carbon-11- or fluorine-18-labeled radiotracers with appropriate affinity and specificity for tau would allow noninvasive quantification of tau burden using positron emission tomography (PET) imaging. We have synthesized [(18)F]lansoprazole, [(11)C]N-methyl lansoprazole, and [(18)F]N-methyl lansoprazole and identified them as high affinity radiotracers for tau with low to subnanomolar binding affinities. Herein, we report radiosyntheses and extensive preclinical evaluation with the aim of selecting a lead radiotracer for translation into human PET imaging trials. We demonstrate that [(18)F]N-methyl lansoprazole, on account of the favorable half-life of fluorine-18 and its rapid brain entry in nonhuman primates, favorable kinetics, low white matter binding, and selectivity for binding to tau over amyloid, is the lead compound for progression into clinical trials.	f	\N
24902046	Infection, graft-versus-host disease (GVHD), and to a lesser extent sinusoidal obstructive syndrome (SOS) represent the major causes of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). During the last decade, progress in prevention and treatment of these complications led to improvement in the outcome of these patients. Despite the fact that nonmyeloablative regimens have been increasingly used in elderly patients and in patients with co-morbidities, the nonrelapse related mortality remains a challenge and long-term follow-up is required. The objective of this manuscript is to provide an updated concise review of the complications of AHSCT and of the available treatment interventions.	f	\N
24910429	Acute myeloid leukemia (AML) therapy involves compounds that are cytotoxic to both normal and cancer cells, and relapsed AML is resistant to subsequent chemotherapy. Thus, agents are needed that selectively kill AML cells with minimal toxicity. Here, we report that AML is dependent on DDX5 and that inhibiting DDX5 expression slows AML cell proliferation in vitro and AML progression in vivo but is not toxic to cells from normal bone marrow. Inhibition of DDX5 expression in AML cells induces apoptosis via induction of reactive oxygen species (ROS). This apoptotic response can be blocked either by BCL2 overexpression or treatment with the ROS scavenger N-acetyl-L-cysteine. Combining DDX5 knockdown with a BCL2 family inhibitor cooperates to induce cell death in AML cells. By inhibiting DDX5 expression in vivo, we show that DDX5 is dispensable for normal hematopoiesis and tissue homeostasis. These results validate DDX5 as a potential target for blocking AML.	f	\N
24924164	Drug resistance mutations (DRMs) can serve as distinct, nonpolymorphic markers for evaluating diversity of expressed HIV-1. We screened for DRMs during early-acute viremia and examined the diversity in reverse transcriptase (RT) relative to envelope (env) in cases of transmitted drug resistance. We evaluated 111 longitudinal plasma samples collected every 2-7 days from 15 individuals who seroconverted for HIV-1 infection in 1994-2000. The samples were screened with sensitive polymerase chain reaction assays for the commonly transmitted M41L and K70R mutations and for K65R, which was undetected by bulk sequencing. Mutation-positive samples were further characterized by clonal sequencing of RT and env V1-V3. Drug resistance mutations were detected in 4 of 15 seroconverters at 5-50 days of viral nucleic acid expression; most mutations disappeared about the time of seroconversion. Clonal sequencing verified low-level K65R at frequencies of 0.4%-4.9%. In each case, K65R coexisted unlinked with variants carrying 2-5 thymidine analog mutations at frequencies of 1.6%-23.0%. In one seroconverter, variants with M184V and nonnucleoside RT inhibitor mutations were also identified at first RNA expression. Each seroconverter displayed a homogeneous V1-V3 env population. Reverse-transcriptase DRMs demonstrate that the breadth of variants in transmission may be greater than what is reflected in envelope sequences.	f	\N
24935472	In the context of cancer, transforming growth factor β (TGF-β) is a cell growth suppressor; however, it is also a critical inducer of invasion and metastasis. SMAD is the important mediator of TGF-β signaling pathway, which includes receptor-regulated SMADs (R-SMADs), common-mediator SMADs (co-SMADs), and inhibitory SMADs (I-SMADs). I-SMADs block the activation of R-SMADs and co-SMADs and thus play important roles especially in the SMAD-dependent signaling. SMAD7 belongs to the I-SMADs. As an inhibitor of TGF-β signaling, SMAD7 is overexpressed in numerous cancer types and its abundance is positively correlated to the malignancy. Emerging evidence has revealed the switch-in-role of SMAD7 in cancer, from a TGF-β inhibiting protein at the early stages that facilitates proliferation to an enhancer of invasion at the late stages. This role change may be accompanied or elicited by the tumor microenvironment and/or somatic mutation. Hence, current knowledge suggests a tumor-favorable timer nature of SMAD7 in cancer progression. In this review, we summarized the advances and recent findings of SMAD7 and TGF-β signaling in cancer, followed by specific discussion on the possible factors that account for the functional changes of SMAD7.	f	\N
24940479	Although the pathophysiology of facioscapulohumeral dystrophy (FSHD) has been controversial over the last decades, progress in recent years has led to a model that incorporates these decades of findings and is gaining general acceptance in the FSHD research community. Here we review how the contributions from many labs over many years led to an understanding of a fundamentally new mechanism of human disease. FSHD is caused by inefficient repeat-mediated epigenetic repression of the D4Z4 macrosatellite repeat array on chromosome 4, resulting in the variegated expression of the DUX4 retrogene, encoding a double-homeobox transcription factor, in skeletal muscle. Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD. Although some disagreements regarding the details of mechanisms remain in the field, the coalescing agreement on a central model of pathophysiology represents a pivot-point in FSHD research, transitioning the field from discovery-oriented studies to translational studies aimed at developing therapies based on a sound model of disease pathophysiology.	f	\N
24944260	To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH). Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100-600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities. From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in "dizziness/lightheadedness." Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for "standing a long time." Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥ 3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events. In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated. This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days.	f	\N
24948193	Acute inflammation is the result of a complex signal transduction pathway that protects and heals our body and is necessary for our good health and normal wellbeing. Whereas, chronic inflammation can be correlated well with the onset of a plethora of autoimmune disorders; rheumatoid arthritis, systemic lupus and polymyalgia, rheumatic and other diseases like asthma, inflammatory bowel diseases, cardiovascular disorders, ulcerative colitis and Crohn's disease. Also, it has been reported to be associated with the onset of various cancers. An effective anti-inflammatory drug should be able to inhibit the development of chronic inflammation without interfering in normal homeostasis. A number of herbal drugs have been identified in the past that can target inflammatory cytokines. Among these, Ganoderma lucidum: a powerful medicinal mushroom has been found to possess immune-modulating and immune-potentiating capabilities and has been characterized as a wonder herb. This review mainly focuses on the molecular mechanism of anti-inflammatory and antiallergic action of this mushroom and also sheds light on various patent studies related to its pharmacological action.	f	\N
24952923	Extraosseous Gaucher cell deposits are a rare complication of Gaucher disease that can mimic malignancy. We describe a case of Gaucher cell deposition in the subcutaneous soft tissues overlying the lower thoracic spine in an 18-year-old woman with known type III Gaucher disease. This case is unique in the literature because this subcutaneous Gaucher mass was not associated with extension from underlying bone involvement or clear lymph node origin. It demonstrated no discernible continuity with the adjacent thoracic spinous processes, the cortices of which appeared intact. Although patients with Gaucher disease are at increased risk of malignancy, Gaucher cell deposition should remain a differential consideration for soft tissue masses with or without adjacent bone involvement in patients with known Gaucher disease.	f	\N
24953225	The association between the C3435T polymorphism in the MDR1 gene and refractory epilepsy remains controversial. The association appears to be influenced by ethnicity and region. We have performed a systematic review and meta-analysis to assess the link between the MDR1 C3435T polymorphism and refractory epilepsy in the Chinese population. We searched the Cochrane Library, MIDLINE, EMBASE, CBM disc, CNKI, VIP, and WANFANG databases for literature published through August 2013 for case-control studies that evaluated the association between the MDR1 C3435T polymorphism and refractory epilepsy. Twenty-one case-control studies involving 4269 patients (1863 cases in the group with drug-resistant epilepsy and 2406 in the group with drug-responsive epilepsy) were included in the systematic review and meta-analysis. The analysis showed that there were significantly more cases with the MDR1 3435 CC genotype in the group with drug-resistant epilepsy than in the group with drug-responsive epilepsy [odds ratio (OR)=1.50, 95% confidence interval (CI)=1.09-2.06, P=0.01]. In a subanalysis of patients from the southern regions of China, the correlation was not significant [odds ratio (OR)=1.2, 95% confidence interval (CI)=0.89-1.64, P=0.24]. The relationship established in a subset of the Chinese population between the MDR1 C3435T polymorphism and refractory epilepsy will guide epilepsy treatment and development of new AEDs.	f	\N
24955837	Pulmonary arterial hypertension (PAH) is a life-threatening disorder that is associated with elevated pulmonary pressures and right heart failure resulting from progressive loss and thickening of small pulmonary arteries. Despite their ability to improve symptoms, current therapies fail to prevent disease progression, leaving lung transplantation as the only therapy in end-stage PAH. To overcome the limitations of current therapies, there is an active search for disease-modifying agents capable of altering the natural history of, and improving clinical outcomes in, PAH. The Wnt signaling pathways have emerged as attractive treatment targets in PAH given their role in the preservation of pulmonary vascular homeostasis and the recent development of Wnt-specific compounds and biological therapies capable of modulating pathway activity. In this review, we summarize the literature describing the role of Wnt signaling in the pulmonary circulation and discuss promising advances in the field of Wnt therapeutics that could lead to novel clinical therapies capable of preventing and/or reversing pulmonary vascular pathology in patients with this devastating disease.	f	\N
24962034	The HIV Modes of Transmission (MOT) model estimates the annual fraction of new HIV infections (FNI) acquired by different risk groups. It was designed to guide country-specific HIV prevention policies. To determine if the MOT produced context-specific recommendations, we analyzed MOT results by region and epidemic type, and explored the factors (e.g. data used to estimate parameter inputs, adherence to guidelines) influencing the differences. We systematically searched MEDLINE, EMBASE and UNAIDS reports, and contacted UNAIDS country directors for published MOT results from MOT inception (2003) to 25 September 2012. We retrieved four journal articles and 20 UNAIDS reports covering 29 countries. In 13 countries, the largest FNI (range 26 to 63%) was acquired by the low-risk group and increased with low-risk population size. The FNI among female sex workers (FSWs) remained low (median 1.3%, range 0.04 to 14.4%), with little variability by region and epidemic type despite variability in sexual behaviour. In India and Thailand, where FSWs play an important role in transmission, the FNI among FSWs was 2 and 4%, respectively. In contrast, the FNI among men who have sex with men (MSM) varied across regions (range 0.1 to 89%) and increased with MSM population size. The FNI among people who inject drugs (PWID, range 0 to 82%) was largest in early-phase epidemics with low overall HIV prevalence. Most MOT studies were conducted and reported as per guidelines but data quality remains an issue. Although countries are generally performing the MOT as per guidelines, there is little variation in the FNI (except among MSM and PWID) by region and epidemic type. Homogeneity in MOT FNI for FSWs, clients and low-risk groups may limit the utility of MOT for guiding country-specific interventions in heterosexual HIV epidemics.	f	\N
24965397	Several studies indicated that the expression level of MLL3 gene in gastric cancer tissue was associated with prognosis, and previous studies also suggested that genetic polymorphisms of MLL3 were related to the risk for gastric cancer. The present study aimed to investigate the association of a missense mutation (S3660L) in the MLL3 gene with gastric cancer risk in a Chinese population. In the present study, we identified a novel missense mutation in MLL3 gene (S3660L) by directly sequencing method in 48 gastric cancer patients. To further explore the relation between gastric cancer and this mutation, we selected 354 gastric cancer patients and 377 healthy control subjects and designed a case-control study. We found that the AG genotype (14.9 vs 6.40%, odds ratio/OR=2.58, 95% CI: 1.33-4.54, p<0.001) and A allele (7.5 vs 3.2%, OR=2.46, 95% CI: 1.55~5.34, p<0.001) were common in the gastric cancer patients than in the control subjects. We concluded that this novel missense (S3660L) mutation in MLL3 gene is likely to increase the gastric cancer risk.	f	\N
24970372	During the 2009 A(H1N1) influenza pandemic, a suite of studies conducted in Canada showed an unexpected finding, that patients with medically attended laboratory-confirmed pandemic influenza were more likely to have received seasonal influenza vaccination than test-negative control patients. Different bodies, including scientific journals and government scientific advisory committees, reviewed the evidence simultaneously to determine its scientific validity and implications. Decision-making was complicated when the findings made their way into the media. The normal trajectory of non-urgent research includes peer-review publication after which decision-makers can process the information taking into account other evidence and logistic considerations. In the situation that arose, however, the congruence of an unexpected finding and the simultaneous review of the evidence both within and outside the traditional peer-review sphere raised several interesting issues about how to deal with emerging evidence during a public health emergency. These events are used in this article to aid discussion of the complex interrelationship between researchers, public health decision-makers and scientific journals, the trade-offs between sharing information early and maintaining the peer-review quality assurance process, and to emphasise the need for critical reflection on the practical and ethical norms that govern the way in which research is evaluated, published and communicated in public health emergencies.	f	\N
24973485	This study explored the care challenges experienced by older patients with multimorbidity, their informal caregivers and family physicians. Semi-structured interviews were conducted with 27 patients, their informal caregivers and family physicians. Qualitative description was used to identify key themes in the interview transcripts. Participants experienced many common challenges when managing multimorbidity, including a lack of decision-making support, poor communication and uncoordinated health services. Within these themes, unique perspectives specific to the role of being a patient, caregiver or family physician emerged. The study adds to a limited evidence base on the experience of patients with multimorbidity. By including the perspectives of their family caregivers and physicians, we provide important insight into the management of multimorbidity and recommend the uptake of specific strategies to address them.	f	\N
24986275	Cyclical outbreaks of mumps have been noticed across Chandigarh city during winter months. Chandigarh does not provide measles, mumps and rubella (MMR) vaccination in the State immunization schedule. Epidemiological shift in age at diagnosis of mumps was noticed with higher incidence in older children and adults. Increased occurrence of complications can be predicted with this age shift. Silent burden of rubella with serious outcomes in newborns further strengthen the case for MMR vaccine inclusion in routine immunization program of Chandigarh.	f	\N
24988612	Autophagy, the process of degradation of unwanted or damaged cell elements, is extremely important for a variety of human diseases, especially cancers. This process influences various stages of initiation and progression of cancer, which is caused by overlapping signaling pathways of autophagy and carcinogenesis. However, due to the complexity of cancer as a systemic disease, the fate of tumor cells is not determined by one signal pathway. Chronic autophagy inhibition leads to tumor promotion, due to instability of the genome, defective cell growth, also as a result of cellular stress. However, increased induction of autophagy may be a mechanism for tumor cell survival in the state of hypoxia, acidosis, as well as under the influence of chemotherapy. Therefore, in the context of cancer development, the process of autophagy should be considered in two directions. Determination of the molecular mechanisms underlying the process of autophagy and its role in the carcinogenesis is a key element of the anticancer strategy. The main objective of modern oncology, which should eventually lead to personalized therapy, is the possibility to predict the response of a particular type of cancer to the used drug. Results of in vitro and in vivo studies show the magnitude of the relationship between changes in the genome, and response to the therapy. This information indicates the mechanism and thereby the target point of the drugs. In this review we focus on the mechanism of autophagy and its role in cancer therapy, which can help to understand the autophagy-cancer relationship and indicate the direction for the design of new drugs with anticancer activity.	f	\N
24989056	Flow volume loops (FVLs) are considered part of the workup of patients with thyroid enlargement presenting to the endocrinology clinic. They are used to detect upper airway obstruction (UAO) secondary to tracheal compression (TC) from a goitre. Surgical assessment in contrast tends to focus on clinical evaluation supplemented when required by imaging. The aim of this study was to investigate whether FVLs influence the decision to operate in patients with a goitre. We identified patients with a goitre referred by the department of endocrinology for FVLs between 2006 and 2011. The results of the FVL were collated, and their impact on patient management was assessed. Ninety-six patients were referred for FVL. In 38 patients, the indication was specifically to evaluate the effects of a goitre. Of these, 33 were reported as normal. Five FVLs were reported as abnormal (3 suggesting lung pathology and 2 TC). Both patients with TC on FVL presented no CT evidence of TC and underwent surgery due to abnormal cytology. Of the 33 normal FVLs, 7 underwent surgery: 2 for local compression, 4 for abnormal cytology and 1 for Graves' disease. None of the FVLs influenced the decision to operate. FVLs may detect subradiological TC, but rarely influence management in patients with a goitre. In view of this and the cost of £235 per investigation, FVL should be reserved for goitre patients with suspected primary lung pathology, where the distinction between large and small airway compression is likely to influence management.	f	\N
24994677	Uveal melanoma (UM) is the most common primary tumor of the eye in adults. There is no standard adjuvant treatment to prevent metastasis and no effective therapy in the metastatic setting. We have established a unique panel of 7 UM cell lines from either patient's tumors or patient-derived tumor xenografts (PDXs). This panel recapitulates the molecular landscape of the disease in terms of genetic alterations and mutations. All the cell lines display GNAQ or GNA11 activating mutations, and importantly four of them display BAP1 (BRCA1 associated protein-1) deficiency, a hallmark of aggressive disease. The mTOR pathway was shown to be activated in most of the cell lines independent of AKT signaling. mTOR inhibitor Everolimus reduced the viability of UM cell lines and significantly delayed tumor growth in 4 PDXs. Our data suggest that mTOR inhibition with Everolimus, possibly in combination with other agents, may be considered as a therapeutic option for the management of uveal melanoma.	f	\N
25003989	Understanding how the immune system facilitates or controls HIV-1 disease progression has important implications for the design of effective interventions. We report that although B-cell dysregulations associated with HIV-1 disease progression are accompanied by an overall decrease in the percentage of total blood B-cells, we observe an increase in relative frequencies of cells presenting characteristics of both transitional immature and first-line marginal zone (MZ) B-cell populations, we designated as precursor MZ-like B-cells. B-cells with similar attributes have been associated with IL-10 expression and "regulatory" potential. As such, the relative frequencies of precursor MZ-like B-cells expressing IL-10 are increased in the blood of viremic HIV-1-infected individuals when compared to HIV-negative subjects. Importantly, in aviremic HIV-1 Elite-Controllers (EC), we found unaltered relative percentages of precursor MZ-like B-cells which presented normal IL-10 expression patterns. Furthermore, EC had increased relative frequencies of blood MZ-like B-cells expressing LT-α. Thus in contrast to viremic HIV-1-infected individuals, EC present MZ-like B-cell populations which IL-10 and LT-α expression profiles may favour homeostasis of immune responses and lymphoid microenvironments.	f	\N
25011952	We recently demonstrated a beneficial effect of metformin compared with glipizide in type 2 diabetic patients regarding cardiovascular outcomes for 3-year treatment in the SPREAD-DIMCAD study. However, the potential mechanism for the clinical effects remains unclear. Here, we performed a comprehensive lipidomics study to evaluate the different lipid metabolites in serum samples obtained from participants in this study. Liquid chromatography-quadrupole time of flight-mass spectrometry was used to evaluate the different lipid metabolites in serum samples obtained from the participants (21 patients in glipizide group and 23 patients in metformin group) before and after each year of treatment (at 0 [baseline], 1, 2, and 3 years of study drug administration). A total of 118 serum lipid molecular species was identified and quantified. During treatment, metformin induced a substantially greater change in serum lipid species compared with glipizide, especially at the 2- and 3-year time points (with 2, 11, and 12 lipid species being significantly different between the groups after each year of treatment [1, 2, or 3 years], P < 0.05). Among the significantly changed lipid species, three lipid metabolites were linked to long-term composite cardiovascular events (adjusted P < 0.05). After treatment, triacylglycerols (TAGs) of a relatively higher carbon number showed a clearly increased trend in metformin group compared with the glipizide group, whereas the changes in TAGs with different double bonds were minimal. Our findings revealed the differential therapeutic effects of metformin and glipizide on comprehensive lipidomics, which were comparable with their different long-term effects on cardiovascular outcomes.	f	\N
25014130	To conduct the first population size estimation and biological and behavioral surveillance survey among men who have sex with men (MSM) in Angola. Population size estimation with multiplier method and a cross-sectional study using respondent-driven sampling. Luanda Province, Angola. Study was conducted in a large hospital. Seven hundred ninety-two self-identified MSM accepted a unique object for population size estimation. Three hundred fifty-one MSM were recruited with respondent-driven sampling for biological and behavioral surveillance survey. Interviews and testing for HIV and syphilis were conducted on-site. Analysis used Respondent-Driven Sampling Analysis Tool and STATA 11.0. Univariate, bivariate, and multivariate analyses examined factors associated with HIV and unprotected sex. Six imputation strategies were used for missing data for those refusing to test for HIV. A population size of 6236 MSM was estimated. Twenty-seven of 351 individuals were tested positive. Adjusted HIV prevalence was 3.7% (8.7% crude). With imputation, HIV seroprevalence was estimated between 3.8% [95% confidence interval (CI): 1.6 to 6.5] and 10.5% (95% CI: 5.6 to 15.3). Being older than 25 (odds ratio = 10.8, 95% CI: 3.5 to 32.8) and having suffered episodes of homophobia (odds ratio = 12.7, 95% CI: 3.2 to 49.6) significantly increased the chance of HIV seropositivity. Risk behaviors are widely reported, but HIV seroprevalence is lower than expected. The difference between crude and adjusted values was mostly due to treatment of missing values in Respondent-Driven Sampling Analysis Tool. Solutions are proposed in this article. Although concerns were raised about feasibility and adverse outcomes for MSM, the study was successfully and rapidly completed with no adverse effects.	f	\N
25015744	Endoscopic ultrasound (EUS)-guided drainage is an effective treatment for many abscesses in the abdomen. We review our experience with EUS-guided drainage of pelvic abscesses. Thirty consecutive patients who underwent EUS-guided pelvic abscess drainage were evaluated after excluding three patients with distance to transducer >2 cm or organized abscess. Thirty patients (25 male) aged 60 ± 4.5 years (mean ± SD) had 4 prostatic abscesses, 7 perisigmoid abscesses, and 19 perirectal abscesses with mean ± SD sizes of 2.5 ± 0.3, 4.7 ± 0.6, and 5.4 ± 0.4 cm, respectively. Surgery was the most common predisposing factor (n = 14, 46.6 %) followed by diverticulitis (n = 5, 16.6 %). Interventions included aspiration only (2 prostatic and 3 perisigmoid), aspiration and dilatation (2 patients in each group), and dilatation and stenting (2 perisigmoid and 17 perirectal). Five (16.6 %) patients needed re-intervention, and two (6.6 %) needed surgery. There were no recurrences. Technical success of EUS-guided pelvic abscess drainage overall was 90.9 % (30/33) and was 93.3 % (27/30) in patients in whom EUS-guided drainage was attempted, with 16.5 % (n = 5) re-intervention rate. EUS-guided drainage has an excellent success rate in drainage of pelvic abscesses.	f	\N
25022060	The measurement of antinuclear antibodies (ANA) is used for screening of connective tissue diseases (CTD) in the laboratory. ANA detection is performed by indirect immunofluorescence (IF) assay on HEp-2 cells from human larynx carcinoma. However, it lacks specificity for the identification of specific diseases and antigen reactivity. The aim of the present study was to evaluate the EliA CTD Screen (EliA), a new enzyme fluoroimmunoassay (Phadia AB, Uppsala, Sweden) for detection of ANA in human serum. The study involved a total of 732 serum samples, 200 from healthy donors, 297 from patients with CTD and 235 from patients with rheumatoid arthritis, vasculitis syndrome and relative disease of CTD. For all sera, ANA was measured by IF, commercial assay (MESACUP) and EliA. The sensitivity and specificity of EliA were 73.7% and 78.7%, respectively, whereas those of MESACUP were 80.8% and 64.7%, respectively. Area under the receiver operating curves for EliA, MESACUP and IF were 0.821, 0.786 and 0.730, respectively. The concordance rate between EliA and MESACUP was 84.2%. These discrepancies between those 2 assays were found in 84 sera. Further investigation were done by each ANA antigen tests for the discrepant results of EliA in 83 sera. The discrepancies might be occurred by antigen difference or non-specific response. AUC results showed that the diagnostic performance of EliA was superior to MESACUP and IF. EliA had a good performance as method for screening of CTD.	f	\N
25027632	This longitudinal, exploratory study was designed to better understand the lived experience of spousal caregivers age 60 and older providing care to partners with Alzheimer's disease and related dementias resident in a care facility. Twenty eight spousal caregivers were interviewed up to three times over a period of 2 years, and long-term care facility staff from four locations across British Columbia (BC), Canada participated in four focus groups. Thematic analysis of interview and focus group transcripts revealed a central, unifying theme 'together but apart'. The results identify key targets for policy makers and service providers to support positive health and well-being outcomes for spousal caregivers providing care to their partners diagnosed with Alzheimer's disease and related dementia and living in care facilities.	f	\N
25034390	Patients with multiple myeloma (MM) manifesting acute kidney injury (AKI) and who later recover renal function and independence from renal replacement therapy (RRT) are considered to have a better outcome. The aim of this work was to study the factors associated with renal function recovery (independence of hemodialysis) and longer survival in these patients. A retrospective single center study including patients with a diagnosis of MM and severe AKI, defined as stage 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) criteria: 3.0 times baseline increase in serum creatinine (sCr) or increase in sCr to ≥4.0mg/dL or initiation of RRT, was conducted. Data was registry-based and collected between January 2000 and December 2011. We examined demographic and laboratorial data, presenting clinical features, precipitating factors, need for RRT and chemotherapy. Death was considered the primary endpoint. Lower serum β2-microglobulin was the only independent factor associated with recovery of renal function and independence of RRT (OR 0.95, 95% CI: 0.91-0.99, P=0.02). The median survival after AKI was 10.7±12.1months. The factors associated with longer survival were independence of RRT (HR 2.21; 95% CI: 1.08-4.49; P=0.02), lower CRP (HR 1.07; 95% CI: 1.03-1.12; P=0.001) and younger age (HR 1.03; 95% CI: 1.01-1.06; P=0.005). Our study suggests that MM patients with lower serum β2-microglobulin have a higher likelihood of recovering renal function after severe AKI. Independence of RRT, lower CRP and younger age are associated with longer survival.	f	\N
25038555	The rapidly increasing availability of electronic health records (EHRs) from multiple heterogeneous sources has spearheaded the adoption of data-driven approaches for improved clinical research, decision making, prognosis, and patient management. Unfortunately, EHR data do not always directly and reliably map to medical concepts that clinical researchers need or use. Some recent studies have focused on EHR-derived phenotyping, which aims at mapping the EHR data to specific medical concepts; however, most of these approaches require labor intensive supervision from experienced clinical professionals. Furthermore, existing approaches are often disease-centric and specialized to the idiosyncrasies of the information technology and/or business practices of a single healthcare organization. In this paper, we propose Limestone, a nonnegative tensor factorization method to derive phenotype candidates with virtually no human supervision. Limestone represents the data source interactions naturally using tensors (a generalization of matrices). In particular, we investigate the interaction of diagnoses and medications among patients. The resulting tensor factors are reported as phenotype candidates that automatically reveal patient clusters on specific diagnoses and medications. Using the proposed method, multiple phenotypes can be identified simultaneously from data. We demonstrate the capability of Limestone on a cohort of 31,815 patient records from the Geisinger Health System. The dataset spans 7years of longitudinal patient records and was initially constructed for a heart failure onset prediction study. Our experiments demonstrate the robustness, stability, and the conciseness of Limestone-derived phenotypes. Our results show that using only 40 phenotypes, we can outperform the original 640 features (169 diagnosis categories and 471 medication types) to achieve an area under the receiver operator characteristic curve (AUC) of 0.720 (95% CI 0.715 to 0.725). Moreover, in consultation with a medical expert, we confirmed 82% of the top 50 candidates automatically extracted by Limestone are clinically meaningful.	f	\N
25044634	The potential benefit of vitamin K as a therapeutic in osteoporosis is controversial and the vitamin K regimen being used clinically (45 mg/day) employs doses that are many times higher than required to ensure maximal gamma-carboxylation of the vitamin K-dependent bone proteins. We therefore tested the hypothesis that vitamin K catabolites, 5-carbon (CAN5C) and 7-carbon carboxylic acid (CAN7C) aliphatic side-chain derivatives of the naphthoquinone moiety exert an osteotrophic role consistent with the treatment of osteoporosis. Osteoblast-like MG63 cell cultures were challenged with lipopolysaccharide and the levels of interleukin-6, an osteoclastogenic cytokine, measured with and without catabolites; low concentrations of CAN7C significantly inhibited interleukin-6 release, but CAN5C did not. In models of bone loss induced by ovariectomy or sciatic neurectomy in C57BL/6 mice, we found that the rarer CAN7C catabolite markedly restricted ovariectomy-induced bone loss and possibly limited sciatic neurectomy-induced bone loss. CAN7C activity depends on a free carboxylic acid and its particular side-chain structure. These in vivo data indicate for the first time that the clinical utility of vitamin K for osteoporosis may reside in an unusual catabolite.	f	\N
25046696	Cystic and alveolar hydatid disease of humans caused by infection with Echinococcus granulosus or Echinococcus multilocularis are significant zoonoses in developing countries. For human infections, the main definitive host is the dog, and reduction in the population of unwanted dogs, together with anthelmintic treatment of wanted dogs, are recommended control procedures for these zoonoses. Both owned and unowned dogs have been shown to be a major source of Echinococcus spp. infection in developing countries. Unowned dogs are the most challenging category in dog population management for the control of major zoonotic diseases. Unowned dogs are those dogs that do not have an owner, and those dogs whose owner cannot readily be identified. Control of numbers of unowned dogs can be done in various ways if funds are available. Fertility control and humane euthanasia are likely to be the most effective procedures in developing countries. Fertility control requires significant funding, and where resources are scarce humane euthanasia may be the most effective option. Both procedures are ongoing events, with no predictable end point. This paper examines the sociology and technology for the population management of owned and unowned dogs, specifically for the reduction of human hydatid disease. Examples are given for developing and developed countries. Although a "One Health" approach is desirable, the technology for hydatid control is different from that for rabies, and FAO Animal Welfare recommendations for dog population management should be adjusted accordingly.	f	\N
25051669	The paper presents data on the frequency of polymorphisms of candidate genes involved in the formation of endothelial dysfunction--endothelin-1 (EDN1 Lys198Asn) and endothelial nitric oxide synthase (NOS3 T786C) together with the concentrations of their active products (nitric oxide, endothelin-1) in individuals with chronic mercury intoxication. The concentration change of nitric oxide and endothelin-1 indicates the presence of endothelial dysfunction in the individuals examined. The studied polymorphisms appeared to play a minor role in the pathogenesis of endothelial dysfunction in patients with chronic mercury intoxication.	f	\N
25055486	Postoperative intracranial infectious complications are one of the most topical problems of neurosurgical intensive care due to theirs significant capability to impair outcomes of the main disease. To define the risk factors of postoperative meningitis in patients with chiasm-sellar tumors. 1. to define the effect of somatic and intracranial risk factors on occurrence of postoperative meningitis in patients after transsphenoidal and transcranial approaches to the tumor. 2. To define the effect of postoperative meningitis on outcomes of treatment in patients after transsphenoidal and transcranial approaches to the tumor. Somatic and intracranial risk factors of occurrence of postoperative meningitis (pneumonia, urinary tract infection, sepsis, intra-abdominal hypertension, the presence of external ventricular and lumbar drainage, monitoring of intracranial pressure, cerebrospinal fluid, and reoperation) were fixed every day. The study was conducted in the ICU of the Burdenko from October, 2010 to July, 2012. The 34 patients (19 males, 15 females) were included in the study (average age 47.5 years). The patients were divided into two groups; 17 patients each group. The group-1 included patients after transcranial approach to the tumor and the group-2 included patients after transsphenoidal approach. In the group-1 a meningitis occurred in 3 patients (17.6% +/- 9.2%, DI [-0.4 - 35.6]). In the group-2 a meningitis occurred in 7 patients (41.2% +/- 11.9) DI 95% [17.8 - 64.4]. Accumulation of cerebrospinal fluid under the skin flap authentically increased a risk of a meningitis occurrence in patients after transcranial approach to the tumor (p = 0.031). There was no defined statistical significance of other risk factors. But there was defined a trend of the increasing of meningitis occurrence in patients after transsphenoidal approach in case of lumbar drainage or reoperation. Duration of mechanical ventilation and ICU stay in patients with meningitis was authentically longer than in patients without meningitis in both groups. In the group-2 the duration of mechanical ventilation and ICU stay was significantly shorter than in the group-1. Meningitis is not a typical complication of postoperative period in patients with transcranial approach to the tumor. After transsphenoidal approach a meningitis occurrence is likely in case of postoperative liquorrhea, lumbar drainage or reoperation. Subcutaneous accumulation of cerebrospinal fluid is a single defined statistically significant risk factor of meningitis. Postoperative meningitis impairs a condition of patients with chiasm-sellar tumors, increases the duration of mechanical ventilation and impairs treatment outcomes.	f	\N
25056937	Cancer is responsible for many deaths and is a major source of healthcare expenditures. The identification of new, non-invasive biomarkers might allow improvement of the direct diagnostic or prognostic ability of already available tools. Here, we took the innovative approach of interrogating the activity of exopeptidases in the serum of cancer patients with the aim of establishing a distinction based on enzymatic function, instead of simple protein levels, as a means to biomarker discovery. We first analyzed two well-characterized mouse models of prostate cancer, each with a distinct genetic lesion, and established that broad exopeptidase and targeted aminopeptidase activity tests reveal proteolytic changes associated with tumor development. We also describe new peptide-based freeze-frame reagents uniquely suited to probe the altered balance of selected aminopeptidases, as opposed to the full array of exopeptidases, and/or their modulators in patient serum or plasma. One particular proteolytic activity was impaired in animals with aggressive disease relative to cancer-free littermates. We identified the protease in question as dipeptidyl peptidase 4 (DPP4) by analyzing selected knockout mice and evaluating the effect of specific inhibitors. DPP4 activity was also reduced in the sera of patients with metastatic prostate cancer relative to patients with localized disease or healthy controls. However, no significant differences in DPP4 serum levels were observed, which established the loss of activity as the result of impaired enzymatic function. Biochemical analysis indicated that reduced activity was the result not of post-translational modifications or allosteric changes, but instead of a low-molecular-weight inhibitor. After we adjusted for age and total prostate-specific antigen, reduced DPP4 activity remained a significant predictor of cancer status. The results of this proof-of-principle study suggest that DPP4 activity might be a potential blood-based indicator of the presence of metastatic cancer of prostatic origin, either by itself or, more likely, as a means to improve the sensitivity and specificity of existing markers.	f	\N
25063009	When microinvasion cannot be ruled out on core needle biopsy (CNB) in the setting of ductal carcinoma in situ (DCIS), the surgeon must decide whether to perform a sentinel lymph node biopsy (SLNB) at the time of surgery. Up to 10 % of patients with T1mi have nodal disease, but the utility of SLNB in DCIS suspicious for microinvasion (Smic) is unclear. The University of Chicago pathology database was queried for a diagnosis of Smic or definite microinvasion (Mic) on CNB from 2000 to 2014. We analyzed histology, imaging, core needle size, and the use of myoepithelial immunohistochemistry (IHC) markers. We identified 103 women, 72 with Smic and 31 with Mic on CNB. After surgery, 32 % of Smic patients had infiltrating ductal carcinoma (IDC). Seventy-two percent of Smic patients underwent SLNB, with 67 % performed at the initial surgery. SLNB was positive in 6 % and 10 % of Smic and Mic patients, respectively (p = 0.66). Excluding N1mic, the incidence of macrometastatic nodal disease was 1.9 % for Smic patients and 3.3 % for Mic patients (p = 1.00). For Smic patients, IDC was associated with a larger lesion size and smaller CNB needle. In the setting of Smic, grade, necrosis, or presence of a mass did not increase the risk of IDC. In patients with Smic on CNB, the incidence of macrometastatic nodal disease after SLNB is rare. Surgeons may consider omitting SLNB until IDC is definitively confirmed, especially in patients with Smic apart from other high-risk features.	f	\N
25065742	Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive oxygen species (ROS) are generated during aerobic respiration in mitochondria, mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease. Hence, the correlation between mt tRNA activity and mitochondrial dysfunction has been assessed. Then, cybrid cells, which are constructed by the fusion of an enucleated cell harboring altered mtDNA with a ρ(0) cell, have long been used for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease. The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was successfully translocated to the mitochondrial matrix. Additionally, mt tRNA cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity, was observed.	f	\N
25076776	Schizophrenia and bipolar disorder are severe neuropsychiatric disorders, affecting about 1% of the population. Identifying endophenotypes in the brains of neuropsychiatric patients is now considered the way to understand the underlying mechanisms and to improve therapeutic outcomes. However, the endophenotypes and brain mechanisms of the disorders remain unknown. We have previously reported that alpha-CaMKII heterozygous knockout mice show abnormal behaviors related to neuropsychiatric disorders. In these mutant mice, almost all neurons in the hippocampal dentate gyrus stay at a pseudo-immature state, which we refer to as "immature dentate gyrus (iDG)." So far, the iDG phenotype and similar behavioral abnormalities have been found in Schnurri-2 knockout, SNAP-25 mutant, and forebrain-specific calcineurin knockout mice. In addition, we found that both chronic fluoxetine treatment and pilocarpine-induced seizures can reverse the maturation state of the mature neurons, resulting in the iDG phenotype in wild-type mice. Such an iDG-like phenomenon was observed in the post-mortem brains from patients with schizophrenia/bipolar disorder. Recent studies suggest that cortex and amygdala of schizophrenia patients are also at a pseudo-immature state. Based on the findings, we proposed that immaturity of certain types of cells in the brain is a potential endophenotype of neuropsychiatric disorders.	f	\N
25081727	To retrospectively review the safety and clinical efficacy of bevacizumab concomitant with chemotherapy in Chinese patients with advanced non-squamous non-small cell lung cancer (NSNSCLC). Clinical data for 79 patients with NSNSCLC who received bevacizumab concomitant with chemotherapy in Chinese PLA General Hospital from April 28th 2009 to May 5th 2013 were retrospectively reviewed to analyze the clinical efficacy including disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), the Eastern Cooperative Oncology Group (ECOG) score and the safety. The Eastern Cooperative Oncology Group (ECOG) score was 0-2. By the final cutoff date (June 9, 2013), 54 (68.4%) patients had disease progression and 37 (46.8%) died. The ORR was 32.9% and the DCR was 83.5%. The ORR of the first-, second-, and third- or later-line treatments were 51.4%, 25.0% and 12.5%, while the DCR were 94.3%, 80.0% and 70.8%, respectively. The median OS (mOS) and PFS (mPFS) were 13.5 and 5.83 months, respectively. The mOS of patients with the first-, second-, and third- or later-line treatments were 16.2, 10.9 and 8.30 months, while the mPFS were 7.27, 5.90 and 5.17 months, respectively. Chemotherapy-related adverse events included myelosuppression, vomiting, hepatic dysfunction and renal dysfunction, while the common serious bevacizumab-related adverse events were thromboembolic problems, gastrointestinal perforation and reversible posterior leukoencephalopathy syndrome, which could be well managed. Bevacizumab concomitant with chemotherapy is effective and the related toxicity can be well tolerated in Chinese patients with NSNSCLC.	f	\N
25083284	Diagnosing coeliac disease (CD) can be challenging, despite highly specific autoantibodies and typical mucosal changes in the small intestine. The T-cell response to gluten is a hallmark of the disease that has been hitherto unexploited in clinical work-up. We aimed to develop a new method that directly visualizes and characterizes gluten-reactive CD4+ T cells in blood, independently of gluten challenge, and to explore its diagnostic potential. We performed bead-enrichment of DQ2.5-glia-α1a and DQ2.5-glia-α2 tetramer+ cells in the blood of control individuals, treated (TCD) and untreated patients (UCD). We visualized these cells by flow cytometry, sorted them and cloned them. We assessed their specificity by antigen stimulation and re-staining with tetramers. We detected significantly more gliadin-tetramer+ CD4+ effector memory T cells (TEM) in UCD and TCD patients, compared to controls. Significantly more gliadin-tetramer+ TEM in the CD patients than in controls expressed the gut-homing marker integrin-β7. Quantification of gut-homing, gluten-specific TEM in peripheral blood, visualized with human leukocyte antigen (HLA) -tetramers, may be used to distinguish CD patients from healthy individuals. Easy access to gluten-reactive blood T cells from diseased and healthy individuals may lead to new insights on the disease-driving CD4+ T cells in CD.	f	\N
25095816	Falls in people with Parkinson's disease (PD) are frequent and recurrent events with devastating and widespread consequences. Despite this, understanding of the predictive and explanatory value of fall risk factors, as well as the development and testing of interventions aimed at reducing falls, are in their infancy. This review focuses on fall prediction and risk factors that are potentially remediable with physical interventions. We show that falls can be predicted with high accuracy using a simple three-step clinical tool. Evidence from recently published randomized controlled trials supports the implementation of balance-challenging exercises in reducing falls. Larger scale trials utilizing technologically advanced monitoring methods will further elucidate those interventions most likely to be cost effective according to individual risk factor profiles.	f	\N
25097994	Results of surgical treatment of 1220 patients, suffering inguinal hernia, were analyzed. Among the patients there were 810 ageing more than 60 yrs old (main group), from 40 to 59 yrs--410 (control group). There was established, that in patients older than 60 yrs, due to presence of age-related atrophic-dystrophic changes in the inguinal channel muscles, the disease recurrence rate is more than in younger patients. That is why in the inguinal channel hernioplasty the priority must be on the side of alloplastic methods with application of miniinvasive and endoscopic procedures. There was not trustworthy difference between the groups of patients for the rate of intraoperative and early postoperative complications.	f	\N
25115192	Good prognostic tools for predicting disease progression in early stage prostate cancer (PCa) are still missing. Detection of molecular subtypes, for instance by using microarray gene technology, can give new prognostic information which can assist personalized treatment planning. The detection of new subtypes with validation across additional and larger patient cohorts is important for bringing a potential prognostic tool into the clinic. We used fresh frozen prostatectomy tissue of high molecular quality to further explore four molecular subtype signatures of PCa based on Gene Set Enrichment Analysis (GSEA) of 15 selected gene sets published in a previous study. For this analysis we used a statistical test of dependent correlations to compare reference signatures to signatures in new normal and PCa samples, and also explore signatures within and between sample subgroups in the new samples. An important finding was the consistent signatures observed for samples from the same patient independent of Gleason score. This proves that the signatures are robust and can surpass a normally high tumor heterogeneity within each patient. Our data did not distinguish between four different subtypes of PCa as previously published, but rather highlighted two groups of samples which could be related to good and poor prognosis based on survival data from the previous study.The poor prognosis group highlighted a set of samples characterized by enrichment of ESC, ERG-fusion and MYC + rich signatures in patients diagnosed with low Gleason score,. The other group consisted of PCa samples showing good prognosis as well as normal samples. Accounting for sample composition (the amount of benign structures such as stroma and epithelial cells in addition to the cancer component) was important to improve subtype assignments and should also be considered in future studies. Our study validates a previous molecular subtyping of PCa in a new patient cohort, and identifies a subgroup of PCa samples highly interesting for detecting high risk PCa at an early stage. The importance of taking sample tissue composition into account when assigning subtype is emphasized.	f	\N
25120773	Hirschsprung's disease (HSCR) is characterized by the absence of enteric ganglion cells along variable regions of the colon. Established theory demonstrates that HSCR is the consequence caused by the abnormal arrest of the migration and differentiation of neural crest-derived stem cells (NCSCs). And retinoid signaling was considered to be involved. We speculated that, HA117, a retinoid-related transcript of a long noncoding RNA (LncRNA), may be involved in the genesis of HSCR. In current research, colon specimens were collected from 25 HSCR patients and grouped into 3 segments: proximal anastomosis, dilated segment and stenotic segment. Real-Time PCR was used to analyze the expression profiles of HA117 and its neighboring gene DPF3 in different colon segments. Fluorescence in situ hybridization (FISH) was employed to detect the distribution of HA117 in the gut wall. Immunohistochemistry was performed to analyze the protein expression of DPF3 in different colon segments. HA117 expression in stenotic segment was higher compared to proximal anastomosis and dilated segment (p < 0.05). Whereas DPF3b mRNA was lower in stenotic segment than that in two other segments (p < 0.05). FISH detected HA117 was distributed in mucosa and muscle layer, mainly present in stenotic segment. Immunohistochemical staining showed that intensive DPF3 staining occurred in proximal anastomosis and the positive staining was hardly observed in stenotic segment. The results suggested that HA117 may be a factor exerting an anti-differentiation or or anti-maturation role in the genesis of HSCR. This gave us a novel cue for better understanding the etiology of HSCR.	f	\N
25132753	More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori eradication and H. pylori induced related gastric disease prevention.	f	\N
25142630	To describe metastatic pattern of uterine leiomyosarcomas (ULMS) and correlate it with clinical and histopathologic parameters. We included 113 women (mean age, 53 years; range, 29 to 72 years) with histopathology-confirmed ULMS from 2000 to 2012. Distribution of metastases was noted from imaging by two radiologists in consensus. Predictors of development of metastases were analyzed with univariate and multivariate analysis. Impact of various clinical and histopathologic parameters on survival was compared using Log-rank test and Cox proportional hazard regression model. Distant metastases were seen in 81.4% (92/113) of the patients after median interval of 7 months (interquartile range, 1 to 21). Lung was most common site of metastases (74%) followed by peritoneum (41%), bones (33%), and liver (27%). Local tumor recurrence was noted in 57 patients (50%), 51 of whom had distant metastases. Statistically significant correlation was noted between local recurrence and peritoneal metastases (p<0.001) and between lung and other common sites of hematogeneous metastases (p<0.05). Age, serosal involvement, local recurrence, and the International Federation of Gynecology and Obstetrics (FIGO) stage were predictive factors for metastases. At the time of reporting, 65% (74/113) of the patients have died; median survival was 45 months. Stage, local recurrence, and age were poor prognostic factors. ULMS metastasizes most frequently to lung, peritoneum, bone, and liver. Local recurrence was associated with peritoneal spread and lung metastases with other sites of hematogeneous metastases. Age, FIGO stage and local recurrence predicted metastatic disease and advanced stage, older age and local recurrence predicted poor outcome.	f	\N
25148165	The purpose of this study is to compare CT urography (CTU) with unenhanced CT in the evaluation of upper urinary tracts in adults younger than 50 years with asymptomatic microscopic hematuria. In this study, 1516 CTU examinations were reviewed in adults younger than 50 years. Inclusion criteria were no significant prior urologic disease and asymptomatic microscopic hematuria with at least one urinalysis with greater than or equal to 3 RBCs/high-power field and less than or equal to 50 RBCs/high-power field. Upper urinary tract findings on CTU were classified as malignancy-related or non-malignancy-related hematuria and incidental non-hematuria-related findings. A blinded radiologist reviewed the unenhanced images, recording upper urinary tract findings and recommendations for further contrast-enhanced imaging. The modified Wald equation at a 95% CI, the "Rule of Threes" equation, and binomial distribution were used for malignancy-related findings. Four hundred forty-five examinations in 442 patients met inclusion criteria. CTU reports showed zero malignancy-related hematuria findings, 64 non-malignancy-related hematuria findings (62 renal calculi and two others), and 138 incidental non-hematuria-related findings. Unenhanced CT interpretation had a sensitivity of 100% (64/64) and a specificity of 89.2% (337/378). The theoretic risk of an upper urinary tract malignancy is 0-1.1%. CTU added no additional diagnostic benefit versus unenhanced CT in evaluating the upper urinary tracts of adults younger than 50 years with asymptomatic microscopic hematuria. Using only unenhanced CT can reduce radiation and minimize contrast agent-associated risk, with a less than 1.0% risk of missing upper urinary tract hematuria-related malignancy.	f	\N
25151899	To assess the effects of neoadjuvant chemoradiotherapy on survival outcomes of low rectal cancer after sphincter-preserving or removing surgery. A total of 135 patients with rectal cancer within 10 cm from anal verge after neoadjuvant chemoradiotherapy were enrolled into this retrospective study from 2005 to 2012 at a single institute. There were 79 males and 56 females with a mean age of (58 ± 12) years and an average distance of (5.2 ± 2.1) cm from anal verge. The effects of gender, age, distance of tumor from anal verge, surgical procedure, T-stage downstaging, lateral resection margin and post-treatment lymphatic node status on 3-year disease-free survival (DFS) were examined. The overall 3-year DFS was 85.2% (115/135). Among 95 sphincter-preserving operations, there were anterior resection (n = 79), anterior perineal plane for ultra low anterior resection (APPEAR) technique (n = 12), Hartmann procedure (n = 3) and Parks procedure (n = 1). Among 40 sphincter-removing operations, there were abdominoperineal resection (APR) procedure (n = 39) and intersphincteric resection(ISR) (n = 1). The survival of patients undergoing sphincter-preserving or removing procedures did not differ in 3-year DFS (85.3% (81/95) vs 85.0% (34/40) , χ(2) = 0.000, P = 0.985) . Lateral resection margin and post-treatment lymphatic node status significantly affected DFS. The differential level from anal verge showed a trend of close relationship to 3-year DFS (81.5% (22/27) for 2-3 cm, 82.5% (47/57) for 4-5 cm vs 95.1% (39/41) for 6-7 cm), but without statistic significance (χ(2) = 3.111, 3.522; P = 0.078, 0.061). The survival rate for patients with sphincter-preserving at 6-7 cm from anal verge was significantly higher than that at 4-5 cm (95.0% (38/40) vs 79.5% (31/39) ,χ(2) = 4.227, P = 0.039) , but showed no differences to that with sphincter-removing at 2-3 cm from anal verge (81.0% (17/21),χ(2) = 2.864, P = 0.091) . The multivariate analysis showed that post-treatment lymphatic node status was the only prognostic factor to 3-year DFS (Wald = 4.454, P = 0.035) . Lateral resection margin and post-treatment lymphatic node status play an important role on DFS for patients with low rectal cancer after neoadjuvant chemoradiotherapy. The distance from anal verge is correlated with 3-year disease-free survival. Patients with tumor at 4-5 cm from annal verge can not benefit for survival when they get sphincter-preserving operations.	f	\N
25155018	Frontotemporal dementia (FTD) is the most common cause of dementia in people under 60 yr of age and is pathologically associated with mislocalization of TAR DNA/RNA binding protein 43 (TDP-43) in approximately half of cases (FLTD-TDP). Mutations in the gene encoding progranulin (GRN), which lead to reduced progranulin levels, are a significant cause of familial FTLD-TDP. Grn-KO mice were developed as an FTLD model, but lack cortical TDP-43 mislocalization and neurodegeneration. Here, we report retinal thinning as an early disease phenotype in humans with GRN mutations that precedes dementia onset and an age-dependent retinal neurodegenerative phenotype in Grn-KO mice. Retinal neuron loss in Grn-KO mice is preceded by nuclear depletion of TDP-43 and accompanied by reduced expression of the small GTPase Ran, which is a master regulator of nuclear import required for nuclear localization of TDP-43. In addition, TDP-43 regulates Ran expression, likely via binding to its 3'-UTR. Augmented expression of Ran in progranulin-deficient neurons restores nuclear TDP-43 levels and improves their survival. Our findings establish retinal neurodegeneration as a new phenotype in progranulin-deficient FTLD, and suggest a pathological loop involving reciprocal loss of Ran and nuclear TDP-43 as an underlying mechanism.	f	\N
25159901	Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic acid (ALA, 18 : 3n-3), a plant-derived long-chain essential n-3 fatty acid, is associated with a lower risk of these outcomes is unclear. The aim of the present study was to examine the associations of plasma phospholipid and dietary ALA with the risk of mortality, CHD and stroke among older adults who participated in the Cardiovascular Health Study, a cohort study of adults aged ≥ 65 years. A total of 2709 participants were included in the plasma phospholipid ALA analysis and 2583 participants were included in the dietary ALA analysis. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with the risk of mortality, incident CHD and stroke. In minimally and multivariable-adjusted models, plasma phospholipid ALA was found to be not associated with the risk of mortality, incident CHD or stroke. After adjustment for age, sex, race, enrolment site, education, smoking status, diabetes, BMI, alcohol consumption, treated hypertension and total energy intake, higher dietary ALA intake was found to be associated with a lower risk of total and non-cardiovascular mortality; on comparing the highest quintiles of dietary ALA with the lowest quintiles, the HR for total mortality and non-cardiovascular mortality were found to be 0·73 (95 % CI 0·61, 0·88) and 0·64 (95 % CI 0·52, 0·80), respectively. Dietary ALA was found to be not associated with the risk of cardiovascular mortality, incident CHD or stroke. In conclusion, the results of the present suggest study that dietary ALA, but not plasma phospholipid ALA, is associated with a lower risk of total and non-cardiovascular mortality in older adults.	f	\N
25176287	Oxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests. COPD patients (n=40), mean FEV1 58% predicted normal, received single-dose inhaled formoterol 9μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler(®) 320/9μg or formoterol Turbuhaler(®). OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function. OE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p<0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p<0.05) and increased oxygen extraction from the lung by 58% (p<0.01). Single-dose formoterol increased both lung wash-out time (+47%, p<0.05) and lung oxygenation time (+47%, p<0.05). FEV1 was improved by single-dose formoterol (+12%, p<0.001) and 8 weeks of budesonide/formoterol (+ 18%, p<0.001), consistent with published studies. In COPD, OE-MRI parameters showed response to both single-dose bronchodilatory effects of a β2-agonist, formoterol, and 8-week treatment with an inhaled corticosteroid, budesonide, and the measurements are feasible in a small-scale multi-center trial setting.	f	\N
25178342	In the last decade, the clinical picture of primary hyperparathyroidism has changed, with the majority of patients being diagnosed while asymptomatic and the "classical" clinical pattern characterized by bone disease, recurrent nephrolithiasis, peptic ulcer disease, neurological or psychiatric disorders being rarely encountered. In this context, most patients have minimal hypercalcemia and small parathyroid adenomas. Not surprisingly, giant parathyroid adenomas have seldom been described in the literature. We herein report three cases of giant parathyroid adenomas weighing more than 30 g and discuss their clinicopathological and therapeutic particularities. We also review the relevant literature, with the principal aim of outlining the rarity of these giant parathyroid adenomas and the issues concerning their diagnosis and treatment.	f	\N
25179307	To explore if inhibition of vitronectin can be used for the treatment of hepatocellular carcinoma. RNAi technology was used to silence the expression of VTN in HepG2 and SMMC 7721 cells. Change of growth characteristics in these cells was evaluated. VTN silencing does not affect growth characteristics of cancer cells in monolayer cell culture, but could suppress the colonized growth of cells in soft agar. VTN-siRNA suppresses colony formation more than 80% compared with that of control in SMMC7721cells and leads to the inhibition of colony formation of over 70% in HepG2 cells. In addition, VTN silencing decreases the size of tumor xenografts in nude mice, particularly in male mice, with an inhibition rate of 46.6%. VTN plays a significant role in the malignant growth of tumor. Inhibition of VTN could potentially be applied for the treatment of hepatocellular carcinoma.	f	\N
25182131	The difficulties arising from association analysis with rare variants underline the importance of suitable reference population cohorts, which integrate detailed spatial information. We analyzed a sample of 1684 individuals from Western France, who were genotyped at genome-wide level, from two cohorts D.E.S.I.R and CavsGen. We found that fine-scale population structure occurs at the scale of Western France, with distinct admixture proportions for individuals originating from the Brittany Region and the Vendée Department. Genetic differentiation increases with distance at a high rate in these two parts of Northwestern France and linkage disequilibrium is higher in Brittany suggesting a lower effective population size. When looking for genomic regions informative about Breton origin, we found two prominent associated regions that include the lactase region and the HLA complex. For both the lactase and the HLA regions, there is a low differentiation between Bretons and Irish, and this is also found at the genome-wide level. At a more refined scale, and within the Pays de la Loire Region, we also found evidence of fine-scale population structure, although principal component analysis showed that individuals from different departments cannot be confidently discriminated. Because of the evidence for fine-scale genetic structure in Western France, we anticipate that rare and geographically localized variants will be identified in future full-sequence analyses.	f	\N
25185440	To estimate the prevalence and risk factors of dry eye disease (DED) in a female cohort in the UK. Population-based cross-sectional association study of 3824 women from the TwinsUK cohort aged 20-87 years. A questionnaire was used to evaluate DED and several risk factors. Binary logistic regression, corrected for age, was used to examine the association between DED and risk factors. 9.6% of women had a DED diagnosis and concomitant use of artificial tears, and 20.8% experienced DED symptoms in the past 3 months. Risk factors that were significantly associated with DED were age, asthma, eczema, the presence of any allergy, cataract surgery, rheumatoid arthritis, osteoarthritis, migraine and stroke. The highest effect sizes were found with depression, pelvic pain, irritable bowel syndrome and chronic widespread pain syndrome (all p<0.0005). Subjects with DED symptoms scored significantly lower on self-perceived health, compared with controls (p=0.001). DED is common and increases with age within this cohort of female twins. We confirmed established risk factors for the first time in a British population, and found important risk factors that might relate to an underlying aetiology involving chronic pain predisposition or somatisation.	f	\N
25187623	The phenomenon that adverse environmental exposures in early life are associated with increased susceptibilities for many adult, particularly metabolic diseases, is now referred to as 'developmental origins of health and disease (DOHAD)' or 'Barker' hypothesis. Fetal overnutrition and undernutrition have similar long-lasting effects on the setting of the neuroendocrine control systems, energy homeostasis, and metabolism, leading to life-long increased morbidity. There are sensitive time windows during early development, where environmental cues can program persistent epigenetic modifications which are generally assumed to mediate these gene-environment interactions. Most of our current knowledge on fetal programing comes from animal models and epidemiological studies in humans, in particular the Dutch famine birth cohort. In industrialized countries, there is more concern about adverse long-term consequences of fetal overnutrition, i.e. by exposure to gestational diabetes mellitus and/or maternal obesity which affect 10-20% of pregnancies. Epigenetic changes due to maternal diabetes/obesity may predispose the offspring to develop metabolic disease later in life and, thus, transmit the adverse environmental exposure to the next generation. This vicious cycle could contribute significantly to the worldwide metabolic disease epidemics. In this review article, we focus on the epigenetics of an adverse intrauterine environment, in particular gestational diabetes, and its implications for the prevention of complex disease.	f	\N
25197402	After 3 months of combination treatment using interferon α-2a and Ribavirin, a case of 59-year-old female patient with chronic viral hepatitis C demonstrated symptoms such as headache, dizziness accompanied by nausea, vomiting, dry cough, breathing difficulty, and shortness of breath. Dynamic electrocardiogram showed occasional atrial premature beats, paroxysmal tachycardia, and abnormal ST-T (T wave inversion and prolongation of the QT interval). Ambulatory blood pressure indicated that mean blood pressure was elevated than before. Myocardial radionuclide scan showed focal myocardial ischemia in left ventricular inferior wall. Pulmonary function tests showed that pulmonary diffusion function was decreased, indicating the possibility of interstitial pneumonia. The patient had no history of coronary heart disease or chest X-ray abnormalities before medication, but had hypertensive medical history for 8 years with good blood pressure control. After withdrawal of antiviral drugs, symptoms such as dry cough, breathing difficulty and T wave inversion were gradually relieved. This case indicated that myocardial ischemia and pulmonary lesions were associated with the application of pegylated interferon α-2a.	f	\N
25204216	Acquired immunodeficiency syndrome (AIDS) is a major health problem worldwide. The number of infected people is increasing daily. Knowledge and awareness toward prevention and control of the disease is necessary among both educated and illiterate people. This study is aimed at assessing the knowledge and awareness about human immunodeficiency virus (HIV)/AIDS among undergraduate students studying in a technical institute in Gorakhpur, Uttar Pradesh, India. A community-based cross-sectional study was conducted among youths aged 15-30 years studying in a technical institution in Gorakhpur. Data were collected using a semistructured questionnaire developed with the help of existing literature, from 250 participants (students). The main source of information was the television; knowledge about the difference between HIV/AIDS was satisfactory. The findings showed that the knowledge about modes of prevention (blood checkup, needle/syringe sterilization) was satisfactory. There were several misconceptions about the modes of transmission of the disease, such as through mosquito bites, eating/drinking, and kissing. The knowledge of the study population was satisfactory, and there is a need for innovation and comprehensive education to impart better knowledge and understanding about HIV/AIDS.	f	\N
25204587	Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder involving both upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Vascular endothelial growth factor (VEGF) was originally described as a factor with a regulatory role in vascular growth and development, and now it also functions as a neurotrophic factor protecting motoneurons from insults such as oxidative stress, hypoxia and glutamate-excitotoxicity, but the role of VEGF in ALS is still unclear. The aim of this study is to measure cerebrospinal fluid (CSF) and serum VEGF levels in patients with ALS, and to investigate whether there are correlations between CSF and serum VEGF levels and clinical parameters of the disease and whether VEGF has a prognostic and evaluating potential for ALS. Results showed that VEGF levels were found to increase significantly in CSF and serum in ALS patients studied; they were positively and significantly correlated with the disease duration in ALS patients and inversely and significantly correlated with disease progression rate (DPR) of ALS patients. Moreover, CSF and serum from ALS patients with long duration and slow disease progression rate revealed higher VEGF levels as compared to ALS patients with short duration and rapid disease progression rate. In conclusion, VEGF upregulation may indicate an activation of compensatory responses in ALS which may reflect or in fact account for increased duration and slow disease progression rate. We propose that VEGF may be a useful biomarker having the prognostic and evaluating potential for ALS.	f	\N
25216396	Whether carotid artery stenosis predicts stroke after noncardiac surgery remains unknown. We therefore tested the primary hypothesis that degree of carotid artery stenosis is associated with in-hospital stroke or 30-day all-cause mortality after noncardiac surgery. As carotid artery stenosis is also a marker for cardiovascular disease, our secondary hypothesis was that degree of carotid artery stenosis is associated with postoperative myocardial injury. We included adults who had noncardiac, noncarotid surgery at Cleveland Clinic from 2007 to 2011 and had carotid duplex ultrasound performed either within 6 months before or 1 month after surgery. Internal carotid artery peak systolic velocity (ICA PSV) was used as a measure of carotid artery stenosis severity. A multivariate (i.e., multiple outcomes per patient) generalized estimating equation model was used to assess the association between highest ICA PSV and the composite of stroke and 30-day mortality after adjusting for predefined potentially confounding variables. Of 2,110 patients included, 112 (5.3%) died within 30 days and 54 (2.6%) suffered postoperative in-hospital stroke. ICA PSV was not associated with this composite outcome (odds ratio of 1.0 [95% confidence interval: 0.99, 1.02] for a 10-unit increase, P = 0.55). ICA PSV was also not associated with postoperative myocardial injury (odds ratio 1.00 [0.99, 1.02], P = 0.49). This cohort represents a high-risk population, as carotid duplex examinations were likely prompted by neurological symptoms. There was nonetheless no association between carotid artery stenosis and perioperative stroke or 30-day mortality after noncardiac surgery.	f	\N
25222481	Thrombocytopenia (defined as a platelet count <150×10(9)) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×10(9) to 75×10(9)) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease.	f	\N
25225437	Cabozantinib (XL184), an oral inhibitor of multiple receptor tyrosine kinases such as MET and VEGFR2, was evaluated in a phase II nonrandomized expansion study in castration-resistant prostate cancer (CRPC). Patients received open-label cabozantinib at daily starting doses of 100 mg or 40 mg until disease progression or unacceptable toxicity. The primary end point was bone scan response, defined as ≥ 30% reduction in bone scan lesion area. Other efficacy end points included overall survival, pain, analgesic use, and biomarkers. One hundred forty-four patients sequentially enrolled in either a 100-mg (n = 93) or 40-mg (n = 51) study cohort. Ninety-one patients (63%) had a bone scan response, often by week 6. Treatment resulted in clinically meaningful pain relief (57% of patients) and reduction or discontinuation of narcotic analgesics (55% of patients), as well as improvements in measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Improvements in each of these outcomes were observed in both cohorts: bone scan response in 73% and 45%, respectively; reductions in measurable soft tissue disease in 80% and 79%, respectively. Median overall survival was 10.8 months for the entire population. Most common grade 3 or 4 adverse events were fatigue (22%) and hypertension (14%). Fewer dose reductions because of toxicity were required in the 40-mg group. The evidence suggests that cabozantinib has clinically meaningful activity in CRPC. Cabozantinib resulted in improvements in bone scans, pain, analgesic use, measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Taken together, these phase II observations warrant further development of cabozantinib in prostate cancer.	f	\N
25230241	Chagas disease (CD) has been associated with an elevated risk of stroke, but current data are conflicting and prospective controlled studies are lacking. We performed a systematic review and meta-analysis examining the association between stroke and CD. Pubmed, Embase, Cochrane Central, Latin American database, and unpublished data were searched with the use of the following terms: ("Chagas" OR "American trypanosomiasis") AND ("dilated" OR "ischemic" OR "idiopathic" OR "nonChagasic" OR "stroke" OR "cerebrovascular"). We included studies that reported prevalence or incidence of stroke in a CD group compared with a non-CD control group. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed with the use of a random-effects model. A total of 8 studies and 4,158 patients were included, of whom 1,528 (36.7%) had CD. Risk of stroke was elevated in the group of patients with CD (OR 2.10, 95% CI 1.17-3.78). Similar results were observed in a subanalysis of cardiomyopathy patients (OR 1.74, 95% CI 1.02-3.00) and in sensitivity analysis with removal of each individual study. Furthermore, exclusion of studies at higher risk for bias also yielded consistent results (OR 1.70, 95% CI 1.06-2.71). Subanalysis restricted to studies that included patients with the indeterminate form found no significant difference in the stroke prevalence between CD and non-CD patients (OR 3.10, 95% CI 0.89-10.77). CD is significantly associated with cerebrovascular events, particularly among patients with cardiomyopathy. These findings underline the need for prospective controlled studies in patients with Chagas cardiomyopathy to ascertain the prognostic significance of cerebrovascular events and to evaluate the role of therapeutic anticoagulation in primary prevention.	f	\N
25231249	Drug-induced liver injury (DILI) is a major safety concern during drug development and remains one of the main reasons for withdrawal of drugs from the market. Although it is crucial to develop methods that will detect potential hepatotoxicity of drug candidates as early and as quickly as possible, there is still a lack of sensitive and specific biomarkers for DILI that consequently leads to a scarcity of reliable hepatotoxic data. Hence, in this study, we assessed characteristic molecular signatures in rat liver treated with drugs (pyrazinamide, ranitidine, enalapril, carbamazepine and chlorpromazine) that are known to cause DILI in humans. Unsupervised hierarchical clustering analysis of transcriptome changes induced by DILI-causing drugs resulted in three different subclusters on dendrogram, i.e., hepatocellular, cholestatic and mixed type of DILI at early time points (2 days), and multiclassification analysis suggested 31 genes as discernible markers for each DILI pattern. Further analysis for characteristic molecular signature of each DILI pattern provided a molecular basis for different modes of DILI action. A proteomics study of the same rat livers was used to confirm the results, and the two sets of data showed 60 matching classifiers. In conclusion, the data of different DILI-causing drug treatments from genomic analysis in a rat model suggest that DILI-specific molecular signatures can discriminate different patterns of DILI at an early exposure time point, and that they provide useful information for mechanistic studies that may lead to a better understanding of the molecular basis of DILI.	f	\N
25297522	Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered.	f	\N
25302175	Cervical cancer is a worldwide disease that constitutes a significant public health problem, especially in developing countries, not only due to its high incidence but also because the most affected population comprises women who belong to marginalized socio-economic classes. Clinical and molecular research has identified immunological impairment in squamous intraepithelial cervical lesions and cervical cancer patients. Human Papillomavirus (HPV) has several mechanisms for avoiding the immune system: it down-regulates the expression of interferon and upregulates interleukin (IL)-10 and transforming growth factor (TGF)-β1 to produce a local immunosuppressive environment, which, along with altered tumor surface antigens, forms an immunosuppressive network that inhibits the antitumor immune response. In this review we analyzed the available data on several deregulated cellular immune functions in patients with NIC I, NIC II and NIC III and cervical cancer. The effects of immunosuppressive cytokines on innate immune response, T-cell activation and cellular factors that promote tumor cell proliferation in cervical cancer patients are summarized. We discuss the functional consequences of HPV E2, E6, and E7 protein interactions with IL-10 and TGF-β1 promoters in the induction of these cytokines and postulate its effect on the cellular immune response in squamous intraepithelial cervical lesions and cervical cancer patients. This review provides a comprehensive picture of the immunological functions of IL-10 and TGF-β1 in response to HPV in humans.	f	\N
25305425	Vascular blowout syndrome is a well-known, life-threatening condition complicating advanced-stage head and neck malignancies but has rarely been reported in the gynecologic oncology realm in association with the femoral circulation. A 50-year-old woman with metastatic vulvar squamous cell carcinoma presented with left threatened femoral arterial blowout, secondary to an exophytic neoplastic mass originating from the left inguinal lymph nodes. Bland embolization of the tumor as well as 3 vessel covered stent revascularization was successfully performed with excellent tumor devascularization and reinstitution of arterial integrity. Successful devascularization of the tumor, with no non-target embolization was achieved, with excellent apposition and deployment of 3 covered stents in the femoral artery bifurcation. We present a unique case of threatened femoral artery blowout syndrome in the setting of metastatic vulvar carcinoma requiring various endovascular techniques for palliation. These endovascular techniques can be invaluable in minimally invasive palliation of advanced stage neoplasms abutting the iliofemoral circulation.	f	\N
25312087	Despite the pressing need for novel cancer treatments, our improved understanding of tumor biology is not being successfully translated into better therapies. Here we present a lentiviral vector that enables in vivo validation of cancer therapeutic targets when combined with existing cancer animal models that faithfully reproduce the natural history of human disease. Unlike the conventional genetic approaches with targeted alleles, the outlined experimental strategy could be used to assess the preclinical efficacy of a growing number of putative therapeutic hits in a rapid and cost-effective manner.	f	\N
25313751	There is a rising trend in the incidence of (colorectal carcinoma) colorectal cancer (CRC) in India. Nuclear factor kappa B (NFkB) is a transcription factor which belongs to the Rel family. It has an impact on phenomena such as apoptosis, tumor progression and differentiation. (1) To evaluate the grade and stage in 50 cases of colorectal carcinoma. (2) To evaluate the NFkB translocation into the nucleus of the cells. (3) To compare the benign and malignant areas with the degree of NFkB translocation and compare the translocation with the grade and pathological stage. The grade and stage of the tumors was evaluated. NFkB staining was performed on the tissues. The results of the immunostaining were analyzed semi quantitatively as a percentage of positive cells. Statistical Package for Social Sciences 13.0 statistical package program (SPSS, Lead Technologies Inc, USA) for windows was used. Correlation was carried out using the Pearson's correlation co-efficient and the Chi-square test. There were 29 males (58%) and 21 females (42%). Most of the cases were well-differentiated adenocarcinomas (58%). There was a significant difference between NFkB translocation in the epithelial cells and lymphocytes in the benign and malignant areas (P - 0.04 and P - 0.001 respectively). There was a significant correlation between the grade of NFkB staining in the malignant epithelial cells with the tumor and nodal status (P - 0.001 and P - 0.001). It is likely that NFkB is an important factor in the pathogenesis of CRC. Further studies including therapeutic intervention using strategies which prevent activation of NFkB in colorectal carcinoma patients will tell if we could alter the course of the disease favorably.	f	\N
25320726	Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.	f	\N
25323223	Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored. Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children. The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality. PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.	f	\N
25326379	Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is highly expressed in neurons. A possible role for UCH-L1 in neurodegeneration has been highlighted because of its presence in Lewy bodies associated with Parkinson disease and neurofibrillary tangles observed in Alzheimer disease. UCH-L1 exists in two forms in neurons, a soluble cytoplasmic form (UCH-L1(C)) and a membrane-associated form (UCH-L1(M)). Alzheimer brains show reduced levels of soluble UCH-L1(C) correlating with the formation of UCH-L1-immunoreactive tau tangles, whereas UCH-L1(M) has been implicated in α-synuclein dysfunction. Given these reports of divergent roles, we investigated the properties of UCH-L1 membrane association. Surprisingly, our results indicate that UCH-L1 does not partition to the membrane in the cultured cell lines we tested. Furthermore, in primary cultured neurons, a proportion of UCH-L1(M) does partition to the membrane, but, contrary to a previous report, this does not require farnesylation. Deletion of the four C-terminal residues caused the loss of protein solubility, abrogation of substrate binding, increased cell death, and an abnormal intracellular distribution, consistent with protein dysfunction and aggregation. These data indicate that UCH-L1 is differently processed in neurons compared with clonal cell lines and that farnesylation does not account for the membrane association in neurons.	f	\N
25332150	We conducted this pilot randomized clinical trial to determine the feasibility of a large clinical trial aimed at testing whether early use of catheter ablation of ventricular tachycardia (VT) is superior to antiarrhythmic medications at reducing mortality. Patients were enrolled at 4 sites if they had ischemic heart disease, an implantable cardioverter defibrillator (ICD), and received ≥1 ICD shock or ≥3 antitachycardia pacing therapies for VT. Patients were randomized to 2 arms: (1) antiarrhythmic medication (n = 14) and (2) catheter ablation (n = 13); patients were followed at 3 and 6 months. Endpoints included recurrent VT, time to first ICD therapy for VT, and death. Of 243 screened patients, 27 were enrolled. Main reasons for screen failures were: (1) patient was already on an antiarrhythmic medication (88 [41%]), (2) VT due to a reversible cause (23 [11%]), and (3) incessant VT (20 [9%]). Fourteen patients had recurrent VT, 8 (62%) in the ablation arm and 6 (43%) in the antiarrhythmic medication arm. Median time to recurrent VT was 75 days (25th, 75th: 51, 89) in the ablation arm and 57 days (30, 145) in the antiarrhythmic arm. Four patients died, 2 in each arm. This clinical trial shows that most patients in clinical practice have already failed antiarrhythmic drug therapy before catheter ablation is considered, and the VT recurrence rates and death in these patients are high. For a large clinical trial to be feasible, factors limiting early consideration of catheter ablation need to be identified and addressed.	f	\N
25336691	To evaluate the relevance between lumican expression patterns and the clinical course of patients with pancreatic ductal adenocarcinoma (PDAC), and to investigate the role of lumican in PDAC progression. One hundred thirty-one patient tumors were chosen for tissue microarray staining, and Cox regression analysis was used to test the associations between lumican expression and clinical, pathologic, and oncologic outcomes in all patients. Primary PDAC cells and recombinant human lumican protein were used to establish a working model to mimic the in vivo interactions between stromal lumican and PDAC cells. Using this model, we tested the effects of lumican on EGFR signaling via Akt and hypoxia-inducible factor-1α (HIF1α) and its subsequent influence on glucose consumption, lactate production, intracellular ATP, and apoptotic cell death. Lumican was present in the stroma surrounding PDAC cells in roughly one-half of primary tumors and the direct xenografts. Patients with stromal lumican were associated with a profound reduction in metastatic recurrence after surgery and 3-fold longer survival than patients without stromal lumican. In PDAC cells, extracellular lumican reduced EGFR expression and phosphorylation through enhanced dimerization and internalization of EGFR and the resultant inhibition of Akt kinase activity. Lumican also reduced HIF1α expression and activity via Akt. PDAC cells with enhanced HIF1α activity were resistant to lumican-induced inhibition of glucose consumption, lactate production, intracellular ATP, and apoptosis. There is a positive association between stromal lumican in primary PDAC tumors and prolonged survival after tumor resection. Lumican plays a restrictive role in EGFR-expressing pancreatic cancer progression.	f	\N
25348595	Bioorthogonal cleavable linkers are attractive building blocks for compounds that can be manipulated to study biological and cellular processes. Sodium dithionite sensitive azobenzene-containing (Abc) peptides were applied for the temporary stabilization of recombinant MHC complexes, which can then be employed to generate libraries of MHC tetramers after exchange with a novel epitope. This technology represents an important tool for high-throughput studies of disease-specific T cell responses.	f	\N
25348708	Papillary squamous cell carcinoma (PSCC) of the uterine cervix is difficult to diagnose due to its rarity and limited data regarding its clinical behavior. We attempted to assess the degree of stromal invasion using magnetic resonance imaging (MRI) and evaluate possible treatments for this lesion in view of its clinical behavior. We analyzed 28 cases of PSCC diagnosed on the colposcopic selective biopsies. We studied the rate of accuracy of diagnoses of the colposcopic selective biopsies compared with the final diagnoses, and compared the rate of stromal invasion between the MRI and pathological findings while focusing on surgical methods and the clinical prognosis. Of the 28 patients, only 12 exhibited true PSCC. The other 16 patients were ultimately diagnosed with SCC or adenosquamous carcinoma based on the finding of the surgical specimens and exhibited relatively poor prognoses. Among the 12 true PSCC cases, the rate of diagnostic accuracy of stromal invasion (with or without) was only 58% (7/12) on the colposcopic selective biopsies. However, we were able to predict the presence of stromal invasion (microscopic borderline: approximately 3 mm) before surgery using MRI. None of the 10 patients treated with radical surgery displayed lymph node metastases. In addition, all 12 study patients exhibited no recurrence (mean: 49 months) and survived. MRI can be used to detect preinvasive and microinvasive disease before surgery. It is possible to select a less invasive surgical method than radical surgery in cases of preinvasive and microinvasive PSCC in view of the indolent clinical behavior of this disease.	f	\N
25348855	This perspective discusses the report by Pinsky and colleagues, which addresses whether noncalcified pulmonary nodules identified on CT screening carry short- and long-term risk for lung cancer. We are facing challenges related to distinguishing a large majority of benign nodules from malignant ones and among those a majority of aggressive from indolent cancers. Key questions in determining individual probabilities of disease, given their history, findings on CT, and upcoming biomarkers of risk, remain most challenging. Reducing the false positives associated with current low-dose computed tomography practices and identification of individuals who need therapy and at what time during tumor surveillance could reduce costs and morbidities associated with unnecessary interventions.	f	\N
25359996	To determine whether the prescription of co-trimoxazole with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker is associated with sudden death. Population based nested case-control study. Ontario, Canada, from 1 April 1994 to 1 January 2012. Ontario residents aged 66 years or older treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. Each case was matched with up to four controls on age, sex, chronic kidney disease, and diabetes. Odds ratio for the association between sudden death and exposure to each antibiotic relative to amoxicillin, after adjustment for predictors of sudden death according to a disease risk index. Of 39,879 sudden deaths, 1027 occurred within seven days of exposure to an antibiotic and were matched to 3733 controls. Relative to amoxicillin, co-trimoxazole was associated with an increased risk of sudden death (adjusted odds ratio 1.38, 95% confidence interval 1.09 to 1.76). The risk was marginally higher at 14 days (adjusted odds ratio 1.54, 1.29 to 1.84). This corresponds to approximately three sudden deaths within 14 days per 1000 co-trimoxazole prescriptions. Ciprofloxacin (a known cause of QT interval prolongation) was also associated with an increased risk of sudden death (adjusted odds ratio 1.29, 1.03 to 1.62), but no such risk was observed with nitrofurantoin or norfloxacin. In older patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers, co-trimoxazole is associated with an increased risk of sudden death. Unrecognized severe hyperkalemia may underlie this finding. When appropriate, alternative antibiotics should be considered in such patients.	f	\N
25372658	In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date. From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors. Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, >93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007). Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%.	f	\N
25375073	As of October 29, 2014, a total of 6,454 Ebola virus disease (Ebola) cases had been reported in Liberia by the Liberian Ministry of Health and Social Welfare, with 2,609 deaths. Although the national strategy for combating the ongoing Ebola epidemic calls for construction of Ebola treatment units (ETUs) in all 15 counties of Liberia, only a limited number are operational, and most of these are within Montserrado County. ETUs are intended to improve medical care delivery to persons whose illnesses meet Ebola case definitions, while also allowing for the safe isolation of patients to break chains of transmission in the community. Until additional ETUs are constructed, the Ministry of Health and Social Welfare is supporting development of community care centers (CCCs) for isolation of patients who are awaiting Ebola diagnostic test results and for provision of basic care (e.g., oral rehydration salts solutions) to patients confirmed to have Ebola who are awaiting transfer to ETUs. CCCs often have less bed capacity than ETUs and are frequently placed in areas not served by ETUs; if built rapidly enough and in sufficient quantity, CCCs will allow Ebola-related health measures to reach a larger proportion of the population. Staffing requirements for CCCs are frequently lower than for ETUs because CCCs are often designed such that basic patient needs such as food are provided for by friends and family of patients rather than by CCC staff. (It is customary in Liberia for friends and family to provide food for hospitalized patients.) Creation of CCCs in Liberia has been led by county health officials and nongovernmental organizations, and this local, community-based approach is intended to destigmatize Ebola, to encourage persons with illness to seek care rather than remain at home, and to facilitate contact tracing of exposed family members. This report describes one Liberian county's approach to establishing a CCC.	f	\N
25378846	The world-wide use of fireworks with their consequent detrimental effect on the air quality is widely recognized with elevated ambient air levels of particulate matter and its several metallic components and gases identified in several studies carried out during such events. Exposed individuals may be at risk following inhalation of such produced pollutants. This review focuses on the impact of fireworks on air quality and the potential effect of fireworks on the respiratory system of healthy individuals as well as those suffering from underlying respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). This applies not only to spectators including children but also to pyrotechnicians themselves. An extensive Medline search revealed that a strong evidence of the impact of fireworks on respiratory health is lacking in susceptible as well as healthy individuals with no formal studies on COPD or asthma, other than a few case reports in the latter. The implementation of global strategies to control the use of fireworks and hence improve air quality could possibly reduce their likely detrimental effect on human respiratory health in exposed individuals, but clearly a more targeted research is needed.	f	\N
25380207	In this paper a review of the researches on the role of Escherichia coli strain Nissle 1917 (EcN) in gastrointestinal diseases was presented. EcN is a non-pathogenic strain of the Enterobacteriaceae family, which has probiotic properties. In a number of studies conducted among humans and  experimental animals the application of EcN in treatment of gastrointestinal diseases was observed. Most studies about EcN has been devoted to this organism efficacy in ulcerative colitis treatment. Comparable results were obtained, by citied authors, in the treatment (sustaining remission) of EcN and mesalazine in ulcerative colitis. Moreover, this probiotic therapy, compared to placebo, contributes to obtaining a faster remission and improvement of intestinal histopathology. The use of EcN in Crohn's disease has not been the subject of as many studies as in the case of ulcerative colitis. Assessing the importance of EcN in treatment of other gastrointestinal disorders, authors of the studies observed, that in patients with irritable bowel syndrome, who receiving this probiotic there was a pain, nausea and bloating reduction. In studies conducted among children a positive impact of EcN in prevention and treatment of diarrhea was demonstrated. Similar results were obtained in studies conducted in experimental animals. Based on the presented review it can be concluded that the strain of Escherichia coli Nissle 1917 is useful in treatment of gastrointestinal diseases, especially in treatment of ulcerative colitis. This probiotic may constitute a part of treatment of irritable bowel syndrome and diarrhea. The effectiveness of this strain in treatment of Crohn's disease is not clearly established and further research are require.	f	\N
25385258	The objective of this meta-analysis was to determine the association of the apolipoprotein E (ApoE) gene with exceptional longevity (EL) (i.e., reaching 100+ years) by identifying possible unequal distribution of alleles/genotypes in the common variants ε2, ε3, and ε4 among centenarians and younger population. The association of ApoE with EL was analyzed in a total of 2776 centenarians (cases) and 11,941 younger controls (from 13 case-control studies) using the chi-squared test with the Yates correction. We conducted combined and separate analyses for all ethnic groups studied in the literature (Caucasian and Asian). The main result for all ethnic groups combined was that the likelihood of reaching EL was negatively associated with ε4 allele carriage [pooled odds ratio (OR)=0.43; 95% confidence interval (CI) 0.36, 0.50; p<0.001] and with ε4/ε4 (OR=0.18; 95% CI 0.08, 0.39; p<0.001), ε3/ε4 (OR=0.44; 95% CI 0.37, 0.53; p<0.001) and ε2/ε4 genotypes (OR=0.48; 95% CI 0.31, 0.74; p<0.001). In contrast, the ε2/ε3 genotype was positively associated with EL (OR=1.35; 95% CI 1.06, 1.72; p=0.017). When compared with the ε3 allele, the ε2 allele was not associated with increased odds of EL (OR=1.08; 95% CI 0.77, 1.50, p=0.660). The present meta-analysis confirms that, besides its previously documented influence on Alzheimer's and cardiovascular disease risk, the ApoE gene is associated with the likelihood of reaching EL.	f	\N
25386825	Hypertension is the most common cardiovascular disease and remains the most prevalent risk factor for cardiovascular diseases and a major cause of death worldwide. Despite the large number of antihypertensive drugs available, in the majority of patients blood pressure still remains not optimally controlled and persists at high risk of cardiovascular complications. The limitations of current therapies have stimulated the research and development of new classes of antihypertensive agents, with different mechanisms of action, that provide a better blood pressure control, greater protection against organ damage, better tolerability and more effective prevention of cardiovascular diseases. However, essential hypertension is a multifactorial and multigenic disorder, which means that various mechanisms contribute to a greater or lesser extent to increase BP. Recent advances in the understanding of the multiple and complex cellular signalling pathways that modulate vascular smooth muscle cell contraction and growth involved in the regulation of vascular tone and in hypertension-induced end-organ damage have provided valuable insight in identifying new therapeutic targets. This article reviews new antihypertensive drugs under development, focusing on their mechanisms of action and possible advantages compared with traditional drugs.	f	\N
25391248	We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution within the mineralized matrix. We show that calcium gluconate supplementation can increase bone mineral density in gastrectomized individuals and performs superior to calcium carbonate in restoring calcium/skeletal homoeostasis in a mouse model of achlorhydria.	f	\N
25391854	Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons. Therefore, the expression level of glutamate transporters could be important in essential tremor pathogenesis. Using Western blotting, we compared the expression levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched controls. We also studied the localization of EAAT1 and EAAT2 using immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein levels were similar in cases and controls (1.12 ± 0.83 vs. 1.01 ± 0.69, p =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of that in controls (0.35 ± 0.23 vs. 1.00 ± 0.62, p < 0.01). Interestingly, EAAT2, but not EAAT1, was expressed in astrocytic processes surrounding the Purkinje cell axon initial segment, a region of previously observed pathological changes in essential tremor. Our main finding, a significant reduction in cerebellar cortical EAAT2 protein levels in essential tremor, suggests that Purkinje cells in essential tremor might be more vulnerable to excitotoxic damage than those of controls.	f	\N
25400038	Schistosomiasis, one of the most important neglected tropical diseases worldwide, is caused by flatworms (blood flukes or schistosomes) that live in the bloodstream of humans. The hepatointestinal form of this debilitating disease results from a chronic infection with Schistosoma mansoni or Schistosoma japonicum. No vaccine is available to prevent schistosomiasis, and treatment relies predominantly on the use of a single drug, praziquantel. In spite of considerable research effort over the years, very little is known about the complex in vivo events that lead to granuloma formation and other pathological changes during infection. Here we use, for the first time, a lentivirus-based transduction system to deliver microRNA-adapted short hairpin RNAs (shRNAmirs) into the parasite to silence and explore selected protein-encoding genes of S. mansoni implicated in the disease process. This gene-silencing system has potential to be used for functional genomic-phenomic studies of a range of socioeconomically important pathogens.	f	\N
25400122	We report a 10-year-old male with relapsing Ph-like acute lymphoblastic leukemia (ALL) bearing ATF7IP/PDGFRB translocation. He was refractory to conventional therapy, and was finally treated with single-agent second-generation TKI dasatinib. The therapeutic response was prompt, with the disappearance of minimum residual disease (MRD) based on genomic PCR analysis within 3 months, and he has maintained complete molecular remission for 12 months. This case report describes an early-phase response to TKI monotherapy on Ph-like ALL, and technical tips for MRD monitoring on long-term follow-up.	f	\N
25404522	Untreated human immunodeficiency virus type 1 (HIV) infection is associated with persistent immune activation, which is an independent driver of disease progression in European and United States cohorts. In Uganda, HIV-1 subtypes A and D and recombinant AD viruses predominate and exhibit differential rates of disease progression. HIV-1 seroconverters (n = 156) from rural Uganda were evaluated to assess the effects of T-cell activation, viral load, and viral subtype on disease progression during clinical follow-up. The frequency of activated T cells was increased in HIV-1-infected Ugandans, compared with community matched uninfected individuals, but did not differ significantly between viral subtypes. Higher HIV-1 load, subtype D, older age, and high T-cell activation levels were associated with faster disease progression to AIDS or death. In a multivariate Cox regression analysis, HIV-1 load was the strongest predictor of progression, with subtype also contributing. T-cell activation did not emerge an independent predictor of disease progression from this particular cohort. These findings suggest that the independent contribution of T-cell activation on morbidity and mortality observed in European and North American cohorts may not be directly translated to the HIV epidemic in East Africa. In this setting, HIV-1 load appears to be the primary determinant of disease progression.	f	\N
25406883	Periorbital burns are an infrequent but potentially devastating injury. This study aimed to elucidate the spectrum of such injuries presenting to a UK burns centre and the outcome achieved in the cases requiring periorbital reconstruction for the restoration of function and form. Patients admitted to a UK regional burns centre between January 2005 and January 2011 with periorbital burns were identified from the Patient Administration System (PAS), theatre logs and the International Burns Injury database (IBID). Multiple parameters were assessed using patient notes, ITU and hospital image databases. Over 6 years, 167 patients with facial burns requiring surgery were treated, including 103 patients with eyelid burns. The mean burn size was 33% total body surface area. The eyelid burn depth varied; 67% superficial partial thickness, 17% deep dermal and 16% full thickness. Two patients lost complete vision in one eye, one patient underwent amniotic membrane grafting. In total 16 patients required periorbital reconstruction to maintain eye closure, with 1.8 operations on average per patient. Acute surgery was required in 11 patients, whilst late intervention (>3 months) was needed in 5, 2 patients had both acute and delayed surgery. Of the 5 late intervention patients 4 were treated with full thickness skin grafts and 1 with a Z plasty. Average time for final reconstruction with delayed surgery was 4.5 months. The goal in management of periorbital burns is preservation of vision, prevention of future complications and restoration of an acceptable aesthetic outcome. Total visual loss is thankfully rare, but early ophthalmology intervention is vital given the evidence of corneal damage as a brief therapeutic window exists.	f	\N
25410176	The goal of this cross-sectional observational study was to quantify the pattern-shift visual evoked potentials (VEP) and the thickness as well as the volume of retinal layers using optical coherence tomography (OCT) across a cohort of Parkinson's disease (PD) patients and age-matched controls. Forty-three PD patients and 38 controls were enrolled. All participants underwent a detailed neurological and ophthalmologic evaluation. Idiopathic PD cases were included. Cases with glaucoma or increased intra-ocular pressure were excluded. Patients were assessed by VEP and high-resolution Fourier-domain OCT, which quantified the inner and outer thicknesses of the retinal layers. VEP latencies and the thicknesses of the retinal layers were the main outcome measures. The mean age, with standard deviation (SD), of the PD patients and controls were 63.1 (7.5) and 62.4 (7.2) years, respectively. The patients were predominantly in the initial Hoehn-Yahr (HY) disease stages (34.8% in stage 1 or 1.5, and 55.8 % in stage 2). The VEP latencies and the thicknesses as well as the volumes of the retinal inner and outer layers of the groups were similar. A negative correlation between the retinal thickness and the age was noted in both groups. The thickness of the retinal nerve fibre layer (RNFL) was 102.7 μm in PD patients vs. 104.2 μm in controls. The thicknesses of retinal layers, VEP, and RNFL of PD patients were similar to those of the controls. Despite the use of a representative cohort of PD patients and high-resolution OCT in this study, further studies are required to establish the validity of using OCT and VEP measurements as the anatomic and functional biomarkers for the evaluation of retinal and visual pathways in PD patients.	f	\N
25412555	Ovary cancer is a disease charged of paradigms and a serious health problem. It's important to know its natural history, because has a multifactor origins, and understanding its behavior since risk factors until patient's death because metastatic disease is a challenger for oncology group. In this work we made a bibliographic, analytic review that brings up concepts related to its origin, evolution, risk factors, preclinical horizon, and clinical symptoms until the death of patient.	f	\N
25424781	While a PhD candidate, doing my thesis at the Oak Ridge National Laboratory, Biology Division under Dr. Charles Congdon, my introduction to the immune response was studying graft vs. host (GVH) disease as a consequence of bone marrow transplantation in mice. The sequalae of GVH was impressive, and demonstrated the potential of negative clinical consequences of the immune system. The idea of harnessing this immunological phenomena in cancer therapy was appealing even in the late 1960s. The problem was that at the time T-cells as a component of the immune system were identified but not defined. We moved to soluble antigen stimulation in mice and recognized and described the post antigen stimulation changes in lymphatic tissue germinal centers during the first 48 h after the induction of the humoral immune response. We described the extracellular localization of soluble antigens on the surface of dendritic reticular cells of the stroma, directing a response of B-cells to produce antibody against non-self. The ensuing reaction was the rapid proliferation of B-cells toward antibody secreting plasma cells.	f	\N
25428209	The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) is a multicenter randomized trial of stenting versus endarterectomy in patients with symptomatic and asymptomatic carotid disease. This study assesses management of vascular risk factors. Management was provided by the patient's physician, with biannual monitoring results collected by the local site. Therapeutic targets were low-density lipoprotein, cholesterol <100 mg/dL, systolic blood pressure <140 mm Hg, fasting blood glucose <126 mg/dL, and nonsmoking status. Optimal control was defined as achieving all 4 goals concurrently. Generalized estimating equations were used to compare risk factors at baseline with those observed in scheduled follow-up visits for up to 48 months. In the analysis cohort of 2210, significant improvements in risk-factor control were observed across risk factors for all follow-up visits compared with baseline. At 48 months, achievement of the low-density lipoprotein cholesterol goal improved from 59.1% to 73.6% (P<0.001), achievement of the systolic blood pressure goal improved from 51.6% to 65.1% (P<0.001), achievement of the glucose goal improved from 74.9% to 80.7% (P=0.0101), and nonsmoking improved from 74.4% to 80.9% (P<0.0001). The percentage with optimal risk-factor control also improved significantly, from 16.7% to 36.2% (P<0.001), but nearly 2 of 3 study participants did not achieve optimal control during the study. Site-based risk-factor control improved significantly in the first 6 months and over the long term in CREST but was often suboptimal. Intensive medical management should be considered for future trials of carotid revascularization. ClinicalTrials.gov. Unique identifier: NCT00004732.	f	\N
25439075	Gastric cancer is the third cause of cancer death worldwide, and Helicobacter pylori infection causes almost 90% of non-cardia cancers, the predominant type. H. pylori infection is treatable, and in clinical trials there is evidence of a 30-40% reduction in incidence of gastric cancer among treated subjects. However, with a few exceptions, there are no public health programmes for gastric cancer prevention. In December 2013, the International Agency for Research on Cancer (IARC), organized a Working Group of international experts to discuss and make recommendations for gastric cancer control. The Working Group considered that the enormous burden of disease, which is not expected to decline in the coming decades, requires decisive public health action to include gastric cancer in cancer control programmes. Interventions should be tailored to the local conditions and consider population-based screening and eradication of H. pylori, in the context of evaluation of feasibility, efficacy and adverse consequences.	f	\N
25439990	We report a case of KSHV/EBV associated germinotropic lymphoproliferative disorder (LPG) in a 49-year-old African patient, without immunosuppression. LPG is a rare entity arising in immunocompetent patients in opposition to other lymphoproliferative disorders associated to Kaposi sarcoma-associated herpes virus (KSHV). The disease presents itself as localized lymphadenopathy with an infiltration of germinal centers by plasmablastic cells coinfected by KSHV and EBV (Epstein-Barr Virus). After treatment, the outcome is favorable. Differential diagnosis in our case, due to the presence of clusters of Hodgkin-like cells in the mantle zone, included lymphocyte rich classic Hodgkin lymphoma (LHCRL) and nodular lymphocyte predominant Hodgkin lymphoma (LHNPL). Finally, we highlight the differential diagnostic criteria of KSHV lymphoproliferative diseases.	f	\N
25440885	While important efforts were made in the development of positron emission tomography (PET) tracers for the in vivo molecular diagnosis of Alzheimer's disease, very few investigations to develop magnetic resonance imaging (MRI) probes were performed. Here, a new generation of Gd(III)-based contrast agents (CAs) is proposed to detect the amyloid β-protein (Aβ) aggregates by MRI, one of the earliest biological hallmarks of the pathology. A building block strategy was used to synthesize a library of 16 CAs to investigate structure-activity relationships (SARs) on physicochemical properties and binding affinity for the Aβ aggregates. Three types of blocks were used to modulate the CA structures: (i) the Gd(III) chelates (Gd(III)-DOTA and Gd(III)-PCTA), (ii) the biovectors (2-arylbenzothiazole, 2-arylbenzoxazole and stilbene derivatives) and (iii) the linkers (neutrals, positives and negatives with several lengths). These investigations revealed unexpected SARs and a difficulty of these probes to cross the blood-brain barrier (BBB). General insights for the development of Gd(III)-based CAs to detect the Aβ aggregates are described.	f	\N
25445322	Aleutian disease virus (ADV, Amdovirus, Parvoviridae) primarily infects farmed mustelids (mink and ferrets) but also other fur-bearing animals and humans. Three Aleutian disease (AD) cases have been described in captive striped skunks; however, little is known about the relevance of AD in free-ranging carnivores. This work describes the pathological findings and temporospatial distribution in 7 cases of AD in free-ranging striped skunks. All cases showed neurologic disease and were found in a 46-month period (2010-2013) within a localized geographical region in California. Lesions included multisystemic plasmacytic and lymphocytic inflammation (ie, interstitial nephritis, myocarditis, hepatitis, meningoencephalitis, pneumonia, and splenitis), glomerulonephritis, arteritis with or without fibrinoid necrosis in several organs (ie, kidney, heart, brain, and spleen), splenomegaly, ascites/hydrothorax, and/or encephalomalacia with cerebral microangiopathy. ADV infection was confirmed in all cases by specific polymerase chain reaction and/or in situ hybridization. The results suggest that AD is an emerging disease in free-ranging striped skunks in California.	f	\N
25445432	The relationship between pre-hospital care and the prognosis of out-of-hospital cardiac arrest (OHCA) caused by respiratory disease is unclear. This study aimed to assess the impact of pre-hospital care on the prognosis of OHCA caused by respiratory disease. In a nationwide, population-based, observational study, we enrolled 121,081 adults aged ≥18 years who experienced OHCA from January 1, 2010, to December 31, 2010. The primary endpoint was favourable neurological outcomes. Of the 120,256 eligible adult OHCA patients, 7,071 (5.9%) experienced OHCA caused by respiratory disease. Of these 7,071 patients, 3,911 (55.3%) received no cardiopulmonary resuscitation (CPR), 2,403 (34.0%) received chest-compression-only CPR, and 757 (10.7%) received conventional CPR by a bystander. There was no significant difference between the three types of bystander CPR with regard to the neurological outcome (no CPR: OR 0.68, 95%CI 0.39-1.24, p=0.1951; chest-compression-only CPR: OR 0.68, 95%CI 0.37-1.29, p=0.2295; and conventional CPR: as a reference). Pre-hospital administration of epinephrine (OR 0.37, 95%CI 0.13-0.85, p=0.0170) and the implementation of advanced airway management (OR 0.32, 95%CI 0.19-0.52, p<0.0001) were associated with poor neurological outcomes. Even in OHCA caused by respiratory disease, not only pre-hospital epinephrine administration but also pre-hospital advanced airway management and rescue breathing in bystander CPR may not be critical.	f	\N
25456683	Group A streptococcal (GAS) infections are frequent in developing countries but the epidemiology is incompletely known. In 2005, 90 % of symptomatic pharyngitis, 96 % of invasive diseases and 97 % of deaths due to GAS were observed in these countries. Clinical features of GAS invasive infections are identical to those reported in developed countries, but frequency and mortality are higher, as is the number of the different emm types involved. In the world, from 15.6 to 19.6 millions of persons are affected by rheumatic heart disease (282,000 new cases and 233,000-468,000 deaths per year). Incidence of acute post-streptococcal glomerulonephritis varies with time and location: in 2005, 472,000 new cases have been reported in the world (83 % in a developing country). World Heart Federation recently aimed at reducing the burden of rheumatic heart diseases by 25 % among < 25 years persons in 2025.	f	\N
25467562	Patients are increasingly being admitted with chronic atrial fibrillation, and disease-specific management might reduce recurrent admissions and prolong survival. However, evidence is scant to support the application of this therapeutic approach. We aimed to assess SAFETY--a management strategy that is specific to atrial fibrillation. We did a pragmatic, multicentre, randomised controlled trial in patients admitted with chronic, non-valvular atrial fibrillation (but not heart failure). Patients were recruited from three tertiary referral hospitals in Australia. 335 participants were randomly assigned by computer-generated schedule (stratified for rhythm or rate control) to either standard management (n=167) or the SAFETY intervention (n=168). Standard management consisted of routine primary care and hospital outpatient follow-up. The SAFETY intervention comprised a home visit and Holter monitoring 7-14 days after discharge by a cardiac nurse with prolonged follow-up and multidisciplinary support as needed. Clinical reviews were undertaken at 12 and 24 months (minimum follow-up). Coprimary outcomes were death or unplanned readmission (both all-cause), measured as event-free survival and the proportion of actual versus maximum days alive and out of hospital. Analyses were done on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTRN 12610000221055). During median follow-up of 905 days (IQR 773-1050), 49 people died and 987 unplanned admissions were recorded (totalling 5530 days in hospital). 127 (76%) patients assigned to the SAFETY intervention died or had an unplanned readmission (median event-free survival 183 days [IQR 116-409]) and 137 (82%) people allocated standard management achieved a coprimary outcome (199 days [116-249]; hazard ratio 0·97, 95% CI 0·76-1·23; p=0·851). Patients assigned to the SAFETY intervention had 99·5% maximum event-free days (95% CI 99·3-99·7), equating to a median of 900 (IQR 767-1025) of 937 maximum days alive and out of hospital. By comparison, those allocated to standard management had 99·2% (95% CI 98·8-99·4) maximum event-free days, equating to a median of 860 (IQR 752-1047) of 937 maximum days alive and out of hospital (effect size 0·22, 95% CI 0·21-0·23; p=0·039). A post-discharge management programme specific to atrial fibrillation was associated with proportionately more days alive and out of hospital (but not prolonged event-free survival) relative to standard management. Disease-specific management is a possible strategy to improve poor health outcomes in patients admitted with chronic atrial fibrillation. National Health and Medical Research Council of Australia.	f	\N
25470167	This article provides a practical clinical approach for the role of exercise in the treatment and management of neurologic disorders. A number of clinical studies have reported positive benefits from exercise in various neurologic disease states, suggesting that this mode of intervention should be considered as another option in clinical management. Significant evidence-based data exists confirming the positive effects of exercise in otherwise healthy populations. Good evidence also exists that physical activity may benefit people with long-term neurologic conditions. Despite this evidence, exercise is often neglected in patients with normal aging or neurologic disease progression. Neurologists should counsel patients on this therapeutic adjunct and provide specific recommendations when possible.	f	\N
25476560	Cardiovascular risk remains uncertain in patients with cardiovascular disease despite achieving target lipid levels. Serum levels of lipoprotein(a) [Lp(a)] can be risk factors for adverse events. The aim of this study was to determine the role of Lp(a) as a residual risk factor in patients who achieve target lipid levels by the time of treatment by percutaneous coronary intervention (PCI). A total of 3,508 patients were treated by PCI from 1997 to 2011 at our institution. Among them, we analyzed consecutive 569 patients who achieved target lipid levels of low-density lipoprotein cholesterol <100 mg/dl, high-density lipoprotein cholesterol ≥40 mg/dl, and triglycerides <150 mg/dl at PCI. A total of 411 eligible patients were assigned to groups according to Lp(a) levels of ≥30 mg/dl (high Lp(a); n = 119) or <30 mg/dl (low Lp(a); n = 292). The primary outcome was a composite of all-cause death and acute coronary syndrome. The median follow-up period was 4.7 years. Cumulative event-free survival was significantly worse for the group with high Lp(a) than with low Lp(a) group (p = 0.04). Multivariate analysis selected a high Lp(a) level as an independent predictor of primary outcomes (hazard ratio 1.68, 95% confidence interval 1.03 to 2.70, p = 0.04). In conclusion, a high Lp(a) value (≥30 mg/dl) could be associated with a poor prognosis after PCI even for patients who achieved target lipid levels.	f	\N
25481243	The presence of somatic mutations in splicing factor 3b subunit 1 (SF3B1) in patients with Myelodysplastic syndromes with ring sideroblasts (MDS-RS) highlights the importance of the RNA-splicing machinery in MDS. We previously reported the presence of bone marrow (BM) RS in Sf3b1 heterozygous (Sf3b1 (+/-)) mice which are rarely found in mouse models of MDS. Sf3b1 (+/-) mice were originally engineered to study the interaction between polycomb genes and other proteins. We used routine blood tests and histopathologic analysis of BM, spleen, and liver to evaluate the hematologic and morphologic characteristics of Sf3b1 (+/-) mice in the context of MDS by comparing the long term follow-up (15 months) of Sf3b1 (+/-) and Sf3b1 (+/+) mice. We then performed a comprehensive RNA-sequencing analysis to evaluate the transcriptome of BM cells from Sf3b1 (+/-) and Sf3b1 (+/+) mice. Sf3b1 (+/-) exhibited macrocytic anemia (MCV: 49.5 ± 1.6 vs 47.2 ± 1.4; Hgb: 5.5 ± 1.7 vs 7.2 ± 1.0) and thrombocytosis (PLTs: 911.4 ± 212.1 vs 878.4 ± 240.9) compared to Sf3b1 (+/+) mice. BM analysis showed dyserythropoiesis and occasional RS in Sf3b1 (+/-) mice. The splenic architecture showed increased megakaryocytes with hyperchromatic nuclei, and evidence of extramedullary hematopoiesis. RNA-sequencing showed higher expression of a gene set containing Jak2 in Sf3b1 (+/-) compared to Sf3b1 (+/+). Our study indicates that Sf3b1 (+/-) mice manifest features of low risk MDS-RS and may be relevant for preclinical therapeutic studies.	f	\N
25482988	Cancer cell metabolism is deregulated, and signalling pathways can be involved. For instance, PI3K/Akt/mTOR is associated with normal proliferation and differentiation, and its alteration is detectable in cancer cells, that exploit the normal mechanisms to overcome apoptosis. On the other hand, also the family of Phospholipase C (PLC) enzymes play a critical role in cell growth, and any change concerning these enzymes or their downstream targets can be associated with neoplastic transformation. Here, we review the role of PLC and PI3K/Akt/mTOR signal transduction pathways in pathophysiology.	f	\N
25486686	The current economic difficulties and the changed epidemiological picture, characterized by an increase in life expectancy, which shows in the elderly, chronically ill and disabled the main, both health and social, care needs,r equires a remark on the hospital network and organization. Today, most of the application assistance is usually at low intensity of care, whereas the acute event is shrinking. The prevalence of hospital admissions concern the elderly, who get into acute events but on a substrate of chronicity and co-morbidity conditions. There must be a new model of hospital network, with the possibility of converting some hospital centres for medium intensity care and selecting few centres for high intensity care, where concentrating the more expensive technology and the skill and expertise of the professional. The -suggestion is a renewed health planning that detects:- hospitals for widespread disease, equipped with emergency war for minor codes-hospital at high intensity of care for emergency-urgency- hospital for particular fields of medical speciality and research.	f	\N
25497401	We present a Dutch family with a novel disease-causing mutation in the mitochondrial tRNA(Ser(UCN)) gene, m.7507A>G. The index patient died during the neonatal period due to cardio-respiratory failure and fatal lactic acidosis. A second patient, his cousin, has severe hearing loss necessitating cochlear implants and progressive exercise intolerance. Laboratory investigations of both patients revealed combined deficiencies of the enzyme complexes of the mitochondrial respiratory chain in several tissues. Reduced levels of fully assembled complexes I and IV in fibroblasts by BN-PAGE associated with (near) homoplasmic levels of the m.7507A>G mutation in several tissues and a severe reduction in the steady-state level of mt-tRNA(Ser(UCN)) in fibroblasts were observed. The novel mitochondrial DNA mutation was shown to segregate with disease; several healthy maternal family members showed high heteroplasmy levels (up to 76 ± 4% in blood and 68 ± 4% in fibroblasts) which did not lead to any alterations in the activities of the enzyme complexes of the respiratory chain in fibroblasts or clinical signs and symptoms. We hereby conclude that the m.7507A>G mutation causes a heterogeneous clinical phenotype and is only pathogenic at very high levels of mtDNA heteroplasmy.	f	\N
25500436	The abnormal formation and insufficient clearance of neutrophil extracellular traps (NETs) has been reported to be involved in the pathogenesis of lupus nephritis (LN). The abnormal regulation of NETs may contribute to increases in the levels of circulating cell-free DNA (cfDNA). The present study tested the hypothesis that elevated plasma cfDNA levels are related to LN. Fifty-four systemic lupus erythematosus (SLE) patients and 43 control subjects were included in this study. The cfDNA concentrations were measured using the Picogreen Kit, the low-density granulocyte (LDG) percentage in peripheral blood mononuclear cells (PBMCs) was tested using a flow cytometer and the DNase I activity was measured according to the radial enzyme-diffusion method. The mean cfDNA concentration in the SLE group was 236.66±40.09 ng/mL, which was significantly higher than that observed in the healthy control group (187.96±40.55 ng/mL, p<0.0001). Meanwhile, the mean cfDNA concentration in the patients with LN was significantly higher than that observed in the patients without LN (247.27±46.79 ng/mL vs. 213.56±31.34 ng/mL, p=0.0094), and the mean cfDNA concentration in the patients with active LN was significantly higher than that observed in the patients with inactive LN (254.22±50.16 ng/mL vs. 215.93±29.10 ng/mL, p=0.0349). In the SLE group, the cfDNA concentration was to positively correlate with the quantitative 24-hour urinary protein (r=0.350, p=0.013), LDG (r=0.6361, p=0.0019) and neutrophil (r=0.5990, p<0.0001) levels and inversely correlate with the albumin level (r=-0.500, p<0.0001) and endogenous creatinine clearance rate (r=-0.354, p=0.044). Compared to that observed in the control group, the SLE group exhibited a significantly increased percentage of LDGs in PBMCs and a significantly decreased DNase I activity. Our data indicate that elevated plasma cfDNA concentrations may be associated with active LN and partially attributed to the abnormal regulation of NETs in SLE patients, thus suggesting that NETs constitute an intrinsic link between cfDNA and active LN.	f	\N
25524212	The cause of type 1 diabetes remains unknown. To dissect the link between hyperexpression of human leukocyte antigen (HLA) class I on the islet cells, we examined its expression in subjects with recent-onset type 1 diabetes. IHC showed seemingly pronounced hyperexpression in subjects with recent-onset type 1 diabetes, as well as in some nondiabetic subjects. In all subjects, HLA class I expression on exocrine tissue was low. However, no difference in the level of HLA class I expression was found between islet and exocrine tissue using Western blot, flow cytometry, real-time quantitative PCR, or RNA sequencing analyses. Also, the level of HLA class I expression on the messenger level was not increased in islets from subjects with recent-onset type 1 diabetes compared with that in nondiabetic subjects. Consistently, the HLA class I specific enhanceosome (NLRC5) and related transcription factors, as well as interferons, were not enhanced in islets from recent-onset type 1 diabetic subjects. In conclusion, a discrepancy in HLA class I expression in islets assessed by IHC was observed compared with that using quantitative techniques showing similar expression of HLA class I in islets and exocrine tissue in subjects with recent-onset type 1 diabetes, nor could any differences be found between type 1 diabetic and nondiabetic subjects. Results presented provide important clues for a better understanding on how this complex disease develops.	f	\N
25536728	Brucellosis is an important disease in developing countries. We aimed to determine the epidemiologic, clinical, and laboratory characteristics of brucellosis, which still has a high morbidity in Turkey. Seventy-two patients with brucellosis, monitored at our clinic from January 2004 to July 2010, were reviewed retrospectively. The average age was determined to be 44.8 ± 18 years, and 40 of the patients were female (55.6%). The most frequent transmission route was the use of raw milk and dairy products, in 45 of the patients (62.5%). The most frequent complaints were joint pain, high fever, weakness, low back pain, and gastrointestinal symptoms, whereas the most frequent physical examination findings were fever, osteoarticular involvement, splenomegaly, hepatomegaly, and lymphadenopathy. All of the patients were positive for Rose Bengal testing. The standard tube agglutination titer was 1/160 or higher in 64 (88.9%) patients. Brucella melitensis was isolated from blood cultures of 13 (18.1%) patients and bone marrow cultures of 7 (9.7%) patients. Complications of sacroiliitis in 6 (8.3%), spondylodiscitis in 4 (5.6%), endocarditis in 2 (2.8%), neurobrucellosis in 1 (1.4%), and epididymo-orchitis in 1 (1.4%) of the patients were observed. Brucellosis has various clinical presentations. It should be included in the differential diagnosis of high fever and joint pains in endemic countries.	f	\N
25539271	Pancreatic adenocarcinoma is a rapidly progressive malignancy characterized by its tendency for early metastatic spread. MDCT is the primary diagnostic modality for the preoperative staging of patients with pancreatic cancer, with an accuracy established in multiple studies. However, for a variety of reasons, there is often a prolonged interval between staging MDCT and the surgical intervention. This study examines the relationship between the interval between imaging and surgery and the accuracy of MDCT in determining the presence or absence of metastatic disease at surgery in patients with pancreatic cancer. Patients were identified who had undergone surgery for pancreatic cancer at our institution with a dedicated preoperative pancreas-protocol MDCT performed in our department. Findings from the preoperative MDCT report were correlated with the operative findings, as well as the time between imaging and surgery. Two hundred ninety-two MDCT scans were performed on 256 patients who underwent exploration for pancreatic adenocarcinoma. The patients had a median age of 67 years (range, 30-95 years), and 51.6% (132/256) were male. The median time between MDCT and surgical exploration was 15.5 days (range, 1-198 days). MDCT correctly predicted the absence of metastatic disease at surgery in 233 of 274 (85.0%) studies. MDCT was more accurate in predicting the absence of metastatic disease if the study was performed within 25 days of surgery than it was if the study was performed within more than 25 days of surgery (89.3% vs 77.0%; p = 0.0097). Furthermore, regression models showed that the negative predictive value of a given MDCT significantly decreased after approximately 4 weeks. MDCT is an accurate method to stage patients with pancreatic cancer, but its accuracy in excluding distant metastatic disease depreciates over time. Patients should undergo a repeat MDCT within 25 days of any planned definitive operative intervention for pancreatic cancer to avoid unexpectedly finding metastatic disease at surgery.	f	\N
25545990	Dependence on invasive procedures for classification of patients with Sjögren's syndrome (SS) hampers timely diagnosis and suitable patient followup. The aim of this study was to recapitulate the diagnosis of SS through noninvasive means and to define the biologic state of SS patients' salivary glands. Using a 187-plex capture antibody-based assay, salivary proteomic biomarker profiles were generated from patients with primary SS, patients with rheumatoid arthritis, and asymptomatic controls. Discriminant function analyses and Gene Ontology-based network analyses allowed data analyses with a reductionist approach and with a focus on systems biology. Characterized by significant changes in 61 and 55 proteins, respectively, the salivary proteome of SS patients appeared profoundly altered compared to that of individuals without SS. On this basis, 4-plex and 6-plex biomarker signatures, both including interleukin-4 (IL-4), IL-5, and clusterin, achieved accurate prediction of an individual's group membership for at least 94% of cases. Of note, all misclassified SS patients presented with ectopic germinal center-like structures. Systematic inference of biologic meaning identified SS-related protein patterns delineating B cell-dominated immune responses, macrophage differentiation, and signs of T cell chemotaxis. In addition, proteomic Multi-Analyte Profiles provided insight about proteins related to collagen, cytokine, and growth factor synthesis as well as lipid transport. The SS-related molecular landscape conveyed by saliva showed great congruence with histopathologic features found in SS and advances understanding of this disease at a molecular level. Such salivary biomarker signatures harbor great potential for improving timeliness of SS diagnosis and enabling suitable patient followup.	f	\N
25546563	Sjögren's Syndrome (SS) is an autoimmune disease that causes sicca (dryness) symptoms by affecting secretions most notably of the lacrimal and salivary glands. Voice disorders have been documented in patients with SS, but the true prevalence and relationships among possible contributing factors remain unknown. This preliminary epidemiological investigation examined prevalence and risk factors for voice disorders in SS. Self-report epidemiological questionnaire. One hundred and one (101) patients with SS (94 females, 7 males; M age = 59.4 years; standard deviation [SD] = 14.1 years) completed an extensive interview using a previously validated questionnaire involving the patient's medical, family, occupational, psychosocial, social/lifestyle, voice use, and general health histories. Summary statistics, chi-squares, risk ratios, and multiple logistic regression were used to determine the frequency and severity of voice disorders in individuals with SS, as well as associations with demographic, lifestyle, health, disease severity, and voice use factors. The prevalence of a current voice disorder in individuals with SS was 59.4%. In general, voice disorders began gradually; were chronic; and correlated with SS disease severity independent of age, sex, duration of the disease, comorbid autoimmune conditions, and use of SS-related medication. Specific voice symptoms including chronic throat dryness and soreness were significantly associated with SS disease severity. Voice disorders are relatively common in SS and are more frequent as disease severity worsens. These findings have important implications for evaluation and treatment of patients with SS. 4.	f	\N
25549186	After injection into muscle and peripheral nerves, a variety of viral vectors undergo retrograde transport to lower motor neurons. However, because of its attractive safety profile and durable gene expression, adeno-associated virus (AAV) remains the only vector to have been applied to the human nervous system for the treatment of neurodegenerative disease. Nonetheless, only a very small fraction of intramuscularly injected AAV vector arrives at the spinal cord. To engineer a novel AAV vector by inserting a neuronal targeting peptide (Tet1), with binding properties similar to those of tetanus toxin, into the AAV1 capsid. Integral to this approach was the use of structure-based design to increase the effectiveness of functional capsid engineering. This approach allowed the optimization of scaffolding regions for effective display of the foreign epitope while minimizing disruption of the native capsid structure. We also validated an approach by which low-titer tropism-modified AAV vectors can be rescued by particle mosaicism with unmodified capsid proteins. Importantly, our rationally engineered AAV1-based vectors exhibited markedly enhanced transduction of cultured motor neurons, diminished transduction of nontarget cells, and markedly superior retrograde delivery compared with unmodified AAV1 vector. This approach promises a significant advancement in the rational engineering of AAV vectors for diseases of the nervous system and other organs.	f	\N
25549677	To explore the clinical features of neuromyelitis optica (NMO) spectrum disease (NMOSD) with connective tissue disease (CTD). The clinical features of 184 NMO/NMOSD patients (NMO/NMOSD: 119/184, 64.7%; NMO/NMOSD-CTD: 65/184, 35.3%) from May 2013 to May 2014 were analyzed retrospectively. And the effectiveness of long-term treatment of immunosuppressive drugs in NMOSD was evaluated. NMO/NMOSD-CTD patients had significantly higher female percentage (93.8% vs 83.2%, P < 0.05) and significantly higher percentage of patients with cerebral spinal fluid (CSF)-restricted oligoclonal band (OB)(41.5% vs 21.9%, P < 0.05). As compared with NMO/NMOSD-CTD counterparts, NMO/NMOSD patients had significantly higher percentage of non-specific lesions on brain MRI (62.5% vs 35.9%, P < 0.01). After >6 months consecutive long-term treatment of immunosuppressive drugs, the relapse rate post-treatment (0.36 ± 0.85) was significantly lower than that pre-treatment (2.91 ± 4.10, P < 0.01). And no significant difference existed in expanded disability status scale (EDSS) score between pre-and post-treatment. When using azathioprine (AZA), the percentage of relapse was significantly higher in NMO/NMOSD-CTD patients (50.0%) versus NMO/NMOSD ones (18.5%, P = 0.064); When using cyclophosphamide (CTX), there was no such significant difference. Female patients are more susceptible to have NMO/NMOSD with CTD. NMO/NMOSD-CTD patients tend to have higher percentage of CSF-restricted OB and fewer non-specific lesions on brain MRI. AZA and CTX may effectively reduce relapses in both NMO/NMOSD and NMO/NMOSD-CTD patients. However CTX is superior to AZA for reducing relapses in NMO/NMOSD-CTD patients.	f	\N
25551964	The aim of this study was to investigate if vaginal preparation procedure affects the occurrence of oocyte pickup-associated pelvic inflammation (OPU-PI) and the reproductive outcome in an in vitro fertilization (IVF) program. The occurrence of OPU-PI and the reproductive outcome were compared between 956 infertile patients undergoing vaginal preparation with saline douching alone versus 1,216 infertile patients undergoing a combination ofpovidone iodine disinfection and subsequent saline douching in an IVF program. OPU-PI occurred in four patients (0.042%) in the saline douching alone group, whereas there were no cases in the combination group (p = 0.016). There were no significant differences in the rate of fertilization, morphologically good embryo acquisition, clinical and ongoing pregnancy between the two groups (p > 0.23). This large cohort study demonstrated that a combination of vaginal povidone iodine disinfection and subsequent saline douching is more effective procedure than saline douching alone to prevent OPU-PI, without spoiling the oocyte quality.	f	\N
25553466	Hemophilia is an X-linked inherited bleeding disorder consisting of two classifications, hemophilia A and hemophilia B, depending on the underlying mutation. Although the disease is currently treatable with intravenous delivery of replacement recombinant clotting factor, this approach represents a significant cost both monetarily and in terms of quality of life. Gene therapy is an attractive alternative approach to the treatment of hemophilia that would ideally provide life-long correction of clotting activity with a single injection. In this review, we will discuss the multitude of approaches that have been explored for the treatment of both hemophilia A and B, including both in vivo and ex vivo approaches with viral and nonviral delivery vectors.	f	\N
25553772	Farnesoid x receptor (FXR) belongs to the group of nuclear receptors (NRs), which regulate the expression of various genes by binding to DNA either as a monomer or a heterodimer with retinoid x receptor. FXR affects several metabolic pathways through its specific target genes, regulating bile acid (BA) synthesis and homeostasis, glucose and lipid metabolism, also exhibiting a crucial role in intestinal bacterial growth and liver regeneration. Additionally, FXR is involved in the pathogenesis of different cholestatic diseases, as well as non-alcoholic fatty liver disease, inflammatory bowel disease (IBD) and primary idiopathic BA malabsorption. Analyses of certain FXR polymorphisms revealed associations with clinical phenotypes and susceptibility to various human diseases. FXR single-nucleotide polymorphisms seem to be correlated with differences in glucose homeostasis, gallstone formation, intrahepatic cholestasis of pregnancy, IBD and therapeutic response to hypolipidemic therapy, among studied populations. Unfortunately, little data are still available and more studies remain to be done to determine the contribution of FXR polymorphisms in estimating risk factors and clinical outcomes for several diseases.	f	\N
25575898	The Hundred Person Wellness Project is an ambitious pilot undertaking, which aims to intensely monitor 100 individuals over 10 months. Patients with abnormal findings will be treated, in hopes that this early intervention will avoid, or delay, symptomatic disease. Google's "Baseline Study" is of similar scope and will enroll 10,000 people over 2 to 3 years. I here speculate that these approaches will likely not be effective in preventing disease, but instead, lead to unnecessary and potentially harmful interventions. Examples from the cancer screening experience over the last 30 years are provided, which show that intensive testing may uncover indolent disease or incidental findings which, when treated, may cause more harm than good. Additional examples show that aggressive treatments for cancer and other diseases do not always lead to better patient outcomes. I conclude that the recent advances in omics provide us with unprecedented opportunities for high content clinical testing, but such testing should be used with caution to avoid the harmful consequences of over-diagnosis and over-treatment. Despite the detailed rebuttals by Hood and colleagues in another commentary in BMC Medicine, time will show the actual benefits and harms of these ambitious initiatives.	f	\N
25585384	In 2014, a major epidemic of human Ebola virus disease emerged in West Africa, where human-to-human transmission has now been sustained for greater than 12 months. In the summer of 2014, there was great uncertainty about the answers to several key policy questions concerning the path to containment. What is the relative importance of nosocomial transmission compared with community-acquired infection? How much must hospital capacity increase to provide care for the anticipated patient burden? To which interventions will Ebola transmission be most responsive? What must be done to achieve containment? In recent years, epidemic models have been used to guide public health interventions. But, model-based policy relies on high quality causal understanding of transmission, including the availability of appropriate dynamic transmission models and reliable reporting about the sequence of case incidence for model fitting, which were lacking for this epidemic. To investigate the range of potential transmission scenarios, we developed a multi-type branching process model that incorporates key heterogeneities and time-varying parameters to reflect changing human behavior and deliberate interventions in Liberia. Ensembles of this model were evaluated at a set of parameters that were both epidemiologically plausible and capable of reproducing the observed trajectory. Results of this model suggested that epidemic outcome would depend on both hospital capacity and individual behavior. Simulations suggested that if hospital capacity was not increased, then transmission might outpace the rate of isolation and the ability to provide care for the ill, infectious, and dying. Similarly, the model suggested that containment would require individuals to adopt behaviors that increase the rates of case identification and isolation and secure burial of the deceased. As of mid-October, it was unclear that this epidemic would be contained even by 99% hospitalization at the planned hospital capacity. A new version of the model, updated to reflect information collected during October and November 2014, predicts a significantly more constrained set of possible futures. This model suggests that epidemic outcome still depends very heavily on individual behavior. Particularly, if future patient hospitalization rates return to background levels (estimated to be around 70%), then transmission is predicted to remain just below the critical point around Reff = 1. At the higher hospitalization rate of 85%, this model predicts near complete elimination in March to June, 2015.	f	\N
25590983	Pseudomonas aeruginosa, the predominant cause of chronic airway infections of patients with cystic fibrosis, exhibits extensive phenotypic diversity among isolates within and between sputum samples, but little is known about the underlying genetic diversity. To characterize the population genetic structure of transmissible P. aeruginosa Liverpool Epidemic Strain in chronic infections of nine patients with cystic fibrosis, and infer evolutionary processes associated with adaptation to the cystic fibrosis lung. We performed whole-genome sequencing of P. aeruginosa isolates and pooled populations and used comparative analyses of genome sequences including phylogenetic reconstructions and resolution of population structure from genome-wide allele frequencies. Genome sequences were obtained for 360 isolates from nine patients. Phylogenetic reconstruction of the ancestry of 40 individually sequenced isolates from one patient sputum sample revealed the coexistence of two genetically diverged, recombining lineages exchanging potentially adaptive mutations. Analysis of population samples for eight additional patients indicated coexisting lineages in six cases. Reconstruction of the ancestry of individually sequenced isolates from all patients indicated smaller genetic distances between than within patients in most cases. Our population-level analysis demonstrates that coexistence of distinct lineages of P. aeruginosa Liverpool Epidemic Strain within individuals is common. In several cases, coexisting lineages may have been present in the infecting inoculum or assembled through multiple transmissions. Divergent lineages can share mutations via homologous recombination, potentially aiding adaptation to the airway during chronic infection. The genetic diversity of this transmissible strain within infections, revealed by high-resolution genomics, has implications for patient segregation and therapeutic strategies.	f	\N
25595571	Noonan Syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Autoimmune Hepatitis (AIH) is a cryptogenic, chronic and progressive necroinflammatory liver disease. Common features of AIH are hypergammaglobulinemia (IgG), presence of circulating autoantibodies, histological picture of interface hepatitis and response to immunosuppressant drugs. Conventional treatment with Prednisone and Azathioprine is effective in most patients. We describe the case of a 6 years-old girl with Noonan Syndrome and Autoimmune Hepatitis type 1. Molecular analysis of PTPN11 gene showed heterozygous mutation c.923A>G (Asn308Ser) in exon 8. Though association between NS and autoimmune disorders is known, this is the second case of association between Noonan Syndrome and Autoimmune Hepatitis type 1 described in literature. In the management of NS, an accurate clinical evaluation would be recommended. When there is a clinical suspicion of autoimmune phenomena, appropriate laboratory tests should be performed with the aim of clarifying whether the immune system is involved in NS. We think that autoimmunity represents a characteristic of NS, even if the etiopathogenesis is still unknown.	f	\N
25600917	Hepatitis B virus surface antigen (HBsAg) levels reflect disease status and can predict the clinical response to antiviral treatment; however, the emergence of HBsAg mutant strains has become a challenge. The Abbott HBsAg quantification assay provides enhanced detection of HBsAg and HBsAg mutants. We aimed to evaluate the performance of the Abbott HBsAg quantification assay with automatic sample dilutions (shortened as automatic Architect assay), compared with the Abbott HBsAg quantification assay with manual sample dilutions (shortened as manual Architect assay) and the Roche HBsAg quantification assay with automatic sample dilutions (shortened as Elecsys). A total of 130 sera samples obtained from 87 hepatitis B virus (HBV)-infected patients were collected to assess the correlation between the automatic and manual Architect assays. Among the 87 patients, 41 provided 42 sera samples to confirm the linearity and reproducibility of the automatic Architect assay, and find out the correlation among the Elecsys and two Architect assays. The coefficients of variation (0.44-9.53%) and R(2) = 0.996-1, which were both determined using values obtained from the automatic Architect assay, showed good reproducibility and linearity. Results of the two Architect assays demonstrated a feasible correlation (n = 130 samples; R = 0.898, p < 0.01). With regard to subgroups, correlations between the two Architect assays were better in the hepatitis B e antigen (HBeAg)-negative group (HBeAg-negative group vs. HBeAg-positive group: R = 0.885 vs. R = 0.865, both p < 0.01) and low HBV DNA group (low DNA group vs. high DNA group: R = 0.886 vs. R = 0.844, both p < 0.01). Significant correlations were also found between the results of the Elecsys and Architect assays (R > 0.93 in all cases). In conclusion, the correlation between the automatic and manual dilution Architect assays was feasible, particularly in the HBeAg-negative and low DNA groups. With lower labor costs and less human error than the manual version, the Abbott automatic dilution Architect assay provided a good clinical performance with regard to the HBsAg levels.	f	\N
25601965	Many cancer patients receive supplemental ascorbate (vitamin C) in the belief that it synergizes the anticancer effects of chemotherapy and reduces its toxicity. A systematic review was performed to evaluate the antitumor effects and toxicity of ascorbate treatment. Medline (1946 to March 2014), EMBASE (1947 to March 2014), and the Cochrane central register (1993 to March 2014) were searched for randomized and observational studies. Of 696 identified records, 61 full-text articles were screened and 34 were included. In total, 5 randomized controlled trials (RCTs) (n = 322), 12 phase I/II trials (n = 287), 6 observational studies (n = 7,599), and 11 case reports (n = 267) were identified. Because of study heterogeneity, no meta-analyses were performed. No RCTs reported any statistically significant improvements in overall or progression-free survival or reduced toxicity with ascorbate relative to control arm. Evidence for ascorbate's antitumor effects was limited to case reports and observational and uncontrolled studies. There is no high-quality evidence to suggest that ascorbate supplementation in cancer patients either enhances the antitumor effects of chemotherapy or reduces its toxicity. Given the high financial and time costs to patients of this treatment, high-quality placebo-controlled trials are needed.	f	\N
25602998	No current therapy for relapsing-remitting multiple sclerosis (MS) results in significant reversal of disability. To determine the association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability and other clinical outcomes in patients with MS. Case series of patients with relapsing-remitting MS (n = 123) or secondary-progressive MS (n = 28) (mean age, 36 years; range, 18-60 years; 85 women) treated at a single US institution between 2003 and 2014 and followed up for 5 years. Final follow-up was completed in June 2014. Treatment with cyclophosphamide and alemtuzumab (22 patients) or cyclophosphamide and thymoglobulin (129 patients) followed by infusion of unmanipulated peripheral blood stem cells. Primary end point was reversal or progression of disability measured by change in the Expanded Disability Status Scale (EDSS) score of 1.0 or greater (score range, 0-10). Secondary outcomes included changes in the Neurologic Rating Scale (NRS) score of 10 or greater (score range, 0-100), Multiple Sclerosis Functional Composite (MSFC) score, quality-of-life Short Form 36 questionnaire scores, and T2 lesion volume on brain magnetic resonance imaging scan. Outcome analysis was available for 145 patients with a median follow-up of 2 years and a mean of 2.5 years. Scores from the EDSS improved significantly from a pretransplant median of 4.0 to 3.0 (interquartile range [IQR], 1.5 to 4.0; n = 82) at 2 years and to 2.5 (IQR, 1.9 to 4.5; n = 36) at 4 years (P < .001 at each assessment). There was significant improvement in disability (decrease in EDSS score of ≥1.0) in 41 patients (50%; 95% CI, 39% to 61%) at 2 years and in 23 patients (64%; 95% CI, 46% to 79%) at 4 years. Four-year relapse-free survival was 80% and progression-free survival was 87%. The NRS scores improved significantly from a pretransplant median of 74 to 88.0 (IQR, 77.3 to 93.0; n = 78) at 2 years and to 87.5 (IQR, 75.0 to 93.8; n = 34) at 4 years (P < .001 at each assessment). The median MSFC scores were 0.38 (IQR, -0.01 to 0.64) at 2 years (P < .001) and 0.45 (0.04 to 0.60) at 4 years (P = .02). Total quality-of-life scores improved from a mean of 46 (95% CI, 43 to 49) pretransplant to 64 (95% CI, 61 to 68) at a median follow-up of 2 years posttransplant (n = 132) (P < .001). There was a decrease in T2 lesion volume from a pretransplant median of 8.57 cm3 (IQR, 2.78 to 22.08 cm3) to 5.74 cm3 (IQR, 1.88 to 14.45 cm3) (P < .001) at the last posttransplant assessment (mean follow-up, 27 months; n = 128). Among patients with relapsing-remitting MS, nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes. These preliminary findings from this uncontrolled study require confirmation in randomized trials.	f	\N
25622254	The accumulation and aggregation of misfolded proteins in the brain, such as amyloid-β (Aβ) and hyperphosphorylated tau, is a neuropathological hallmark of Alzheimer's disease (AD). Previously, we developed and validated a novel non-human primate model for sporadic AD (sAD) research using intracerebroventricular administration of streptozotocin (icv STZ). To date, no characterization of AD-related genes in different brain regions has been performed. Therefore, in the current study, the expression of seven amyloid precursor protein (APP) pathway-related and five tau phosphorylation-related genes was investigated by quantitative real-time PCR experiments, using two matched-pair brain samples from control and icv STZ-treated cynomolgus monkeys. The genes showed similar expression patterns within the control and icv STZ-treated groups; however, marked differences in gene expression patterns were observed between the control and icv STZ-treated groups. Remarkably, other than β-secretase (BACE1) and cyclin-dependent kinase 5 (CDK5), all the genes tested showed similar expression patterns in AD models compared to controls, with increased levels in the precuneus and occipital cortex. However, significant changes in gene expression patterns were not detected in the frontal cortex, hippocampus, or posterior cingulate. Based on these results, we conclude that APP may be cleaved via the general metabolic mechanisms of increased α- and γ-secretase levels, and that hyperphosphorylation of tau could be mediated by elevated levels of tau protein kinase, specifically in the precuneus and occipital cortex.	f	\N
25631478	The dihydropteroate sulfate (DHPS) gene is associated with resistance to sulfa/sulfone drugs in Pneumocystis jirovecii. We investigated the DHPS mutation rate in three groups of Iranian HIV-positive and HIV-negative patients by polymerase chain reaction-restricted fragment length polymorphism analysis. Furthermore, an association between P. jirovecii DHPS mutations and strain typing was investigated based on direct sequencing of internal transcribed spacer region 1 (ITS1) and ITS2. The overall P. jirovecii DHPS mutation rate was (5/34; 14.7%), the lowest rate identified was in HIV-positive patients (1/16; 6.25%) and the highest rate was in malignancies patients (3/11; 27.3%). A moderate rate of mutation was detected in chronic obstructive pulmonary disease (COPD) patients (1/7; 14.3%). Most of the isolates were wild type (29/34; 85.3%). Double mutations in DHPS were detected in patients with malignancies, whereas single mutations at codons 55 and 57 were identified in the HIV-positive and COPD patients, respectively. In this study, two new and rare haplotypes were identified with DHPS mutations. Additionally, a positive relationship between P. jirovecii strain genotypes and DHPS mutations was identified. In contrast, no DHPS mutations were detected in the predominant (Eg) haplotype. This should be regarded as a warning of an increasing incidence of drug-resistant P. jirovecii strains.	f	\N
25636578	Psoriasis is a T cell-dependent immune-mediated disease of the skin and joints. It is clear that co-stimulatory and co-inhibitory molecules (currently named co-signaling molecules collectively) synergize with TCR signaling to promote or inhibit T cell activation and function. In recent years, enthusiasm in the field of co-signaling research has been fueled by the success of co-stimulatory and co-inhibitory immunotherapy for the treatment of human diseases. This review outlines the involvement of several sets of co-signaling molecules in the immunopathogenesis of psoriasis. We then describe the relevant preclinical studies and summarize recent clinical findings on targeting these molecules for the treatment of psoriasis.	f	\N
25648029	Western blot is the gold standard method to determine individual protein expression levels. However, western blot is technically difficult to perform in large sample sizes because it is a time consuming and labor intensive process. Dot blot is often used instead when dealing with large sample sizes, but the main disadvantage of the existing dot blot techniques, is the absence of signal normalization to a housekeeping protein. In this study we established a one dot two development signals (ODTDS) dot blot method employing two different signal development systems. The first signal from the protein of interest was detected by horseradish peroxidase (HRP). The second signal, detecting the housekeeping protein, was obtained by using alkaline phosphatase (AP). Inter-assay results variations within ODTDS dot blot and western blot and intra-assay variations between both methods were low (1.04-5.71%) as assessed by coefficient of variation. ODTDS dot blot technique can be used instead of western blot when dealing with large sample sizes without a reduction in results accuracy.	f	\N
25656590	The purpose of this study was to examine the practice patterns of intraoperative completion imaging (CI) for lower extremity bypass (LEB) in the Vascular Quality Initiative (VQI). A retrospective review of all LEB procedures in the VQI database from January 2003 to October 2013 was performed. Regions with fewer than 200 LEB procedures were excluded from the regional analysis. The modality of CI was defined as duplex ultrasound, angiography, or both. A total of 14,140 LEBs were captured, with the rate of CI being 43%. After exclusion of three regions for insufficient volume (<200 LEBs), 13,945 LEB operations across 13 regions were available for regional analysis. Use of any type of intraoperative CI varied across regions from a low of 8% to a high of 70%, with angiography being performed most frequently. When CI was performed, the type of imaging modality varied between regions from a high of 99% for angiography to a high of 75% for duplex ultrasound. CI was more common in male patients (44% of male patients vs 42% of female patients; P = .032), diabetics (44% of diabetic patients vs 42% of nondiabetic patients; P = .026), and patients with coronary artery disease (45% of patients with coronary artery disease vs 42% of patients with no coronary artery disease; P = .0015). CI was performed less frequently in LEB using single-segment great saphenous vein vs LEB using lesser saphenous, arm, or composite vein (48% vs 57%; P < .0001). CI was used in 51% of LEBs with a tibial or pedal target vessel vs 38% of LEBs with a more proximal target vessel (P < .0001). Patients with an indication of critical limb ischemia underwent CI in 45% of LEBs vs 39% with an indication other than critical limb ischemia (P < .0001). Within the VQI database, considerable practice pattern variation exists in the use of CI. Currently, CI is most commonly employed for patients with critical limb ischemia, infrageniculate target vessel, and disadvantaged venous conduit. Further study is required to standardize and to define the appropriate use of CI for LEBs.	f	\N
25659158	Dengue virus infection is a leading cause of morbidity among children in the Philippines in recent years. In order to investigate the association of HLA Class I and II alleles and dengue disease severity in a cohort of Filipino children, we performed a case control study in 2 hospitals in Metro Manila from June 2008 to December 2009. A total of 250 laboratory confirmed dengue patients and 300 healthy individuals aged 5 to 15 years old were typed for HLA-A, B and DRB1 alleles. The frequency of HLA-A*33:01 was significantly decreased in severe dengue (DHF/ DSS; Pc = 0.0016)) and DSS (Pc = 0.0032) compared to the background population. These findings support a previous study that this allele may confer protection against the severe form of dengue and provide the first evidence of HLA association with dengue in the Philippines. Future studies should be directed in investigating the possible mechanisms of protection.	f	\N
25659380	The 18th WHO Global Tuberculosis Annual Report indicates that there were an estimated 8.6 million incident cases of tuberculosis (TB) in 2012, which included 2.9 million women and 530,000 children. TB caused 1.3 million deaths including 320,000 human immunodeficiency virus (HIV)-infected people; three-quarters of deaths occurred in Africa and Southeast Asia. With one-third of the world's population latently infected with Mycobacterium tuberculosis (Mtb), active TB disease is primarily associated with a break down in immune surveillance. This explains the strong link between active TB disease and other communicable diseases (CDs) or noncommunicable diseases (NCDs) that exert a toll on the immune system. Comorbid NCD risk factors include diabetes, smoking, malnutrition, and chronic lung disease, all of which have increased relentlessly over the past decade in developing countries. The huge overlap between killer infections such as TB, HIV, malaria, and severe viral infections with NCDs, results in a "double burden of disease" in developing countries. The current focus on vertical disease programs fails to recognize comorbidities or to encourage joint management approaches. This review highlights major disease overlaps and discusses the rationale for better integration of tuberculosis care with services for NCDs and other infectious diseases to enhance the overall efficiency of the public health responses.	f	\N
25662376	To determine the number, distribution and cost of hospital admissions for chronic obstructive pulmonary disease (COPD) in New Zealand. National patient-level routine data on admissions with a principal diagnosis of COPD (mostly ICD-10- AN J440 and J441) were obtained for the period July 1st 2008 to June 30th 2013. Admissions with length of stay (LOS) = 90 days were excluded. There were 61,516 admissions in 5 years. Admission rates and budget impact (in 2012/13 dollar values) were stable but the average length of stay (ALOS) declined from 5.09 to 4.37 days. In FY2012/13 the admission rate was 2.82 per 1000 population, with age standardised rate (ASR) 4.4- and 3.6-fold higher for Maori and Pacific peoples respectively than for European/others. For age = 15 years the ASR was 2.55 per 1000. Admission rates were higher for men than women and increased steeply with age and socioeconomic deprivation (NZDep06). The mean age at discharge was lower for Maori and Pacific peoples than for European/Others (63.4, 67.1 and 72.3 years). The mean 30-day readmission rate was 6.7%. The average LOS increased with age and was shorter for Maori (3.6 days) and Pacific peoples (3.5 days) than for European/Others (4.7 days). Admission rates varied widely across District Health Boards, and were higher in rural than urban regions. The estimated cost of admissions in FY2012/13 was $NZ59.6m. Hospital admissions for COPD are costly and are over-represented in high risk groups including rural, elderly, socioeconomically deprived and Maori and Pacific peoples. Effective interventions that are targeted to high risk groups are required to improve equity and reduce the burden of COPD.	f	\N
25664604	A novel oral octreotide formulation was tested for efficacy and safety in a phase III, multicenter, open-label, dose-titration, baseline-controlled study in patients with acromegaly. We enrolled 155 complete or partially controlled patients (IGF-1 <1.3 × upper limit of normal [ULN], and 2-h integrated GH <2.5 ng/mL) receiving injectable somatostatin receptor ligand (SRL) for ≥ 3 months. Subjects were switched to 40 mg/d oral octreotide capsules (OOCs), and the dose escalated to 60 and then up to 80 mg/d to control IGF-1. Subsequent fixed doses were maintained for a 7-month core treatment, followed by a voluntary 6-month extension. Of 151 evaluable subjects initiating OOCs, 65% maintained response and achieved the primary endpoint of IGF-1 <1.3 × ULN and mean integrated GH <2.5 ng/mL at the end of the core treatment period and 62% at the end of treatment (up to 13 mo). The effect was durable, and 85 % of subjects initially controlled on OOCs maintained this response up to 13 months. When controlled on OOCs, GH levels were reduced compared to baseline, and acromegaly-related symptoms improved. Of 102 subjects completing the core treatment, 86% elected to enroll in the 6-month extension. Twenty-six subjects who were considered treatment failures (IGF-1 ≥ 1.3 × ULN) terminated early, and 23 withdrew for adverse events, consistent with those known for octreotide or disease related. OOC, an oral therapeutic peptide, achieves efficacy in controlling IGF-1 and GH after switching from injectable SRLs for up to 13 months, with a safety profile consistent with approved SRLs. OOC appears to be effective and safe as an acromegaly monotherapy.	f	\N
25675517	Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by joint destruction and severe morbidity. Methotrexate (MTX) is the standard first-line therapy of RA. However, about 40% of RA patients are unresponsive to MTX treatment. Regulatory T cells (Tregs, CD4(+)CD25(+)FoxP3(+)) are thought to play an important role in attenuating RA. To investigate the role of Tregs in MTX resistance, we recruited 122 RA patients (53 responsive, R-MTX; 69 unresponsive, UR-MTX) and 33 healthy controls. Three months after MTX treatment, R-MTX but not UR-MTX showed higher frequency of peripheral blood CD39(+)CD4(+)CD25(+)FoxP3(+) Tregs than the healthy controls. Tregs produce adenosine (ADO) through ATP degradation by sequential actions of two cell surface ectonucleotidases: CD39 and CD73. Tregs from UR-MTX expressed a lower density of CD39, produced less ADO, and had reduced suppressive activity than Tregs from R-MTX. In a prospective study, before MTX treatment, UR-MTX expressed a lower density of CD39 on Tregs than those of R-MTX or control (P < 0.01). In a murine model of arthritis, CD39 blockade reversed the antiarthritic effects of MTX treatment. Our results demonstrate that MTX unresponsiveness in RA is associated with low expression of CD39 on Tregs and the decreased suppressive activity of these cells through reduced ADO production. Our findings thus provide hitherto unrecognized mechanism of immune regulation in RA and on mode of action of MTX. Furthermore, our data suggest that low expression of CD39 on Tregs could be a noninvasive biomarker for identifying MTX-resistant RA patients.	f	\N
25675716	Cardiorehabilitation of patients with multivessel coronary lesions is an obligatory component of ambulatory stage of care. With the aim of potentiating cardioprotective and antiischemic impact of rehabilitative preventive measures in 36 patients with ischemic heart disease (IHD) and multivessel coronary artery involvement who had undergone percutaneous coronary intervention we studied cardioprotective and antiischemic effect of long-term (24 weeks) administration of 70 mg/day trimetazidine in combination with moderate intensity physical training with the use of distance surveillance by a physician. The chosen therapeutic approach in patients with residual ischemia after incomplete anatomical revascularization provided early persistent formation of cardioprotective and antiischemic effect proven by increase of tolerance to physical exercise, improvement of diastolic function, and positive dynamics of both ECG parameters and biochemical markers of myocardial ischemia.	f	\N
25678847	5-Fluorouracil (5Fu) chemotherapy is the first treatment of choice for advanced gastric cancer (GC), but its effectiveness is limited by drug resistance. Emerging evidence suggests that the existence of cancer stem cells (CSCs) contributes to chemoresistance. The aim of the present study was to determine whether 5Fu chemotherapy generates residual cells with CSC-like properties in GC. Human GC cell lines, SGC7901 and AGS, were exposed to increasing 5Fu concentrations. The residual cells were assessed for both chemosensitivity and CSC-like properties. B lymphoma Mo-MLV insertion region 1 (BMI1), a putative CSC protein, was analyzed by immunohistochemical staining and subjected to pairwise comparison in GC tissues treated with or without neoadjuvant 5Fu-based chemotherapy. The correlation between BMI1 expression and recurrence-free survival in GC patients who received 5Fu-based neoadjuvant chemotherapy was then examined. The residual cells exhibited 5Fu chemoresistance. These 5Fu-resistant cells displayed some CSC features, such as a high percentage of quiescent cells, increased self-renewal ability and tumorigenicity. The 5Fu-resistant cells were also enriched with cells expressing cluster of differentiation (CD)133+, CD326+ and CD44+CD24-. Moreover, the BMI1 gene was overexpressed in 5Fu-resistant cells, and BMI1 knockdown effectively reversed chemoresistance. The BMI1 protein was highly expressed consistently in the remaining GC tissues after 5Fu-based neoadjuvant chemotherapy, and BMI1 levels were correlated positively with recurrence-free survival in GC patients who received 5Fu-based neoadjuvant chemotherapy. Our data provided molecular evidence illustrating that 5Fu chemotherapy in GC resulted in acquisition of CSC-like properties. Moreover, enhanced BMI1 expression contributed to 5Fu resistance and may serve as a potential therapeutic target to reverse chemoresistance in GC patients.	f	\N
25679282	There is inconsistency among the perioperative management strategies currently used for chronic subdural hematoma (cSDH). Moreover, postoperative complications such as acute intracranial bleeding and cSDH recurrence affect clinical outcome of cSDH surgery. This study evaluated the risk factors associated with acute intracranial bleeding and cSDH recurrence and identified an effective perioperative strategy for cSDH patients. A retrospective study of patients who underwent bur hole craniostomy for cSDH between 2008 and 2012 was performed. A consecutive series of 303 cSDH patients (234 males and 69 females; mean age 67.17 years) was analyzed. Postoperative acute intracranial bleeding developed in 14 patients (4.57%) within a mean of 3.07 days and recurrence was observed in 37 patients (12.21%) within a mean of 31.69 days (range 10-104 days) after initial bur hole craniostomy. The comorbidities of hematological disease and prior shunt surgery were clinical factors associated with acute bleeding. There was a significant risk of recurrence in patients with diabetes mellitus, but recurrence did not affect the final neurological outcome (p = 0.776). Surgical details, including the number of operative bur holes, saline irrigation of the hematoma cavity, use of a drain, and type of postoperative ambulation, were not significantly associated with outcome. However, a large amount of drainage was associated with postoperative acute bleeding. Bur hole craniostomy is an effective surgical procedure for initial and recurrent cSDH. Patients with hematological disease or a history of prior shunt surgery are at risk for postoperative acute bleeding; therefore, these patients should be carefully monitored to avoid overdrainage. Surgeons should consider informing patients with diabetes mellitus that this comorbidity is associated with an increased likelihood of recurrence.	f	\N
25680251	The orbital manifestations of acquired immunodeficiency syndrome(AIDS) are uncommon. To provide a review of orbital manifestations of AIDS, the predisposing factors, investigations, treatment and outcome. Meticulous and systematic literature search of Pubmed to identify manuscripts describing orbital manifestations of AIDS was done and the articles were reviewed.The keywords used in the search were “orbit and AIDS”, “HIV positive and orbit”,“orbit manifestations in AIDS”, “orbital disease and AIDS” and “orbital infections and AIDS”. The orbital involvement in AIDS may present with opportunistic infections from organisms like fungi, viruses, bacteria and protozoa or with malignancies like Kaposi’s sarcoma, squamous cell carcinoma, smooth muscle cell tumors and lymphoma.The predisposing factors for orbital involvement in AIDS are low CD4+ cell count and the immunosuppressive states like diabetes, diabetic ketoacidosis, intravenous drug abuse and neutropenia. A patient may present with fever, headache, nausea, vomiting,decreased vision, ocular pain, and, in cases of mass formation, there is periorbital swelling, axial proptosis, globe displacement and swollen optic disc. Radiologically,mass formation, orbital bony destruction, and spread of disease to contiguous structures including the central nervous system may be seen. The medical management includes therapy for infection and HIV-1 protease inhibitors (highly active antiretroviral therapy)to suppress HIV-1 replication. For tumors, radical surgery including debulking followed by postoperative radiotherapy is generally needed. Orbital involvements with AIDS in any form, infective or malignancy, causes significant morbidity and mortality and should be diagnosed and managed as early as possible.	f	\N
25682204	The goal of this study is to validate a new, continuous, noninvasive stroke volume (SV) method, known as transbrachial electrical bioimpedance velocimetry (TBEV). TBEV SV was compared to SV obtained by cardiac magnetic resonance imaging (cMRI) in normal humans devoid of clinically apparent heart disease. Thirty-two (32) volunteers were enrolled in the study. Each subject was evaluated by echocardiography to assure that no aortic or mitral valve disease was present. Subsequently, each subject underwent electrical interrogation of the brachial artery by means of a high frequency, low amplitude alternating current. A first TBEV SV estimate was obtained. Immediately after the initial TBEV study, subjects underwent cMRI, using steady-state precession imaging to obtain a volumetric estimate of SV. Following cMRI, the TBEV SV study was repeated. Comparing the cMRI-derived SV to that of TBEV, the two TBEV estimates were averaged and compared to the cMRI standard. CO was computed as the product of SV and heart rate. Statistical methods consisted of Bland-Altman and linear regression analysis. TBEV SV and CO estimates were obtained in 30 of the 32 subjects enrolled. Bland-Altman analysis of pre- and post-cMRI TBEV SV showed a mean bias of 2.87 % (2.05 mL), precision of 13.59% (11.99 mL) and 95% limits of agreement (LOA) of +29.51% (25.55 mL) and -23.77% (-21.45 mL). Regression analysis for pre- and post-cMRI TBEV SV values yielded y = 0.76x + 25.1 and r(2) = 0.71 (r = 0.84). Bland-Altman analysis comparing cMRI SV with averaged TBEV SV showed a mean bias of -1.56% (-1.53 mL), precision of 13.47% (12.84 mL), 95% LOA of +24.85% (+23.64 mL) and -27.97% (-26.7 mL) and percent error = 26.2 %. For correlation analysis, the regression equation was y = 0.82x + 19.1 and correlation coefficient r(2) = 0.61 (r = 0.78). Bland-Altman analysis of averaged pre- and post-cMRI TBEV CO versus cMRI CO yielded a mean bias of 5.01% (0.32 L min(-1)), precision of 12.85% (0.77 L min(-1)), 95% LOA of +30.20 % (+0.1.83 L min(-1)) and -20.7% (-1.19 L min(-1)) and percent error = 24.8%. Regression analysis yielded y = 0.92x + 0.78, correlation coefficient r(2) = 0.74 (r = 0.86). TBEV is a novel, noninvasive method, which provides satisfactory estimates of SV and CO in normal humans.	f	\N
25713121	Lyme disease is the most important vector-borne disease in the Northern hemisphere and represents a major public health challenge with insufficient means of reliable diagnosis. Skin is rarely investigated in proteomics but constitutes in the case of Lyme disease the key interface where the pathogens can enter, persist, and multiply. Therefore, we investigated proteomics on skin samples to detect Borrelia proteins directly in cutaneous biopsies in a robust and specific way. We first set up a discovery gel prefractionation-LC-MS/MS approach on a murine model infected by Borrelia burgdorferi sensu stricto that allowed the identification of 25 Borrelia proteins among more than 1300 mouse proteins. Then we developed a targeted gel prefractionation-LC-selected reaction monitoring (SRM) assay to detect 9/33 Borrelia proteins/peptides in mouse skin tissue samples using heavy labeled synthetic peptides. We successfully transferred this assay from the mouse model to human skin biopsies (naturally infected by Borrelia), and we were able to detect two Borrelia proteins: OspC and flagellin. Considering the extreme variability of OspC, we developed an extended SRM assay to target a large set of variants. This assay afforded the detection of nine peptides belonging to either OspC or flagellin in human skin biopsies. We further shortened the sample preparation and showed that Borrelia is detectable in mouse and human skin biopsies by directly using a liquid digestion followed by LC-SRM analysis without any prefractionation. This study thus shows that a targeted SRM approach is a promising tool for the early direct diagnosis of Lyme disease with high sensitivity (<10 fmol of OspC/mg of human skin biopsy).	f	\N
25716730	Allogeneic bone marrow transplantation (allo-BMT) is currently the only way to cure many hematoproliferative disorders. However, allo-BMT use is limited by severe complications, the foremost being graft-versus-host disease (GVHD). Due to the lack of efficiency of the existing methods of GVHD prophylaxis, new methods are being actively explored, including the use of donors' multipotent mesenchymal stromal cells (MMSC). In this work, we analyzed the results of acute GVHD (aGVHD) prophylaxis by means of MMSC injections after allo-BMT in patients with hematological malignancies. The study included 77 patients. They were randomized into two groups - those receiving standard prophylaxis of aGVHD and those who were additionally infused with MMSC derived from the bone marrow of hematopoietic stem cell donors. We found that the infusion of MMSC halves the incidence of aGVHD and increases the overall survival of patients. Four of 39 MMSC samples were ineffective for preventing aGVHD. Analysis of individual donor characteristics (gender, age, body mass index) and the MMSC properties of these donors (growth parameters, level of expression of 30 genes involved in proliferation, differentiation, and immunomodulation) revealed no significant difference between the MMSC that were effective or ineffective for preventing aGVHD. We used multiple logistic regression to establish a combination of features that characterize the most suitable MMSC samples for the prevention of aGVHD. A model predicting MMSC sample success for aGVHD prophylaxis was constructed. Significant model parameters were increased relative expression of the FGFR1 gene in combination with reduced expression levels of the PPARG and IGF1 genes. Depending on the chosen margin for probability of successful application of MMSC, this model correctly predicts the outcome of the use of MMSC in 82-94% of cases. The proposed model of prospective evaluation of the effectiveness of MMSC samples will enable prevention of the development of aGVHD in the maximal number of patients.	f	\N
25721731	Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR-TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45-15.33] and nonsteroidal anti-inflammatory drugs (OR: 6.54; 95% CI: 3.19-12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33-0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63-2.34), smoking (OR: 1.93; 95% CI: 1.54-2.61), family history of GC (OR: 2.83; 95% CI: 2.01-3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07-1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12-1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16-1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse-type GC (hazard ratio: 1.85; 95% CI: 1.12-3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians.	f	\N
25727171	In this study, we investigated the vasorelaxant and antihypertensive effects of gallic acid (GA), a polyphenol isolated from the green alga Spirogyra sp., to assess its suitability as a therapeutic for cardiovascular diseases (CVDs). We examined the effect of GA on endothelium-dependent vasorelaxation in human umbilical vein endothelial cells (HUVECs). GA increased nitric oxide (NO) levels by increasing phosphorylation of endothelial nitric oxide synthase (eNOS), and its effect on NO production was attenuated by pretreatment with the eNOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). We also investigated its antihypertensive effect by examining GA-mediated inhibition of angiotensin-I converting enzyme (ACE). GA inhibited ACE with a half-maximal inhibitory concentration (IC50) value of 37.38 ± 0.39 μg/ml. In silico simulations revealed that GA binds to the active site of ACE (PDB: 1O86) with a binding energy of -270.487 kcal/mol. Furthermore, GA clearly reduced blood pressure in spontaneously hypertensive rats (SHR) to an extent comparable to captopril. These results suggest that GA isolated from Spirogyra sp. exerts multiple therapeutic effects and has potential as a CVD treatment.	f	\N
25728727	The American Heart Association (AHA) established recommendations based on 7 ideal health behaviors and factors with the goal of improving cardiovascular health (CVH) and reducing both morbidity and mortality from cardiovascular disease by 20% by 2020. Few studies have investigated their association with subclinical coronary heart disease. We sought to examine whether the 7 AHA CVH metrics were associated with calcified atherosclerotic plaque in the coronary arteries. In a cross-sectional design, we studied 1,731 predominantly white men and women from the National Heart, Lung, and Blood Institute Family Heart Study without prevalent coronary heart disease. Diet was assessed by a semiquantitative food frequency questionnaire. Coronary artery calcium (CAC) was measured by cardiac computed tomography. We defined prevalent CAC using an Agatston score of 100+ and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age was 56.8 years, and 41% were male. The median number of ideal CVH metrics was 3, and no participant met all 7. There was a strong inverse relationship between number of ideal CVH metrics and prevalent CAC. Odds ratios (95% CI) for CAC of 100+ were 1.0 (reference), 0.37 (0.29-0.45), 0.35 (0.26-0.44), and 0.27 (0.20-0.36) among subjects with 0 to 1, 2, 3, and 4+ ideal CVH metrics, respectively (P = .0001), adjusting for sex, age, field center, alcohol, income, education, and energy consumption. These data demonstrate a strong and graded inverse relationship between AHA ideal CVH metrics and prevalent CAC in adult men and women.	f	\N
25738293	Celiac disease (CD) is an autoimmune disease induced by an autoimmune reaction to indigested gluten, which occurs in genetically predisposed population. The etiology of CD is linked to innate and adaptive immunity, mostly mediated by lymphocytes, especially T cells, infiltrating into the small intestinal wall. The subpopulations of T cells that infiltrate inflamed intestinal tissues comprise various CD4+ T cells and CD8+ T cells. The plethora of T cell subtypes activated in CD leads to simultaneous activation of different signaling cascades including GATA1, NF-kB, JAK or STAT5 the activity of which may be modified by diet or drugs. It was recently showed that food allergens may accelerate CD by altering the interaction between IL-15 and CD4+ T cells in the activation of CD8+ T cells. Increased levels of cytokines like IL-15 are considered to play a role in CD development. Furthermore it was showed that some drugs like tofacitinib or ruxolitinib may influence CD by blocking IL-15 signaling and CD8+ T cell activity. This mini-review will summarize the current knowledge on the role of CD4+ T cell and CD8+ T cell in clinical and experimental CD and will describe how T cell-activated signaling pathways and locally released proteins may be influenced by dietary factors and drugs used in CD treatment.	f	\N
25750286	Herpesvirus entry mediator (HVEM) has been recently suggested to play certain roles in cancer biology. We examined HVEM expression in human colorectal cancer (CRC) to reveal its clinical importance. Immunohistochemical staining was carried-out in normal epithelium, benign and malignant lesions. While intense HVEM expression was not observed in normal epithelium and hyperplastic polyps, 24% of adenoma and more than half of CRCs had high HVEM expression. In 234 CRCs, HVEM expression was significantly associated with tumor status and pathological stage. Patients with high HVEM expression had a significantly poorer prognosis than those with low expression. Importantly, HVEM status had an independent prognostic value in CRC. Furthermore, HVEM status was inversely corrected with the presence of tumor-infiltrating T-cells. HVEM may play a critical role in tumor progression and immune evasion, and may also be a novel prognostic marker and potential therapeutic target in human CRC.	f	\N
25770253	Although obesity has been viewed traditionally as a disease of excess nutrition, evidence suggests that it may also be a disease of malnutrition. Specifically, thiamin deficiency was found in 15.5-29% of obese patients seeking bariatric surgery. It can present with vague signs and symptoms and is often overlooked in patients without alcohol use disorders. This review explores the relatively new discovery of high rates of thiamin deficiency in certain populations of people with obesity, including the effects of thiamin deficiency and potential underlying mechanisms of deficiency in people with obesity. The 2 observational studies that examined the prevalence in preoperative bariatric surgery patients and gaps in our current knowledge (including the prevalence of thiamin deficiency in the general obese population and whether the current RDA for thiamin meets the metabolic needs of overweight or obese adults) are reviewed. Suggestions for future areas of research are included.	f	\N
25774918	We sought to determine whether genomic polymorphism in collagen IX genes (COL9A) was associated with Kashin-Beck disease (KBD). Twenty seven single nucleotide polymorphisms (SNPs) in COL9AI, COL9A2 and COL9A3 were genotyped in 274 KBD cases and 248 healthy controls using the Sequenom MassARRAY system. Associations between the COL9A polymorphism and KBD risk were detected using an unconditional logistic regression model. Linkage disequilibrium (LD) and haplotypes analysis were performed with the Haploview software. After Bonferroni correction, the frequency distribution of genotypes in rs6910140 in COL9A1 was significantly different between the KBD and the control groups (X2 = 16.74, df = 2, P = 0.0002). Regression analysis showed that the allele "C" in SNP rs6910140 had a significant protective effect on KBD [odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.34-0.70, P = 0.0001]. The frequencies of alleles and genotypes in rs6910140 were significantly different among subjects of different KBD stages (allele: X2 = 7.82, df = 2, P = 0.02, genotype: X2 = 14.81, df = 4, P = 0.005). However, haplotype analysis did not detect any significant association between KBD and COL9A1, COL9A2 and COL9A3. We observed a significant association between rs6910140 of COL9A1 and KBD, suggesting a role of COL9A1 in the development of KBD.	f	\N
25795200	The study aims to compare the efficacy and safety of capecitabine plus oxaliplatin (XELOX) with 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOXs) in patients with advanced gastric cancer. Five databases were searched up to June 2014, without language restrictions. The outcomes included overall response rate (ORR), clinical benefit rate (CBR), and toxicity. Twenty-six eligible trials were selected from 178 studies that initially were identified. All trials were published in Chinese journals between 2005 and 2014 and included 1585 patients (787 in XELOX group and 798 in FOLFOXs group). The pooled results failed to show statistical significance of XELOX regimen on ORR (OR 1.18, 95% CIs 1.00-1.41, P = 0.057) and CBR (OR 1.10, 95% CIs 0.95-1.28, P = 0.191) as compared with FOLFOXs regimen. None of the 26 clinical trials reported progression-free survival, and only one reported overall survival rate. The meta-analysis demonstrated that XELOX regimen was associated with a significant lower risk with nausea, stomatitis, diarrhea and alopecia, and a significant higher risk of hand-foot syndrome. The evidence is limited to suggest that XELOX may share similar efficacy as FOLFOXs and reduce toxicities of chemotherapy in advanced gastric cancer therapy. However, owing to limited data and potential bias of the included studies, further rigorously controlled trials are required.	f	\N
25801012	Eccentric distribution of atheroma has been associated with plaques likely to rupture and cause an acute coronary syndrome, but the factors responsible for the development of eccentricity remain unknown. Endothelial shear stress (ESS) drives plaque formation. We aimed to investigate the role of the local ESS characteristics in the de novo development and progressive worsening of plaque eccentricity in humans. Vascular profiling (3-vessel 3D coronary reconstruction by angiography/intravascular ultrasound, and blood flow simulation for ESS computation) was performed in 374 patients at baseline & 6-10 months follow-up. At baseline, we identified (i) disease-free segments (n=2157), and (ii) diseased regions of luminal obstructions (n=408). In disease-free regions, baseline low ESS magnitude (p<0.001), marked ESS circumferential heterogeneity (p=0.001), and their interaction (p=0.026) were associated with an increased probability of de novo eccentric plaque formation at follow-up. In diseased regions, baseline low ESS (odds ratio [OR]: 2.33, p=0.003) and large plaque burden (OR: 2.46, p=0.002) were independent predictors of substantially increasing plaque eccentricity index with worsening lumen encroachment. This combined outcome was more frequent in obstructions with both features vs. all others (33 vs. 12%; p<0.001). The incidence of percutaneous coronary intervention in worsening obstructions with increasing plaque eccentricity was higher (13.3 vs. 4.3%, p=0.011). The local hemodynamic environment has a critical effect on the development of eccentric coronary plaques at both an early and advanced stage of atherosclerosis. Local ESS assessment could help in predicting sites prone to plaque disruption and acute coronary syndromes in humans.	f	\N
25811383	Nephropathic cystinosis is a lysosomal storage disorder caused by mutations in the CTNS gene encoding cystine transporter cystinosin that results in accumulation of amino acid cystine in the lysosomes throughout the body and especially affects kidneys. Early manifestations of the disease include renal Fanconi syndrome, a generalized proximal tubular dysfunction. Current therapy of cystinosis is based on cystine-lowering drug cysteamine that postpones the disease progression but offers no cure for the Fanconi syndrome. We studied the mechanisms of impaired reabsorption in human proximal tubular epithelial cells (PTEC) deficient for cystinosin and investigated the endo-lysosomal compartments of cystinosin-deficient PTEC by means of light and electron microscopy. We demonstrate that cystinosin-deficient cells had abnormal shape and distribution of the endo-lysosomal compartments and impaired endocytosis, with decreased surface expression of multiligand receptors and delayed lysosomal cargo processing. Treatment with cysteamine improved surface expression and lysosomal cargo processing but did not lead to a complete restoration and had no effect on the abnormal morphology of endo-lysosomal compartments. The obtained results improve our understanding of the mechanism of proximal tubular dysfunction in cystinosis and indicate that impaired protein reabsorption can, at least partially, be explained by abnormal trafficking of endosomal vesicles.	f	\N
25813338	Poor data regarding skin involvement in Myotonic Dystrophy, also named Dystrophia Myotonica type 1, have been reported. This study aimed to investigate the prevalence and types of skin disorders in adult patients with Myotonic Dystrophy type 1. Fifty-five patients and one hundred age- and sex-matched healthy subjects were referred to a trained dermatologist for a complete skin examination to check for potential cutaneous hallmarks of disease. No difference in prevalence of preneoplastic, neoplastic, and cutaneous lesions was detected between the two groups. Among morphofunctional, proliferative and inflammatory lesions, focal hyperhidrosis (p < 0.0001), follicular hyperkeratosis (p = 0.0003), early androgenic alopecia (p = 0.01), nail pitting (p = 0.003), pedunculus fibromas (p = 0. 01), twisted hair (p = 0.01), seborrheic dermatitis (p = 0.02), macules of hyperpigmentation (p = 0.03) were significantly more frequent in patients compared with controls. In patients with Myotonic Dystrophy type 1 significant differences according to sex were found for: early androgenic alopecia, twisted hair and seborrheic dermatitis, whose prevalence was higher in males (p < 0.0001). Our preliminary results seem to rule out an increased prevalence of pre-neoplastic, and neoplastic skin lesions in Myotonic Dystrophy type 1. On the other hand, an increased prevalence of morphofunctional, inflammatory, and proliferative diseases involving adnexal structures seems to characterize adult patients with Myotonic Dystrophy type 1.	f	\N
25834326	To investigate whether transarterial chemoembolization (TACE) before liver transplantation (LT) improves long-term survival in hepatocellular carcinoma (HCC) patients. A retrospective study was conducted among 204 patients with HCC who received LT from January 2002 to December 2010 in PLA General Hospital. Among them, 88 patients received TACE before LT. Prognostic factors of serum α-fetoprotein (AFP), intraoperative blood loss, intraoperative blood transfusion, disease-free survival time, survival time with tumor, number of tumor nodules, tumor size, tumor number, presence of blood vessels and bile duct invasion, lymph node metastasis, degree of tumor differentiation, and preoperative liver function were determined in accordance with the Child-Turcotte-Pugh (Child) classification and model for end-stage liver disease. We also determined time of TACE before transplant surgery and tumor recurrence and metastasis according to different organs. Cumulative survival rate and disease-free survival rate curves were prepared using the Kaplan-Meier method, and the log-rank and χ(2) tests were used for comparisons. In patients with and without TACE before LT, the 1, 3 and 5-year cumulative survival rate was 70.5% ± 4.9% vs 91.4% ± 2.6%, 53.3% ± 6.0% vs 83.1% ± 3.9%, and 46.2% ± 7.0% vs 80.8% ± 4.5%, respectively. The median survival time of patients with and without TACE was 51.857 ± 5.042 mo vs 80.930 ± 3.308 mo (χ(2) = 22.547, P < 0.001, P < 0.05). The 1, 3 and 5-year disease-free survival rates for patients with and without TACE before LT were 62.3% ± 5.2% vs 98.9% ± 3.0%, 48.7% ± 6.7% vs 82.1% ± 4.1%, and 48.7% ± 6.7% vs 82.1% ± 4.1%, respectively. The median survival time of patients with and without TACE before LT was 50.386 ± 4.901 mo vs 80.281 ± 3.216 mo (χ(2) = 22.063, P < 0.001, P < 0.05). TACE before LT can easily lead to pulmonary or distant metastasis of the primary tumor. Although there was no significant difference between the two groups, the chance of metastasis of the primary tumor in the group with TACE was significantly higher than that of the group without TACE. TACE pre-LT for HCC patients increased the chances of pulmonary or distant metastasis of the primary tumor, thus reducing the long-term survival rate.	f	\N
25836637	The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD.	f	\N
25857492	Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment.	f	\N
25861414	Chronic kidney disease (CKD) is characterized by increased levels of oxidative stress and inflammation. Oxidative stress and inflammation promote renal injury via damage to molecular components of the kidney. Unfortunately, relationships between inflammation and oxidative stress are cyclical in that the inflammatory processes that exist to repair radical-mediated damage may be a source of additional free radicals, resulting in further damage to renal tissue. Oxidative stress and inflammation also have the ability to become systemic, serving to injure tissues distal to the site of original insult. This review describes select mediators in the exacerbatory relationship between oxidative stress, inflammation, and CKD. This review also discusses oxidative stress, inflammation, and CKD as they pertain to the development and progression of common CKD-associated comorbidities. Lastly, the utility of several widely accessible and cost-effective lifestyle interventions and their ability to reduce oxidative stress and inflammation are discussed and recommendations for future research are provided.	f	\N
25897458	As of late 2014, interferon beta injection was the standard "disease-modifying" treatment for patients with relapsing-remitting multiple sclerosis, in the absence of a better alternative. Alemtuzumab (Lemtrada degree, Genzyme Therapeutics), an antilymphocyte monoclonal antibody first used in some types of leukaemia, is authorised in the European Union, at a different dosage, for patients with multiple sclerosis. Clinical evaluation in multiple sclerosis is based on three unblinded trials comparing alemtuzumab with interferon beta-1a. These trials were all biased in favour of alemtuzumab and thus fail to establish the potential value of this immunosuppressant. Overall, adverse effects, including the most severe, were more frequent with alemtuzumab than with interferon beta-1a. The adverse effects of alemtuzumab reported in these trials had already been observed in cancer patients. They included potentially severe reactions to the infusion, as well as a risk of infections and cancer due to profound and prolonged immunosuppression. At the dosage authorised in multiple sclerosis, autoimmune disorders such as thyroid disorders and immune thrombocytopenic purpura are particularly frequent and serious. In practice, patients with multiple sclerosis already have difficulty coping with the troublesome consequences of their underlying disease. They should not be subjected to the serious adverse effects of alemtuzumab, especially given the absence of any proven benefit.	f	\N
25924288	The paper describes the development of alopecia with a patient with echinocccosis alveolaris during treatment with Nemozole (albandazole). To decide to continue or to discontinue Nemozole treatment in the development of alopecia, the patient should be given full information on the risk of alopecia to his life and quality of life as compared to the sequels of recurrent hydatid disease when Nemozole is discontinued.	f	\N
25924757	Hypercalcaemia is a common biochemical abnormality in the blood that can be caused by malignancy, hyperparathyroidism, medications or underlying medical conditions. Initial signs and symptoms are often vague, however, if someone has severe hypercalcaemia it is treated as an emergency, requiring prompt management to prevent life-threatening complications such as dehydration, cardiac arrhythmias or coma. Understanding the pathophysiology, signs and symptoms of hypercalcaemia enables effective diagnosis and holistic management of the patient with complex health needs.	f	\N
25925920	Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically susceptible individuals. CD-related enteropathy leads to multiple nutritional deficiencies involving macro- and micronutrients. Currently, medical nutrition therapy consisting of the gluten-free diet (GFD) is the only accepted treatment for CD. The GFD is the cornerstone of treatment for CD. Prior published studies have concluded that maintenance of the GFD results in improvement of the majority of nutritional deficiencies. In the past, counseling for CD focused mainly on the elimination of gluten in the diet. However, the GFD is not without its inadequacies; compliance to the GFD may result in certain deficiencies such as fiber, B vitamins, iron, and trace minerals. Paucity of fortified gluten-free foods may be responsible for certain deficiencies which develop on the GFD. Weight gain and obesity have been added to the list of nutritional consequences while on the GFD and have been partially attributed to hypercaloric content of commercially available gluten-free foods. Follow-up of patients diagnosed with CD after starting the GFD has been reported to be irregular and, hence, less than ideal. Monitoring of the nutritional status using blood tests and use of appropriate gluten-free supplementation are integral components in the management of CD. The ideal GFD should be nutrient-dense with naturally gluten-free foods, balanced with macro- and micronutrients, reasonably priced, and easily accessible. Rotation of the pseudo-cereals provides a good source of complex carbohydrates, protein, fiber, fatty acids, vitamins and minerals. Fortification/enrichment of commonly consumed gluten-free commercial grain products should be encouraged. Dietitians specializing in CD play a critical role in the education and maintenance of the GFD for patients with CD.	f	\N
25934387	C5a plays a central role in antineutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. A previous study showed that C5a played a crucial role in the regulation of high mobility group box 1 (HMGB1) release from human neutrophils. The current study further investigated the interaction between C5a and HMGB1 in ANCA-induced neutrophil activation. The effects of HMGB1 inhibitors on the translocation of ANCA antigens, ANCA-induced respiratory burst and degranulation of C5a-primed neutrophils were tested. We found that blocking HMGB1 decreased C5a-mediated translocation of ANCA antigens, as well as ANCA-induced respiratory burst and degranulation of C5a-primed neutrophils. Further study showed that supernatant of C5a-primed neutrophils, which contained HMGB1, also caused translocation of ANCA antigens of primary neutrophils, whereas blocking HMGB1 decreased the translocation. In conclusion, blocking HMGB1 may attenuate ANCA-induced activation of C5a-primed neutrophils. The interaction between HMGB1 and C5a might play an important role in ANCA-induced neutrophil activation.	f	\N
25945002	To compare ultrasound-based acoustic structure quantification (ASQ) with established non-invasive techniques for grading and staging fatty liver disease. Type 2 diabetic patients at risk of non-alcoholic fatty liver disease (n = 50) and healthy volunteers (n = 20) were evaluated using laboratory analysis and anthropometric measurements, transient elastography (TE), controlled attenuation parameter (CAP), proton magnetic resonance spectroscopy ((1)H-MRS; only available for the diabetic cohort), and ASQ. ASQ parameters mode, average and focal disturbance (FD) ratio were compared with: (1) the extent of liver fibrosis estimated from TE and non-alcoholic fatty liver disease (NAFLD) fibrosis scores; and (2) the amount of steatosis, which was classified according to CAP values. Forty-seven diabetic patients (age 67.0 ± 8.6 years; body mass index 29.4 ± 4.5 kg/m²) with reliable CAP measurements and all controls (age 26.5 ± 3.2 years; body mass index 22.0 ± 2.7 kg/m²) were included in the analysis. All ASQ parameters showed differences between healthy controls and diabetic patients (P < 0.001, respectively). The ASQ FD ratio (logarithmic) correlated with the CAP (r = -0.81, P < 0.001) and (1)H-MRS (r = -0.43, P = 0.004) results. The FD ratio [CAP < 250 dB/m: 107 (102-109), CAP between 250 and 300 dB/m: 106 (102-114); CAP between 300 and 350 dB/m: 105 (100-112), CAP ≥ 350 dB/m: 102 (99-108)] as well as mode and average parameters, were reduced in cases with advanced steatosis (ANOVA P < 0.05). However, none of the ASQ parameters showed a significant difference in patients with advanced fibrosis, as determined by TE and the NAFLD fibrosis score (P > 0.08, respectively). ASQ parameters correlate with steatosis, but not with fibrosis in fatty liver disease. Steatosis estimation with ASQ should be further evaluated in biopsy-controlled studies.	f	\N
25971299	Cancer recurrence and disease-free survival are key outcomes for measuring the burden of illness, assessing the quality of cancer care, and informing decisions about increasingly costly cancer therapies. Yet information about recurrence is not collected in cancer registries or other population-based data sources. To address the lack of population-based recurrence information, researchers are increasingly using algorithms applied to health claims to infer recurrence. However, the validity of these approaches has not been comprehensively evaluated. In this commentary, we review existing studies and discuss options for improving the availability of recurrence data. We found that the validity of claims-based approaches appears promising in small, single institution studies, but larger population-based studies have identified substantial limitations with using claims to identify recurrence. With the increasing availability of health data, there are potential options that can be implemented to enhance information about recurrence. These options include design of software for the electronic medical record that enables rapid and standardized reporting of recurrence, use of electronic pathology reports to facilitate streamlined collection of recurrence by cancer registries, and mandates by insurers to require reporting of recurrence on health claims submitted by physicians. All of these options will require that governmental agencies, health insurers, professional societies, and other groups recognize the importance of population-based recurrence data and determine that this information is a priority for assessing cancer outcomes and costs.	f	\N
25972525	Relations of the 25 mammalian selenoprotein genes with obesity and the associated inflammation remain unclear. This study explored impacts of high-fat diet-induced obesity on inflammation and expressions of selenoprotein and obesity-related genes in 10 tissues of pigs. Plasma and 10 tissues were collected from pigs (n = 10) fed a corn-soy-based control diet or that diet containing 3-7% lard from weanling to finishing (180 d). Plasma concentrations (n = 8) of cytokines and thyroid hormones and tissue mRNA abundance (n = 4) of 25 selenoprotein genes and 16 obesity-related genes were compared between the pigs fed the control and high-fat diets. Stepwise regression was applied to analyze correlations among all these measures, including the previously reported body physical and plasma biochemical variables. The high-fat diet elevated (P < 0.05) plasma concentrations of tumor necrosis factor α, interleukin-6, leptin, and leptin receptor by 29-42% and affected (P < 0.05-0.1) tissue mRNA levels of the selenoprotein and obesity-related genes in 3 patterns. Specifically, the high-fat diet up-regulated 12 selenoprotein genes in 6 tissues, down-regulated 13 selenoprotein genes in 7 tissues, and exerted no effect on 5 genes in any tissue. Body weights and plasma triglyceride concentrations of pigs showed the strongest regressions to tissue mRNA abundances of selenoprotein and obesity-related genes. Among the selenoprotein genes, selenoprotein V and I were ranked as the strongest independent variables for the regression of phenotypic and plasma measures. Meanwhile, agouti signaling protein, adiponectin, and resistin genes represented the strongest independent variables of the obesity-related genes for the regression of tissue selenoprotein mRNA. The high-fat diet induced inflammation in pigs and affected their gene expression of selenoproteins associated with thioredoxin and oxidoreductase systems, local tissue thyroid hormone activity, endoplasmic reticulum protein degradation, and phosphorylation of lipids. This porcine model may be used to study interactive mechanisms between excess fat intake and selenoprotein function.	f	\N
25998164	In atopic dermatitis (AD), the inflammatory response between skin-infiltrating T cells and keratinocytes is fundamental to the development of chronic lesional eczema. The aim of this study was to investigate whether skin-derived T cells from AD patients could induce an inflammatory response in mice through keratinocyte activation and consequently cause the development of eczematous lesions. Punch biopsies of the lesional skin from AD patients were used to establish skin-derived T cell cultures, which were transferred to NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that the subcutaneous injection of the human AD skin-derived T cells resulted in the migration of the human T cells from subcutis to the papillary dermis followed by the development of erythema and oedema in the mouse skin. Furthermore, the human T cells induced a transient proliferative response in the mouse keratinocytes shown as increased numbers of Ki-67(+) keratinocytes and increased epidermal thickness. Out of six established AD skin-derived T cell cultures, two were superior at inducing a skin reaction in the mice, and these cultures were found to contain >10% CCR10(+) T cells compared to <2% for the other cultures. In comparison, blood-derived in vitro-differentiated Th2 cells only induced a weak response in a few of the mice. Thus, we conclude that human AD skin-derived T cells can induce a reaction in the mouse skin through the induction of a proliferative response in the mouse keratinocytes.	f	\N
26026650	The aim of the Activating Schoolyards Study is to develop, implement, document and assess a comprehensive schoolyard intervention to promote physical activity (PA) during school recess for primary school children (grade 4-8). The intervention is designed to implement organizational and structural changes in the physical environment. The study builds on a quasi-experimental study design using a mixed method approach including: 1) an exploratory study aimed at providing input for the developing process; 2) an evaluation of the effect of the interventions using a combination of accelerometer, GPS and GIS; 3) a process evaluation facilitating the intervention development process and identifying barriers and facilitators in the implementation process; 4) a post-intervention end-user evaluation aimed at exploring who uses the schoolyards and how the schoolyards are used. The seven project schools (cases) were selected by means of an open competition and the interventions were developed using a participatory bottom-up approach. The participatory approach and case selection strategy make the study design novel. The use of a mixed methods design including qualitative as well as quantitative methods can be seen as a strength, as the different types of data complement each other and results of one part of the study informed the following parts. A unique aspect of our study is the use of accelerometers in combination with GPS and GIS in the effect evaluation to objectively determine where and how active the students are in the schoolyard, before and after the intervention. This provides a type of data that, to our knowledge, has not been used before in schoolyard interventions. Exploring the change in behavior in relation to specific intervention elements in the schoolyard will lead to recommendations for schools undergoing schoolyard renovations at some point in the future.	f	\N
26029704	Many common diseases have a complex genetic basis in which large numbers of genetic variations combine with environmental factors to determine risk. However, quantifying such polygenic effects has been challenging. In order to address these difficulties we developed a global measure of the information content of an individual's genome relative to a reference population, which may be used to assess differences in global genome structure between cases and appropriate controls. Informally this measure, which we call relative genome information (RGI), quantifies the relative "disorder" of an individual's genome. In order to test its ability to predict disease risk we used RGI to compare single-nucleotide polymorphism genotypes from two independent samples of women with early-onset breast cancer with three independent sets of controls. We found that RGI was significantly elevated in both sets of breast cancer cases in comparison with all three sets of controls, with disease risk rising sharply with RGI. Furthermore, these differences are not due to associations with common variants at a small number of disease-associated loci, but rather are due to the combined associations of thousands of markers distributed throughout the genome. Our results indicate that the information content of an individual's genome may be used to measure the risk of a complex disease, and suggest that early-onset breast cancer has a strongly polygenic component.	f	\N
26037125	Vaginal inflammation (vaginitis) is the most common disease caused by the human-pathogenic fungus Candida albicans. Secretory aspartyl proteinases (Sap) are major virulence traits of C. albicans that have been suggested to play a role in vaginitis. To dissect the mechanisms by which Sap play this role, Sap2, a dominantly expressed member of the Sap family and a putative constituent of an anti-Candida vaccine, was used. Injection of full-length Sap2 into the mouse vagina caused local neutrophil influx and accumulation of the inflammasome-dependent interleukin-1β (IL-1β) but not of inflammasome-independent tumor necrosis factor alpha. Sap2 could be replaced by other Sap, while no inflammation was induced by the vaccine antigen, the N-terminal-truncated, enzymatically inactive tSap2. Anti-Sap2 antibodies, in particular Fab from a human combinatorial antibody library, inhibited or abolished the inflammatory response, provided the antibodies were able, like the Sap inhibitor Pepstatin A, to inhibit Sap enzyme activity. The same antibodies and Pepstatin A also inhibited neutrophil influx and cytokine production stimulated by C. albicans intravaginal injection, and a mutant strain lacking SAP1, SAP2, and SAP3 was unable to cause vaginal inflammation. Sap2 induced expression of activated caspase-1 in murine and human vaginal epithelial cells. Caspase-1 inhibition downregulated IL-1β and IL-18 production by vaginal epithelial cells, and blockade of the IL-1β receptor strongly reduced neutrophil influx. Overall, the data suggest that some Sap, particularly Sap2, are proinflammatory proteins in vivo and can mediate the inflammasome-dependent, acute inflammatory response of vaginal epithelial cells to C. albicans. These findings support the notion that vaccine-induced or passively administered anti-Sap antibodies could contribute to control vaginitis. Candidal vaginitis is an acute inflammatory disease that affects many women of fertile age, with no definitive cure and, in its recurrent forms, causing true devastation of quality of life. Unraveling the fungal factors causing inflammation is important to be able to devise novel tools to fight the disease. In an experimental murine model, we have discovered that aspartyl proteinases, particularly Sap2, may cause the same inflammatory signs of vaginitis caused by the fungus and that anti-Sap antibodies and the protease inhibitor Pepstatin A almost equally inhibit Sap- and C. albicans-induced inflammation. Sap-induced vaginitis is an early event during vaginal infection, is uncoupled from fungal growth, and requires Sap and caspase-1 enzymatic activities to occur, suggesting that Sap or products of Sap activity activate an inflammasome sensor of epithelial cells. Our data support the notion that anti-Sap antibodies could help control the essence of candidal vaginitis, i.e., the inflammatory response.	f	\N
26041263	Several mutations in nuclear genes encoding for mitochondrial components have been associated with an increased cancer risk or are even causative, e.g. succinate dehydrogenase (SDHB, SDHC and SDHD genes) and iso-citrate dehydrogenase (IDH1 and IDH2 genes). Recently, studies have suggested an eminent role for mitochondrial DNA (mtDNA) mutations in the development of a wide variety of cancers. Various studies associated mtDNA abnormalities, including mutations, deletions, inversions and copy number alterations, with mitochondrial dysfunction. This might, explain the hampered cellular bioenergetics in many cancer cell types. Germline (e.g. m.10398A>G; m.6253T>C) and somatic mtDNA mutations as well as differences in mtDNA copy number seem to be associated with cancer risk. It seems that mtDNA can contribute as driver or as complementary gene mutation according to the multiple-hit model. This can enhance the mutagenic/clonogenic potential of the cell as observed for m.8993T>G or influences the metastatic potential in later stages of cancer progression. Alternatively, other mtDNA variations will be innocent passenger mutations in a tumor and therefore do not contribute to the tumorigenic or metastatic potential. In this review, we discuss how reported mtDNA variations interfere with cancer treatment and what implications this has on current successful pharmaceutical interventions. Mutations in MT-ND4 and mtDNA depletion have been reported to be involved in cisplatin resistance. Pharmaceutical impairment of OXPHOS by metformin can increase the efficiency of radiotherapy. To study mitochondrial dysfunction in cancer, different cellular models (like ρ(0) cells or cybrids), in vivo murine models (xenografts and specific mtDNA mouse models in combination with a spontaneous cancer mouse model) and small animal models (e.g. Danio rerio) could be potentially interesting to use. For future research, we foresee that unraveling mtDNA variations can contribute to personalized therapy for specific cancer types and improve the outcome of the disease.	f	\N
26083239	Dual-isotope simultaneous-acquisition (DISA) rest-stress myocardial perfusion SPECT (MPS) protocols offer a number of advantages over separate acquisition. However, crosstalk contamination due to scatter in the patient and interactions in the collimator degrade image quality. Compensation can reduce the effects of crosstalk, but does not entirely eliminate image degradations. Optimizing acquisition parameters could further reduce the impact of crosstalk. In this paper we investigate the optimization of the rest Tl-201 energy window width and relative injected activities using the ideal observer (IO), a realistic digital phantom population and Monte Carlo (MC) simulated Tc-99m and Tl-201 projections as a means to improve image quality. We compared performance on a perfusion defect detection task for Tl-201 acquisition energy window widths varying from 4 to 40 keV centered at 72 keV for a camera with a 9% energy resolution. We also investigated 7 different relative injected activities, defined as the ratio of Tc-99m and Tl-201 activities, while keeping the total effective dose constant at 13.5 mSv. For each energy window and relative injected activity, we computed the IO test statistics using a Markov chain Monte Carlo (MCMC) method for an ensemble of 1,620 triplets of fixed and reversible defect-present, and defect-absent noisy images modeling realistic background variations. The volume under the 3-class receiver operating characteristic (ROC) surface (VUS) was estimated and served as the figure of merit. For simultaneous acquisition, the IO suggested that relative Tc-to-Tl injected activity ratios of 2.6-5 and acquisition energy window widths of 16-22% were optimal. For separate acquisition, we observed a broad range of optimal relative injected activities from 2.6 to 12.1 and acquisition energy window of widths 16-22%. A negative correlation between Tl-201 injected activity and the width of the Tl-201 energy window was observed in these ranges. The results also suggested that DISA methods could potentially provide image quality as good as that obtained with separate acquisition protocols. We compared observer performance for the optimized protocols and the current clinical protocol using separate acquisition. The current clinical protocols provided better performance at a cost of injecting the patient with approximately double the injected activity of Tc-99m and Tl-201, resulting in substantially increased radiation dose.	f	\N
26086077	Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the 'human blood metabolome-transcriptome interface' (BMTI). Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease.	f	\N
26109487	The aim of this study was to evaluate the long-term outcomes of patients with colorectal cancer liver metastasis (CRCLM) exhibiting disease progression after portal vein embolization (PVE). Patients with CRCLM requiring PVE before hepatectomy between 2003 and 2014 were included. Clinical variables, and liver and tumour volumes determined by three-dimensional CT volumetry were assessed before and after PVE. Overall and disease-free survival data were obtained. Univariable and multivariable logistic regression analyses were performed to identify predictors of tumour progression after PVE. Of 141 patients who underwent PVE, 93 (66.0 per cent) had tumour progression and 17 (12.1 per cent) developed new contralateral lesions. Significantly fewer patients had resectable disease in the group with disease progression than among those with stable disease: 43 (46 per cent) of 93 versus 36 (75 per cent) of 48 respectively (P = 0.001). Median survival was similar in patients with and without tumour growth after PVE: 22.5 versus 26.0 months for patients with unresectable tumours (P = 0.706) and 46.2 versus 52.2 months for those with resectable disease (P = 0.953). However, disease-free survival for patients with tumour progression after PVE was shorter than that for patients with stable disease (6.0 versus 20.2 months; P = 0.045). Response to neoadjuvant chemotherapy was the only significant factor associated with tumour progression in multivariable analysis. Tumour progression after PVE did not affect overall survival, but patients with resected tumours who had tumour growth after embolization experienced earlier recurrence. A borderline response to neoadjuvant chemotherapy seemed to be associated with tumour progression after PVE.	f	\N
26118068	There has been a significant increase in diabetes morbidity in the past years. Prolonged asymptomatic progression of disease presents a problem and leads to late diagnosis and development of complications. Present study shows efficiency of screening measures to determine actual spread of carbohydrate metabolism disorders among residents of Odessa, frequency of type 2 diabetes mellitus risk factors determination and prevention of complications.	f	\N
26141335	In the past few years, new biological insights into the myelodysplastic syndromes (MDS) resulting from molecular genetic analysis have improved pathologic understanding, but treatment advances have not kept pace. More than 40 genes are now known to be recurrently mutated in MDS. However, because most of these genes encode spliceosome components, chromatic remodeling factors, epigenetic pattern modulators, or transcription factors rather than more easily inhibited activated tyrosine kinases, there are as of yet few narrowly targeted therapies available for MDS. Three drugs--azacitidine, decitabine, and lenalidomide--were approved by the US Food and Drug Administration for MDS indications a decade ago, and these agents can improve hematopoiesis, delay disease progression, and improve survival and quality of life for a subset of patients. However, only a few patients with MDS respond to these agents, and their benefit is temporary. The only potentially curative therapy for MDS is allogeneic hematopoietic stem cell transplant, but owing to the advanced age of many patients with MDS and the frequency of serious comorbid conditions, less than 10% of patients currently undergo stem cell transplant. This narrative review summarizes the current understanding of MDS and treatment options for these challenging disorders.	f	\N
26143070	Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95 % CI 2.5-14.5, p = 0.004) with high resolution CT. In the multivariate analysis ethnicity (p = 0.02) and disease state (p < 0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95 % CI 2.5-14.5, p = 0.004) and in HAM/TSP patients compared with all other categories 8.4 (95 % CI 2.7-26.1, p = 0.0002). Subjects not of African/Afro-Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95 % 1.2-9.7, p = 0.02). Bronchiectasis was common in the cohort (3.4 %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis.	f	\N
26148061	In humans, neurodegenerative disorders such as Huntington's disease (HD) and many spinocerebellar ataxias (SCAs) have been found to be associated with CAG trinucleotide repeat expansion. An important RNA-mediated mechanism that causes these diseases involves the binding of the splicing regulator protein MBNL1 (Muscleblind-like 1 protein) to expanded r(CAG) repeats. Moreover, mutant huntingtin protein translated from expanded r(CAG) also yields toxic effects. To discern the role of mutant RNA in these diseases, it is essential to gather information about its structure. Detailed insight into the different structures and conformations adopted by these mutant transcripts is vital for developing therapeutics targeting them. Here, we report the crystal structure of an RNA model with a r(CAG) motif, which is complemented by an NMR-based solution structure obtained from restrained Molecular Dynamics (rMD) simulation studies. Crystal structure data of the RNA model resolved at 2.3 Å reveals non-canonical pairing of adenine in 5´-CAG/3´-GAC motif samples in different syn and anti conformations. The overall RNA structure has helical parameters intermediate to the A- and B-forms of nucleic acids due to the global widening of major grooves and base-pair preferences near internal AA loops. The comprehension of structural behaviour by studying the spectral features and the dynamics also supports the flexible nature of the r(CAG) motif.	f	\N
26149802	The importance of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo-HSCT. These consisted of leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999-2008. The Mantel-Byar approach was used to assess allo-HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo-HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41-60. The CIR demonstrated that allo-HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo-HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41-60. The allo-HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis.	f	\N
26160211	The objective of this study was to compare the efficacy and comfort of inelastic bandages (IBs) and adjustable Velcro compression devices (AVCDs) in reducing venous leg edema in the initial treatment phase. Forty legs from 36 patients with untreated venous edema (C3EpsAsdPr) were randomized to two groups. Patients in the first group received IBs (n = 20) and those in the second AVCDs (n = 20). Both compression devices were left on the leg day and night, and were renewed after 1 day. Patients in the AVCD group were asked to re-adjust the device as needed when it felt loose. Leg volume was calculated using the truncated cone formula at baseline (T0), after 1 day (T1) and after 7 days (T7). The interface pressure of the two compression devices was measured by an air filled probe, and the static stiffness index calculated after applying compression at T0 and T1, and just before removal of compression on T1 and T7. Patient comfort with regard to the two compression systems was assessed by grading signs and symptoms using a visual analog scale. At T1, the median percent volume reduction was 13% for the IB group versus 19% for the AVCD group; at T7 it was 19% versus 26%, respectively (p < .001). The pressure of the IBs was significantly higher compared with the AVCDs at T0 (63 vs. 43 mmHg) but dropped by > 50% over time, while it remained unchanged with AVCDs owing to the periodic readjustment by the patient. Comfort was reported to be similar with the two compression devices. Re-adjustable AVCDs with a resting pressure of around 40 mmHg are more effective in reducing chronic venous edema than IBs with a resting pressure of around 60 mmHg. AVCDs are effective and well tolerated, not only during maintenance therapy, but also in the initial decongestive treatment phase of patients with venous leg edema.	f	\N
26163286	Thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine that has been studied extensively in atopic diseases and more recently in various rheumatic disorders. It is involved in T cell development in the thymus and promotes homeostatic T cell expansion by classical dendritic cells. However, deregulated TSLP expression in various rheumatic diseases has implicated this cytokine as a strong mediator in immunopathology. Overexpressed TSLP induces strong T cell activation and production of pro-inflammatory cytokines in human cells and animal models for RA, SSc and LN, underscoring the therapeutic potential of targeting the TSLP-TSLP receptor axis.	f	\N
26174498	The 14(th) -century Black Death was one of the most devastating epidemics in human history, killing tens of millions of people in a short period of time. It is not clear why mortality rates during the epidemic were so high. One possibility is that the affected human populations were particularly stressed in the 14(th) century, perhaps as a result of repeated famines in areas such as England. This project examines survival and mortality in two pre-Black Death time periods, 11-12(th) centuries vs 13(th) century CE, to determine if demographic conditions were deteriorating before the epidemic occurred. This study is done using a sample of individuals from several London cemeteries that have been dated, in whole or in part, either to the 11-12(th) centuries (n = 339) or 13(th) century (n = 258). Temporal trends in survivorship and mortality are assessed via Kaplan-Meier survival analysis and by modeling time period as a covariate affecting the Gompertz hazard of adult mortality. The age-at-death distributions from the two pre-Black Death time periods are significantly different, with fewer older adults in 13(th) century. The results of Kaplan-Meier survival analysis indicate reductions in survival before the Black Death, with significantly lower survival in the 13(th) century (Mantel Cox p < 0.001). Last, hazard analysis reveals increases in mortality rates before the Black Death. Together, these results suggest that health in general was declining in the 13(th) century, and this might have led to high mortality during the Black Death. This highlights the importance of considering human context to understand disease in past and living human populations.	f	\N
26175069	Dengue hemorrhagic fever (DHF), although predominantly associated with secondary infections, has also been reported in primary infections. An enhanced immune response including antibodies and cytokines is implicated in the pathogenesis of secondary DHF. However, the factors operating in primary DHF are poorly understood. To understand the role of the antibody response, the relative levels of different antibody isotypes during the acute phase of infection in primary and secondary dengue infections were determined. Levels of DENV-specific IgM, IgG, IgA and IgE were measured in the serum samples of 200 dengue patients and 20 dengue-naïve individuals. Samples were collected within 15 days of onset of illness. The DENV-specific IgM levels were significantly higher in DF cases compared to DHF, which was more evident in secondary infections and in post-defervescence samples. The levels of IgG, IgA and IgE were higher in DHF cases, with greater significance in primary infections. A higher level of IgG in DHF cases was evident in pre-defervescence samples, whilst the IgE level was higher in pre- and post-defervescence samples. There was a significant correlation of IgG titres with platelet counts, with higher titres associated with lower platelet counts. It is speculated that IgG, IgA and IgE produced in response to primary infections may contribute to pathogenesis, whilst IgM produced in response to secondary infections may protect against progression to severe disease.	f	\N
26189088	To determine the statistical correlation between visual acuity (VA) and various quantitative parameters relevant to birdshot retinochoroidopathy (BRC) evaluation. Hospital-based retrospective observational study. setting: Institutional. Consecutive HLA29+ BRC patients were included between May and August 2013 at a single tertiary center (Pitié-Salpétrière Hospital, Paris). Demographic data and quantitative parameters relevant to BRC at baseline were collected: VA, degree of anterior and posterior inflammatory reaction, foveal thickness measured by optical coherence tomography (OCT), Arden ratio, and electrooculography (EOG) light peak. Correlation between VA and the other parameters of the ipsilateral and fellow eye was performed using Spearman rank correlation coefficients. Fifty-five patients were included. Mean VA was 6/9.5 in the right eye (OD) and 6/12 in the left eye (OS). Mean foveal thickness was 240 μm OD (range: 112-606) and 251 μm OS (range: 85-662). Mean Arden ratio was 159% OD and 160% OS. EOG light peak was 714 mV OD (range: 316-1379) and 746 mV OS (range: 272-1652). VA of a given eye was moderately correlated with VA of the contralateral eye (r = 0.4). On the contrary, all other parameters showed a strong correlation between both eyes (all r > 0.7, P < .01). Overall, none of the studied parameters was correlated with its VA (all r < 0.5). In BRC, visual acuity alone does not seem to fully reflect the disease severity in terms of clinical or ancillary quantitative findings at baseline.	f	\N
26204159	Dividing cells that experience chromosome mis-segregation generate aneuploid daughter cells, which contain an incorrect number of chromosomes. Although aneuploidy interferes with the proliferation of untransformed cells, it is also, paradoxically, a hallmark of cancer, a disease defined by increased proliferative potential. These contradictory effects are also observed in mouse models of chromosome instability (CIN). CIN can inhibit and promote tumorigenesis. Recent work has provided insights into the cellular consequences of CIN and aneuploidy. Chromosome mis-segregation per se can alter the genome in many more ways than just causing the gain or loss of chromosomes. The short- and long-term effects of aneuploidy are caused by gene-specific effects and a stereotypic aneuploidy stress response. Importantly, these recent findings provide insights into the role of aneuploidy in tumorigenesis.	f	\N
26211602	Small cell carcinoma of head and neck region (SmCCHN) represents a rare entity and its management remains a significant clinical challenge. Complete initial response to primary therapy poses a difficult and controversial scenario for radiation oncologists. Prophylactic cranial irradiation (PCI) has long been established in the management of small cell lung cancer; however, its role in SmCCHN is still called into question. The rationale behind PCI lies in the eradication of possible micro-metastatic brain disease, which is often documented in this type of cancer. No randomized trials on this topic are available. This review, based on 20 retrospective studies, addresses the controversies in the use of PCI in SmCCHN management.	f	\N
26253469	Under distinct pathological heart conditions, the expression of a single miRNA can display completely opposite patterns. However, the mechanism underlying the bidirectional regulation of a single miRNA and the clinical implications of this regulation remain largely unknown. To address this issue, we examined the regulation of miR-1, one of the most abundant miRNAs in the heart, during cardiac hypertrophy and ischemia/reperfusion (I/R). Our data indicated that different magnitudes and chronicities of ROS levels in cardiomyocytes resulted in differential expression of miR-1, subsequently altering the expression of myocardin. In animal models, the administration of a miR-1 mimic attenuated cardiac hypertrophy by suppressing the transverse aortic constriction-induced increase in myocardin expression, whereas the administration of anti-miR-1 ameliorated I/R-induced cardiac apoptosis and deterioration of heart function. Our findings indicated that a pathologic stimulus such as ROS can bidirectionally alter the expression of miRNA to contribute to the development of pathological conditions exhibiting distinct phenotypes and that the meticulous adjustment of the pathological miRNA levels is required to improve clinical outcomes.	f	\N
26285805	VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments.	f	\N
26292522	At the death of Cardinal Pietro Basadonna in 1684, his personal physician Romolo Spezioli wrote a report describing the disease, circumstances of death and autopsy findings of the illustrious prelate. This document, kept in the Biblioteca Civica at Jesi, is a significant attestation of the medical terminology and diagnostic and therapeutic procedures of the time. Even with the constraints that interpretation of a clinical account dating back over 300 years inevitably imposes, perusal of this report suggests that Cardinal Basadonna's demise could have been due to septic shock, consequent to a urinary infection caused by a bulky bladder stone.	f	\N
26293802	Leptin is an adipocytokine produced by adipocytes and controlling body weight. It is unclear whether leptin works as a proinflammatory or an anti-inflammatory cytokine. We investigated the effects of hyperleptinemia on leptin transgenic (LepTg) mice in terms of cartilage destruction, bone destruction, joint synovitis, and serum cytokine levels by using a mouse model of collagen-antibody-induced arthritis (CAIA). CAIA was induced for female age-matched 6- to 8-week-old C57BL/6 J control mice and LepTg mice. Mice were injected intraperitoneally with 5 mg of a combination of monoclonal antibody specific for type II collagen on day 0 and 12.5 mg of lipopolysaccharide (LPS) on day 3. Clinical evaluation of arthritis was monitored for 14 days, and hind paws were examined clinically and histologically. Serum cytokine levels of interleukin (IL)-1β, IL-6, IL-10, and IL-17 and tumor necrosis factor alpha (TNF-α) were also analyzed on days 0 and 5. Moreover, THP-1 cells, which are human monocytic cell line derived from an acute monocytic leukemia patient, were cultured and differentiated into macrophages. The effects of leptin on messenger RNA (mRNA) expression of IL-6 were examined by real-time quantitative polymerase chain reaction (RT-PCR). Serum leptin concentrations were approximately ninefold higher in LepTg mice (62.0 ± 20.7 ng/ml) than in control mice (7.2 ± 0.5 ng/ml). Severity of clinical paw swelling, arthritis score, synovial hyperplasia, and cartilage damage were suppressed in LepTg mice with CAIA. Although serum cytokine levels of IL-1β, IL-17, and IL-10 and TNF-α showed no significant changes in two mice, serum levels of IL-6 in LepTg mice were suppressed at day 5. Moreover, in vitro study showed that IL-6 elevation following LPS exposure in THP-1 cells was suppressed with high leptin concentrations. Our finding suggests that hyperleptinemia suppress IL-6 responses and progression of joint inflammation. Leptin may play an anti-inflammatory role under hyperleptinemia.	f	\N
26299076	The aim of this study is to observe the association between venous thromboembolism (VTE) and oxidative stress and to see if there is a diagnostic value in the oxidative/antioxidative balance parameters like total oxidant status (TOS), total antioxidant status (TAS), paraoxonase-(PON1), and arylesterase (ARE) enzyme activities in this specific disease. Sixty-nine patients with deep vein thrombosis and/or pulmonary embolism and 40 control subjects were included in the study. Oxidative stress index, total oxidant status, and antioxidant status were examined in addition to the PON1 and ARE enzyme activities in both groups. Serum PON1 and ARE activities were significantly lower in the VTE patients, whereas total oxidant status was higher in patients compared to the controls. This preliminary study showed that oxidative/antioxidative balance shifted towards the oxidative status in venous thromboembolism. ROC analysis results suggested that the parameters used in this study were not good enough to be used in the diagnosis of VTE.	f	\N
26310351	Google Flu Trends (GFT) was the first application of big data in the public health field. GFT was open online in 2009 and attracted worldwide attention immediately. However, GFT failed catching the 2009 pandemic H1N1 and kept overestimating the intensity of influenza-like illness in the 2012-2014 season in the United States. GFT model has been updated for three times since 2009, making its prediction bias controlled. Here, we summarized the mechanism GFT worked, the strategy GFT used to update, and its influence on public health.	f	\N
26357715	Anal cancer is a relatively uncommon disease, accounting for only 4% of cancers of the lower gastrointestinal tract. To summarize a single-center experience in the treatment of anal carcinoma using various radiation techniques. We conducted a retrospective chart review of consecutive patients who were treated for anal cancer between the years 2002 and 2011. The data extracted included demographics, type of radiation technique, treatment-associated acute toxicity, and patterns of failure and survival. For statistical analysis purposes, the patients were divided into two groups according to radiotherapy technique: 2D (group A) and 3D (group B). A total of 42 patients--25 (59.5%) females and 17 males (40.5%)--underwent definitive chemo-radiation treatment (CRT) for anal cancer. Group A comprised 26 patients and group B 14 patients. Toxicity did not differ significantly between the groups; only in grade 1-2 skin toxicity which was more common in group B. There were significant differences in the unplanned interruptions in treatment, in both the number of patients who needed a treatment break and the number of days needed (more in group A). There were no differences in treatment response and patterns of failure between these two techniques, or in overall survival between the two groups. Our study results are consistent with reported large randomized trials, indicating that current treatments for anal carcinomas are associated with high grade acute toxicity that may result in significant treatment interruptions. The 2D technique was associated with significantly more treatment interruptions but did not differ from 3D with regard to treatment efficacy.	f	\N
26375933	There has been considerable effort over the last 25 years to understand the emergence of complexity in motor output and how this relates to properties of the individual (e.g., age, disease state, etc.), environment (e.g., information) and task (e.g., movement, posture, isometric force). This paper addresses the behavioral dimension of motor complexity in movement and posture from a degrees of freedom (DF) perspective together with the change of complexity through aging, disease and fatigue. The dimension of behavior for a given perceptual-motor output is shown to be relatively low, dependent on the interaction between the individual, environmental, and task constraints and varies within a limited adaptive range for a given motor task. The determination of dimension in movement and posture has taken us beyond the traditional motor performance scores of behavior but it is not a sufficient characterization of the adaptive and emergent processes of complexity.	f	\N
26381985	Assessment of the global burden of disease is based on epidemiological cohort studies that connect premature mortality to a wide range of causes, including the long-term health impacts of ozone and fine particulate matter with a diameter smaller than 2.5 micrometres (PM2.5). It has proved difficult to quantify premature mortality related to air pollution, notably in regions where air quality is not monitored, and also because the toxicity of particles from various sources may vary. Here we use a global atmospheric chemistry model to investigate the link between premature mortality and seven emission source categories in urban and rural environments. In accord with the global burden of disease for 2010 (ref. 5), we calculate that outdoor air pollution, mostly by PM2.5, leads to 3.3 (95 per cent confidence interval 1.61-4.81) million premature deaths per year worldwide, predominantly in Asia. We primarily assume that all particles are equally toxic, but also include a sensitivity study that accounts for differential toxicity. We find that emissions from residential energy use such as heating and cooking, prevalent in India and China, have the largest impact on premature mortality globally, being even more dominant if carbonaceous particles are assumed to be most toxic. Whereas in much of the USA and in a few other countries emissions from traffic and power generation are important, in eastern USA, Europe, Russia and East Asia agricultural emissions make the largest relative contribution to PM2.5, with the estimate of overall health impact depending on assumptions regarding particle toxicity. Model projections based on a business-as-usual emission scenario indicate that the contribution of outdoor air pollution to premature mortality could double by 2050.	f	\N
26383059	Multiple sclerosis (MS) is a demyelinating disease that affects young adults; in that age group, it represents the second leading cause of disability in our setting. Its precise aetiology has not been elucidated, but it is widely accepted to occur in genetically predisposed patients who are exposed to certain environmental factors. The discovery of the regulatory role played by intestinal microbiota in various autoimmune diseases has opened a new line of research in this field, which is discussed in this review. We reviewed published studies on the role of the microbiota in the development of both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In mice, it has been shown that intestinal microorganisms regulate the polarisation of T helper cells from Th1-Th17 up to Th2, the function of regulatory T cells, and the activity of B cells; they participate in the pathogenesis of EAE and contribute to its prevention and treatment. In contrast, evidence in humans is still scarce and mainly based on case-control studies that point to the presence of differences in certain bacterial communities. Multiple evidence points to the role of microbiota in EAE. Extrapolation of these results to MS is still in the early stages of research, and studies are needed to define which bacterial populations are associated with MS, the role they play in pathogenesis, and the therapeutic possibilities this knowledge offers us.	f	\N
26402460	Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. Perforin-2 is a transmembrane protein of cytosolic vesicles -derived from multiple organelles- that translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and forms large clusters of 100 Å pores in the bacterial surface with Perforin-2 cleavage products present in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal effector molecule of the innate immune system.	f	\N
26427384	The ubiquitin-proteasome pathway (UPP) is the primary degradation system of short-lived regulatory proteins. Cellular processes such as the cell cycle, signal transduction, gene expression, DNA repair and apoptosis are regulated by this UPP and dysfunctions inthis system have important implications in the development of cancer, neurodegenerative, cardiac and other human pathologies. UPP seems also to be very important in the function of eukaryote cells of the human parasites like Plasmodium falciparum, thecausal agent of the neglected disease Malaria. Hence, the UPP could be considered as an attractive target for the development of compounds with Anti-Malarial or Anti-cancer properties. Recent online databases like ChEMBL contains a larger quantity of information in terms of pharmacological assay protocols and compounds tested as UPP inhibitors under many different conditions. This large amount of data give new openings for the computer-aided identification of UPP inhibitors, but the intrinsic data diversity is an obstacle for the development of successful classifiers. To solve this problem here we used the Bob-Jenkins moving average operators and the atom-based quadratic molecular indices calculated with the software TOMOCOMD-CARDD (TC) to develop a quantitative model for the prediction of the multiple outputs in this complex dataset. Our multi-target model can predict results for drugs against 22 molecular or cellular targets of different organisms with accuracies above 70% in both training and validation sets.	f	\N
26432016	The continuous search for drugs targeting type 2 diabetes mellitus (T2DM) has led to the identification of small molecules that disrupt the binding between glucokinase and glucokinase regulatory protein (GKRP). Although mice studies are encouraging, it will take years before these disruptors can be introduced to T2DM patients. Recently, genome-wide association studies (GWASs) have shown that variants in the gene encoding GKRP protect against T2DM and kidney disease but predispose to gout, nonalcoholic fatty liver disease, and dyslipidemia. These genetic data, together with previous experience with systemic and hepatospecific glucokinase activators, provide insight into the anticipated efficacy and safety of small-molecule disruptors in humans. Interestingly, they suggest that the opposite--enhanced GKRP-glucokinase binding--could be beneficial in selected patients.	f	\N
26470622	Hidradenitis suppurativa (HS) is a chronic inflammatory disease that commonly develops painful, deep dermal abscesses and chronic, draining sinus tracts. Classically, pharmacologic and surgical therapies have been effective for reducing lesion activity and inflammation, but provide only modest success in the prevention of future recurrences and disease progression. Adjunctive therapies, such as laser and light-based therapies, have become more commonly used in the management of HS. These therapies work to reduce the occurrence of painful HS flare-ups by decreasing the number of hair follicles, sebaceous glands, and bacteria in affected areas, and by ablatively debulking chronic lesions. The best results are seen when treatment is individualized, taking disease severity into consideration when selecting specific energy-based approaches. This article will discuss various light-based therapies and the evidence supporting their use in the management of HS.	f	\N
26525918	Micrographia is a common symptom in Parkinson's disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks.	f	\N
26527069	Cancer, more than any other human disease, now has a surfeit of potential molecular targets poised for therapeutic exploitation. Currently, a number of attractive and validated cancer targets remain outside of the reach of pharmacological regulation. Some have been described as undruggable, at least by traditional strategies. In this article, we outline the basis for the undruggable moniker, propose a reclassification of these targets as undrugged, and highlight three general classes of this imposing group as exemplars with some attendant strategies currently being explored to reclassify them. Expanding the spectrum of disease-relevant targets to pharmacological manipulation is central to reducing cancer morbidity and mortality.	f	\N
26574670	The neurodegenerative synucleinopathies, which include Parkinson disease, multiple-system atrophy, and Lewy body disease, are characterized by the presence of abundant neuronal inclusions called Lewy bodies and Lewy neurites. These disorders remain incurable, and a greater understanding of the pathologic processes is needed for effective treatment strategies to be developed. Recent data suggest that pathogenic misfolding of the presynaptic protein, α-synuclein (α-syn), and subsequent aggregation and accumulation are fundamental to the disease process. It is hypothesized that the misfolded isoform is able to induce misfolding of normal endogenous α-syn, much like what occurs in the prion diseases. Recent work highlighting the seeding effect of pathogenic α-syn has largely focused on the detergent-insoluble species of the protein. In this study, we performed intracerebral inoculations of the sarkosyl-insoluble or sarkosyl-soluble fractions of human Lewy body disease brain homogenate and show that both fractions induce CNS pathology in mice at 4 months after injection. Disease-associated deposits accumulated both near and distal to the site of the injection, suggesting a cell-to-cell spread via recruitment of α-syn. These results provide further insight into the prion-like mechanisms of α-syn and suggest that disease-associated α-syn is not homogeneous within a single patient but might exist in both soluble and insoluble isoforms.	f	\N
26622256	Endometriosis is a frequent gynecologic disease with a severe impact on the quality of life in the affected women; its pathogenesis is yet to be fully understood, with an altered immunity as a possible key factor. The present study aimed to investigate the serum anti-inflammatory cytokine profile in the patients with endometriosis compared with the healthy controls. One hundred and sixty women were included, divided into two study groups (Group I - endometriosis; Group 2 - healthy women). We evaluated the serum levels of interleukin-1 receptor antagonist (IL-1Ra), IL-2, IL-2R, IL-4, IL-10, IL-13, and IL-15 with the use of Human multiplex cytokine panels. Statistical analyses (normality distribution analysis, independent t-test, Mann-Whitney U-test) were performed using IBM SPSS software (version 22.0) and GraphPad Prism (version 5.00); receiver operating characteristic curve were used to demonstrate the diagnostic performance of the studied markers. The mean serum level of IL-1Ra, IL-4, and IL-10 were significantly higher in women with endometriosis compared to women free of disease from the control group (30.155, 138.459, and 1.489, respectively, compared to 14.109, 84.710, and 0.688, respectively; P < 0.001, P < 0.001, and P = 0.002, respectively.). No significant differences in the mean serum levels of IL-2, IL-13, and IL-15 were observed between the studied groups and IL-2R had a very low detection rate. Endometriosis is associated with elevated levels of anti-inflammatory cytokines, IL-1Ra, IL-4, and IL-10, markers that have a potential role as a prognostic factor for endometriosis.	f	\N
26628350	Adult tissue-derived mesenchymal stromal cells (MSCs) are showing promise in clinical trials for systemic lupus erythematosus (SLE). However, the inability to manufacture large quantities of functional cells from a single donor as well as donor-dependent variability in quality limits their clinical utility. Human embryonic stem cell (hESC)-derived MSCs are an alternative to adult MSCs that can circumvent issues regarding scalability and consistent quality due to their derivation from a renewable starting material. Here, we show that hESC-MSCs prevent the progression of fatal lupus nephritis (LN) in NZB/W F1 (BWF1) mice. Treatment led to statistically significant reductions in proteinuria and serum creatinine and preserved renal architecture. Specifically, hESC-MSC treatment prevented disease-associated interstitial inflammation, protein cast deposition, and infiltration of CD3(+) lymphocytes in the kidneys. This therapy also led to significant reductions in serum levels of tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), two inflammatory cytokines associated with SLE. Mechanistically, in vitro data support these findings, as co-culture of hESC-MSCs with lipopolysaccharide (LPS)-stimulated BWF1 lymphocytes decreased lymphocyte secretion of TNFα and IL-6, and enhanced the percentage of putative regulatory T cells. This study represents an important step in the development of a commercially scalable and efficacious cell therapy for SLE/LN.	f	\N
26633764	Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third.	f	\N
26646939	Non-alcoholic fatty liver disease (NAFLD) is a consequence of sedentary life style and high fat diets with an estimated prevalence of about 30% in western countries. It is associated with insulin resistance, obesity, glucose intolerance and drug toxicity. Additionally, polymorphisms within, e.g., APOC3, PNPLA3, NCAN, TM6SF2 and PPP1R3B, correlate with NAFLD. Several studies have already investigated later stages of the disease. This study explores the early steatosis stage of NAFLD with the aim of identifying molecular mechanisms underlying the etiology of NAFLD. We analyzed liver biopsies and serum samples from patients with high- and low-grade steatosis (also pre-disease states) employing transcriptomics, ELISA-based serum protein analyses and metabolomics. Here, we provide a detailed description of the various related datasets produced in the course of this study. These datasets may help other researchers find new clues for the etiology of NAFLD and the mechanisms underlying its progression to more severe disease states.	f	\N
26666493	Studies have addressed the immunomodulatory effects of helminths and their protective effects upon asthma. However, anti-Ascaris IgE has been reported to be associated with an increased risk of asthma symptoms. We examined the association between serum levels of anti-Ascaris IgE and bronchial hyper-responsiveness (BHR) in children living in rural Bangladesh. Serum anti-Ascaris IgE level was measured and the BHR test done in 158 children aged 9 years selected randomly from a general population of 1705 in the Matlab Health and Demographic Surveillance Area of the International Centre for Diarrhoeal Disease Research, Bangladesh. We investigated wheezing symptoms using a questionnaire from the International Study of Asthma and Allergies in Childhood. BHR tests were successfully done on 152 children (108 'current wheezers'; 44 'never-wheezers'). We examined the association between anti-Ascaris IgE level and wheezing and BHR using multiple logistic regression analyses. Of 108 current-wheezers, 59 were BHR-positive; of 44 never-wheezers, 32 were BHR-negative. Mean anti-Ascaris IgE levels were significantly higher (12.51 UA/ml; 95% confidence interval (CI), 9.21-17.00) in children with current wheezing with BHR-positive than in those of never-wheezers with BHR-negative (3.89; 2.65-5.70; t test, p < 0.001). A BHR-positive test was independently associated with anti-Ascaris IgE levels with an odds ratio (OR) = 7.30 [95% CI, 2.28-23.33], p = 0.001 when adjusted for total IgE, anti-Dermatophagoides pteronyssinus IgE, pneumonia history, parental asthma, Trichuris infection, forced expiratory volume in one second, eosinophilic leukocyte count, and sex. Anti-Ascaris IgE level is associated with an increased risk of BHR among 9-year-old rural Bangladeshi children.	f	\N
26685524	In the first century B.C.E., a group of Greek physicians called the Methodists denied that medicine could be based on such "hidden causes" as humors, atoms, or elements. They argued that the inner workings of the body were ultimately unknowable, existing beyond the limits of human knowledge and inference. Yet they insisted that medical certainty was still possible, claiming that every disease shared one of three directly apprehensible "manifest commonalities"--stricture, laxity, or some mixture of the two. Medicine could therefore be a science; it was simply noncausal in structure. This essay examines these medical theories in light of Herbert Simon's concept of "bounded rationality," suggesting that the Methodists were proposing a type of medical "heuristic" in response to the limitations of human knowledge and processing power. At the same time, the essay suggests that such an epistemology had its consequences, setting up an ontological crunch whereby the demands formerly placed on diseases and their causes transferred to "affections" and the commonalities, with successive generations of Methodists disagreeing about the status of symptoms, signs, and diseased states. Borrowing vocabulary from the Methodists themselves, the essay calls the consequent ontological slippage between causes and effects "metalepsis".	f	\N
26700806	Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the stem-cell compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a stem-cell compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of stem-cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.	f	\N
26722363	Matrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate cancer (ARCaP) cells, transfected with sense or anti-sense MMP-26 cDNA, are directly correlated with those of the pro-apoptotic marker Bax. Immunohistochemical staining of prostate cancer tissue samples shows similar protein expression patterns, correlating the expression levels of MMP-26 and Bax in benign, neoplastic, and invasive prostate cancer tissues. The MMP-26 protein levels were upregulated in high grade prostate intraepithelial neoplasia (HGPIN) and decreased during the course of disease progression. Further analysis using an indirect terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that many tumor cells expressing MMP-26 were undergoing apoptosis. This study showed that the high level of MMP-26 expression is positively correlated with the presence of apoptotic cells. This pro-apoptotic role of MMP-26 in human prostate cancer cells and tissues may enhance our understanding of the paradoxical roles of MMP-26 in tumor invasion and progression.	f	\N
26749833	Twenty bromotyrosine alkaloids, including a new compound, 13-oxosubereamolline D (5), were isolated from the Thai sponge Acanthodendrilla sp. Their structures were determined by analyses of 1D- and 2D-NMR, high-resolution mass, and circular dichroism data. The complete 1H and 13C NMR assignments of 5,7β-dichlorocavernicolin (19) and 5,7α-dichlorocavernicolin (20) are described herein for the first time. The acetylcholinesterase (AChE) inhibitory activity of all isolated compounds was evaluated. Only homoaerothionin (7) and fistularin 1 (10) exhibited inhibitory activity against human recombinant AChE (hrAChE) with IC50s of 4.5 and 47.5 µM, respectively. The hrAChE inhibition kinetics of 7, the most potent alkaloid, showed increased Km and unchanged Vmaxvalues, suggesting its competitive mode of inhibition. The spirocyclohexadienylisoxazole and the length of the alkyl diamine linkage were proposed as the crucial parts for its strong inhibitory activity. This finding indicates a therapeutic potential for 7 in acetylcholine-related diseases, most importantly Alzheimer's disease.	f	\N
26769066	Genetic ancestry, sex, and individual alleles have been associated with multiple sclerosis (MS) susceptibility. To determine whether established risk factors for disease onset are associated with relapse rate in pediatric MS. Whole-genome genotyping was performed for 181 MS or high-risk clinically isolated syndrome patients from two pediatric MS centers. Relapses and disease-modifying therapies were recorded as part of continued follow-up. Participants were characterized for 25-hydroxyvitamin D serum status. Ancestral estimates (STRUCTURE v2.3.1), human leukocyte antigen (HLA)-DRB1*15 carrier status (direct sequencing), sex, and a genetic risk score (GRS) of 110 non-HLA susceptibility single-nucleotide polymorphisms (SNPs) were evaluated for association with relapse rate with Cox and negative binomial regression models. Over 622 patient-years, 408 relapses were captured. Girls had greater relapse rate than boys (incident rate ratio (IRR) = 1.40, 95% confidence interval (CI) = 1.04-1.87, p = 0.026). Participants were genetically diverse; ~40% (N = 75) had <50% European ancestry. HLA-DRB1*15 status modified the association of vitamin D status (pixn = 0.022) with relapse rate (per 10 ng/mL, in DRB1*15+ hazard ratio (HR) = 0.72, 95% CI = 0.58-0.88, p = 0.002; in DRB1*15- HR = 0.96, 95% CI = 0.83-1.12, p = 0.64). Neither European ancestry nor GRS was associated with relapse rate. We demonstrate that HLA-DRB1*15 modifies the association of vitamin D status with relapse rate. Our findings emphasize the need to pursue disease-modifying effects of MS genes in the context of environmental factors.	f	\N
26789921	Viruses are obligate parasites and thus require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy hosts use to suppress viral replication and a potential pan-antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling and genetic and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication, we have identified targetable host factors for broad-spectrum antiviral therapies.	f	\N
22511225	The proteasome was first identified as a high MW protease complex that gets resolved into a series of low MW protein species upon denaturation. As the dominant protease dedicated to protein turnover, the proteasome shapes the cellular protein repertoire. Our knowledge of proteasome regulation and activity has improved considerably over the past decade. Novel inhibitors, in particular, have helped to advance our understanding of proteasome biology. They range from small peptide-based structures that can be modified to vary target specificity to large macromolecular inhibitors that include proteins. Although these reagents have an important role in establishing our current knowledge of the proteasome's catalytic mechanism, many questions remain. The future lies in designing compounds that can function as drugs to target processes involved in disease progression. Our focus in this chapter is to highlight the use of various classes of inhibitors to probe the mechanism of the proteasome and to identify its physiological significance in the cell, so that the mechanism of inhibition of proteasome will work as a definite source for design of protocols for newer therapeutic agents for the treatment of inflammation and in cancer therapy.	f	\N
20047084	Compared to high school graduates, adolescents who drop out of school are more likely to have a range of negative outcomes, including lower verbal capacities; however, the true nature of this association is not well-understood. Dropping out of school could have an important effect on reducing verbal skills, or the link between dropping out of school and diminished verbal skills could be a spurious association that is the result of unmeasured confounding variables. The current study tested these two competing perspectives by using propensity-score-matching (PSM) to unpack the association between school dropout and verbal skills among 7,317 respondents from the National Longitudinal Study of Adolescent Health (51% female, 49% male; 62% Caucasian, 38% minority). The results of the PSM models indicated a small yet meaningful statistically significant effect of dropout on verbal skills in adulthood even after taking into account a range of confounders. We conclude by discussing the implications of our results.	\N	\N
20236795	To determine the effectiveness of gore-tex medialization thyroplasty for the management of glottic incompetence (GI) in patients with mobile vocal folds. Twenty patients with glottic incompetence (GI) and mobile vocal folds were retrospectively analyzed after gore-tex medialization laryngoplasty. Pre- and postoperative outcome measures including grade, roughness, breathiness, asthenia, strain of the voice (GRBAS), glottal function index (GFI), and voice-related quality of life (VRQOL) were compared to detect surgical effectiveness. Two anesthetic subgroups were identified and compared: general anesthesia, via laryngeal mask airway (LMA) anesthetic, and local anesthesia. Statistically significant differences were identified between pre- and postoperative VRQOL (P<0.0001), GFI (P<0.01), and composite GRBAS (P<0.0001) after a mean follow-up time of 7.8 months. Both the LMA and the local anesthetic subgroups demonstrated similar significance across these measures. GFI and VRQOL scores demonstrate a moderate correlation (ρ=0.71). Perceptual voice quality (GRBAS) correlates slightly better with VRQOL scores (ρ=-0.6; P<0.01) than qualitative measures of glottal function (GFI) (ρ=0.43). Gore-tex thyroplasty provides reliable medium-term improvement in both perceptual and subjective voice parameters in the setting of GI with mobile vocal folds.	\N	\N
20388591	Electroencephalogram (EEG) recordings, and especially the Mu-rhythm over the sensorimotor cortex that relates to the activation of the mirror neuron system (MNS), were acquired from two subject groups (orchestral musicians and nonmusicians), in order to explore action representation processes involved in the perception and performance of musical pieces. Two types of stimuli were used, i.e., an auditory one consisting of an excerpt of Beethoven's fifth symphony and a visual one presenting a conductor directing an orchestra performing the same excerpt of the piece. Three tasks were conducted including auditory stimulation, audiovisual stimulation, and visual stimulation only, and the acquired signals were processed using fractal [time-dependent fractal dimension (FD) estimation] and statistical analysis (analysis of variance, Mann-Whitney). Experimental results showed significant differences between the two groups while desychronization of the Mu-rhythm, which can be linked to MNS activation, was observed during all tasks for the musicians' group, as opposed to the nonmusicians' group who exhibited similar response only when the visual stimulus was present. The mobility of the conductor was also correlated to the estimated FD signals, showing significantly higher correlation for the case of musicians compared to nonmusicians' one. The present study sheds light upon the difference in action representation in auditory perception between musicians and nonmusicians and paves the way for better comprehension of the underlying mechanisms of the MNS.	\N	\N
20447726	The purpose of the study was to compare the speech recognition capacity between listeners with and without acoustic reflex using different types of noises and intensities. We studied 18 women allocated to 2 groups: acoustic reflex present (20 ears) and absent (16 ears). They were presented with 180 disyllable words (90 to each ear), emitted randomly at a fixed intensity of 40 dB above the pure tone average hearing level. At the same time, 3 types of noises were presented ipsilaterally (white, pink, and speech), one at a time, at 3 intensities: 40, 50, and 60 dB above the pure tone average hearing level. The ages and auditory thresholds were statistically equal between the groups. There was a significant difference in mean number of hits between the 2 groups for the 3 types of noises used. There was also a significant difference in mean number of hits for noise type and intensity when white and pink noise was used at 40 and 50 dB and for all the intensities when speech was used. Acoustic reflex helps communication in high-noise environments and is more efficient for speech sounds.	\N	\N
20507830	On its 43rd anniversary the Simon effect can look back at a long and varied history. First treated as a curious observation with implications for human factors research, it slowly evolved not only into a valuable target of psychological theorizing itself but also into a handy means to investigate attentional operations, the representation of space and of one's body, the cognitive representation of intentional action, and executive control. This article discusses the major characteristics of the Simon effect and the Simon task that laid the ground for this success and reviews the major lines of research, theoretical developments, and ongoing controversies on and around the Simon Effect and the cognitive processes it reflects.	\N	\N
20557486	Predominantly, the impact of environmental noise is measured using sound level, ignoring the influence of other factors on subjective experience. The present study tested physiological responses to natural urban soundscapes, using functional magnetic resonance imaging and vector cardiogram. City-based recordings were matched in overall sound level (71 decibel A-weighted scale), but differed on ratings of pleasantness and vibrancy. Listening to soundscapes evoked significant activity in a number of auditory brain regions. Compared with soundscapes that evoked no (neutral) emotional response, those evoking a pleasant or unpleasant emotional response engaged an additional neural circuit including the right amygdala. Ratings of vibrancy had little effect overall, and brain responses were more sensitive to pleasantness than was heart rate. A novel finding is that urban soundscapes with similar loudness can have dramatically different effects on the brain's response to the environment.	\N	\N
20562170	Estrogen may be involved in schizophrenia by inhibiting serotonin-1A (5-HT(1A)) receptor function. We examined the effects of estrogen pre-treatment on modulation of loudness dependence of the auditory evoked potential (LDAEP) and mismatch negativity by the 5-HT(1A) receptor partial agonist, buspirone. Using a double-blind, placebo-controlled, repeated-measures design in healthy female volunteers, we observed that buspirone treatment significantly increased LDAEP slope. Estrogen increased LDAEP slope on its own, and a further LDAEP increase by buspirone was not seen after estrogen pre-treatment. Similar results were observed for mismatch negativity, where buspirone caused a small increase of latency, although not amplitude, after placebo but not estrogen pre-treatment, which enhanced mismatch negativity latency on its own. These results are in line with our previous findings on prepulse inhibition showing an inhibitory effect of estrogen on the action of buspirone. Taken together, these data suggest that estrogen may inhibit 5-HT(1A) receptor-mediated disruptions of auditory processing.	\N	\N
20570253	An increasing number of neuroimaging studies in music cognition research suggest that "language areas" are involved in the processing of musical syntax, but none of these studies clarified whether these areas are a prerequisite for normal syntax processing in music. The present electrophysiological experiment tested whether patients with lesions in Broca's area (N=6) or in the left anterior temporal lobe (N=7) exhibit deficits in the processing of structure in music compared to matched healthy controls (N=13). A chord sequence paradigm was applied, and the amplitude and scalp topography of the Early Right Anterior Negativity (ERAN) was examined, an electrophysiological marker of musical syntax processing that correlates with activity in Broca's area and its right hemisphere homotope. Left inferior frontal gyrus (IFG) (but not anterior superior temporal gyrus - aSTG) patients with lesions older than 4 years showed an ERAN with abnormal scalp distribution, and subtle behavioural deficits in detecting music-syntactic irregularities. In one IFG patient tested 7 months post-stroke, the ERAN was extinguished and the behavioural performance remained at chance level. These combined results suggest that the left IFG, known to be crucial for syntax processing in language, plays also a functional role in the processing of musical syntax. Hence, the present findings are consistent with the notion that Broca's area supports the processing of syntax in a rather domain-general way.	\N	\N
20672879	The purpose of the present study was to investigate the relationship between perception and production of metrical patterns in Swedish children with language impairment (LI), in order to add to the knowledge on underlying explanations of LI. A further aim was to explore whether omissions are mainly related to prosodic aspects or to linguistic function. Children with LI omitted significantly more unstressed syllables than did children with typical language development. Exploration of the relationship between perception and production of phrasal stress patterns demonstrated that children with LI might be divided into three subgroups: Group a: children who perform better on perception than production; Group b: children who perform better on production than perception; and Group c: children with rather poor results on both perception and production.	\N	\N
20689026	To use eye tracking to investigate age differences in real-time lexical processing in quiet and in noise in light of the fact that older adults find it more difficult than younger adults to understand conversations in noisy situations. Twenty-four younger and 24 older adults followed spoken instructions referring to depicted objects, for example, "Look at the candle." Eye movements captured listeners' ability to differentiate the target noun (candle) from a similar-sounding phonological competitor (e.g., candy or sandal). Manipulations included the presence/absence of noise, the type of phonological overlap in target-competitor pairs, and the number of syllables. Having controlled for age-related differences in word recognition accuracy (by tailoring noise levels), similar online processing profiles were found for younger and older adults when targets were discriminated from competitors that shared onset sounds. Age-related differences were found when target words were differentiated from rhyming competitors and were more extensive in noise. Real-time spoken word recognition processes appear similar for younger and older adults in most conditions; however, age-related differences may be found in the discrimination of rhyming words (especially in noise), even when there are no age differences in word recognition accuracy. These results highlight the utility of eye movement methodologies for studying speech processing across the life span.	\N	\N
20689036	In this study, the authors investigated the effects of age on the use of fundamental frequency differences (ΔF(0)) in the perception of competing synthesized vowels in simulations of electroacoustic and cochlear-implant hearing. Twelve younger listeners with normal hearing and 13 older listeners with (near) normal hearing were evaluated in their use of ΔF(0) in the perception of competing synthesized vowels for 3 conditions: unprocessed synthesized vowels (UNP), envelope-vocoded synthesized vowels that simulated a cochlear implant (VOC), and synthesized vowels processed to simulate electroacoustic stimulation (EAS) hearing. Tasks included (a) multiplicity, which required listeners to identify whether a stimulus contained 1 or 2 sounds and (b) double-vowel identification, which required listeners to attach phonemic labels to the competing synthesized vowels. Multiplicity perception was facilitated by ΔF(0) in UNP and EAS but not in VOC, with no age-related deficits evident. Double-vowel identification was facilitated by ΔF(0), with ΔF(0) benefit largest in UNP, reduced in EAS, and absent in VOC. Age adversely affected overall identification and ΔF(0) benefit on the double-vowel task. Some but not all older listeners derived ΔF(0) benefit in EAS hearing. This variability may partly be due to how listeners are able to draw on higher-level processing resources in extracting and integrating cues in EAS hearing.	\N	\N
20695697	In object substitution masking (OSM) a sparse, temporally trailing 4-dot mask impairs target identification, even though it has different contours from, and does not spatially overlap with the target. Here, we demonstrate a previously unknown characteristic of OSM: Observers show reduced masking at prolonged (e.g., 640 ms) relative to intermediate mask durations (e.g., 240 ms). We propose that with prolonged exposure, the mask's visual representation is consolidated, which allows processing of the lingering target icon to be reinitiated, thereby improving performance. Our findings suggest that when the visual system is confronted with 2 temporally contiguous stimuli, although one may initially gain access to consciousness above the other, the "losing" stimulus is not irreversibly lost to awareness.	\N	\N
20810622	Multisensory events in our natural environment unfold at multiple temporal scales over extended periods of time. This functional magnetic resonance imaging study investigated whether the brain uses transient (onset, offset) or sustained temporal codes to effectively integrate incoming visual and auditory signals within the cortical hierarchy. Subjects were presented with 1) velocity-modulated radial motion, 2) amplitude-modulated sound, or 3) an in phase combination of both in blocks of variable durations to dissociate transient and sustained blood oxygen level-dependent responses. Audiovisual interactions emerged primarily for transient onset and offset responses highlighting the importance of rapid stimulus transitions for multisensory integration. Strikingly, audiovisual interactions for onset and offset transients were dissociable at the functional and anatomical level. Low-level sensory areas integrated audiovisual inputs at stimulus onset in a superadditive fashion to enhance stimulus salience. In contrast, higher order association areas showed subadditive integration profiles at stimulus offset possibly reflecting the formation of higher order representations. In conclusion, multisensory integration emerges at multiple levels of the cortical hierarchy using different temporal codes and integration profiles. From a methodological perspective, these results highlight the limitations of conventional event related or block designs that cannot characterize these rich dynamics of audiovisual integration.	\N	\N
20814962	Auditory functional magnetic resonance imaging (fMRI) was used to assess neural activation in the human auditory brainstem (AB) and cortex (AC) as a function of bandwidth (BW). We recorded brain activation of 22 normal hearing listeners induced by band pass filtered pink noise stimuli with equal sound pressure level of 70 dB SPL. Tested bandwidths were 50, 500, 1,500, 3,000, 6,000, and 8,000 Hz. The center frequency was 4,000 Hz. Categorical loudness scaling had been performed in a silent booth with all of these stimuli. Loudness as a function of bandwidth followed a concave-shaped curve which reflected the influence of spectral loudness summation (SLS) for higher BW and the influence of large amplitude fluctuations for very low BW, which itself could be explained by peak-listening. While neural activation of the AB, as measured by the percent signal change from baseline (PSC), was tuned to the physical BW of the stimuli in a straight linear fashion, the trend of perceived loudness as a function of BW was reflected in several aspects by corresponding neural activation in the primary auditory cortex (PAC). Finally, from the absolute differences of the PSC between PAC and AB, gains in perceived loudness associated with SLS and the effect of large amplitude fluctuations could be predicted with an accuracy of 1-2 dB for the whole group of participants.	\N	\N
20829245	Several perisylvian brain regions show preferential activation for spoken language above and beyond other complex sounds. These "speech-selective" effects might be driven by regions' intrinsic biases for processing the acoustical or informational properties of speech. Alternatively, such speech selectivity might emerge through extensive experience in perceiving and producing speech sounds. This functional magnetic resonance imaging (fMRI) study disambiguated such audiomotor expertise from speech selectivity by comparing activation for listening to speech and music in female professional violinists and actors. Audiomotor expertise effects were identified in several right and left superior temporal regions that responded to speech in all participants and music in violinists more than actresses. Regions associated with the acoustic/information content of speech were identified along the entire length of the superior temporal sulci bilaterally where activation was greater for speech than music in all participants. Finally, an effect of performing arts training was identified in bilateral premotor regions commonly activated by finger and mouth movements as well as in right hemisphere "language regions." These results distinguish the seemingly speech-specific neural responses that can be abolished and even reversed by long-term audiomotor experience.	\N	\N
20838845	We examined horizontal directional hearing in patients with acquired severe unilateral conductive hearing loss (UCHL). All patients (n = 12) had been fitted with a bone conduction device (BCD) to restore bilateral hearing. The patients were tested in the unaided (monaural) and aided (binaural) hearing condition. Five listeners without hearing loss were tested as a control group while listening with a monaural plug and earmuff, or with both ears (binaural). We randomly varied stimulus presentation levels to assess whether listeners relied on the acoustic head-shadow effect (HSE) for horizontal (azimuth) localization. Moreover, to prevent sound localization on the basis of monaural spectral shape cues from head and pinna, subjects were exposed to narrow band (1/3 octave) noises. We demonstrate that the BCD significantly improved sound localization in 8/12 of the UCHL patients. Interestingly, under monaural hearing (BCD off), we observed fairly good unaided azimuth localization performance in 4/12 of the patients. Our multiple regression analysis shows that all patients relied on the ambiguous HSE for localization. In contrast, acutely plugged control listeners did not employ the HSE. Our data confirm and further extend results of recent studies on the use of sound localization cues in chronic and acute monaural listening.	\N	\N
20858647	There have been few reports showing a correlation between hearing levels and life style in young people. In this study, we succeeded in sensitively evaluating hearing levels in 51 young male adults of 21-23 years in age by 12 k Hz extra-high-frequency auditory thresholds, which cannot be measured by usual audiometry devices for clinical use. Noise exposure, alcohol consumption and sleeping time did not affect hearing levels in young adults. Auditory thresholds of 12 kHz frequency in smokers were significantly (p < 0.05) higher than those in non-smokers, while there were no differences in 1 kHz, 4 kHz and 8 kHz frequencies of hearing levels between smokers and non-smokers. Since the Brinkman Index (BI; cigarettes/day multiplied by number of years) of smokers in this study was from 12 to 60, our results suggest that even light smoking of less than 20 cigarettes/day for 3 years can result in the development of hearing loss of 12 kHz frequency in young adults. Binary logistic regression analysis again showed a correlation between hearing loss (≥ 40 dB of auditory thresholds in 12 kHz frequency) and light smoking (12 ≤ BI ≤ 60). Thus, this study showed that auditory threshold at 12 kHz frequency could be a sensitive marker for hearing in young adults. More importantly, we for the first time provided epidemiological evidence that light smoking might affect hearing level at 12 kHz frequency and revealed a new risk of light smoking.	\N	\N
20862531	In this paper we use information theory to quantify the information in the output spike trains of modeled cochlear nucleus globular bushy cells (GBCs). GBCs are part of the sound localization pathway. They are known for their precise temporal processing, and they code amplitude modulations with high fidelity. Here we investigated the information transmission for a natural sound, a recorded vowel. We conclude that the maximum information transmission rate for a single neuron was close to 1,050 bits/s, which corresponds to a value of approximately 5.8 bits per spike. For quasi-periodic signals like voiced speech, the transmitted information saturated as word duration increased. In general, approximately 80% of the available information from the spike trains was transmitted within about 20 ms. Transmitted information for speech signals concentrated around formant frequency regions. The efficiency of neural coding was above 60% up to the highest temporal resolution we investigated (20 μs). The increase in transmitted information to that precision indicates that these neurons are able to code information with extremely high fidelity, which is required for sound localization. On the other hand, only 20% of the information was captured when the temporal resolution was reduced to 4 ms. As the temporal resolution of most speech recognition systems is limited to less than 10 ms, this massive information loss might be one of the reasons which are responsible for the lack of noise robustness of these systems.	\N	\N
20869305	The present study examined the differential effects of voice auditory feedback perturbation direction and magnitude on voice fundamental frequency (F(0)) responses and event-related potentials (ERPs) from EEG electrodes on the scalp. The voice F(0) responses and N1 and P2 components of ERPs were examined from 12 right-handed speakers when they sustained a vowel phonation and their mid-utterance voice pitch feedback was shifted ±100, ±200, and ±500 cents with 200 ms duration. Downward voice pitch feedback perturbations led to larger voice F(0) responses than upward perturbations. The amplitudes of N1 and P2 components were larger for downward compared with upward pitch-shifts for 200 and 500 cents stimulus magnitudes. Shorter N1 and P2 latencies were also associated with larger magnitudes of pitch feedback perturbations. Corresponding changes in vocal and neural responses to upward and downward voice pitch feedback perturbations suggest that the N1 and P2 components of ERPs reflect neural concomitants of the vocal responses. The findings of interactive effects between the magnitude and direction of voice feedback pitch perturbation on N1 and P2 ERP components indicate that the neural mechanisms underlying error detection and correction in voice pitch auditory feedback are differentially sensitive to both the magnitude and direction of pitch perturbations.	\N	\N
20878201	Practice can lead to dramatic improvements in the discrimination of auditory stimuli. In this study, we investigated changes of the frequency-following response (FFR), a subcortical component of the auditory evoked potentials, after a period of pitch discrimination training. Twenty-seven adult listeners were trained for 10 h on a pitch discrimination task using one of three different complex tone stimuli. One had a static pitch contour, one had a rising pitch contour, and one had a falling pitch contour. Behavioral measures of pitch discrimination and FFRs for all the stimuli were measured before and after the training phase for these participants, as well as for an untrained control group (n = 12). Trained participants showed significant improvements in pitch discrimination compared to the control group for all three trained stimuli. These improvements were partly specific for stimuli with the same pitch modulation (dynamic vs. static) and with the same pitch trajectory (rising vs. falling) as the trained stimulus. Also, the robustness of FFR neural phase locking to the sound envelope increased significantly more in trained participants compared to the control group for the static and rising contour, but not for the falling contour. Changes in FFR strength were partly specific for stimuli with the same pitch modulation (dynamic vs. static) of the trained stimulus. Changes in FFR strength, however, were not specific for stimuli with the same pitch trajectory (rising vs. falling) as the trained stimulus. These findings indicate that even relatively low-level processes in the mature auditory system are subject to experience-related change.	\N	\N
20883593	This study aimed to evaluate the effect of lengthening the transition duration of selected speech segments upon the perception of those segments in individuals with auditory dys-synchrony. Thirty individuals with auditory dys-synchrony participated in the study, along with 30 age-matched normal hearing listeners. Eight consonant-vowel syllables were used as auditory stimuli. Two experiments were conducted. Experiment one measured the 'just noticeable difference' time: the smallest prolongation of the speech sound transition duration which was noticeable by the subject. In experiment two, speech sounds were modified by lengthening the transition duration by multiples of the just noticeable difference time, and subjects' speech identification scores for the modified speech sounds were assessed. Subjects with auditory dys-synchrony demonstrated poor processing of temporal auditory information. Lengthening of speech sound transition duration improved these subjects' perception of both the placement and voicing features of the speech syllables used. These results suggest that innovative speech processing strategies which enhance temporal cues may benefit individuals with auditory dys-synchrony.	\N	\N
20884355	Developmental differences in phonological and orthographic processing of Chinese spoken words were examined in 9-year-olds, 11-year-olds and adults using functional magnetic resonance imaging (fMRI). Rhyming and spelling judgments were made to two-character words presented sequentially in the auditory modality. Developmental comparisons between adults and both groups of children combined showed that age-related changes in activation in visuo-orthographic regions depended on a task. There were developmental increases in the left inferior temporal gyrus and the right inferior occipital gyrus in the spelling task, suggesting more extensive visuo-orthographic processing in a task that required access to these representations. Conversely, there were developmental decreases in activation in the left fusiform gyrus and left middle occipital gyrus in the rhyming task, suggesting that the development of reading is marked by reduced involvement of orthography in a spoken language task that does not require access to these orthographic representations. Developmental decreases may arise from the existence of extensive homophony (auditory words that have multiple spellings) in Chinese. In addition, we found that 11-year-olds and adults showed similar activation in the left superior temporal gyrus across tasks, with both groups showing greater activation than 9-year-olds. This pattern suggests early development of perceptual representations of phonology. In contrast, 11-year-olds and 9-year-olds showed similar activation in the left inferior frontal gyrus across tasks, with both groups showing weaker activation than adults. This pattern suggests late development of controlled retrieval and selection of lexical representations. Altogether, this study suggests differential effects of character acquisition on development of components of the language network in Chinese as compared to previous reports on alphabetic languages.	\N	\N
20888628	Mechanisms of cortical reorganization underlying the enhancement of speech processing have been poorly investigated. In the present study, we addressed changes in functional and effective connectivity induced in subjects who learned to deliberately increase activation in the right inferior frontal gyrus (rIFG), and improved their ability to identify emotional intonations by using a real-time fMRI Brain-Computer Interface. At the beginning of their training process, we observed a massive connectivity of the rIFG to a widespread network of frontal and temporal areas, which decreased and lateralized to the right hemisphere with practice. Volitional control of activation strengthened connectivity of this brain region to the right prefrontal cortex, whereas training increased its connectivity to bilateral precentral gyri. These findings suggest that changes of connectivity in a functionally specific manner play an important role in the enhancement of speech processing. Also, these findings support previous accounts suggesting that motor circuits play a role in the comprehension of speech.	\N	\N
20933093	The reproducibility of three different aspects of fMRI activations-namely binary activation maps, effect size and spatial distribution of local maxima-was evaluated for an auditory sentence comprehension task with high attention demand on a group of 17 subjects that were scanned on five different occasions. While in the scanner subjects were asked to listen to a series of six short everyday sentences from the CUNY sentence test. Comprehension and attention to the stimuli were monitored after each listen condition epoch by having subjects answer a series of multiple-choice questions. Statistical maps of activation for the listen condition were computed at three different levels: overall results for all imaging sessions, group-level/single-session results for each of the five imaging occasions, and single-subject/single-session results computed for each subject and each scanning occasion independently. The experimental task recruited a distributed bilateral network with processing nodes located in the lateral temporal cortex, inferior frontal cortex, medial BA6, medial occipital cortex and subcortical structures such as the putamen and the thalamus. Reproducibility of these activations at the group level was high (83.95% of the imaged volume was consistently classified as active/inactive across all five imaging sessions), indicating that sites of neuronal activity associated with auditory comprehension can reliably be detected with fMRI in healthy subjects, across repeated measures after group averaging. At the single-subject level reproducibility ranged from moderate to high, although no significant differences were found on behavioral measures across subjects or sessions. This result suggests that contextual differences-i.e., those specific to each imaging session, can modulate our ability to detect fMRI activations associated with speech comprehension in individual subjects.	\N	\N
20951812	Auditory event-related potentials (ERPs) have been used to understand how the brain processes auditory input, and to track developmental change in sensory systems. Localizing ERP generators can provide invaluable insights into how and where auditory information is processed. However, age-appropriate infant brain templates have not been available to aid such developmental mapping. In this study, auditory change detection responses of brain ERPs were examined in 6-month-old infants using discrete and distributed source localization methods mapped onto age-appropriate magnetic resonance images. Infants received a passive oddball paradigm using fast-rate non-linguistic auditory stimuli (tone doublets) with the deviant incorporating a pitch change for the second tone. Data was processed using two different high-pass filters. When a 0.5 Hz filter was used, the response to the pitch change was a large frontocentral positive component. When a 3 Hz filter was applied, two temporally consecutive components associated with change detection were seen: one with negative voltage, and another with positive voltage over frontocentral areas. Both components were localized close to the auditory cortex with an additional source near to the anterior cingulate cortex. The sources for the negative response had a more tangential orientation relative to the supratemporal plane compared to the positive response, which showed a more lateral, oblique orientation. The results described here suggest that at 6 months of age infants generate similar response patterns and use analogous cortical areas to that of adults to detect changes in the auditory environment. Moreover, the source locations and orientations, together with waveform topography and morphology provide evidence in infants for feature-specific change detection followed by involuntary switching of attention.	\N	\N
20961171	The present study addresses the question whether accentuation and prosodic phrasing can have a similar function, namely, to group words in a sentence together. Participants listened to locally ambiguous sentences containing object- and subject-control verbs while ERPs were measured. In Experiment 1, these sentences contained a prosodic break, which can create a certain syntactic grouping of words, or no prosodic break. At the disambiguation, an N400 effect occurred when the disambiguation was in conflict with the syntactic grouping created by the break. We found a similar N400 effect without the break, indicating that the break did not strengthen an already existing preference. This pattern held for both object- and subject-control items. In Experiment 2, the same sentences contained a break and a pitch accent on the noun following the break. We argue that the pitch accent indicates a broad focus covering two words [see Gussenhoven, C. On the limits of focus projection in English. In P. Bosch & R. van der Sandt (Eds.), Focus: Linguistic, cognitive, and computational perspectives. Cambridge: University Press, 1999], thus grouping these words together. For object-control items, this was semantically possible, which led to a "good-enough" interpretation of the sentence. Therefore, both sentences were interpreted equally well and the N400 effect found in Experiment 1 was absent. In contrast, for subject-control items, a corresponding grouping of the words was impossible, both semantically and syntactically, leading to processing difficulty in the form of an N400 effect and a late positivity. In conclusion, accentuation can group words together on the level of information structure, leading to either a semantically "good-enough" interpretation or a processing problem when such a semantic interpretation is not possible.	\N	\N
20966383	Delayed auditory feedback (DAF) of a speaker's voice disturbs normal speech production. Various traditional theories assume that the content of the delayed feedback signal interferes with the actual production of a particular speech unit (phonemic content hypothesis). The displaced rhythm hypothesis as an alternative explanation suggests that speech disturbances arise from a disruptive rhythm that is produced by the delayed speech signal. The present experimental study directly contrasted the role of rhythm and speech content in a DAF task using speech units as stimuli. One hundred fifty-one participants read aloud 4 different sequences of double syllables that varied in phonemic content and rhythm while auditory feedback was either nondelayed or delayed by 200 or 400 ms. In line with previous studies, the authors found a peak of disturbances at a delay of about 200 ms, independent of speech rate. More important, the present results clearly support the displaced rhythm hypothesis. A speech rate dependency of this effect was also found. Rhythm seems to be a significant criterion of speech monitoring, and hence a mismatch between spoken words and auditory feedback realized by DAF induces obvious speech problems on rhythmic level regardless of phonemic discrepancy at the same time.	\N	\N
21054432	Performance improvement during an hour of auditory perceptual training is accompanied by rapid physiological changes. These changes may reflect learning or simply task repetition independent of learning. We assessed the contribution of learning and task repetition to changes in auditory evoked potentials during a difficult speech identification task and an easy tone identification task. We posited that only task repetition effects would occur in the tone task but that task repetition and learning would interact in the speech task. Speech identification improved with practice (increased sensitivity d' with a constant response bias β). This behavioral improvement coincided with a decrease in the amplitude of sensory evoked responses (N1, P2) and a decrease in the amplitude of a slow wave (peak=320 ms after onset) over the left frontal and parietal sites. Results show rapid physiological changes associated with learning, distinct from changes related to task repetition.	\N	\N
21060139	Improved speech recognition in binaurally combined acoustic-electric stimulation (otherwise known as bimodal hearing) could arise when listeners integrate speech cues from the acoustic and electric hearing. The aims of this study were (a) to identify speech cues extracted in electric hearing and residual acoustic hearing in the low-frequency region and (b) to investigate cochlear implant (CI) users' ability to integrate speech cues across frequencies. Normal-hearing (NH) and CI subjects participated in consonant and vowel identification tasks. Each subject was tested in 3 listening conditions: CI alone (vocoder speech for NH), hearing aid (HA) alone (low-pass filtered speech for NH), and both. Integration ability for each subject was evaluated using a model of optimal integration--the PreLabeling integration model (Braida, 1991). Only a few CI listeners demonstrated bimodal benefit for phoneme identification in quiet. Speech cues extracted from the CI and the HA were highly redundant for consonants but were complementary for vowels. CI listeners also exhibited reduced integration ability for both consonant and vowel identification compared with their NH counterparts. These findings suggest that reduced bimodal benefits in CI listeners are due to insufficient complementary speech cues across ears, a decrease in integration ability, or both.	\N	\N
21068039	Noise-vocoded (NV) speech is often regarded as conveying phonetic information primarily through temporal-envelope cues rather than spectral cues. However, listeners may infer the formant frequencies in the vocal-tract output-a key source of phonetic detail-from across-band differences in amplitude when speech is processed through a small number of channels. The potential utility of this spectral information was assessed for NV speech created by filtering sentences into six frequency bands, and using the amplitude envelope of each band (≤30 Hz) to modulate a matched noise-band carrier (N). Bands were paired, corresponding to F1 (≈N1 + N2), F2 (≈N3 + N4) and the higher formants (F3' ≈ N5 + N6), such that the frequency contour of each formant was implied by variations in relative amplitude between bands within the corresponding pair. Three-formant analogues (F0 = 150 Hz) of the NV stimuli were synthesized using frame-by-frame reconstruction of the frequency and amplitude of each formant. These analogues were less intelligible than the NV stimuli or analogues created using contours extracted from spectrograms of the original sentences, but more intelligible than when the frequency contours were replaced with constant (mean) values. Across-band comparisons of amplitude envelopes in NV speech can provide phonetically important information about the frequency contours of the underlying formants.	\N	\N
21086218	Two experiments investigated the role that different face regions play in a variety of social judgements that are commonly made from facial appearance (sex, age, distinctiveness, attractiveness, approachability, trustworthiness, and intelligence). These judgements lie along a continuum from those with a clear physical basis and high consequent accuracy (sex, age) to judgements that can achieve a degree of consensus between observers despite having little known validity (intelligence, trustworthiness). Results from Experiment 1 indicated that the face's internal features (eyes, nose, and mouth) provide information that is more useful for social inferences than the external features (hair, face shape, ears, and chin), especially when judging traits such as approachability and trustworthiness. Experiment 2 investigated how judgement agreement was affected when the upper head, eye, nose, or mouth regions were presented in isolation or when these regions were obscured. A different pattern of results emerged for different characteristics, indicating that different types of facial information are used in the various judgements. Moreover, the informativeness of a particular region/feature depends on whether it is presented alone or in the context of the whole face. These findings provide evidence for the importance of holistic processing in making social attributions from facial appearance.	\N	\N
21092939	The ratio of scalp-recorded brain responses occurring 50 msec after paired clicks (S2-evoked P50/S1-evoked P50) serves as a measure of sensory gating. An abnormally large ratio is commonly found in schizophrenia and is considered as a sign of reduced sensory gating or otherwise dysfunctional organization of the auditory/verbal system as a factor contributing to psychopathology and cognitive dysfunction in schizophrenia. This initial randomized clinical trial compared the efficacy of two 4-week, computer-based cognitive training methods that emphasize either auditory discrimination and verbal memory or a broader range of cognitive functions in schizophrenia. Thirty-nine schizophrenia patients (ICD-F20.0 diagnosis) were assigned to Cognitive Exercises (CE) or Cognitive Package (Cogpack). The M50, the magnetoencephalographic analogue of electroencephalographic P50, and performance on verbal learning and memory tests were used to evaluate training effects. As expected, patients exhibited higher pretreatment gating ratios than 28 age-matched healthy comparison participants. Gating ratios decreased after CE but not after Cogpack. Cognitive test performance improved more after CE than after Cogpack. Appropriately specific psychological training changes the neural performance in schizophrenia, normalizing sensory and cognitive function.	\N	\N
21105829	The problem of multimodal clustering arises whenever the data are gathered with several physically different sensors. Observations from different modalities are not necessarily aligned in the sense there there is no obvious way to associate or compare them in some common space. A solution may consist in considering multiple clustering tasks independently for each modality. The main difficulty with such an approach is to guarantee that the unimodal clusterings are mutually consistent. In this letter, we show that multimodal clustering can be addressed within a novel framework: conjugate mixture models. These models exploit the explicit transformations that are often available between an unobserved parameter space (objects) and each of the observation spaces (sensors). We formulate the problem as a likelihood maximization task and derive the associated conjugate expectation-maximization algorithm. The convergence properties of the proposed algorithm are thoroughly investigated. Several local and global optimization techniques are proposed in order to increase its convergence speed. Two initialization strategies are proposed and compared. A consistent model selection criterion is proposed. The algorithm and its variants are tested and evaluated within the task of 3D localization of several speakers using both auditory and visual data.	\N	\N
21106695	To examine resource allocation and sentence processing, this study examined the effects of auditory distraction on grammaticality judgment (GJ) of sentences varied by semantics (reversibility) and short-term memory requirements. Experiment 1: Typical young adult females (N = 60) completed a whole-sentence GJ task in distraction (Quiet, Noise, or Talk). Participants judged grammaticality of Passive sentences varied by sentence (length), grammaticality, and reversibility. Reaction time (RT) data were analyzed using a mixed analysis of variance. Experiment 2: A similar group completed a self-paced reading GJ task using the similar materials. Experiment 1: Participants responded faster to Bad and to Nonreversible sentences, and in the Talk distraction. The slowest RTs were noted for Good-Reversible-Padded sentences in the Quiet condition. Experiment 2: Distraction did not differentially affect RTs for sentence components. Verb RTs were slower for Reversible sentences. Results suggest that narrative distraction affected GJ, but by speeding responses, not slowing them. Sentence variables of memory and reversibility slowed RTs, but narrative distraction resulted in faster processing times regardless of individual sentence variables. More explicit, deliberate tasks (self-paced reading) resulted in less effect from distraction. Results are discussed in terms of recent theories about auditory distraction.	\N	\N
21112404	Visual dominance refers to the observation that in bimodal environments vision often has an advantage over other senses in human. Therefore, a better memory performance for visual compared to, e.g., auditory material is assumed. However, the reason for this preferential processing and the relation to the memory formation is largely unknown. In this fMRI experiment, we manipulated cross-modal competition and attention, two factors that both modulate bimodal stimulus processing and can affect memory formation. Pictures and sounds of objects were presented simultaneously in two levels of recognisability, thus manipulating the amount of cross-modal competition. Attention was manipulated via task instruction and directed either to the visual or the auditory modality. The factorial design allowed a direct comparison of the effects between both modalities. The resulting memory performance showed that visual dominance was limited to a distinct task setting. Visual was superior to auditory object memory only when allocating attention towards the competing modality. During encoding, cross-modal competition and attention towards the opponent domain reduced fMRI signals in both neural systems, but cross-modal competition was more pronounced in the auditory system and only in auditory cortex this competition was further modulated by attention. Furthermore, neural activity reduction in auditory cortex during encoding was closely related to the behavioural auditory memory impairment. These results indicate that visual dominance emerges from a less pronounced vulnerability of the visual system against competition from the auditory domain.	\N	\N
21133642	Tonsillar hypertrophy is common in young children and affects several aspects of the speech such as distortions of the dento-alveolar consonants. The study objective was to assess /s/-articulation, perceptually and acoustically, in children with tonsillar hypertrophy and compare effects of two types of surgery, total tonsillectomy and tonsillotomy. Sixty-seven children, aged 50-65 months, on the waiting list for surgery, were randomized to tonsillectomy or tonsillotomy. The speech material was collected preoperatively and 6 months postoperatively. Two groups of age-matched children were controls. /S/-articulation was affected acoustically with lower spectral peak locations and perceptually with less distinct /s/-production before surgery, in comparison to controls. After surgery /s/-articulation was normalized perceptually, but acoustic differences remained. No significant differences between surgical methods were found.	\N	\N
21145901	The allocation of visual processing capacity is a key topic in studies and theories of visual attention. The load theory of Lavie (1995) proposes that allocation happens in two steps where processing resources are first allocated to task-relevant stimuli and secondly remaining capacity 'spills over' to task-irrelevant distractors. In contrast, the Theory of Visual Attention (TVA) proposed by Bundesen (1990) assumes that allocation happens in a single step where processing capacity is allocated to all stimuli, both task-relevant and task-irrelevant, in proportion to their relative attentional weight. Here we present data from two partial report experiments where we varied the number and discriminability of the task-irrelevant stimuli (Experiment 1) and perceptual load (Experiment 2). The TVA fitted the data of the two experiments well thus favoring the simple explanation with a single step of capacity allocation. We also show that the effects of varying perceptual load can only be explained by a combined effect of allocation of processing capacity as well as limits in visual working memory. Finally, we link the results to processing capacity understood at the neural level based on the neural theory of visual attention by Bundesen et al. (2005).	\N	\N
21147178	We investigated the effects of non-native language (English) exposure on event-related potentials (ERPs) in first- and second-year (four- and five-year-old) preschool Japanese native speakers while they listened to semantically congruent and incongruent Japanese sentences. The children were divided into a non-native language exposed group (exposed group) and a group without such experiences (control group) on the basis of their exposure to non-native language. We compared the ERPs recorded from the two groups in each of the two preschool years. N400 was observed both in the first- and second-year preschoolers. Differences owing to exposure to non-native language appeared in the second-year preschoolers but not in the first-year preschoolers. In the second-year preschoolers, the N400 onset in the exposed group was shorter than that in the control group, but there was no difference in the N400 offset between the exposed and control groups. Furthermore, the scalp distribution of the N400 in the exposed group was broader than that in the control group. These results indicate that the time course and scalp distribution of semantic processing for native language sentences in young children fluctuated depending on exposure to non-native language.	\N	\N
21148089	Numerous studies have demonstrated effects of spatial attention within single sensory modalities (within-modal spatial attention) and the effect of directing attention to one sense compared with the other senses (intermodal attention) on cortical neuronal activity. Furthermore, recent studies have been revealing that the effects of spatial attention directed to a certain location in a certain sense spread to the other senses at the same location in space (cross-modal spatial attention). The present study used magnetoencephalography to examine the temporal dynamics of the effects of within-modal and cross-modal spatial and intermodal attention on cortical processes responsive to visual stimuli. Visual or tactile stimuli were randomly presented on the left or right side at a random interstimulus interval and subjects directed attention to the left or right when vision or touch was a task-relevant modality. Sensor-space analysis showed that a response around the occipitotemporal region at around 150 ms after visual stimulation was significantly enhanced by within-modal, cross-modal spatial, and intermodal attention. A later response over the right frontal region at around 200 ms was enhanced by within-modal spatial and intermodal attention, but not by cross-modal spatial attention. These effects were estimated to originate from the occipitotemporal and lateral frontal areas, respectively. Thus the results suggest different spatiotemporal dynamics of neural representations of cross-modal attention and intermodal or within-modal attention.	\N	\N
21185855	External noise paradigms have been widely used to probe different levels of visual processing (Pelli & Farell, 1999). A basic assumption of this paradigm is that the processing strategy is noise-invariant, remaining the same in low and high external noise. We tested this assumption by examining crowding in a detection task where traditionally crowding has no effect. In the first experiment, we measured detection thresholds for a vertically oriented sine wave grating (target) surrounded by four sine wave gratings (flankers) that were either vertically or horizontally oriented. At low noise levels, the detection threshold for the target was unaffected by the orientation of the flankers--there was no crowding. Surprisingly, however, there was crowding for detection at high noise levels: the threshold increased for the similarly-oriented flankers. This suggests that high noise triggered a change in processing strategy, increasing the range of space or features over which the visual signal was sampled. In a second experiment, we evaluated the impact of the spatial and temporal window of the noise on this crowding effect. Although crowding was observed for detection when the spatial and/or temporal window of the noise was localized (i.e. identical to the signal window), no crowding was observed when the noise was spatially and temporally extended (i.e. continuously displayed, full screen dynamic noise). Our results show that certain spatiotemporal distributions of external noise can elicit a change in processing strategy, invalidating the noise-invariant assumption that underlies external noise paradigms. In contrast, spatiotemporally extended noise maintains the required noise-indifference, perhaps because it matches the characteristics of the internal noise that determines the contrast threshold in low noise.	\N	\N
21187749	Sentence stress is a vital attribute of speech since it indicates the importance of specific words within an utterance. Basic acoustic correlates of stress are syllable duration, intensity, and fundamental frequency (F0). Objectives of the study were to determine cochlear implant (CI) users' perception of the acoustic correlates and to uncover which cues are used for stress identification. Several experiments addressed the discrimination of changes in syllable duration, intensity, and F0 as well as stress identification based on these cues. Moreover, the discrimination of combined cues and identification of stress in conversational speech was examined. Both natural utterances and artificial manipulations of the acoustic cues were used as stimuli. Discrimination of syllable duration did not differ significantly between CI recipients and a control group of normal-hearing listeners. In contrast, CI users performed significantly worse on tasks of discrimination and stress identification based on F0 as well as on intensity. Results from these measurements were significantly correlated with the ability to identify stress in conversational speech. Discrimination performance for covarying F0 and intensity changes was more strongly correlated to identification performance than was found for discrimination of either F0 or intensity alone. Syllable duration was not related to stress identification in natural utterances. The outcome emphasizes the importance of both F0 and intensity for CI users' identification of sentence-based stress. Both cues were used separately for stress perception, but combining the cues provided extra benefit for most of the subjects.	\N	\N
21187751	The current study was designed to see how hearing-impaired individuals judge level differences between speech sounds with and without hearing amplification. It was hypothesized that hearing aid compression should adversely affect the user's ability to judge level differences. Thirty-eight hearing-impaired participants performed an adaptive tracking procedure to determine their level-discrimination thresholds for different word and sentence tokens, as well as speech-spectrum noise, with and without their hearing aids. Eight normal-hearing participants performed the same task for comparison. Level discrimination for different word and sentence tokens was more difficult than the discrimination of stationary noises. Word level discrimination was significantly more difficult than sentence level discrimination. There were no significant differences, however, between mean performance with and without hearing aids and no correlations between performance and various hearing aid measurements. There is a clear difficulty in judging the level differences between words or sentences relative to differences between broadband noises, but this difficulty was found for both hearing-impaired and normal-hearing individuals and had no relation to hearing aid compression measures. The lack of a clear adverse effect of hearing aid compression on level discrimination is suggested to be due to the low effective compression ratios of currently fit hearing aids.	\N	\N
21190394	The purpose of the present study was to test the hypothesis that cochlear implant (CI) users' music perception is correlated with their lexical tone perception, and the two types of perception share similar mechanisms in electric hearing. A lexical tone perception test and a pitch interval discrimination test were administered to a group of CI users and a group of normal-hearing (NH) listeners. SAMPLE STUDY: Nineteen adult CI users and 10 NH listeners who are native-Mandarin-Chinese speakers participated in the study. Tone-perception performance of the CI group was, on average, 58.3% correct (± 19.78% correct), and performance of the NH group was near perfect. The CI group had a mean threshold of 5.66 semitones (± 5.57 semitones) in pitch discrimination as compared to the threshold of 0.44 semitone from the NH group. There was a strong correlation between the CI users' tone-perception performance and their pitch discrimination threshold (r = -0.75, p < 0.001). Musical and lexical pitch perceptions are strongly correlated with each other and they might share similar mechanisms in electric hearing.	\N	\N
21206391	The round window application of the Vibrant Sound bridge, the so-called round window vibroplasty, is gaining increasing popularity for hearing rehabilitation of patients with mixed hearing loss or conductive hearing loss. In these patients, conventional hearing amplification and/or surgical restoration is either not possible or has failed because of chronic ear disease, extensive otosclerosis, or malformations. The exact mechanisms of direct cochlear stimulation via the round window membrane are not yet completely understood. It is unclear what kind and what degree of contact is required between the floating mass transducer (FMT) and the round window membrane (RWM) to elicit a functional hearing perception with the implant. We investigated the coupling efficiency between the FMT and the RWM and how the efficiency is altered by the FMT position, the degree of FMT-RWM contact, and the use of a soft tissue coupler. Prospective cohort study. Tertiary referral center in Western Australia. Patients undergoing round window vibroplasty for a mixed or conductive hearing loss otherwise not aidable. Patients underwent round window vibroplasty and received audiological and coupling analysis in the follow-up. These data were then correlated with FMT positioning and the extent of FMT-RWM interface as determined by postoperative high-resolution temporal bone computed tomography. Coupling and hearing levels in relation to FMT positioning and degree of FMT-RWM contact. Of 10 patients, 8 were available for vibroplasty behavioral threshold testing. In 2 patients, testing could not be done because of wound breakdown requiring device explantation in 1 case, and in the other case, the bone conduction thresholds dropped 2 months after implantation, thus falling out of the performance range of the device. Postoperative FMT migration occurred in 50% of the patients (3/6) with recurrent chronic ear disease and status after multiple previous ear operations. All patients, including the 3 patients requiring surgical repositioning of the FMT, attained significantly improved speech in quiet and speech in noise when compared with the preoperatively best aided performance. All patients showed significantly improved average Abbreviated Profile of Hearing Benefit scores with the use of the FMT. Direct (partial or complete) contact with the RWM resulted in good coupling efficiency; soft tissue coupling resulted in a reduced coupling efficiency.	\N	\N
21258612	This study had three goals: (1) to document the literacy skills of deaf adolescents who received cochlear implants (CIs) as preschoolers; (2) to examine reading growth from elementary grades to high school; (3) to assess the contribution of early literacy levels and phonological processing skills, among other factors, to literacy levels in high school. A battery of reading, spelling, expository writing, and phonological processing assessments were administered to 112 high school (CI-HS) students, ages 15.5 to 18.5 yrs, who had participated in a reading assessment battery in early elementary grades (CI-E), ages 8.0 to 9.9 yrs. The CI-HS students' performance was compared with either a control group of hearing peers (N = 46) or hearing norms provided by the assessment developer. Many of the CI-HS students (47 to 66%) performed within or above the average range for hearing peers on reading tests. When compared with their CI-E performance, good early readers were also good readers in high school. Importantly, the majority of CI-HS students maintained their reading levels over time compared with hearing peers, indicating that the gap in performance was, at the very least, not widening for most students. Written expression and phonological processing tasks posed a great deal of difficulty for the CI-HS students. They were poorer spellers, poorer expository writers, and displayed poorer phonological knowledge than hearing age-mates. Phonological processing skills were a critical predictor of high school literacy skills (reading, spelling, and expository writing), accounting for 39% of variance remaining after controlling for child, family, and implant characteristics. Many children who receive CIs as preschoolers achieve age-appropriate literacy levels as adolescents. However, significant delays in spelling and written expression are evident compared with hearing peers. For children with CIs, the development of phonological processing skills is not just important for early reading skills, such as decoding, but is critical for later literacy success as well.	\N	\N
21261633	Humans must often focus attention onto relevant sensory signals in the presence of simultaneous irrelevant signals. This type of attention has been explored in vision with the N2pc component, and the present study sought to find an analogous auditory effect. In Experiment 1, two 750-ms sounds were presented simultaneously, one from each of two lateral speakers. On each trial, participants indicated whether one of the two sounds was a pre-defined target. We found that targets elicited an N2ac component: a negativity in the N2 latency range at anterior contralateral electrodes. We also observed a later and more posterior contralateral positivity. Experiment 2 replicated these effects and demonstrated that they arose from competition between attended and unattended tones rather than reflecting lateralized effects of attention for individual tones. The N2ac component may provide a useful tool for studying selective attention within auditory scenes.	\N	\N
21264649	In two experiments, each including a simple reaction time (RT) task, a localization task, and a passive oddball paradigm, the physical similarity between two dichotically presented auditory stimuli was manipulated. In both experiments, a redundant signals effect (RSE), high localization performance, and a reliable mismatch negativity (MMN) was observed for largely differing stimuli, suggesting that these are coded separately in auditory memory. In contrast, no RSE and a localization rate close to chance level (experiment 1) or at chance (experiment 2) were observed for stimuli differing to a lesser degree. Crucially, for such stimuli a small (experiment 1) or no (experiment 2) MMN were observed. These MMN results indicate that such stimuli tend to fuse into a single percept and that this fusion occurs rather early within information processing.	\N	\N
21264730	Fundamental limitations in performing multiple tasks concurrently are well illustrated by the attentional blink (AB) deficit, which refers to the difficulty in reporting a second target (T2) when it is presented shortly after a first target (T1). Surprisingly, recent studies have shown that the AB, which is often thought of as a manifestation of capacity limitations in central processing, can be reduced when the AB task is performed simultaneously with concurrent distracting activities. In the present study, we sought to investigate whether such concurrency benefits would also be observed when the AB task was performed concurrently with a central demanding timing task. The AB was reduced under concurrent-task conditions, as compared with single-AB-task conditions, even though T1 performance was unaffected by the concurrent task. Moreover, shifts in decision criteria were found to be associated with the concurrency benefit effect.	\N	\N
21277208	Crowding by nearby features causes identification failures in the peripheral visual field. However, prominent visual features can sometimes fail to reach awareness, causing scenes to be incorrectly interpreted. Here we examine whether awareness of the flanking features is necessary for crowding to occur. Flankers that were physically present were rendered perceptually absent with adaptation-induced blindness. In a letter identification task, targets were presented unflanked or with up to four flanker letters. On each trial, observers reported both the number of letters they perceived and the identity of a target letter. This paradigm allowed trial-by-trial assessment of awareness and crowding and ensured that both targets and flankers were attended. Target-letter identification performance was correlated with the number of flanking letters that were perceived on a given trial, regardless of the number that were physically present. Our data demonstrate that crowding can be released when flanking elements at attended locations are suppressed from visual awareness.	\N	\N
21299272	We argue that 4 fundamental gestalt phenomena in perception apply to the control of motor action. First, a motor gestalt, like a perceptual gestalt, is holistic in the sense that it is processed as a single unit. This notion is consistent with reaction time results indicating that all gestures for a brief unit of action must be programmed prior to initiation of any part of the movement. Additional reaction time results related to initiation of longer responses are consistent with processing in terms of a sequence of indivisible motor gestalts. Some actions (e.g., many involving coordination of the hands) can be carried out effectively only if represented as a unitary gestalt. Second, a perceptual gestalt is independent of specific sensory receptors, as evidenced by perceptual constancy. In a similar manner a motor gestalt can be represented independently of specific muscular effectors, thereby allowing motor constancy. Third, just as a perceptual pattern (e.g., a Necker cube) is exclusively structured into only 1 of its possible configurations at any moment in time, processing prior to action is limited to 1 motor gestalt. Fourth, grouping in apparent motion leads to stream segregation in visual and auditory perception; this segregation is present in motor action and is dependent on the temporal rate. We discuss congruence of gestalt phenomena across perception and motor action (a) in relation to a unitary perceptual-motor code, (b) with respect to differences in the role of awareness, and (c) in conjunction with separate neural pathways for conscious perception and motor control.	\N	\N
21300112	Children's foreign-language (FL) learning is a matter of much social as well as scientific debate. Previous behavioral research indicates that starting language learning late in life can lead to problems in phonological processing. Inadequate phonological capacity may impede lexical learning and semantic processing (phonological bottleneck hypothesis). Using both behavioral and neuroimaging data, here we examine the effects of age of first exposure (AOFE) and total hours of exposure (HOE) to English, on 350 Japanese primary-school children's semantic processing of spoken English. Children's English proficiency scores and N400 event-related brain potentials (ERPs) were analyzed in multiple regression analyses. The results showed (1) that later, rather than earlier, AOFE led to higher English proficiency and larger N400 amplitudes, when HOE was controlled for; and (2) that longer HOE led to higher English proficiency and larger N400 amplitudes, whether AOFE was controlled for or not. These data highlight the important role of amount of exposure in FL learning, and cast doubt on the view that starting FL learning earlier always produces better results.	\N	\N
21308886	Anxiety Sensitivity (AS), the tendency to fear the thoughts, symptoms, and social consequences associated with the experience of anxiety, is associated with increased risk for developing anxiety disorders. Some evidence suggests that higher scores on the Anxiety Sensitivity Index (ASI), a measure of the AS construct, are associated with activation of the anterior insular cortex during overt emotion perception. Although the ASI provides subscale scores measuring Physical, Mental Incapacitation, and Social Concerns of AS, no study has examined the relationship between these factors and regional brain activation during affect processing. We hypothesized that insular responses to fear-related stimuli would be primarily related to the Physical Concerns subscale of the ASI, particularly for a sample of subjects with specific phobias. Adult healthy controls (HC; n = 22) and individuals with specific phobia, small animal subtype (SAP; n = 17), completed the ASI and underwent functional magnetic resonance imaging while engaged in a backward-masked affect perception task that presents emotional facial stimuli below the threshold of conscious perception. Groups did not differ in ASI, state or trait anxiety scores, or insula activation. Total ASI scores were positively correlated with activation in the right middle/anterior insula for the combined sample and for the HC and SAP groups separately. Multiple regression analysis revealed that the relationship between AS and insular activation was primarily accounted for by Physical Concerns only. Findings support the hypothesized role of the right anterior insula in the visceral/interoceptive aspects of AS, even in response to masked affective stimuli.	\N	\N
21315438	Using the mismatch negativity (MMN) response, we examined how Standard French and Southern French speakers access the meaning of words ending in /e/ or /ε/ vowels which are contrastive in Standard French but not in Southern French. In Standard French speakers, there was a significant difference in the amplitude of the brain response after the deviant-minus-standard subtraction between the frontocentral (FC) and right lateral (RL) recording sites for the final-/ε/ word but not the final-/e/ word. In contrast, the difference in the amplitude of the brain response between the FC and RL recording sites did not significantly vary as a function of the word's final vowel in Southern French speakers. Our findings provide evidence that access to lexical meaning in spoken word recognition depends on the speaker's native regional accent.	\N	\N
21315875	The present study examined the occurrence and content of auditory hallucinatory experiences in 41 non-clinical participants scoring high or low on the Oxford-Liverpool Inventory of Feelings and Experiences (brief version; OLIFE-B) measure of schizotypy. Participants listened to 10 1-min recordings of white noise, some of which contained embedded concrete or abstract words, and were asked to record the words that they had heard. High scorers on the unusual experiences (UE) scale of the OLIFE-B reported hearing more words, not actually present, relative to low scorers on that measure. In addition, high UE scorers showed a bias toward making hallucinatory reports of an abstract type over a concrete type. These results suggest a bias toward more auditory hallucinatory reports in high scorers in schizotypy, and particularly to those of an abstract type.	\N	\N
21319937	A Danish version of the hearing in noise test (HINT) has been developed and evaluated in normal-hearing (NH) and hearing-impaired (HI) listeners. The speech material originated from Nielsen & Dau (2009) where a sentence-based intelligibility equalization method was presented. In the present study, the speech material was evaluated for naturalness and a subset of sentences selected. The new sentence lists were validated, and after three weeks retested. An additional experiment investigated how recollection of sentences affected the listeners' performance. 16 NH and 16 HI listeners participated in the validation and retest. Twelve HI listeners participated in the experiment on recollection. The average speech recognition threshold in noise (SRT(N)) for the NH listeners was -2.52 dB, with an overall standard deviation of 0.87 dB. The within-subject standard deviation was similar for the NH and the HI listeners. In the retest, the SRT(N) decreased by 0.4 dB in both groups. The Danish HINT consists of 10 test lists and three practice lists each containing 20 sentences. The validation results are comparable to those of other versions of HINT. The test seems equally reliable for NH and HI listeners. After three weeks, reliable results can be obtained when sentence lists are reused with the same listeners.	\N	\N
21324531	In recent years, new speech coding strategies have been developed with the aim of improving the transmission of temporal fine structure to cochlear implant recipients. This study reports on the implementation of one such strategy (fine structure processing, FSP) in children. This was a prospective study investigating the upgrade to a new speech processor. The upgrade used a repeated measures design with an alternating order of conditions (A-B-A-B design). Twelve pre- and perilingually deaf children with MED-EL C40+ cochlear implants were enrolled in the study. Patients were upgraded from their Tempo+ speech processor, which used continuous interleaved sampling (CIS) in combination with a frequency spectrum of 200-8500 Hz, to an Opus speech processor, which used FSP with an extended frequency spectrum of 70-8500 Hz. The primary means of testing was an HSM (Hochmair, Schulz and Moser) sentence test at 65 and 80 dB in quiet. In addition, the "Mainzer Kindersprachtest" (Mainz audiometric speech test for children) was applied at 65 and 70 dB. When the new FSP speech processor was used together with the extended low frequency range, HSM sentence tests at 65 and 80 dB resulted in scores indicating statistically significant improvements of 7.1 and 9.9 percentage points, respectively. Scores in the "Mainzer Kindersprachtest" at 65 and 70 dB indicated statistically significant improvements of 9.3 and 6.1 percentage points, respectively. The present study clearly shows that children benefit from the fine structure speech coding strategy in combination with an extended frequency spectrum in the low frequencies, as is offered by the Opus speech processors. This should be taken into consideration when fitting pre- and perilingually deaf children implanted almost a decade previously.	\N	\N
21329941	Children with speech sound disorder (SSD) and reading disability (RD) have poor phonological awareness, a problem believed to arise largely from deficits in processing the sensory information in speech, specifically individual acoustic cues. However, such cues are details of acoustic structure. Recent theories suggest that listeners also need to be able to integrate those details to perceive linguistically relevant form. This study examined abilities of children with SSD, RD, and SSD+RD not only to process acoustic cues but also to recover linguistically relevant form from the speech signal. Ten- to 11-year-olds with SSD (n=17), RD (n=16), SSD+RD (n=17), and Controls (n=16) were tested to examine their sensitivity to (1) voice onset times (VOT); (2) spectral structure in fricative-vowel syllables; and (3) vocoded sentences. Children in all groups performed similarly with VOT stimuli, but children with disorders showed delays on other tasks, although the specifics of their performance varied. Children with poor phonemic awareness not only lack sensitivity to acoustic details, but are also less able to recover linguistically relevant forms. This is contrary to one of the main current theories of the relation between spoken and written language development. Readers will be able to (1) understand the role speech perception plays in phonological awareness, (2) distinguish between segmental and global structure analysis of speech perception, (3) describe differences and similarities in speech perception among children with speech sound disorder and/or reading disability, and (4) recognize the importance of broadening clinical interventions to focus on recognizing structure at all levels of speech analysis.	\N	\N
21330649	English proficiency must be considered when a bilingual individual is to be evaluated clinically with English speech material. This study describes the minimum level of self-reported English proficiency that identifies bilingual individuals who may perform on par with monolingual listeners on an English word recognition test. A total of 125 normal hearing bilingual listeners rated their English proficiency in listening, speaking, and reading on an 11-point scale. Other related linguistic variables were also obtained. A randomly selected Northwestern University Auditory Test No. 6 (NU-6) list (50 English monosyllabic words) was presented to all participants at 45 dB HL in quiet. Over 90% of the listeners self-rated to have at least "good" proficiency in English listening, speaking, or reading. Of these participants, more than 30% did not achieve a monolingual normative level in English as delimited by binomial distribution. Composite proficiency ratings across language domains better predicted word recognition performance than self-ratings for listening proficiency only. Combining language dominance and age of English acquisition with proficiency ratings further improved prediction specificity. Self-rated English proficiency can predict bilingual listeners' performance on the NU-6 test. For desirable sensitivity and specificity in predicting monolingual-like performance, a minimum rating of 8 out of 10 across all language domains is recommended.	\N	\N
21331781	Data are limited on the role of psychotherapy in the treatment of Ménière disease. We sought to document the effect of a psychotherapeutic technique known as autogenic training on clinical outcome in Ménière disease. Six patients with Ménière disease were studied. Retrospective chart review was conducted. All patients were refractory to conventional therapy and completed a course of autogenic training, which was offered as a complementary treatment. Autogenic training with initial psychological counseling was conducted by a clinical psychologist during 45-min sessions. Outcome measures assessed were the frequency of vertigo and functional levels 2 years after initiation of autogenic training. Functional levels were evaluated according to the 1995 guidelines of the American Academy of Otolaryngology-Head Neck Surgery (AAO-HNS). As a personality measure, we used the Maudsley Personality Inventory (MPI), devised by Eysenck, which measures neuroticism (N), extraversion (E), and propensity to lie (L). Five of six patients showed improved functional level after three to eight sessions of psychotherapy; hearing level did not change. The score of the N scale of the MPI was closely related to the number of psychotherapy sessions. Prognosis was evaluated based on the AAO-HNS reporting guidelines, as follows: A = 3, B = 1, C = 1, F = 1. The value of N in MPI was closely related to the number of psychological counseling sessions (R = 0.97, P < 0.05). In conclusion, autogenic training may enhance the mental well-being of patients with Ménière disease and improve clinical outcome.	\N	\N
21332488	Although a deficit perceiving phonemes, as indexed by the mismatch negativity (MMN), is apparent in developmental dyslexia (DD), studies have not yet addressed whether this deficit might be a result of deficient native language speech representations. The present study examines how a native-vowel prototype and an atypical vowel are discriminated by 9-year-old children with (n = 14) and without (n = 12) DD. MMN was elicited in all conditions in both groups. The control group revealed enhanced MMN to the native-vowel prototype in comparison to the atypical vowel. Children with DD did not show enhanced MMN amplitude to the native-vowel prototype, suggesting impaired tuning to native language speech representations. Furthermore, higher MMN amplitudes to the native-vowel prototype correlated with more advanced reading (r = - .47) and spelling skills (r = - .52).	\N	\N
21336137	Werner and Bargones (1991) observed that a 4-10-kHz noise band can mask a 1-kHz signal during infancy. The purpose of this study was to examine whether remote-noise masking extends into the school-aged years. Listeners were 4-6-yr-olds, 7-9-yr-olds, and adults. Detection thresholds were measured for the 1-kHz signal in quiet and in the presence of the remote-frequency noise. In separate conditions, masker level was either 40 or 60 dB SPL. On average, thresholds for the 1-kHz signal were elevated in the presence of the remote-frequency noise for 4-6-yr-olds, but not for 7-9-yr-olds or adults. Group average thresholds were similar across masker levels, indicating nonperipheral effects. Susceptibility to remote-frequency masking in children extends to 4-6 yrs of age for some children.	\N	\N
21340665	The songbird model is widely established in a number of laboratories for the investigation of the neurobiology and development of vocal learning. While vocal learning is rare in the animal kingdom, it is a trait that songbirds share with humans. The neuroanatomical and physiological organization of the brain circuitry that controls learned vocalizations has been extensively characterized, particularly in zebra finches (Taeniopygia guttata). Recently, several powerful molecular and genomic tools have become available in this organism, making it an attractive choice for neurobiologists interested in the neural and genetic basis of a complex learned behavior. Here, we briefly review some of the main features of vocal learning and associated brain structures in zebra finches and comment on some examples that illustrate how themes related to nutrition and addiction can be explored using this model organism.	\N	\N
21346208	Research on the control of visually guided limb movements indicates that the brain learns and continuously updates an internal model that maps the relationship between motor commands and sensory feedback. A growing body of work suggests that an internal model that relates motor commands to sensory feedback also supports vocal control. There is evidence from arm-reaching studies that shows that when provided with a contextual cue, the motor system can acquire multiple internal models, which allows an animal to adapt to different perturbations in diverse contexts. In this study we show that trained singers can rapidly acquire multiple internal models regarding voice fundamental frequency (F(0)). These models accommodate different perturbations to ongoing auditory feedback. Participants heard three musical notes and reproduced each one in succession. The musical targets could serve as a contextual cue to indicate which direction (up or down) feedback would be altered on each trial; however, participants were not explicitly instructed to use this strategy. When participants were gradually exposed to altered feedback adaptation was observed immediately following vocal onset. Aftereffects were target specific and did not influence vocal productions on subsequent trials. When target notes were no longer a contextual cue, adaptation occurred during altered feedback trials and evidence for trial-by-trial adaptation was found. These findings indicate that the brain is exceptionally sensitive to the deviations between auditory feedback and the predicted consequence of a motor command during vocalization. Moreover, these results indicate that, with contextual cues, the vocal control system may maintain multiple internal models that are capable of independent modification during different tasks or environments.	\N	\N
21354285	This study investigates behavioural and objective measures of temporal auditory processing and their relation to the ability to understand speech in noise. The experiments were carried out on a homogeneous group of seven hearing-impaired listeners with normal sensitivity at low frequencies (up to 1 kHz) and steeply sloping hearing losses above 1 kHz. For comparison, data were also collected for five normal-hearing listeners. Temporal processing was addressed at low frequencies by means of psychoacoustical frequency discrimination, binaural masked detection and amplitude modulation (AM) detection. In addition, auditory brainstem responses (ABRs) to clicks and broadband rising chirps were recorded. Furthermore, speech reception thresholds (SRTs) were determined for Danish sentences in speech-shaped noise. The main findings were: (1) SRTs were neither correlated with hearing sensitivity as reflected in the audiogram nor with the AM detection thresholds which represent an envelope-based measure of temporal resolution; (2) SRTs were correlated with frequency discrimination and binaural masked detection which are associated with temporal fine-structure coding; (3) The wave-V thresholds for the chirp-evoked ABRs indicated a relation to SRTs and the ability to process temporal fine structure. Overall, the results demonstrate the importance of low-frequency temporal processing for speech reception which can be affected even if pure-tone sensitivity is close to normal.	\N	\N
21355809	This study examined listeners' endorsement of cognitive, linguistic, segmental, and suprasegmental strategies employed when listening to speakers with dysarthria. The study also examined whether strategy endorsement differed between listeners who earned the highest and lowest intelligibility scores. Speakers were eight individuals with dysarthria and cerebral palsy. Listeners were 80 individuals who transcribed speech stimuli and rated their use of each of 24 listening strategies on a 4-point scale. Results showed that cognitive and linguistic strategies were most highly endorsed. Use of listening strategies did not differ between listeners with the highest and lowest intelligibility scores. Results suggest that there may be a core of strategies common to listeners of speakers with dysarthria that may be supplemented by additional strategies, based on characteristics of the speaker and speech signal.	\N	\N
21368051	Certain features of objects or events can be represented by more than a single sensory system, such as roughness of a surface (sight, sound, and touch), the location of a speaker (audition and sight), and the rhythm or duration of an event (by all three major sensory systems). Thus, these properties can be said to be sensory-independent or amodal. A key question is whether common multisensory cortical regions process these amodal features, or does each sensory system contain its own specialized region(s) for processing common features? We tackled this issue by investigating simple duration-detection mechanisms across audition and touch; these systems were chosen because fine duration discriminations are possible in both. The mismatch negativity (MMN) component of the human event-related potential provides a sensitive metric of duration processing and has been elicited independently during both auditory and somatosensory investigations. Employing high-density electroencephalographic recordings in conjunction with intracranial subdural recordings, we asked whether fine duration discriminations, represented by the MMN, were generated in the same cortical regions regardless of the sensory modality being probed. Scalp recordings pointed to statistically distinct MMN topographies across senses, implying differential underlying cortical generator configurations. Intracranial recordings confirmed these noninvasive findings, showing generators of the auditory MMN along the superior temporal gyrus with no evidence of a somatosensory MMN in this region, whereas a robust somatosensory MMN was recorded from postcentral gyrus in the absence of an auditory MMN. The current data clearly argue against a common circuitry account for amodal duration processing.	\N	\N
21375597	The neural processing of auditory motion information shows a pronounced interhemispheric asymmetry. In previous electrophysiological studies, the so-called motion-onset response (MOR), a prominent auditory-evoked potential to the onset of sound motion, was stronger over the hemisphere contralateral to the side of motion. Here, effects of lateral-onset position and direction of motion on MOR contralaterality were investigated. Eighteen listeners were presented with free-field sound stimuli that, after an initial stationary phase at a lateral spatial position within the left or right hemifield, started to move either left- or rightward. The early part of the MOR, the so-called change-N1, exhibited contralaterality that depended on the lateral motion-onset position with stronger activations over the hemisphere contralateral to the side of motion onset, whereas the contralaterality of the later part of the MOR, the so-called change-P2, merely depended on the direction of motion. Cortical source localization indicated that this pattern of contralaterality primarily resulted from asymmetric activation in primary auditory cortex and insula. These findings suggest that the early and late parts of the MOR reflect different phases in auditory motion perception, supporting the notion of a modular organization of discrete processing stages.	\N	\N
21382389	Evidence from event-related potential (ERP) analyses of English spoken words suggests that the time course of English word recognition in monosyllables is cumulative. Different types of phonological competitors (i.e., rhymes and cohorts) modulate the temporal grain of ERP components differentially (Desroches, Newman, & Joanisse, 2009). The time course of Chinese monosyllabic spoken word recognition could be different from that of English due to the differences in syllable structure between the two languages (e.g., lexical tones). The present study investigated the time course of Chinese monosyllabic spoken word recognition using ERPs to record brain responses online while subjects listened to spoken words. During the experiment, participants were asked to compare a target picture with a subsequent picture by judging whether or not these two pictures belonged to the same semantic category. The spoken word was presented between the two pictures, and participants were not required to respond during its presentation. We manipulated phonological competition by presenting spoken words that either matched or mismatched the target picture in one of the following four ways: onset mismatch, rime mismatch, tone mismatch, or syllable mismatch. In contrast to the English findings, our findings showed that the three partial mismatches (onset, rime, and tone mismatches) equally modulated the amplitudes and time courses of the N400 (a negative component that peaks about 400ms after the spoken word), whereas, the syllable mismatched words elicited an earlier and stronger N400 than the three partial mismatched words. The results shed light on the important role of syllable-level awareness in Chinese spoken word recognition and also imply that the recognition of Chinese monosyllabic words might rely more on global similarity of the whole syllable structure or syllable-based holistic processing rather than phonemic segment-based processing. We interpret the differences in spoken word processing between Chinese and English listeners as being due to morphosyllabic structural differences between the two languages.	\N	\N
21382438	Emotions signal the particular relevance of situations, threatening or rewarding, and influence perception and behaviour accordingly. Research to date has predominantly investigated the impact of negative emotional stimuli. However, rapid reactions to positive emotional stimuli are similarly adaptive. Here, we tested the influence of positive emotional stimuli on attentional control, which enables reacting to conflicting stimulation. We therefore presented positive emotional and neutral words in an auditory Simon task. Reaction times revealed faster resolution of conflict when target stimuli were positive compared to neutral words. Also, emotion modulated the first conflict-sensitive event-related brain potential, a negativity at 420 ms, indicating an influence on early stages of conflict processing. These results complement recent data on negative stimuli and suggest that positive stimuli are equally salient. The rapid impact on attentional control is evolutionary highly adaptive as it reduces the time that conflict yields an organism incapable of responding to reward-signalling stimuli.	\N	\N
21385014	The objective of this study was to describe the auditory evoked response to silent gaps for a group of older adults using stimulus conditions identical to those used in psychophysical studies of gap detection. The P1-N1-P2 response to the onsets of stimuli (markers) defining a silent gap for within-channel (spectrally identical markers) and across-channel (spectrally different markers) conditions was examined using four perceptually-equated gap durations. A group of 24 older adults (mean age = 63 years) with normal hearing or minimal hearing loss participated. Older adults exhibited neural activation patterns that were qualitatively different and more frontally oriented than those observed in a previous study (Lister et al., 2007) of younger listeners. Older adults showed longer P2 latencies and larger P1 amplitudes than younger adults, suggesting relatively slower neural travel time and altered auditory inhibition/arousal by irrelevant stimuli. Older adults appeared to recruit later-occurring T-complex-like generators for gap processing, compared to earlier-occurring T-complex-like generators by the younger group. Early and continued processing of channel cues with later processing of gap cues may represent the inefficiency of the aging auditory system and may contribute to poor speech understanding in noisy, real-world listening environments.	\N	\N
21387016	Important sounds can be easily missed or misidentified in the presence of extraneous noise. We describe an auditory illusion in which a continuous ongoing tone becomes inaudible during a brief, non-masking noise burst more than one octave away, which is unexpected given the frequency resolution of human hearing. Participants strongly susceptible to this illusory discontinuity did not perceive illusory auditory continuity (in which a sound subjectively continues during a burst of masking noise) when the noises were short, yet did so at longer noise durations. Participants who were not prone to illusory discontinuity showed robust early electroencephalographic responses at 40-66 ms after noise burst onset, whereas those prone to the illusion lacked these early responses. These data suggest that short-latency neural responses to auditory scene components reflect subsequent individual differences in the parsing of auditory scenes.	\N	\N
21391255	Semantic knowledge is supported by a widely distributed neuronal network, with differential patterns of activation depending upon experimental stimulus or task demands. Despite a wide body of knowledge on semantic object processing from the visual modality, the response of this semantic network to environmental sounds remains relatively unknown. Here, we used fMRI to investigate how access to different conceptual attributes from environmental sound input modulates this semantic network. Using a range of living and manmade sounds, we scanned participants whilst they carried out an object attribute verification task. Specifically, we tested visual perceptual, encyclopedic, and categorical attributes about living and manmade objects relative to a high-level auditory perceptual baseline to investigate the differential patterns of response to these contrasting types of object-related attributes, whilst keeping stimulus input constant across conditions. Within the bilateral distributed network engaged for processing environmental sounds across all conditions, we report here a highly significant dissociation within the left hemisphere between the processing of visual perceptual and encyclopedic attributes of objects.	\N	\N
21401449	There is no significant difference in speech recognition scores obtained with the Vibrant Soundbridge and the open-fit hearing aid. However, the Vibrant Soundbridge may be superior to open-fit hearing aids in improving hearing at high frequencies (4-8 kHz). To assess whether an improvement in speech recognition conferred by Vibrant Soundbridge is more marked than that afforded by open-fit hearing aids in patients with sloping high frequency sensorineural hearing loss (SNHL). This study had a self-control prospective design. Seven patients aged 21-62 years with sloping high frequency SNHL were recruited into the study. Each patient received a Vibrant Soundbridge middle ear implant (Vibrant MED-EL) and wore an open-fit hearing aid (Danavox, DOT 10). Speech recognition tests were performed according to protocols suggested by árpád Götze's speech definition test in Hungarian language. In the first session, conventional hearing thresholds (unaided pure tone thresholds) were measured. In the second session, the aided sound-field threshold, speech understanding score and functional gain obtained using middle ear implants and open-fit hearing aids were determined after programming of the devices. Regarding speech recognition scores, there were no significant differences between data obtained with the middle ear implant and those with the open-fit hearing aid.	\N	\N
21417673	The effects of asymmetric directional microphone fittings (i.e., an omnidirectional microphone on one ear and a directional microphone on the other) on speech understanding in noise and acceptance of background noise were investigated in 15 full-time hearing aid users. Subjects were fitted binaurally with four directional microphone conditions (i.e., binaural omnidirectional, right asymmetric directional, left asymmetric directional and binaural directional microphones) using Siemens Intuis Directional behind-the-ear hearing aids. Speech understanding in noise was assessed using the Hearing in Noise Test, and acceptance of background noise was assessed using the Acceptable Noise Level procedure. Speech was presented from 0° while noise was presented from 180° azimuth. The results revealed that speech understanding in noise improved when using asymmetric directional microphones compared to binaural omnidirectional microphone fittings and was not significantly hindered compared to binaural directional microphone fittings. The results also revealed that listeners accepted more background noise when fitted with asymmetric directional microphones as compared to binaural omnidirectional microphones. Lastly, the results revealed that the acceptance of noise was further increased for the binaural directional microphones when compared to the asymmetric directional microphones, maximizing listeners' willingness to accept background noise in the presence of noise. Clinical implications will be discussed.	\N	\N
21425399	Multisensory integration assists us to identify objects by providing multiple cues with respect to object category and spatial location. We used a semantic audiovisual object matching task to determine the effect of spatial congruency on response behavior and fMRI brain activation. Fifteen subjects responded in a four-alternative response paradigm, which visual quadrant contained the object best matched to the sound presented. Realistic sounds based on head-related transfer functions were presented binaurally with the simulated sound source corresponding to one of the four quadrants. Following a random sequence, the location of the sound corresponded to the quadrant containing the semantically congruent target on half the trials, whereas on other trials the sound arose from an incongruent location. We examined the effects of spatial congruency on response latencies, hit-rates and fMRI responses. Preliminary behavioral results revealed a significant effect of spatial congruency on response latency or performance for stimuli with noise added. In the fMRI experiment, spatial congruency had a significant effect on the BOLD response. A cluster in the right middle and superior temporal gyrus was more activated when the auditory sound sources were spatially congruent with the semantically matching visual stimulus. In an exploratory post-hoc analysis, in which we correlated the BOLD signal with the subjects' ability to locate the sound sources, we found a significant cluster in the left inferior frontal cortex, where the BOLD response increased with sound-source localization performance. Thus spatial congruency appears to enhance the semantic integration of audiovisual object information in these brain regions.	\N	\N
21425900	Absolute pitch is a rare pitch-naming ability with unknown etiology. Some scientists maintain that its manifestation depends solely on environmental factors, while others suggest that genetic factors contribute to it. We sought to further investigate the hypothesis that genetic factors support the acquisition of absolute pitch and to better elucidate the inheritance pattern of this trait. To this end, we conducted a twin study and a segregation analysis using data collected from a large population of absolute pitch possessors. The casewise concordance rate of 14 monozygotic twin pairs, 78.6%, was significantly different from that of 31 dizygotic twin pairs, 45.2%, assuming single ascertainment (x(2) = 5.57, 1 df, p = .018), supporting a role for genetics in the development of absolute pitch. Segregation analysis of 1463 families, assuming single ascertainment, produced a segregation ratio p(D) = .089 with SEp(D) = 0.006. Unlike an earlier segregation analysis on a small number of absolute pitch probands from musically educated families, our study indicates that absolute pitch is not inherited in a simple Mendelian fashion. Based on these data, absolute pitch is likely genetically heterogeneous, with environmental, epigenetic, and stochastic factors also perhaps contributing to its genesis. These findings are in agreement with the results of our recent linkage analysis.	\N	\N
21425948	Acute migraine could be associated with neurophysiological and cognitive changes. This study evaluates the neurophysiological changes in auditory information processing in adolescents with acute migraine by means of magnetoencephalography. The multifeature sound mismatch negativity (MMN) paradigm was used to study nine adolescents with an acute migraine and nine age- and gender-matched healthy controls. Latencies and amplitudes of M100, M150, M200, and MMNm responses were evaluated. Migraine subjects had smaller M150 amplitudes than healthy subjects. The latencies of MMNm response for the frequency change were delayed in both hemispheres in migraine subjects, as compared with healthy controls. Our results indicate that the function of neural substrates, responsible for different stages of auditory information processing, is impaired during the acute migraine. The identification of underlying cortical dysfunction during an acute migraine can lead to future identification of neurophysiological biomarkers for studying acute migraine and response to treatment.	\N	\N
21426312	To examine the social cognitive vulnerabilities mediating delusion formation in children presenting with hallucinatory experiences. A sample of 259 12- and 13-year-old children, from a baseline case-control sample of children with and without auditory hallucinations (AH), were re-assessed after 5 years for presence of AH. Presence of delusions and theory of mind (ToM) were also assessed, to examine the hypothesized moderating role of ToM in delusion formation in children hearing voices. In children with AH at age 7-8 and/or 12-13 years, the risk of delusion formation was significantly higher (P interaction = 0.027) in those with lower ToM skills (OR = 4.3, 95% CI 1.9-9.9, P = 0.000), compared to those with higher ToM skills (OR 1.6, 95% CI 0.7-3.7, P = 0.26), independently from secondary school level. The results suggest that better mentalizing abilities confer protection against delusion formation in children experiencing perceptual anomalies, not reducible to general cognitive ability.	\N	\N
21429648	Dichotic listening (DL) techniques have been used extensively as a non-invasive procedure to assess language lateralization among children with and without learning disabilities (LD), and with individuals who have other auditory system related brain disorders. Results of studies using DL have indicated that language is lateralized in children with LD and that the lateralized language asymmetries do not develop after age 6 nor are they affected by gender. Observed differences in lateralized language processes between control children and those with LD were found not due to delayed cerebral dominance, but rather to deficits in selective attention. In addition, attention factors have a greater influence on auditory processing of verbal than nonverbal stimuli for children with LD, and children with LD exhibit a general processing bias to the same hemisphere unlike control children. Furthermore, employing directed attention conditions in DL experiments has played an important role in explaining learning disabled children's performance on DL tasks. We conclude that auditory perceptual asymmetries as assessed by DL with children who experience LD are the result of the interaction of hemispheric capability and attention factors.	\N	\N
21439268	Studies using event related potentials have shown that men are more likely than women to rely on semantic cues when understanding emotional speech. In a previous functional Magnetic Resonance Imaging (fMRI) study, using an affective sentence classification task, we were able to separate areas involved in semantic processing and areas involved in the processing of affective prosody (Beaucousin et al., 2007). Here we searched for sex-related differences in the neural networks active during emotional speech processing in groups of men and women. The ortholinguistic abilities of the participants did not differ when evaluated with a large battery of tests. Although the neural networks engaged by men and women during emotional sentence classification were largely overlapping, sex-dependent modulations were detected during emotional sentence classification, but not during grammatical sentence classification. Greater activity was observed in men, compared with women, in inferior frontal cortical areas involved in emotional labeling and in attentional areas. In conclusion, at equivalent linguistic abilities and performances, men activate semantic and attentional cortical areas to a larger extent than women during emotional speech processing.	\N	\N
21439350	Bone-conducted ultrasound (BCU) modulated by speech sound is recognized as speech sound and activates the auditory cortex similar to audible sound. To investigate the mechanisms of perception, the effects of stimulus duration on N1m were compared among air-conducted audible speech sound (AC speech), AC speech with carrier BCU and speech-modulated BCU in eight native Japanese with normal hearing. The Japanese vowel sound /a/ was used as a stimulus with durations of 10, 15, 20, 30, 40 and 60 ms. Comparison between AC speech with and without carrier showed that the presentation of carrier had no effect on N1m evoked by AC speech. Comparison among the three conditions showed that N1m amplitude for speech-modulated BCU differed from that for the two AC speeches. Moreover, N1m amplitude growth saturated at 40 ms for speech-modulated BCU, and at 20 ms for two AC speeches. These results suggest a difference in temporal integration of N1m between speech-modulated BCU and AC speech. Considering these results, it is reasonable to conclude that N1m evoked by speech-modulated BCU is influenced mainly by the ultrasonic component rather than demodulated audible sound. Given this finding, the notion needs to be considered that the mechanisms underlying perception and recognition of speech-modulated BCU depend on the ultrasonic component to some extent.	\N	\N
21441013	Many reports have described that individuals with Alzheimer's disease show neural breakdown in the brainstem nuclei, hippocampus and auditory cortex in the temporal lobe of the brain. However, it is still unclear whether auditory skills mediated by these areas differ across individuals with and without Alzheimer's disease and how these auditory skills are further confounded by reduction in cognitive function in individuals with AD. The aim of this study is to discover the hidden and nonlinear associations among higher-order auditory and cognitive processes in individuals with and without Alzheimer's disease through artificial neural network analysis. The analyses were based on auditory test data obtained from nine clinically confirmed Alzheimer's disease cases and nine age-matched controls. Hearing threshold sensitivity was equivalent across groups, indicating similar peripheral auditory function. Auditory function was evaluated by standardized tests of auditory closure, auditory attention, and auditory figure ground in listeners with and without Alzheimer's disease. The inputs used for analyses were cognitive status and auditory function. The dependent variables were RAU scores computed from scores of auditory tests. Artificial neural networks showed a complex relationship between the input variables (cognitive status and auditory function) that cannot be predicted simply on the basis of cognition differences between individuals with and without Alzheimer's disease. The results of this study suggest that central auditory function declines with age, regardless of changes in cognitive function.	\N	\N
21452943	In this work, we show that electrophysiological responses during pitch perception are best explained by distributed activity in a hierarchy of cortical sources and, crucially, that the effective connectivity between these sources is modulated with pitch strength. Local field potentials were recorded in two subjects from primary auditory cortex and adjacent auditory cortical areas along the axis of Heschl's gyrus (HG) while they listened to stimuli of varying pitch strength. Dynamic causal modeling was used to compare system architectures that might explain the recorded activity. The data show that representation of pitch requires an interaction between nonprimary and primary auditory cortex along HG that is consistent with the principle of predictive coding.	\N	\N
21455973	The loudness dependence of auditory evoked potentials (LDAEP) has been described as a measure of central serotonergic activity. Single-electrode estimation and dipole source analysis (DSA) are the most utilized methods for the estimation of LDAEP. To date, it is assumed that both methods are equally reliable. Nevertheless, according to our knowledge, the advantage of either method has not yet been shown directly. The aim of our study was to compare single-electrode estimation and dipole source analysis in the determination of the LDAEP. Tones of five different intensities were presented binaurally to 10 healthy volunteers. Amplitudes of N1/P2 and LDAEP were determined at the central electrode site referenced to average and to linked mastoids and with DSA in the left and the right hemispheres. Scores were normalized (z-scores), compared, and correlated. Contrary to our expectations, we found a significant difference between scores obtained with single-electrode estimation and with DSA. The difference may be caused by confounding activation of a frontal source in the single-electrode method. The single-electrode approach cannot be equated with DSA in the determination of the LDAEP. This should be considered when comparing the results of different LDAEP studies using only one of these methods.	\N	\N
21458862	The purposes of the present study were to establish the Standard-Chinese version of Lexical Neighborhood Test (LNT) and to examine the lexical and age effects on spoken-word recognition in normal-hearing children. Six lists of monosyllabic and six lists of disyllabic words (20 words/list) were selected from the database of daily speech materials for normal-hearing (NH) children of ages 3-5 years. The lists were further divided into "easy" and "hard" halves according to the word frequency and neighborhood density in the database based on the theory of Neighborhood Activation Model (NAM). Ninety-six NH children (age ranged between 4.0 and 7.0 years) were divided into three different age groups of 1-year intervals. Speech-perception tests were conducted using the Standard-Chinese monosyllabic and disyllabic LNT. The inter-list performance was found to be equivalent and inter-rater reliability was high with 92.5-95% consistency. Results of word-recognition scores showed that the lexical effects were all significant. Children scored higher with disyllabic words than with monosyllabic words. "Easy" words scored higher than "hard" words. The word-recognition performance also increased with age in each lexical category. A multiple linear regression analysis showed that neighborhood density, age, and word frequency appeared to have increasingly more contributions to Chinese word recognition. The results of the present study indicated that performances of Chinese word recognition were influenced by word frequency, age, and neighborhood density, with word frequency playing a major role. These results were consistent with those in other languages, supporting the application of NAM in the Chinese language. The development of Standard-Chinese version of LNT and the establishment of a database of children of 4-6 years old can provide a reliable means for spoken-word recognition test in children with hearing impairment.	\N	\N
21461784	Four eyetracking experiments examined whether semantic and visual-shape representations are routinely retrieved from printed word displays and used during language-mediated visual search. Participants listened to sentences containing target words that were similar semantically or in shape to concepts invoked by concurrently displayed printed words. In Experiment 1, the displays contained semantic and shape competitors of the targets along with two unrelated words. There were significant shifts in eye gaze as targets were heard toward semantic but not toward shape competitors. In Experiments 2-4, semantic competitors were replaced with unrelated words, semantically richer sentences were presented to encourage visual imagery, or participants rated the shape similarity of the stimuli before doing the eyetracking task. In all cases, there were no immediate shifts in eye gaze to shape competitors, even though, in response to the Experiment 1 spoken materials, participants looked to these competitors when they were presented as pictures (Huettig & McQueen, 2007). There was a late shape-competitor bias (more than 2,500 ms after target onset) in all experiments. These data show that shape information is not used in online search of printed word displays (whereas it is used with picture displays). The nature of the visual environment appears to induce implicit biases toward particular modes of processing during language-mediated visual search.	\N	\N
21467806	Vital-sign checks and physical assessment have been performed by physicians and nurses among medical staff in particular. However, pharmacists must also have basic skills of vital-sign checking and physical assessment to evaluate the patient condition/drug efficacy or prevent adverse reactions to drugs. To promote the acquisition of these skills, we prepared simulation programs with an emergency-care simulator, which facilitate the reproduction of excess-dose drug administration/condition changes. We used an emergency-care simulator equipped with a personal computer. General condition was established using the blinking velocity, cardiac/respiratory sounds and blood pH as parameters. As a results, concerning drug administration, the simulation programs facilitated the reproduction of symptoms related to the excess-dose insulin administration. With respect to changes in the condition, it facilitated the reproduction of asthma, hyperglycemia, and hemorrhage. This facilitated the palpation-, visual perception-, and auditory perception-mediated understanding of changes in the patient condition through fingertips and warnings/alarms on the monitor. Evaluation of the student for these program contents increased significantly (p<0.01). These programs can be downloaded via the Internet. Experience regarding excess-dose drug administration/condition changes with an emergency-care simulator is useful for checking patients' vital signs, evaluating the drug efficacy, and confirming adverse reactions to drugs. By the practice of these programs, we can teach pharmacy students how to check for vital signs (pulse palpation, auscultation, blood pressure measurement, and electrocardiography) in a school setting, not a hospital setting. Mastering these techniques may allow pharmacy students to determine the efficacy of a drug and adverse reactions.	\N	\N
21476651	Recently, it has been suggested that the annoyance of residents at a given aircraft noise exposure level increases over the years. The objective of the present study was to verify the hypothesized trend and to identify its possible causes. To this end, the large database used to establish earlier exposure-response relationships on aircraft noise was updated with original data from several recent surveys, yielding a database with data from 34 separate airports. Multilevel grouped regression was used to determine the annoyance response per airport, after which meta-regression was used to investigate whether study characteristics could explain the heterogeneity in annoyance response between airports. A significant increase over the years was observed in annoyance at a given level of aircraft noise exposure. Furthermore, the type of annoyance scale, the type of contact, and the response percentage were found to be sources of heterogeneity. Of these, only the scale factor could statistically account for the trend, although other findings rule it out as a satisfactory explanation. No evidence was found for increased self-reported noise sensitivity. The results are of importance to the applicability of current exposure-annoyance relationships for aircraft noise and provide a basis for decisions on whether these need to be updated.	\N	\N
21476675	Key features of the voice--fundamental frequency (F(0)) and formant frequencies (Fn)--can vary extensively among individuals. Some of this variation might cue fitness-related, biosocial dimensions of speakers. Three experiments tested the independent, joint and relative effects of F(0) and Fn on listeners' assessments of the body size, masculinity (or femininity), and attractiveness of male and female speakers. Experiment 1 replicated previous findings concerning the joint and independent effects of F(0) and Fn on these assessments. Experiment 2 established frequency discrimination thresholds (or just-noticeable differences, JND's) for both vocal features to use in subsequent tests of their relative salience. JND's for F(0) and Fn were consistent in the range of 5%-6% for each sex. Experiment 3 put the two voice features in conflict by equally discriminable amounts and found that listeners consistently tracked Fn over F(0) in rating all three dimensions. Several non-exclusive possibilities for this outcome are considered, including that voice Fn provides more reliable cues to one or more dimensions and that listeners' assessments of the different dimensions are partially interdependent. Results highlight the value of first establishing JND's for discrimination of specific features of natural voices in future work examining their effects on voice-based social judgments.	\N	\N
21477130	Evaluation of clinical characteristics, bacteriology and hearing in paediatric patients with and without chronic suppurative otitis media (CSOM) in Luanda, Angola. Interview, clinical examination, ear-discharge culture, open air pure-tone audiometry and brainstem auditory-evoked potentials of 23 outpatients with CSOM and 23 controls in a paediatric hospital. Of the CSOM vs. control children, 35% vs. 26% had running water, 70% vs. 70% electricity, 64% vs. 0% HIV (p<0.0001) and 36% vs. 0% tuberculosis in history (p=0.002). Ten (43%) children had bilateral CSOM. The major ear-discharge pathogens were Proteus spp. (44%) and Pseudomonas (22%). Hearing impairment of >25 dB was present in 52% of CSOM-affected ears and bilateral hearing loss in 7 (30%) CSOM children vs. zero control child (p=0.009). Only one hearing-impaired child's family had previously detected the handicap. CSOM occurred in children with high co-morbidity. Persistent otorrhoea was usually caused by Proteus spp. or Pseudomonas, and often suggestive of either HIV or hearing impairment. In the developing countries, prompt diagnosis and treatment of CSOM would enhance the children's linguistic and academic development.	\N	\N
21477198	To investigate the interaction between segmental and supra-segmental stress-related information in early word learning, two experiments were conducted with 20- to 24-month-old English-learning children. In an adaptation of the object categorization study designed by Nazzi and Gopnik (2001), children were presented with pairs of novel objects whose labels differed by their initial consonant (Experiment 1) or their medial consonant (Experiment 2). Words were produced with a stress initial (trochaic) or a stress final (iambic) pattern. In both experiments successful word learning was established when the to-be-remembered contrast was embedded in a stressed syllable, but not when embedded in unstressed syllables. This was independent of the overall word pattern, trochaic or iambic, or the location of the phonemic contrast, word-initial or -medial. Results are discussed in light of the use of phonetic information in early lexical acquisition, highlighting the role of lexical stress and ambisyllabicity in early word processing.	\N	\N
21479656	It is well established that sounds can enhance visual-target detection, but the mechanisms that govern these cross-sensory effects, as well as the neural pathways involved, are largely unknown. Here, we tested behavioral predictions stemming from the neurophysiologic and neuroanatomic literature. Participants detected near-threshold visual targets presented either at central fixation or peripheral to central fixation that were sometimes paired with sounds that originated from widely misaligned locations (up to 104° from the visual target). Our results demonstrate that co-occurring sounds improve the likelihood of visual-target detection (1) regardless of retinal eccentricity and (2) despite wide audiovisual misalignments. With regard to the first point, these findings suggest that auditory facilitation of visual-target detection is unlikely to operate through previously described corticocortical pathways from auditory cortex that predominantly terminate in regions of visual cortex that process peripheral visual space. With regard to the second point, auditory facilitation of visual-target detection seems to operate through a spatially non-specific modulation of visual processing.	\N	\N
21483666	Acute stress is a stereotypical, but multimodal response to a present or imminent challenge overcharging an organism. Among the different branches of this multimodal response, the consequences of glucocorticoid secretion have been extensively investigated, mostly in connection with long-term memory (LTM). However, stress responses comprise other endocrine signaling and altered neuronal activity wholly independent of pituitary regulation. To date, knowledge of the impact of such "paracorticoidal" stress responses on higher cognitive functions is scarce. We investigated the impact of an ecological stressor on the ability to direct selective attention using event-related potentials in humans. Based on research in rodents, we assumed that a stress-induced imbalance of catecholaminergic transmission would impair this ability. The stressor consisted of a single cold pressor test. Auditory negative difference (Nd) and mismatch negativity (MMN) were recorded in a tonal dichotic listening task. A time series of such tasks confirmed an increased distractibility occurring 4-7 minutes after onset of the stressor as reflected by an attenuated Nd. Salivary cortisol began to rise 8-11 minutes after onset when no further modulations in the event-related potentials (ERP) occurred, thus precluding a causal relationship. This effect may be attributed to a stress-induced activation of mesofrontal dopaminergic projections. It may also be attributed to an activation of noradrenergic projections. Known characteristics of the modulation of ERP by different stress-related ligands were used for further disambiguation of causality. The conjuncture of an attenuated Nd and an increased MMN might be interpreted as indicating a dopaminergic influence. The selective effect on the late portion of the Nd provides another tentative clue for this. Prior studies have deliberately tracked the adrenocortical influence on cognition, as it has proven most influential with respect to LTM. However, current cortisol-optimized study designs would have failed to detect the present findings regarding attention.	\N	\N
21487700	Anxious individuals have been shown to interpret others' emotional states negatively. Since most studies have used facial expressions as emotional cues, we examined whether trait anxiety affects the recognition of emotion in a dynamic face and voice that were presented in synchrony. The face and voice cues conveyed either matched (e.g., happy face and voice) or mismatched emotions (e.g., happy face and angry voice). Participants with high or low trait anxiety were to indicate the perceived emotion using one of the cues while ignoring the other. The results showed that individuals with high trait anxiety were more likely to interpret others' emotions in a negative manner, putting more weight on the to-be-ignored angry cues. This interpretation bias was found regardless of the cue modality (i.e., face or voice). Since trait anxiety did not affect recognition of the face or voice cues presented in isolation, this interpretation bias appears to reflect an altered integration of the face and voice cues among anxious individuals.	\N	\N
21491276	In order to determine how the interior of a car should sound, automotive manufacturers often rely on obtaining data from individual evaluations of vehicle sounds. Company identity could play a role in these appraisals, particularly when individuals are comparing cars from opposite ends of the performance spectrum. This research addressed the question: does company identity influence the evaluation of automotive sounds belonging to cars of a similar performance level and from the same market segment? Participants listened to car sounds from two competing manufacturers, together with control sounds. Before listening to each sound, participants were presented with the correct company identity for that sound, the incorrect identity or were given no information about the identity of the sound. The results showed that company identity did not influence appraisals of high performance cars belonging to different manufacturers. These results have positive implications for methodologies employed to capture the perceptions of individuals. STATEMENT OF RELEVANCE: A challenge in automotive design is to set appropriate targets for vehicle sounds, relying on understanding subjective reactions of individuals to such sounds. This paper assesses the role of company identity in influencing these subjective reactions and will guide sound evaluation studies, in which the manufacturer is often apparent.	\N	\N
21493243	To determine whether patterns of functional connectivity of cortical regions responsible for auditory processing and executive functions differ in children with unilateral hearing loss (UHL) versus their normal-hearing (NH) siblings. Prospective observational study. Academic medical center. Children with severe-to-profound UHL (9 right UHL, 7 left UHL) and 10 NH sibling controls were imaged using resting state functional connectivity magnetic resonance imaging (rs-fcMRI). All MRI images were transformed to a single common atlas; regions of interest (ROI) were chosen based on previous literature and unpublished results. Mean regionwise correlations and conjunction analyses were performed across 34 seed ROIs to identify temporally synchronized, low-frequency spontaneous fluctuations in the resting state blood oxygenation level-dependent signal that reveal functionally related regions. Mean regionwise Student t tests found a left posterior opercular region with more correlated resting state activity with the inferior parietal lobule seed in the children with both left and right UHL than NH. In conjunction analysis, 4 regions showed different resting-state functional interactions between the NH and both UHL groups. These differences were in left medial globus pallidus, left middle temporal gyrus, right parahippocampal gyrus, and mid-cingulate cortex. These regions include areas associated with auditory processing, executive function, and memory formation. Resting state fcMRI identified differences in brain network interconnections between children with UHL and NH and may inform further investigation into the educational and behavioral difficulties experienced by children with UHL.	\N	\N
21495790	To assess factors that contribute to Tinnitus Handicap Inventory (THI) scores in Japan. Case series with chart review. Two hundred and eighty-five tinnitus patients at tertiary referral center, who completed the Japanese version of the THI, the Self-rating Depression Scale (SDS), and the State Trait Anxiety Inventory (STAI). In multiple regression analysis, the SDS score contributed the most to the THI score. The state section of the STAI score and pure tone average (PTA) at four high frequencies also contributed significantly, but to lesser degrees. The other following factors were not statistically significant: age, gender, time from the onset of tinnitus to the first clinical visit, PTA at three mid frequencies, and trait section of the STAI score. This model may account for approximately 45% of THI score variability. The THI scores may be influenced by depressive symptoms, state anxiety, and pure tone thresholds in Japan.	\N	\N
21502927	Mismatch negativity (MMN) is an event-related potential that is elicited by deviant sounds that are presented along with frequent sounds in the absence of attention. Auditory MMN is generated by the comparison process between sensory memory trace of a frequent auditory event and a deviant event. It is well known that frequent sounds are encoded in memory trace and processed as a single unit within 160-170 ms. This study examined whether deviant sound would be similarly processed as a temporal unit. Twelve healthy men were presented with relatively short standard sounds and relatively long deviant sounds that contained an omitted (i.e. silent) part. Three types of deviant sounds were designed to vary in duration. The MMN amplitude was gradually enhanced from the short to long duration deviant events that contained an omitted part. In contrast, MMN latency showed no significant differences among the deviants. These findings show that deviant sounds are also processed as a unitary event.	\N	\N
21503649	Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis.	\N	\N
21507543	Dichotic listening originally was a means of studying attention. Half a century ago Doreen Kimura parlayed the dichotic method into a noninvasive indicator of lateralized cerebral language representation. The ubiquitous right-ear advantage (REA) for verbal material was accepted as a concomitant of left-sided language lateralization and preferential conduction of right-ear messages to the left hemisphere. As evidence has accumulated over the past 50years showing the REA to be dynamic and modifiable, the concept of attention has become essential for interpreting the findings. Progress in understanding the role of attention has been manifested as a transition from efforts to document attention effects to efforts to characterize their mechanisms. We summarize the relevant evidence, trace the evolution of explanatory models, and outline contemporary accounts of the role of attention in dichotic listening.	\N	\N
21508086	Recent evidence demonstrates that perceptual rivalry rate can be modulated by perturbation of the serotonergic system. Specifically, pharmacologically lowering the availability of serotonin results in slower rivalry rates. As it has been suggested that brain serotonin is low during the interictal phase of migraine, we hypothesized that perceptual rivalry rates would be reduced in individuals with migraine. Visual and auditory perceptual rivalry measures were obtained for a group of 30 participants with migraine (15 migraine with aura, 15 migraine without aura) and 20 non-headache control individuals. Our experiments reveal fewer perceptual rivalry switches within both visual and auditory domains for our migraine without aura group, while the with-aura group performed similarly to non-headache controls. Dividing the data by headache frequency rather than headache subtype classification revealed fewer perceptual switches in those with more frequent headaches. Our data provides further support for interictal differences in brain sensory reactivity in migraine, with the observed effects being in the same direction as those caused by pharmacologically reducing brain availability of serotonin in normal observers.	\N	\N
21509624	Elderly persons frequently complain about problems with speech understanding especially in complex acoustic situations. Besides hearing impairment the decline of cognitive functions might explain these problems. In 12 normal hearing young subjects and 14 elderly listeners with extraordinarily good hearing speech perception was measured in a broad range of different acoustic situations. Cognitive functioning was evaluated with different neuropsychological tests. Despite comparable pure tone thresholds the elderly listeners revealed worse speech discrimination than the young subjects in almost all test situations. Largest differences were found in situations with fluctuating maskers and competing talkers. Most of the speech perception results revealed significant correlations with the outcome from a neuropsychological test addressing declarative verbal memory. In complex listening situations elderly persons reveal worse speech understanding than younger subjects. Differences in speech perception can partly be attributed to cognitive abilities. In particular, working memory seems to be an important factor.	\N	\N
21512805	The purpose of this study was to investigate whether multi-stimulus auditory steady-state responses were capable of estimating hearing thresholds in high-risk infants. A retrospective chart review study. Three tertiary referral centers. Infants born between January 2004 and December 2006 who met the criteria for risk factors of congenital hearing loss were enrolled in the study. While under sedation, the multi-stimulus auditory steady-state response was used to determine multi-channel auditory steady-state response thresholds for high-risk infants younger than 13 months. Conditioned play audiometry was then applied to these children at 23-48 months of age to obtain pure tone audiograms. Auditory steady-state response thresholds and pure tone thresholds were then compared. A total of 249 high-risk infants were enrolled in the study. 39 infants were lost during follow-up. The remaining 216 infants completed both examinations. The Pearson correlation coefficients (r) between the ASSR levels and pure tone thresholds were 0.88, 0.94, 0.94 and 0.97 at 500, 1,000, 2,000 and 4,000 Hz, respectively. The strength of the relationship between the auditory steady-state responses and pure tone thresholds increased with more severe degrees of hearing loss and higher frequencies. We conclude that initial multichannel ASSR thresholds measured under sedation are highly correlated with pure tone thresholds obtained 2 or 3 years later. ASSR can be used to predict the frequency-specific hearing thresholds of high-risk infants and can provide information for early hearing intervention.	\N	\N
21524014	Recent research provides evidence that individuals shift in their perception of variants depending on social characteristics attributed to the speaker.This paper reports on a speech perception experiment designed to test the degree to which the age attributed to a speaker influences the perception of vowels undergoing a chain shift. As a result of the shift, speakers from different generations produce different variants from one another. Results from the experiment indicate that a speaker's perceived age can influence vowel categorization in the expected direction. However, only older participants are influenced by perceived speaker age.This suggests that social characteristics attributed to a speaker affect speech perception differently depending on the salience of the relationship between the variant and the characteristic.The results also provide evidence of an unexpected interaction between the sex of the participant and the sex of the stimulus.The interaction is interpreted as an effect of the participants' previous exposure with male and female speakers.The results are analyzed under an exemplar model of speech production and perception where social information is indexed to acoustic information and the weight of the connection varies depending on the perceived salience of sociophonetic trends.	\N	\N
21526589	In a sample of 18 European nations, suicide rates were positively associated with the proportion of low notes in the national anthems and, albeit less strongly, with students' ratings of how gloomy and how sad the anthems sounded, supporting a hypothesis proposed by Rihmer.	\N	\N
21534716	We suggest that cochlear implantation (CI) should be a good therapeutic modality for hearing restoration in patients with common cavity malformed ears. To analyze hearing improvement from CI performed in common cavity malformed cochleae. A total of 11 patients (5 male and 6 female, mean age 4.5 ± 2.8 years) and 12 ears were enrolled in this study. During the insertion of electrodes, we used C-arm fluoroscopy to avoid intrameatal placement. We evaluated hearing improvement every 6 months and the mean follow-up period was 80.5 ± 24.1 months (53-125 months). During the operation, there were only four cases with fully inserted electrodes. Cerebrospinal fluid gushed out in two cases during the cochleostomy and postoperative meningitis occurred in two patients. One patient had to undergo reimplantation 4 years later due to device failure and recurrent meningitis. During the 48 months follow-up hearing evaluation, the ability of hearing increased along with the age. The final average MAIS, CAP, SIR, and open set one- and two-syllable word scores were 90.3 ± 18.1%, 4.9 ± 1.6, 3.1 ± 0.9, 24.1 ± 25.9%, and 48.6 ± 38.7%, respectively.	\N	\N
21537615	Profound hearing loss is a disability that affects personality and when it involves teenagers before language acquisition, these bio-psychosocial conflicts can be exacerbated, requiring careful evaluation and choice of them for cochlear implant. To evaluate speech perception by adolescents with profound hearing loss, users of cochlear implants. Prospective. Twenty-five individuals with severe or profound pre-lingual hearing loss who underwent cochlear implantation during adolescence, between 10 to 17 years and 11 months, who went through speech perception tests before the implant and 2 years after device activation. For comparison and analysis we used the results from tests of four choice, recognition of vowels and recognition of sentences in a closed setting and the open environment. The average percentage of correct answers in the four choice test before the implant was 46.9% and after 24 months of device use, this value went up to 86.1% in the vowels recognition test, the average difference was 45.13% to 83.13% and the sentences recognition test together in closed and open settings was 19.3% to 60.6% and 1.08% to 20.47% respectively. All patients, although with mixed results, achieved statistical improvement in all speech tests that were employed.	\N	\N
21545766	This paper presents longitudinal case studies of children who received (cochlear implants) CIs and a controlled sample of children with normal hearing (NH). Phoneme discrimination (i.e., /sa-ma/, /a-i/, /a-u/, /u-i/, /ta-da/, /pa-ka/) was assessed prior to receiving CIs and monthly for 3 mo following CI activation. Case studies. Three cochlear implant recipients and seven NH control participants were recruited through the University of Colorado Hospital and the University of Colorado, Boulder. The study utilized the visual reinforcement audiometry and interactive play assessment of speech pattern contrasts (VRASPAC) algorithm. A comparison of scoring was conducted using Cohen's kappa to determine interrater reliability. Findings from this study revealed that CI recipients could discriminate at least three out of five phoneme contrasts at mastery level (≥90%) by 2 mo of device use. None of the CI recipients reached mastery prior to implantation. Following 3 mo of CI use there was no difference in contrast discrimination performance between the CI users and their NH age-matched peers (with the exception of /pa-ka/ for one CI user. The CI users in this case study, who were implanted between 12 and 16 mo of age, were able to master the phoneme contrasts regardless of bilateral or unilateral CI, socioeconomic status, or language spoken at home.	\N	\N
21552274	Responses of neurons that integrate multiple sensory inputs are traditionally characterized in terms of a set of empirical principles. However, a simple computational framework that accounts for these empirical features of multisensory integration has not been established. We propose that divisive normalization, acting at the stage of multisensory integration, can account for many of the empirical principles of multisensory integration shown by single neurons, such as the principle of inverse effectiveness and the spatial principle. This model, which uses a simple functional operation (normalization) for which there is considerable experimental support, also accounts for the recent observation that the mathematical rule by which multisensory neurons combine their inputs changes with cue reliability. The normalization model, which makes a strong testable prediction regarding cross-modal suppression, may therefore provide a simple unifying computational account of the important features of multisensory integration by neurons.	\N	\N
21553997	Using a novel variant of dichotic selective listening, we examined the control of auditory selective attention. In our task, subjects had to respond selectively to one of two simultaneously presented auditory stimuli (number words), always spoken by a female and a male speaker, by performing a numerical size categorization. The gender of the task-relevant speaker could change, as indicated by a visual cue prior to auditory stimulus onset. Three experiments show clear performance costs with instructed attention switches. Experiment 2 varied the cuing interval to examine advance preparation for an attention switch. Experiment 3 additionally isolated auditory switch costs from visual cue priming by using two cues for each gender, so that gender repetition could be indicated by a changed cue. Experiment 2 showed that switch costs decreased with prolonged cuing intervals, but Experiment 3 revealed that preparation did not affect auditory switch costs but only visual cue priming. Moreover, incongruent numerical categories in competing auditory stimuli produced interference and substantially increased error rates, suggesting continued processing of task-relevant information that often leads to responding to the incorrect auditory source. Together, the data show clear limitations in advance preparation of auditory attention switches and suggest a considerable degree of inertia in intentional control of auditory selection criteria.	\N	\N
21559468	In humans, emotions from music serve important communicative roles. Despite a growing interest in the neural basis of music perception, action and emotion, the majority of previous studies in this area have focused on the auditory aspects of music performances. Here we investigate how the brain processes the emotions elicited by audiovisual music performances. We used event-related functional magnetic resonance imaging, and in Experiment 1 we defined the areas responding to audiovisual (musician's movements with music), visual (musician's movements only), and auditory emotional (music only) displays. Subsequently a region of interest analysis was performed to examine if any of the areas detected in Experiment 1 showed greater activation for emotionally mismatching performances (combining the musician's movements with mismatching emotional sound) than for emotionally matching music performances (combining the musician's movements with matching emotional sound) as presented in Experiment 2 to the same participants. The insula and the left thalamus were found to respond consistently to visual, auditory and audiovisual emotional information and to have increased activation for emotionally mismatching displays in comparison with emotionally matching displays. In contrast, the right thalamus was found to respond to audiovisual emotional displays and to have similar activation for emotionally matching and mismatching displays. These results suggest that the insula and left thalamus have an active role in detecting emotional correspondence between auditory and visual information during music performances, whereas the right thalamus has a different role.	\N	\N
21564122	We studied whether a multifeature mismatch negativity (MMN) paradigm using naturally produced speech stimuli is feasible for studies of auditory discrimination accuracy of adult participants. A naturally produced trisyllabic pseudoword was used in the paradigm, and MMNs were recorded to changes that were acoustic (changes in fundamental frequency or intensity) or potentially phonological (changes in vowel identity or vowel duration). All the different changes were presented in three different word segments (initial, middle, or final syllable). All changes elicited an MMN response, but the vowel duration change elicited a different response pattern than the other deviant types. Changes in vowel duration and identity also had an effect on MMN lateralization. Our results show that assessing speech sound discrimination of several features in word context is possible in a short recording time (30 min) with the multifeature paradigm.	\N	\N
21568161	Although receptive priming has long been used as a way to examine lexical access in adults, few studies have applied this method to children and rarely in an auditory modality. We compared auditory associative priming in children and adults. A testing battery and a Lexical Decision (LD) task was administered to 42 adults and 27 children (8;1-10; 11 years-old) from Spain. They listened to Spanish word pairs (semantically related/unrelated word pairs and word-pseudoword pairs), and tone pairs. Then participants pressed one key for word pairs, and another for pairs with a word and a pseudoword. They also had to press the two keys alternatively for tone pairs as a basic auditory control. Both groups of participants, children and adults, exhibited semantic priming, with significantly faster Reaction Times (RTs) to semantically related word pairs than to unrelated pairs and to the two word-pseudoword sets. The priming effect was twice as large in the adults compared to children, and the children (not the adults) were significantly slower in their response to word-pseudoword pairs than to the unrelated word pairs. Moreover, accuracy was somewhat higher in adults than children for each word pair type, but especially in the word-pseudoword pairs. As expected, children were significantly slower than adults in the RTs for all stimulus types, and their RTs decreased significantly from 8 to 10 years of age and they also decreased in relation to some of their language abilities development (e.g., relative clauses comprehension). In both age groups, the Reaction Time average for tone pairs was lower than for speech pairs, but only all adults obtained 100% accuracy (which was slightly lower in children). Auditory processing and semantic networks are still developing in 8-10 year old children.	\N	\N
21568376	The corruption of intonation contours has detrimental effects on sentence-based speech recognition in normal-hearing listeners Binns and Culling [(2007). J. Acoust. Soc. Am. 122, 1765-1776]. This paper examines whether this finding also applies to cochlear implant (CI) recipients. The subjects' F0-discrimination and speech perception in the presence of noise were measured, using sentences with regular and inverted F0-contours. The results revealed that speech recognition for regular contours was significantly better than for inverted contours. This difference was related to the subjects' F0-discrimination providing further evidence that the perception of intonation patterns is important for the CI-mediated speech recognition in noise.	\N	\N
21568411	This study examined the time course of cochlear suppression using a tone-burst suppressor to measure decrement of distortion-product otoacoustic emissions (DPOAEs). Seven normal-hearing subjects with ages ranging from 19 to 28 yr participated in the study. Each subject had audiometric thresholds ≤ 15 dB HL [re ANSI (2004) Specifications for Audiometers] for standard octave and inter-octave frequencies from 0.25 to 8 kHz. DPOAEs were elicited by primary tones with f(2) = 4.0 kHz and f(1) = 3.333 kHz (f(2)/f(1) = 1.2). For the f(2), L(2) combination, suppression was measured for three suppressor frequencies: One suppressor below f(2) (3.834 kHz) and two above f(2) (4.166 and 4.282 kHz) at three levels (55, 60, and 65 dB SPL). DPOAE decrement as a function of L(3) for the tone-burst suppressor was similar to decrements obtained with longer duration suppressors. Onset- and setoff- latencies were ≤ 4 ms, in agreement with previous physiological findings in auditory-nerve fiber studies that suggest suppression results from a nearly instantaneous compression of the waveform. Persistence of suppression was absent for the below-frequency suppressor (f(3) = 3.834 kHz) and was ≤ 3 ms for the two above-frequency suppressors (f(3) = 4.166 and 4.282 kHz).	\N	\N
21568423	The octave or Deutsch illusion occurs when two tones, separated by about one octave, are presented simultaneously but alternating between ears, such that when the low tone is presented to the left ear the high tone is presented to the right ear and vice versa. Most subjects hear a single tone that alternates both between ears and in pitch; i.e., they hear a low pitched tone in one ear alternating with a high pitched tone in the other ear. The present study examined whether the illusion can be elicited by aperiodic signals consisting of low-frequency band-pass filtered noises with overlapping spectra. The amount of spectral overlap was held constant, but the high- and low-frequency content of the signals was systematically varied. The majority of subjects perceived an auditory illusion in terms of a dominant ear for pitch and lateralization by frequency, as proposed by Deutsch [(1975a) Sci. Am. 233, 92-104]. Furthermore, the salience of the illusion increased as the high frequency of the content in the signal increased. Since no harmonics were present in the stimuli, it is highly unlikely that this illusion is perceived on the basis of binaural diplacusis or harmonic binaural fusion.	\N	\N
21569617	After a prolonged exposure to a paired presentation of different types of signals (e.g., color and motion), one of the signals (color) becomes a driver for the other signal (motion). This phenomenon, which is known as contingent motion aftereffect, indicates that the brain can establish new neural representations even in the adult's brain. However, contingent motion aftereffect has been reported only in visual or auditory domain. Here, we demonstrate that a visual motion aftereffect can be contingent on a specific sound. Dynamic random dots moving in an alternating right or left direction were presented to the participants. Each direction of motion was accompanied by an auditory tone of a unique and specific frequency. After a 3-minutes exposure, the tones began to exert marked influence on the visual motion perception, and the percentage of dots required to trigger motion perception systematically changed depending on the tones. Furthermore, this effect lasted for at least 2 days. These results indicate that a new neural representation can be rapidly established between auditory and visual modalities.	\N	\N
21598839	This study examined the relationship between proactive learning in hypnosis, post-hypnotic suggestion, and academic performance. Participants (N = 56) were randomly assigned to a control group or a treatment group. The treatment group was hypnotized and read a passage while in hypnosis. Concurrently, they were given a post-hypnotic suggestion, which attempted to aid recognition and performance on a test immediately following the hypnosis session. Both groups completed a multiple-choice test based on the aforementioned passage. An analysis of covariance discerned the effect of proactive learning and post-hypnotic suggestion on test performance, while controlling for the variance introduced by scholastic aptitude as measured by the ACT. Results indicated that the hypnosis sessions predicted significantly impaired test performance.	\N	\N
21599613	To develop and evaluate the Mandarin speech signal content on the acceptable noise level (ANL) test in listeners with normal hearing in mainland China. The Mandarin ANL tests were conducted using three different sets of Mandarin running speech materials which were chosen from textbooks for primary school, secondary school, and high school, respectively. For each discourse, two ANL measurements were obtained and averaged for each experimental condition using ANL test procedures. Thirty-one normal-hearing listeners participated in this study. There were significant differences for ANLs among the normal-hearing listeners, but no differences were found for MCLs and ANLs for the three sets of test materials. The Pearson correlations suggested significant correlations between MCL and ANL among the three test materials; also the results showed that the correlation coefficient between MCL-ANL of the primary material was much better than other two materials. (1) The contents of different Mandarin running speeches may not affect the acceptable noise level in Mandarin normal-hearing listeners; (2) The running speech selected from the primary school ought to be used as the Mandarin acceptable noise level test material to evaluate the outcomes of hearing aid fitting.	\N	\N
21604474	To enhance speech recognition in noise, as well as tone recognition, we presented a new kind of speech coding strategy, called one-octave wavelet transform zero-crossing stimulation (WTZS), for cochlear implants based on amplitude and frequency modulation. We selected 15 volunteers with normal hearing ability to carry out hearing simulation experiments by picking up the amplitude (amplitude modulation, AM), zero-crossings (frequency modulation, FM) and gradient parameters from processed speech signal in the domain of one-octave wavelet transform to synthesize the stimulating pulstile series. The experimental results demonstrated that the phonetic recognition in quiet surroundings with amplitude modulation only strategy (CIS) is similar to that of amplitude and frequency modulations strategies (FAME and WTZS), while the tone perception of CIS is inferior to that of FAME and WTZS strategies. However, in noisy environment, the phonetic recognition, tone perception, as well as sentence recognition of WTZS strategy are better than those of CIS and FAME strategies. WTZS strategy, utilizing amplitude (AM), zero-crossings (FM) and gradient parameters to synthesize stimulus, can enhance the phonetic and tonal language recognition in noise environment effectively, and could be used in cochlear implant system for speech processor design after arithmetic optimization.	\N	\N
21613467	There is an increasing interest to integrate electrophysiological and hemodynamic measures for characterizing spatial and temporal aspects of cortical processing. However, an informative combination of responses that have markedly different sensitivities to the underlying neural activity is not straightforward, especially in complex cognitive tasks. Here, we used parametric stimulus manipulation in magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) recordings on the same subjects, to study effects of noise on processing of spoken words and environmental sounds. The added noise influenced MEG response strengths in the bilateral supratemporal auditory cortex, at different times for the different stimulus types. Specifically for spoken words, the effect of noise on the electrophysiological response was remarkably nonlinear. Therefore, we used the single-subject MEG responses to construct parametrization for fMRI data analysis and obtained notably higher sensitivity than with conventional stimulus-based parametrization. fMRI results showed that partly different temporal areas were involved in noise-sensitive processing of words and environmental sounds. These results indicate that cortical processing of sounds in background noise is stimulus specific in both timing and location and provide a new functionally meaningful platform for combining information obtained with electrophysiological and hemodynamic measures of brain function.	\N	\N
21613485	Growing evidence from electrophysiological data in animal and human studies suggests that multisensory interaction is not exclusively a higher-order process, but also takes place in primary sensory cortices. Such early multisensory interaction is thought to be mediated by means of phase resetting. The presentation of a stimulus to one sensory modality resets the phase of ongoing oscillations in another modality such that processing in the latter modality is modulated. In humans, evidence for such a mechanism is still sparse. In the current study, the influence of an auditory stimulus on visual processing was investigated by measuring the electroencephalogram (EEG) and behavioral responses of humans to visual, auditory, and audiovisual stimulation with varying stimulus-onset asynchrony (SOA). We observed three distinct oscillatory EEG responses in our data. An initial gamma-band response around 50 Hz was followed by a beta-band response around 25 Hz, and a theta response around 6 Hz. The latter was enhanced in response to cross-modal stimuli as compared to either unimodal stimuli. Interestingly, the beta response to unimodal auditory stimuli was dominant in electrodes over visual areas. The SOA between auditory and visual stimuli--albeit not consciously perceived--had a modulatory impact on the multisensory evoked beta-band responses; i.e., the amplitude depended on SOA in a sinusoidal fashion, suggesting a phase reset. These findings further support the notion that parameters of brain oscillations such as amplitude and phase are essential predictors of subsequent brain responses and might be one of the mechanisms underlying multisensory integration.	\N	\N
21615286	Research into speech perception by nonhuman animals can be crucially informative in assessing whether specific perceptual phenomena in humans have evolved to decode speech, or reflect more general traits. Birds share with humans not only the capacity to use complex vocalizations for communication but also many characteristics of its underlying developmental and mechanistic processes; thus, birds are a particularly interesting group for comparative study. This review first discusses commonalities between birds and humans in perception of speech sounds. Several psychoacoustic studies have shown striking parallels in seemingly speech-specific perceptual phenomena, such as categorical perception of voice-onset-time variation, categorization of consonants that lack phonetic invariance, and compensation for coarticulation. Such findings are often regarded as evidence for the idea that the objects of human speech perception are auditory or acoustic events rather than articulations. Next, I highlight recent research on the production side of avian communication that has revealed the existence of vocal tract filtering and articulation in bird species-specific vocalization, which has traditionally been considered a hallmark of human speech production. Together, findings in birds show that many of characteristics of human speech perception are not uniquely human but also that a comparative approach to the question of what are the objects of perception--articulatory or auditory events--requires careful consideration of species-specific vocal production mechanisms.	\N	\N
21616132	Presbycusis, or age-related hearing loss is a growing problem as the general population ages. In this longitudinal study, the influence of noise or styrene exposure on presbycusis was investigated in Brown Norway rats. Animals were exposed at 6 months of age, either to a band noise centered at 8 kHz at a Lex,8h = 85 dB (86.2 dB SPL for 6 h), or to 300 ppm of styrene for 6 h per day, five days per week, for four weeks. Cubic distortion product otoacoustic emissions (2f1-f2 DPOAEs) were used to test the capacity of the auditory receptor over the lifespan of the animals. 2f1-f2DPOAE measurements are easy to implement and efficiently track the age-related deterioration of mid- and high-frequencies. They are good indicators of temporary auditory threshold shift, especially with a level of primaries close to 60 dB SPL. Post-exposure hearing defects are best identified using moderate, rather than high, levels of primaries. Like many aging humans, aging rats lose sensitivity to high-frequencies faster than to medium-frequencies. Although the results obtained with the styrene exposure were not entirely conclusive, histopathological data showed the presbycusis process to be enhanced. Noise-exposed rats exhibit a loss of spiral ganglion cells from 12 months and a 7 dB drop in 2f1-f2DPOAEs at 24 months, indicating that even moderate-intensity noise can accelerate the presbycusis process. Even though the results obtained with the styrene exposure are less conclusive, the histopathological data show an enhancement of the presbycusis process.	\N	\N
21630061	Since air-conducted (AC) and clinical (mastoid) bone-conducted (BC) sounds interact in the cochlea (e.g. pitch, cancellation, masking, beats), it has been thought that both AC and BC stimulations lead to a mechanical wave in the cochlea. However, there are also "non-osseous" forms of BC, i.e. auditory sensation produced when the clinical bone vibrator is applied to "non-osseous" soft tissue sites. In the present study, such "non-osseous" sites were identified (e.g. eye, cheek, neck) and they interacted with AC and osseous BC (pitch matching, beats, masking), indicating that all of these forms of auditory stimulation converge in the cochlea, producing the same pattern of mechanical activity, leading to their interactions.	\N	\N
21632920	The integration of multisensory information has been shown to be guided by spatial and temporal proximity, as well as to be influenced by attention. Here we used neural measures of the multisensory spread of attention to investigate the spatial and temporal linking of synchronous versus near-synchronous auditory and visual events. Human participants attended selectively to one of two lateralized visual-stimulus streams while task-irrelevant tones were presented centrally. Electrophysiological measures of brain activity showed that tones occurring simultaneously or delayed by 100 ms were temporally linked to an attended visual stimulus, as reflected by robust cross-modal spreading-of-attention activity, but not when delayed by 300 ms. The neural data also indicated a ventriloquist-like spatial linking of the auditory to the attended visual stimuli, but only when occurring simultaneously. These neurophysiological results thus provide unique insight into the temporal and spatial principles of multisensory feature integration and the fundamental role attention plays in such integration.	\N	\N
21632945	Contemporary models of the neural system that supports reading propose that activity in a ventral occipitotemporal area (vOT) drives activity in higher-order language areas, for example, those in the posterior superior temporal sulcus (pSTS) and anterior superior temporal sulcus (aSTS). We used fMRI with dynamic causal modeling (DCM) to investigate evidence for other routes from visual cortex to the left temporal lobe language areas. First we identified activations in posterior inferior occipital (iO) and vOT areas that were more activated for silent reading than listening to words and sentences; and in pSTS and aSTS areas that were commonly activated for reading relative to false-fonts and listening to words relative to reversed words. Second, in three different DCM analyses, we tested whether visual processing of words modulates activity from the following: (1) iO→vOT, iO→pSTS, both, or neither; (2) vOT→pSTS, iO→pSTS, both or neither; and (3) pSTS→aSTS, vOT→aSTS, both, or neither. We found that reading words increased connectivity (1) from iO to both pSTS and vOT; (2) to pSTS from both iO and vOT; and (3) to aSTS from both vOT and pSTS. These results highlight three potential processing streams in the occipitotemporal cortex: iO→pSTS→aSTS; iO→vOT→aSTS; and iO→vOT→pSTS→aSTS. We discuss these results in terms of cognitive models of reading and propose that efficient reading relies on the integrity of all these pathways.	\N	\N
21637344	Previous cue integration studies have examined continuous perceptual dimensions (e.g., size) and have shown that human cue integration is well described by a normative model in which cues are weighted in proportion to their sensory reliability, as estimated from single-cue performance. However, this normative model may not be applicable to categorical perceptual dimensions (e.g., phonemes). In tasks defined over categorical perceptual dimensions, optimal cue weights should depend not only on the sensory variance affecting the perception of each cue but also on the environmental variance inherent in each task-relevant category. Here, we present a computational and experimental investigation of cue integration in a categorical audio-visual (articulatory) speech perception task. Our results show that human performance during audio-visual phonemic labeling is qualitatively consistent with the behavior of a Bayes-optimal observer. Specifically, we show that the participants in our task are sensitive, on a trial-by-trial basis, to the sensory uncertainty associated with the auditory and visual cues, during phonemic categorization. In addition, we show that while sensory uncertainty is a significant factor in determining cue weights, it is not the only one and participants' performance is consistent with an optimal model in which environmental, within category variability also plays a role in determining cue weights. Furthermore, we show that in our task, the sensory variability affecting the visual modality during cue-combination is not well estimated from single-cue performance, but can be estimated from multi-cue performance. The findings and computational principles described here represent a principled first step towards characterizing the mechanisms underlying human cue integration in categorical tasks.	\N	\N
21638105	In two experiments, we examined the impact of the degree of match between sequential auditory perceptual organization processes and the demands of a short-term memory task (memory for order vs. item information). When a spoken sequence of digits was presented so as to promote its perceptual partitioning into two distinct streams by conveying it in alternating female (F) and male (M) voices (FMFMFMFM)--thereby disturbing the perception of true temporal order--recall of item order was greatly impaired (as compared to recall of item identity). Moreover, an order error type consistent with the formation of voice-based streams was committed more quickly in the alternating-voice condition (Exp. 1). In contrast, when the perceptual organization of the sequence mapped well onto an optimal two-group serial rehearsal strategy--by presenting the two voices in discrete clusters (FFFFMMMM)--order, but not item, recall was enhanced (Exp. 2). The results are consistent with the view that the degree of compatibility between perceptual and deliberate sequencing processes is a key determinant of serial short-term memory performance. Alternative accounts of talker variability effects in short-term memory, based on the concept of a dedicated phonological short-term store and a capacity-limited focus of attention, are also reviewed.	\N	\N
21646423	To determine the rate of word learning for children with hearing loss (HL) in quiet and in noise compared to normal-hearing (NH) peers. The effects of digital noise reduction (DNR) were examined for children with HL. Forty-one children with NH and 26 children with HL were grouped by age (8-9 years and 11-12 years). The children learned novel words associated with novel objects through a process of trial and error. Functions relating performance across trials were calculated for each child in each listening condition and were compared. Significant effects were observed for age (older > younger) in the children with NH and listening condition (quiet > noise) in the children with HL. Significant effects of hearing status were also observed across groups (NH > HL), indicating that the children with HL required more trials to learn the new words. However, word learning improved significantly in noise with the use of DNR for the older but not for the younger children with HL. Hearing aid history and signal-to-noise ratio did not contribute to performance. Word learning was significantly reduced in younger children, in noise, and in the presence of hearing loss. Age-related benefits of DNR were apparent for children over 10 years of age.	\N	\N
21646931	The perception of pitch has recently gained attention. At present, clinical audiologic tests to assess this are hardly available. This article reports on the development of a clinical test using harmonic intonation (HI) and disharmonic intonation (DI). Prospective collection of normative data and pilot study in hearing-impaired subjects. Tertiary referral center. Normative data were collected from 90 normal-hearing subjects recruited from 3 different language backgrounds. The pilot study was conducted on 18 hearing-impaired individuals who were selected into 3 pathologic groups: high-frequency hearing loss (HF), low-frequency hearing loss (LF), and cochlear implant users (CI). Normative data collection and exploratory diagnostics by means of the newly constructed HI/DI tests using intonation patterns to find the just noticeable difference (JND) for pitch discrimination in low-frequency harmonic complex sounds presented in a same-different task. JND for pitch discrimination using HI/DI tests in the hearing population and pathologic groups. Normative data are presented in 5 parameter statistics and box-and-whisker plots showing median JNDs of 2 (HI) and 3 Hz (DI). The results on both tests are statistically abnormal in LF and CI subjects, whereas they are not significantly abnormal in the HF group. The HI and DI tests allow the clinical assessment of low-frequency pitch perception. The data obtained in this study define the normal zone for both tests. Preliminary results indicate possible abnormal TFS perception in some hearing-impaired subjects.	\N	\N
21664147	Homonyms, i.e. ambiguous words like 'score', have different meanings in different contexts. Previous research indicates that all potential meanings of a homonym are first accessed in parallel before one of the meanings is selected in a competitive race. If these processes are automatic, these processes of selection should even be observed when homonyms are shown subliminally. This study measured the time course of subliminal and supraliminal priming by homonyms with a frequent (dominant) and a rare (subordinate) meaning in a neutral context, using a lexical decision task. In the subliminal condition, priming across prime-target asynchronies ranging from 100 ms to 1.5 s indicated that the dominant meaning of homonyms was facilitated and the subordinate meaning was inhibited. This indicates that selection of meaning was much faster with subliminal presentation than with supraliminal presentation. Awareness of a prime might decelerate an otherwise rapid selection process.	\N	\N
21666515	The cortical processing of musical sounds is influenced by listeners' sensitivity to the structural regularities of music, and particularly by sensitivity to harmonic relationships. As subcortical and cortical processing dynamically interact to shape auditory perception in an experience-dependent manner, we asked whether subcortical processing of musical sounds would be sensitive to harmonic relationships. We examined auditory brainstem responses to a chord that was preceded either by a harmonically related chord, by an unrelated chord, or was repeated. We observed higher spectral response magnitudes in the related than in the unrelated or repeated conditions, for both musician and nonmusician listeners. Our results suggest that listeners' implicit knowledge of musical regularities influences subcortical auditory processing.	\N	\N
21669238	The fast detection of novel or deviant stimuli is a striking property of the auditory processing which reflects basic organizational principles of the auditory system and at the same time is of high practical significance. In human electrophysiology, deviance detection has been related to the occurrence of the mismatch negativity (MMN)--a component of the event-related potential (ERP) evoked 100 to 250 ms after the occurrence of a rare irregular sound. Recently, it has been shown in animal studies that a considerable portion of neurons in the auditory pathway exhibits a property called stimulus-specific adaptation enabling them to encode inter-sound relationships and to discharge at higher rates to rare changes in the acoustic stimulation. These neural responses have been linked to the deviant-evoked potential measured at the human scalp, but such responses occur at lower levels anatomically (e.g. the primary auditory cortex as well as the inferior colliculi) and are elicited earlier (20-30 ms after sound onset) in comparison to MMN. Further, they are not considerable enough in size to be interpreted as a direct neural correlate of the MMN. We review here a series of recent findings that provides a first step toward filling this gap between animal and human recordings by showing that comparably early modulations due to a sound's deviancy can be observed in humans, particularly in the middle-latency portion of the ERP within the first 50 ms after sound onset. The existence of those early indices of deviance detection preceding the well-studied MMN component strongly supports the idea that the encoding of regularities and the detection of violations is a basic principle of human auditory processing acting on multiple levels. This sustains the notion of a hierarchically organized novelty and deviance detection system in the human auditory system.	\N	\N
21680846	The attentional effects triggered by emotional stimuli in humans have been substantially investigated, but little is known about the impact of affective valence on the processing of meaning. Here, we used a cross-modal priming paradigm involving visually presented adjective-noun dyads and environmental sounds of controlled affective valence to test the contributions of conceptual relatedness and emotional congruence to priming. Participants undergoing event-related potential recording indicated whether target environmental sounds were related in meaning to adjective-noun dyads presented as primes. We tested spontaneous emotional priming by manipulating the congruence between the affective valence of the adjective in the prime and that of the sound. While the N400 was significantly reduced in amplitude by both conceptual relatedness and emotional congruence, there was no interaction between the 2 factors. The same pattern of results was found when participants judged the emotional congruence between environmental sounds and adjective-noun dyads. These results support the hypothesis that conceptual and emotional processes are functionally independent regardless of the specific cognitive focus of the comprehender.	\N	\N
21682421	Cross-channel envelope correlations are hypothesized to influence speech intelligibility, particularly in adverse conditions. Acoustic analyses suggest speech envelope correlations differ for syllabic and phonemic ranges of modulation frequency. The influence of cochlear filtering was examined here by predicting cross-channel envelope correlations in different speech modulation ranges for normal and impaired auditory-nerve (AN) responses. Neural cross-correlation coefficients quantified across-fiber envelope coding in syllabic (0-5 Hz), phonemic (5-64 Hz), and periodicity (64-300 Hz) modulation ranges. Spike trains were generated from a physiologically based AN model. Correlations were also computed using the model with selective hair-cell damage. Neural predictions revealed that envelope cross-correlation decreased with increased characteristic-frequency separation for all modulation ranges (with greater syllabic-envelope correlation than phonemic or periodicity). Syllabic envelope was highly correlated across many spectral channels, whereas phonemic and periodicity envelopes were correlated mainly between adjacent channels. Outer-hair-cell impairment increased the degree of cross-channel correlation for phonemic and periodicity ranges for speech in quiet and in noise, thereby reducing the number of independent neural information channels for envelope coding. In contrast, outer-hair-cell impairment was predicted to decrease cross-channel correlation for syllabic envelopes in noise, which may partially account for the reduced ability of hearing-impaired listeners to segregate speech in complex backgrounds.	\N	\N
21683500	Responses to threat occur via two known independent processing routes. We propose that early, reflexive processing is predominantly tuned to the detection of congruent combinations of facial cues that signal threat, whereas later, reflective processing is predominantly tuned to incongruent combinations of threat. To test this prediction, we examined responses to threat-gaze expression pairs (anger versus fear expression by direct versus averted gaze). We report on two functional magnetic resonance imaging (fMRI) studies, one employing prolonged presentations (2s) of threat-gaze pairs to allow for reflective processing (Study 1), and one employing severely restricted (33 ms), backward masked presentations of threat-gaze pairs to isolate reflexive neural responding (Study 2). Our findings offer initial support for the conclusion that early, reflexive responses to threat are predominantly tuned to congruent threat-gaze pairings, whereas later reflective responses are predominantly tuned to ambiguous threat-gaze pairings. These findings highlight a distinct dual function in threat perception.	\N	\N
21683995	Electrophysiological studies investigating similarities between music and language perception have relied exclusively on the signal averaging technique, which does not adequately represent oscillatory aspects of electrical brain activity that are relevant for higher cognition. The current study investigated the patterns of brain oscillations during simultaneous processing of music and language using visually presented sentences and auditorily presented chord sequences. Music-syntactically regular or irregular chord functions were presented in sync with syntactically or semantically correct or incorrect words. Irregular chord functions (presented simultaneously with a syntactically correct word) produced an early (150-250 ms) spectral power decrease over anterior frontal regions in the theta band (5-7 Hz) and a late (350-700 ms) power increase in both the delta and the theta band (2-7 Hz) over parietal regions. Syntactically incorrect words (presented simultaneously with a regular chord) elicited a similar late power increase in delta-theta band over parietal sites, but no early effect. Interestingly, the late effect was significantly diminished when the language-syntactic and music-syntactic irregularities occurred at the same time. Further, the presence of a semantic violation occurring simultaneously with regular chords produced a significant increase in later delta-theta power at posterior regions; this effect was marginally decreased when the identical semantic violation occurred simultaneously with a music syntactical violation. Altogether, these results show that low frequency oscillatory networks get activated during the syntactic processing of both music and language, and further, these networks may possibly be shared.	\N	\N
21689048	The purpose of this study was to develop a music quality rating test battery (MQRTB) and pilot test it by comparing appraisal ratings from cochlear implant (CI) recipients using the fine-structure processing (FSP) and high-definition continuous interleaved sampling (HDCIS) speech processing strategies. The development of the MQRTB involved three stages: (1) Selection of test items for the MQRTB; (2) Verification of its length and complexity with normally-hearing individuals; and (3) Pilot testing with CI recipients. Part 1 involved 65 adult listeners, Part 2 involved 10 normally-hearing adults, and Part 3 involved five adult MED-EL CI recipients. The MQRTB consisted of ten songs, with ratings made on scales assessing pleasantness, naturalness, richness, fullness, sharpness, and roughness. Results of the pilot study, which compared FSP and HDCIS for music, indicated that acclimatization to a strategy had a significant effect on ratings (p < 0.05). When acclimatized to FSP, the group rated FSP as closer to 'exactly as I want it to sound' than HDCIS (p < 0.05), and that HDCIS sounded significantly sharper and rougher than FSP. However when acclimatized to HDCIS, there were no significant differences between ratings. There was no effect of song familiarity or genre on ratings. Overall the results suggest that the use of FSP as the default strategy for MED-EL recipients would have a positive effect on music appreciation, and that the MQRTB is an effective tool for assessing music sound quality.	\N	\N
21692141	The aim of this functional magnetic resonance imaging (fMRI) study was to identify human brain areas that are sensitive to the direction of auditory motion. Such directional sensitivity was assessed in a hypothesis-free manner by analyzing fMRI response patterns across the entire brain volume using a spherical-searchlight approach. In addition, we assessed directional sensitivity in three predefined brain areas that have been associated with auditory motion perception in previous neuroimaging studies. These were the primary auditory cortex, the planum temporale and the visual motion complex (hMT/V5+). Our whole-brain analysis revealed that the direction of sound-source movement could be decoded from fMRI response patterns in the right auditory cortex and in a high-level visual area located in the right lateral occipital cortex. Our region-of-interest-based analysis showed that the decoding of the direction of auditory motion was most reliable with activation patterns of the left and right planum temporale. Auditory motion direction could not be decoded from activation patterns in hMT/V5+. These findings provide further evidence for the planum temporale playing a central role in supporting auditory motion perception. In addition, our findings suggest a cross-modal transfer of directional information to high-level visual cortex in healthy humans.	\N	\N
21701947	Phenomena in a variety of verbal tasks--for example, masked priming, lexical decision, and word naming--are typically explained in terms of similarity between word-forms. Despite the apparent commonalities between these sets of phenomena, the representations and similarity measures used to account for them are not often related. To show how this gap might be bridged, we build on the work of Hannagan, Dupoux, and Christophe, Cognitive Science 35:79-118, (2011) to explore several methods of representing visual word-forms using holographic reduced representations and to evaluate them on their ability to account for a wide range of effects in masked form priming, as well as data from lexical decision and word naming. A representation that assumes that word-internal letter groups are encoded relative to word-terminal letter groups is found to predict qualitative patterns in masked priming, as well as lexical decision and naming latencies. We then show how this representation can be integrated with the BEAGLE model of lexical semantics (Jones & Mewhort, Psychological Review 114:1-37, 2007) to enable the model to encompass a wider range of verbal tasks.	\N	\N
21707205	In reaction time research, there has been an increasing appreciation that response-initiation processes are sensitive to recent experience and, in particular, the difficulty of previous trials. From this perspective, the authors propose an explanation for a perplexing property of masked priming: Although primes are not consciously identified, facilitation of target processing by a related prime is magnified in a block containing a high proportion of related primes and a low proportion of unrelated primes relative to a block containing the opposite mix (Bodner & Masson, 2001). In the present study, this phenomenon is explored with a parity (even/odd) decision task in which a prime (e.g., 2) precedes a target that can be either congruent (e.g., 4) or incongruent (e.g., 3). It is shown that the effect of congruence proportion with masked primes cannot be explained in terms of the blockwise prime-target contingency. Specifically, with masked primes, there is no congruency disadvantage in a block containing a high proportion of incongruent primes, but there is a congruency advantage when the block contains an equal proportion of congruent and incongruent primes. In qualitative contrast, visible primes are sensitive to the blockwise prime-target contingency. The authors explain the relatedness proportion effect found with masked primes in terms of a model according to which response-initiation processes adapt to the statistical structure of the environment, specifically the difficulty of recent trials. This account is supported with an analysis at the level of individual trials using the linear mixed effects model.	\N	\N
21707266	We report a single case study of a synesthete (PS) who has complex visual experiences from sounds, including human voices. Different vowel sounds from different speakers and modified to be of different pitch (f0) were presented to PS and controls who were asked to draw an (abstract) visual image of the sound noting colors, sizes, and locations. PS tended to be more consistent over time than controls. For both PS and controls, the pitch of the vowel influenced the choice of luminance (higher pitch being lighter) and vertical position (higher pitch being higher in space). However, the gender of the speaker influenced the size of the 'image' independently of pitch (vowels from males being larger).	\N	\N
21710713	To investigate the contralateral suppressions of transient evoked otoacoustic emissions (TEOAE) in diabetes mellitus patients with normal hearing. The pure tone audiometry, acoustic immittance and TEOAE tests were performed in 30 diabetes mellitus patients with normal hearing and 30 healthy controls. The efferent system functions were evaluated by contralateral suppression of TEOAE. There were no significant differences of pure tone thresholds and amplitudes of TEOAE between the two groups. The contralateral suppressions of TEOAE in diabetes mellitus patients were significantly lower than that in controls (P<0.05 at 2000 and 4000 Hz respectively). The nerve functions of central nerve system can be damaged in diabetes mellitus patients with normal hearing.	\N	\N
21714708	We investigated if linguistic complexity contributes to the variation of the speech reception threshold in noise (SRTN) and thus should be employed as an additional design criterion in sentence tests used for audiometry. Three test lists were established with sentences from the Göttingen sentence test ( Kollmeier & Wesselkamp, 1997 ). One list contained linguistically simple sentences, the other two lists contained sentences with two types of linguistic complexity. For each listener the SRTN was determined for each list. Younger and older listeners with normal hearing and older listeners with hearing impairment were tested. Younger listeners with normal hearing showed significantly worse SRTNs on the complex lists than on the simple list. This difference could not be found for either of the older groups. The effect of linguistic complexity on speech recognition seems to depend on age and/or hearing status. Hence, pending further research, linguistic complexity seems less relevant as a sentence test design criterion for clinical-audiological purposes, but we argue that a test with larger variation in linguistic complexity across sentences might show a relation between linguistic complexity and speech recognition even in a clinical population.	\N	\N
21719027	Web based speech training for dysarthric speakers, such as E-learning based Speech Therapy (EST), puts considerable demands on auditory discrimination abilities. To discuss the development and the evaluation of an auditory discrimination test (ADT) for the assessment of auditory speech discrimination skills in Dutch adult dysarthric speakers as a prelude to EST. Five ADT subtests were developed, each addressing a vital speech dimension in speech therapy: articulation (segmental elements), intensity, overall pitch, speech rate and intonation. A healthy control group of 36 participants performed a 'same-different task' in each subtest. ADT items yielding scores of at least 80% but below 100% correctly responding healthy controls were considered sensitive to diminished auditory discrimination. Subsequently, the ADT was carried out by 14 neurological patients with dysarthric speech and 14 matched healthy controls. Score percentages, sensitivity indices and reaction times (ms) on only sensitive items were compared. The majority of the ADT items met the 'minimal 80% to below 100% criterion' in the healthy control group. The neurological participants performed lower on all outcome measures across all subtests than the healthy controls, although not all of these differences achieved statistical significance. The results of the healthy control group show that the majority of the ADT items meet our criterion for sensitivity to diminished auditory discrimination. The poorer performance of dysarthric patients across all subtests supports the sensitivity of the ADT. However, further research involving larger and more homogeneous groups of neurological patients is required. Readers will be encouraged to (1) identify potential factors that may hinder web based speech training and (2) estimate the value of assessing auditory discrimination skills as a vital condition for (web based) speech training in dysarthric patients.	\N	\N
21723130	Human voices play a fundamental role in social communication, and areas of the adult "social brain" show specialization for processing voices and their emotional content (superior temporal sulcus, inferior prefrontal cortex, premotor cortical regions, amygdala, and insula). However, it is unclear when this specialization develops. Functional magnetic resonance (fMRI) studies suggest that the infant temporal cortex does not differentiate speech from music or backward speech, but a prior study with functional near-infrared spectroscopy revealed preferential activation for human voices in 7-month-olds, in a more posterior location of the temporal cortex than in adults. However, the brain networks involved in processing nonspeech human vocalizations in early development are still unknown. To address this issue, in the present fMRI study, 3- to 7-month-olds were presented with adult nonspeech vocalizations (emotionally neutral, emotionally positive, and emotionally negative) and nonvocal environmental sounds. Infants displayed significant differential activation in the anterior portion of the temporal cortex, similarly to adults. Moreover, sad vocalizations modulated the activity of brain regions involved in processing affective stimuli such as the orbitofrontal cortex and insula. These results suggest remarkably early functional specialization for processing human voice and negative emotions.	\N	\N
21723376	Older human listeners demonstrate perceptual deficits in temporal processing even when audibility has been controlled. These age-related auditory deficits in temporal processing are thought to originate in the central auditory pathway. Precise temporal processing is necessary to detect and discriminate auditory cues such as modulation frequency, modulation depth and envelope shape which are critical for perception of speech and environmental sounds. This study aims to further understanding of temporal processing in aging using non-invasive electrophysiological measurements. Amplitude modulation following responses (AMFRs) and frequency modulation following responses (FMFRs) were recorded from aged (92-95-weeks old) and young (9-12-weeks old) Fischer-344 (F-344) rats for sinusoidally amplitude modulated (sAM) tones, sinusoidally frequency modulated (sFM) tones and ramped and damped amplitude modulation (AM) stimuli which differ in their envelope shapes. The modulation depth for the sAM and sFM stimuli and envelope shape for the ramped and damped stimuli were systematically varied. There was a monotonic decrease in AMFR and FMFR amplitudes with decreases in modulation depth across age for sAM and sFM stimuli. There was no significant difference between the response amplitudes of the young and aged animals for the largest modulation depths. However, a reduction in modulation depth resulted in a significant decrease in the response amplitudes and higher modulation detection thresholds for sAM and sFM stimuli with age. The aged animals showed significantly lower response amplitudes for ramped stimuli but not for damped stimuli. Cross correlating the responses with the ramped, symmetric, or damped stimulus envelopes revealed a decreased fidelity in encoding envelope shapes with age. These results indicate that age related temporal processing deficits become apparent only with reduced modulation depths or when discriminating envelope shapes. This has implications for psychophysical or diagnostic testing as well as for constraining potential cellular and network mechanisms responsible for these deficits.	\N	\N
21724244	In a neuroimaging study focusing on young bilinguals, we explored the brains of bilingual and monolingual babies across two age groups (younger 4-6 months, older 10-12 months), using fNIRS in a new event-related design, as babies processed linguistic phonetic (Native English, Non-Native Hindi) and non-linguistic Tone stimuli. We found that phonetic processing in bilingual and monolingual babies is accomplished with the same language-specific brain areas classically observed in adults, including the left superior temporal gyrus (associated with phonetic processing) and the left inferior frontal cortex (associated with the search and retrieval of information about meanings, and syntactic and phonological patterning), with intriguing developmental timing differences: left superior temporal gyrus activation was observed early and remained stably active over time, while left inferior frontal cortex showed greater increase in neural activation in older babies notably at the precise age when babies' enter the universal first-word milestone, thus revealing a first-time focal brain correlate that may mediate a universal behavioral milestone in early human language acquisition. A difference was observed in the older bilingual babies' resilient neural and behavioral sensitivity to Non-Native phonetic contrasts at a time when monolingual babies can no longer make such discriminations. We advance the "Perceptual Wedge Hypothesis" as one possible explanation for how exposure to greater than one language may alter neural and language processing in ways that we suggest are advantageous to language users. The brains of bilinguals and multilinguals may provide the most powerful window into the full neural "extent and variability" that our human species' language processing brain areas could potentially achieve.	\N	\N
21728463	Gestalt phenomena are often so powerful that mere demonstrations can confirm their existence, but Gestalts have proven hard to define and measure. Here we outline a theory of basic Gestalts (TBG) that defines Gestalts as emergent features (EFs). The logic relies on discovering wholes that are more discriminable than are the parts from which they are built. These wholes contain EFs that can act as basic features in human vision. As context is added to a visual stimulus, a hierarchy of EFs appears. Starting with a single dot and adding a second yields the first two potential EFs: the proximity (distance) and orientation (angle) between the two dots. A third dot introduces two more potential EFs: symmetry and linearity; a fourth dot produces surroundedness. This hierarchy may extend to collinearity, parallelism, closure, and more. We use the magnitude of Configural Superiority Effects to measure the salience of EFs on a common scale, potentially letting us compare the strengths of various grouping principles. TBG appears promising, with our initial experiments establishing and quantifying at least three basic EFs in human vision.	\N	\N
21730860	Auditory temporal processing frequently appears more affected in old subjects than would be predicted by the degree of peripheral hearing loss, pointing to an age-dependent central processing deficit. In parallel, an age-dependent decline of inhibitory function has been demonstrated in the auditory pathway, suggesting a causal relationship between temporal processing and inhibition. Gabapentin has been specifically synthesized as a potential gamma-amino-butyric-acid (GABA) mimetic with the capability to cross the blood-brain barrier. Gabapentin treatment ameliorated tinnitus in a rat model and improved tinnitus annoyance in humans with acoustic trauma. Consequently, the present study evaluated the effect of gabapentin on auditory temporal processing in the gerbil model. Psychometric functions were collected for different test paradigms. (A) "Gap detection": The detection of a gap in the middle of a 800 msec broadband noise pulse was determined either at 15 or at 30 dB SL. (B) "Forward masking": The detection of a 20 msec probe stimulus following 2.5 msec after a 400 msec 40 dB SPL masker was determined with masker and probe frequency at 2.85 kHz. The effect of gabapentin was evaluated by collecting gap detection and forward masking functions before, during, and after treating gerbils with gabapentin doses of 115 or 350 mg/kg/day administered via drinking water. Data under different experimental conditions were collected for groups of 3 to 5 young (<2 years) and 6 to 10 old (>2 years) gerbils. Two-way analyses of variance for the factors age groups and treatment groups with subsequent pairwise comparisons for significant effects were used for the statistical evaluation of the data. For gap detection, mean thresholds were significantly increased in the group of old as compared with the young gerbils at 30 dB SL (young 2.0 msec; old 3.2 msec) and at 15 dB SL (young 2.9 msec; old 9.1 msec). Gabapentin had no significant effect on gap detection, and there was no significant interaction between age group and gabapentin treatment. Mean thresholds in the forward masking paradigm were significantly elevated in old (45.5 dB SPL) as compared with young (35.0 dB SPL) gerbils. Overall, gabapentin had no significant effect on masked thresholds; however, there was a significant interaction between treatment and age. Subsequent pairwise comparisons revealed no significant effect on masked thresholds in old gerbils but showed significantly elevated thresholds of young gerbils during 350 mg/kg gabapentin (38.3 dB SPL) compared with thresholds obtained in young gerbils before (32.3 dB SPL) and after (33.5 dB SPL) treatment. Gabapentin did not exert a therapeutic effect on impaired gap detection and forward masking in old gerbils. The lack of an effect of gabapentin on impaired auditory temporal processing in old gerbils and the finding of elevated masked thresholds in young gerbils can be reconciled with reports of only moderate GABAergic effects compared with other drugs (e.g., comparing elevation of GABA levels in the brain by gabapentin and vigabatrin) and effects due to binding of gabapentin to alpha-2-delta units of voltage-gated calcium channels.	\N	\N
21732223	Increasing the target-field luminance aids detection for a simultaneously presented black target disc and a black masking annulus. At an intermediate interval separating the onset of the target from the mask, increasing the target-field luminance reduces target detection. This decrease in performance occurs with both temporal and spatial forced choice tasks. With a spatial forced choice, an observer's performance can fall below chance. We associate below-chance performance with a brightness reversal of the black target disc, such that the target disc appears brighter than its surround. The occurrence of brightness reversals follows from our model of the Broca-Sulzer effect, and nonmonotone masking functions result from a generalization of luminance summation.	\N	\N
21736456	The aim of this study was to examine the influence of musical expertise in 9-year-old children on passive (as reflected by MMN) and active (as reflected by discrimination accuracy) processing of speech sounds. Musician and nonmusician children were presented with a sequence of syllables that included standards and deviants in vowel frequency, vowel duration, and VOT. Both the passive and the active processing of duration and VOT deviants were enhanced in musician compared with nonmusician children. Moreover, although no effect was found on the passive processing of frequency, active frequency discrimination was enhanced in musician children. These findings are discussed in terms of common processing of acoustic features in music and speech and of positive transfer of training from music to the more abstract phonological representations of speech units (syllables).	\N	\N
21736927	We used a new virtual program in two experiments to prepare subjects to perform the Morris water task (www.nesplora.com). The subjects were Psychology students; they were trained to locate a safe platform amidst the presence of four pinpoint landmarks spaced around the edge of the pool (i.e., two landmarks relatively near the platform and two landmarks relatively distant away from it). At the end of the training phase, we administered one test trial without the platform and recorded the amount of time that the students had spent in the platform quadrant. In Experiment 1, we conducted the test trial in the presence of one or two of the distant landmarks. When only one landmark was present during testing, performance fell to chance. However, the men outperformed the women when the two distant landmarks were both present. Experiment 2 replicated the previous results and extended it by showing that no sex differences exist when the searching process is based on the near landmarks. Both the men and the women had similarly good performances when the landmarks were present both individually and together. When present together, an addition effect was found. Far landmark tests favor configural learning processes, whereas near landmark tests favor elemental learning. Our findings suggest that other factors in addition to the use of directional cues can underlie the sex differences in the spatial learning process. Thus, we expand upon previous research in the field.	\N	\N
21752361	A controversial issue in the cognitive neuroscience of language is the question whether independent lexical representations need to be included in cognitive models. Recent models claim to account for the available data without including phonological or orthographic lexicons. These models base their lexical decision ("Is it a word or not?") either on familiarity of the input string or alternatively, on semantic information. These two alternatives were evaluated in a series of experiments with an individual suffering from word-meaning deafness. This is a rare disorder of auditory word comprehension which affects mapping of a word's phonology to its meaning. The participant, BB, was unaffected by the 'word-likeness' of nonwords with comparable accuracy for plausible and abstruse nonwords. She was further able to make lexical decisions despite her severe impairment in comprehending the word's meaning. Lexical and semantic processing were assessed on an item-specific basis providing a methodological advancement over previous studies. The comprehension tasks involved word-picture matching as well as definition tasks. The results suggest that BB's lexical decisions are based neither on familiarity of the input string nor on semantic information, which was largely unavailable. The only alternative are lexical representations on which she could base her decisions.	\N	\N
21753000	Feeling the beat and meter is fundamental to the experience of music. However, how these periodicities are represented in the brain remains largely unknown. Here, we test whether this function emerges from the entrainment of neurons resonating to the beat and meter. We recorded the electroencephalogram while participants listened to a musical beat and imagined a binary or a ternary meter on this beat (i.e., a march or a waltz). We found that the beat elicits a sustained periodic EEG response tuned to the beat frequency. Most importantly, we found that meter imagery elicits an additional frequency tuned to the corresponding metric interpretation of this beat. These results provide compelling evidence that neural entrainment to beat and meter can be captured directly in the electroencephalogram. More generally, our results suggest that music constitutes a unique context to explore entrainment phenomena in dynamic cognitive processing at the level of neural networks.	\N	\N
21756455	Cochlear implant (CI) devices are the choice of treatment for individuals with severe to profound hearing loss. The CI devices provide the opportunity for children who are deaf to perceive sound by electrical stimulation of the auditory nerve, with the goal of optimizing oral communication. A natural benefit of acquiring hearing using CIs is the ability to hear, and perhaps enjoy, music. Music is a non-verbal auditory stimulus and a powerful tool for transmitting emotion. Identifying emotional cues is an important part of normal social development and communication and thus music may play an important role in establishing these skills during development. To date, it is not known whether children who use cochlear implants to hear can identify the emotional content carried in music. Our objective in the present study was to determine whether children who have been deaf from infancy and are experienced CI users have acquired the ability to identify emotion in musical phrases. Study participants were 18 CI users (ages 7-13 years) who received right unilateral CIs (mean age at CI activation of 2.9 years) and 18 age-and gender-matched controls. Participants were asked to judge 32 brief musical excerpts as happy or sad by pointing to simple graphics of a smiling or frowning face. Children using CIs were able to correctly distinguish happy versus sad music well above chance levels, but performed more poorly on this task than their peers with typical hearing. Age at CI activation and time since CI activation were both uncorrelated with outcome measures. Children with CIs show the ability to perceive emotion in music but do so less accurately than typically hearing peers.	\N	\N
21756504	To describe the rate of occurrence of unsuspected decrease in sensitivity of the sound processor microphone and to evaluate its effect on the patient's audiological performance in terms of reduction in speech recognition scores. Speech processor microphones were tested by connecting the speech processor acoustic monitor circuit to a hearing aid analyzer. The response curves were compared with those obtained from fully working microphones. During a 6-month investigation period, microphone response curves were measured from a group of cochlear implant recipients who had not reported any problems. Despite the absence of any subjective problem, some microphones were found to show a loss of sensitivity. Their users, aged between 4 and 67 years, were tested both with the defective and a working microphone in order to calculate the correlation between the degree of microphone failure and the decline in audiological performance. To quantify the effect of microphone failure, patients' speech recognition skills were measured by live voice connected discourse tracking series administered in different conditions and by recorded sentences lists. A total of 120 apparently fully functioning sound processors were tested in the investigation: 33 (27.5%) were affected by a subjectively unreported sensitivity decrease. Speech-tracking scores correlated significantly with the loss of microphone sensitivity in all test conditions (r = 0.69-0.77, P < 0.05). A high degree of correlation was also found for speech audiometry tests (r = 0.70-0.73, P < 0.05). Microphone sensitivity loss affected speech recognition skills, especially without lip reading and in the presence of background noise. The results indicate that any reduction in sound processor microphone sensitivity causes a degree of hearing decline that negatively affects the cochlear recipient's clinical performance. Microphone faults are often unreported events, and their occurrence rate is underestimated. To establish that the microphone is providing correct input to the speech processor a standard control procedure, including technical and clinical checks, is needed in clinical practice.	\N	\N
21756841	The overall goal of the current study was to examine the relationships among uncompensated admittance (Ya) at ambient pressure extracted from tympanograms, energy reflectance (ER) measures at ambient pressure from wideband acoustic transfer functions (WATF), and distortion product otoacoustic emissions (DPOAEs). If WATF measures of Ya are comparable to tympanometric measures of Ya at ambient pressure, it would be further evidence that the two systems provide comparable information at ambient pressure. Such a relationship could be used as a cross-check or validation for WATF measures and support the use of WATFs in lieu of tympanograms in some applications. Finally, if WATF measures of Ya and/or ER at DPOAE stimulus frequencies can account for some of the variability observed in DPOAE levels and/or signal-to-noise ratios (SNRs) in ears with normal hearing, the relationships could be used to improve hearing screening procedures. The hypotheses were as follows: (1) measures of Ya at ambient pressure are significantly correlated as measured with tympanometric and WATF procedures and (2) measures of Ya and ER at DPOAE stimulus frequencies are significantly correlated with DPOAE level and SNR. Repeated measures in human adults. Forty ears of 20 adults with normal hearing and middle ear function were included in the final sample. Tympanograms were obtained using probe frequencies of 226, 678, and 1000 Hz; WATFs were obtained using a click probe, and DPOAEs were elicited with f2's of 1000, 2000, and 4000 Hz. A repeated measures analysis of variance (RM-ANOVA) was completed to identify significant differences between ears and among probe frequencies for Ya measured at ambient pressure from the Tympstar and for Ya measured at the three closest frequencies on the WATFs. Lines were fit to the comparison of Ya from the Tympstar and WATF, and percent variance accounted for (r2) was calculated. Ya and ER were extracted at all stimulus frequencies that were used to elicit DPOAEs and were compared to DPOAE levels and SNRs. RM-ANOVAs were completed to identify any significant differences in DPOAE level and SNR between ears and among f2 conditions. Lines were fit to the comparison of Ya and ER measures at f1 and f2 with the DPOAE levels and SNRs. The relationship between behavioral air conduction threshold at each f2 and DPOAE level (and SNR) was examined with regression analysis. Ya was significantly correlated between the tympanometric and WATF measures at all three probe-tone frequencies. Ya and ER at f1 and f2 were significantly correlated with DPOAE level for f2 = 4000 Hz. The implications are as follows: (1) WATFs, which can be obtained with the same probe microphone system as DPOAEs, could be used as a supplement to tympanometry in a diagnostic test battery, and the relationship between Ya measured on the two systems could be used for verification, and (2) Ya and ER measures from WATFs at both DPOAE stimulus frequencies account for some of the variability observed in DPOAE levels at f2 = 4000 Hz in normal ears.	\N	\N
21760512	Good test-retest reliability of high frequency (≥ 8 kHz) pure-tone audiometry (HFPTA) is essential to detect significant changes in hearing threshold caused by ototoxicity. While the test-retest reliability of HFPTA in adults has been extensively studied, such investigations in children are scant. This study aimed to evaluate the test-retest reliability of the HFPTA in normal-hearing children with particular reference to the criteria for ototoxicity. Participants were 125 children aged between 4 and 13 yr, with normal hearing in the 0.25 to 4 kHz range and normal tympanometric findings. The participants were divided into three age groups, 4 to 6 yr (16M; 16F); 7 to 9 yr (22M; 30F); and 10 to 13 yr (24M; 17F), for investigating possible age effects in the test-retest reliability of HFPTA. The instrumentation for the HFPTA procedure was an Interacoustics AC40 audiometer with Koss R/80 high-frequency headphones, calibrated to meet Australian standards. Hearing thresholds at 8, 9, 10, 11.2, 12.5, 14, and 16 kHz were measured in a sound-treated chamber using a modified Hughson-Westlake procedure with a 5 dB step size. Testing began with an ear and test frequency selected at random; the subsequent test frequencies were randomly selected. After acquisition of hearing threshold data at all frequencies, the other ear was tested using the same procedure. After the first HFPTA test, the headphones were removed and carefully replaced. A second HFPTA test was performed with the ear order reversed. The order of testing the ear for the next participant was reversed. Good test-retest reliability of HFPTA was achieved with no significant difference in mean HFPTA thresholds across test and retest conditions for all age groups. An age effect in the test-retest reliability of HFPTA was evident with the 4- to 6-yr-old, 7- to 9-yr-old, and 10- to 13-yr-old children demonstrating normal variability of thresholds (within ±10 dB) in 89.9%, 93.0%, and 97% of ears tested, respectively. When the variability of test-retest thresholds was assessed at each frequency, the 4 to 6 yr group showed significantly lower percentage of normal variability at 14 kHz. In identifying significant deterioration of hearing thresholds across test-retest conditions in relation to the ASHA (1994) ototoxicity criteria, the three age groups (youngest to oldest) demonstrated false-positive rates of 24.6%, 11%, and 7.6%, respectively. : Overall, this study demonstrated high test-retest reliability of HFPTA in all but the 4 to 6 yr group. With a false-positive rate of 24.6% for ototoxicity for the youngest group, it is recommended that the HFPTA should not be used alone in assessing the possibility of a genuine threshold shift for this age group. If possible, the HFPTA should be supplemented with an objective test of auditory function to confirm the diagnosis. For children aged 7 yr or older, the HFPTA test is promising as a useful tool to identify hearing impairment in the extended high-frequency range (>8 kHz). However, interpretation of HFPTA findings in serial testing for monitoring hearing in a child should be made with due attention being given to the frequency of the stimulus, age of the child, and the associated nonzero false-positive rates.	\N	\N
21763342	During the last decades music neuroscience has become a rapidly growing field within the area of neuroscience. Music is particularly well suited for studying neuronal plasticity in the human brain because musical training is more complex and multimodal than most other daily life activities, and because prospective and professional musicians usually pursue the training with high and long-lasting commitment. Therefore, music has increasingly been used as a tool for the investigation of human cognition and its underlying brain mechanisms. Music relates to many brain functions like perception, action, cognition, emotion, learning and memory and therefore music is an ideal tool to investigate how the human brain is working and how different brain functions interact. Novel findings have been obtained in the field of induced cortical plasticity by musical training. The positive effects, which music in its various forms has in the healthy human brain are not only important in the framework of basic neuroscience, but they also will strongly affect the practices in neuro-rehabilitation.	\N	\N
21769535	Previous work has demonstrated that the ability to keep track of moving objects is improved when the objects have unique visual features, such as color or shape. In the present study, we investigated how orientation information is used during the tracking of objects. Orientation is an interesting feature to explore in moving objects because it is directional and is often informative of the direction of motion. Most objects move forward, in the direction they are oriented. In the present experiments, participants tracked a subset of moving isosceles triangles whose orientations were constant, related, or unrelated to the direction of motion. In the standard multiple object tracking (MOT) task, tracking performance improved when orientations were unique and remained constant, but not when orientation and direction of motion were aligned. In the target recovery task, in which MOT was interrupted by a brief blanking of the display, performance did improve when orientation and direction were aligned. In the final experiment, results showed that orientation was not used before the blank to predict future target locations, but was instead used after the blank. We concluded that people use orientation to compare a stored representation to target position for recovery of lost targets.	\N	\N
21771217	There is strong evidence that bilinguals have a deficit in speech perception for their second language compared with monolingual speakers under unfavourable listening conditions (e.g., noise or reverberation), despite performing similarly to monolingual speakers under quiet conditions. This deficit persists for speakers highly proficient in their second language and is greater in those who learned the language later in life. These findings have important educational implications because the number of multilingual children is increasing worldwide, and many of these children are being taught in their non-native language under poor classroom acoustic conditions. The performance of monolingual, bilingual and trilingual speakers on an English speech perception task was examined in both quiet and noisy conditions. Trilingual performance was compared with that of monolingual and bilingual speakers. Monolingual speakers of English and early bilingual and trilingual speakers (i.e., acquired English as a second/third language before the age of 6 years) were recruited. Their fluency in English was tested by interview and by a questionnaire assessing their knowledge and use of the language. Audiological evaluation confirmed normal hearing in all participants. English speech perception was tested in quiet and in different levels of noise (50, 55, 60, 65 and 70 dB SPL) using the Speech Perception in Noise (SPIN) Test. Bilingual and trilingual listeners performed similarly to monolingual listeners in quiet conditions, but their performance declined more rapidly in noise and was significantly poorer at 65 and 70 dB SPL. Trilingual listeners performed less well than bilinguals at these noise levels, but not significantly so. A subgroup of five bilingual speakers who learned Arabic and English simultaneously since birth were poorer at higher levels of noise than monolinguals, but not significantly so. The results replicate previous findings of poorer speech perception in noise with bilingual speakers compared with monolinguals and extend the findings to trilingual speakers.	\N	\N
21786870	The ability to obtain reliable phonetic information from a talker's face during speech perception is an important skill. However, lip-reading abilities vary considerably across individuals. There is currently a lack of normative data on lip-reading abilities in young normal-hearing listeners. This letter describes results obtained from a visual-only sentence recognition experiment using CUNY sentences and provides the mean number of words correct and the standard deviation for different sentence lengths. Additionally, the method for calculating T-scores is provided to facilitate the conversion between raw and standardized scores. This metric can be utilized by clinicians and researchers in lip-reading studies. This statistic provides a useful benchmark for determining whether an individual's lip-reading score falls within the normal range, or whether it is above or below this range.	\N	\N
21786905	Spectral ripple discrimination thresholds were measured in 15 cochlear-implant users with broadband (350-5600 Hz) and octave-band noise stimuli. The results were compared with spatial tuning curve (STC) bandwidths previously obtained from the same subjects. Spatial tuning curve bandwidths did not correlate significantly with broadband spectral ripple discrimination thresholds but did correlate significantly with ripple discrimination thresholds when the rippled noise was confined to an octave-wide passband, centered on the STC's probe electrode frequency allocation. Ripple discrimination thresholds were also measured for octave-band stimuli in four contiguous octaves, with center frequencies from 500 Hz to 4000 Hz. Substantial variations in thresholds with center frequency were found in individuals, but no general trends of increasing or decreasing resolution from apex to base were observed in the pooled data. Neither ripple nor STC measures correlated consistently with speech measures in noise and quiet in the sample of subjects in this study. Overall, the results suggest that spectral ripple discrimination measures provide a reasonable measure of spectral resolution that correlates well with more direct, but more time-consuming, measures of spectral resolution, but that such measures do not always provide a clear and robust predictor of performance in speech perception tasks.	\N	\N
21790494	Three experiments tested how the physical format and information content of forward and backward masks affected the extent of visual pattern masking. This involved using different types of forward and backward masks with target discrimination measured by percentage correct in the first experiment (with a fixed target duration) and by an adaptive threshold procedure in the last two. The rationale behind the manipulation of the content of the masks stemmed from masking theories emphasizing attentional and/or conceptual factors rather than visual ones. Experiment 1 used word masks and showed that masking was reduced (a masking reduction effect) when the forward and backward masks were the same word (although in different case) compared to when the masks were different words. Experiment 2 tested the extent to which a reduction in masking might occur due to the physical similarity between the forward and backward masks by comparing the effect of the same content of the masks in the same versus different case. The result showed a significant reduction in masking for same content masks but no significant effect of case. The last experiment examined whether the reduction in masking effect would be observed with nonword masks--that is, having no high-level representation. No reduction in masking was found from same compared to different nonword masks (Experiment 3). These results support the view that the conscious perception of a rapidly displayed target stimulus is in part determined by high-level perceptual/cognitive factors concerned with masking stimulus grouping and attention.	\N	\N
21796943	The spray drying technique was used to obtain the roxithromycin containing microcapsules with high taste masking efficiency. Eudragit L30D-55 was chosen as a barrier coating. The taste was evaluated by an electronic tongue, and taste-masking effect in water lasted at least several dozen hours.	\N	\N
21799207	We investigated training-related improvements in listening in noise and the biological mechanisms mediating these improvements. Training-related malleability was examined using a program that incorporates cognitively based listening exercises to improve speech-in-noise perception. Before and after training, auditory brainstem responses to a speech syllable were recorded in quiet and multitalker noise from adults who ranged in their speech-in-noise perceptual ability. Controls did not undergo training but were tested at intervals equivalent to the trained subjects. Trained subjects exhibited significant improvements in speech-in-noise perception that were retained 6 months later. Subcortical responses in noise demonstrated training-related enhancements in the encoding of pitch-related cues (the fundamental frequency and the second harmonic), particularly for the time-varying portion of the syllable that is most vulnerable to perceptual disruption (the formant transition region). Subjects with the largest strength of pitch encoding at pretest showed the greatest perceptual improvement. Controls exhibited neither neurophysiological nor perceptual changes. We provide the first demonstration that short-term training can improve the neural representation of cues important for speech-in-noise perception. These results implicate and delineate biological mechanisms contributing to learning success, and they provide a conceptual advance to our understanding of the kind of training experiences that can influence sensory processing in adulthood.	\N	\N
21801242	We investigated the effect of long-term musical training on the time course of development of neuronal representations within the auditory cortex by means of magnetoencephalography. In musicians but not in nonmusicians, pre-attentive encoding of a complex regularity within a tone sequence was evident by a constant increase of the pattern mismatch negativity within < 10 min. The group difference was more pronounced in the left hemisphere, indicating stronger plastic changes in its structures supporting temporal analysis and sound pattern encoding. The results suggest an effect of long-term musical training on short-term auditory learning processes. This has implications not only for cognitive neuroscience in showing how short-term and long-term neuronal plasticity can interact within the auditory cortex, but also for educational and clinical applications of implicit auditory learning where beneficial effects of (musical) experience might be exploited.	\N	\N
21805200	It has recently been shown that spatially uninformative sounds can cause a visual stimulus to pop out from an array of similar distractor stimuli when that sound is presented in temporal proximity to a feature change in the visual stimulus. Until now, this effect has predominantly been demonstrated by using stationary stimuli. Here, we extended these results by showing that auditory stimuli can also improve the sensitivity of visual motion change detection. To accomplish this, we presented moving visual stimuli (small dots) on a computer screen. At a random moment during a trial, one of these stimuli could abruptly move in an orthogonal direction. Participants' task was to indicate whether such an abrupt motion change occurred or not by making a corresponding button press. If a sound (a short 1,000 Hz tone pip) co-occurred with the abrupt motion change, participants were able to detect this motion change more frequently than when the sound was not present. Using measures derived from signal detection theory, we were able to demonstrate that the effect on accuracy was due to increased sensitivity rather than to changes in response bias.	\N	\N
21817932	The transmission of fine structure information to cochlear implant users is an expanding area of research. Previous studies comparing the fine structure processing (FSP) speech coding strategy to the envelope-based continuous interleaved sampling (CIS) strategy indicated improved speech perception when using the fine structure strategy. Those investigations were performed with an extended frequency spectrum in the low frequencies together with the fine structure strategy. The current study addresses the question whether these improvements are due to the presentation of fine structure per se or rather the extended frequency spectrum. Hence, this cross over study compares the two strategies using an identical frequency spectrum. Randomized crossover study. 31 patients were randomly assigned to two groups. One group was fitted with a CIS map for 4 weeks, tested and subsequently fitted with a FSP map for 4 weeks. The other group followed the same pattern in reverse. Test material consisted of sentence tests in noise, monosyllables in quiet and melody recognition. No statistical significance was noted between the different speech coding strategies at an identical frequency spectrum. This study shows that there is no difference in speech perception with FSP compared to CIS at an extended frequency spectrum. Therefore, the extended frequency spectrum in the low frequencies might explain a benefit of FSP observed in previous studies.	\N	\N
21818631	When a single brief flash is accompanied by two auditory beeps, participants often report perceiving two flashes. The present experiment examined whether the perception of illusory redundant flashes can result in faster responses as compared to the perception of a single flash, because previous research has shown such a redundancy gain for physical stimuli. To this end, participants were asked to respond as rapidly as possible to the onset of any flash. Following their response, they additionally indicated whether they perceived a single flash or a double flash. Most importantly, we observed significant shorter reaction times in response to redundant flashes, irrespective of whether they were physically presented or illusorily perceived. Taken together, our results suggest that an illusory percept can affect simple reaction time in much the same manner as the corresponding physical stimulation.	\N	\N
21826003	A number of clinical measures of directivity, including the front-to-back ratio (FBR) and front-to-side ratio (FSR), have been suggested to audiologists to monitor the functionality of hearing aids with directional microphones. These suggestions, however, are based on the assumption that directivity measured clinically changes monotonically when compared with changes measured using the directivity index (DI) and perceptual directional benefit. The objective of the present study was to empirically examine this assumption. In addition, the reliability of the clinical directivity measure was estimated to establish a referral threshold for defective directional microphone hearing aids. The directivity of the directional microphones of two behind-the-ear hearing aids was systematically degraded by plugging the microphone ports. The directivity was measured using four clinical measures: the FBR and FSR performed in the test chamber of a hearing aid analyzer and in sound field. Each measure was repeated four times in each directivity-degraded condition. The degraded directivity was also assessed using the DI measure in an anechoic chamber. The perceptual directional benefit in each directivity-degraded condition was obtained by testing 10 hearing-impaired adults in a sound field with diffuse noise using the Hearing in Noise Test (HINT). The results of the DI and HINT measures showed strong correlation between the two FSRs (test chamber and sound field), while the two FBRs showed no correlation. The directivity generated by the FBRs could remain unchanged even when the directional microphone had lost more than 50% of its directivity. The results further indicated that the measures performed in the sound field were more reliable than those performed in the test chamber. Based on the results of the reliability measures, a 30% change in directivity was suggested as the referral threshold signifying defective directional systems. Because the FSR predicts the DI and HINT measurements more accurately than does the FBR, it is suggested that clinicians use the FSR to monitor hearing aid directivity. By using the FSR measure and informed by the suggested referral threshold, clinicians would be able to correctly identify defective directional microphone hearing aids at an early stage, rather than at a point when the directivity has been diminished completely or even reversed.	\N	\N
21826552	Strong cross-modal interactions exist between visual and auditory processing. The relative contributions of perceptual versus decision-related processes to such interactions are only beginning to be understood. We used methodological and statistical approaches to control for potential decision-related contributions such as response interference, decisional criterion shift, and strategy selection. Participants were presented with rising-, falling-, and constant-amplitude sounds and were asked to detect change (increase or decrease) in sound amplitude while ignoring an irrelevant visual cue of a disk that grew, shrank, or stayed constant in size. Across two experiments, testing context was manipulated by varying the grouping of visual cues during testing, and cross-modal congruency showed independent perceptual and decision-related effects. Whereas a change in testing context greatly affected criterion shifts, cross-modal effects on perceptual sensitivity remained relatively consistent. In general, participants were more sensitive to increases in sound amplitude and less sensitive to sounds paired with dynamic visual cues. As compared with incongruent visual cues, congruent cues enhanced detection of amplitude decreases, but not increases. These findings suggest that the relative contributions of perceptual and decisional processing and the impacts of these processes on cross-modal interactions can vary significantly depending on asymmetries in within-modal processing, as well as consistencies in cross-modal dynamics.	\N	\N
21833562	A bone-anchored hearing aid (Baha) is used in patients with single-sided sensorineural deafness (SSD) to overcome the head shadow effect. Of all the patients with SSD, treated at our hospital, 196 patients used a Baha on trial between November 2001 and April 2010. The objective of this study is to evaluate what factors determine the decision of a SSD patient whether or not to opt for a Baha device following a Baha trial period. 196 patients with SSD were enrolled for a trial period of 2 weeks at the Antwerp University Hospital, a tertiary referral centre. 93% of these patients suffered from an acquired hearing loss. 44% of all the patients (87/196) chose to wear a Baha device after the trail period, either on an abutment or on a headband. The collected data were analysed to determine correlations between the decision of a patient following a Baha trial period on the one hand, and Fletcher Index ipsi- and contralaterally, bone conduction hearing thresholds at the better hearing ear, aetiology, age at the start of the trial period, duration of hearing loss at the start of the trial period and the type of device used during the trial period, on the other hand. Although 66% of all the patients (109/196) declined the Baha after a trial, reasons not to choose a Baha were diverse and no crucial factors could be found that determine the success of a Baha trial period. Lack of improvement concerning speech understanding in noise was the most important reason mentioned by patients who declined the Baha. The authors advocate that all patients, suffering from SSD, should be offered the opportunity to try a Baha device as no factors could be found that determine the decision of a patient following the trial period.	\N	\N
21844339	"Normal hearing" is typically defined by threshold audibility, even though everyday communication relies on extracting key features of easily audible sound, not on sound detection. Anecdotally, many normal-hearing listeners report difficulty communicating in settings where there are competing sound sources, but the reasons for such difficulties are debated: Do these difficulties originate from deficits in cognitive processing, or differences in peripheral, sensory encoding? Here we show that listeners with clinically normal thresholds exhibit very large individual differences on a task requiring them to focus spatial selective auditory attention to understand one speech stream when there are similar, competing speech streams coming from other directions. These individual differences in selective auditory attention ability are unrelated to age, reading span (a measure of cognitive function), and minor differences in absolute hearing threshold; however, selective attention ability correlates with the ability to detect simple frequency modulation in a clearly audible tone. Importantly, we also find that selective attention performance correlates with physiological measures of how well the periodic, temporal structure of sounds above the threshold of audibility are encoded in early, subcortical portions of the auditory pathway. These results suggest that the fidelity of early sensory encoding of the temporal structure in suprathreshold sounds influences the ability to communicate in challenging settings. Tests like these may help tease apart how peripheral and central deficits contribute to communication impairments, ultimately leading to new approaches to combat the social isolation that often ensues.	\N	\N
21860975	The electrical stimulation generated by the Cochlear Implant (CI) may improve the neural synchrony and hence contribute to the development of auditory skills in patients with Auditory Neuropathy/Auditory Dyssynchrony (AN/AD). Prospective cohort cross-sectional study to evaluate the auditory performance and the characteristics of the electrically evoked compound action potential (ECAP) in 18 children with AN/AD and cochlear implants. The auditory perception was evaluated by sound field thresholds and speech perception tests. To evaluate ECAP's characteristics, the threshold and amplitude of neural response were evaluated at 80 Hz and 35 Hz. No significant statistical difference was found concerning the development of auditory skills. The ECAP's characteristics differences at 80 and 35 Hz stimulation rate were also not statistically significant. The CI was seen as an efficient resource to develop auditory skills in 94% of the AN/AD patients studied. The auditory perception benefits and the possibility to measure ECAP showed that the electrical stimulation could compensate for the neural dyssynchrony caused by the AN/AD. However, a unique clinical procedure cannot be proposed at this point. Therefore, a careful and complete evaluation of each AN/AD patient before recommending a Cochlear Implant is advised. Clinical Trials: NCT01023932.	\N	\N
21860978	Hearing has an important role in human development and social adaptation in blind people. To evaluate the performance of temporal auditory processing in blind people; to characterize the temporal resolution ability; to characterize the temporal ordinance ability and to compare the performance of the study population in the applied tests. Fifteen blind adults participated in this study. A cross-sectional study was undertaken; approval was obtained from the Pernambuco Catholic University Ethics Committee, no. 003/2008. Temporal auditory processing was excellent--the average composed threshold in the original RGDT version was 4. 98 ms; it was 50 ms for all frequencies in the expanded version. PPS and DPS results ranged from 95% to 100%. There were no quantitative differences in the comparison of tests; but oral reports suggested that the original RGDT original version was more difficult. The study sample performed well in temporal auditory processing; it also performed well in temporal resolution and ordinance abilities.	\N	\N
21862680	To evaluate potential contributions of broadband spectral integration in the perception of static vowels. Specifically, can the auditory system infer formant frequency information from changes in the intensity weighting across harmonics when the formant itself is missing? Does this type of integration produce the same results in the lower (first formant [F1]) and higher (second formant [F2]) regions? Does the spacing between the spectral components affect a listener's ability to integrate the acoustic cues? Twenty young listeners with normal hearing identified synthesized vowel-like stimuli created for adjustments in the F1 region (/Λ/-/α/, /i/-/ε/) and in the F2 region (/Λ/-/æ/). There were 2 types of stimuli: (a) 2-formant tokens and (b) tokens in which 1 formant was removed and 2 pairs of sine waves were inserted below and above the missing formant; the intensities of these harmonics were modified to cause variations in their spectral center of gravity (COG). The COG effects were tested over a wide range of frequencies. Obtained patterns were consistent with calculated changes to the spectral COG, in both the F1 and F2 regions. The spacing of the sine waves did not affect listeners' responses. The auditory system may perform broadband integration as a type of auditory wideband spectral analysis.	\N	\N
21877769	This study investigated the ability to use temporal-envelope (E) cues in a consonant identification task when presented within one or two frequency bands. Syllables were split into five bands spanning the range 70-7300 Hz with each band processed to preserve E cues and degrade temporal fine-structure cues. Identification scores were measured for normal-hearing listeners in quiet for individual processed bands and for pairs of bands. Consistent patterns of results were obtained in both the single- and dual-band conditions: identification scores increased systematically with band center frequency, showing that E cues in the higher bands (1.8-7.3 kHz) convey greater information.	\N	\N
21877806	A functional simulation of hearing loss was evaluated in its ability to reproduce the temporal masking functions for eight listeners with mild to severe sensorineural hearing loss. Each audiometric loss was simulated in a group of age-matched normal-hearing listeners through a combination of spectrally-shaped masking noise and multi-band expansion. Temporal-masking functions were obtained in both groups of listeners using a forward-masking paradigm in which the level of a 110-ms masker required to just mask a 10-ms fixed-level probe (5-10 dB SL) was measured as a function of the time delay between the masker offset and probe onset. At each of four probe frequencies (500, 1000, 2000, and 4000 Hz), temporal-masking functions were obtained using maskers that were 0.55, 1.0, and 1.15 times the probe frequency. The slopes and y-intercepts of the masking functions were not significantly different for listeners with real and simulated hearing loss. The y-intercepts were positively correlated with level of hearing loss while the slopes were negatively correlated. The ratio of the slopes obtained with the low-frequency maskers relative to the on-frequency maskers was similar for both groups of listeners and indicated a smaller compressive effect than that observed in normal-hearing listeners.	\N	\N
21877812	The auditory system takes advantage of early reflections (ERs) in a room by integrating them with the direct sound (DS) and thereby increasing the effective speech level. In the present paper the benefit from realistic ERs on speech intelligibility in diffuse speech-shaped noise was investigated for normal-hearing and hearing-impaired listeners. Monaural and binaural speech intelligibility tests were performed in a virtual auditory environment where the spectral characteristics of ERs from a simulated room could be preserved. The useful ER energy was derived from the speech intelligibility results and the efficiency of the ERs was determined as the ratio of the useful ER energy to the total ER energy. Even though ER energy contributed to speech intelligibility, DS energy was always more efficient, leading to better speech intelligibility for both groups of listeners. The efficiency loss for the ERs was mainly ascribed to their altered spectrum compared to the DS and to the filtering by the torso, head, and pinna. No binaural processing other than a binaural summation effect could be observed.	\N	\N
21878379	Otoacoustic emission (OAE) amplitude can be reduced by acoustic stimulation. This effect is produced by the medial olivocochlear (MOC) reflex. Past studies have shown that the MOC reflex is related to listening in noise and attention. In the present study, the relationship between strength of the contralateral MOC reflex and masked threshold was investigated in 19 adults. Detection thresholds were determined for 1000-Hz, 300-ms tone presented simultaneously with one repetition of a 300-ms masker in an ongoing train of masker bursts. Three masking conditions were tested: 1) broadband noise 2) a fixed-frequency 4-tone complex masker and 3) a random-frequency 4-tone complex masker. Broadband noise was expected to produce energetic masking and the tonal maskers were expected to produce informational masking in some listeners. DPOAEs were recorded at fine frequency intervals from 500 to 4000 Hz, with and without contralateral acoustic stimulation. MOC reflex strength was estimated as a reduction in baseline level and a shift in frequency of DPOAE fine-structure maxima near 1000-Hz. MOC reflex and psychophysical testing were completed in separate sessions. Individuals with poorer thresholds in broadband noise and in random-frequency maskers were found to have stronger MOC reflexes.	\N	\N
21886362	Event-related potential (ERPs) provide an exquisite means to monitor the extent of processing of external stimulus input during sleep. The processing of relatively high intensity stimuli has been well documented. Sleep normally occurs in much less noisy environments. The present study therefore employed ERPs to examine the extent of processing of very low intensity (near-hearing threshold) stimuli. Brief duration 1000 Hz auditory tone bursts varying in intensity at random from -5 to +45 dB from normative hearing level (nHL) in 10 dB steps were presented every 1.5 to 2.5 s when the subject was awake and reading a book and again during all-night sleep. n = 10 healthy young adults. In the waking state, the auditory stimuli elicited a negative-going deflection, N1, peaking at about 100 ms, followed by a smaller positivity, P2, peaking at about 180 ms. N1-P2 gradually decreased in amplitude with decreases in stimulus intensity and remained visible at near-hearing threshold levels. During NREM sleep, the amplitude of N1 was at baseline level and was reduced to only 15% to 20% of its waking amplitude during REM sleep. P2 was much larger in sleep than in wakefulness. Importantly, during sleep, P2 could be reliably elicited by the auditory stimuli to within 15 dB of threshold. During NREM, a large amplitude negativity peaking at about 350 ms was elicited by the higher intensity stimuli. This N350 was much reduced in amplitude during REM sleep. A significant N350 was not, however, elicited when stimuli intensity levels were below 25 dB nHL. Auditory stimuli that are only slightly above hearing threshold appear to be processed extensively during a 200 to 400 ms interval in both NREM and REM sleep. The nature of this processing is, however, very different compared to the waking state.	\N	\N
21889805	Auditory training has been advocated as a management strategy for children with hearing, listening or language difficulties. Because poor speech-in-noise perception is commonly reported, previous research has focused on the use of complex (word/sentence) stimuli as auditory training material to improve sentence-in-noise perception. However, some evidence suggests that engagement with the training stimuli is more important than the type of stimuli used for training. The aim of this experiment was to assess if sentence-in-noise perception could be improved using simpler auditory training stimuli. We recruited 41 typically developing, normal-hearing children aged 8-10 years divided into four groups. Groups 1-3 trained over 4 weeks (12 × 30 min sessions) on either: (1) pure-tone frequency discrimination (FD), (2) FD in a modulated noise (FDN) or, (3) mono-syllabic words in a modulated noise (WN). Group 4 was an untrained Control. In the training tasks, either tone frequency (Group 1), or tone (Group 2) or speech (Group 3) level was varied adaptively. All children completed pre- and post-training tests of sentence perception in modulated (SMN) and unmodulated (SUN) noise and a probe measure of each training task. All trained groups improved significantly on the trained tasks. Transfer of training occurred between FDN training and FD, WN and SMN testing, and between WN training and SMN testing. A significant performance suppression on the SUN test resulted from FD and FDN training. The pattern of training-induced improvement, relative to Controls, suggests that transfer of training is more likely when some stimulus dimensions (tone frequency, speech, modulated noise) are shared between training tasks and outcomes. This and the finding of suppressed post-training performance, relative to Controls, between tasks not sharing a stimulus dimension both favour the use of outcome-specific material for auditory training.	\N	\N
21895071	Human listening tests were conducted to investigate if participants could distinguish between samples of target echoes and clutter obtained from a broadband active sonar experiment. For each echo, the listeners assigned a rating based on how confident they were that it was a target echo or clutter. The measure of performance was the area under the binormal receiver-operating-characteristic (ROC) curve, A(z). The mean performance was A(z)=0.95 ± 0.04 when signals were presented with their full available acoustic bandwidth of approximately 0-2 kHz. It was A(z)=0.77 ± 0.08 when the bandwidth was reduced to 0.5-2 kHz. The error bounds are stated as 95% confidence intervals. These results show that the listeners could definitely hear differences, but their performance was significantly degraded when the low-frequency signal information was removed. The performance of an automatic aural classifier was compared against this human-performance baseline. Results of statistical tests showed that it outperformed 2 of 13 listeners and 5 of 9 human listeners in the full-bandwidth and reduced-bandwidth tests, respectively, and performed similarly to the other listeners. Given its performance, the automatic aural classifier may prove beneficial to Navy sonar systems.	\N	\N
21895094	In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent electrodes can produce intermediate pitch percepts between those of the component electrodes. However, it is unclear whether simultaneous and sequential virtual channels (VCs) can be discriminated. In this study, CI users were asked to discriminate simultaneous and sequential VCs; discrimination was measured for monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and focused stimulation modes. For sequential VCs, the interpulse interval (IPI) varied between 0.0 and 1.8 ms. All stimuli were presented at comfortably loud, loudness-balanced levels at a 250 pulse per second per electrode (ppse) stimulation rate. On average, CI subjects were able to reliably discriminate between sequential and simultaneous VCs. While there was no significant effect of IPI or stimulation mode on VC discrimination, some subjects exhibited better VC discrimination with BP + 1 stimulation. Subjects' discrimination between sequential and simultaneous VCs was correlated with electrode discrimination, suggesting that spatial selectivity may influence perception of sequential VCs. To maintain equal loudness, sequential VC amplitudes were nearly double those of simultaneous VCs, presumably resulting in a broader spread of excitation. These results suggest that perceptual differences between simultaneous and sequential VCs might be explained by differences in the spread of excitation.	\N	\N
21895095	Three experiments were designed to examine temporal envelope processing by cochlear implant (CI) listeners. In experiment 1, the hypothesis that listeners' modulation sensitivity would in part determine their ability to discriminate between temporal modulation rates was examined. Temporal modulation transfer functions (TMTFs) obtained in an amplitude modulation detection (AMD) task were compared to threshold functions obtained in an amplitude modulation rate discrimination (AMRD) task. Statistically significant nonlinear correlations were observed between the two measures. In experiment 2, results of loudness-balancing showed small increases in the loudness of modulated over unmodulated stimuli beyond a modulation depth of 16%. Results of experiment 3 indicated small but statistically significant effects of level-roving on the overall gain of the TMTF, but no impact of level-roving on the average shape of the TMTF across subjects. This suggested that level-roving simply increased the task difficulty for most listeners, but did not indicate increased use of intensity cues under more challenging conditions. Data obtained with one subject, however, suggested that the most sensitive listeners may derive some benefit from intensity cues in these tasks. Overall, results indicated that intensity cues did not play an important role in temporal envelope processing by the average CI listener.	\N	\N
21912929	Previous research examining cross-modal conflicts in object recognition has often made use of animal vocalizations and images, which may be considered natural and ecologically valid, thus strengthening the association in the congruent condition. The current research tested whether the same cross-modal conflict would exist for man-made object sounds as well as comparing the speed and accuracy of auditory processing across the two object categories. Participants were required to attend to a sound paired with a visual stimulus and then respond to a verification item (e.g., "Dog?"). Sounds were congruent (same object), neutral (unidentifiable image), or incongruent (different object) with the images presented. In the congruent and neutral condition, animals were recognized significantly faster and with greater accuracy than man-made objects. It was hypothesized that in the incongruent condition, no difference in reaction time or error rate would be found between animals and man-made objects. This prediction was not supported, indicating that the association between an object's sound and image may not be that disparate when comparing animals to man-made objects. The findings further support cross-modal conflict research for both the animal and man-made object category. The most important finding, however, was that auditory processing is enhanced for living compared to nonliving objects, a difference only previously found in visual processing. Implications relevant to both the neuropsychological literature and sound research are discussed.	\N	\N
21913927	In prior studies, we have used a conditional linkage between rare deviations in a regular sound pattern to determine if the auditory system can use the first deviation to anticipate the probable features of the second deviation (i.e., make a conditional inference). This study was designed to test two hypotheses about why the mismatch negativity (MMN) to a duration deviant sound seems more susceptible to conditional inference effects. The MMNs to duration and frequency glide deviant sounds were significantly smaller when their occurrence was conditionally linked to the identity of a prior deviant as opposed to when they occurred randomly in a sequence. Results provide support for the learned conditional inference interpretation of reduced MMN size to linked deviants. We discuss alternate explanations and conclude that conditional inference studies could provide insight into the dynamics of probability-based prediction in the auditory system.	\N	\N
21920411	Tinnitus is described as an auditory perception in the absence of any external sound source. Tinnitus loudness has been correlated to sustained high frequency gamma-band activity in auditory cortex. It remains unknown whether unilateral tinnitus is always generated in the left auditory cortex, irrespective of the side on which the tinnitus is perceived, or in the contralateral auditory cortex. In order to solve this enigma source localized electroencephalographic (EEG) recordings of a homogenous group of unilateral left and right-sided tinnitus patients presenting with noise-like tinnitus was analyzed. Based on a region of interest analysis, the most important result of this study is that tinnitus lateralization depended on the gamma-band activity of the contralateral parahippocampal area. As for the auditory cortex no differences were found between left-sided and right-sided tinnitus patients. However, in comparison to a control group both left and right-sided tinnitus patients had an increased gamma-band activity in both the left and right primary and secondary auditory cortex. Thus whereas in tinnitus the primary and secondary auditory cortices of both sides are characterized by increased gamma-band activity, the side on which the tinnitus is perceived relates to gamma-band activity in the contralateral parahippocampal area.	\N	\N
21926628	The purpose of this study was to determine the reliability of the electrophysiological binaural beat steady state response as a gauge of temporal fine structure coding, particularly as it relates to the aging auditory system. The hypothesis was that the response would be more robust in a lower, than in a higher, frequency region and in younger, than in older, adults. Two experiments were undertaken. The first measured the 40 Hz binaural beat steady state response elicited by tone pairs in two frequency regions: lower (390 and 430 Hz tone pair) and higher (810 and 850 Hz tone pair). Frequency following responses (FFRs) evoked by the tones were also recorded. Ten young adults with normal hearing participated. The second experiment measured the binaural beat and FFRs in older adults but only in the lower frequency region. Fourteen older adults with relatively normal hearing participated. Response metrics in both experiments included response component signal-to-noise ratio (F statistic) and magnitude-squared coherence. Experiment 1 showed that FFRs were elicited in both frequency regions but were more robust in the lower frequency region. Binaural beat responses elicited by the lower frequency pair of tones showed greater amplitude fluctuation within a participant than the respective FFRs. Experiment 2 showed that older adults exhibited similar FFRs to younger adults, but proportionally fewer older participants showed binaural beat responses. Age differences in onset responses were also observed. The lower prevalence of the binaural beat response in older adults, despite the presence of FFRs, provides tentative support for the sensitivity of this measure to age-related deficits in temporal processing. However, the lability of the binaural beat response advocates caution in its use as an objective measure of fine structure coding.	\N	\N
21928934	An experiment is reported that investigates the relation between the suffix effect and the effect of irrelevant sound on the serial recall of short sequences of spoken material. The main issue was whether there is an effect of irrelevant sound under articulatory suppression in the presence of a spoken suffix. As in Hanley and Bakopoulou (2003), the irrelevant sound comprised speech that was presented during the retention interval. When a spoken suffix appeared at the end of the list, a significant effect of irrelevant sound remained when participants were able to rehearse list items. However, it disappeared under articulatory suppression. The effects of irrelevant sound remained significant under suppression when the suffix was an auditory tone but was confined to the final position of the serial position curve. These results parallel those reported by Jones, Macken, and Nicholls (2004) and Jones, Hughes, and Macken (2006) when they examined the effect of articulatory suppression on the phonological similarity effect. The results are consistent with Jones et al.'s (2006, 2004) view that an acoustic-perceptual representation of the terminal list items is the source of the effects of irrelevant sound and phonological similarity when they occur in the presence of articulatory suppression.	\N	\N
21928935	Serial recall from working memory is known to be impaired by the presence of irrelevant background speech, but several prior studies have concluded that the magnitude of the impairment is independent of the phonological relationship between to-be-remembered (TBR) and to-be-ignored (TBI) sources of information. In the present study, we examined the influence of between-stream phonological similarity in serial recall while attending to a heretofore uncontrolled variable, the phonetic feature. We found that TBI items sharing many phonetic features with TBR items produced significantly stronger working-memory impairments than TBI items with minimal phonetic feature overlap. In addition, participants were more likely to report remembering incorrect items that incorporated phonological characteristics of the TBI stream in the high-overlap condition. These findings provide evidence for subphonemic between-stream interactions and suggest that multiple parallel processes contribute to the irrelevant speech effect. We propose that a 2-component model, which combines the assumptions of process- and content-based accounts for the irrelevant speech effect, offers the best explanation for these findings.	\N	\N
21930137	In daily communication, we often use indirect speech to convey our intention. However, little is known about the brain mechanisms that underlie the comprehension of indirect speech. In this study, we conducted a functional MRI experiment using a scenario reading task to compare the neural activity induced by an indirect reply (a type of indirect speech) and a literal sentence. Participants read a short scenario consisting of three sentences. The first two sentences explained the situation of the protagonists, whereas the third sentence had an indirect, literal, or unconnected meaning. The indirect reply condition primarily activated the bilateral fronto-temporal networks (Brodmann's Areas (BA) 47 and 21) and the dorso-medial prefrontal cortex (dmPFC). In the literal sentence condition, only the left fronto-temporal network (BA 45 and 21) and the dmPFC (posterior region) were activated. In addition, we found greater activation resulting from comprehension of an indirect reply than from literal sentence comprehension in the dmPFC, the left middle frontal area (BA 9), the bilateral inferior frontal area (BA 9/47), and the right middle temporal area (BA 21). Our findings indicate that the right and left fronto-temporal networks play a crucial role in detecting contextual violations, whereas the medial frontal cortex is important for generating inferences to make sense of remarks within a context.	\N	\N
21932257	To examine how musical expertise tunes the brain to subtle metric anomalies in an ecological musical context, we presented piano compositions ending on standard and deviant cadences (endings) to expert pianists and musical laymen, while high-density EEG was recorded. Temporal expectancies were manipulated by substituting standard "masculine" cadences at metrically strong positions with deviant, metrically unaccented, "feminine" cadences. Experts detected metrically deviant cadences better than laymen. Analyses of event-related potentials demonstrated that an early P3a-like component (~150-300 ms), elicited by musical closure, was significantly enhanced at frontal and parietal electrodes in response to deviant endings in experts, whereas a reduced response to deviance occurred in laymen. Putative neuronal sources contributing to the modulation of this component were localized in a network of brain regions including bilateral supplementary motor areas, middle and posterior cingulate cortex, precuneus, associative visual areas, as well as in the right amygdala and insula. In all these regions, experts showed enhanced responses to metric deviance. Later effects demonstrated enhanced activations within the same brain network, as well as higher processing speed for experts. These results suggest that early brain responses to metric deviance in experts may rely on motor representations mediated by the supplementary motor area and motor cingulate regions, in addition to areas involved in self-referential imagery and relevance detection. Such motor representations could play a role in temporal sensory prediction evolved from musical training and suggests that rhythm evokes action more strongly in highly trained instrumentalists.	\N	\N
21934538	The processing of case-marking and argument structures was investigated in children at the age of 3 years, 4 years and 6 months, and 6 years. Two event-related potential (ERP) experiments were conducted in a case-marked language, i.e. German, comparing the processing of (a) double-nominative violations with subject-initial structures and (b) double-accusative violations with object-initial structures. It is known that for both violation types, adults display a biphasic N400/P600 ERP response, reflecting thematic-semantic, and syntactic processes. For double-nominative violations, 3-year-old children already show an adult-like processing pattern revealing their abilities to repair the tested structure. For double-accusative violations, ERP results indicate developmental processing differences with even 6-year-old children not showing an adult pattern. This suggests a late development of the complete function of the accusative case.	\N	\N
21936745	To evaluate the feasibility, the duration and results of sedation by intrarectal pentobarbital and oral alimemazine for auditory brain stem responses (ABR) and auditory steady-state responses (ASSR) recordings in children aged 2 to 5 years. Prospective study. 180 consecutive children aged 2 to 5 years, referred for language retardation and/or behavioral problems, who could not be tested by behavioral methods, underwent ABR and ASSR recordings. The children who did not spontaneously nap were sedated by intrarectal pentobarbital eventually potentiated by oral alimemazine. A spontaneous nap was obtained in only 23 cases, 72 children received only pentobarbital, and 85 received both pentobarbital and alimemazine. Even so, recording was impossible in 16 cases, and interrupted before completion of the ASSR recordings in 45 cases. Children went to sleep in average 64 min +/- 40. The average recording time for the ABR was 20 minutes, and for the ASSR 25 minutes. Sedation by pentobarbital, eventually completed by oral alimemazine, allows ABR and/or ASSR recordings in 89.8% of the children who did not nap in the recording room, and is therefore a good alternative to general anesthesia in these children.	\N	\N
21940982	The goal of this study was to assess the functional utility of transient noise reduction (TNR) algorithms available in hearing aids via speech intelligibility and user preferences. Two pairs of hearing aids, 1 pair each from Siemens and Unitron, were programmed for 17 hearing impaired individuals after a hearing evaluation. Intelligibility was measured for each participant for sentences presented in quiet, with 2 types of transient noise, multitalker babble, and in a combination of each type of transient noise and multitalker babble. Each condition was tested with TNR activated and TNR deactivated in a counterbalanced, single-blinded format. Subjective ratings of overall speech understanding, comfort, and sound quality were obtained for each condition. A significant improvement in speech intelligibility was measured with the TNR activated when speech was presented in multitalker babble, in the presence of chair clang transient noises, and when combining these noises. Activation of the TNR algorithm did not result in significant improvements for any of the subjective ratings. While improvements were limited to certain conditions, specifically those with the chair clang transient and/or multitalker babble, TNR appears to offer an incremental step in improving the listening experience for hearing aid users.	\N	\N
21945467	The different response characteristics of the different auditory cortical responses under conventional central masking conditions were examined by comparing the effects of contralateral white noise on the cortical component of 40-Hz auditory steady state fields (ASSFs) and the N100 m component in auditory evoked fields (AEFs) for tone bursts using a helmet-shaped magnetoencephalography system in 8 healthy volunteers (7 males, mean age 32.6 years). The ASSFs were elicited by monaural 1000 Hz amplitude modulation tones at 80 dB SPL, with the amplitude modulated at 39 Hz. The AEFs were elicited by monaural 1000 Hz tone bursts of 60 ms duration (rise and fall times of 10 ms, plateau time of 40 ms) at 80 dB SPL. The results indicated that continuous white noise at 70 dB SPL presented to the contralateral ear did not suppress the N100 m response in either hemisphere, but significantly reduced the amplitude of the 40-Hz ASSF in both hemispheres with asymmetry in that suppression of the 40-Hz ASSF was greater in the right hemisphere. Different effects of contralateral white noise on these two responses may reflect different functional auditory processes in the cortices.	\N	\N
21954871	This study examined the development of uncertainty monitoring in early childhood. Specifically, this study tested the prediction that preschoolers can reflect on their sense of certainty about the likely accuracy of their decisions, and it examined whether this ability differs across domains. Three-, 4-, and 5-year-olds (N = 74) completed a perceptual identification and a lexical identification task in which they reported whether they were certain or uncertain about their answers. Results showed that even 3-year-olds provided confidence judgments that discriminated accurate from inaccurate responses, but this discrimination increased with age. Furthermore, results suggest that 3-year-olds primarily rely on response latency to assess certainty, whereas older preschoolers do not. Overall, these findings suggest that uncertainty monitoring emerges and develops during the preschool years.	\N	\N
21962945	While grammatical aspects of language are preserved, executive deficits are prominent in Lewy body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's dementia (PDD) and dementia with Lewy bodies (DLB). We examined executive control during sentence processing in LBSD by assessing temporary structural ambiguities. Using an on-line word detection procedure, patients heard sentences with a syntactic structure that has high-compatibility or low-compatibility with the main verb's statistically preferred syntactic structure, and half of the sentences were lengthened strategically between the onset of the ambiguity and its resolution. We found selectively slowed processing of lengthened ambiguous sentences in the PDD/DLB subgroup. This correlated with impairments on measures of executive control. Regression analyses related the working memory deficit during ambiguous sentence processing to significant cortical thinning in frontal and parietal regions. These findings emphasize the role of prefrontal disease in the executive limitations that interfere with processing ambiguous sentences in LBSD.	\N	\N
21967269	Six experiments studied relative frequency judgment and recall of sequentially presented items drawn from 2 distinct categories (i.e., city and animal). The experiments show that judged frequencies of categories of sequentially encountered stimuli are affected by certain properties of the sequence configuration. We found (a) a first-run effect whereby people overestimated the frequency of a given category when that category was the first repeated category to occur in the sequence and (b) a dissociation between judgments and recall; respondents may judge 1 event more likely than the other and yet recall more instances of the latter. Specifically, the distribution of recalled items does not correspond to the frequency estimates for the event categories, indicating that participants do not make frequency judgments by sampling their memory for individual items as implied by other accounts such as the availability heuristic (Tversky & Kahneman, 1973) and the availability process model (Hastie & Park, 1986). We interpret these findings as reflecting the operation of a judgment heuristic sensitive to sequential patterns and offer an account for the relationship between memory and judged frequencies of sequentially encountered stimuli.	\N	\N
21973363	Spectral-ripple discrimination has been used widely for psychoacoustical studies in normal-hearing, hearing-impaired, and cochlear implant listeners. The present study investigated the perceptual mechanism for spectral-ripple discrimination in cochlear implant listeners. The main goal of this study was to determine whether cochlear implant listeners use a local intensity cue or global spectral shape for spectral-ripple discrimination. The effect of electrode separation on spectral-ripple discrimination was also evaluated. Results showed that it is highly unlikely that cochlear implant listeners depend on a local intensity cue for spectral-ripple discrimination. A phenomenological model of spectral-ripple discrimination, as an "ideal observer," showed that a perceptual mechanism based on discrimination of a single intensity difference cannot account for performance of cochlear implant listeners. Spectral modulation depth and electrode separation were found to significantly affect spectral-ripple discrimination. The evidence supports the hypothesis that spectral-ripple discrimination involves integrating information from multiple channels.	\N	\N
21974502	Thresholds of vowel formant discrimination for F1 and F2 of isolated vowels with full and partial vowel spectra were measured for normal-hearing listeners at fixed and roving speech levels. Performance of formant discrimination was significantly better for fixed levels than for roving levels with both full and partial spectra. The effect of vowel spectral range was present only for roving levels, but not for fixed levels. These results, consistent with studies of profile analysis, indicated different perceptual mechanisms for listeners to discriminate vowel formant frequency at fixed and roving levels.	\N	\N
21986211	Hearing loss is routinely estimated from the audiogram, even though this measure gives only a rough approximation of hearing. Indeed, cochlear regions functioning poorly, if at all, called dead regions, are not detected by a simple audiogram. To detect cochlear dead regions, additional measurements of psychophysical tuning curves or thresholds in background noise (TEN test) are required. A first aim of this study was to assess the presence of dead regions after impulse noise trauma using psychophysical tuning curves. The procedure we used was based on a compromise between the need to collect reliable estimates of psychophysical tuning curves and the limited time available to obtain these estimates in a hospital setting. Psychophysical tuning curves were measured using simultaneous masking with a 2-alternative forced choice paradigm, where the target was randomly placed in one of the two masker presentations. It is well known that some components of noise-induced hearing loss are reversible. A second aim of this study was to examine the potential recovery of dead regions after acoustic trauma. A third issue addressed in this article was the relationship between noise-induced dead regions and tinnitus. We found that 70% of the subjects had dead regions after noise trauma, while 88% reported tinnitus. Moreover, we found that the extent of dead regions probably diminished in about 50% of subjects, which highlights the ability of the human auditory system to recover from noise-induced hearing loss.	\N	\N
21993050	Prescriptive methods have been at the core of modern hearing aid fittings for the past several decades. Every decade or so, there have been revisions to existing methods and/or the emergence of new methods that become widely used. In 2001 Byrne et al provided a comparison of insertion gain for generic prescriptive methods available at that time. The purpose of this article was to compare National Acoustic Laboratories-Non-linear 1 (NAL-NL1), National Acoustic Laboratories-Non-linear 2 (NAL-NL2), Desired Sensation Level Multistage Input/Output (DSL m[i/o]), and Cambridge Method for Loudness Equalization 2-High-Frequency (CAMEQ2-HF) prescriptive methods for adults on the amplification characteristics of prescribed insertion gain and compression ratio. Following the differences observed in prescribed insertion gain among the four prescriptive methods, analyses of predicted specific loudness, overall loudness, and bandwidth of cochlear excitation and effective audibility as well as speech intelligibility of the international long-term average speech spectrum (ILTASS) at an average conversational input level were completed. These analyses allow for the discussion of similarities and differences among the present-day prescriptive methods. The impact of insertion gain differences among the methods is examined for seven hypothetical hearing loss configurations using models of loudness perception and speech intelligibility. Hearing loss configurations for adults of various types and degrees were selected, five of which represent sensorineural impairment and were used by Byrne et al; the other two hearing losses provide an example of mixed and conductive impairment. Prescribed insertion gain data were calculated in 1/3-octave frequency bands for each of the seven hearing losses from the software application of each prescriptive method over multiple input levels. The insertion gain data along with a diffuse field-to-eardrum transfer function were used to calculate output levels at the eardrums of the hypothetical listeners. Levels of hearing loss and output were then used in the Moore and Glasberg loudness model and the ANSI S3.5-1997 Speech Intelligibility Index model. NAL-NL2 and DSL m[i/o] provided comparable overall loudness of approximately 8 sones for the five sensorineural hearing losses for a 65 dB SPL ILTASS input. This loudness was notably less than that perceived by a normal-hearing person for the same input signal, 18.6 sones. NAL-NL2 and DSL m[i/o] also provided comparable predicted speech intelligibility in quiet and noise. CAMEQ2-HF provided a greater average loudness, similar to NAL-NL1, with more high-frequency bandwidth but no significant improvement to predicted speech intelligibility. Definite variation in prescribed insertion gain was present among the prescriptive methods. These differences when averaged across the hearing losses were, by and large, negligible with regard to predicted speech intelligibility at normal conversational speech levels. With regard to loudness, DSL m[i/o] and NAL-NL2 provided the least overall loudness, followed by CAMEQ2-HF and NAL-NL1 providing the most loudness. CAMEQ2-HF provided the most audibility at high frequencies; even so, the audibility became less effective for improving speech intelligibility as hearing loss severity increased.	\N	\N
22013241	Interactions between auditory and somatosensory information are relevant to the neural processing of speech since speech processes and certainly speech production involves both auditory information and inputs that arise from the muscles and tissues of the vocal tract. We previously demonstrated that somatosensory inputs associated with facial skin deformation alter the perceptual processing of speech sounds. We show here that the reverse is also true, that speech sounds alter the perception of facial somatosensory inputs. As a somatosensory task, we used a robotic device to create patterns of facial skin deformation that would normally accompany speech production. We found that the perception of the facial skin deformation was altered by speech sounds in a manner that reflects the way in which auditory and somatosensory effects are linked in speech production. The modulation of orofacial somatosensory processing by auditory inputs was specific to speech and likewise to facial skin deformation. Somatosensory judgments were not affected when the skin deformation was delivered to the forearm or palm or when the facial skin deformation accompanied nonspeech sounds. The perceptual modulation that we observed in conjunction with speech sounds shows that speech sounds specifically affect neural processing in the facial somatosensory system and suggest the involvement of the somatosensory system in both the production and perceptual processing of speech.	\N	\N
22023487	The aim of this study was to assess differences between real ear insertion gains (REIG) measured with the modified pressure concurrent equalization (MPCE) and modified pressure stored equalization (MPSE) methods for open fittings in a typical audiology patient population. REIGs were compared for the two methods using a warble tone sweep at 65 dB SPL. The differences between the two methods at 0.25, 0.5, 1, 2, 3, 4 and 6 kHz were recorded. Eighty-three ears of a consecutive sample of 48 candidates for open-fit hearing aids were included. The mean difference between MPSE and MPCE REIGs was less than 1 dB at all frequencies. Analysis of variance showed that the main effect of method was not significant, and there was no significant interaction between method and frequency. The results for the MPSE and MPCE methods did not differ significantly for the patients with mild-to-moderate hearing losses tested here, for whom REIGs were generally less than 20 dB. Further research is needed to identify the REIG values at which the differences between MPCE and MPSE methods become clinically significant.	\N	\N
22030970	Frontonasal dysplasia (FND) is a rare malformative complex affecting the frontal portion of the face, the eyes and the nose; it may occur singly or associated with other clinical signs. No systematic studies describing hearing in this condition were found. To evaluate hearing sensitivity and sound stimulus conduction from cochlea to brainstem in patients with clinical signs of FND. 21 patients with isolated or syndromic FND were submitted to a clinical (otological/vestibular antecedents and otoscopy) and instrumental (pure tone and speech audiometry, tympanometry and brainstem auditory evoked response) hearing evaluation. A clinical, cross-sectional observational prospective study. Hearing thresholds were normal in 15 (70%) patients, abnormal in 5 (25%), mostly with conductive hearing loss; one patient did not cooperate with testing. The tympanometric curve was type A in 30 (72%) ears, type C in 5 (12%), type As in 4 (9%) and type B in 3 (7%). The auditory brainstem response (ABR) showed no abnormalities. Patients with FND showed no abnormalities in the auditory system from cochlea to brainstem in this study. Mild conductive hearing loss found in some is probably related to cleft palate. Further evaluation of hearing pathways at higher levels is recommended.	\N	\N
22030972	Accurate information about type, degree, and configuration of hearing loss are necessary for successful audiological early interventions. Auditory brainstem response with tone burst stimuli (TB ABR) and auditory steady-state response (ASSR) exams provide this information. To analyze the clinical applicability of TB ABR and ASSR at 2 kHz in infants, comparing responses in full-term and premature neonates. The study was cross-sectional, clinical and experimental. Subjects consisted of 17 premature infants and 19 full-term infants. TB ABR and ASSR exams at 2000 Hz were done during natural sleep. The electrophysiological minimum response obtained with TB ABR was 32.4 dBnHL (52.4 dBSPL); the ASSR minimum was 13.8 dBHL (26.4 dBSPL). The exams required 21.1 min and 22 min, respectively. Premature and full-term infant responses showed no statistically significant differences, except for auditory steady-state response duration. Both exams have clinical applicability at 2 kHz in infants, with 20 min of duration, on average. In general, there are no differences between premature and full-term individuals.	\N	\N
22033983	We are constantly exposed to our own face and voice, and we identify our own faces and voices as familiar. However, the influence of self-identity upon self-speech perception is still uncertain. Speech perception is a synthesis of both auditory and visual inputs; although we hear our own voice when we speak, we rarely see the dynamic movements of our own face. If visual speech and identity are processed independently, no processing advantage would obtain in viewing one's own highly familiar face. In the present experiment, the relative contributions of facial and vocal inputs to speech perception were evaluated with an audiovisual illusion. Our results indicate that auditory self-speech conveys a processing advantage, whereas visual self-speech does not. The data thereby support a model of visual speech as dynamic movement processed separately from speaker recognition.	\N	\N
22035565	Frequency modulation (FM) is an important building block of communication signals for animals and human. Attempts to predict the response of central neurons to FM sounds have not been very successful, though achieving successful results could bring insights regarding the underlying neural mechanisms. Here we proposed a new method to predict responses of FM-sensitive neurons in the auditory midbrain. First we recorded single unit responses in anesthetized rats using a random FM tone to construct their spectro-temporal receptive fields (STRFs). Training of neurons in the artificial neural network to respond to a second random FM tone was based on the temporal information derived from the STRF. Specifically, the time window covered by the presumed trigger feature and its delay time to spike occurrence were used to train a finite impulse response neural network (FIRNN) to respond to this random FM. Finally we tested the model performance in predicting the response to another similar FM stimuli (third random FM tone). We found good performance in predicting the time of responses if not also the response magnitudes. Furthermore, the weighting function of the FIRNN showed temporal 'bumps' suggesting temporal integration of synaptic inputs from different frequency laminae. This article is part of a Special Issue entitled: Neural Coding.	\N	\N
22037719	The aim of this study was to investigate audio-vestibular function in patients with essential tremor. Twenty-three patients with essential tremor (46 ears) and 21 health control subjects (42 ears) were included in the present study. Patients and comparison subjects were matched for age and gender. All patient and control subjects underwent pure tone audiometric test, tympanogram, transient-evoked otoacoustic emissions and auditory brainstem response. Vestibular system was evaluated by bitermal caloric test. Comparison of variables between the groups was performed. Investigation of the relationship between parameters about ET disease and hearing levels were also studied. Pure tone thresholds significantly differed between patients and controls in 250 and 500 Hz frequencies (p < 0.05). There was no statistically significant difference in 1,000, 2,000, 4,000, and 6,000 Hz frequencies in essential tremor patients in comparison to the control subjects. A correlation between tremor severity and audiometric scores in low frequencies was not found. In addition, statistical analysis did not demonstrate a correlation between audiometric scores and tremor duration. The otoacoustic emission responses were found significantly different in patient and control group. The latencies of waves I, V and I-V inter-peak latencies on the ABR were not different between the groups. Our findings indicated that, abnormalities are due to cochlea rather than the retro cochlear pathology which is responsible for hearing loss associated with essential tremor.	\N	\N
22056210	When speaking or producing music, people rely in part on auditory feedback - the sounds associated with the performed action. Three experiments investigated the degree to which alterations of auditory feedback (AAF) during music performances influence the experience of agency (i.e., the sense that your actions led to auditory events) and the possible link between agency and the disruptive effect of AAF on production. Participants performed short novel melodies from memory on a keyboard. Auditory feedback during performances was manipulated with respect to its pitch contents and/or its synchrony with actions. Participants rated their experience of agency after each trial. In all experiments, AAF reduced judgments of agency across conditions. Performance was most disrupted (measured by error rates and slowing) when AAF led to an ambiguous experience of agency, suggesting that there may be some causal relationship between agency and disruption. However, analyses revealed that these two effects were probably independent. A control experiment verified that performers can make veridical judgments of agency.	\N	\N
22057984	Binaural hearing in cochlear implant (CI) users can be achieved either by bilateral implantation or bimodally with a contralateral hearing aid (HA). Binaural-bimodal hearing has the advantage of complementing the high-frequency electric information from the CI by low-frequency acoustic information from the HA. We examined the contribution of a contralateral HA in 25 adult implantees to their perception of fundamental frequency-cued speech characteristics (initial consonant voicing, intonation, and emotions). Testing with CI alone, HA alone, and bimodal hearing showed that all three characteristics were best perceived under the bimodal condition. Significant differences were recorded between bimodal and HA conditions in the initial voicing test, between bimodal and CI conditions in the intonation test, and between both bimodal and CI conditions and between bimodal and HA conditions in the emotion-in-speech test. These findings confirmed that such binaural-bimodal hearing enhances perception of these speech characteristics and suggest that implantees with residual hearing in the contralateral ear may benefit from a HA in that ear.	\N	\N
22067074	The irrelevant sound effect (ISE) describes reduced verbal short-term memory during irrelevant changing-state sounds which consist of different and distinct auditory tokens. Steady-state sounds lack such changing-state features and do not impair performance. An EEG experiment (N=16) explored the distinguishing neurophysiological aspects of detrimental changing-state speech (3-token sequence) compared to ineffective steady-state speech (1-token sequence) on serial recall performance. We analyzed evoked and induced activity related to the memory items as well as spectral activity during the retention phase. The main finding is that the behavioral sound effect was exclusively reflected by attenuated token-induced gamma activation most pronounced between 50-60 Hz and 50-100 ms post-stimulus onset. Changing-state speech seems to disrupt a behaviorally relevant ongoing process during target presentation (e.g., the serial binding of the items).	\N	\N
22073929	The majority of the patients with unilateral auditory neuropathy spectrum disorder (UANSD) were pediatric and mostly showed a great degree of hearing loss when diagnosed. Abnormal auditory brainstem response (ABR) and preserved otoacoustic emissions (OAEs) and/or cochlear microphonics (CM) were important features to differentiate it from common sensorineural deafness and central nerve hearing loss. To identify the clinical characteristics of patients with UANSD. This was a retrospective study involving 14 patients diagnosed as having UANSD between 2004 and 2010 in the Chinese PLA Hospital. In all, 50% of the cases were males (1:1 sex ratio) and the average age of onset was 4.1 years. Of the 14 affected ears with UANSD in these cases, 6 were left-sided, while 8 were right-sided. Of the 14 contralateral ears, 4 presented with sensorineural hearing loss, while the other 10 showed normal hearing. The degree of hearing loss in the 14 affected ears varied, including moderate in 1, moderately severe in 4, severe in 5, and profound in 4. ABRs were absent in the 14 affected ears, while the OAEs, and/or CM were present.	\N	\N
22074449	Stapedotomy is, in our opinion, the technique of choice in stapes surgery. The precision of this technique allows clinicians to perform the surgical procedure in day surgery under local anesthesia. There is a strong emphasis on increasing the number of elective day surgery cases, especially in the patients' best interest, as it decreases the likelihood of late cancellation and hospital-acquired morbidity. A prospective study was performed to determine whether stapes surgery for otosclerosis could be performed safely in an outpatient setting. We present a series of stapes surgery cases for otosclerosis performed on a day-case basis. We performed a classic stapedotomy in 9 patients, a reverse classic step stapedotomy in 2 patients, a partial reverse classic step stapedotomy in 11 patients, and a hemi-stapedectomy in two patients. Three of 24 patients (12.5%) treated with classic stapedotomy, 1 patient with partial reverse classic step stapedotomy, and 1 patient with hemi-stapedectomy were formally admitted to the hospital after surgery (length of stay, 23 h). The indications were vertigo (two patients) and asthenia (one patient). These patients were treated under general anesthesia. Two of these patients resided more than 250 km away from the hospital.	\N	\N
22082232	The present study investigated the lexical representations underlying the production of English schwa words. Two types of schwa words were compared: words with a schwa in poststress position (e.g., mackerel), whose schwa and reduced variants differ in a categorical way, and words with a schwa in prestress position (e.g., salami), whose variants differ in a noncategorical way. Participants named pseudohomophones and matched pseudowords corresponding to schwa and reduced variants of these words. Results revealed an advantage for pseudohomophones over matched pseudowords for both variants of poststress schwa words but only for schwa variants of prestress schwa words. As the pseudohomophone advantage is assumed to reflect the activation of a phonologically matching stored phonological representation, these results suggest that both variants of poststress schwa words are lexically represented while only schwa variants of prestress schwa words are. This result extends the proposal that words with two categorically distinct variants are stored in the production lexicon with 2 representations to another language and demonstrates that this 2-lexeme account does not generalize to pronunciation variants differing from one another in a noncategorical fashion. This finding challenges one of the widely shared assumption of generative models of word production: that content words have only 1 phonological representation. On the other hand, it provides further evidence in favor of another fundamental assumption of these models: that lexical representations are abstract sets of segments rather than fully detailed exemplars.	\N	\N
22087888	To examine the role of perceived gender on fricative identification, a study was conducted in which listeners identified /s/-/∫/ and /s/-/θ/ continua combined with vowels produced by a man and a woman. These were acoustically modified to be consistent with different-sized vocal tracts (VT), and were presented with pictures of men or women. Listeners identified more tokens of /s/ in the /s/-/∫/ and more tokens of /θ/ in the /s/-/θ/ continuum when these sounds were combined with men's vowels, with vowels consistent with a 17 cm VT, and with pictures of men. Results support the hypothesis that listeners incorporate information about talker gender during fricative perception.	\N	\N
22087912	Cochlear hearing loss is often associated with a loss of basilar-membrane (BM) compression, which in turn may contribute to degraded processing of suprathreshold stimuli. Behavioral estimates of compression may therefore be useful as long as they are valid over a wide range of levels and frequencies. Additivity of forward masking (AFM) may provide such a measure, but research to date lacks normative data from normal-hearing (NH) listeners at high sound levels, which is necessary to evaluate data from hearing-impaired (HI) listeners. The present study measured AFM in six NH listeners for signal frequencies of 500, 1500, and 4000 Hz in the presence of background noise, designed to elevate signal thresholds to levels similar to those experienced by HI listeners. Results consistent with compressive BM responses were found for all six listeners at 500 Hz, five listeners at 1500 Hz, but only two listeners at 4000 Hz. Further measurements in the absence of background noise also indicated a lack of consistent compression at 4000 Hz at higher signal levels, in contrast to earlier results collected at lower levels. A better understanding of this issue will be required before AFM can be used as a general behavioral estimate of BM compression.	\N	\N
22087920	The factors influencing the stream segregation of discrete tones and the perceived continuity of discrete tones as continuing through an interrupting masker are well understood as separate phenomena. Two experiments tested whether perceived continuity can influence the build-up of stream segregation by manipulating the perception of continuity during an induction sequence and measuring streaming in a subsequent test sequence comprising three triplets of low and high frequency tones (LHL-[ellipsis (horizontal)]). For experiment 1, a 1.2-s standard induction sequence comprising six 100-ms L-tones strongly promoted segregation, whereas a single extended L-inducer (1.1 s plus 100-ms silence) did not. Segregation was similar to that following the single extended inducer when perceived continuity was evoked by inserting noise bursts between the individual tones. Reported segregation increased when the noise level was reduced such that perceived continuity no longer occurred. Experiment 2 presented a 1.3-s continuous inducer created by bridging the 100-ms silence between an extended L-inducer and the first test-sequence tone. This configuration strongly promoted segregation. Segregation was also increased by filling the silence after the extended inducer with noise, such that it was perceived like a bridging inducer. Like physical continuity, perceived continuity can promote or reduce test-sequence streaming, depending on stimulus context.	\N	\N
22087922	This work was aimed at determining whether binaural interference occurs in electric hearing, and if so, whether it occurs as a consequence of perceptual grouping (central explanation) or if it is related to the spread of excitation in the cochlea (peripheral explanation). Six bilateral cochlear-implant listeners completed a series of experiments in which they judged the lateral position of a target pulse train, lateralized via interaural time or level differences, in the presence of an interfering diotic pulse train. The target and interferer were presented at widely separated electrode pairs (one basal and one apical). The results are broadly similar to those reported for acoustic hearing. All listeners but one showed significant binaural interference in at least one of the stimulus conditions. In all cases of interference, a robust recovery was observed when the interferer was presented as part of an ongoing stream of identical pulse trains, suggesting that the interference was at least partly centrally mediated. Overall, the results suggest that both simultaneous and sequential grouping mechanisms operate in electric hearing, at least for stimuli with a wide tonotopic separation.	\N	\N
22087923	The present study examined the effect of combined spectral and temporal enhancement on speech recognition by cochlear-implant (CI) users in quiet and in noise. The spectral enhancement was achieved by expanding the short-term Fourier amplitudes in the input signal. Additionally, a variation of the Transient Emphasis Spectral Maxima (TESM) strategy was applied to enhance the short-duration consonant cues that are otherwise suppressed when processed with spectral expansion. Nine CI users were tested on phoneme recognition tasks and ten CI users were tested on sentence recognition tasks both in quiet and in steady, speech-spectrum-shaped noise. Vowel and consonant recognition in noise were significantly improved with spectral expansion combined with TESM. Sentence recognition improved with both spectral expansion and spectral expansion combined with TESM. The amount of improvement varied with individual CI users. Overall the present results suggest that customized processing is needed to optimize performance according to not only individual users but also listening conditions.	\N	\N
22093438	In auditory-visual synaesthesia, all kinds of sound can induce additional visual experiences. To identify the brain regions mainly involved in this form of synaesthesia, functional magnetic resonance imaging (fMRI) has been used during non-linguistic sound perception (chords and pure tones) in synaesthetes and non-synaesthetes. Synaesthetes showed increased activation in the left inferior parietal cortex (IPC), an area involved in multimodal integration, feature binding and attention guidance. No significant group-differences could be detected in area V4, which is known to be related to colour vision and form processing. The results support the idea of the parietal cortex acting as sensory nexus area in auditory-visual synaesthesia, and as a common neural correlate for different types of synaesthesia.	\N	\N
22095215	The behavioral and neurofunctional consequences of blindness often include performance enhancements and recruitment of occipital regions for nonvisual tasks. How the neuroanatomical changes resulting from this sensory loss relate to these functional changes is, however, less clear. Previous studies using cortical thickness (CT) measures have shown thicker occipital cortex in early-blind (EB) individuals compared with sighted controls. We hypothesized that this finding reflects the crossmodal plasticity often observed in blind individuals and thus could reflect behavioral adaptations. To address this issue, CT measures in blind (early and late) and sighted subjects were obtained along with several auditory behavioral measures in an attempt to relate behavioral and neuroanatomical changes. Group contrasts confirmed previous results in showing thicker occipital cortex in the EB. Regression analyses between CT measures across the whole brain of all blind individuals with the behavioral scores from 2 tasks in which EB subjects were superior (pitch and melody discrimination) showed that CT of occipital areas was directly related to behavioral enhancements. These findings constitute a compelling demonstration that anatomical changes in occipital areas are directly related to heightened behavioral abilities in the blind and hence support the idea that these anatomical features reflect adaptive compensatory plasticity.	\N	\N
22097102	Daily life in today's society is filled with moments of high state anxiety. State anxiety is the amount of anxiety one is experiencing in the present moment; it is not a personality trait. Many people need simple, cost-effective ways to self-regulate themselves so they can sleep, be more productive, and attend to their activities of daily life. Therefore, the present study questioned whether listening to a steady beat will decrease feelings of state anxiety in healthy subjects. Participants (N=36) between the ages of 20 and 50 volunteered for the study. During this study, experimental anxiety was induced and the Visual Analog Scale served as the measurement tool for both tests. Subjects in the control group sat in silence, while subjects in the experimental group listened to a steady beat of 66 beats per minute. The results of an independent-samples t test indicated significant differences between the groups on the posttest measure, t (34)=2.41, p=.02. Subjects who listened to the steady beat reported less anxiety than subjects who sat in silence. This study suggests that steady beat alone can reduce state anxiety, thus providing a cost-effective and accessible means for self-regulation in the midst of high state anxiety.	\N	\N
22101495	The purpose of the present study was to establish whether the validity effect produced by masked eye gaze cues should be attributed to strictly reflexive mechanisms or to volitional top-down mechanisms. While we find that masked eye gaze cues are effective in producing a validity effect in a central cueing paradigm, we also find that the efficacy of masked gaze cues is sharply constrained by the experimental context. Specifically, masked gaze cues only produced a validity effect when they appeared in the context of unmasked and predictive gaze cues. Unmasked gaze cues, in contrast, produced reliable validity effects across a range of experimental contexts, including Experiment 4 where 80% of the cues were invalid (counter-predictive). Taken together, these results suggest that the effective processing of masked gaze cues requires volitional control, whereas the processing of unmasked (clearly visible) gaze cues appears to benefit from both reflexive and top-down mechanisms.	\N	\N
22102362	The neural events that lead to successful or failed detection of suprathreshold sounds are not well established. In this experiment, event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) were recorded while participants performed two tasks: a primary difficult duration judgment task on a sequence of tones presented to one ear, and a secondary target detection task on an auditory oddball stream presented to the other ear. The paradigm was designed to elicit competition and variability in detection of auditory targets despite identical input. Successful detection of auditory targets was associated mainly with greater fMRI activity in superior parietal cortex and thalamus. In the ERPs, successful detection was linked with a larger fronto-central negativity at 200-400 ms, and a later centro-posterior positivity. Failure to detect targets was associated with greater fMRI signal in the default mode network, a significantly smaller electrical fronto-central negativity and no late positivity. These findings demonstrate that variability in auditory detection is related to modulation of activity in multimodal parietal and frontal networks active ∼ 200 ms after target onset. Results are consistent with a limited capacity and late selection view of attention.	\N	\N
22107896	Auditory perception and learning take place during the third trimester of gestation. Fetuses and newborns who lack typical auditory experience can go on to develop typical socioemotional attachment and language, given a supportive environment. For hospitalized preterm infants in developmentally sensitive neonatal intensive care units, detrimental effects of deviant early auditory experience may be remediated by later experience, but much is unknown about the causes of language deficits of prematurity. Prenatal auditory stimulation programs that incorporate audio speakers against the maternal belly should be discouraged because of possible overstimulation effects on the developing auditory system and sleep/wake state organization.	\N	\N
22108539	Tracing the temporal structure of acoustic events is crucial in order to efficiently adapt to dynamic changes in the environment. In turn, regularity in temporal structure may facilitate tracing of the acoustic signal and its likely spatial source. However, temporal processing in audition extends beyond a domain-general facilitatory function. Temporal regularity and temporal order of auditory events correspond to contextually extracted, statistically sampled relations among sounds. These relations are the backbone of prediction in audition, determining both when an event is likely to occur (temporal structure) and also what type of event can be expected at a specific point in time (formal structure, e.g. spectral information). Here, we develop a model of temporal processing in audition and speech that involves a division of labor between the cerebellum and the basal ganglia in tracing acoustic events in time. As for the cerebellum and its associated thalamo-cortical connections, we refer to its role in the automatic encoding of event-based temporal structure with high temporal precision, while the basal ganglia-thalamo-cortical system engages in the attention-dependent evaluation of longer-range intervals. Recent electrophysiological and neurofunctional evidence suggests that neocortical processing of spectral structure relies on concurrent extraction of event-based temporal information. We propose that spectrotemporal predictive processes may be facilitated by subcortical coding of relevant changes in sound energy as temporal event markers.	\N	\N
22111542	The objectives were: (1) to examine the effects of a directional microphone with different directivity patterns and different microphone combinations on wind noise levels at the hearing aid output; and (2) to derive strategies appropriate for hearing aid selection and future designs. The in-situ frequency responses of a behind-the-ear hearing aid (BTE1) were matched when the hearing aid was programmed to dipole, hypercardioid, cardioids, or adaptive microphone mode. The in-situ frequency responses of another hearing aid (BTE2) were matched among an omnidirectional microphone (OMNI), an adaptive directional microphone (ADM), and a combination of an omnidirectional microphone at low frequencies and an adaptive directional microphone at high frequencies (MIXED). Flow noise was recorded at flow velocities of 0, 4.5, 9.0, and 13.5 m/s. Measurements were repeated for the hypercardioid pattern of BTE1. Flow noise recorded using directional microphones with four directivity patterns and using OMNI, ADM, and MIXED. Directional microphones with different directivity patterns generated similar flow noise levels. ADM yielded higher overall levels than OMNI and MIXED, which had similar overall levels. The adaptive directional microphone is the most versatile microphone for use in wind. The mixed microphone mode is a viable wind noise reduction option.	\N	\N
22115685	Cochlear implants have become a viable treatment option for individuals who present with severe to profound hearing loss. While there are several parameters that affect the successful use of this technology, quality programming of the cochlear implant system is crucial. This review chapter focuses on general device programming techniques, programming techniques specific to children, objective programming techniques, a brief overview of programming parameters of the currently commercially available multichannel systems, and managing patient complaints and device failures. The chapter also provides what the authors believe the future may hold for new programming techniques.	\N	\N
22119935	The loudness dependence of the auditory evoked potential (LDAEP) is considered a noninvasive in vivo marker of central serotonergic functioning in humans. Nevertheless, results of genetic association studies point towards a modulation of this biomarker by dopaminergic neurotransmission. We examined the effect of dopaminergic modulation on the LDAEP using L-3,4-dihydroxyphenylalanine (levodopa)/benserazide (Madopar®) as a challenge agent in healthy volunteers. A double-blind placebo-controlled challenge design was chosen. Forty-two healthy participants (21 females and 21 males) underwent two LDAEP measurements, following a baseline LDAEP measurement either placebo or levodopa (levodopa 200 mg/benserazide 50 mg) were given orally. Changes in the amplitude and dipole source activity of the N1/P2 intensities (60, 70, 80, 90, and 100 dB) were analyzed. The participants of neither the levodopa nor the placebo group showed any significant LDAEP alterations compared to the baseline measurement. The test-retest reliability (Cronbachs Alpha) between baseline and intervention was 0.966 in the verum group and 0.759 in the placebo group, respectively. The administration of levodopa showed no effect on the LDAEP. These findings are in line with other trials using dopamine receptor agonists.	\N	\N
22122114	In this article we report on listener categorization of meaningful environmental sounds. A starting point for this study was the phenomenological taxonomy proposed by Gaver (1993b). In the first experimental study, 15 participants classified 60 environmental sounds and indicated the properties shared by the sounds in each class. In a second experimental study, 30 participants classified and described 56 sounds exclusively made by solid objects. The participants were required to concentrate on the actions causing the sounds independent of the sound source. The classifications were analyzed with a specific hierarchical cluster technique that accounted for possible cross-classifications, and the verbalizations were submitted to statistical lexical analyses. The results of the first study highlighted 4 main categories of sounds: solids, liquids, gases, and machines. The results of the second study indicated a distinction between discrete interactions (e.g., impacts) and continuous interactions (e.g., tearing) and suggested that actions and objects were not independent organizational principles. We propose a general structure of environmental sound categorization based on the sounds' temporal patterning, which has practical implications for the automatic classification of environmental sounds.	\N	\N
22122401	To assess the potential risk of hearing loss to young listeners, due to the use of personal listening devices (PLDs). The study included two parts: (1) A self-report questionnaire on music listening habits, and (2) Physical measurements of preferred listening levels, in quiet and in everyday background noise. Young teenagers aged 13 to 17 years. Part 1 included 289 participants with mean age of 14 years. Part 2 included 11 and 74 participants (2A and 2B) with a mean age of 15 years. Eleven listened to PLDs in quiet conditions (2A) and 74 in everyday background noise (2B). Questionnaire main findings indicated that most of the participants reported high or very high volume settings and demonstrated low awareness towards loud music listening consequences. Physical measurements corrected for diffuse field indicated mean preferred listening levels of: 82 (SD = 9) dBA in quiet, and 89 (SD = 9) dBA in the presence of background noise. The potential risk to hearing of PLDs users was calculated using the 8 hour equivalent level. More than 25% of the participants in the noisy condition were found to be at risk according to occupational damage risk criteria NIOSH, 1998.	\N	\N
22123457	Evidence for cortical sensory activation in the human fetus at the beginning of the third trimester of pregnancy was provided in a recent imaging study. Although hearing is functional before birth, it is not clear whether recognition of the mother's voice is learned in utero or rapidly following delivery. We developed an original fMRI procedure that allows for the specific exploration of fetal brain response to auditory stimuli. This procedure provides the first in vivo evidence for the development of maternal voice recognition in utero between 33 and 34 weeks of gestation. This methodology could have crucial implications in the study of fetal cognition.	\N	\N
22133495	A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between cognitive performance and cerebellar integrity in a specific degeneration of the cerebellar cortex: Spinocerebellar Ataxia type 6 (SCA6). The results demonstrate a critical relationship between verbal working memory and grey matter density in superior (bilateral lobules VI and crus I of lobule VII) and inferior (bilateral lobules VIIIa and VIIIb, and right lobule IX) parts of the cerebellum. We demonstrate that distinct cerebellar regions subserve different components of the prevalent psychological model for verbal working memory based on a phonological loop. The work confirms the involvement of the cerebellum in verbal working memory and defines specific subsystems for this within the cerebellum.	\N	\N
22137677	We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing.	\N	\N
22143297	To demonstrate whether there are differences in the outcomes of children with cochlear implants using the techniques between mastoidectomy with posterior tympanotomy (MPTA) and suprameatal approach (SMA). A total of 44 congenitally deaf children who underwent cochlear implantation before the age of 5 years at the Sixth Hospital Affiliated to Shanghai Jiao tong University from January 2005 to March 2008 were included in this study. Children with severe mental retardation or with cochlear malformations were excluded. Each group had 22 patients; however, 4 patients in the SMA group and 5 in the MPTA group were not included in this study because the assessments for these patients were not available. All children were assessed before surgery and 6, 12, and 24 months after surgery with Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR). Each assessment was given by the child's speech therapist in the familiar environment of the child's home or school. At each interval, the CAP and SIR scores of each group were compared. For the both groups, CAP and SIR scores increased with the time of implant usage during the follow-up period after implantation. However, there were no significant differences in scores of CAP and SIR at the 4 time points between the SMA group and the MPTA group. Intelligible speech and auditory performance of children with cochlear implantation using the SMA were good. There were no differences between children implanted with the SMA technique versus the MPTA technique.	\N	\N
22155324	Temporal congruency promotes perceptual binding of multisensory inputs. Here, we used EEG frequency-tagging to track cortical activities elicited by auditory and visual inputs separately, in the form of steady-state evoked potentials (SS-EPs). We tested whether SS-EPs could reveal a dynamic coupling of cortical activities related to the binding of auditory and visual inputs conveying synchronous vs. non-synchronous temporal periodicities, or beats. The temporally congruent audiovisual condition elicited markedly enhanced auditory and visual SS-EPs, as compared to the incongruent condition. Furthermore, an increased inter-trial phase coherence of both SS-EPs was observed in that condition. Taken together, these observations indicate that temporal congruency enhances the processing of multisensory inputs at sensory-specific stages of cortical processing, possibly through a dynamic binding by synchrony of the elicited activities and/or improved dynamic attending. Moreover, we show that EEG frequency-tagging with SS-EPs constitutes an effective tool to explore the neural dynamics of multisensory integration in the human brain.	\N	\N
22163041	Insects often communicate by sound in mixed species choruses; like humans and many vertebrates in crowded social environments they thus have to solve cocktail-party-like problems in order to ensure successful communication with conspecifics. This is even more a problem in species-rich environments like tropical rainforests, where background noise levels of up to 60 dB SPL have been measured. Using neurophysiological methods we investigated the effect of natural background noise (masker) on signal detection thresholds in two tropical cricket species Paroecanthus podagrosus and Diatrypa sp., both in the laboratory and outdoors. We identified three 'bottom-up' mechanisms which contribute to an excellent neuronal representation of conspecific signals despite the masking background. First, the sharply tuned frequency selectivity of the receiver reduces the amount of masking energy around the species-specific calling song frequency. Laboratory experiments yielded an average signal-to-noise ratio (SNR) of -8 dB, when masker and signal were broadcast from the same side. Secondly, displacing the masker by 180° from the signal improved SNRs by further 6 to 9 dB, a phenomenon known as spatial release from masking. Surprisingly, experiments carried out directly in the nocturnal rainforest yielded SNRs of about -23 dB compared with those in the laboratory with the same masker, where SNRs reached only -14.5 and -16 dB in both species. Finally, a neuronal gain control mechanism enhances the contrast between the responses to signals and the masker, by inhibition of neuronal activity in interstimulus intervals. Thus, conventional speaker playbacks in the lab apparently do not properly reconstruct the masking noise situation in a spatially realistic manner, since under real world conditions multiple sound sources are spatially distributed in space. Our results also indicate that without knowledge of the receiver properties and the spatial release mechanisms the detrimental effect of noise may be strongly overestimated.	\N	\N
22166679	To evaluate the effect of different lipid fractions on auditory brainstem evoked responses in hyperlipidaemia. We conducted a single institution (medical college), prospective, cross-sectional study of 25 hyperlipidaemic patients and 25 normolipidaemic controls, all with a normal hearing threshold on pure tone audiometry. Brainstem evoked response audiometry results were recorded in both groups. The hyperlipidaemic group were further divided into two subgroups, based on the serum value of each lipid fraction: those with less than and those with greater than the mean serum value. These two subgroups were further compared with the control group. The hyperlipidaemic and normolipidaemic groups had statistically significant differences for all audiometry waves apart from the wave I and the III-V interpeak latencies. The subgroups had a statistically significant difference in brainstem evoked responses. We found a statistically significant association between low-density lipoproteins and many waveforms in the hyperlipidaemic group. We found that low-density lipoproteins were significantly associated with many waveforms in hyperlipidaemic patients. Thus, low-density lipoproteins may be important in auditory dysfunction.	\N	\N
22171054	Oscillatory entrainment mechanisms are invoked during attentional processing of rhythmically occurring stimuli, whereby their phase alignment regulates the excitability state of neurons coding for anticipated inputs. These mechanisms have been examined in the delta band (1-3 Hz), where entrainment frequency matches the stimulation rate. Here, we investigated entrainment for subdelta rhythmic stimulation, recording from intracranial electrodes over human auditory cortex during an intersensory audiovisual task. Audiovisual stimuli were presented at 0.67 Hz while participants detected targets within one sensory stream and ignored the other. It was found that entrainment operated at twice the stimulation rate (1.33 Hz), and this was reflected by higher amplitude values in the FFT spectrum, cyclic modulation of alpha-amplitude, and phase-amplitude coupling between delta phase and alpha power. In addition, we found that alpha-amplitude was relatively increased in auditory cortex coincident with to-be-ignored auditory stimuli during attention to vision. Thus, the data suggest that entrainment mechanisms operate within a delimited passband such that for subdelta task rhythms, oscillatory harmonics are invoked. The phase of these delta-entrained oscillations modulates alpha-band power. This may in turn increase or decrease responsiveness to relevant and irrelevant stimuli, respectively.	\N	\N
22171970	Coupling of thalamocortical networks through synchronous oscillations at gamma frequencies (30-80 Hz) has been suggested as a mechanism for binding of auditory sensory information into an object representation, which then becomes accessible for perception and cognition. This study investigated whether contralateral noise interferes with this step of central auditory processing. Neuromagnetic 40-Hz oscillations were examined in young healthy participants while they listened to amplitude-modulated sound in one ear and a multi-talker masking noise in the contralateral ear. Participants were engaged in a gap-detection task, for which their behavioural performance declined under masking. The amplitude modulation of the stimulus elicited steady 40-Hz oscillations with sources in bilateral auditory cortices. Analysis of the temporal dynamics of phase synchrony between source activity and the stimulus revealed two oscillatory components; the first was indicated by an instant onset in phase synchrony with the stimulus while the second showed a 200-ms time constant of gradual increase in phase synchrony after phase resetting by the gap. Masking abolished only the second component. This coincided with masking-related decrease of the P2 wave of the transient auditory-evoked responses whereas the N1 wave, reflecting early sensory processing, was unaffected. Given that the P2 response has been associated with object representation, we propose that the first 40-Hz component is related to representation of low-level sensory input whereas the second is related to internal auditory processing in thalamocortical networks. The observed modulation of oscillatory activity is discussed as reflecting a neural mechanism critical for speech understanding in noise.	\N	\N
22172546	Wernicke's aphasia is a condition which results in severely disrupted language comprehension following a lesion to the left temporo-parietal region. A phonological analysis deficit has traditionally been held to be at the root of the comprehension impairment in Wernicke's aphasia, a view consistent with current functional neuroimaging which finds areas in the superior temporal cortex responsive to phonological stimuli. However behavioural evidence to support the link between a phonological analysis deficit and auditory comprehension has not been yet shown. This study extends seminal work by Blumstein, Baker, and Goodglass (1977) to investigate the relationship between acoustic-phonological perception, measured through phonological discrimination, and auditory comprehension in a case series of Wernicke's aphasia participants. A novel adaptive phonological discrimination task was used to obtain reliable thresholds of the phonological perceptual distance required between nonwords before they could be discriminated. Wernicke's aphasia participants showed significantly elevated thresholds compared to age and hearing matched control participants. Acoustic-phonological thresholds correlated strongly with auditory comprehension abilities in Wernicke's aphasia. In contrast, nonverbal semantic skills showed no relationship with auditory comprehension. The results are evaluated in the context of recent neurobiological models of language and suggest that impaired acoustic-phonological perception underlies the comprehension impairment in Wernicke's aphasia and favour models of language which propose a leftward asymmetry in phonological analysis.	\N	\N
22176307	The parents' evaluation of aural/oral performance of children (PEACH) scale was developed to assess the effectiveness of amplification for children, based on a systematic use of parents' observations of children's performance in real-world environments. The purpose of the present study was to adapt the PEACH scale into the Malay language, and to collect normative data on a group of children with normal hearing. The participants were parents of 74 children aged between 3 months and 13 years of age. Parents were requested to observe their children's auditory/oral behavior in everyday life and to record their observations in the PEACH booklet. High internal consistency (Cronbach's alpha = 0.93) and item-total correlation were found (0.52-0.85). Similar to the published norms for English-speaking children, near-perfect scores were achieved by Malaysian children around 40 months of age. The adapted version can be used to evaluate amplification for children in the Malay speaking environment. The normative curve relating age to scores for the Malay PEACH can be used as a reference against which functional aural/oral performance of hearing-impaired Malaysian children can be evaluated.	\N	\N
22177319	To compare the audiologic outcome and feasibility of bone-anchored hearing aid (BAHA) and external auditory canal reconstruction (EACR) surgeries in pediatric patients presenting a congenital aural atresia (CAA). A retrospective chart review of 40 patients operated in our tertiary pediatric care center between 2002 and 2010 was performed. 20 patients underwent EACR, whereas another 20 patients were implanted with a BAHA device. Air conduction (AC), bone conduction (BC), pure tone average (PTA) and speech discrimination score (SDS) were compared preoperatively, and hearing gain (HG) postoperatively at 6 and at 12 months at frequencies of 500, 1000, 2000 and 4000 Hz. Operative time, complications and associated microtia were documented as well. EACR patients were graded retrospectively upon Jahrsdoerfer's classification. Preoperative AC were significantly different between groups, at 500, 1000 and 2000 Hz but not at 4000 Hz. BAHA group compared postoperatively to EACR group showed significantly a superior HG of 46.9 ± 7.0 dB (p<0.001) and of 39.8(7) ± 7.2(6.9)dB (p<0.001) at 6 months and at 1 year, respectively. Moreover, aided air thresholds from the EACR group revealed an audiologic status similar to those of the BAHA group patients, at 6 months and one year postoperatively. Both groups had a similar evolution of their BC, as well as of the incidence of complications. We report one case of transient facial paralysis in the EACR group. Total operative time is significantly lower (p<0.001) for a BAHA implantation (56 ± 21 min) than for EACR surgery (216 ± 174 min). No preoperative or postoperative correlation (Pearson correlation test; p>0.05) was found between patient's Jahrsdoerfer's score and their audiologic outcome. HG does not seem to be influenced by the presence of microtia. EACR, although constituting an attractive option, does not give acceptable results alone. It can however, when combined to conventional air conduction hearing aids, provide excellent audiologic outcomes comparable to BAHA. BAHA implantation is a reliable, safe and efficient therapeutic option that allows a significantly better audiologic outcome when compared to unaided EACR for patients with CAA.	\N	\N
22178340	Determine the prevalence of 35delG mutation in GJB2 gene in patients with prelingual deafness of no defined etiology whose underwent cochlear implant in the Otolaryngology Department at the Hospital de Clínicas de Porto Alegre and compare the speech recognition index using an open-set of sentences according to the presence or absence of the 35delG mutation. Cross-sectional study nested in a cohort. Were analyzed 37 patients with indeterminate etiology for deafness that underwent to cochlear implant. DNA was extracted and the mutations were studied using Polymerase Chain Reaction followed by gene sequencing. The prevalence of 35delG mutation was 11%. The speech recognition index was 72% in the group with 35delG mutation, and 30% in the group without this mutation (p>0.05). Prevalence of 35delG mutation in this study confirmed findings in the Brazilian literature. There was a clinically significant difference in hearing performance in patients with 35delG. Absence of statistical significance in this result might be attributed to the small number of patients with 35delG in our sample.	\N	\N
22178454	When speech is interrupted by noise, listeners often perceptually "fill-in" the degraded signal, giving an illusion of continuity and improving intelligibility. This phenomenon involves a neural process in which the auditory cortex (AC) response to onsets and offsets of acoustic interruptions is suppressed. Since meaningful visual cues behaviorally enhance this illusory filling-in, we hypothesized that during the illusion, lip movements congruent with acoustic speech should elicit a weaker AC response to interruptions relative to static (no movements) or incongruent visual speech. AC response to interruptions was measured as the power and inter-trial phase consistency of the auditory evoked theta band (4-8 Hz) activity of the electroencephalogram (EEG) and the N1 and P2 auditory evoked potentials (AEPs). A reduction in the N1 and P2 amplitudes and in theta phase-consistency reflected the perceptual illusion at the onset and/or offset of interruptions regardless of visual condition. These results suggest that the brain engages filling-in mechanisms throughout the interruption, which repairs degraded speech lasting up to ~250 ms following the onset of the degradation. Behaviorally, participants perceived speech continuity over longer interruptions for congruent compared to incongruent or static audiovisual streams. However, this specific behavioral profile was not mirrored in the neural markers of interest. We conclude that lip-reading enhances illusory perception of degraded speech not by altering the quality of the AC response, but by delaying it during degradations so that longer interruptions can be tolerated.	\N	\N
22178980	When hearing thresholds are measured with high-frequency resolution there is a pseudo-periodic variation in thresholds across frequency of up to 15-20dB. This variation is called threshold fine structure (previously referred to as threshold microstructure). Consequently, estimates of auditory status based on threshold measures can depend greatly on the specific frequency evaluated. The impact of threshold fine structure on the prediction of auditory status was examined by measuring detection thresholds of pure tones (providing an indication of threshold fine structure) and comparing them with thresholds obtained using linear sweeps, sinusoidally frequency modulated tones, and narrow-band noise. Spontaneous otoacoustic emissions (SOAEs) were also obtained to confirm the established relationship between threshold fine structure and SOAEs. Thresholds obtained using linear sweeps and narrow-band noise provided stable threshold estimates indicating that such threshold estimates were less influenced by threshold fine structure. Consequently, thresholds obtained with these stimuli may provide estimates of cochlear status less dependent of the exact frequency being evaluated, permitting better prediction of performance on other psychoacoustic measures (such as cochlear tuning and loudness perception) and the properties of their more objective measures (such as otoacoustic emissions).	\N	\N
22180019	The purpose of the study was to determine why perceived spatial separation provides a greater release from informational masking in Chinese than English when target sentences in each of the languages are masked by other talkers speaking the same language. Monolingual speakers of English and Mandarin Chinese listened to semantically anomalous sentences in their own language when 1 of 3 maskers was present (speech-spectrum noise, a 2-talker speech masker in the same language, and a 2-talker speech masker in the other language). Both groups benefitted equally from spatial separation when the maskers were speech-spectrum noise or cross-language. Chinese listeners benefitted less from spatial separation than did English listeners when a same-language masker was used. Performance was scored in terms of the number of target words correctly identified; because Chinese target words were composed of 2 "stand-alone" morphemes, the authors also scored Chinese target words as correct when either of the morphemes was correctly identified. When this was done, Chinese and English listeners benefitted equally from spatial separation in all conditions. These results support a model in which release from informational masking in both monolingual English and Chinese listeners occurs because spatial separation facilitates morpheme access in both languages.	\N	\N
22183905	To evaluate the long-term results and predictive factors of a good outcome with the use of a total ossicular replacement prosthesis in children. Retrospective case review. Tertiary referral center. The study included 114 children (116 ears). A total of 116 ears underwent total ossicular chain reconstruction with a titanium prosthesis. Cartilage was always used for tympanic membrane reconstruction. Audiological results were evaluated according to the guidelines of the American Academy of Otolaryngology-Head and Neck Surgery. Predictive factors of audiological results were determined. Logistic regression and χ(2) tests were used for statistical analysis. The mean age at surgery was 9.8 years. Ossiculoplasty was performed during second-look surgery in 91 ears (78.4%) and during another stage in 25 ears (21.6%). The first-stage procedure was always performed for cholesteatoma. Audiometric results were available for 116 ears at 1 year, for 89 ears (76.7%) at 2 years, and for 42 ears (36.2%) at 5 years. Closure of the average air-bone gap (ABG) to within 20 dB was achieved in 65 ears (56%) at 1 year. The mean (SD) preoperative and postoperative (at 1 year) ABGs were 41.0 (9.5) dB and 22.4 (12.6) dB, respectively. There were no cases of extrusion, but 17 luxations of the prosthesis were confirmed by computed tomography. Luxation occurred on average at 31.4 months. Only three 4000-Hz degradations of bone conduction were reported, with no dead ears. We examined 3 predictive factors of auditory results: preoperative ABG, footplate status, and postoperative otoscopic findings. Total ossiculoplasty is a reliable technique in children. Long-term hearing outcomes are stable and satisfactory, but luxation can occur at any time. Preoperative ABG and footplate status are negative predictive factors of auditory results.	\N	\N
22196341	It has recently been conjectured that dyslexia arises from abnormal auditory sampling. What sampling rate is altered and how it affects reading remains unclear. We hypothesized that by impairing phonemic parsing abnormal low-gamma sampling could yield phonemic representations of unusual format and disrupt phonological processing and verbal memory. Using magnetoencephalography and behavioral tests, we show in dyslexic subjects a reduced left-hemisphere bias for phonemic processing, reflected in less entrainment to ≈30 Hz acoustic modulations in left auditory cortex. This deficit correlates with measures of phonological processing and rapid naming. We further observed enhanced cortical entrainment at rates beyond 40 Hz in dyslexics and show that this particularity is associated with a verbal memory deficit. These data suggest that a single auditory anomaly, i.e., phonemic oversampling in left auditory cortex, accounts for three main facets of the linguistic deficit in dyslexia.	\N	\N
22196745	Prosody can be expressed not only by modification to the timing, stress and intonation of auditory speech but also by modifying visual speech. Studies have shown that the production of visual cues to prosody is highly variable (both within and across speakers), however behavioural studies have shown that perceivers can effectively use such visual cues. The latter result suggests that people are sensitive to the type of prosody expressed despite cue variability. The current study investigated the extent to which perceivers can match visual cues to prosody from different speakers and from different face regions. Participants were presented two pairs of sentences (consisting of the same segmental content) and were required to decide which pair had the same prosody. Experiment 1 tested visual and auditory cues from the same speaker and Experiment 2 from different speakers. Experiment 3 used visual cues from the upper and the lower face of the same talker and Experiment 4 from different speakers. The results showed that perceivers could accurately match prosody even when signals were produced by different speakers. Furthermore, perceivers were able to match the prosodic cues both within and across modalities regardless of the face area presented. This ability to match prosody from very different visual cues suggests that perceivers cope with variation in the production of visual prosody by flexibly mapping specific tokens to abstract prosodic types.	\N	\N
22199181	In perception studies, it is common to use vowel stimuli from standardized recordings or synthetic stimuli created using values from well-known published research. Although the use of standardized stimuli is convenient, unconsidered dialect and regional accent differences may introduce confounding effects. The goal of this study was to examine the effect of regional accent variation on vowel identification. The authors analyzed formant values of 8 monophthong vowels produced by 12 talkers from the region where the research took place and compared them with standardized vowels. Fifteen listeners with normal hearing identified synthesized vowels presented in varying levels of noise and at varying spectral distances from the local-dialect values. Acoustically, local vowels differed from standardized vowels, and distance varied across vowels. Perceptually, there was a robust effect of accent similarity such that identification was reduced for vowels at greater distances from local values. Researchers and clinicians should take care in choosing stimuli for perception experiments. It is recommended that regionally validated vowels be used instead of relying on standardized vowels in vowel perception tasks.	\N	\N
22199197	The current study measured, objectively and subjectively, how changes in speech rate affect recognition of English passages in bilingual listeners. Ten native monolingual, 20 English-dominant bilingual, and 20 non-English-dominant bilingual listeners repeated target words in English passages at five speech rates (unprocessed, two expanded, and two compressed), in quiet and in noise. For noise conditions, performance was measured at a signal-to-noise ratio that was determined through an adaptive procedure to avoid ceiling and floor effects. Listeners also made subjective judgments of speech rate, speech clarity, and performance confidence. In noise, stepwise improvement was observed as rate slowed down. A similar effect was not found in quiet. This pattern in performance was largely comparable across listener groups but was most robust in English-dominant listeners. Changes in speech rate and presence of noise significantly affected listeners' subjective ratings; however, no intergroup differences were observed for any of the subjective ratings. Bilingual listeners benefited from slow speech rates, more evidently so in noise than in quiet. Their performance, however, did not reach a monolingual level, even at the most favorable rate. Nonetheless, all listeners reported comparable confidence when processing temporally manipulated English passages.	\N	\N
22207311	We used eyetracking, perceptual discrimination, and production tasks to examine the influences of perceptual similarity and linguistic experience on word recognition in nonnative (L2) speech. Eye movements to printed words were tracked while German and Dutch learners of English heard words containing one of three pronunciation variants (/t/, /s/, or /f/) of the interdental fricative /θ/. Irrespective of whether the speaker was Dutch or German, looking preferences for target words with /θ/ matched the preferences for producing /s/ variants in German speakers and /t/ variants in Dutch speakers (as determined via the production task), while a control group of English participants showed no such preferences. The perceptually most similar and most confusable /f/ variant (as determined via the discrimination task) was never preferred as a match for /θ/. These results suggest that linguistic experience with L2 pronunciations facilitates recognition of variants in an L2, with effects of frequency outweighing effects of perceptual similarity.	\N	\N
22212698	Auditory-evoked potentials represent the response of the auditory pathway to an auditory stimulus. Specific language impairment (SLI) children have delayed language development with difficulties in both understanding and producing spoken language. Hence, the purpose of this study was to determine whether a group of children with SLI had abnormal changes in the auditory middle latency response (AMLR). AMLR was obtained for 19 SLI children and they were studied and compared to normal. Audiological assessment and speech language tests were done for the study group. The results revealed no significant statistical differences between SLI children and the normal with regard to AMLR (P > 0.05). Our results suggest that children with SLI do not have abnormal auditory system response at the level measured by AMLR casting doubt on affection of the hypnotized origin of AMLR, mainly primary auditory cortex, as a cause for delayed language development in those children.	\N	\N
22212767	The LiSN & Learn auditory training software was developed specifically to improve binaural processing skills in children with suspected central auditory processing disorder who were diagnosed as having a spatial processing disorder (SPD). SPD is defined here as a condition whereby individuals are deficient in their ability to use binaural cues to selectively attend to sounds arriving from one direction while simultaneously suppressing sounds arriving from another. As a result, children with SPD have difficulty understanding speech in noisy environments, such as in the classroom. To develop and evaluate the LiSN & Learn auditory training software for children diagnosed with the Listening in Spatialized Noise-Sentences Test (LiSN-S) as having an SPD. The LiSN-S is an adaptive speech-in-noise test designed to differentially diagnose spatial and pitch-processing deficits in children with suspected central auditory processing disorder. Participants were nine children (aged between 6 yr, 9 mo, and 11 yr, 4 mo) who performed outside normal limits on the LiSN-S. In a pre-post study of treatment outcomes, participants trained on the LiSN & Learn for 15 min per day for 12 weeks. Participants acted as their own control. Participants were assessed on the LiSN-S, as well as tests of attention and memory and a self-report questionnaire of listening ability. Performance on all tasks was reassessed after 3 mo where no further training occurred. The LiSN & Learn produces a three-dimensional auditory environment under headphones on the user's home computer. The child's task was to identify a word from a target sentence presented in background noise. A weighted up-down adaptive procedure was used to adjust the signal level of the target based on the participant's response. On average, speech reception thresholds on the LiSN & Learn improved by 10 dB over the course of training. As hypothesized, there were significant improvements in posttraining performance on the LiSN-S conditions where the target and distracter stimuli are spatially separated and which specifically evaluate binaural processing ability (p ranging from <.003 to .0001, η2 ranging from 0.694 to 0.873). In contrast, there was no improvement on the LiSN-S control conditions where the target and distracter stimuli emanate from the same direction (p ranging from .07 to .86, η2 ranging from 0.362 to 0.004). Significant improvements were found posttraining on measures of memory, on one measure of attention, and on self-reported ratings of listening ability. There were no significant differences between post- and 3 mo posttraining scores on any of the assessment tools. The initial LiSN & Learn study has shown that children as young as 6 yr of age are able to complete the training (although some coaxing was needed in a minority of cases). Both parents and children have reported benefits from the training, and feedback from the trial has resulted in extra features being added to the software. In order to further evaluate the efficacy of LiSN & Learn to remediate binaural processing deficits in children a clinical trial is currently under way utilizing a randomized blinded control group design.	\N	\N
22212768	The Australian version of the Listening in Spatialized Noise-Sentences Test (LiSN-S) was originally developed to assess auditory stream segregation skills in children aged 6 to 11 yr with suspected central auditory processing disorder. The LiSN-S creates a three-dimensional auditory environment under headphones. A simple repetition-response protocol is used to assess a listener's speech reception threshold (SRT) for target sentences presented in competing speech maskers. Performance is measured as the improvement in SRT in decibels gained when either pitch, spatial, or both pitch and spatial cues are incorporated in the maskers. To collect additional normative data on the Australian LiSN-S for adolescents and adults up to 60 yr of age, to analyze the effects of age on LiSN-S performance, to examine retest reliability in the older population, and to extrapolate findings from the Australian data so that the North American version of the test can also be used clinically with older adults. In a descriptive design, normative and test-retest reliability data were collected from adolescents and adults and combined with previously published data from Australian children aged 6 to 11 yr. One hundred thirty-two participants with normal hearing aged 12 yr, 0 mo, to 60 yr, 7 mo, took part in the normative data study. Fifty-five participants returned between 2 and 4 mo after the initial assessment for retesting. Analysis of variance revealed a significant effect of age on LiSN-S performance (p < .01 for all LiSN-S measures, ηp2 ranging from 0.16 to 0.54). On the low and high cue SRT measures, planned contrasts revealed significant differences between adults and children aged 13 yr and younger, as well as between 50- to 60-yr-olds and younger adults aged 18-29 yr. Whereas there were significant differences between adults and children on the talker, spatial, and total advantage measures, there were no significant differences in performance in adults aged 18-60 yr. There was a small but significant improvement on retest ranging from 0.5 to 1.2 dB across the four LiSN-S test conditions (p ranging from .01 to <.001). However, there was no significant difference between test and retest on the advantage measures (p ranging from .143 to .768). Test-retest differences across all LiSN-S measures were significantly correlated (r ranging from 0.2 to 0.7, p ranging from .023 to <.00000001) and did not differ as a function of age (p ranging from .178 to .980). As there was no significant difference among adults aged 18-60 yr on the LiSN-S talker, spatial, and total advantage measures, it appears that the decline in ability to understand speech in noise experienced by 50- to 60-yr-olds is not related to their ability to use either spatial or pitch cues. This result suggests that some other factor/s contributes to the decline in speech perception in noise experienced by older adults that is reported in the literature and was demonstrated in this study on the LiSN-S low and high cue SRT measures.	\N	\N
22213908	Contrasting results have been reported regarding the phonetic acquisition of bilinguals. A lack of discrimination has been observed for certain native contrasts in 8-month-old Catalan-Spanish bilingual infants (Bosch & Sebastián-Gallés, 2003a), though not in French-English bilingual infants (Burns, Yoshida, Hill & Werker, 2007; Sundara, Polka & Molnar, 2008). At present, the data for Catalan-Spanish bilinguals constitute an exception in the early language acquisition literature. This study contributes new findings that show that Catalan-Spanish bilingual infants do not lose the capacity to discriminate native contrasts. We used an adaptation of the anticipatory eye movement paradigm (AEM; McMurray & Aslin, 2004) to explore this question. In two experiments we tested the ability of infants from Catalan and Spanish monolingual families and from Catalan-Spanish bilingual families to discriminate a Spanish-Catalan common and a Catalan-specific vowel contrast. Results from both experiments revealed that Catalan-Spanish bilingual infants showed the same discrimination abilities as those shown by their monolingual peers, even in a phonetic contrast that had not been discriminated in previous studies. Our results demonstrate that discrimination can be observed in 8-month-old bilingual infants when tested with a measure not based on recovery of attention. The high ratio of cognates in Spanish and Catalan may underlie the reason why bilinguals failed to discriminate the native vowels when tested with the familiarization-preference procedure but succeeded with the AEM paradigm.	\N	\N
22216557	The purpose of this research was twofold: firstly, to develop a music perception test (MPT) for hearing-aid users, and secondly, to evaluate the influence of non-linear frequency compression (NFC) on music perception with the use of the self-compiled test. This article focuses on the description of the development and validation of the MPT. To date, the main direction in frequency-lowering hearing-aid studies has been in relation to speech perception abilities. As hearing-aid technology has improved, interest has grown in musical perception as a dimension that could improve hearing-aid users' quality of life. The MPT was designed to evaluate different aspects of rhythm, timbre, pitch and melody. The development of the MPT could be described as design-based. Phase 1 of the study included test development and recording, while phase 2 entailed presentation of stimuli to normal hearing listeners (n = 15) and hearing-aid users (n = 4). Based on the findings of phase 2, item analysis was performed to eliminate or change stimuli that resulted in high error rates. During phase 3 the adapted version of the test was performed on a smaller group of normal hearing listeners (n = 4) and 20 hearing-aid users. Results proved that adults with normal hearing as well as adults using hearing aids were able to complete all the sub-tests of the MPT, although hearing-aid users scored lower on the various sub-tests than normal hearing listeners. For the rhythm section of the MPT normal hearing listeners scored on average 93.8% versus 75.5% of hearing-aid users; for the timbre section the scores were 83% versus 62.3% respectively. Normal hearing listeners obtained an average score of 86.3% for the pitch section and 88.2% for the melody section, compared with the 70.8% and 61.9% respectively obtained by hearing-aid users. This implies that the MPT can be used successfully for assessment of music perception in hearing-aid users within the South African context and may therefore result in more effective hearing-aid fittings taking place. The test can be used as a counselling tool to assist audiologists and patients in understanding the problems they experience regarding music perception, and might be used for future musical training in areas where participants experience problems in customising individual fittings.	\N	\N
22217385	Various recent studies attest that reading involves creating an implicit prosodic representation of the written text which may systematically affect the resolution of syntactic ambiguities in sentence comprehension. Research up to now suggests that implicit prosody itself depends on a partial syntactic analysis of the text, raising the question of whether implicit prosody contributes to the parsing process, or whether it merely interprets the syntactic analysis. The present reading experiments examine the influence of stress-based linguistic rhythm on the resolution of local lexical-syntactic ambiguities in German. Both speech production data from unprepared oral reading and eye-tracking results from silent reading demonstrate that readers favor syntactic analyses that allow for a prosodic representation in which stressed and unstressed syllables alternate rhythmically. The findings contribute evidence confirming immediate and guiding effects of linguistic rhythm on the earliest stages of syntactic parsing in reading.	\N	\N
22221469	Auditory sustained responses have been recently suggested to reflect neural processing of speech sounds in the auditory cortex. As periodic fluctuations below the pitch range are important for speech perception, it is necessary to investigate how low frequency periodic sounds are processed in the human auditory cortex. Auditory sustained responses have been shown to be sensitive to temporal regularity but the relationship between the amplitudes of auditory evoked sustained responses and the repetitive rates of auditory inputs remains elusive. As the temporal and spectral features of sounds enhance different components of sustained responses, previous studies with click trains and vowel stimuli presented diverging results. In order to investigate the effect of repetition rate on cortical responses, we analyzed the auditory sustained fields evoked by periodic and aperiodic noises using magnetoencephalography. Sustained fields were elicited by white noise and repeating frozen noise stimuli with repetition rates of 5-, 10-, 50-, 200- and 500 Hz. The sustained field amplitudes were significantly larger for all the periodic stimuli than for white noise. Although the sustained field amplitudes showed a rising and falling pattern within the repetition rate range, the response amplitudes to 5 Hz repetition rate were significantly larger than to 500 Hz. The enhanced sustained field responses to periodic noises show that cortical sensitivity to periodic sounds is maintained for a wide range of repetition rates. Persistence of periodicity sensitivity below the pitch range suggests that in addition to processing the fundamental frequency of voice, sustained field generators can also resolve low frequency temporal modulations in speech envelope.	\N	\N
22224482	We reported a case of an elderly female patient affected by musical hallucinations (MHs) as the unique symptom of a right temporal ischemic stroke. A functional magnetic resonance imaging examination was performed in the patient and in five age- and sex-matched normal controls (NC) to detect the complex neural substrate subserving MHs in such a context. Although an activation pattern involving the primary auditory cortex and the temporal associative areas bilaterally was found in the patient and NC, a significant increased activation mostly located in right temporal cortex (in the ischemic area), was observed in the patient. Further functional neuroimaging studies should be performed to detect the complex neural pathways underlying MHs and to find out differences between these hallucinations and real music perception.	\N	\N
22227006	Aging disrupts neural timing, reducing the nervous system's ability to precisely encode sound. Given that the neural representation of temporal features is strengthened with musical training in young adults, can musical training offset the negative impact of aging on neural processing? By comparing auditory brainstem timing in younger and older musicians and nonmusicians to a consonant-vowel speech sound /da/. we document a musician's resilience to age-related delays in neural timing.	\N	\N
22232409	To compare the development of phonological skills in children with specific language impairment (SLI) with and without literacy delay and to examine whether kindergarten phonological skills could discriminate these 2 groups. In a longitudinal study, 8 children with SLI and literacy delay, 10 children with SLI and normal literacy, and 14 typically developing children were studied from the last year of kindergarten to the start of Grade 3. A wide range of phonological tasks (phonological awareness [PA], verbal short-term memory [vSTM], and rapid automatized naming [RAN]) were administered yearly. The SLI group with literacy delay scored significantly lower than the typically developing children on almost all phonological tasks in all grades, whereas the SLI group with normal literacy scored significantly lower only on demanding PA and vSTM tasks. A combination of kindergarten PA and RAN skills could correctly classify 75% of the children with SLI. By including vSTM, the discriminatory value did not increase. Children with SLI and normal literacy at age 8;1 [years;months] continued to have difficulties with demanding PA and vSTM tasks. Children with SLI and poor PA and RAN in kindergarten were at high risk of developing literacy problems in a transparent orthography.	\N	\N
22237762	The objective of the study was to compare the performance of cochlear implantation between post-meningitic and non-meningitic patients, and to evaluate the impact on hearing outcome of technical advances in cochlear implant technology. Retrospective chart review was used as the study design. Twenty adults with post-meningitic profound hearing loss receiving unilateral or bilateral cochlear implants between 1990 and 2008 were tested. Results were compared to a control group of 46 adults implanted for a non-meningitic hearing loss, with the same pre-operative speech scores. Speech scores were poorer in post-meningitic patients compared to those of control group, whatever the duration after implantation (p < 0.0001). Speech scores of subjects implanted and fitted before 2001 were compared to those of subjects implanted after 2001, with the same duration of hearing loss. Performance improved with implants and processors available after 2001, with a magnitude of improvement higher in post-meningitic patients (p < 0.0001 and p < 0.05 in post-meningitic and control groups, respectively, two-way ANOVA). Consequently, speech scores of post-meningitic patients implanted after 2001 achieved those of control subjects (two-way ANOVA). Advances in cochlear implant technology and coding strategy improve hearing outcome in post-meningitic adult patients, who now achieve similar performance as those of non-meningitic patients.	\N	\N
22246139	Dynamic-range compression is routinely used in bilaterally fitted hearing devices. The objective of this study was to investigate how compression applied independently at each ear affects spatial perception in normal-hearing listeners and to relate the effects to changes in binaural cues caused by the compression for different types of sound. A semantic-differential method was used to measure the spatial attributes of sounds. Eleven normal-hearing participants responded to questions addressing certainty of location, diffuseness, movement, image splits, and externalization of sounds. Responses were given on seven-point scales between pairs of opposing terms. Stimuli included speech and a range of synthetic sounds with varying characteristics. Head-related transfer functions were used to simulate a source at an azimuth of -60° or +60°. Three processing conditions were compared: (1) an unprocessed reference condition; (2) fast-acting, wide-dynamic-range compression operating independently at each ear; and (3) imposition of a static bias in interaural level difference (ILD) equivalent to that generated by the compression under steady state conditions. All processing was applied in a high-frequency channel above 2 kHz. The three processing conditions were compared separately in two bandwidth conditions: a high-pass condition in which the high-frequency channel was presented to listeners in isolation and a full-bandwidth condition in which the high-frequency channel was recombined with the unprocessed low-frequency channel. Hierarchical cluster analysis was used to group related questions based on similarity of participants' responses. This led to the calculation of composite scores for four spatial attributes: "diffuseness," "movement," "image split," and "externalization." Compared with the unprocessed condition, fast-acting compression significantly increased diffuseness, movement, and image-split scores and significantly reduced externalization scores. The effects of compression were greater when listeners heard the high-frequency channel in isolation than when it was recombined with the unprocessed low-frequency channel. The effects were apparent only for sounds containing gradual onsets and offsets, including speech. Dynamic compression had a much more pronounced effect on the spatial attributes of sounds than imposition of a static bias in ILD. Fast-acting compression at high frequencies operating independently at each ear can adversely affect the spatial attributes of sounds in normal-hearing listeners by increasing diffuseness, increasing or giving rise to a sense of movement, causing images to split, and affecting the externalization of sounds. The effects are reduced, but not eliminated, when listeners have access to undisturbed low-frequency cues. Sounds containing gradual onsets and offsets, including speech, are most affected. The effects arise primarily as a result of relatively slow changes in ILD that are generated as the sound level at one or both ears crosses the compression threshold. The results may have implications for the use of compression in bilaterally fitted hearing devices, specifically in relation to spatial perception in dynamic situations.	\N	\N
22248574	Feedback connections among auditory cortical regions may play an important functional role in processing naturalistic speech, which is typically considered a problem solved through serial feed-forward processing stages. Here, we used fMRI to investigate whether activity within primary auditory cortex (PAC) is sensitive to the perceived clarity of degraded sentences. A region-of-interest analysis using probabilistic cytoarchitectonic maps of PAC revealed a modulation of activity, in the most primary-like subregion (area Te1.0), related to the intelligibility of naturalistic speech stimuli that cannot be driven by stimulus differences. Importantly, this effect was unique to those conditions accompanied by a perceptual increase in clarity. Connectivity analyses suggested sources of input to PAC are higher-order temporal, frontal and motor regions. These findings are incompatible with feed-forward models of speech perception, and suggest that this problem belongs amongst modern perceptual frameworks in which the brain actively predicts sensory input, rather than just passively receiving it.	\N	\N
22251287	Previous behavioural research suggests that infants possess phonologically detailed representations of the vowels and consonants in familiar words. These tasks examine infants' sensitivity to mispronunciations of a target label in the presence of a target and distracter image. Sensitivity to the mispronunciation may, therefore, be contaminated by the degree of mismatch between the distracter label and the heard mispronounced label. Event-related potential (ERP) studies allow investigation of infants' sensitivity to the relationship between a heard label (correct or mispronounced) and the referent alone using single picture trials. ERPs also provide information about the timing of lexico-phonological activation in infant word recognition. The current study examined 14-month-olds' sensitivity to vowel mispronunciations of familiar words using ERP data from single picture trials. Infants were presented with familiar images followed by a correct pronunciation of its label, a vowel mispronunciation or a phonologically unrelated non-word. The results support and extend previous behavioural findings that 14-month-olds are sensitive to mispronunciations of the vowels in familiar words using an ERP task. We suggest that the presence of pictorial context reinforces infants' sensitivity to mispronunciations of words, and that mispronunciation sensitivity may rely on infants accessing the cross-modal associations between word forms and their meanings.	\N	\N
22256834	This study investigated the impact of an established behavioural dysarthria treatment on acoustic and perceptual measures of speech in two adults with Down syndrome (DS) and dysarthria to obtain preliminary measures of treatment effect, effect size and treatment feasibility. A single-subject A-B-A experimental design was used to measure the effects of the Lee Silverman Voice treatment (LSVT®) on speech in two adults with DS and dysarthria. Dependent measures included vocal sound pressure level (dB SPL), phonatory stability and listener intelligibility scores. Statistically significant improvements (p < 0.05) in vocal dB SPL and phonatory stability were present following treatment in both participants. Speech intelligibility scores improved in one of the two participants. These data suggest that people with DS and dysarthria can respond positively to intensive speech treatment such as LSVT. Further investigations are needed to develop speech treatments specific to DS.	\N	\N
22265373	We discuss experimental support for the existence of a corollary discharge signal of attention movement control and its formulation in terms of the corollary discharge of attention model of attention movement (CODAM). The data is from fMRI, MEG and EEG activity observed about 200 ms after stimulus onset in various attention paradigms and in which the activity is mainly sited in parietal and extra-striate visual areas. Moreover the data arises from neural activity observed before report of a subject's experience occurs. The overall experimental support for the existence of a copy of the attention movement control signal generates, it is suggested, a viable route to explore the relation between this signal and human consciousness, as concluded in the paper.	\N	\N
22280585	Despite many studies investigating auditory spatial impressions in rooms, few have addressed the impact of simultaneous visual cues on localization and the perception of spaciousness. The current research presents an immersive audiovisual environment in which participants were instructed to make auditory width judgments in dynamic bi-modal settings. The results of these psychophysical tests suggest the importance of congruent audio visual presentation to the ecological interpretation of an auditory scene. Supporting data were accumulated in five rooms of ascending volumes and varying reverberation times. Participants were given an audiovisual matching test in which they were instructed to pan the auditory width of a performing ensemble to a varying set of audio and visual cues in rooms. Results show that both auditory and visual factors affect the collected responses and that the two sensory modalities coincide in distinct interactions. The greatest differences between the panned audio stimuli given a fixed visual width were found in the physical space with the largest volume and the greatest source distance. These results suggest, in this specific instance, a predominance of auditory cues in the spatial analysis of the bi-modal scene.	\N	\N
22280586	When speech is in competition with interfering sources in rooms, monaural indicators of intelligibility fail to take account of the listener's abilities to separate target speech from interfering sounds using the binaural system. In order to incorporate these segregation abilities and their susceptibility to reverberation, Lavandier and Culling [J. Acoust. Soc. Am. 127, 387-399 (2010)] proposed a model which combines effects of better-ear listening and binaural unmasking. A computationally efficient version of this model is evaluated here under more realistic conditions that include head shadow, multiple stationary noise sources, and real-room acoustics. Three experiments are presented in which speech reception thresholds were measured in the presence of one to three interferers using real-room listening over headphones, simulated by convolving anechoic stimuli with binaural room impulse-responses measured with dummy-head transducers in five rooms. Without fitting any parameter of the model, there was close correspondence between measured and predicted differences in threshold across all tested conditions. The model's components of better-ear listening and binaural unmasking were validated both in isolation and in combination. The computational efficiency of this prediction method allows the generation of complex "intelligibility maps" from room designs.	\N	\N
22280718	The high soprano range was investigated by acoustic and electroglottographic measurements of 12 sopranos and high-speed endoscopy of one of these. A single laryngeal transition was observed on glissandi above the primo passaggio. It supports the existence of two distinct laryngeal mechanisms in the high soprano range: M2 and M3, underlying head and whistle registers. The laryngeal transition occurred gradually over several tones within the interval D#5-D6. It occurred over a wider range and was completed at a higher pitch for trained than untrained sopranos. The upper limit of the laryngeal transition during glissandi was accompanied by pitch jumps or instabilities, but, for most singers, it did not coincide with the upper limit of R1:f(0) tuning (i.e., tuning the first resonance to the fundamental frequency). However, pitch jumps could also be associated with changes in resonance tuning. Four singers demonstrated an overlap range over which they could sing with a full head or fluty resonant quality. Glottal behaviors underlying these two qualities were similar to the M2 and M3 mechanisms respectively. Pitch jumps and discontinuous glottal and spectral changes characteristic of a M2-M3 laryngeal transition were observed on decrescendi produced within this overlap range.	\N	\N
22289805	Human speech perception is highly resilient to acoustic distortions. In addition to distortions from external sound sources, degradation of the acoustic structure of the sound itself can substantially reduce the intelligibility of speech. The degradation of the internal structure of speech happens, for example, when the digital representation of the signal is impoverished by reducing its amplitude resolution. Further, the perception of speech is also influenced by whether the distortion is transient, coinciding with speech, or is heard continuously in the background. However, the complex effects of the acoustic structure and continuity of the distortion on the cortical processing of degraded speech are unclear. In the present magnetoencephalography study, we investigated how the cortical processing of degraded speech sounds as measured through the auditory N1m response is affected by variation of both the distortion type (internal, external) and the continuity of distortion (transient, continuous). We found that when the distortion was continuous, the N1m was significantly delayed, regardless of the type of distortion. The N1m amplitude, in turn, was affected only when speech sounds were degraded with transient internal distortion, which resulted in larger response amplitudes. The results suggest that external and internal distortions of speech result in divergent patterns of activity in the auditory cortex, and that the effects are modulated by the temporal continuity of the distortion.	\N	\N
22292057	To the extent that sensorineural systems are efficient, redundancy should be extracted to optimize transmission of information, but perceptual evidence for this has been limited. Stilp and colleagues recently reported efficient coding of robust correlation (r = .97) among complex acoustic attributes (attack/decay, spectral shape) in novel sounds. Discrimination of sounds orthogonal to the correlation was initially inferior but later comparable to that of sounds obeying the correlation. These effects were attenuated for less-correlated stimuli (r = .54) for reasons that are unclear. Here, statistical properties of correlation among acoustic attributes essential for perceptual organization are investigated. Overall, simple strength of the principal correlation is inadequate to predict listener performance. Initial superiority of discrimination for statistically consistent sound pairs was relatively insensitive to decreased physical acoustic/psychoacoustic range of evidence supporting the correlation, and to more frequent presentations of the same orthogonal test pairs. However, increased range supporting an orthogonal dimension has substantial effects upon perceptual organization. Connectionist simulations and Eigenvalues from closed-form calculations of principal components analysis (PCA) reveal that perceptual organization is near-optimally weighted to shared versus unshared covariance in experienced sound distributions. Implications of reduced perceptual dimensionality for speech perception and plausible neural substrates are discussed.	\N	\N
22292257	To investigate the effect of regular scuba diving on the hearing thresholds of sport divers who have no history of noise exposure or ear-related accidents. Comprehensive topographic examination of the peripheral hearing system of sport divers. Cross-sectional study. General sport diving community. 81 sport divers with a mean of 300 dives each were compared to a control group of 81 non-divers. Participants were classified into three age groups. Examination included microscopic otoscopy, tympanometry, pure-tone audiometry (PTA) including air and bone conduction, speech audiometry and otoacoustic emissions (OAE). PTA suggested significant differences of the hearing thresholds at several frequencies between sport divers and non-divers in all age groups, although a Bonferroni correction for multiple testing was applied. Interestingly, the results were contradictory. Divers obtained better hearing results in air conduction, whereas non-divers showed better results in bone conduction. Speech audiometry and OAE did not reveal significant differences. There are no published studies of the peripheral cochlear system of divers that have used a combination of PTA, speech audiometry and OAE. All studies suggesting hearing impairment in divers were based on PTA and might have been influenced by a lack of accuracy of PTA. Our results suggest that diving does not adversely affect the hearing system of sport divers. A thorough test battery of audiological methods implying PTA, speech audiometry and OAE may contribute to offer more reliable results to answer the question of whether commercial or military divers are at higher risk for hearing detoriation.	\N	\N
22293014	More than 100 years ago, Huey (1908/1968) indicated that the upper part of words was more relevant for perception than the lower part. Here we examined whether mutilated words, in their upper/lower portions (e.g., ), can automatically access their word units in the mental lexicon. To that end, we conducted four masked repetition priming experiments with the lexical decision task. Results showed that mutilated primes produced a sizeable masked repetition priming effect. Furthermore, the magnitude of the masked repetition priming effect was greater when the upper part of the primes was preserved than when the lower portion was preserved-this was the case not only when the mutilated words were presented in lower case but also when the mutilated words were presented in upper case. Taken together, these findings suggest that the front-end of computational models of visual-word recognition should be modified to provide a more realistic account at the level of letter features.	\N	\N
22305992	To form a unified percept of our environment, the human brain integrates information within and across the senses. This MEG study investigated interactions within and between sensory modalities using a frequency analysis of steady-state responses that are elicited time-locked to periodically modulated stimuli. Critically, in the frequency domain, interactions between sensory signals are indexed by crossmodulation terms (i.e. the sums and differences of the fundamental frequencies). The 3 × 2 factorial design, manipulated (1) modality: auditory, visual or audiovisual (2) steady-state modulation: the auditory and visual signals were modulated only in one sensory feature (e.g. visual gratings modulated in luminance at 6 Hz) or in two features (e.g. tones modulated in frequency at 40 Hz & amplitude at 0.2 Hz). This design enabled us to investigate crossmodulation frequencies that are elicited when two stimulus features are modulated concurrently (i) in one sensory modality or (ii) in auditory and visual modalities. In support of within-modality integration, we reliably identified crossmodulation frequencies when two stimulus features in one sensory modality were modulated at different frequencies. In contrast, no crossmodulation frequencies were identified when information needed to be combined from auditory and visual modalities. The absence of audiovisual crossmodulation frequencies suggests that the previously reported audiovisual interactions in primary sensory areas may mediate low level spatiotemporal coincidence detection that is prominent for stimulus transients but less relevant for sustained SSR responses. In conclusion, our results indicate that information in SSRs is integrated over multiple time scales within but not across sensory modalities at the primary cortical level.	\N	\N
22306805	In human communication, direct speech (e.g., Mary said, "I'm hungry") is perceived as more vivid than indirect speech (e.g., Mary said that she was hungry). This vividness distinction has previously been found to underlie silent reading of quotations: Using functional magnetic resonance imaging (fMRI), we found that direct speech elicited higher brain activity in the temporal voice areas (TVA) of the auditory cortex than indirect speech, consistent with an "inner voice" experience in reading direct speech. Here we show that listening to monotonously spoken direct versus indirect speech quotations also engenders differential TVA activity. This suggests that individuals engage in top-down simulations or imagery of enriched supra-segmental acoustic representations while listening to monotonous direct speech. The findings shed new light on the acoustic nature of the "inner voice" in understanding direct speech.	\N	\N
22310087	To review outcomes following paediatric cholesteatoma surgery performed between 1999 and 2009 in a tertiary paediatric ENT unit. Retrospective case note review. A total of 137 mastoid procedures were recorded. Fifty-four per cent of children were observed to have disease involving the entire middle-ear cleft and mastoid complex. The revision rate was 25 per cent. Time to recurrence was one to three years in 17 patients, three to six years in five patients, and six to nine years in three cases. Eight of 25 revision cases demonstrated spontaneous improvement in air conduction thresholds following primary surgery. A high facial ridge and inadequate meatoplasty correlated highly with disease recurrence. Children tend to present with aggressive disease. Disease extent and ossicular chain involvement are associated with a higher risk of recurrent disease. Spontaneous improvement in hearing thresholds following cholesteatoma surgery should alert the clinician to recurrent disease.	\N	\N
22310374	The use of cochlear implants in the rehabilitation of hearing-impaired patients is now widely established and offers great benefits for children. To evaluate these benefits, the Evaluation of Auditory Responses to Speech (EARS®) assessment tool was designed in 1995. The objectives of this study were to assess the auditory perceptual skills in a large paediatric population over time, as well as to provide standardised values. An international multicentre study was conducted in 35 clinics from 1996 to 2009. During this period, 765 children were assessed with the EARS in 10 test intervals: pre-operative, first fitting and then 1, 3, 6, and 12 months after the first fitting and annually thereafter, up to a maximum period of 5 years. The auditory skills improved significantly over time for all speech perception tests and questionnaires as well as between single test intervals: pre-operative to 6 months, 6 months to 1 year and 1 year to 2 years. Standardised values of the children stratified according to their age at implantation were calculated. The auditory perceptual skills significantly improved over time. The standardised values will help professionals set therapeutic goals and counsel parents accordingly.	\N	\N
22314920	Although cochlear implant (CI) users frequently report deterioration of sound quality when listening to music, few methods exist to quantify these subjective claims. 1) To design a novel research method for quantifying sound quality perception in CI users during music listening; 2) To validate this method by assessing one attribute of music perception, bass frequency perception, which is hypothesized to be relevant to overall musical sound quality perception. Limitations in bass frequency perception contribute to CI-mediated sound quality deteriorations. The proposed method will quantify this deterioration by measuring CI users' impaired ability to make sound quality discriminations among musical stimuli with variable amounts of bass frequency removal. A method commonly used in the audio industry (multiple stimulus with hidden reference and anchor [MUSHRA]) was adapted for CI users, referred to as CI-MUSHRA. CI users and normal hearing controls were presented with 7 sound quality versions of a musical segment: 5 high pass filter cutoff versions (200-, 400-, 600-, 800-, 1000-Hz) with decreasing amounts of bass information, an unaltered version ("hidden reference"), and a highly altered version (1,000-1,200 Hz band pass filter; "anchor"). Participants provided sound quality ratings between 0 (very poor) and 100 (excellent) for each version; ratings reflected differences in perceived sound quality among stimuli. CI users had greater difficulty making overall sound quality discriminations as a function of bass frequency loss than normal hearing controls, as demonstrated by a significantly weaker correlation between bass frequency content and sound quality ratings. In particular, CI users could not perceive sound quality difference among stimuli missing up to 400 Hz of bass frequency information. Bass frequency impairments contribute to sound quality deteriorations during music listening for CI users. CI-MUSHRA provided a systematic and quantitative assessment of this reduced sound quality. Although the effects of bass frequency removal were studied here, we advocate CI-MUSHRA as a user-friendly and versatile research tool to measure the effects of a wide range of acoustic manipulations on sound quality perception in CI users.	\N	\N
22316007	To measure the acceptable noise level (ANL) with and without noise reduction algorithms (NRAs), and to predict ΔANL, i.e. the difference in acceptable noise level with and without NRAs. The ANL test was applied to three NRAs. Furthermore, the measured ΔANL was predicted using several methods based on either the calculation of the signal-to-noise ratio or correlation methods of the processed signals with an unprocessed reference signal. Ten normal-hearing and eleven hearing-impaired subjects accomplished the ANL test. In general, the ANL test could determine an increased acceptance of noise with some NRAs. However, great inter-individual differences also resulted that were attributed to audible distortions when an NRA was used. Prediction of the mean measured DANL was possible, but individual prediction of DANL failed due to inter-individual differences. Mean DANL was predicted more accurately for hearing-impaired subjects when individual hearing loss was taken into account. The ANL test is a suitable tool for measuring the advantage of one NRA. A prediction of the measured individual ΔANL failed. However, mean DANL could be predicted with some methods. Furthermore, the individual hearing loss should be taken into account for a more accurate prediction for hearing-impaired subjects.	\N	\N
22325920	Factors affecting perceptions of occupational suitability were examined for speakers who stutter and speakers who do not stutter. In Experiment 1, 58 adults who do not stutter heard one of two audio recordings (less severe stuttering, more severe stuttering) of a speaker who stuttered. Participants rated the speaker's communicative functioning, personal attributes, and suitability for 32 occupations, along with perceptions of the occupations' speaking demands and educational requirements. Perceived speaking demand strongly affected occupational suitability ratings at both levels of stuttering severity. In Experiment 2, 58 additional adults who do not stutter heard a recording of another adult in one of two conditions (fluent speech, pseudo-stuttering), and provided the same ratings as in Experiment 1. In the pseudo-stuttering condition, participants' perceptions of occupational speaking demand again had a strong effect on occupational suitability ratings. In the fluent condition, suitability ratings were affected primarily by perceived educational demand; perceived speaking demand was of secondary importance. Across all participants in Experiment 2, occupational suitability ratings were associated with ratings of the speaker's personal attributes and communicative functioning. In both experiments, speakers who stuttered received lower suitability ratings for high speaking demand occupations than for low speaking demand occupations. Ratings for many high speaking occupations, however, fell just below the midpoint of the occupational suitability scale, suggesting that participants viewed these occupations as less appropriate, but not necessarily inappropriate, for people who stutter. Overall, the findings support the hypothesis that people who stutter may face occupational stereotyping and/or role entrapment in work settings. At the end of this activity the reader will be able to (a) summarize main findings on research related to the work-related experiences of people who stutter, (b) describe factors that affect perceptions of which occupations are best suited for speakers who stutter and speakers who do not stutter, and (c) discuss how findings from the present study relate to previous findings on occupational advice for people who stutter.	\N	\N
22326589	The present study was aimed at investigating the relationship between the mismatch negativity (MMN) and psychoacoustical effects of sequential streaming on comodulation masking release (CMR). The influence of sequential streaming on CMR was investigated using a psychoacoustical alternative forced-choice procedure and electroencephalography (EEG) for the same group of subjects. The psychoacoustical data showed, that adding precursors comprising of only off-signal-frequency maskers abolished the CMR. Complementary EEG data showed an MMN irrespective of the masker envelope correlation across frequency when only the off-signal-frequency masker components were present. The addition of such precursors promotes a separation of the on- and off-frequency masker components into distinct auditory objects preventing the auditory system from using comodulation as an additional cue. A frequency-specific adaptation changing the representation of the flanking bands in the streaming conditions may also contribute to the reduction of CMR in the stream conditions, however, it is unlikely that adaptation is the primary reason for the streaming effect. A neurophysiological correlate of sequential streaming was found in EEG data using MMN, but the magnitude of the MMN was not correlated with the audibility of the signal in CMR experiments. Dipole source analysis indicated different cortical regions involved in processing auditory streaming and modulation detection. In particular, neural sources for processing auditory streaming include cortical regions involved in decision-making.	\N	\N
22326590	The primary goal of this study was to characterize the variability in auditory-nerve temporal response patterns obtained with the electrically evoked compound action potential (ECAP) within and across a relatively large group of cochlear-implant recipients. ECAPs were recorded in response to each of 21 pulses in a pulse train for five rates (900, 1200, 1800, 2400, and 3500 pps) and three cochlear regions (basal, middle, and apical). An alternating amplitude pattern was typically observed across the pulse train for slower rates, reflecting refractory properties of individual nerve fibers. For faster rates, the alternation ceased and overall amplitudes were substantially lower relative to the first pulse in the train, reflecting cross-fiber desynchronization. The following specific parameters were examined: (1) the rate at which the alternating pattern ceased (termed stochastic rate), (2) the alternation depth and the rate at which the maximum alternation occurred, and (3) the average normalized ECAP amplitude across the pulse train (measure of overall adaptation/desynchronization). Data from 29 ears showed that stochastic rates for the group spanned the entire range of rates tested. The majority of subjects (79%) had different stochastic rates across the three cochlear regions. The stochastic rate occurred most frequently at 2400 pps for basal and middle electrodes, and at 3500 pps for apical electrodes. Stimulus level was significantly correlated with stochastic rate, where higher levels yielded faster stochastic rates. The maximum alternation depth averaged 19% of the amplitude for the first pulse. Maximum alternation occurred most often at 1800 pps for basal and apical electrodes, and at 1200 pps for middle electrodes. These differences suggest some independence between alternation depth and stochastic rate. Finally, the overall amount of adaptation or desynchronization ranged from 63% (for 900 pps) to 23% (for 3500 pps) of the amplitude for the first pulse. Differences in temporal response properties across the cochlea within subjects may have implications for developing new speech-processing strategies that employ varied rates across the array.	\N	\N
22326591	There is evidence that humans represent numbers in the form of a mental number line (MNL). Here we show that the MNL modulates the representation of visual and haptic space both in healthy individuals and right-brain-damaged patients, both with and without left unilateral spatial neglect (USN). Participants were asked to estimate the midpoint of visually or haptically explored rods while listening to task-irrelevant stimuli: a small digit ("2"), a large digit ("8"), or a non-numerical auditory stimulus ("blah"). In a control silent condition, the bisection error of USN patients was biased rightwards (namely, the marker of USN) only in the visual modality. Regardless of the direction of the bisection error committed in silent trials, listening to the small digit shifted the perceived midline leftwards, and listening to the large digit shifted the perceived midline rightwards, compared to a control condition in which a neutral syllable ("blah") was presented. The shift induced by listening to numbers occurred independently of the modality of response (i.e., both in vision and haptics), and in every group of participants. Interestingly, the effect of auditory numbers processing on space estimation was overall larger for haptically than for visually explored space in all participants. In conclusion, the present data show that listening to irrelevant numbers affects space perception also in patients with left USN, indicating that the spatial representation and attention processes disrupted by USN are not involved in these numerical magnitude-spatial effects.	\N	\N
22326876	Individuals diagnosed with schizophrenia show deficiencies of basic neurophysiological sorting mechanisms. This study further investigated this issue, focusing on the two phenomena, laterality of coding and auditory forward masking. A specific audiometric method for use in psychiatry was the measuring set up to register brain stem audiograms (ABRs). A sample of 49 schizophrenic patients was compared with three control groups consisting of healthy reference subjects (n=49), attention deficit hyperactivity disorder (ADHD) patients (n=29), Asperger syndrome (AS) patients (n=13) and drug-induced psychotic patients (n=14). Schizophrenic patients showed significant abnormal laterality of brainstem activity in wave II of the auditory brainstem response (ABR) in comparison with all other study groups. Forward masking effects in the superior olive complex were coded significantly differently by schizophrenic patients compared to control groups except for the AS group. The results suggest deficits in the coding of auditory stimuli in the lower parts of the auditory pathway in schizophrenia and indicate that increased peripheral lateral asymmetry and forward masking aberrances could be neurophysiological markers for the disorder.	\N	\N
22327619	Visual cues are known to aid auditory processing when they provide direct information about signal content, as in lip reading. However, some studies hint that visual cues also aid auditory perception by guiding attention to the target in a mixture of similar sounds. The current study directly tests this idea for complex, nonspeech auditory signals, using a visual cue providing only timing information about the target. Listeners were asked to identify a target zebra finch bird song played at a random time within a longer, competing masker. Two different maskers were used: noise and a chorus of competing bird songs. On half of all trials, a visual cue indicated the timing of the target within the masker. For the noise masker, the visual cue did not affect performance when target and masker were from the same location, but improved performance when target and masker were in different locations. In contrast, for the chorus masker, visual cues improved performance only when target and masker were perceived as coming from the same direction. These results suggest that simple visual cues for when to listen improve target identification by enhancing sounds near the threshold of audibility when the target is energetically masked and by enhancing segregation when it is difficult to direct selective attention to the target. Visual cues help little when target and masker already differ in attributes that enable listeners to engage selective auditory attention effectively, including differences in spectrotemporal structure and in perceived location.	\N	\N
22329567	To determine the optimal seating position in a noisy classroom for students with unilateral hearing loss (UHL) without any auditory rehabilitation as compared to normal-hearing adults and student peers. Speech discrimination scores (SDS) for babble noise at distances of 3, 4, 6, 8, and 10 m from a speaker were measured in a simulated classroom measuring 300 m3 (reverberation time = 0.43 s). Students with UHL (n = 25, 10-19 years old), normal-hearing students (n = 25), and normal-hearing adults (n = 25). The SDS for the normal-hearing adults at the 3, 4, 6, 8, and 10 m distances were 90.0±6.4%, 84.7±7.9%, 80.6±10.0%, 75.5±12.6%, and 68.8±13.0%, respectively. Those for the normal-hearing students were 90.1±6.2%, 78.1±9.4%, 66.4±10.7%, 61.8±11.2%, and 60.8±10.9%. Those for the UHL group were 81.7±9.0%, 70.2±12.4%, 62.1±17.2%, 52.4±17.1%, and 48.9±17.9%. The UHL group needed a seating position of 4.35 m to achieve an equivalent mean SDS as those for normal-hearing adults seated at 10 m. Likewise, the UHL group needed to be seated at 6.27 m to have an equivalent SDS as the normal-hearing students seated at 10 m. Students with UHL in noisy classrooms require seating ranging from 4.35 m to no further than 6.27 m away from a teacher to obtain a SDS comparable to normal hearing adults and student peers.	\N	\N
22337493	Complete psychometric functions for phoneme and word recognition scores at 8 signal-to-noise ratios from -15 dB to 20 dB were generated for the first 10, 20, and 25, as well as all 50, three-word presentations of the Tri-Word or Computer Assisted Speech Recognition Assessment (CASRA) Test (Gelfand, 1998) based on the results of 12 normal-hearing young adult participants from the original study. The psychometric functions for both phoneme and word scores were very similar and essentially overlapping for all set sizes. Performance on the shortened tests accounted for 98.8% to 99.5% of the full (50-set) test variance with phoneme scoring, and 95.8% to 99.2% of the full test variance with word scoring. Shortening the tests accounted for little if any of the variance in the slopes of the functions. The psychometric functions for abbreviated versions of the Tri-Word speech recognition test using 10, 20, and 25 presentation sets were described and are comparable to those of the original 50-presentation approach for both phoneme and word scoring in healthy, normal-hearing, young adult participants.	\N	\N
22341758	The neural mechanisms used in tone rises and falls in Mandarin were investigated. Nine participants were scanned while they named one-character pictures that required rising or falling tone responses in Mandarin: the left insula and right putamen showed stronger activation between rising and falling tones; the left brainstem showed weaker activation between rising and falling tones. Connectivity analysis showed that the significant projection from the laryngeal motor cortex to the brainstem which was present in rising tones was absent in falling tones. Additionally, there was a significant difference between the connection from the insula to the laryngeal motor cortex which was negative in rising tones but positive in falling tones. These results suggest that the significant projection from the laryngeal motor cortex to the brainstem used in rising tones was not active in falling tones. The connection from the left insula to the laryngeal motor cortex that differs between rising and falling tones may control whether the rise mechanism is active or not.	\N	\N
22343068	Interaural intensity disparities (IIDs), the cues all animals use to localize high frequency sounds, are initially processed in the lateral superior olive (LSO) by a subtractive process where inputs from one ear excite and inputs from the other ear inhibit LSO neurons. Such cells are called excitatory-inhibitory (EI) neurons and are prominent not only in the LSO but also in higher nuclei, which include the dorsal nucleus of the lateral lemniscus (DNLL) and inferior colliculus (IC). The IC is of particular interest since its EI cells receive diverse innervation patterns from a large number of lower nuclei, which include the DNLLs and LSOs, and thus comprise a population with diverse binaural properties. The first part of this review focuses on the circuits that create EI cells in the LSO, DNLL and IC. The second section then turns to the responses evoked by dynamic IIDs that change over time, as with multiple sounds that emanate from different regions of space or moving sound sources. I show that many EI neurons in the IC respond to dynamic IIDs in ways that are not predictable from their responses to static IIDs, IIDs presented one at a time. In the final section, results from in vivo whole cell recording in the IC are presented and address the connectional basis for the responsiveness to dynamic IIDs. The principal conclusion is that EI cells comprise a diverse population. The diversity is created by the particular set of inputs each EI type receives and is expressed in the differences in the responses to dynamic IIDs that are generated by those inputs. These results show that the construction of EI neurons in the IC imparts features that not only encode the location of an individual sound source, but also that allow animals to determine the direction of a moving sound and to focus and localize a single sound in midst of many sounds, as typically occurs in the daily lives of all animals.	\N	\N
22344314	To assess the effects of spatial frequency and phase alignment of mask components in pattern masking, target threshold vs. mask contrast (TvC) functions for a sine-wave grating (S) target were measured for five types of mask: a sine-wave grating (S), a square-wave grating (Q), a missing fundamental square-wave grating (M), harmonic complexes consisting of phase-scrambled harmonics of a square wave (Qp), and harmonic complexes consisting of phase-scrambled harmonics of a missing fundamental square wave (Mp). Target and masks had the same fundamental frequency (0.46 cpd) and the target was added in phase with the fundamental frequency component of the mask. Under monocular viewing conditions, the strength of masking depends on phase relationships among mask spatial frequencies far removed from that of the target, at least 3 times the target frequency, only when there are common target and mask spatial frequencies. Under dichoptic viewing conditions, S and Q masks produced similar masking to each other and the phase-scrambled masks (Qp and Mp) produced less masking. The results suggest that pattern masking is spatial frequency broadband in nature and sensitive to the phase alignments of spatial components.	\N	\N
22352523	Knowledge-based speech recognition systems extract acoustic cues from the signal to identify speech characteristics. For channel-deteriorated telephone speech, acoustic cues, especially those for stop consonant place, are expected to be degraded or absent. To investigate the use of knowledge-based methods in degraded environments, feature extrapolation of acoustic-phonetic features based on Gaussian mixture models is examined. This process is applied to a stop place detection module that uses burst release and vowel onset cues for consonant-vowel tokens of English. Results show that classification performance is enhanced in telephone channel-degraded speech, with extrapolated acoustic-phonetic features reaching or exceeding performance using estimated Mel-frequency cepstral coefficients (MFCCs). Results also show acoustic-phonetic features may be combined with MFCCs for best performance, suggesting these features provide information complementary to MFCCs.	\N	\N
22352610	Recent acoustic descriptions have shown that Spanish and Portuguese vowels are produced differently in Europe and Latin America. The present study investigates whether comparable between-variety differences exist in vowel perception. Spanish, Peruvian, Portuguese, and Brazilian listeners were tested in a vowel identification task with stimuli sampled from the whole vowel space. The mean perceived first (F1) and second formant (F2) of every vowel category were compared across varieties. For both languages, perception exhibited the same between-variety differences as production for F1 but not F2, which suggests correspondence between produced F1 and perceived vowel height but not between F2 and frontness.	\N	\N
22352612	It is hypothesized that in sine-wave replicas of natural speech, lexical tone recognition would be severely impaired due to the loss of F0 information, but the linguistic information at the sentence level could be retrieved even with limited tone information. Forty-one native Mandarin-Chinese-speaking listeners participated in the experiments. Results showed that sine-wave tone-recognition performance was on average only 32.7% correct. However, sine-wave sentence-recognition performance was very accurate, approximately 92% correct on average. Therefore the functional load of lexical tones on sentence recognition is limited, and the high-level recognition of sine-wave sentences is likely attributed to the perceptual organization that is influenced by top-down processes.	\N	\N
22352622	The combined effect of low-pass filtering (cut-off frequencies between 500 and 3000 Hz) and periodic interruptions (1.5 and 10 Hz) on speech intelligibility was investigated. When combined, intelligibility was lower than each manipulation alone, even in some conditions where there was no effect from a single manipulation (such as the fast interruption rate of 10 Hz). By using young normal-hearing listeners, potential suprathreshold deficits and aging effects that may occur due to hearing impairment were eliminated. Thus, the results imply that reduced audibility of high-frequency speech components may partially explain the reduced intelligibility of interrupted speech in hearing impaired persons.	\N	\N
22352624	In the context of binaural audio rendering, choosing the best head-related transfer function (HRTF) for an individual from large databases poses several problems. This study proposes a method to reduce the size of a given HRTF database. Participants, 45 in total, were asked to rate the quality of binaural synthesis for 46 HRTFs. The lack of reciprocity in the ratings was noted. Results were used to create a perceptually optimized HRTF subset which satisfied all participants' judgments. The subset was validated using localization tests on a separate group of subjects with results showing reduced errors when subjects were given their best choice, rather than their worst choice HRTF.	\N	\N
22353565	Exposure to synchronous but spatially discordant auditory and visual inputs produces adaptive recalibration of the respective localization processes, which manifest themselves in measurable aftereffects. Here we report two experiments that examined the time course of visual recalibration of apparent sound location in order to establish the build-up and dissipation of recalibration. In Experiment 1 participants performed a sound localization task before and during exposure to an auditory-visual discrepancy. In Experiment 2, participants performed a sound localization task before and after 60, 180 or 300 exposures to the discrepancy and aftereffects were measured across a series of post-adaptation sound localization trials. The results show that recalibration is very fast. Substantial aftereffects are obtained after only 18-24 exposures and asymptote appears to be reached between 60 and 180 exposures. The rate of adaptation was independent of the size of the discrepancy. The retention of the aftereffect was strong, as we found no dissipation, not even after as few as 60 exposure trials.	\N	\N
22356177	Talkers hyperarticulate vowels when communicating with listeners that require increased speech intelligibility. Vowel hyperarticulation is said to be motivated by knowledge of the listener's linguistic needs because it typically occurs in speech to infants, foreigners and hearing-impaired listeners, but not to non-verbal pets. However, the degree to which vowel hyperarticulation is determined by feedback from the listener is surprisingly less well understood. This study examines whether mothers' speech input is driven by knowledge of the infant's linguistic competence, or by the infant's feedback cues. Specifically, we manipulated (i) mothers' knowledge of whether they believed their infants could hear them or not, and (ii) the audibility of the speech signal available to the infant (full or partial audibility, or inaudible). Remarkably, vowel hyperarticulation was completely unaffected by mothers' knowledge; instead, there was a reduction in the degree of hyperarticulation such that vowels were hyperarticulated to the greatest extent in the full audibility condition, there was reduced hyperarticulation in the partially audible condition, and no hyperarticulation in the inaudible condition. Thus, while it might be considered adaptive to hyperarticulate speech to the hearing-impaired adult or infant, when these two factors (infant and hearing difficulty) are coupled, vowel hyperarticulation is sacrificed. Our results imply that infant feedback drives talker behavior and raise implications for intervention strategies used with carers of hearing-impaired infants.	\N	\N
22359341	To date, the underlying cognitive and neural mechanisms of absolute pitch (AP) have remained elusive. In the present fMRI study, we investigated verbal and tonal perception and working memory in musicians with and without absolute pitch. Stimuli were sine wave tones and syllables (names of the scale tones) presented simultaneously. Participants listened to sequences of five stimuli, and then rehearsed internally either the syllables or the tones. Finally participants indicated whether a test stimulus had been presented during the sequence. For an auditory stroop task, half of the tonal sequences were congruent (frequencies of tones corresponded to syllables which were the names of the scale tones) and half were incongruent (frequencies of tones did not correspond to syllables). Results indicate that first, verbal and tonal perception overlap strongly in the left superior temporal gyrus/sulcus (STG/STS) in AP musicians only. Second, AP is associated with the categorical perception of tones. Third, the left STG/STS is activated in AP musicians only for the detection of verbal-tonal incongruencies in the auditory stroop task. Finally, verbal labelling of tones in AP musicians seems to be automatic. Overall, a unique feature of AP appears to be the similarity between verbal and tonal perception.	\N	\N
22361102	The ability of infants to develop recognition of a common stress pattern that is language specific has been tested mainly in trochaic languages with a strong-weak (SW) stress pattern. The goals of the present study were: (a) to test Hebrew-learning infants on their stress pattern preference in the Hebrew language, for which the weak-strong (WS) stress pattern is the common one, and (b) to test whether the infants would generalize any preference for the common stress pattern in Hebrew to English words, which belong to a different rhythmic class. Fifty-six 9-month-old Hebrew-learning infants were tested on their preference for SW and WS stress patterns using Hebrew and English bisyllabic words with the head-turn preference procedure. The infants showed preference for WS Hebrew words but not for SW English words. Hebrew-learning infants recognize the common stress pattern in their native language, supporting language-specific distributional learning by infants. This recognition, however, is not generalized to a foreign language with different prosodic characteristics.	\N	\N
22361320	The aim of this study was to determine which level-dependent hearing aid digital signal-processing strategy (DSP) participants preferred when listening to music and/or performing a speech-in-noise task. Two receiver-in-the-ear hearing aids were compared: one using 32-channel adaptive dynamic range optimization (ADRO) and the other wide dynamic range compression (WDRC) incorporating dual fast (4 channel) and slow (15 channel) processing. The manufacturers' first-fit settings based on participants' audiograms were used in both cases. Results were obtained from 18 participants on a quick speech-in-noise (QuickSIN; Killion, Niquette, Gudmundsen, Revit, & Banerjee, 2004) task and for 3 music listening conditions (classical, jazz, and rock). Participants preferred the quality of music and performed better at the QuickSIN task using the hearing aids with ADRO processing. A potential reason for the better performance of the ADRO hearing aids was less fluctuation in output with change in sound dynamics. ADRO processing has advantages for both music quality and speech recognition in noise over the multichannel WDRC processing that was used in the study. Further evaluations of which DSP aspects contribute to listener preference are required.	\N	\N
22362394	Schizophrenia is associated with deficits in the ability to perceive emotion based on tone of voice. The basis for this deficit remains unclear, however, and relevant assessment batteries remain limited. The authors evaluated performance in schizophrenia on a novel voice emotion recognition battery with well-characterized physical features, relative to impairments in more general emotional and cognitive functioning. The authors studied a primary sample of 92 patients and 73 comparison subjects. Stimuli were characterized according to both intended emotion and acoustic features (e.g., pitch, intensity) that contributed to the emotional percept. Parallel measures of visual emotion recognition, pitch perception, general cognition, and overall outcome were obtained. More limited measures were obtained in an independent replication sample of 36 patients, 31 age-matched comparison subjects, and 188 general comparison subjects. Patients showed statistically significant large-effect-size deficits in voice emotion recognition (d=1.1) and were preferentially impaired in recognition of emotion based on pitch features but not intensity features. Emotion recognition deficits were significantly correlated with pitch perception impairments both across (r=0.56) and within (r=0.47) groups. Path analysis showed both sensory-specific and general cognitive contributions to auditory emotion recognition deficits in schizophrenia. Similar patterns of results were observed in the replication sample. The results demonstrate that patients with schizophrenia show a significant deficit in the ability to recognize emotion based on tone of voice and that this deficit is related to impairment in detecting the underlying acoustic features, such as change in pitch, required for auditory emotion recognition. This study provides tools for, and highlights the need for, greater attention to physical features of stimuli used in studying social cognition in neuropsychiatric disorders.	\N	\N
22366255	The aim of this study was to test a multimodal event-related potential (ERP) paradigm in chronic solvent encephalopathy (CSE) to develop a sensitive method for the clinical diagnostics to CSE. The study comprised 11 CSE patients and 13 healthy controls. We used three tasks: an auditory odd-ball (AUD), a visual detection (VIS), and a recognition memory (MEM) task. The auditory and visual stimuli were presented in single- and dual-task conditions. The auditory P300 amplitude in single-task condition was smaller in the patient group than in the control group at the parietal (Pz) but not at the frontal midline electrode location. The auditory P300 response in the dual task condition AUD+VIS was unrecognizable in 8 of 11 patients and in 1 of 13 controls and in the AUD+MEM condition in 10 of 11 patients and in 4 of 13 controls. In the AUD+MEM condition, the auditory P300 amplitude at Pz was smaller in the patient group than in the control group. Reaction time for auditory stimuli in both dual conditions as well as for visual stimuli in AUD+VIS condition were in the patient group prolonged. The ERP results indicate that CSE patients present with slowed performance speed and difficulties in allocation of attention. Based on ERP results, the disturbance in brain activity in CSE seems to affect posterior aspects of the frontoparietal continuity. The multimodal paradigm seems promising as a tool for the clinical diagnostics of CSE.	\N	\N
22367093	A major focus of recent attempts to enhance cochlear implant (CI) systems has been to increase the rate at which pulses are delivered to the electrode array. One basis for these attempts has been the expectation that faster stimulation rates would lead to an enhanced representation of temporal modulation information. However, there is recent physiological and behavioral evidence to suggest that the reverse may be the case. Here, the effects of stimulation rate on the perception of amplitude modulation were assessed using both modulation detection and modulation frequency discrimination tasks for a range of pulse rates extending considerably higher than the highest rate tested in previous studies and for different speech-relevant modulation frequencies. Detection of sinusoidal amplitude modulation was assessed in five CI users using monopolar pulse trains presented to a single electrode at rates of 482, 723, 1447, 2894, and 5787 pulses per second (pps). Adaptive procedures were used to find the minimal detectable modulation depth at modulation frequencies of 10 and 100 Hz and at carrier levels of 25%, 50%, and 75% of the electrode's dynamic range. Discrimination of modulation frequency was examined for the same range of pulse rates for the highest carrier level. Similar adaptive procedures determined the minimum increase in modulation frequency that could be detected relative to reference modulation frequencies of 10, 100, and 200 Hz. In both tasks, level roving was implemented to minimize possible loudness cues. Consistent with previous evidence, modulation detection thresholds were better for higher carrier levels and lower modulation frequencies. When modulation depth at threshold was expressed in terms of the ratio of the depth of the modulation and the carrier level in dB (i.e., 20 log m), performance was significantly better at lower pulse rates. However, when modulation depth was expressed relative to dynamic range, the effect of pulse rate was no longer significant, reflecting the fact that dynamic range increases with pulse rate. Modulation frequency discrimination clearly worsened with increasing modulation frequency, but there was no significant effect of pulse rate. In contrast to some recent evidence, no clearly harmful effect of higher pulse rates on modulation perception was found. However, even with very fast stimulation rates, tested over a wide range of modulation frequencies and with two different tasks, there is no evidence of benefit from faster stimulation rates in the perception of amplitude modulation.	\N	\N
22384211	Recent behavioral neuroscience research revealed that elementary reactive behavior can be improved in the case of cross-modal sensory interactions thanks to underlying multisensory integration mechanisms. Can this benefit be generalized to an ongoing coordination of movements under severe physical constraints? We choose a juggling task to examine this question. A central issue well-known in juggling lies in establishing and maintaining a specific temporal coordination among balls, hands, eyes and posture. Here, we tested whether providing additional timing information about the balls and hands motions by using external sound and tactile periodic stimulations, the later presented at the wrists, improved the behavior of jugglers. One specific combination of auditory and tactile metronome led to a decrease of the spatiotemporal variability of the juggler's performance: a simple sound associated to left and right tactile cues presented antiphase to each other, which corresponded to the temporal pattern of hands movement in the juggling task. A contrario, no improvements were obtained in the case of other auditory and tactile combinations. We even found a degraded performance when tactile events were presented alone. The nervous system thus appears able to integrate in efficient way environmental information brought by different sensory modalities, but only if the information specified matches specific features of the coordination pattern. We discuss the possible implications of these results for the understanding of the neuronal integration process implied in audio-tactile interaction in the context of complex voluntary movement, and considering the well-known gating effect of movement on vibrotactile perception.	\N	\N
22401989	We used structural magnetic resonance imaging (MRI) and voxel based morphometry (VBM) to investigate whether the efficiency of word processing in the non-native language (lexical efficiency) and the number of non-native languages spoken (2+ versus 1) were related to local differences in the brain structure of bilingual and multilingual speakers. We dissociate two different correlates for non-native language processing. Firstly, multilinguals who spoke 2 or more non-native languages had higher grey matter density in the right posterior supramarginal gyrus compared to bilinguals who only spoke one non-native language. This is interpreted in relation to previous studies that have shown that grey matter density in this region is related to the number of words learnt in bilinguals relative to monolinguals and in monolingual adolescents with high versus low vocabulary. Our second result was that, in bilinguals, grey matter density in the left pars opercularis was positively related to lexical efficiency in second language use, as measured by the speed and accuracy of lexical decisions and the number of words produced in a timed verbal fluency task. Grey matter in the same region was also negatively related to the age at which the second language was acquired. This is interpreted in terms of previous findings that associated the left pars opercularis with phonetic expertise in the native language.	\N	\N
22406661	Detection performance is impaired for a visual target presented in an apparent motion (AM) trajectory, and this AM interference weakens when orientation information is inconsistent between the target and AM stimuli. These indicate that the target is perceptually suppressed by internal object representations of AM stimuli established along the AM trajectory. Here, we showed that transient sounds presented together with AM stimuli could enhance the magnitude of AM interference. Furthermore, this auditory effect attenuated when frequencies of the sounds were inconsistent during AM. We also confirmed that the sounds wholly elevated the magnitude of AM interference irrespective of the inconsistency in orientation information between the target and AM stimuli when the saliency of the sounds was maintained. These results suggest that sounds can contribute to the robust establishment and spatiotemporal maintenance of the internal object representation of an AM stimulus.	\N	\N
22410729	To compare temporal aspects of peripheral neural responses and central auditory perception between groups of younger adult and elderly cochlear implant users. Cohort study. Academic hospital and cochlear implant center. Adult cochlear implant users aged 28 to 57 years in the younger group (n = 5) and 61 to 89 years (n = 9) in the elderly group. All subjects used Advanced Bionics devices. Diagnostic. Time constants of neural (i.e., electrically evoked compound action potentials [ECAPs]) and perceptual recovery from forward masking. Interstimulus intervals (ISIs) were varied in both experiments. ECAP recovery rates were equivalent between groups, and no correlation was found between ECAP recovery and age. No correlations were found between ECAP recovery and speech perception. Psychophysical recovery was significantly slower in the elderly compared with the younger subjects (p < 0.0005), with a significant effect of age (R2 = 0.70, p < 0.0005). At the longest ISI (240 ms), elderly subjects experienced a mean maximum threshold shift of 35.2% (relative to 1 ms ISI) versus 14.8% for younger subjects. There was a significant positive relationship between psychophysical recovery and consonant-nucleus-consonant word scores (R2 = 0.62, p < 0.001), although no relationship was found with Hearing in Noise Test sentences. These findings suggest that difficulties observed in speech perception by elderly CI users may be due to age-related changes in the central rather than peripheral auditory system. With further study, these results may provide information to allow clinicians to assess patients' temporal processing abilities and facilitate setting program parameters that will maximize their auditory perceptual experience with a cochlear implant.	\N	\N
22411592	Gender priming studies have demonstrated facilitation of noun production following pre-activation of a target noun's grammatical gender. Findings provide support for models in which syntactic information relating to words is stored within the lexicon and activated during lexical retrieval. Priming effects are observed in the context of determiner plus noun phrase production. Few studies demonstrate gender priming effects in bare noun production (i.e., nouns in isolation). We investigated the effects of English determiner primes on bare mass and count noun production. In two experiments, participants named pictures after exposure to primes involving congruent, incongruent and neutral determiners. Facilitation of noun production by congruent and neutral determiner primes was found in both experiments. The results suggest that noun phrase syntax is activated in lexical retrieval, even when not explicitly required for production. Post hoc analysis of the relative frequency of congruent and incongruent prime-target pairs provides support for a frequency-based interpretation of the data.	\N	\N
22423705	The frequency response and sensitivity of the ER-3A and ER-2 insert earphones are measured in the occluded-ear simulator using three ear canal extensions. Compared to the other two extensions, the DB 0370 (Brüel & Kjær), which is recommended by the international standards, introduces a significant resonance peak around 4500 Hz. The ER-3A has an amplitude response like a band-pass filter (1400 Hz, 6 dB/octave -4000 Hz, -36 dB/octave), and a group delay with "ripples" of up to ±0.5 ms, while the ER-2 has an amplitude response, and a group delay which are flat and smooth up to above 10000 Hz. Both earphones are used to record auditory brainstem responses, ABRs, from 22 normal-hearing ears in response to two chirps and a click at levels from 20 to 80 dB nHL. While the click-ABRs are slightly larger for ER-2 than for ER-3A, the chirp-ABRs are much larger for ER-2 than for ER-3A at levels below 60 dB nHL. With a simulated amplitude response of the ER-3A and the smooth group delay of the ER-2 it is shown that the increased chirp-ABR amplitude with the ER-2 is caused by its broader amplitude response and not by its smoother group delay.	\N	\N
22426232	Rapid information processing in the human brain is vital to survival in a highly dynamic environment. The key tool humans use to exchange information is spoken language, but the exact speed of the neuronal mechanisms underpinning speech comprehension is still unknown. Here we investigate the time course of neuro-lexical processing by analyzing neuromagnetic brain activity elicited in response to psycholinguistically and acoustically matched groups of words and pseudowords. We show an ultra-early dissociation in cortical activation elicited by these stimulus types, emerging ∼50 ms after acoustic information required for word identification first becomes available. This dissociation is the earliest brain signature of lexical processing of words so far reported, and may help explain the evolutionary advantage of human spoken language.	\N	\N
22436117	Assessment of interaural asymmetry (IA) on dichotic listening tests becomes challenging when accuracy on one or both ears are at ceiling. Cognitive task demands are often increased to avoid this situation, raising the possibility that non-auditory-specific processes will further influence IA estimation. To investigate the utility of low-pass filtered dichotic speech stimuli (dichotic filtered words [DFWs]) as a potential auditory-specific technique for increasing task difficulty in the dichotic listening paradigm. A prospective experimental study investigating differences in IA observed for a group of young adults on three dichotic listening tasks differentiated on the basis of stimulus type (unfiltered words, DFWs) and/or mode of test administration (divided attention [DIV]; directed attention [DIR]). Thirty-two adults between 18 and 34 yr of age participated in the study. Accuracy scores on each ear and normalized values of IA (via laterality index) served as dependent measures evaluated in a repeated-measures ANOVA design. Correlation and regression analyses were carried out to investigate potential relationships between participants' behavioral accuracy to experimental stimuli and the magnitude of observed IA. Behavioral profiles of IA were constructed for each participant. Using a traditional DIV test mode, DFW stimuli produced a significantly larger right-ear advantage (REA) as compared to unfiltered speech. The magnitude of the average REA to DFW stimuli was not statistically different between DIV and DIR test modes for the group. Inspection of individual performances, however, revealed that out of the participants who demonstrated meaningful IA during DIV, approximately half produced the same or greater amount of IA during DIR whereas half showed a relative decrease. Participants' accuracy to left-sided stimuli was most related to the magnitude of observed IA across tasks. The utility of low-pass filtered speech may be helpful in the evaluation of IA obtained during dichotic testing.	\N	\N
22436413	The aim of this study was to report speech performance in quiet and in noise, sound localization with cochlear implanted children bilaterally. Their performances were compared also in unilateral conditions. In addition, speech and language evaluation was analyzed. Twenty-three children implanted with Neurelec Digisonic SP devices in 3 tertiary centres were tested on a battery of speech perception tests in quiet and in noise. Localization was assessed by lateralization tasks (90° and 30°). Progress in speech and language development and subjective assessment of benefit were assessed using several rating scales and questionnaires (categories of auditory perception, speech intelligibility rating, family participating rating scale). Children scored better when tested in bilateral conditions rather than in unilateral conditions. In quiet, the mean scores for the poorer and better side were 52% and 73%, respectively. In the bilateral condition, the mean score increased to 83%. In noise, the mean scores were 39% and 57% respectively, which increased to a mean of 70% in the bilateral condition. Nine children (<9 years) completed the ±90° lateralization task. For both unilateral conditions performance was not significantly different from chance level. In the bilateral condition, the mean score was 86%. The ±30° lateralization score was completed by eight of the older children (>9 years). The scores in the unilateral conditions were closed to chance level, but significantly better in the bilateral condition (mean of 86%). Performances in bilateral conditions were significantly better than in unilateral conditions on speech perception in quiet and in noise. Localization was significantly better when tested in the bilateral condition for ±90° lateralization task for the younger children and the ±30° task for the older children. All these results supported the hypothesis than bilateral cochlear implantation is more beneficial than unilateral implantation in children.	\N	\N
22436438	It has been demonstrated that written and spoken language processing are tightly linked. Here we focus on the development of this relationship at the time children start reading and writing. We hypothesize that the newly acquired knowledge about graphemes shapes lexical access in neural spoken word recognition. A group of preliterate children (six years old) and two groups of beginning readers (six and eight years old) were tested in a spoken word identification task. Using word onset priming we compared behavioural and neural facilitation for target words in identical prime-target pairs (e.g., mon-monster) and in prime target pairs that varied in the first speech sound (e.g., non-monster, Variation condition). In both groups of beginning readers priming was less effective in the Variation condition than in the Identity condition. This was indexed by less behavioural facilitation and enhanced P350 amplitudes in the event related potentials (ERPs). In the group of preliterate children, by contrast, both conditions did not differ. Together these results reveal that lexical access in beginning readers is based on more acoustic detail than lexical access in preliterate children. The results are discussed in the light of bidirectional speech and print interactions in readers.	\N	\N
22445915	Developmental dyslexia is associated with impaired speech-in-noise perception. The goal of the present research was to further characterize this deficit in dyslexic adults. In order to specify the mechanisms and processing strategies used by adults with dyslexia during speech-in-noise perception, we explored the influence of background type, presenting single target-words against backgrounds made of cocktail party sounds, modulated speech-derived noise or stationary noise. We also evaluated the effect of three listening configurations differing in terms of the amount of spatial processing required. In a monaural condition, signal and noise were presented to the same ear while in a dichotic situation, target and concurrent sound were presented to two different ears, finally in a spatialised configuration, target and competing signals were presented as if they originated from slightly differing positions in the auditory scene. Our results confirm the presence of a speech-in-noise perception deficit in dyslexic adults, in particular when the competing signal is also speech, and when both signals are presented to the same ear, an observation potentially relating to phonological accounts of dyslexia. However, adult dyslexics demonstrated better levels of spatial release of masking than normal reading controls when the background was speech, suggesting that they are well able to rely on denoising strategies based on spatial auditory scene analysis strategies.	\N	\N
22465105	Increased early identification of hearing loss has led to infants younger than 24 months of age being implanted with cochlear implants. The objective of this study was to assess early speech development in children implanted with a cochlear implant before 24 months of age using the German questionnaire Elternfragebogen für Risikokinder 2 (ELFRA-2), and to compare these results to normative data of the ELFRA-2 in order to determine any performance differences. Two groups of children were included in this study. The first group included 6 children with a mean age at implantation of 11 months (range: 8-14 months). These children were tested by their parents or caretakers with the ELFRA-2 at the chronological age of 24 months. The second group included 9 children with a mean age at implantation of 13 months (range: 6-20 months) who were tested with the ELFRA-2 after 24 months of cochlear implant use. Comparison analyses of children tested with the ELFRA-2 demonstrated a statistically significant difference in all ELFRA-2 scales between children with cochlear implants (CIs) at the chronological age of 24 months and the norm group (productive vocabulary: p=0.002; syntax: p=0.003; and morphology: p<0.001), and no significant difference between children with CIs at 24 months of device use and the norm group in all scales (productive vocabulary: p=0.335; syntax: p=0.965; and morphology: p=0.304). Children implanted before 24 months of age reach a speech production level after 24 months of device use that is comparable to that of their normal hearing peers.	\N	\N
22477057	Response interference (or response conflict) refers to the phenomenon whereby response times to a target stimulus are longer in the presence of distractor stimuli that indicate contrary motor responses. Response interference has been observed even when the distractor stimuli cannot be discriminated above chance levels. These results raise the question of whether response interference might be driven automatically by the physical distractor stimuli, independently of one's subjective perception of the distractors. Using a modified version of the Eriksen flanker task, we applied metacontrast masks to the flanker stimuli and measured their subjective visibility after each trial. We found converging lines of evidence that the subjective perception of flankers contributed to response interference, over and above the contribution of automatic processing of the stimulus itself. A factorial analysis revealed that the objective, physical congruency of target and flankers and the subjective, perceptual congruency of target and flankers make additive, noninteracting contributions to target response interference, suggesting that the two interference effects originate from independent levels or stages of cognitive processing.	\N	\N
22480024	The majority of research on prosody in conversation to date has focused on exploring the role of individual prosodic features, such as certain types of pitch accent, pitch register or voice quality, for the accomplishment of specified social actions. From this research the picture emerges that when it comes to the implementation of specific actions at specific sequential locations conversationalists employ prosodic features systematically, but also with considerable variation, and indeed flexibility. This paper suggests a further line of enquiry, which pursues a wider, more fundamental role of prosody for interaction, and which does not focus on individual prosodic practices or features, but on participants' collaborative use of prosody for the implementation of one of the most basic interactional decisions: whether to continue a previously established action trajectory, or whether to start a new one. The data and findings of recent research make it clear that prosody, and in fact talk-in-interaction as such, is not appropriately defined by reference to individual features, speakers, locations and actions alone, but must be approached as a resource and negotiating strategy for social interaction. Prosody, therefore, must be described according to its role for both the accomplishment, and the coordination of actions across turns and participants.	\N	\N
22484251	It has been argued that the human visual system is optimized for identification of broadband objects embedded in stimuli possessing orientation averaged power spectra fall-offs that obey the 1/f(β) relationship typically observed in natural scene imagery (i.e., β=2.0 on logarithmic axes). Here, we were interested in whether individual spatial channels leading to recognition are functionally optimized for narrowband targets when masked by noise possessing naturalistic image statistics (β=2.0). The current study therefore explores the impact of variable β noise masks on the identification of narrowband target stimuli ranging in spatial complexity, while simultaneously controlling for physical or perceived differences between the masks. The results show that β=2.0 noise masks produce the largest identification thresholds regardless of target complexity, and thus do not seem to yield functionally optimized channel processing. The differential masking effects are discussed in the context of contrast gain control.	\N	\N
22485043	To examine the role of morphology in verbal working memory. Forty nine children, all native speakers of Arabic from the same region and of the same dialect, performed a Listening Word Span Task, whereby they had to recall Arabic uninflected words (i.e., base words), inflected words with regular (possessive) morphology, or inflected words with irregular (broken plural) morphology. Each of these words was at the end of a sentence (henceforth, target word). The participant's task was to listen to a series of sentences and then recall the target words. Recall of inflected words was significantly poorer than uninflected words, and recall of words with regular morphology was significantly poorer than recall of words with irregular morphology. These findings, albeit preliminary, suggest a role of morphology in verbal working memory. They also suggest that, at least in Arabic, regular morphological forms are decomposed into their component elements and hence impose an extra load on the central executive and episodic buffer components of working memory. Furthermore, in concert with findings from other studies, they suggest that the effect of morphology on working memory is probably language-specific. The clinical implications of the present findings are addressed.	\N	\N
22488914	The relationship between the evoked responses (ERPs/ERFs) and the event-related changes in EEG/MEG power that can be observed during sentence-level language comprehension is as yet unclear. This study addresses a possible relationship between MEG power changes and the N400m component of the event-related field. Whole-head MEG was recorded while subjects listened to spoken sentences with incongruent (IC) or congruent (C) sentence endings. A clear N400m was observed over the left hemisphere, and was larger for the IC sentences than for the C sentences. A time-frequency analysis of power revealed a decrease in alpha and beta power over the left hemisphere in roughly the same time range as the N400m for the IC relative to the C condition. A linear regression analysis revealed a positive linear relationship between N400m and beta power for the IC condition, not for the C condition. No such linear relation was found between N400m and alpha power for either condition. The sources of the beta decrease were estimated in the LIFG, a region known to be involved in semantic unification operations. One source of the N400m was estimated in the left superior temporal region, which has been related to lexical retrieval. We interpret our data within a framework in which beta oscillations are inversely related to the engagement of task-relevant brain networks. The source reconstructions of the beta power suppression and the N400m effect support the notion of a dynamic communication between the LIFG and the left superior temporal region during language comprehension.	\N	\N
22501035	Masked detection thresholds can often be improved by introducing coherent masker amplitude modulation across frequency, a phenomenon referred to as comodulation masking release (CMR). While CMR can be large for detection, it is smaller for supra-threshold tasks, such as intensity discrimination. In this experiment, frequency discrimination for a 1000-Hz tone near threshold was found to be poorer in an amplitude-modulated than a steady bandpass noise. These results parallel previous findings for intensity discrimination. Although this study examined the relatively simple task of frequency discrimination, the results may have implications for more complex tasks, such as speech recognition in fluctuating noise.	\N	\N
22502488	Simultaneous, on-frequency masking is commonly assumed to be linear with increasing noise intensity. However, some evidence suggests that, expressed in terms of signal-to-noise ratio changes with background level changes, masking slopes can vary from 0 dB/dB. These results and evidence from a large sample of subjects with normal and impaired hearing demonstrate level-dependent changes in masking, large individual differences in masking among subjects with similar thresholds in quiet, and significant correlations of masking slope with other estimates of auditory function measured in the same backgrounds.	\N	\N
22503556	Several studies show that the perception of occlusion may affect various aspects of motion perception. Here we present data indicating that occlusion cues also influence the visual interpolation of sampled motion. Normally, sampled motion stimuli are perceived as less smooth and jerkier when the spatial gaps between successive presentations of the "moving" target stimulus increase. Adding surfaces occluding the spatial gaps, however, we found that the perceived smoothness of motion was not only better, but also independent of the gap width. We argue that this effect occurs because the visual system attributes the interruptions in the motion path to occlusion rather than to the moving object itself.	\N	\N
22503904	Motion-induced blindness (MIB) is an illusory phenomenon, in which a static target surrounded by moving distracters is perceived to disappear. We determined the electrocorticographic (ECoG) correlates of MIB. While undergoing intracranial ECoG recording, a patient with focal epilepsy was instructed to report the transitions of a visual target, which was designed to illusorily or physically disappear and reappear. We then determined the neural modulations associated with illusory and physical transitions of the target. We also tested whether the phase of local delta activity could predict exclusively illusory transitions. High-gamma activity at 80-150 Hz was attenuated in the fusiform region prior to the reports of illusory and real visual target disappearance. Conversely, such high-gamma activity was augmented prior to the report of real target reappearance. Exclusively around illusory disappearance but not around real one, the delta phases in the fusiform region showed a highly skewed distribution with preference of the negative peak. Neuronal modulations in the fusiform region may be involved in visual awareness, while spontaneous fluctuations of neural states entrained on delta rhythm may be involved in generation of MIB. Our study increases our understanding of the mechanisms of visual awareness.	\N	\N
22505222	Scholars have documented similarities in the way voice and music convey emotions. By using functional magnetic resonance imaging (fMRI) we explored whether these similarities imply overlapping processing substrates. We asked participants to trace changes in either the emotion or pitch of vocalizations and music using a joystick. Compared to music, vocalizations more strongly activated superior and middle temporal cortex, cuneus, and precuneus. However, despite these differences, overlapping rather than differing regions emerged when comparing emotion with pitch tracing for music and vocalizations, respectively. Relative to pitch tracing, emotion tracing activated medial superior frontal and anterior cingulate cortex regardless of stimulus type. Additionally, we observed emotion specific effects in primary and secondary auditory cortex as well as in medial frontal cortex that were comparable for voice and music. Together these results indicate that similar mechanisms support emotional inferences from vocalizations and music and that these mechanisms tap on a general system involved in social cognition.	\N	\N
22509533	It has been proposed that OAEs be classified not on the basis of the stimuli used to evoke them, but on the mechanisms that produce them (Shera and Guinan, 1999). One branch of this taxonomy focuses on a coherent reflection model and explicitly describes interrelationships between spontaneous emissions (SOAEs) and stimulus-frequency emissions (SFOAEs). The present study empirically examines SOAEs and SFOAEs from individual ears within the context of model predictions, using a low stimulus level (20 dB SPL) to evoke SFOAEs. Emissions were recorded from ears of normal-hearing young adults, both with and without prominent SOAE activity. When spontaneous activity was observed, SFOAEs demonstrated a localized increase about the SOAE peaks. The converse was not necessarily true though, i.e., robust SFOAEs could be measured where no SOAE peaks were observed. There was no significant difference in SFOAE phase-gradient delays between those with and without observable SOAE activity. However, delays were larger for a 20 dB SPL stimulus level than those previously reported for 40 dB SPL. The total amount of SFOAE phase accumulation occurring between adjacent SOAE peaks tended to cluster about an integral number of cycles. Overall, the present data appear congruous with predictions stemming from the coherent reflection model and support the notion that such comparisons ideally are made with emissions evoked using relatively lower stimulus levels.	\N	\N
22509989	This study investigated the effect of short-term visual deprivation on auditory steady-state response (ASSR) to amplitude-modulated tones. Magnetoencephalography data were acquired while subjects performed an auditory detection task under both monaural and dichotic presentation conditions. Analyses were performed on the spectral power, mean amplitudes and dipole positions of the ASSR at the onset of blindfolding, as well as after 2, 4 and 6 h of visual deprivation. Results show a modulation of the spectral power of the ASSR at the frequencies that were present in the stimulus after 6 h of sensory deprivation, and this was especially true for the dichotic condition. Moreover, participants showed two spectral peaks in the occipital cortex at the end of the visual deprivation period, a phenomenon normally observed in the auditory cortex. Our results shed light not only on the timeline associated with short-term crossmodal recruitment of input-deprived sensory cortices but also demonstrate that the visual cortex can display auditory cortex-like functioning in response to the ASSR. Importantly, our results also highlight the importance of taking into consideration individual differences when investigating crossmodal plastic phenomena. Indeed, the occipital spectral peaks were only observed in half the subjects following short-term deprivation.	\N	\N
22511853	Several studies have reported optimal population decoding of sensory responses in two-alternative visual discrimination tasks. Such decoding involves integrating noisy neural responses into a more reliable representation of the likelihood that the stimuli under consideration evoked the observed responses. Importantly, an ideal observer must be able to evaluate likelihood with high precision and only consider the likelihood of the two relevant stimuli involved in the discrimination task. We report a new perceptual bias suggesting that observers read out the likelihood representation with remarkably low precision when discriminating grating spatial frequencies. Using spectrally filtered noise, we induced an asymmetry in the likelihood function of spatial frequency. This manipulation mainly affects the likelihood of spatial frequencies that are irrelevant to the task at hand. Nevertheless, we find a significant shift in perceived grating frequency, indicating that observers evaluate likelihoods of a broad range of irrelevant frequencies and discard prior knowledge of stimulus alternatives when performing two-alternative discrimination.	\N	\N
22513340	Both functional magnetic resonance imaging (fMRI) and event-related brain potential (ERP) studies have shown that verbal working memory plays an important role during sentence processing. There is growing evidence from outside of sentence processing that human alpha oscillations (7-13 Hz) play a critical role in working memory. This study aims to link this to the sentence processing domain. Time-frequency analyses and source localization were performed on electroencephalography (EEG) data that were recorded during the processing of auditorily presented sentences involving either a short or a long distance between an argument (subject or object) and the respective sentence-final verb. We reasoned that oscillatory activity in the alpha band should increase during sentences with longer argument-verb distances, since decreased temporal proximity should result in increased memory demands. When verbal working memory-intensive long-dependency sentences were compared to short-dependency sentences, a sustained oscillatory enhancement at 10 Hz was found during storage prior to the sentence-final verb, turning into a transient power increase in the beta band (13-20 Hz) at the sentence-final verb. The sources of the alpha oscillations were localized to bilaterally occipital and left parietal cortices. Only the source activity in the left parietal cortex was negatively correlated with verbal working memory abilities. These findings indicate that the parsimonious role of alpha oscillations in domain-general working memory can be extended to language, that is, sentence processing. We suggest that the function of left parietal cortex underlying verbal working memory storage during sentence processing is to inhibit the premature release of verbal information that will subsequently be integrated.	\N	\N
22517303	Professional and community concerns about the potentially dangerous noise levels for common leisure activities has led to increased interest on providing hearing health information to participants. However, noise reduction programmes aimed at leisure activities (such as music listening) face a unique difficulty. The noise source that is earmarked for reduction by hearing health professionals is often the same one that is viewed as pleasurable by participants. Furthermore, these activities often exist within a social setting, with additional peer influences that may influence behavior. The current study aimed to gain a better understanding of social-based factors that may influence an individual's motivation to engage in positive hearing health behaviors. Four hundred and eighty-four participants completed questionnaires examining their perceptions of the hearing risk associated with listening to music listening and asking for estimates of their own and their peer's music listening behaviors. Participants were generally aware of the potential risk posed by listening to personal stereo players (PSPs) and the volumes likely to be most dangerous. Approximately one in five participants reported using listening volumes at levels perceived to be dangerous, an incidence rate in keeping with other studies measuring actual PSP use. However, participants showed less awareness of peers' behavior, consistently overestimating the volumes at which they believed their friends listened. Misperceptions of social norms relating to listening behavior may decrease individuals' perceptions of susceptibility to hearing damage. The consequences of hearing health promotion are discussed, along with suggestions relating to the development of new programs.	\N	\N
22521874	Although activity in premotor and motor cortices is commonly observed in neuroimaging studies of spoken language processing, the degree to which this activity is an obligatory part of everyday speech comprehension remains unclear. We hypothesised that rather than being a unitary phenomenon, the neural response to speech perception in motor regions would differ across listeners as a function of individual cognitive ability. To examine this possibility, we used functional magnetic resonance imaging (fMRI) to investigate the neural processes supporting speech perception by comparing active listening to pseudowords with matched tasks that involved reading aloud or repetition, all compared to acoustically matched control stimuli and matched baseline tasks. At a whole-brain level there was no evidence for recruitment of regions in premotor or motor cortex during speech perception. A focused region of interest analysis similarly failed to identify significant effects, although a subset of regions approached significance, with notable variability across participants. We then used performance on a battery of behavioural tests that assessed meta-phonological and verbal short-term memory abilities to investigate the reasons for this variability, and found that individual differences in particular in low phonotactic probability pseudoword repetition predicted participants' neural activation within regions in premotor and motor cortices during speech perception. We conclude that normal listeners vary in the degree to which they recruit premotor and motor cortex as a function of short-term memory ability. This is consistent with a resource-allocation approach in which recruitment of the dorsal speech processing pathway depends on both individual abilities and specific task demands.	\N	\N
22522927	Humans possess a remarkable ability to attend to a single speaker's voice in a multi-talker background. How the auditory system manages to extract intelligible speech under such acoustically complex and adverse listening conditions is not known, and, indeed, it is not clear how attended speech is internally represented. Here, using multi-electrode surface recordings from the cortex of subjects engaged in a listening task with two simultaneous speakers, we demonstrate that population responses in non-primary human auditory cortex encode critical features of attended speech: speech spectrograms reconstructed based on cortical responses to the mixture of speakers reveal the salient spectral and temporal features of the attended speaker, as if subjects were listening to that speaker alone. A simple classifier trained solely on examples of single speakers can decode both attended words and speaker identity. We find that task performance is well predicted by a rapid increase in attention-modulated neural selectivity across both single-electrode and population-level cortical responses. These findings demonstrate that the cortical representation of speech does not merely reflect the external acoustic environment, but instead gives rise to the perceptual aspects relevant for the listener's intended goal.	\N	\N
22524352	In various paradigms of modern neurosciences of music, experts of Western classical music have displayed superior brain architecture when compared with individuals without explicit training in music. In this paper, we show that chord violations embedded in musical cadences were neurally processed in a facilitated manner also by musicians trained in Finnish folk music. This result, obtained by using early right anterior negativity (ERAN) as an index of harmony processing, suggests that tonal processing is advanced in folk musicians by their long-term exposure to both Western and non-Western music.	\N	\N
22524356	Recent research has shown that music training enhances music-related sensorimotor associations, such as the relationship between a key press on the keyboard and its associated musical pitch (auditory feedback). Such results suggest that the role of auditory feedback in performance may be based on learned associations that are task specific. Here, results from various studies will be presented that suggest that the real state of affairs is more complex. Several recent studies have shown similar effects of altered auditory feedback during piano performance for pianists and individuals with no piano training. Other recent research suggests dramatic differences between pianists and nonmusicians concerning the influence of auditory feedback on melody switching that suggest greater influence of auditory feedback among nonmusicians than pianists. Taken together, results suggest that musical training refines preexisting sensorimotor associations.	\N	\N
22524361	This paper examines the role of mental imagery in music performance. Self-reports by musicians, and various other sources of anecdotal evidence, suggest that covert auditory, motor, and/or visual imagery facilitate multiple aspects of music performance. The cognitive and motor mechanisms that underlie such imagery include working memory, action simulation, and internal models. Together these mechanisms support the generation of anticipatory images that enable thorough action planning and movement execution that is characterized by efficiency, temporal precision, and biomechanical economy. In ensemble performance, anticipatory imagery may facilitate interpersonal coordination by enhancing online predictions about others' action timing. Overlap in brain regions subserving auditory imagery and temporal prediction is consistent with this view. It is concluded that individual differences in anticipatory imagery may be a source of variation in expressive performance excellence and the quality of ensemble cohesion. Engaging in effortful musical imagery is therefore justified when artistic perfection is the goal.	\N	\N
22524378	Congenital amusia is a neurodevelopmental disorder of musical perception and production. Much research has focused on characterizing the deficits within this special population; however, it is also important from both a psychological and educational perspective to determine which aspects of the disorder may be subject to change because this will also constrain theorizing about the nature of the disorder, as well as facilitating possible future remediation programs. In this small-scale study, a professional singing teacher used a broad-brush intervention approach with five individuals diagnosed with congenital amusia. The compensatory elements were designed to enhance vocal efficiency and health, singing technique, musical understanding, pitch perception, and production. Improvements were observed in most individuals in perception, indexed via the Montreal Battery for the Evaluation of Amusia scale subtest and in the vocal performance of familiar songs. The workshop setting gave a unique opportunity for observation and discussion to inform further investigations of this disorder.	\N	\N
22525854	When people experience an unchanging sensory input for a long period of time, their perception tends to switch stochastically and unavoidably between alternative interpretations of the sensation; a phenomenon known as perceptual bi-stability or multi-stability. The huge variability in the experimental data obtained in such paradigms makes it difficult to distinguish typical patterns of behaviour, or to identify differences between switching patterns. Here we propose a new approach to characterising switching behaviour based upon the extraction of transition matrices from the data, which provide a compact representation that is well-understood mathematically. On the basis of this representation we can characterise patterns of perceptual switching, visualise and simulate typical switching patterns, and calculate the likelihood of observing a particular switching pattern. The proposed method can support comparisons between different observers, experimental conditions and even experiments. We demonstrate the insights offered by this approach using examples from our experiments investigating multi-stability in auditory streaming. However, the methodology is generic and thus widely applicable in studies of multi-stability in any domain.	\N	\N
22534571	Event Related Potentials (ERPs) were recorded from Spanish-English bilinguals (N=10) to test pre-attentive speech discrimination in two language contexts. ERPs were recorded while participants silently read magazines in English or Spanish. Two speech contrast conditions were recorded in each language context. In the phonemic in English condition, the speech sounds represented two different phonemic categories in English, but represented the same phonemic category in Spanish. In the phonemic in Spanish condition, the speech sounds represented two different phonemic categories in Spanish, but represented the same phonemic categories in English. Results showed pre-attentive discrimination when the acoustics/phonetics of the speech sounds match the language context (e.g., phonemic in English condition during the English language context). The results suggest that language contexts can affect pre-attentive auditory change detection. Specifically, bilinguals' mental processing of stop consonants relies on contextual linguistic information.	\N	\N
22537033	To develop, optimize, and evaluate a new Spanish sentence test in noise. The test comprises a basic matrix of ten names, verbs, numerals, nouns, and adjectives. From this matrix, test lists of ten sentences with an equal syntactical structure can be formed at random, with each list containing the whole speech material. The speech material represents the phoneme distribution of the Spanish language. The test was optimized for measuring speech reception thresholds (SRTs) in noise by adjusting the presentation levels of the individual words. Subsequently, the test was evaluated by independent measurements investigating the training effects, the comparability of test lists, open-set vs. closed-set test format, and performance of listeners of different Spanish varieties. In total, 68 normal-hearing native Spanish-speaking listeners. SRTs measured using an adaptive procedure were 6.2 ± 0.8 dB SNR for the open-set and 7.2 ± 0.7 dB SNR for the closed-set test format. The residual training effect was less than 1 dB after using two double-lists before data collection. No significant differences were found for listeners of different Spanish varieties indicating that the test is applicable to Spanish as well as Latin American listeners. Test lists can be used interchangeably.	\N	\N
22541369	Neuroimaging studies of English suggest that speech comprehension engages two interdependent systems: a bilateral fronto-temporal network responsible for general perceptual and cognitive processing, and a specialised left-lateralised network supporting specifically linguistic processing. Using fMRI we test this hypothesis in Polish, a Slavic language with rich and diverse morphology. We manipulated general perceptual complexity (presence or absence of an onset-embedded stem, e.g. kotlet 'cutlet' vs. kot 'cat') and specifically linguistic complexity (presence of an inflectional affix, e.g. dom 'house, Nom' vs. dom-u 'house, Gen'). Non-linguistic complexity activated a bilateral network, as in English, but we found no differences between inflected and uninflected nouns. Instead, all types of words activated left inferior frontal areas, suggesting that all Polish words can be considered linguistically 'complex' in processing terms. The results support a dual network hypothesis, but highlight differences between languages like English and Polish, and underline the importance of cross-linguistic comparisons.	\N	\N
22542727	Impaired auditory sensitivity to amplitude rise time (ART) has been suggested to be a primary deficit in developmental dyslexia. The present study investigates whether impaired ART-sensitivity at a pre-reading age precedes and predicts later emerging reading problems in a sample of Dutch children. An oddball paradigm, with a deviant that differed from the standard stimulus in ART, was administered to 41-month-old children (30 genetically at-risk for developmental dyslexia and 14 controls) with concurrent EEG measurement. A second deviant that differed from the standard stimulus in frequency served as a control deviant. Grade two reading scores were used to divide the at-risks in a typical-reading and a dyslexic subgroup. We found that both ART- and frequency processing were related to later reading skill. We however also found that irrespective of reading level, the at-risks in general showed impaired basic auditory processing when compared to controls and that it was impossible to discriminate between the at-risk groups on basis of both auditory measures. A relatively higher quality of early expressive syntactic skills in the typical-reading at-risk group might indicate a protective factor against negative effects of impaired auditory processing on reading development. Based on these results we argue that ART- and frequency-processing measures, although they are related to reading skill, lack the power to be considered single-cause predictors of developmental dyslexia. More likely, they are genetically driven risk factors that may add to cumulative effects on processes that are critical for learning to read.	\N	\N
22543320	The purpose of this study was to determine daily noise doses and 8-hour time weighted averages for rock band musicians, crew members, and spectators during a typical rehearsal and performance using both Occupational Safety and Health Administration (OSHA) and National Institute of Occupational Safety and Health (NIOSH) measurement criteria. Personal noise dosimetry was completed on five members of a rock band during one 2-hr rehearsal and one 4-hr performance. Time-weighted averages (TWA) and daily dose values were calculated using both OSHA and NIOSH criteria and compared to industry guidelines for enrollment in hearing conservation programs and the use of hearing protection devices. TWA values ranged from 84.3 to 90.4 dBA (OSHA) and from 90.0 to 96.4 dBA (NIOSH) during the rehearsal. The same values ranged from 91.0 to 99.7 dBA (OSHA) and 94.0 to 102.8 dBA (NIOSH) for the performance. During the rehearsal, daily noise doses ranged from 45.54% to 106.7% (OSHA) and from 317.74% to 1396.07% (NIOSH). During the performance, doses ranged from 114.66% to 382.49% (OSHA) and from 793.31% to 5970.15% (NIOSH). The musicians in this study were exposed to dangerously high levels of noise and should be enrolled in a hearing conservation programs. Hearing protection devices should be worn, especially during performances. The OSHA measurement criteria yielded values significantly more conservative than those produced by NIOSH criteria. Audiologists should counsel musician-patients about the hazards of excessive noise (music) exposure and how to protect their hearing.	\N	\N
22559370	The "combined-stimulation advantage" refers to an improvement in speech recognition when cochlear-implant or vocoded stimulation is supplemented by low-frequency acoustic information. Previous studies have been interpreted as evidence for "super-additive" or "synergistic" effects in the combination of low-frequency and electric or vocoded speech information by human listeners. However, this conclusion was based on predictions of performance obtained using a suboptimal high-threshold model of information combination. The present study shows that a different model, based on Gaussian signal detection theory, can predict surprisingly large combined-stimulation advantages, even when performance with either information source alone is close to chance, without involving any synergistic interaction. A reanalysis of published data using this model reveals that previous results, which have been interpreted as evidence for super-additive effects in perception of combined speech stimuli, are actually consistent with a more parsimonious explanation, according to which the combined-stimulation advantage reflects an optimal combination of two independent sources of information. The present results do not rule out the possible existence of synergistic effects in combined stimulation; however, they emphasize the possibility that the combined-stimulation advantages observed in some studies can be explained simply by non-interactive combination of two information sources.	\N	\N
22559371	Preliminary data [M. Epstein and M. Florentine, Ear. Hear. 30, 234-237 (2009)] obtained using speech stimuli from a visually present talker heard via loudspeakers in a sound-attenuating chamber indicate little difference in loudness when listening with one or two ears (i.e., significantly reduced binaural loudness summation, BLS), which is known as "binaural loudness constancy." These data challenge current understanding drawn from laboratory measurements that indicate a tone presented binaurally is louder than the same tone presented monaurally. Twelve normal listeners were presented recorded spondees, monaurally and binaurally across a wide range of levels via earphones and a loudspeaker with and without visual cues. Statistical analyses of binaural-to-monaural ratios of magnitude estimates indicate that the amount of BLS is significantly less for speech presented via a loudspeaker with visual cues than for stimuli with any other combination of test parameters (i.e., speech presented via earphones or a loudspeaker without visual cues, and speech presented via earphones with visual cues). These results indicate that the loudness of a visually present talker in daily environments is little affected by switching between binaural and monaural listening. This supports the phenomenon of binaural loudness constancy and underscores the importance of ecological validity in loudness research.	\N	\N
22559380	Speech perception requires the integration of information from multiple phonetic and phonological dimensions. A sizable literature exists on the relationships between multiple phonetic dimensions and single phonological dimensions (e.g., spectral and temporal cues to stop consonant voicing). A much smaller body of work addresses relationships between phonological dimensions, and much of this has focused on sequences of phones. However, strong assumptions about the relevant set of acoustic cues and/or the (in)dependence between dimensions limit previous findings in important ways. Recent methodological developments in the general recognition theory framework enable tests of a number of these assumptions and provide a more complete model of distinct perceptual and decisional processes in speech sound identification. A hierarchical Bayesian Gaussian general recognition theory model was fit to data from two experiments investigating identification of English labial stop and fricative consonants in onset (syllable initial) and coda (syllable final) position. The results underscore the importance of distinguishing between conceptually distinct processing levels and indicate that, for individual subjects and at the group level, integration of phonological information is partially independent with respect to perception and that patterns of independence and interaction vary with syllable position.	\N	\N
22559460	Peruvian Spanish (PS) and Iberian Spanish (IS) learners were tested on their ability to categorically discriminate and identify Dutch vowels. It was predicted that the acoustic differences between the vowel productions of the two dialects, which compare differently to Dutch vowels, would manifest in differential L2 perception for listeners of these two dialects. The results show that although PS learners had higher general L2 proficiency, IS learners were more accurate at discriminating all five contrasts and at identifying six of the L2 Dutch vowels. These findings confirm that acoustic differences in native vowel production lead to differential L2 vowel perception.	\N	\N
22563091	Linguistic variables alone cannot fully account for bilingual listeners' perception of English-running speech. In the present study, the authors investigated how linguistic and attitudinal factors, in combination, affect bilingual processing of temporally degraded English passages in quiet and in noise. Thirty-six bilinguals with various linguistic and attitudinal characteristics participated in the study. Bilingual individuals completed questionnaires that assessed their language background, willingness to communicate (WTC), and self-perceived communication competency (SPCC) in English. Participants listened to English passage pairs from the Connected Speech Test, presented at 45 dB HL at 3 rates (unprocessed, expanded, compressed), in quiet and in noise. Language proficiency measures were the most significant linguistic variables, accounting for the largest amount of variance in performance across most conditions. Both WTC and SPCC were associated with performance and contributed to regression models. Subscales assessing listeners' WTC and SPCC in a group were more predictive of performance than communication in an interpersonal or public setting. Performance in noise was more difficult to predict than in quiet. Performance with compression was more difficult to predict than with expansion. To fully understand bilingual clients' perception of English speech, hearing professionals should consider their attitudinal characteristics in addition to language background.	\N	\N
22564903	To evaluate whether a hypothesis suggesting that apraxia of speech results from phonological overspecification could be relevant for childhood apraxia of speech (CAS). High-density EEG was recorded from 5 children with CAS and 5 matched controls, ages 5-8 years, with and without CAS, as they listened to randomized sequences of CV syllables in two oddball paradigms: phonemic (/ba/, /pa/) and allophonic (/pa/, /p(h)a/). In the phonemic contrast condition, mismatch negativity (MMN) responses to oddball sounds were observed for the typically developing (comparison) group but not the CAS group, although a component similar to an immature mismatch response was apparent. The allophonic contrast did not elicit MMN responses in the comparison group, but in the CAS group, an MMN-like response was observed. The authors propose that these preliminary findings are consistent with a view of CAS as a disorder that not only affects motor planning but also has a phonological component.	\N	\N
22565049	Primary facial nerve tumors (FNTs) present in varying ways. In this study, the authors present their institutional experience with the management of facial nerve tumors, including their recommendations for available therapies such as observation, microsurgical decompression or removal, and stereotactic radiation. They emphasize the auditory and facial nerve function outcomes. Retrospective case review. Tertiary referral center. Retrospective review of all cases of FNT seen at the authors' tertiary care academic medical center over a 10-year period (2002-2011). The clinical presentation, treatment modality, and outcome parameters of cochlear and facial nerve function were assessed. Twelve patients were identified. House-Brackmann grades on presentation were 4 grade I, 2 grade II, 2 grade III, 1 grade IV, and 3 grade V, with 2 grade V patients declining to grade VI shortly after presentation. Seven patients presented with serviceable hearing and 4 with nonserviceable hearing. Treatment options/arms included observation with serial clinicoradiological review (2 cases), stereotactic radiation with the CyberKnife (3 cases), wide fallopian canal decompression (3 cases), microsurgical excision and repair (3 cases), and biopsy followed by observation (1 case). At the end of the review period, facial nerve function was stable in 8 patients, improved in 3, and declined in 1, and none had documented worsening of hearing based on American Academy of Otolaryngology--Head and Neck Surgery Foundation classification. Management of FNT is largely based on the clinicoradiological picture. Each treatment arm is different, but overall auditory and facial function can be maintained.	\N	\N
22571290	Vocal emblems, such as shh and brr, are speech sounds that have linguistic and nonlinguistic features; thus, it is unclear how they are processed in the brain. Five adult dextral individuals with left-brain damage and moderate-severe Wernicke's aphasia, five adult dextral individuals with right-brain damage, and five Controls participated in two tasks: (1) matching vocal emblems to photographs ('picture task') and (2) matching vocal emblems to verbal translations ('phrase task'). Cross-group statistical analyses on items on which the Controls performed at ceiling revealed lower accuracy by the group with left-brain damage (than by Controls) on both tasks, and lower accuracy by the group with right-brain damage (than by Controls) on the picture task. Additionally, the group with left-brain damage performed significantly less accurately than the group with right-brain damage on the phrase task only. Findings suggest that comprehension of vocal emblems recruits more left- than right-hemisphere processing.	\N	\N
22584037	Music is an ancient and ubiquitous form of human expression. One important component for which music is sought after is its aesthetic value, whose appreciation has typically been associated with largely learned, culturally determined factors, such as education, exposure, and social pressure. However, neuroscientific evidence shows that the aesthetic response to music is often associated with automatic, physically- and biologically-grounded events, such as shivers, chills, increased heart rate, and motor synchronization, suggesting the existence of an underlying biological platform upon which contextual factors may act. Drawing on philosophical notions and neuroscientific evidence, I argue that, although there is no denying that social and cultural context play a substantial role in shaping the aesthetic response to music, these act upon largely universal, biological mechanisms involved with neural processing. I propose that the simultaneous presence of culturally-influenced and biologically-determined contributions to the aesthetic response to music epitomizes Baumgarten's equation of sensory perception with taste. Taking the argument one step further, I suggest that the heavily embodied aesthetic response to music bridges the cleavage between the two discrepant meanings-the one referring to sensory perception, the other referring to judgments of taste-traditionally attributed to the word "aesthetics" in the sciences and the humanities.	\N	\N
22588234	To identify whether speech recognition outcomes are influenced by the choice of ear for cochlear implantation in adults with bilateral hearing loss who use a hearing aid in 1 ear but have long-term auditory deprivation in the other. Retrospective matched cohort study. Speech recognition results were examined in 30 adults with monaural sound deprivation. Fifteen received the implant in the sound-deprived ear and 15 in the aided ear. Tertiary referral centers with active cochlear implant programs. Adults with bilateral hearing loss and a minimum of 15 years of monaural sound deprivation who received a cochlear implant after meeting the traditional implantation criteria of the referral centers. Cochlear implantation with devices approved by the U.S. Food and Drug Administration. Paired comparisons of postoperative monosyllabic word recognition scores obtained with the implant alone and in the usual listening condition (CI alone or bimodal). With the cochlear implant alone, individuals who received the implant in a sound-deprived ear obtained poorer scores than individuals who received the implant in the aided ear. There was no significant difference, however, in speech recognition results for the 2 groups when tested in their usual listening condition. In particular, poorer speech recognition scores were obtained with the cochlear implant alone by individuals using bimodal hearing. Similar clinical outcomes of cochlear implantation can be achieved by adults with a long-term monaural sound deprivation when comparing the usual listening condition, irrespective of whether the implant is in the sound-deprived or in the aided ear.	\N	\N
22588270	This study aimed to characterize horizontal plane sound localization in interfering noise at different signal-to-noise ratios (SNRs) and to compare performance across normal-hearing listeners and users of unilateral and bilateral cochlear implants (CIs). CI users report difficulties with listening in noisy environments. Although their difficulties with speech understanding have been investigated in several studies, the ability to localize sounds in background noise has not extensively been examined, despite the benefits of binaural hearing being greatest in noisy situations. Sound localization is a measure of binaural processing and is thus well suited to assessing the benefit of bilateral implantation. The results will inform clinicians and implant manufacturers how to focus their efforts to improve localization with CIs in noisy situations. Six normal-hearing listeners, four unilateral, and 10 bilateral CI users indicated the perceived location of sound sources using a light pointer method. Target sounds were noise pulses played from one of 11 loudspeakers placed between -80 and +80 degrees in the frontal horizontal plane in the free field. Localization was assessed in quiet and in diffuse background noise at SNRs between +10 and -7 dB. Speech reception thresholds were measured and their relation to the localization results examined. Localization performance declined with decreasing SNR: target sounds were perceived closer to the median plane and the standard deviation of responses increased. Localization performance across groups was compared using a measure of "Spatial Resolvability" (SR). This measure gives the angular separation between two sound sources that would enable an ideal observer to correctly distinguish them 69.1% of the time. For all participants SR increased with decreasing SNR, that is, at low SNRs the spatial separation between sound sources remained distinguishable only when it was larger. Normal-hearing participants performed best, with SR between 1.4 and 5.1 degrees in quiet. Bilateral CI users showed SR between 8.3 and 43.6 degrees in quiet, corresponding approximately to the spatial resolution of normal-hearing listeners at an SNR of -5 dB. Most bilateral CI users had lost the ability to correctly determine which side the sound came from at an SNR of -3 dB. Overall, the SNR had to be at least +7 dB to achieve localization performance near to that in quiet for all bilateral CI users. No significant correlation was found between spatial resolution and speech reception thresholds, but the speech processor sensitivity setting did significantly affect performance. Unilateral CI users showed the most severe localization problems, with only two of four participants being able to correctly determine which side sounds came from in quiet. This study is the first to examine sound localization with CIs at various SNRs and to compare it with normal hearing. The results confirm that localization with CIs is strongly disrupted in noisy situations. Bilateral CIs were shown to be clearly superior over unilateral CIs for localization in quiet and in noisy situations. With bilateral CIs, localization declined at moderately high absolute noise levels (>63 dB SPL), suggesting that an extension of the acoustic-dynamic range to higher levels would be beneficial. The absence of a relation between speech reception thresholds and spatial resolution highlights the need for additional clinical tests to assess the binaural benefit of a second implant.	\N	\N
22591493	Recent oddball studies showed that auditory change detection responses exist in the first 50 ms after sound onset, upstream of mismatch negativity (MMN). We examined if these early responses could be elicited by feature-specific changes, meaning changes in the value of one attribute of a stimulus, regardless of whether other attributes of the stimulus are changing or not. We used a multifeature paradigm with four types of deviants: frequency, duration, intensity, and interaural time difference. In the middle latency range, only frequency deviants led to an enhanced Nb response. All four feature changes generated significant MMNs. Our results indicate that human brain is capable of detecting a feature-specific change for frequency attributes in the middle latency. The different levels of information being encoded in two separate event-related potential time ranges support the notion of a hierarchical organization of auditory deviance detection.	\N	\N
22606932	We describe the audiometric results following surgery in a consecutive series of patients with a congenital ossicular middle ear disorder that was associated with a mobile stapes footplate. We performed a retrospective analysis of patient charts from a tertiary referral center. A total of 23 patients (23 ears) underwent exploratory tympanotomy and ossicular reconstruction between 1986 and 2001. The main outcome measure was the audiometric results. Overall, we observed a mean gain in air conduction pure tone average of 17 dB (from 47 dB to 30 dB), a sensorineural deterioration of 3 dB, and a mean postoperative air-bone gap of 19 dB (mean preoperative air-bone gap of 38 dB). The air-bone gap closure was 20 dB or less in 15 of the 23 cases (65%), in agreement with the few results reported in the literature. Moreover, the audiometric results remained stable. In the syndromic group, the mean gain in air conduction was only 13 dB, which was worse than that observed for the nonsyndromic ears. Surgery for congenital ossicular chain anomalies with a concomitant mobile stapes footplate provides positive audiometric outcomes. Most ears had some sensorineural impairment (10 to 20 dB), which influenced the final hearing level attained after surgery. Preoperative assessment is mandatory to search for syndromal diagnoses, which might be important for patient counseling and prognosis.	\N	\N
22609773	This study investigated the bandwidth of phase sensitivity. Subjects discriminated amplitude-modulated tones (AM), and quasi-frequency-modulated tones (QFM) in a two-interval, forced-choice task. An adaptive threshold procedure was used to estimate the modulation depth needed to discriminate the stimuli as a function of carrier and modulation frequency. Non-monotonicities in threshold-bandwidth functions were often observed at higher modulation frequencies. The results are discussed in terms of two potential cues: (1) waveform envelope, (2) cubic distortion products. In order to degrade the information obtained from auditory distortions, the phase for the carrier frequency was randomly sampled from a uniform distribution, which diminished the non-monotonicities with minimal effect at lower modulation frequencies. Model simulations demonstrated that phase randomization degrades distortion product cues with only a modest effect on temporal cues. Final results show that maximum bandwidths for phase sensitivity (BW(max)) were not proportional to carrier frequencies.	\N	\N
22615475	In this study, the authors evaluated the effect of frequency compression hearing aids on speech perception ability and the time course and magnitude of acclimatization-related changes. Participants included children ages 11-18 years. Speech perception ability was evaluated over well-controlled baseline, treatment, and withdrawal study phases. Study-worn hearing aids were individually fitted to all participants. The authors evaluated speech perception ability using outcomes of speech detection (/s/ and /[symbol in text]/ sounds), /s-[symbol in text]/ discrimination, and plural and consonant recognition. Indices of change were discussed on a case-by-case basis across all study phases. Significant treatment effects were measured for all cases, on at least one measure, with some listeners displaying significant acclimatization trends following a trial of frequency compression. Findings suggest that frequency compression provided varying outcomes, both in benefit and acclimatization, across listeners. For some, a period of acclimatization was necessary before change could be measured. For others, performance remained stable over the time course under evaluation, suggesting that some but not all children will experience improved speech recognition ability after a period of frequency compression hearing aid use.	\N	\N
22615939	In natural audio-visual environments, a change in depth is usually correlated with a change in loudness. In the present study, we investigated whether correlating changes in disparity and loudness would provide a functional advantage in binding disparity and sound amplitude in a visual search paradigm. To test this hypothesis, we used a method similar to that used by van der Burg et al. to show that non-spatial transient (square-wave) modulations of loudness can drastically improve spatial visual search for a correlated luminance modulation. We used dynamic random-dot stereogram displays to produce pure disparity modulations. Target and distractors were small disparity-defined squares (either 6 or 10 in total). Each square moved back and forth in depth in front of the background plane at different phases. The target's depth modulation was synchronized with an amplitude-modulated auditory tone. Visual and auditory modulations were always congruent (both sine-wave or square-wave). In a speeded search task, five observers were asked to identify the target as quickly as possible. Results show a significant improvement in visual search times in the square-wave condition compared to the sine condition, suggesting that transient auditory information can efficiently drive visual search in the disparity domain. In a second experiment, participants performed the same task in the absence of sound and showed a clear set-size effect in both modulation conditions. In a third experiment, we correlated the sound with a distractor instead of the target. This produced longer search times, indicating that the correlation is not easily ignored.	\N	\N
22616091	Sound localization in the horizontal (azimuth) plane relies mainly on interaural time differences (ITDs) and interaural level differences (ILDs). Both are distorted in listeners with acquired unilateral conductive hearing loss (UCHL), reducing their ability to localize sound. Several studies demonstrated that UCHL listeners had some ability to localize sound in azimuth. To test whether listeners with acquired UCHL use strongly perturbed binaural difference cues, we measured localization while they listened with a sound-attenuating earmuff over their impaired ear. We also tested the potential use of monaural pinna-induced spectral-shape cues for localization in azimuth and elevation, by filling the cavities of the pinna of their better-hearing ear with a mould. These conditions were tested while a bone-conduction device (BCD), fitted to all UCHL listeners in order to provide hearing from the impaired side, was turned off. We varied stimulus presentation levels to investigate whether UCHL listeners were using sound level as an azimuth cue. Furthermore, we examined whether horizontal sound-localization abilities improved when listeners used their BCD. Ten control listeners without hearing loss demonstrated a significant decrease in their localization abilities when they listened with a monaural plug and muff. In 4/13 UCHL listeners we observed good horizontal localization of 65 dB SPL broadband noises with their BCD turned off. Localization was strongly impaired when the impaired ear was covered with the muff. The mould in the good ear of listeners with UCHL deteriorated the localization of broadband sounds presented at 45 dB SPL. This demonstrates that they used pinna cues to localize sounds presented at low levels. Our data demonstrate that UCHL listeners have learned to adapt their localization strategies under a wide variety of hearing conditions and that sound-localization abilities improved with their BCD turned on.	\N	\N
22617829	Lateral prefrontal cortex and basal ganglia work together to mediate working memory and top-down regulation of cognition. This circuit regulates the balance and interactions between automatic and high-order control responses. Using ultra-high-field high-resolution functional magnetic resonance imaging (7T-fMRI), the present study examined the role of subcortical structures in cognitive control during language processing. Participants were asked to judge the grammaticality of unambiguous, ungrammatical and ambiguous sentences. Grammatical unambiguous sentences should elicit an automatic response, while ambiguous and ungrammatical sentences should conflict with the automatic response and, hence, require a high-order control response. Within the control response domain, ambiguity and ungrammaticality represent two different dimensions of conflict resolution, while for a temporarily ambiguous sentence a correct interpretation is available, that is not the case for ungrammatical sentences. Our results reveal an anterior-posterior axis in the dorsomedial striatum with more rostral regions supporting higher levels of cognitive processing. This functional architecture mirrors the rostrocaudal hierarchical organization evidenced within the lateral prefrontal cortex.	\N	\N
22621261	Categorical perception, an increased sensitivity to between- compared with within-category contrasts, is a stable property of native speech perception that emerges as language matures. Although recent research suggests that categorical responses to speech sounds can be found in left prefrontal as well as temporo-parietal areas, it is unclear how the neural system develops heightened sensitivity to between-category contrasts. In the current study, two groups of adult participants were trained to categorize speech sounds taken from a dental/retroflex/velar continuum according to two different boundary locations. Behavioral results suggest that for successful learners, categorization training led to increased discrimination accuracy for between-category contrasts with no concomitant increase for within-category contrasts. Neural responses to the learned category schemes were measured using a short-interval habituation design during fMRI scanning. Whereas both inferior frontal and temporal regions showed sensitivity to phonetic contrasts sampled from the continuum, only the bilateral middle frontal gyri exhibited a pattern consistent with encoding of the learned category scheme. Taken together, these results support a view in which top-down information about category membership may reshape perceptual sensitivities via attention or executive mechanisms in the frontal lobes.	\N	\N
22646315	The study investigated the effect of immediate feedback in training listeners to perceive subtle differences in voice quality, a perceptual skill that is important for speech-language pathologists. Sixty naive listeners were randomly assigned to a feedback group (Group F), a no feedback group (Group NF), and a no training group acting as a control group (Group C). The task was to evaluate the severity of a perceptual voice quality (breathiness) by using a reference-matching paradigm. All participants took part in three rating sessions (pre-training, 2 days after training and 1 week after training). Group F and Group NF participated in a training session immediately after the first rating session, where Group F practiced with immediate feedback given and Group NF practice with no immediate feedback given. The results showed that Group F and Group NF had significant improvement after training, but Group F did not retain the improvement in the third rating session. The use of a reference-matching training paradigm without giving frequent immediate feedback is suggested for auditory-perceptual voice evaluation training. The most effective frequency of immediate feedback is yet to be determined.	\N	\N
22648604	The "pip-and-pop effect" refers to the facilitation of search for a visual target (a horizontal or vertical bar whose color changes frequently) among multiple visual distractors (tilted bars also changing color unpredictably) by the presentation of a spatially uninformative auditory cue synchronized with the color change of the visual target. In the present study, the visual stimuli in the search display changed brightness instead of color, and the crossmodal congruency between the pitch of the auditory cue and the brightness of the visual target was manipulated. When cue presence and cue congruency were randomly varied between trials (Experiment 1), both congruent cues (low-frequency tones synchronized with dark target states or high-frequency tones synchronized with bright target states) and incongruent cues (the reversed mapping) facilitated visual search performance equally, relative to a no-cue baseline condition. However, when cue congruency was blocked and the participants were informed about the pitch-brightness mapping in the cue-present blocks (Experiment 2), performance was significantly enhanced when the cue and target were crossmodally congruent as compared to when they were incongruent. These results therefore suggest that the crossmodal congruency between auditory pitch and visual brightness can influence performance in the pip-and-pop task by means of top-down facilitation.	\N	\N
22659285	The health impacts of environmental noise are a growing concern amongst both the general public and policy-makers in Europe. Environmental noise - especially from road transportation - is widely accepted as an important environmental impact factor that can be taken as a start for the process of evaluating the impact of annoyance on the exposed urban population. Extensive urbanisation and the increase of road transport define the main driving forces for the environmental noise exposure of the population. In urban conditions, it is rather common, regarding road transportation noise, to hear from people that, especially, PTW (Powered Two Wheelers) are annoying, and many times are actually the most annoying environmental noise sources introducing a degradation of the urban environment. In this research, in Athens city centre, both scooters and motorbikes operation patterns are analysed, in the basis of their environmental impact through ad-hoc tests to establish if specific features of their emitted noise are annoying and affect the quality of life. It resulted that PTW are a relevant cause of specific environmental annoyance on pedestrians when low background noise levels and sparse traffic flow allow identifying the PTW. Based on the results of a measurement campaign, both L(max) and roughness indices are identified as characteristic noise signatures of the PTW. Results are compared to laboratory studies on annoyance found in literature and to a specific set of interviews with a large number of pedestrians in selected sites. Annoyance caused by scooters and motorbikes is analysed in the findings and conclusions.	\N	\N
22659582	How do perceivers apply knowledge to instances they have never experienced before? On one hand, listeners might use idealized representations that do not contain specific details. On the other, they might recognize and process information based on more detailed memory representations. The current study examined the latter possibility with respect to musical meter perception, previously thought to be computed based on highly-idealized (isochronous) internal representations. In six experiments, listeners heard sets of metrically-ambiguous melodies. Each melody was played in a simultaneous musical context with unambiguous metrical cues (3/4 or 6/8). Cross-melody similarity was manipulated by pairing certain cues-timbre (musical instrument) and motif content (2-6-note patterns)-with each meter, or distributing cues across meters. After multiple exposures, listeners heard each melody without context, and judged metrical continuations (all Experiments) or familiarity (Experiments 5-6). Responses were assessed for "metrical restoration"-the tendency to make metrical judgments that fit the melody's previously-heard metrical context. Cross-melody similarity affected the presence and degree of metrical restoration, and timbre affected familiarity. Results suggest that metrical processing may be calculated based on fairly detailed representations rather than idealized isochronous pulses, and is dissociated somewhat from familiarity judgments. Implications for theories of meter perception are discussed.	\N	\N
22666424	Sensory attenuation refers to the observation that self-generated stimuli are attenuated, both in terms of their phenomenology and their cortical response compared to the same stimuli when generated externally. Accordingly, it has been assumed that sensory attenuation might help individuals to determine whether a sensory event was caused by themselves or not. In the present study, we investigated whether this dependency is reciprocal, namely whether sensory attenuation is modulated by prior beliefs of authorship. Participants had to judge the loudness of auditory effects that they believed were either self-generated or triggered by another person. However, in reality, the sounds were always triggered by the participants' actions. Participants perceived the tones' loudness attenuated when they believed that the sounds were self-generated compared to when they believed that they were generated by another person. Sensory attenuation is considered to contribute to the emergence of people's belief of authorship. Our results suggest that sensory attenuation is also a consequence of prior belief about the causal link between an action and a sensory change in the environment.	\N	\N
22667466	Cochlear microphonic (CM) measurements may potentially become a supplementary approach to otoacoustic emission (OAE) measurements for assessing low-frequency cochlear functions in the clinic. The objective of this study was to investigate the measurement of CMs in subjects with high-frequency hearing loss. Currently, CMs can be measured using electrocochleography (ECochG or ECoG) techniques. Both CMs and OAEs are cochlear responses, while auditory brainstem responses (ABRs) are not. However, there are inherent limitations associated with OAE measurements such as acoustic noise, which can conceal low-frequency OAEs measured in the clinic. However, CM measurements may not have these limitations. CMs were measured in human subjects using an ear canal electrode. The CMs were compared between the high-frequency hearing loss group and the normal-hearing control group. Distortion product OAEs (DPOAEs) and audiogram were also measured. The DPOAE and audiogram measurements indicate that the subjects were correctly selected for the two groups. Low-frequency CM waveforms (CMWs) can be measured using ear canal electrodes in high-frequency hearing loss subjects. The difference in amplitudes of CMWs between the high-frequency hearing loss group and the normal-hearing group is insignificant at low frequencies but significant at high frequencies.	\N	\N
22670350	Quinn and Watt (2006 Perception 35 267-280) showed that the optimal tempi for pieces of music (ie the appropriate speed for a melody) vary from melody to melody. The current study tested if such tempi responses depend on previous stimulus presentations. To do this, we ran a many-participants single-presentation version of the Quinn and Watt experiment. 616 visitors to the Glasgow Science Centre participated. We found that the results substantially matched those obtained earlier, and demonstrate that participants' responses are essentially independent of previously presented stimuli.	\N	\N
22688920	Previous research suggests that young children have significant difficulty recognizing speech in the presence of background noise as compared with older children and adults. However, limited research exists that examines the developmental effects of speech recognition in noise in separate age groups of young children, especially in a classroom setting. The lack of research may relate to the limited number of tests with multiple, equally intelligible lists in noise that are also appropriate for young children. As a result, the goals of the present study include investigating (1) effects of age and (2) benefits of spatial separation of speech and noise sources on the speech recognition in noise performance of young children with normal-hearing sensitivity. A secondary goal of the study was to establish the validity and reliability of the Phrases in Noise Test (PINT) for assessing the 50% correct speech-in-noise threshold of young children. The investigators used a two-way repeated measures design to examine the main effects of age and spatial separation. Sixty-eight children in separate groups of 3-, 4-, 5-, and 6-year-olds and 17 adults completed two speech-recognition conditions with (1) speech and noise from the same loudspeaker at 0-degree azimuth (S0/N0) and (2) speech and noise from separate loudspeakers at 0- and 180-degree azimuth (S0/N180). Recruiting sites included local preschools and school districts for children and a university for adults. The results of this investigation suggest that younger children (<4 years of age) have significantly poorer speech-in-noise thresholds than older children and adults, and 4- and 5-year-old children also have significantly poorer performance than adults when speech and noise are presented from the same spatial location. All participants obtained significant spatial release from masking. On a parent and teacher screening questionnaire to assess educational risk, five of 12 children with at-risk behaviors had poor speech-in-noise thresholds relative to their peers. When two lists of the PINT are used, the test seems to be a valid and reliable measure for assessing young children's speech-in-noise thresholds. Young children exhibit significantly poorer speech recognition than do older children and adults in a classroom, especially when speech and noise are presented from the same location. Given the poor acoustics of typical classrooms, and the earlier age at which many children are educated, special modifications to classrooms may be necessary to improve listening through acoustic modifications or classroom amplification. A combination of a parent or teacher questionnaire and the PINT may be helpful in identifying children who are at risk for educational delays and listening difficulties in classrooms with typically poor acoustics.	\N	\N
22693344	Hearing and feeling both rely upon the transduction of physical events into frequency-based neural codes, suggesting that the auditory system may be intimately related to the somatosensory system. Here, we provide evidence that the neural substrates for audition and somatosensation are anatomically linked. Using diffusion tensor imaging with both deterministic and probabilistic tractography to measure white matter connectivity, we show that there are extensive ipsilateral connections between the primary auditory cortex and the primary and secondary somatosensory regions in the human cerebral cortex. We further show that these cross-modal connections are exaggerated between the auditory and secondary somatosensory cortex in the lesioned hemisphere of a patient (SR) with acquired auditory-tactile synesthesia, in whom sounds alone produce bodily sensations. These results provide an anatomical basis for multisensory interactions between audition and somatosensation and suggest that cross-talk between these regions may explain why some sounds, such as nails screeching down a chalkboard or an audible mosquito, can induce feelings of touch, especially on the contralesional body surface of patient SR.	\N	\N
22695875	The aim of this study is to compare the hearing thresholds of the diabetic patients with the age- and sex-matched normal control group regarding age, glucose level, duration and complications of diabetes with the degree of hearing impairment. Pure tone audiometry was performed in 58 patients with type 1 and 2 diabetes mellitus and compared with 58 age- and sex-matched controls. The patients were categorized into groups according to age, duration of diabetes, complications and control of diabetes. These observations were compared with those from the control subjects. 15-50 years age group with diabetes showed a significant high frequency hearing loss, as compared to the controls. Complicated and poorly controlled diabetics have significant degree of hearing loss in high frequencies as compared to those who were well controlled and uncomplicated. There was also a correlation between the level of hearing loss and duration of diabetes.	\N	\N
22710551	Superficial siderosis is a progressive disease of the central nervous system associated with chronic subarachnoid hemorrhage. Sensorineural hearing loss occurs early in the disease typically progressing to a profound hearing loss during several years and ultimately affecting 95% of patients. There are published reports of variable outcomes regarding auditory performance for cochlear implantation in cases of superficial siderosis: the objective of this article was to systematically review this evidence. A systematic search of NHS Evidence electronic journal databases AMED (1985 to present), BNI (1985 to present), CINAHL (1981 to present), EMBASE (1980 to present), HEALTH BUSINESS ELITE, HMIC, MEDLINE (1950 to present), and PsycINFO (1806 to present) was performed. Further research using personal communication, Google Scholar, hand searching Otology & Neurotology (2008-2011), and assessment of reference lists identified in other relevant articles yielded additional articles. A total of 24 articles were short-listed based on relevance; no studies were excluded on a basis of quality. Of these 24 articles, 11 were excluded. The 13 articles included in this review report 15 cases of cochlear implantation in superficial siderosis. Of these 15 individual cases, 7 (47%) showed clear sustained benefit from cochlear implantation, 6 showed limited/no benefit from the onset, and the remaining 2 patients' initial benefit was not maintained. Outcomes will depend on the site of lesion and the degree of cochlear nerve functionality, as well as ongoing neural deterioration. Comprehensive assessment of the auditory pathway including electrical auditory brainstem response and magnetic resonance imaging as well as pre/postimplantation counseling is indicated, but these preoperative measures are imperfect predictors of outcomes. There are indications that, where the underlying disease is stable, cochlear implant performance may be sustained, and where there is disease progression (specifically regarding involvement of auditory brainstem nuclei), cochlear implant performance may deteriorate. Further data are needed in this regard; however, results suggest that earlier implantation would provide benefit for a longer period and increase cost-effectiveness.	\N	\N
22712945	Frequency modulation detection limens (FMDLs) were measured for five hearing-impaired (HI) subjects for carrier frequencies f(c) = 1000, 4000, and 6000 Hz, using modulation frequencies f(m) = 2 and 10 Hz and levels of 20 dB sensation level and 90 dB SPL. FMDLs were smaller for f(m) = 10 than for f(m) = 2 Hz for the two higher f(c), but not for f(c) = 1000 Hz. FMDLs were also determined with additional random amplitude modulation (AM), to disrupt excitation-pattern cues. The disruptive effect was larger for f(m) = 10 than for f(m) = 2 Hz. The smallest disruption occurred for f(m) = 2 Hz and f(c) = 1000 Hz. AM detection thresholds for normal-hearing and HI subjects were measured for the same f(c) and f(m) values. Performance was better for the HI subjects for both f(m). AM detection was much better for f(m)  = 10 than for f(m) = 2 Hz. Additional tests showed that most HI subjects could discriminate temporal fine structure (TFS) at 800 Hz. The results are consistent with the idea that, for f(m) = 2 Hz and f(c) = 1000 Hz, frequency modulation (FM) detection was partly based on the use of TFS information. For higher carrier frequencies and for all carrier frequencies with f(m) = 10 Hz, FM detection was probably based on place cues.	\N	\N
22712949	The musical scale is a basis for melodies and can be a simple melody by itself. The present study investigated magnetoencephalographic (MEG) responses to omissions of one tone out of the C major scale. The tone preceding the omitted "target" tone was either prolonged or repeated. In another series, the tone after the target tone was repeated. In "normal" oddball experiments, the complete C major scale was presented more frequently than an incomplete scale lacking one tone, and in "reverse" oddball experiments, the roles were exchanged. In the normal oddball experiments, omission of any tone produced a response significantly different in amplitude from the standard response in the group of non-musicians, although the responses differed depending on the types of omission. The leading tone (B in the C major scale) was shown to elicit a large response when omitted and also when its presence was emphasized. The Reverse oddball experiments showed that repeated presentation of an incomplete scale lacking one tone temporarily reduced the influence of the complete scale but could not even temporarily replace it working as "standard." In addition, an auxiliary study was done to see possible influence of rhythmic variations.	\N	\N
22713383	We report a patient with non-fluent Primary Progressive Aphasia who was premorbidly literate in two alphabetic scripts, Hungarian (L1) and English (L2). Testing was performed over a two-year period to assess the impact of progressive illness on oral reading and repetition of single words. Results showed significant decline in oral reading in both languages, and an effect of language status in favour of oral reading in L1. Phonological complexity was a significant predictor of oral reading decline in both languages. Of interest, we observed an effect of language status on task performance whereby repetition was better in L2 than L1 but oral reading was better in L1 than L2. We conclude that language status has an effect on repetition and oral reading abilities for bilingual speakers with non-fluent Primary Progressive Aphasia.	\N	\N
22714710	It is clear that the ability to learn new speech contrasts changes over development, such that learning to categorize speech sounds as native speakers of a language do is more difficult in adulthood than it is earlier in development. There is also a wealth of data concerning changes in the perception of speech sounds during infancy, such that infants quite rapidly progress from language-general to more language-specific perceptual biases. It is often suggested that the perceptual narrowing observed during infancy plays a causal role in the loss of plasticity observed in adulthood, but the relationship between these two phenomena is complicated. Here I consider the relationship between changes in sensitivity to speech sound categorization over the first 2 years of life, when they appear to reorganize quite rapidly, to the "long tail" of development throughout childhood, in the context of understanding the sensitive period for speech perception.	\N	\N
22716266	This study aimed to discover whether general receptive vocabulary is qualitatively phenotypical in Down syndrome. Sixty-two participants with Down syndrome (M age=16.74 years, SD=3.28) were individually matched on general vocabulary raw total score with 62 participants with intellectual disability of undifferentiated etiology (M age=16.20 years, SD=3.08) and 62 typical children (M age=5.32 years, SD=0.82). Item analyses using the transformed item difficulties method to detect differential item functioning across groups showed that the groups' rank orders of item difficulty were highly similar. It was concluded that the general receptive vocabulary of older children and adolescents with Down syndrome is not qualitatively distinguished when its overall size is held constant. Methodological and theoretical implications of this finding are discussed.	\N	\N
22717687	To develop a predictive model of spatial release from masking (SRM) for cochlear implantees, and validate this model against data from the literature. To establish the spatial configurations for which the model predicts a large advantage of bilateral over unilateral implantation. To collect data to support these predictions and generate predictions of more typical advantages of bilateral implantation. The model initially assumed that bilateral cochlear implantees had equally effective implants on each side, with which they could perform optimal better-ear listening. Predictions were compared with measurements of SRM, using one and two implants with up to three interfering noises. The effect of relaxing the assumption of equally effective implants was explored. Novel measurements of SRM for eight unilateral implantees were collected, including measurements using speech and noise at azimuths of ± 60 degrees, and compared with prediction. A spatial map of bilateral implant benefit was generated for a situation with one interfering noise in anechoic conditions, and predictions of benefit were generated from binaural room impulse responses in a variety of real rooms. The model accurately predicted data from a previous study for multiple interfering noises in a variety of spatial configurations, even when implants were assumed to be equally effective (r = 0.97). It predicted that the maximum benefit of bilateral implantation was 18 dB. Predictions were little affected if the implants were not assumed to be equally effective. The new measurements supported the 18 dB advantage prediction. The spatial map of predicted benefit showed that, for a listener facing the target voice, bilateral implantees could enjoy an advantage of about 10 dB over unilateral implantees in a wide range of situations. Predictions based on real-room measurements with speech and noise at 1 m showed that large benefits can occur even in reverberant spaces. In optimal conditions, the benefit of bilateral implantation to speech intelligibility in noise can be much larger than has previously been reported. This benefit is thus considerably larger than reported benefits of summation or squelch and is robust in reverberation when the interfering source is close.	\N	\N
22721629	Understanding the temporal dynamics underlying cortical processing of auditory categories is complicated by difficulties in equating temporal and spectral features across stimulus classes. In the present magnetoencephalography (MEG) study, female voices and cat sounds were filtered so as to match in most of their acoustic properties, and the respective auditory evoked responses were investigated with a paradigm that allowed us to examine auditory cortical processing of two natural sound categories beyond the physical make-up of the stimuli. Three cat or human voice sounds were first presented to establish a categorical context. Subsequently, a probe sound that was congruent, incongruent, or ambiguous to this context was presented. As an index of a categorical mismatch, MEG responses to incongruent sounds were stronger than the responses to congruent sounds at ~250 ms in the right temporoparietal cortex, regardless of the sound category. Furthermore, probe sounds that could not be unambiguously attributed to any of the two categories ("cat" or "voice") evoked stronger responses after the voice than cat context at 200-250 ms, suggesting a stronger contextual effect for human voices. Our results suggest that categorical templates for human and animal vocalizations are established at ~250 ms in the right temporoparietal cortex, likely reflecting continuous online analysis of spectral stimulus features during auditory categorizing task.	\N	\N
22726605	In a recent study, we reported that the accurate perception of beat structure in music ('perception of musical meter') accounted for over 40% of the variance in single word reading in children with and without dyslexia (Huss et al., 2011). Performance in the musical task was most strongly associated with the auditory processing of rise time, even though beat structure was varied by manipulating the duration of the musical notes. Here we administered the same musical task a year later to 88 children with and without dyslexia, and used new auditory processing measures to provide a more comprehensive picture of the auditory correlates of the beat structure task. We also measured reading comprehension and nonword reading in addition to single word reading. One year later, the children with dyslexia performed more poorly in the musical task than younger children reading at the same level, indicating a severe perceptual deficit for musical beat patterns. They now also had significantly poorer perception of sound rise time than younger children. Longitudinal analyses showed that the musical beat structure task was a significant longitudinal predictor of development in reading, accounting for over half of the variance in reading comprehension along with a linguistic measure of phonological awareness. The non-linguistic musical beat structure task is an important independent longitudinal and concurrent predictor of variance in reading attainment by children. The different longitudinal versus concurrent associations between musical beat perception and auditory processing suggest that individual differences in the perception of rhythmic timing are an important shared neural basis for individual differences in children in linguistic and musical processing.	\N	\N
22732772	The purpose of this study was to determine how combinations of reverberation and noise, typical of environments in many elementary school classrooms, affect normal-hearing school-aged children's speech recognition in stationary and amplitude-modulated noise, and to compare their performance with that of normal-hearing young adults. In addition, the magnitude of release from masking in the modulated noise relative to that in stationary noise was compared across age groups in nonreverberant and reverberant listening conditions. Last, for all noise and reverberation combinations the degree of change in predicted performance at 70% correct was obtained for all age groups using a best-fit cubic polynomial. Bamford-Kowal-Bench sentences and noise were convolved with binaural room impulse responses representing nonreverberant and reverberant environments to create test materials representative of both audiology clinics and school classroom environments. Speech recognition of 48 school-aged children and 12 adults was measured in speech-shaped and amplitude-modulated speech-shaped noise, in the following three virtual listening environments: nonreverberant, reverberant at 2 m, and reverberant at 6 m. Speech recognition decreased in the reverberant conditions and with decreasing age. Release from masking in modulated noise relative to stationary noise decreased with age and was reduced by reverberation. In the nonreverberant condition, participants showed similar amounts of masking release across ages. The slopes of performance-intensity functions increased with age, with the exception of the nonreverberant modulated masker condition. The slopes were steeper in the stationary masker conditions, where they also decreased with reverberation and distance. In the presence of a modulated masker, the slopes did not differ between the two reverberant conditions. The results of this study reveal systematic developmental changes in speech recognition in noisy and reverberant environments for elementary-school-aged children. The overall pattern suggests that younger children require better acoustic conditions to achieve sentence recognition equivalent to their older peers and adults. In addition, this is the first study to report a reduction of masking release in children as a result of reverberation. Results support the importance of minimizing noise and reverberation in classrooms, and highlight the need to incorporate noise and reverberation into audiological speech-recognition testing to improve predictions of performance in the real world.	\N	\N
22743078	This work is a preliminary study that sought to investigate and develop a method for defining and evaluating "success" in paediatric cochlear implantation (PCI) and to apply a process by which a clinical team could optimally achieve this aim. A pilot group of 25 profoundly deaf children who received a unilateral cochlear implant from 1995 to 2008 was used to develop the process. The cases displayed features that are commonly encountered in PCI. Individual case records were examined retrospectively for adverse factors that might impact on the implantation outcome with particular reference to the probability and severity of impact of each factor. Case prognosis was then rated on a 1-4 basis (1: excellent, 2: good, 3: fair, 4: poor). The subsequent outcomes were assessed using standardised speech (GFW, DEAP), language (PLS-4; CELF) and vocabulary (PPVT; EVT) assessments. Auditory performance outcomes were assessed using a new Categories of Auditory Performance Index (CAPI) that incorporated criteria, testing and scoring aspects. Family issues were also evaluated. Case outcomes were rated 1-4 as above and the prognoses and outcomes were then compared. Accurate prognostication was seen in 14 cases, 5 had better outcomes than expected and 6 obtained poorer results. "Success", where the outcome equalled or exceeded the prognosis, occurred in 19 (76%) of cases. The successful group contained some "limited gains" cases where the results were nonetheless in line with expectations and parental satisfaction. The detrimental effect of delayed implantation was evident; Connexin 26 (GJB2) mutation had little influence. Poor general medical condition and adverse family situations commonly produced poorer outcomes. Success in PCI is achieved when the outcome matches or exceeds the pre-operative expectations of the well-counselled family, without adverse side effects. The assessments achieved a good success rate, but further research is required to clearly identify potential problems and a skilled team is needed to evaluate their risk to the PCI outcome. Unforseen events may also intervene. Currently, differing outcome evaluation techniques impede comparison of studies, particularly in the speech and hearing domains. Rationalisation of these is recommended to facilitate future research.	\N	\N
22744139	To determine if short-term computerized speech-in-noise training can produce significant improvements in speech-in-noise perception by cochlear implant (CI) recipients on standardized audiologic testing measures. Five adult postlingually deafened CI recipients participated in 4 speech-in-noise training sessions using the Seeing and Hearing Speech program (Sensimetrics; Malden, MA). Each participant completed lessons concentrating on consonant and vowel recognition at word, phrase, and sentence levels. Speech-in-noise abilities were assessed using the QuickSIN (Killion, Niquette, Gudmundsen, Revit, & Banerjee, 2004) and the Hearing in Noise Test (HINT ( Nilsson, Soli & Sullivan, 1994)). All listeners significantly improved key word identification on the HINT after training, albeit only at the most favorable signal-to-noise ratio (SNR). Listeners also showed a significant reduction in the degree of SNR loss on the QuickSIN after training. Short-term speech-in-noise training may improve speech-in-noise perception in postlingually deafened adult CI recipients.	\N	\N
22760769	Sound localization is a computational process accomplished along the auditory pathway. Once the acoustic information received at each ear is analyzed independently (monaural cues) and comparatively (binaural cues), those cues are integrated to generate a coherent spatial percept. Using adult ferrets trained by positive conditioning in a spatial task, we aimed to study the role of the auditory cortex in the ability to localize sounds under both normal hearing and monaurally occluded conditions, the latter of which requires a reinterpretation of the values of the localization cues. Sound localization deficits were found after lesion or inactivation of the different auditory cortical regions, thereby indicating their participation in spatial processing. The differential impairments found in the approach-to-target and in the head movement responses reveal the complex relationship between cortex and midbrain which are putatively responsible for the voluntary and reflexive aspects of localization behaviour respectively. Furthermore, every auditory cortical region contributes to the adaptation process that follows monaural occlusion, indicating the key role that the auditory cortex plays in experience-dependent plasticity. Also, the selective lesion of the descending projections from the auditory cortex to the inferior colliculus by chromophore-targeted laser photolysis has revealed the essential function that descending pathways play in learning-induced localization plasticity.	\N	\N
22772879	Synesthesia is an unusual condition in which stimulation of one sensory modality causes an experience in another sensory modality or when a sensation in one sensory modality causes another sensation within the same modality. We describe a previously unreported association of auditory-olfactory synesthesia coexisting with auditory-visual synesthesia. Given that many types of synesthesias involve vision, it is important that the clinician provide these patients with the necessary information and support that is available.	\N	\N
22773777	Many neurons adapt their spike output to accommodate the prevailing sensory environment. Although such adaptation is thought to improve coding of relevant stimulus features, the relationship between adaptation at the neural and behavioral levels remains to be established. Here we describe improved discrimination performance for an auditory spatial cue (interaural time differences, ITDs) following adaptation to stimulus statistics. Physiological recordings in the midbrain of anesthetized guinea pigs and measurement of discrimination performance in humans both demonstrate improved coding of the most prevalent ITDs in a distribution, but with highest accuracy maintained for ITDs corresponding to frontal locations, suggesting the existence of a fovea for auditory space. A biologically plausible model accounting for the physiological data suggests that neural tuning is stabilized by inhibition to maintain high discriminability for frontal locations. The data support the notion that adaptive coding in the midbrain is a key element of behaviorally efficient sound localization in dynamic acoustic environments.	\N	\N
22779451	Animals live in cluttered auditory environments, where sounds arrive at the two ears through several paths. Reflections make sound localization difficult, and it is thought that the auditory system deals with this issue by isolating the first wavefront and suppressing later signals. However, in many situations, reflections arrive too early to be suppressed, for example, reflections from the ground in small animals. This paper examines the implications of these early reflections on binaural cues to sound localization, using realistic models of reflecting surfaces and a spherical model of diffraction by the head. The fusion of direct and reflected signals at each ear results in interference patterns in binaural cues as a function of frequency. These cues are maximally modified at frequencies related to the delay between direct and reflected signals, and therefore to the spatial location of the sound source. Thus, natural binaural cues differ from anechoic cues. In particular, the range of interaural time differences is substantially larger than in anechoic environments. Reflections may potentially contribute binaural cues to distance and polar angle when the properties of the reflecting surface are known and stable, for example, for reflections on the ground.	\N	\N
22779484	Previous studies have shown a loss in the precision of horizontal localization responses of older hearing-impaired (HI) individuals, along with potentially poorer neural representations of sound-source location. These deficits could be the result or corollary of greater difficulties in discriminating spatial images, and the insensitivity to punctate sound sources. This hypothesis was tested in three headphone-presentation experiments varying interaural coherence (IC), the cue most associated with apparent auditory source width. First, thresholds for differences in IC were measured for a broad sampling of participants. Older HI participants were significantly worse at discriminating IC across reference values than younger normal-hearing participants. These results are consistent with senescent increases in temporal jitter. Performance decreased with age, a finding corroborated in a second discrimination experiment using a separate group of participants matched for hearing loss. This group also completed a third, visual experiment, with both a cross-mapping task where they drew the size of the sound they heard and the identification task where they chose the image that best corresponded to what they heard. The results from the visual tasks indicate that older HI individuals do not hear punctate images and are relatively insensitive to changes in width based on IC.	\N	\N
22783631	This study investigates the phonetic implementation of stress in American English compounds by measuring the interaction of stress cues with different intonation patterns. Participants in an experiment produced compounds and phrases such as greenhouse and green house in different prosodic positions and sentence types to elicit the contrast in a variety of intonational environments. Intonation patterns were labeled and carefully controlled for, and measurements of vowel duration, intensity (dB) and pitch (in semitones) were compared. The results of the experiment reveal clear patterns that distinguish compounds from phrases, and provide acoustic evidence of the characteristic prominence pattern for adjective + noun compounds. Intensity is a significant cue for compound stress in all but the rising intonation environments, such as questions. Duration differences are a reliable cue in exactly this intonational environment, and also in certain clause-final intonation patterns, which similarly contain a high boundary tone. Distinctive pitch patterns were also found. The results suggest that interactions with the intonational and prosodic environment determine which phonetic cues will signal the stress pattern of a compound in a given utterance.	\N	\N
22786953	Auditory spatial perception plays a critical role in day-to-day communication. For instance, listeners utilize acoustic spatial information to segregate individual talkers into distinct auditory "streams" to improve speech intelligibility. However, spatial localization is an exceedingly difficult task in everyday listening environments with numerous distracting echoes from nearby surfaces, such as walls. Listeners' brains overcome this unique challenge by relying on acoustic timing and, quite surprisingly, visual spatial information to suppress short-latency (1-10 ms) echoes through a process known as "the precedence effect" or "echo suppression." In the present study, we employed electroencephalography (EEG) to investigate the neural time course of echo suppression both with and without the aid of coincident visual stimulation in human listeners. We find that echo suppression is a multistage process initialized during the auditory N1 (70-100 ms) and followed by space-specific suppression mechanisms from 150 to 250 ms. Additionally, we find a robust correlate of listeners' spatial perception (i.e., suppressing or not suppressing the echo) over central electrode sites from 300 to 500 ms. Contrary to our hypothesis, vision's powerful contribution to echo suppression occurs late in processing (250-400 ms), suggesting that vision contributes primarily during late sensory or decision making processes. Together, our findings support growing evidence that echo suppression is a slow, progressive mechanism modifiable by visual influences during late sensory and decision making stages. Furthermore, our findings suggest that audiovisual interactions are not limited to early, sensory-level modulations but extend well into late stages of cortical processing.	\N	\N
22790547	Children and adolescents who live in situations of social vulnerability present a series of health problems. Nonetheless, affirmations that sensory and cognitive abnormalities are present are a matter of controversy. The aim of this study was to investigate aspects to auditory processing, through applying the brainstem auditory evoked potential (BAEP) and behavioral auditory processing tests to children living on the streets, and comparison with a control group. Cross-sectional study in the Laboratory of Auditory Processing, School of Medicine, Universidade de São Paulo. The auditory processing tests were applied to a group of 27 individuals, subdivided into 11 children (7 to 10 years old) and 16 adolescents (11 to 16 years old), of both sexes, in situations of social vulnerability, compared with an age-matched control group of 10 children and 11 adolescents without complaints. The BAEP test was also applied to investigate the integrity of the auditory pathway. For both children and adolescents, there were significant differences between the study and control groups in most of the tests applied, with significantly worse performance in the study group, except in the pediatric speech intelligibility test. Only one child had an abnormal result in the BAEP test. The results showed that the study group (children and adolescents) presented poor performance in the behavioral auditory processing tests, despite their unaltered auditory brainstem pathways, as shown by their normal results in the BAEP test.	\N	\N
22813575	To separate neural signals from noise, brain responses measured in neuroimaging are routinely averaged across space and time. However, such procedures may obscure some properties of neural activity. Recently, multi-voxel pattern analysis methods have demonstrated that patterns of activity across voxels contain valuable information that is concealed by spatial averaging. Here we show that temporal patterns of neural activity contain information that can discriminate different stimuli, even within brain regions that show no net activation to that stimulus class. Furthermore, we find that in many brain regions, responses to natural stimuli are highly context dependent. In such cases, prototypical event-related responses do not even exist for individual stimuli, so that averaging responses to the same stimulus within different contexts may worsen the effective signal-to-noise. As a result, analysis of the temporal structures of single events can reveal aspects of neural dynamics which cannot be detected using standard event-related averaging methods.	\N	\N
22821077	The decision about which location should be the goal of the next eye movement is known to be determined by the interaction between auditory and visual input. This interaction can be explained by the vector theory that states that each element (either visual or auditory) in a scene evokes a vector in the oculomotor system. These vectors determine the direction in which the eye movement is initiated. Because auditory input is lateralized and localizable in most studies, it is currently unclear how non-lateralized auditory input interacts with the vectors evoked by visual input. In the current study, we investigated the influence of a non-lateralized auditory non-target on saccade accuracy (saccade angle deviation from the target) and latency in a single-target condition in Experiment 1 and a double-target condition in Experiment 2. The visual targets in Experiment 2 were positioned in such a way that saccades on average landed in between the two targets (i.e., a global effect). There was no effect of the auditory input on saccade accuracy in the single-target condition, but auditory input did influence saccade accuracy in the double-target condition. In both experiments, saccade latency increased when auditory input accompanied the visual target(s). Together, these findings show that non-lateralized auditory input enhances all vectors evoked by visual input. The results will be discussed in terms of their possible neural substrates.	\N	\N
22834336	The coherency characteristics of the brain electrical activity were studied in two groups of subjects: 1) with high and 2) low indexes of "emotional ear" (an ability to successfully recognize emotions in the speech). Comparison of the coherency links between two groups of subjects permitted the authors to make a conclusion that the persons of the first group had a much lower coherency level, especially in the alpha- and gamma-rhythms. The subjects of the second group were characterized by the opposite tendency: an increase in coherent links on the majority of frequency bands.	\N	\N
22836173	Functional networks in the human brain give rise to complex cognitive and perceptual abilities. While the decrease of functional connectivity is linked to neurological and psychiatric disorders, less is known about the consequences of increased functional connectivity. One population that has exceptionally enhanced perceptual abilities is people with absolute pitch (AP) - an ability to categorize tones into pitch classes without reference. AP has been linked to exceptional talent as well as to psychiatric and neurological conditions. Here we show that AP possessors have increased functional activation during music listening, as well as increased degrees, clustering, and local efficiency of functional correlations, with the difference being highest around the left superior temporal gyrus. Our results provide the first evidence that increased functional connectivity in a small-world brain network is related to exceptional perceptual abilities in a healthy population.	\N	\N
22842471	Task-irrelevant perceptual learning (TIPL) refers to the phenomenon where the stimulus features of a subject's task are learned when they are consistently presented at times when behaviorally relevant events occur. In this article, we addressed two points concerning TIPL. First, we address the question, are all behaviorally relevant events equal in their impact on encoding processes? Second, we address the hypothesis that TIPL involves mechanisms of the alerting attentional system. Two experiments of fast-TIPL were conducted in which the attentional state of participants was manipulated by using an alerting cue (visual or auditory) that informed participants of the arrival of an upcoming target. Images were presented with task-related stimuli (cues, targets and distractors) and subjects were tested on their memory of those images. Results indicate that memory for target-paired images was enhanced and cue-paired images were suppressed relative to that of distractor-paired images. The alerting cue increased the ability to recall target-paired images presented after this cue, although this result depended on the proportion of cued trials in a session. These results demonstrate a complex interplay between task-elements and the encoding of stimuli paired with them where both enhancement and suppression of task-paired stimuli can be found depending whether those stimuli are paired with task-targets or cues.	\N	\N
22848464	When a second sound follows a long first sound, its location appears to be perceived away from the first one (the localization/lateralization aftereffect). This aftereffect has often been considered to reflect an efficient neural coding of sound locations in the auditory system. To understand determinants of the localization aftereffect, the current study examined whether it is induced by an interaural temporal difference (ITD) in the amplitude envelope of high frequency transposed tones (over 2 kHz), which is known to function as a sound localization cue. In Experiment 1, participants were required to adjust the position of a pointer to the perceived location of test stimuli before and after adaptation. Test and adapter stimuli were amplitude modulated (AM) sounds presented at high frequencies and their positional differences were manipulated solely by the envelope ITD. Results showed that the adapter's ITD systematically affected the perceived position of test sounds to the directions expected from the localization/lateralization aftereffect when the adapter was presented at ±600 µs ITD; a corresponding significant effect was not observed for a 0 µs ITD adapter. In Experiment 2, the observed adapter effect was confirmed using a forced-choice task. It was also found that adaptation to the AM sounds at high frequencies did not significantly change the perceived position of pure-tone test stimuli in the low frequency region (128 and 256 Hz). The findings in the current study indicate that ITD in the envelope at high frequencies induces the localization aftereffect. This suggests that ITD in the high frequency region is involved in adaptive plasticity of auditory localization processing.	\N	\N
22858614	The purpose of this evidence-based systematic review was to evaluate the efficacy of digital noise reduction and directional microphones for outcome measures of audibility, speech recognition, speech and language, and self- or parent-report in pediatric hearing aid users. The authors searched 26 databases for experimental studies published after 1980 addressing one or more clinical questions and meeting all inclusion criteria. The authors evaluated studies for methodological quality and reported or calculated p values and effect sizes when possible. A systematic search of the literature resulted in the inclusion of 4 digital noise reduction and 7 directional microphone studies (in 9 journal articles) that addressed speech recognition, speech and language, and/or self- or parent-report outcomes. No digital noise reduction or directional microphone studies addressed audibility outcomes. On the basis of a moderate level of evidence, digital noise reduction was not found to improve or degrade speech understanding. Additional research is needed before conclusions can be drawn regarding the impact of digital noise reduction on important speech, language, hearing, and satisfaction outcomes. Moderate evidence also indicates that directional microphones resulted in improved speech recognition in controlled optimal settings; however, additional research is needed to determine the effectiveness of directional microphones in actual everyday listening environments.	\N	\N
22859982	Pitch processing is a critical ability on which humans' tonal musical experience depends, and which is also of paramount importance for decoding prosody in speech. Congenital amusia refers to deficits in the ability to properly process musical pitch, and recent evidence has suggested that this musical pitch disorder may impact upon the processing of speech sounds. Here we present the first electrophysiological evidence demonstrating that individuals with amusia who speak Mandarin Chinese are impaired in classifying prosody as appropriate or inappropriate during a speech comprehension task. When presented with inappropriate prosody stimuli, control participants elicited a larger P600 and smaller N100 relative to the appropriate condition. In contrast, amusics did not show significant differences between the appropriate and inappropriate conditions in either the N100 or the P600 component. This provides further evidence that the pitch perception deficits associated with amusia may also affect intonation processing during speech comprehension in those who speak a tonal language such as Mandarin, and suggests music and language share some cognitive and neural resources.	\N	\N
22866760	Many studies have examined the processes involved in recognizing types of human action through sound, but little is known about whether the physical characteristics of an action (such as kinetic and kinematic parameters) can be perceived and imitated from sound. Twelve young healthy adults listened to recordings of footsteps on a gravel path taken from walks of different stride lengths (SL) and cadences. In 1 protocol, participants performed a real-time reenactment of the walking action depicted in a sound sample. Second, participants listened to 2 different sound samples and discriminated differences in SL. In a 2nd experiment, these procedures were repeated using synthesized sounds derived from the kinetic interactions between the foot and walking surface. A 3rd experiment examined the influence of altered cadence on participants' ability to discriminate changes in SL. Participants significantly adapted their own SL and cadence according to those depicted in both real and synthesized sounds (p < .01). However, although participants accurately discriminated between large changes in SL, these perceptions were heavily influenced by temporal factors, that is, when cadence changed between samples. These findings show that spatial attributes of action sounds can be both mimicked and discriminated, even when only basic kinetic interactions present within the action are specified.	\N	\N
22875083	The aim of the current study was to differentiate between neural activity that represents neural anomalies that are responsible for persistent developmental stuttering (PDS) from the activity that is a result of compensating for stuttering. This was done by investigating alterations to the intrinsic functional architecture of speech-language processes of patients with PDS before and after a short-term intervention. The resting-state functional connectivity (RSFC) and cortical thickness were examined before and after the intervention. The structural data were used to validate the functional results. Fifteen stuttering patients who received intervention (PDS+), 13 stuttering patients who did not receive intervention (PDS-), and 13 fluent controls participated. Before the intervention, both groups of PDS patients showed significant RSFC and cortical thickness reductions in the left pars-opercularis (PO) and RSFC increases in the cerebellum, as compared to fluent controls. The intervention was effective in reducing stuttering in PDS+ patients and lowering their RSFC in the cerebellum to the level of fluent controls. The intervention effect was specific to the PDS+ group (it was not evident in the PDS- group). The intervention did not change RSFC and cortical thickness in the left PO, which remained at its preintervention level. The results suggest that the left PO is a locus where the intrinsic functional architecture of speech-language processes is altered in PDS patients, suggesting an etiologic role of this region in PDS. The cerebellum showed intervention-induced neural reorganization, suggesting a compensatory response when stuttering occurs.	\N	\N
22889186	Two experiments are reported concerning the perception of ground extent to discover whether prior reports of anisotropy between frontal extents and extents in depth were consistent across different measures (visual matching and pantomime walking) and test environments (outdoor environments and virtual environments). In Experiment 1 it was found that depth extents of up to 7 m are indeed perceptually compressed relative to frontal extents in an outdoor environment, and that perceptual matching provided more precise estimates than did pantomime walking. In Experiment 2, similar anisotropies were found using similar tasks in a similar (but virtual) environment. In both experiments pantomime walking measures seemed to additionally compress the range of responses. Experiment 3 supported the hypothesis that range compression in walking measures of perceived distance might be due to proactive interference (memory contamination). It is concluded that walking measures are calibrated for perceived egocentric distance, but that pantomime walking measures may suffer range compression. Depth extents along the ground are perceptually compressed relative to frontal ground extents in a manner consistent with the angular scale expansion hypothesis.	\N	\N
22894208	Artificial bandwidth extension methods have been developed to improve the quality and intelligibility of narrowband telephone speech and to reduce the difference with wideband speech. Such methods have commonly been evaluated with objective measures or subjective listening-only tests, but conversational evaluations have been rare. This article presents a conversational evaluation of two methods for the artificial bandwidth extension of telephone speech. Bandwidth-extended narrowband speech is compared with narrowband and wideband speech in a test setting including a simulated telephone connection, realistic conversation tasks, and various background noise conditions. The responses of the subjects indicate that speech processed with one of the methods is preferred to narrowband speech in noise, but wideband speech is superior to both narrowband and bandwidth-extended speech. Bandwidth extension was found to be beneficial for telephone conversation in noisy listening conditions.	\N	\N
22894315	Studies of spoken-word recognition have revealed that competition from embedded words differs in strength as a function of where in the carrier word the embedded word is found and have further shown embedding patterns to be skewed such that embeddings in initial position in carriers outnumber embeddings in final position. Lexico-statistical analyses show that this skew is highly attenuated in Japanese, a noninflectional language. Comparison of the extent of the asymmetry in the three Germanic languages English, Dutch, and German allows the source to be traced to a combination of suffixal morphology and vowel reduction in unstressed syllables.	\N	\N
22897231	When asked how many animals of each kind Moses took on the Ark, most people respond with "two" despite the substituted name (Moses for Noah) in the question. Possible explanations for semantic illusions appear to be related to processing limitations such as those of working memory. Indeed, individual working memory capacity has an impact upon how sentences containing substitutions are processed. This experiment examined further the role of working memory in the occurrence of semantic illusions using a dual-task working memory load approach. Participants verified statements while engaging in either articulatory suppression or random number generation. Secondary task type had a significant effect on semantic illusion rate, but only when comparing the control condition to the two dual-task conditions. Furthermore, secondary task performance in the random number generation condition declined, suggesting a tradeoff between tasks. Response time analyses also showed a different pattern of processing across the conditions. The findings suggest that the phonological loop plays a role in representing semantic illusion sentences coherently and in monitoring for details, while the role of the central executive is to assist gist-processing of sentences. This usually efficient strategy leads to error in the case of semantic illusions.	\N	\N
22915198	Scalar Expectancy Theory (SET) has been the leading theory in timing research, and has also influenced research into human timing. However, other timing theories exist, such as Learning to Time (LeT). The double bisection task was designed to test the SET and LeT theories in pigeons. The purpose of this experiment was to verify whether similar results emerge from a human adaptation of the double bisection task. The results indicated that humans perform the double bisection task in the same way as pigeons do. However, the assumptions inherent in LeT cannot be applied to humans. Two other explanations are also assessed here.	\N	\N
22915276	A hearing screening among 14- to 15-year-old pupils was performed to estimate the number of hearing-impaired individuals in the adolescent population. A total of 1,298 pupils from 30 schools in Tyrol (Austria) participated in the screening. Hearing tests were performed in a silent room at the school. Sinus tones at frequencies 0.5/1/2/4/6 kHz and at levels of 25/20/20/20/20 dB HL, respectively, were delivered via headphones to either ear. Failure of screening was defined as not hearing one or more frequencies in one or both ears. The screening was failed by 16.3% of the pupils. There was a small but not significant difference between males and females (17.0 vs. 15.2%). Most of the pupils failed at only one frequency (9.6%). Failing at two or more frequencies in the same ear occurred in 3.9% of the pupils, thereof in 1.1% bilaterally. As the specificity of our screening is limited, false-positive results may result. Thus, the rate of hearing deficits in our sample is probably a bit lower than indicated by the figures above. Most of the adolescents who failed the screen failed at only one frequency. These subjects have a small elevation of their hearing threshold, not a hearing loss in the sense of a raised averaged threshold. A hearing loss in the latter sense is supposed to be present in only very few percent of adolescents, a bilateral hearing loss in perhaps less than 1%.	\N	\N
22918112	Current strategies for functional rehabilitation of microtia-atresia patients with bone-anchored implants or surgical atresia repair have been extended by the feasibility of active middle ear implants. The aim of the present research is to evaluate a new flowchart of the treatment of these patients that considers active middle ear implants. Congenital aural atresia and microtia. Bilateral cases are provided with a conductive hearing aid after birth and implanted with an active middle ear implant within the second year. Unilateral cases are provided with a conductive hearing aid and implanted with a middle ear or bone-conduction device in early childhood. Unilateral cases without amplification in the vulnerable time after birth are carefully selected for late implantation. At age 8 to 10, the auricular reconstruction is completed. Feasibility of implantation irrespective of age, functional gain in audiometry. The results of early implantation are as good as those previously published for adolescents. Mean reaction threshold with the Vibrant Soundbridge was 21 dB. Mean functional gain was 48 dB. The local tissues are unaltered and ready for auricular reconstruction. Active middle ear implants allow early and selective stimulation of the auditory pathway in children with congenital conductive hearing loss and are expected to lead to the normal development of the binaural hearing functions. To date, it is the only option if the stimulation is to be started at the age of 12 to 18 months. This was implemented into a new flowchart for aural atresia-microtia.	\N	\N
22921291	To use a randomized design to evaluate the effectiveness of voice training programs for telemarketers via multidimensional analysis. Forty-eight telemarketers were randomly assigned to two groups: voice training group (n=14) who underwent training over an 8-week period and a nontraining control group (n=34). Before and after training, recordings of the sustained vowel /ɛ/ and connected were collected for acoustic and perceptual analyses. Based on pre- and posttraining comparisons, the voice training group presented with a significant reduction in percent jitter (P=0.044). No other significant differences were observed, and inter-rater reliability varied from poor to fair. These findings suggest that voice training improved a single acoustic dimension, but do not change perceptual dimension of telemarketers' voices.	\N	\N
22921292	This study investigated whether listener's experience, presence/absence of vibrato, formant frequency difference, or onset delay affect the ability of experienced and inexperienced listeners to segregate complex vocal stimuli. Repeated measures factorial design. Two sets of stimuli were constructed: one with no vibrato and another with vibrato. For each set, each stimulus was synthesized at four pitches: A3, E4, B4, and F5. Stimuli were synthesized using formant patterns appropriate for the vowel |ɑ|. Frequencies for formants one through four were systematically varied from lower to higher in an attempt to simulate the acoustic results of corresponding changes in vocal tract length. Four formant patterns were synthesized (patterns A-D). Three pairs were created at each pitch, pairing the formants AB (mezzo-soprano/mezzo-soprano), CD (soprano/soprano), and AD (mezzo-soprano/soprano). Each of these three pairs was constructed in three separate conditions: simultaneous onset; the first voice in the pair with an onset delay of 100 milliseconds; and the second voice in the pair with an onset delay of 100 milliseconds. Using a scroll bar, listeners rated how difficult it was for them to hear each stimulus pair as two separate voices. The most difficult combinations to segregate were produced with no vibrato and used simultaneous onset. The easiest conditions to segregate were combinations including a "soprano-like" formant pattern (D) in the vibrato condition. Overall, listener's experience did not affect the perceived difficulty of segregation; however, in the presence of vibrato cues, inexperienced listeners did not use delay cues as an aid in segregation in the same manner as did experienced listeners. Once vibrato was removed from the experimental context, inexperienced listeners were able to use delay to aid in segregation in a similar manner to experienced listeners. Presence/absence of vibrato, formant pattern difference, and onset delay interact in a complex manner to affect the perceived difficulty of voice segregation.	\N	\N
22921368	In spite of its massively parallel architecture [1], the human brain is fundamentally limited if required to perform two tasks at the same time [2, 3]. This limitation can be studied with the psychological refractory period (PRP) paradigm, where two stimuli that require speeded responses occur in close succession [4]. Interference generally takes the form of a delay in the time to respond to the second stimulus [5]. Previous studies suggested that sensory decisions require the accumulation of sensory evidence [6, 7] and that the PRP reflects the inability to form more than one decision at a time [4, 8]. In the present study, we used a psychophysical reverse-correlation technique [9, 10] to measure the time-course of evidence accumulation during the PRP. We found that the accumulation of evidence could occur during the PRP albeit with a reduced efficiency, which implies that multiple decision processes can occur in parallel in the human brain. In addition to the reduced efficiency of evidence accumulation, our results uncover an additional delay in the routing of the decision to motor structures during the PRP, which implies that the process of sensory decision making is separable from the preparation of a motor response [11-13].	\N	\N
22921779	To evaluate the auditory outcomes of children implanted in an ear with eighth nerve hypoplasia or aplasia and to determine whether preoperative characteristics are predictive of auditory performance achieved. retrospective case review. tertiary care medical center. ten children implanted in an ear with eighth nerve hypoplasia or aplasia, as determined by high resolution magnetic resonance imaging. Neural response test measurements, detection and speech awareness thresholds, Meaningful Auditory Integration Scale scores, as well as speech perception level achieved. Post-implantation, three children demonstrated little to no detection of sound, three had improved detection and awareness of environmental sounds, one developed closed-set speech perception and spoken language, and three developed open-set speech perception and spoken language. No imaging findings appeared related to outcomes. Significantly better implant detection thresholds and Meaningful Auditory Integration Scale scores were found in children who had preoperative aided auditory detection (p's ≤ 0.02-0.05). Some children with eighth nerve hypoplasia or aplasia may derive significant benefit from a cochlear implant. In our study high resolution magnetic resonance imaging was more sensitive than high resolution computer tomography in detecting neural deficiency. However, no imaging findings were predictive of auditory performance level achieved post-implantation.	\N	\N
22928919	To investigate speech recognition performance in noise with bilateral open-fit hearing aids and as reference also with closed earmolds, in omnidirectional mode, directional mode, and directional mode in conjunction with noise reduction. A within-subject design with repeated measures across conditions was used. Speech recognition thresholds in noise were obtained for the different conditions. Twenty adults without prior experience with hearing aids. All had symmetric sensorineural mild hearing loss in the lower frequencies and moderate to severe hearing loss in the higher frequencies. Speech recognition performance in noise was not significantly better with an omnidirectional microphone compared to unaided, whereas performance was significantly better with a directional microphone (1.6 dB with open fitting and 4.4 dB with closed earmold) compared to unaided. With open fitting, no significant additional advantage was obtained by combining the directional microphone with a noise reduction algorithm, but with closed earmolds a significant additional advantage of 0.8 dB was obtained. The significant, though limited, advantage of directional microphones and the absence of additional significant improvement by a noise reduction algorithm should be considered when fitting open-fit hearing aids.	\N	\N
22928962	In synaesthetes, stimulation of one sensory pathway provokes a sensory experience (e.g. a colour concurrent) in a different sensory modality or sub-modality. Results of synaesthetic Stroop and priming tests indicate that the perception of a colour concurrent interferes with the processing of a veridical colour in synaesthetes. We here examined the congruency between a stimulus' colour and the colour concurrent both in grapheme-colour synaesthetes and in non-synaesthetes trained on grapheme-colour associations. Electrophysiological (electroencephalogram) and behavioural measurements were collected during a priming task that included grapheme-grapheme and grapheme-colour patch pairs. To investigate covert bidirectional synaesthesia, an additional inverted colour patch-grapheme condition was included. Both groups of participants showed longer reaction time and more negative-going N300 and N400 event-related potential (ERP) components on incongruent trials. Whereas ERP effects in the non-synaesthetes were largely confined to the late cognitive components N300, P300 and N400, the synaesthetes also showed congruency-dependent modulation of the early sensory component N170. Our results suggest that early cognitive processes distinguish cross-modal synaesthetic perceptions from acquired associations. The involvement of both early- and late-stage cognitive components in bidirectional synaesthesia possibly indicates similar feature-binding mechanisms during processing of opposite flow directions of information, namely grapheme-colour and colour-grapheme.	\N	\N
22937153	In everyday life, we need a capacity to flexibly shift attention between alternative sound sources. However, relatively little work has been done to elucidate the mechanisms of attention shifting in the auditory domain. Here, we used a mixed event-related/sparse-sampling fMRI approach to investigate this essential cognitive function. In each 10-sec trial, subjects were instructed to wait for an auditory "cue" signaling the location where a subsequent "target" sound was likely to be presented. The target was occasionally replaced by an unexpected "novel" sound in the uncued ear, to trigger involuntary attention shifting. To maximize the attention effects, cues, targets, and novels were embedded within dichotic 800-Hz vs. 1500-Hz pure-tone "standard" trains. The sound of clustered fMRI acquisition (starting at t = 7.82 sec) served as a controlled trial-end signal. Our approach revealed notable activation differences between the conditions. Cued voluntary attention shifting activated the superior intra--parietal sulcus (IPS), whereas novelty-triggered involuntary orienting activated the inferior IPS and certain subareas of the precuneus. Clearly more widespread activations were observed during voluntary than involuntary orienting in the premotor cortex, including the frontal eye fields. Moreover, we found -evidence for a frontoinsular-cingular attentional control network, consisting of the anterior insula, inferior frontal cortex, and medial frontal cortices, which were activated during both target discrimination and voluntary attention shifting. Finally, novels and targets activated much wider areas of superior temporal auditory cortices than shifting cues.	\N	\N
22938066	There are different reports of the usefulness of the Nasometer™ as a complement to listening, often as correlation calculations between listening and nasalance measurements. Differences between findings have been attributed to listener experience and types of speech stimuli. To compare nasalance scores from the Nasometer with perceptual assessments, for the same and different Swedish speech stimuli, using three groups of listeners with differing levels of experience in judging speech nasality. To compare nasalance scores and blinded listener ratings of randomized recordings using three groups of listeners and two groups of speakers. Speakers were either classified as having hypernasal speech or speech with typical speech resonance. Listeners were speech-language pathologists (SLPs) working predominantly with resonance disorders, other SLPs and untrained listeners. Correlations (r(s)) between hypernasality ratings and nasalance scores for each listener group and speech stimuli were calculated. For both groups of SLPs all correlations between perceptual ratings and nasalance scores were significant at p= 0.01. The correlations between the nasalance scores and ratings by listeners in the SLP groups were higher than those for the untrained listener group regardless of stimulus type. Post-hoc Mann-Whitney U-tests showed that the only difference that was significant was expert SLP group versus untrained listener group. Secondly, correlations between perceptual ratings and oral stimulus nasalance scores were higher when the perceptual ratings were based on spontaneous speech rather than on the oral stimulus. However, a Wilcoxon signed rank test showed that the difference was not significant. A third finding was that correlations between oral stimulus nasalance scores and perceptual scores were higher than those between mixed stimulus nasalance scores and perceptual scores. A Wilcoxon signed rank test showed that the difference was significant. The Nasometer might be useful for the SLP with limited experience in assessing resonance disorders in differentiating between hyper- and hyponasality. With listener reliability for ratings of hypernasality still being an issue, the use of a nasalance score as a complement to the perceptual evaluation will also aid the expert SLP. It will give an alternative way of quantifying speech resonance and might help in especially hard to judge cases.	\N	\N
22944369	Previous studies have demonstrated amygdala activation in response to fearful faces even if presented below the threshold of conscious visual perception. It has also been proposed that subcortical regions are selectively sensitive to low spatial frequency (LSF) information. However, chronic hyperarousal may reduce amygdala activation in panic disorder (PD). Our aim was to establish whether the amygdala is engaged by masked and LSF fearful faces in PD as compared to healthy subjects. Neutral faces were used as the mask stimulus. Thirteen PD patients (seven females, six males; mean age=29.1 (S.D: 5.9)) and 15 healthy volunteers (seven females, eight males; mean age=27.9 (S.D. 4.5)) underwent two passive viewing tasks during a 3T functional magnetic resonance imaging (fMRI) as follows: 1) presentation of faces with fearful versus neutral expressions (17ms) using a backward masking procedure and 2) presentation of the same faces whose spatial frequency contents had been manipulated by low-pass filtering. Level of awareness was confirmed by a forced choice fear-detection task. Whereas controls showed bilateral activation to fearful masked faces versus neutral faces, patients failed to show activation within the amygdala. LSF stimuli did not elicit amygdala response in either group, contrary to the view that LSF information plays a crucial role in the processing of facial expressions in the amygdala. Findings suggest maladaptive amygdala responses to potentially threatening visual stimuli in PD patients.	\N	\N
22962856	It has been suggested that high alexithymia scorers have an 'augmenter' profile which amplifies their physiological and subjective responses to highly arousing stimuli. The aim of this study was to test this theory using several physiological measures. Participants listened to musical excerpts either in a 'weak-to-strong' or a 'strong-to-weak' order of arousing levels of stimuli. The results show that alexithymia was associated with an augmenter profile for subjective reports for the most arousing stimulus and with stronger skin conductance level responses in the 'strong-to-weak' order. These results partially support the augmenter profile and reveal that alexithymia may be associated with higher anticipation for the most arousing excerpt.	\N	\N
22970141	Extensive research shows that inter-talker variability (i.e., changing the talker) affects recognition memory for speech signals. However, relatively little is known about the consequences of intra-talker variability (i.e. changes in speaking style within a talker) on the encoding of speech signals in memory. It is well established that speakers can modulate the characteristics of their own speech and produce a listener-oriented, intelligibility-enhancing speaking style in response to communication demands (e.g., when speaking to listeners with hearing impairment or non-native speakers of the language). Here we conducted two experiments to examine the role of speaking style variation in spoken language processing. First, we examined the extent to which clear speech provided benefits in challenging listening environments (i.e. speech-in-noise). Second, we compared recognition memory for sentences produced in conversational and clear speaking styles. In both experiments, semantically normal and anomalous sentences were included to investigate the role of higher-level linguistic information in the processing of speaking style variability. The results show that acoustic-phonetic modifications implemented in listener-oriented speech lead to improved speech recognition in challenging listening conditions and, crucially, to a substantial enhancement in recognition memory for sentences.	\N	\N
22978875	Simulated room impulse responses have been proven to be both useful and indispensable for comprehensive testing of acoustic signal processing algorithms while controlling parameters such as the reverberation time, room dimensions, and source-array distance. In this work, a method is proposed for simulating the room impulse responses between a sound source and the microphones positioned on a spherical array. The method takes into account specular reflections of the source by employing the well-known image method, and scattering from the rigid sphere by employing spherical harmonic decomposition. Pseudocode for the proposed method is provided, taking into account various optimizations to reduce the computational complexity. The magnitude and phase errors that result from the finite order spherical harmonic decomposition are analyzed and general guidelines for the order selection are provided. Three examples are presented: an analysis of a diffuse reverberant sound field, a study of binaural cues in the presence of reverberation, and an illustration of the algorithm's use as a mouth simulator.	\N	\N
22985274	Whether the mechanisms giving rise to pitch reflect spectral or temporal processing has long been debated. Generally, sounds having strong harmonic structures in their spectra have strong periodicities in their temporal structures. We found that when a wideband harmonic tone complex is passed through a noise vocoder, the resulting sound can have a harmonic structure with a large peak-to-valley ratio, but with little or no periodicity in the temporal structure. To test the role of harmonic structure in pitch perception for a nonhuman mammal, we measured behavioral responses to noise-vocoded tone complexes in chinchillas (Chinchilla laniger) using a stimulus generalization paradigm. Chinchillas discriminated either a harmonic tone complex or an iterated rippled noise from a 1-channel vocoded version of the tone complex. When tested with vocoded versions generated with 8, 16, 32, 64, and 128 channels, responses were similar to those of the 1-channel version. Behavioral responses could not be accounted for based on harmonic peak-to-valley ratio as the acoustic cue, but could be accounted for based on temporal properties of the autocorrelation functions such as periodicity strength or the height of the first peak. The results suggest that pitch perception does not arise through spectral processing in nonhuman mammals but rather through temporal processing. The conclusion that spectral processing contributes little to pitch in nonhuman mammals may reflect broader cochlear tuning than that described in humans.	\N	\N
22986018	Structural priming paradigms have been influential in shaping theories of adult sentence processing and theories of syntactic development. However, until recently there have been few attempts to provide an integrated account that explains both adult and developmental data. The aim of the present paper was to begin the process of integration by taking a developmental approach to structural priming. Using a dialog comprehension-to-production paradigm, we primed participants (3-4year olds, 5-6year olds and adults) with double object datives (Wendy gave Bob a dog) and prepositional datives (Wendy gave a dog to Bob). Half the participants heard the same verb in prime and target (e.g. gave-gave) and half heard a different verb (e.g. sent-gave). The results revealed substantial differences in the magnitude of priming across development. First, there was a small but significant abstract structural priming effect across all age groups, but this effect was larger in younger children than in older children and adults. Second, adding verb overlap between prime and target prompted a large, significant increase in the priming effect in adults (a lexical boost), a small, marginally significant increase in the older children and no increase in the youngest children. The results support the idea that abstract syntactic knowledge can develop independently of verb-specific frames. They also support the idea that different mechanisms may be needed to explain abstract structural priming and lexical priming, as predicted by the implicit learning account (Bock, K., & Griffin, Z. M. (2000). The persistence of structural priming: Transient activation or implicit learning? Journal of Experimental Psychology - General, 129(2), 177-192). Finally, the results illustrate the value of an integrative developmental approach to both theories of adult sentence processing and theories of syntax acquisition.	\N	\N
22989579	The perception of a melody is invariant to the absolute properties of its constituting notes, but depends on the relation between them-the melody's relative pitch profile. In fact, a melody's "Gestalt" is recognized regardless of the instrument or key used to play it. Pitch processing in general is assumed to occur at the level of the auditory cortex. However, it is unknown whether early auditory regions are able to encode pitch sequences integrated over time (i.e., melodies) and whether the resulting representations are invariant to specific keys. Here, we presented participants different melodies composed of the same 4 harmonic pitches during functional magnetic resonance imaging recordings. Additionally, we played the same melodies transposed in different keys and on different instruments. We found that melodies were invariantly represented by their blood oxygen level-dependent activation patterns in primary and secondary auditory cortices across instruments, and also across keys. Our findings extend common hierarchical models of auditory processing by showing that melodies are encoded independent of absolute pitch and based on their relative pitch profile as early as the primary auditory cortex.	\N	\N
22989871	The function of consciousness was explored in two contexts of audio-visual speech, cross-modal visual attention guidance and McGurk cross-modal integration. Experiments 1, 2, and 3 utilized a novel cueing paradigm in which two different flash suppressed lip-streams cooccured with speech sounds matching one of these streams. A visual target was then presented at either the audio-visually congruent or incongruent location. Target recognition differed for the congruent versus incongruent trials, and the nature of this difference depended on the probabilities of a target appearing at these respective locations. Thus, even though the lip-streams were never consciously perceived, they were nevertheless meaningfully integrated with the consciously perceived sounds, and participants learned to guide their attention according to statistical regularities between targets and these unconsciously perceived cross-modal cues. In Experiment 4, McGurk stimuli were presented in which the lip-streams were either flash suppressed (4a) or unsuppressed (4b), and the McGurk effect was found to vanish under conditions of flash suppression. Overall, these results suggest a simple yet fundamental principle regarding the function of consciousness in multisensory integration - cross-modal effects can occur in the absence of consciousness, but the influencing modality must be consciously perceived for its information to cross modalities.	\N	\N
22989933	Distraction is a strategy that is commonly used to cope with pain. Results concerning the efficacy of distraction from both experimental and clinical studies are variable, however, and indicate that its efficacy may depend on particular circumstances. Several models propose that distraction may be less effective for people who display a large attentional bias towards pain-related information. This hypothesis was tested in an experimental context with 53 pain-free volunteers. First, attentional bias towards cues signalling the occurrence of pain (electrocutaneous stimuli) and towards words describing the sensory experience of this painful stimulus was independently assessed by means of 2 behavioural paradigms (respectively, spatial cueing task and dot-probe task). This was followed by a subsequent distraction task during which the efficacy of distraction, by directing attention away from the electrocutaneous stimuli, was tested. In addition, state-trait anxiety, catastrophic thinking, and initial pain intensity were measured. Results indicated that people who display a large attentional bias towards predictive cues of pain or who initially experience the pain as more painful benefit less from distraction on a subsequent test. No effects were found between attentional bias towards pain words, state-trait anxiety, catastrophic thinking, and the efficacy of distraction. Current findings suggest that distraction should not be used as a 'one size fits all' method to control pain, but only under more specific conditions.	\N	\N
22992016	The present study showed that elevation of bone-conduction (BC) thresholds at low frequencies might be a characteristic audiometric finding in cases with otitis media with effusion (OME) with high pepsinogen (PG) concentrations. The objective of this study was to investigate whether there is any characteristic audiometric finding in adult cases with otitis media with high PG compared to those with low PG. Twenty-four adult patients with unilateral OME of undetermined etiology and high PG concentrations (> 500 ng/ml) in their middle ear effusions (high PG group) were selected. The air-conduction and BC thresholds of pure tone audiometry were compared between the affected and healthy ears. Results were compared to those in 23 patients with low PG concentrations (< 50 ng/ml; low PG group). The average BC difference in the threshold at 0.25 kHz between the affected ear and the healthy ear was significantly higher in the high PG group than in the low PG group, with a significantly higher proportion of patients in the high PG group having BC thresholds at 0.25 kHz in the affected ear that were ≥ 15 dB higher than in the healthy ear.	\N	\N
23000014	Music is a stimulus which may give rise to a wide range of emotional and cognitive responses. Therefore, brain reactivity to music has become a focus of interest in cognitive neuroscience. It is possible that individual preference moderates the effectof music on the brain. In the present study we examined whether there are common effects of listening to music even if each subject in a sample chooses their own piece of music. We invited 18 subjects to bring along their favorite relaxing music, and their favourite stimulating music. Additionally, a condition with tactile stimulation on the foot and a baseline condition (rest) without stimulation were used. The tactile stimulation was chosen to provide a simple, non-auditory condition which would be identical for all subjects. The electroencephalogram was recorded for each of the 3 conditions and during rest. We found responses in the alpha range mainly on parietal and occipital sites that were significant compared to baseline in 13 subjects during relaxing music, 15 subjects during activating music, and 16 subjects during tactile stimulation. Most subjects showed an alpha desynchronization in a lower alpha range followed by a synchronization in an upper frequency range. However, some subjects showed an increase in this area, whereas others showed a decrease only. In addition, many subjects showed reactivity in the beta range. Beta activity was especially increased while listening to activating music and during tactile stimulation in most subjects. We found interindividual differences in the response patterns even though the stimuli provoked comparable subjective emotions (relaxation, activation), and even if the stimulus was the same for all subjects (somatosensory stimulation). We suggest that brain responsivity to music should be examined individually by considering individual characteristics.	\N	\N
23009003	Cochlear Implant (CI) is the most advanced method of treatment in receptive type of deafness and profound hearing loss. Good functioning auditory organ plays a significant role not only in auditory perception but also in the process of phonation, giving the possibility of good realization of the process of verbal communication. The aim of the study is to assess the quality of voice and life in adults with pre- and postlingual deafness treated using cochlear implant. Twenty six patients with pre- (group I) and postlingual (group II) deafness deriving no benefit from hearing aids were included into the study. Voice quality was assessed using subjective and objective methods. The endoscopic (VLS) and stroboscopic (VLSS) examination of the larynx and the acoustic voice analysis were carried out. The quality of life was assessed using the Nijmegen Cochlear Implant Questionnaire (NCIQ). Examinations were conducted before implantation and 6 months after activation of speech processor. In the subjective and objective assessment of voice quality the improvement was registered in both groups. The effects were less spectacular in prelingual patients. In this group of patients the subjective assessment of voice quality and stroboscopic examination confirmed the hypofunctional type of dysphonia. In postlingual patients the hyperfunctional type of dysphonia was registered what was confirmed by the analysis of acoustic parameters of voice. The improvement of quality of life was observed in both groups of patients after implantation. The voice quality was improved after implantation in both analyzed groups. In patients with postlingual deafness values of parameters of voice quality assessment were closed to physiological. Results of the subjective assessment of voice quality were confirmed by objective examinations and the acoustic voice analysis. Rehabilitation with cochlear implant gave the opportunity for active participation in private and social life, improving the quality of life in patients with pre- and postlingual deafness.	\N	\N
23017812	Auditory impairments in schizophrenia have been demonstrated previously, especially for tasks requiring precise encoding of frequency, although it is unclear the extent to which they have difficulty using pitch information and other cues to segregate sounds. We determined the extent to which those with schizophrenia have difficulty using pitch information and other auditory cues to segregate sounds that are presented sequentially. Ten participants with schizophrenia and nine healthy/normal control participants completed a battery of tasks that tested for the ability to perform sequential auditory stream segregation using pitch, amplitude modulation, or inter-aural phase difference as cues to segregation. All three sequential segregation tasks showed reduced tendency for those with schizophrenia to perceive segregated sounds, compared to control participants. These findings extend prior research by demonstrating a general impairment on sequential sound segregation tasks in schizophrenia, and not just on tasks that require precise encoding of frequency. Together, the pattern of results provide evidence that auditory impairments in schizophrenia result from selective abnormalities in neural circuits that carry out specific computations necessary for stream segregation, as opposed to an impairment in processing specific cues.	\N	\N
23025161	We examined whether and how sounds influence visually induced illusory self-motion (vection). Visual stimuli were presented for 40 s. They were made radially, expanding or contracting visual motion field and luminance-defined gratings drifting in a vertical or horizontal direction. Auditory stimuli were presented with the visual stimuli in most conditions; we employed sounds that increased or decreased in intensity, or ascended or descended in frequency. As a result, the sound which increased in intensity facilitated forward vection, and the sound which ascended/descended in frequency facilitated upward/downward vection. The perceptual plausibility of the sound for the corresponding self-motion seemed an important factor of enhancing vection.	\N	\N
23025794	Preferences between low delays and phase-frequency responses of behind-the-ear, open-canal hearing aids were investigated with acoustic conditions deemed sensitive to delay effects by normal-hearing listeners. Hearing aids with the following selectable delay and phase response options were fitted at low insertion gain: (1) 1.4 ms delay, minimum phase; (2) 3.4 ms delay, minimum phase; and (3) 3.4 ms delay, linear phase. Blind paired comparisons were made between processing options and between each option and a muted hearing-aid output with two music stimuli. The three alternative forced choice responses were "Slightly prefer", "Prefer", or "Strongly prefer". Twelve hearing-impaired musicians. At the 3.4-ms delay, the minimum-phase response was significantly preferred to the linear-phase response for one music sample and vice-versa for the other sample with a sign test (p < 0.04) but not a Wilcoxon signed rank test that accounted for the low preference strength. Preferences between all other processing conditions were not significant. In acoustic conditions sensitive to delay effects, delays of 1.4 or 3.4 ms were either not detected or no less preferable than no delayed aided signal. It is unclear whether different phase-frequency responses may be preferred with different music stimuli.	\N	\N
23027674	To examine the hypothesis that infants receiving a degraded auditory signal have more difficulty segmenting words from fluent speech if familiarized with the words presented in both speech and sign compared to familiarization with the words presented in speech only. Experiment utilizing an infant-controlled visual preference procedure. Twenty 8.5-month-old normal-hearing infants completed testing. Infants were familiarized with repetitions of words in either the speech + sign (n = 10) or the speech only (n = 10) condition. Infants were then presented with four six-sentence passages using an infant-controlled visual preference procedure. Every sentence in two of the passages contained the words presented in the familiarization phase, whereas none of the sentences in the other two passages contained familiar words. Infants exposed to the speech + sign condition looked at familiar word passages for 15.3 seconds and at nonfamiliar word passages for 15.6 seconds, t (9) = -0.130, p = .45. Infants exposed to the speech only condition looked at familiar word passages for 20.9 seconds and to nonfamiliar word passages for 15.9 seconds. This difference was statistically significant, t (9) = 2.076, p = .03. Infants' ability to segment words from degraded speech is negatively affected when these words are initially presented in simultaneous speech and sign. The current study suggests that a decreased ability to segment words from fluent speech may contribute towards the poorer performance of pediatric cochlear implant recipients in total communication settings on a wide range of spoken language outcome measures.	\N	\N
23030713	The tip-of-the-tongue (TOT) state is a common experience, usually coupled with a frustrating feeling caused by the incapability of retrieving a familiar word. It is thought that TOTs occur when the semantic and syntactic information of the word is retrieved but not its phonology. This study aims to further understand the role of phonology in TOT resolution. Specifically, using a syllabic pseudohomophone priming paradigm, we aim to analyse the role of the phonological syllabic position (first vs. last) and the number of syllables in TOT states resolution. TOT was elicited by a picture naming task, after which a lexical decision task was presented. Here, first, last, or none of the phonological syllables of the target word were embedded in pseudohomophone primes. Results showed a significant syllabic pseudohomophone priming effect facilitating TOT resolution. The effect was stronger for four-syllable words, especially when the last syllable was used as prime. These results seem to reinforce the importance of phonology in TOT states resolution, particularly the role of the syllable as an important sublexical unit in speech processing.	\N	\N
23035086	Humans and other animals with foveate vision make saccadic eye movements to prioritize the visual analysis of behaviorally relevant information. Even before movement onset, visual processing is selectively enhanced at the target of a saccade, presumably gated by brain areas controlling eye movements. Here we assess concurrent changes in visual performance and perceived contrast before saccades, and show that saccade preparation enhances perception rapidly, altering early visual processing in a manner akin to increasing the physical contrast of the visual input. Observers compared orientation and contrast of a test stimulus, appearing briefly before a saccade, to a standard stimulus, presented previously during a fixation period. We found simultaneous progressive enhancement in both orientation discrimination performance and perceived contrast as time approached saccade onset. These effects were robust as early as 60 ms after the eye movement was cued, much faster than the voluntary deployment of covert attention (without eye movements), which takes ∼300 ms. Our results link the dynamics of saccade preparation, visual performance, and subjective experience and show that upcoming eye movements alter visual processing by increasing the signal strength.	\N	\N
23041297	Speech prosody conveys information about important aspects of communication: the meaning of the sentence and the emotional state or intention of the speaker. The present study addressed processing of emotional prosodic changes in natural speech stimuli in school-age children (mean age 10 years) by recording the electroencephalogram, facial electromyography, and behavioral responses. The stimulus was a semantically neutral Finnish word uttered with four different emotional connotations: neutral, commanding, sad, and scornful. In the behavioral sound-discrimination task the reaction times were fastest for the commanding stimulus and longest for the scornful stimulus, and faster for the neutral than for the sad stimulus. EEG and EMG responses were measured during non-attentive oddball paradigm. Prosodic changes elicited a negative-going, fronto-centrally distributed neural response peaking at about 500 ms from the onset of the stimulus, followed by a fronto-central positive deflection, peaking at about 740 ms. For the commanding stimulus also a rapid negative deflection peaking at about 290 ms from stimulus onset was elicited. No reliable stimulus type specific rapid facial reactions were found. The results show that prosodic changes in natural speech stimuli activate pre-attentive neural change-detection mechanisms in school-age children. However, the results do not support the suggestion of automaticity of emotion specific facial muscle responses to non-attended emotional speech stimuli in children.	\N	\N
23043968	The current study examined auditory processing deficits in dyslexia using a dichotic pitch stimulus and functional MRI. Cortical activation by the dichotic pitch task occurred in bilateral Heschl's gyri, right planum temporale, and right superior temporal sulcus. Adolescents with dyslexia, relative to age-matched controls, illustrated greater activity in left Heschl's gyrus for random noise, less activity in right Heschl's gyrus for all auditory conditions, and less activity in right superior temporal sulcus for a dichotic melody. Subsequent analyses showed that these group differences were attributable to dyslexic readers who performed poorly on the psychophysical task. Furthermore, behavioral performance on phonological reading was correlated to activity from dichotic conditions in right Heschl's gyrus and right superior temporal sulcus. It is postulated that these differences between reader groups is primarily due to a noise exclusion deficit shown previously in dyslexia.	\N	\N
23046141	Object-substitution masking (OSM) occurs when a mask, such as four dots that surround a brief target item, onsets simultaneously with the target and offsets a short time after the target, rather than simultaneously with it. OSM is a reduction in accuracy of reporting the target with the temporally trailing mask, compared with the simultaneously offsetting mask. It has been thought that OSM occurs only if attention cannot be rapidly focused, or prefocused, on the target location. One line of evidence for this is a reported interaction between target display set size and the duration of the trailing mask. We analyze the evidence for this interaction and suggest it occurs only as an artifact of data being compressed by a ceiling effect. We report six experiments that support this interpretation by showing that the interaction is always absent unless a ceiling effect is induced. We go on to analyze other evidence to support the notion that attention modulates OSM, and argue that in each case, the data either reflect a ceiling effect or can be explained in another way. Our data and our analyses of the existing literature have strong implications for how OSM should be conceptualized.	\N	\N
23046461	It has been repeatedly shown that the auditory N1 is enhanced for sounds presented at an attended time point. The present study investigated the underlying mechanisms using a temporal cuing paradigm. In each trial, an auditory cue indicated at which time point a second sound could be relevant for response selection. Crucially, in addition to temporal attention, two physical sound features with known effects on the sensory N1 were manipulated: location and intensity. Positive evidence for conjoint effects of attention and location or attention and intensity would corroborate the notion that the sensory N1 was modulated by temporal attention, thus supporting a gain mechanism. However, the N1 effect of temporal attention was not similarly lateralized as the sensory N1, and, moreover, it was independent of sound intensity. Thus, the present results do not provide compelling evidence that temporal attention involves an increase in sensory gain.	\N	\N
23047261	Acoustically evoked neural and hair cell potentials can be measured from the round window (RW) intraoperatively in the general population of cochlear implant recipients. Cochlear implant performance varies greatly among patients. Improved methods to assess and monitor functional hair cell and neural substrate before and during implantation could potentially aid in enhanced nontraumatic intracochlear electrode placement and subsequent improved outcomes. Subjects (1-80 yr) undergoing cochlear implantation were included. A monopolar probe was placed at the RW after surgical access was obtained. The cochlear microphonic (CM), summating potential (SP), compound action potential (CAP), and auditory nerve neurophonic (ANN) were recorded in response to tone bursts at frequencies of 0.25 to 4 kHz at various levels. Measurable hair cell/neural potentials were detected to 1 or more frequencies in 23 of 25 subjects. The greatest proportion and magnitude of cochlear responses were to low frequencies (<1,000 Hz). At these low frequencies, the ANN, when present, contributed to the ongoing response at the stimulus frequency. In many subjects, the ANN was small or absent, whereas hair cell responses remained. In cochlear implant recipients, acoustically evoked cochlear potentials are detectable even if hearing is extremely limited. Sensitive measures of cochlear and neural status can characterize the state of hair cell and neural function before implantation. Whether this information correlates with speech performance outcomes or can help in tailoring electrode type, placement or audiometric fitting, can be determined in future studies.	\N	\N
23049884	Accumulating evidence suggests that basic visual information processing is impaired in schizophrenia. However, deficits in peripheral vision remain largely unexplored. Here we hypothesized that sensory processing of information in the visual periphery would be impaired in schizophrenia patients and, as a result, crowding - the breakdown in target recognition that occurs in cluttered visual environments - would be stronger. Therefore, we assessed visual crowding in the peripheral vision of schizophrenia patients and healthy controls. Subjects were asked to identify a target letter that was surrounded by distracter letters of similar appearance. Targets and distracters were displayed at 8° and 10° of visual angle from the fixation point (eccentricity), and target-distracter spacing was 2°, 3°, 4°, 5°, 6°, 7° or 8° of visual angle. Eccentricity and target-distracter spacing were randomly varied. Accuracy was defined as the proportion of correctly identified targets. Critical spacing was defined as the spacing at which target identification accuracy began to deteriorate, and was assessed at viewing eccentricities of 8° and 10°. Schizophrenia patients were less accurate and showed a larger critical spacing than healthy individuals. These results indicate that crowding is stronger and sensory processing of information in the visual periphery is impaired in schizophrenia. This is in line with previous reports of preferential magnocellular dysfunction in schizophrenia. Thus, deficits in peripheral vision may account for perceptual alterations and contribute to cognitive dysfunction in schizophrenia.	\N	\N
23055485	Older adults frequently report they can hear what is said but cannot understand the meaning, especially in noise. This difficulty may arise from the inability to process rapidly changing elements of speech. Aging is accompanied by a general slowing of neural processing and decreased neural inhibition, both of which likely interfere with temporal processing in auditory and other sensory domains. Age-related reductions in inhibitory neurotransmitter levels and delayed neural recovery can contribute to decreases in the temporal precision of the auditory system. Decreased precision may lead to neural timing delays, reductions in neural response magnitude, and a disadvantage in processing the rapid acoustic changes in speech. The auditory brainstem response (ABR), a scalp-recorded electrical potential, is known for its ability to capture precise neural synchrony within subcortical auditory nuclei; therefore, we hypothesized that a loss of temporal precision results in subcortical timing delays and decreases in response consistency and magnitude. To assess this hypothesis, we recorded ABRs to the speech syllable /da/ in normal hearing younger (18-30 years old) and older (60-67 years old) adult humans. Older adults had delayed ABRs, especially in response to the rapidly changing formant transition, and greater response variability. We also found that older adults had decreased phase locking and smaller response magnitudes than younger adults. Together, our results support the theory that older adults have a loss of temporal precision in the subcortical encoding of sound, which may account, at least in part, for their difficulties with speech perception.	\N	\N
23057507	There is strong evidence of shared acoustic profiles common to the expression of emotions in music and speech, yet relatively limited understanding of the specific psychoacoustic features involved. This study combined a controlled experiment and computational modelling to investigate the perceptual codes associated with the expression of emotion in the acoustic domain. The empirical stage of the study provided continuous human ratings of emotions perceived in excerpts of film music and natural speech samples. The computational stage created a computer model that retrieves the relevant information from the acoustic stimuli and makes predictions about the emotional expressiveness of speech and music close to the responses of human subjects. We show that a significant part of the listeners' second-by-second reported emotions to music and speech prosody can be predicted from a set of seven psychoacoustic features: loudness, tempo/speech rate, melody/prosody contour, spectral centroid, spectral flux, sharpness, and roughness. The implications of these results are discussed in the context of cross-modal similarities in the communication of emotion in the acoustic domain.	\N	\N
23063935	Individuals who have been exposed to two different musical cultures (bimusicals) can be differentiated from those exposed to only one musical culture (monomusicals). Just as bilingual speakers handle the distinct language-syntactic rules of each of two languages, bimusical listeners handle two distinct musical-syntactic rules (e.g., tonal schemas) in each musical culture. This study sought to determine specific brain activities that contribute to differentiating two culture-specific tonal structures. We recorded magnetoencephalogram (MEG) responses of bimusical Japanese nonmusicians and amateur musicians as they monitored unfamiliar Western melodies and unfamiliar, but traditional, Japanese melodies, both of which contained tonal deviants (out-of-key tones). Previous studies with Western monomusicals have shown that tonal deviants elicit an early right anterior negativity (mERAN) originating in the inferior frontal cortex. In the present study, tonal deviants in both Western and Japanese melodies elicited mERANs with characteristics fitted by dipoles around the inferior frontal gyrus in the right hemisphere and the premotor cortex in the left hemisphere. Comparisons of the nature of mERAN activity to Western and Japanese melodies showed differences in the dipoles' locations but not in their peak latency or dipole strength. These results suggest that the differentiation between a tonal structure of one culture and that of another culture correlates with localization differences in brain subregions around the inferior frontal cortex and the premotor cortex.	\N	\N
23064383	1) Describe the association between hearing loss and dysfunction of each of the 5 vestibular end-organs--the horizontal, superior, and posterior semicircular canals; saccule; and utricle--in older individuals. 2) Evaluate whether hearing loss and vestibular end-organ deficits share any risk factors. Cross-sectional study. Academic medical center. Fifty-one individuals age 70 years or older. Audiometry, head-thrust dynamic visual acuity (htDVA), sound-evoked cervical vestibular-evoked myogenic potential (cVEMP), and tap-evoked ocular VEMP (oVEMP). Audiometric pure-tone averages (PTA), htDVA LogMAR scores as a measure of semicircular canal function in each canal plane, and cVEMP and oVEMP amplitudes as a measure of saccular and utricular function, respectively. We observed a significant correlation between hearing loss at high frequencies and reduced cVEMP amplitudes (or reduced saccular function; r = -0.37, p < 0.0001) in subjects age 70 years or older. In contrast, hearing loss was not associated with oVEMP amplitudes (or utricular function), or htDVA LogMAR scores (or semicircular canal function) in any of the canal planes. Age and noise exposure were significantly associated with measures of both cochlear and saccular dysfunction. The concomitant decline in the cochlear and saccular function associated with aging may reflect their common embryologic origin in the pars inferior of the labyrinth. Noise exposure seems to be related to both saccular and cochlear dysfunction. These findings suggest a potential benefit of screening individuals with presbycusis-particularly those with significant noise exposure history-for saccular dysfunction, which may contribute to fall risk in the elderly.	\N	\N
23067726	The ability to control external events through our own actions is a fundamental aspect of human experience. Both the subjective experience of agency, and its neural correlates, remain poorly understood. Previous studies show that the angular gyrus is activated when participants explicitly judge that they lack agency. In contrast, the positive sense of agency over external events is associated with distortions of time perception. Here, we show that the perceived interval between actions and a subsequent tone is shorter than the perceived interval between a physically comparable passive movement and a tone, replicating the 'intentional binding' effect reported previously. We considered this as a potential implicit marker of agency, and investigated its neural basis, by using parametric analyses to identify brain areas whose activation correlated more strongly with the perceived action-tone interval in the action condition, than in the passive condition. Small volume corrections were used to test specific hypotheses about the contribution of the angular gyrus, and of the supplementary motor area (SMA), based on previous literature. We found no correlation between angular gyrus and our temporal measure of sense of agency. In contrast, we found that a lateral, caudal region within the SMA proper was more strongly associated with the perceived action-tone interval than with perception of a control interval following a passive movement. We suggest that the supplementary motor complex contributes to the subjective experience of temporal flow that accompanies goal-directed voluntary actions.	\N	\N
23076114	Following prolonged exposure to adaptor sounds moving in a single direction, participants may perceive stationary-probe sounds as moving in the opposite direction [direction-selective auditory motion aftereffect (aMAE)] and be less sensitive to motion of any probe sounds that are actually moving (motion-sensitive aMAE). The neural mechanisms of aMAEs, and notably whether they are due to adaptation of direction-selective motion detectors, as found in vision, is presently unknown and would provide critical insight into auditory motion processing. We measured human behavioral responses and auditory evoked potentials to probe sounds following four types of moving-adaptor sounds: leftward and rightward unidirectional, bidirectional, and stationary. Behavioral data replicated both direction-selective and motion-sensitive aMAEs. Electrical neuroimaging analyses of auditory evoked potentials to stationary probes revealed no significant difference in either global field power (GFP) or scalp topography between leftward and rightward conditions, suggesting that aMAEs are not based on adaptation of direction-selective motion detectors. By contrast, the bidirectional and stationary conditions differed significantly in the stationary-probe GFP at 200 ms poststimulus onset without concomitant topographic modulation, indicative of a difference in the response strength between statistically indistinguishable intracranial generators. The magnitude of this GFP difference was positively correlated with the magnitude of the motion-sensitive aMAE, supporting the functional relevance of the neurophysiological measures. Electrical source estimations revealed that the GFP difference followed from a modulation of activity in predominantly right hemisphere frontal-temporal-parietal brain regions previously implicated in auditory motion processing. Our collective results suggest that auditory motion processing relies on motion-sensitive, but, in contrast to vision, non-direction-selective mechanisms.	\N	\N
23088548	This study investigates how newly learned words are integrated into the first-language lexicon using masked priming. Two lexical decision experiments are reported, with the aim of establishing whether newly learned words behave like real words in a masked form priming experiment. If they do, they should show a prime lexicality effect (PLE), in which less priming is obtained due to form similarity when the prime is a word. In the first experiment, subjects were taught the meanings of novel words that were neighbors of real words, but no PLE was observed; that is, equally strong form priming was obtained for both trained and untrained novel primes. In the second experiment, 4 training sessions were spread over 4 weeks, and under these conditions, a clear PLE was obtained in the final session. It is concluded that lexicalization requires multiple training sessions. Possible explanations of the PLE are discussed.	\N	\N
23088832	The neuroscience of tinnitus represents an ideal model to explore central issues in brain functioning such as the formation of auditory percepts, in addition to opening up new treatment avenues for the condition in the long-term. The present review discusses the origin and nature of tinnitus-related neural activity. First, we review evidence for the hypothesis that tinnitus is caused by the central nervous system changes induced by sensory deprivation, even when hearing loss is not visible in the audiogram. Second, we suggest that changes in neural activity in individual central structures may not be sufficient to underlie the tinnitus percept. Instead, we propose that tinnitus may arise from functional alterations at multiple levels which promote abnormal propagation of neural activity throughout the network involved in auditory perception. In this context, functional coupling within and between central auditory structures may be especially important to consider. Investigating how sensory deprivation affects functional coupling between areas, which might be reflected in changes in temporal coherence of intrinsic ongoing activity patterns, may give critical insights into the mechanisms of tinnitus.	\N	\N
23095305	To update a 15-year-old study of 800 postlinguistically deaf adult patients showing how duration of severe to profound hearing loss, age at cochlear implantation (CI), age at onset of severe to profound hearing loss, etiology and CI experience affected CI outcome. Retrospective multicenter study. Data from 2251 adult patients implanted since 2003 in 15 international centers were collected and speech scores in quiet were converted to percentile ranks to remove differences between centers. The negative effect of long duration of severe to profound hearing loss was less important in the new data than in 1996; the effects of age at CI and age at onset of severe to profound hearing loss were delayed until older ages; etiology had a smaller effect, and the effect of CI experience was greater with a steeper learning curve. Patients with longer durations of severe to profound hearing loss were less likely to improve with CI experience than patients with shorter duration of severe to profound hearing loss. The factors that were relevant in 1996 were still relevant in 2011, although their relative importance had changed. Relaxed patient selection criteria, improved clinical management of hearing loss, modifications of surgical practice, and improved devices may explain the differences.	\N	\N
23102807	Age-related hearing impairment (ARHI), or presbycusis, is a common condition of the elderly that results in significant communication difficulties in daily life. Clinically, it has been defined as a progressive loss of sensitivity to sound, starting at the high frequencies, inability to understand speech, lengthening of the minimum discernable temporal gap in sounds, and a decrease in the ability to filter out background noise. The causes of presbycusis are likely a combination of environmental and genetic factors. Previous research into the genetics of presbycusis has focused solely on hearing as measured by pure-tone thresholds. A few loci have been identified, based on a best ear pure-tone average phenotype, as having a likely role in susceptibility to this type of hearing loss; and GRM7 is the only gene that has achieved genome-wide significance. We examined the association of GRM7 variants identified from the previous study, which used an European cohort with Z-scores based on pure-tone thresholds, in a European-American population from Rochester, NY (N = 687), and used novel phenotypes of presbycusis. In the present study mixed modeling analyses were used to explore the relationship of GRM7 haplotype and SNP genotypes with various measures of auditory perception. Here we show that GRM7 alleles are associated primarily with peripheral measures of hearing loss, and particularly with speech detection in older adults.	\N	\N
23109085	People often fail to detect changes between successively presented tactile patterns, a phenomenon known as tactile change blindness. In this study, we investigated whether changes introduced to tactile patterns are detected better when a participant's attention is focused on the location where the change occurs. Across two experiments, participants (N = 55) were instructed to detect changes between two consecutively presented tactile patterns. In half of the trials, the stimulated body sites in the two patterns were identical. In the other half of the trials, one of the stimulated body locations differed between the two patterns. Endogenous (or voluntary) attention was manipulated by instructing participants which new bodily location was most likely to be stimulated. We found that changes at the attended location were detected more accurately than changes at bodily locations that were unattended. This finding demonstrates that attention can effectively modulate tactile change detection. We discuss the value of this experimental paradigm for investigating excessive attentional focus or hypervigilance to particular regions of the body in various clinical populations.	\N	\N
23116413	Aiming to further our understanding of fundamental mechanisms of auditory working memory (WM), the present study compared performance for three auditory materials (words, tones, timbres). In a forward recognition task (Experiment 1) participants indicated whether the order of the items in the second sequence was the same as in the first sequence. In a backward recognition task (Experiment 2) participants indicated whether the items of the second sequence were played in the correct backward order. In Experiment 3 participants performed an articulatory suppression task during the retention delay of the backward task. To investigate potential length effects the number of items per sequence was manipulated. Overall findings underline the benefit of a cross-material experimental approach and suggest that human auditory WM is not a unitary system. Whereas WM processes for timbres differed from those for tones and words, similarities and differences were observed for words and tones: Both types of stimuli appear to rely on rehearsal mechanisms, but might differ in the involved sensorimotor codes.	\N	\N
23117535	Noise sensitivity is considered to be a self-perceived indicator of vulnerability to stressors in general and not noise alone. Multiple chemical sensitivity (MCS) has to some extent been accompanied by noise sensitivity, indicating a moderate correspondence between them. The aim of this study is to investigate if the Weinstein's Noise Sensitivity Scale and Quick Environmental Exposure and Sensitivity Inventory's (QEESI) Chemical Intolerance Subscale can differentiate noise sensitivity and MCS as different entities, and if there are overlaps in the characteristics of noise sensitivity and MCS. In 2002, 327 individuals (166 men, 161 women; age range 45 - 66 years) from the Finnish Twin Cohort answered a questionnaire on noise-related and MCS items. Somatic, psychological, and lifestyle factors were obtained through earlier questionnaires for the same individuals. Both confirmatory and exploratory factor analyses (CFA and EFA) of the questionnaire items on the Weinstein's Noise Sensitivity Scale and QEESI's Chemical Intolerance Subscale indicated the presence of three factors - Noise Sensitivity, Chemical Sensitivity, and Ability to Concentrate factors - arising from the forming of two factors from the items of the Weinstein's scale. In the regression analyses, among all subjects, the Noise Sensitivity Factor was associated with neuroticism and smoking, and the Chemical Sensitivity Factor was associated with allergies and alcohol use. The study indicates that the Weinstein's Noise Sensitivity Scale and QEESI's Chemical Intolerance Subscale differentiate noise sensitivity and MCS as different entities.	\N	\N
23122629	To evaluate through a multidimensional protocol voice changes after voice therapy in patients with benign vocal fold lesions. 65 consecutive patients affected by benign vocal fold lesions were enrolled. Depending on videolaryngostroboscopy the patients were divided into 3 groups: 23 patients with Reinke's oedema, 22 patients with vocal fold cysts and 20 patients with gelatinous polyp. Each subject received 10 voice therapy sessions and was evaluated, before and after voice therapy, through a multidimensional protocol including videolaryngostroboscopy, perception, acoustics, aerodynamics and self-rating by the patient. Data were compared using Wilcoxon signed-rank test. Kruskal-Wallis test was used to analyse the mean variation difference between the three groups of patients. Mann-Whitney test was used for post hoc analysis. Only in 11 cases videolaryngostroboscopy revealed an improvement of the initial pathology. However a significant improvement was observed in perceptual, acoustic and self-assessment ratings in the 3 groups of patients. In particular the parameters of G, R and A of the GIRBAS scale, and the noise to harmonic ratio, Jitter and shimmer scores improved after rehabilitation. A significant improvement of all the parameters of Voice Handicap Index after rehabilitation treatment was found. No significant difference among the three groups of patients was visible, except for self-assessment ratings. Voice therapy may provide a significant improvement in perceptual, acoustic and self-assessed voice quality in patients with benign glottal lesions. Utilization of voice therapy may allow some patients to avoid surgical intervention.	\N	\N
23128585	Both the Stroop and the Simon paradigms are often used in research on cognitive control, however, there is evidence that dissociable control processes are involved in these tasks: While conflicts in the Stroop task may be resolved mainly by enhanced task-relevant stimulus processing, conflicts in the Simon task may be resolved rather by suppressing the influence of task-irrelevant information on response selection. In the present study, we show that these control mechanisms interact in different ways with the presentation of accessory stimuli. Accessory stimuli do not affect cognitive control in the Simon task, but they impair the efficiency of cross-trial control processes in the Stroop task. Our findings underline the importance of differentiating between different types of conflicts and mechanisms of cognitive control.	\N	\N
23135617	The purpose of this study was to examine differences between older and younger listeners in the ability to sequentially attend to and ignore words. Participants (n = 13 older adults and 13 younger adults) completed a temporally interleaved word recognition task. On each trial, 10 words were presented, and participants were instructed to repeat back every other word while ignoring the intervening words. Three variables were examined: (1) whether the word strings that were to be attended and to be ignored created syntactically correct sentences; (2) whether the to-be-attended and to-be-ignored words were presented from the same or from different spatial locations; and (3) whether the five target words in each trial (and the five distractor words in each trial) were spoken by a single talker or by five different talkers. In addition, digit-span forward and digit-span backward were measured and used as variables in correlation analyses. As a group, the younger participants outperformed the older listeners, particularly when the to-be-attended and to-be-ignored words were presented from the same spatial location (versus when they were presented with spatial separation). Compared with the younger participants, older listeners also made more error responses that were to-be-ignored words, although the proportion of errors that were not responses involving masking words did not significantly differ between groups. Scores on the digit-span-forward test (but not digit-span-backward scores or the degree of hearing loss) were associated with older individuals' performance on this temporally interleaved speech-recognition task. The overall pattern of results suggests that factors other than threshold elevation contribute to speech-understanding problems experienced by older listeners. However, although younger adults outperformed older listeners on this interleaved sentence task, older and younger adults benefited, to a similar extent, from spatial separation of the to-be-attended and to-be-ignored words, and from having a consistent target talker within a trial.	\N	\N
23138762	Posterior cortical atrophy (PCA) is typically considered to be a visual syndrome, primarily characterised by progressive impairment of visuoperceptual and visuospatial skills. However, patients commonly describe early difficulties with word retrieval. This paper details the first systematic analysis of linguistic function in PCA. Characterising and quantifying the aphasia associated with PCA is important for clarifying diagnostic and selection criteria for clinical and research studies. 15 patients with PCA, seven patients with logopenic/phonological aphasia (LPA) and 18 age matched healthy participants completed a detailed battery of linguistic tests evaluating auditory input processing, repetition and working memory, lexical and grammatical comprehension, single word retrieval and fluency, and spontaneous speech. Relative to healthy controls, PCA patients exhibited language impairments across all of the domains examined, but with anomia, reduced phonemic fluency and slowed speech rate the most prominent deficits. PCA performance most closely resembled that of LPA patients on tests of auditory input processing, repetition and digit span, but was relatively stronger on tasks of comprehension and spontaneous speech. The study demonstrates that in addition to the well reported degradation of vision, literacy and numeracy, PCA is characterised by progressive oral language dysfunction with prominent word retrieval difficulties. Overlap in the linguistic profiles of PCA and LPA, which are both most commonly caused by Alzheimer's disease, further emphasises the notion of a phenotypic continuum between typical and atypical manifestations of the disease. Clarifying the boundaries between Alzheimer's disease phenotypes has important implications for diagnosis, clinical trial recruitment and investigations into biological factors driving phenotypic heterogeneity in Alzheimer's disease. Rehabilitation strategies to ameliorate the phonological deficit in PCA are required.	\N	\N
23143506	This retrospective study aimed to evaluate the efficacy of the Esteem(®) middle ear implant in sensorineural hearing loss (SNHL) of different degree as well as to compare it with that obtained with conventional hearing aids. Fifteen out of 30 adults patients who received an Esteem(®) middle ear device for rehabilitation of sensorineural hearing loss met the primary eligibility criterion of prior, continuous use of conventional hearing aids. Study population included moderate-to-severe SNHL (8 patients) and severe-to-profound SNHL (7 patients). Audiometric measurements included free-field pure-tone and speech audiometry in Esteem(®)-aided, HA-aided, and baseline threshold. For speech audiometry, speech reception threshold (SRT) and word recognition score (WRS) were assessed. Subjective benefit was evaluated by Client Oriented Scale of Improvement (COSI) questionnaire. In all the subjects, SRT and WRS showed improvement both with conventional HA and Esteem(®) in respect to the unaided situation. Although not statistically significant, a slight prevalence of the Esteem(®) performances was recorded both audiometrically and as subjective satisfaction score. The Esteem(®) middle ear device demonstrated appreciable benefit for rehabilitation of SNHL of different degree, comparable to what can be achieved by conventional hearing aids. In addition, this rehabilitative process may enable also individuals presenting with severe-to-profound SNHL to achieve remarkable functional outcomes.	\N	\N
23145620	A modulation-based index is proposed for predicting speech intelligibility by cochlear implant (CI) listeners. The input to the proposed index are speech envelopes extracted using the individual CI user's daily strategy, and as such, this approach incorporates information about the number of active electrodes, shape of the compression function and electrical dynamic range. High correlation (r = 0.96) was achieved with the proposed index when evaluated with speech-reception thresholds (SRTs) obtained by CI users in steady and speech-masker conditions. This outcome suggests that the information contained in electrodograms seems to be sufficient for reliably predicting CI user's performance in noise. The proposed index can be used by clinicians to optimize the selection of fitting parameters of individual CI users for better performance in noise.	\N	\N
23150094	To report the results of cochlear implantation via the middle fossa approach in 4 patients, discuss the complications, and present a detailed description of the programming specifications in these cases. Retrospective case review. Tertiary-care referral center with a well-established cochlear implant program. Four patients with bilateral canal wall down mastoid cavities who underwent the middle fossa approach for cochlear implantation. Cochlear implantation and subsequent rehabilitation. A middle fossa approach with cochleostomy was successfully performed on the most superficial part of the apical turn in 4 patients. A Nucleus 24 cochlear implant system was used in 3 patients and a MED-EL Sonata Medium device in 1 patient. The single electrode array was inserted through a cochleostomy from the cochlear apex and occupied the apical, middle, and basal turns. Telemetry and intraoperative impedance recordings were performed at the end of surgery. A CT scan of the temporal bones was performed to document electrode insertion for all of the patients. Complications, hearing thresholds, and speech perception outcomes were evaluated. Neural response telemetry showed present responses in all but 1 patient, who demonstrated facial nerve stimulation during the test. Open-set speech perception varied from 30% to 100%, despite the frequency allocation order of the MAP. Cochlear implantation via the middle cranial fossa is a safe approach, although it is a challenging procedure, even for experienced surgeons.	\N	\N
23152235	This is an update of a Cochrane Review first published in The Cochrane Library in Issue 12, 2010.Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. Numerous management strategies have been tried for this potentially debilitating, heterogeneous symptom. External noise has been used as a management tool for tinnitus, in different capacities and with different philosophical intent, for over a century. To assess the effectiveness of sound-creating devices (including hearing aids) in the management of tinnitus in adults. Primary outcome measures were changes in the loudness or severity of tinnitus and/or impact on quality of life. Secondary outcome measures were change in pure-tone auditory thresholds and adverse effects of treatment. We searched the Cochrane ENT Group Trials Register; CENTRAL; PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 8 February 2012. Prospective randomised controlled trials recruiting adults with persistent, distressing, subjective tinnitus of any aetiology in which the management strategy included maskers, noise-generating device and/or hearing aids, used either as the sole management tool or in combination with other strategies, including counselling. Two authors independently examined the 387 search results to identify studies for inclusion in the review, of which 33 were potentially relevant. The update searches in 2012 retrieved no further potentially relevant studies. Both authors extracted data independently. Six trials (553 participants) are included in this review. Studies were varied in design, with significant heterogeneity in the evaluation of subjective tinnitus perception, with different scores, scales, tests and questionnaires as well as variance in the outcome measures used to assess the improvement in tinnitus sensation/quality of life. This precluded meta-analysis of the data. There was no long-term follow-up. We assessed the risk of bias as medium in three and high in three studies. Following analysis of the data, no significant change was seen in the loudness of tinnitus or the overall severity of tinnitus following the use of sound therapy compared to other interventions such as patient education, 'relaxation techniques', 'tinnitus coping strategies', counselling, 'tinnitus retraining' and exposure to environmental sounds. No side effects or significant morbidity were reported from the use of sound-creating devices. The limited data from the included studies failed to show strong evidence of the efficacy of sound therapy in tinnitus management. The absence of conclusive evidence should not be interpreted as evidence of lack of effectiveness. The lack of quality research in this area, in addition to the common use of combined approaches (hearing therapy plus counselling) in the management of tinnitus are, in part, responsible for the lack of conclusive evidence. Other combined forms of management, such as tinnitus retraining therapy, have been subject to a Cochrane Review. Optimal management may involve multiple strategies.	\N	\N
23155729	Auditory stimuli are known to improve visual target recognition and detection when both are presented in the same spatial location. However, most studies have focused on crossmodal spatial congruency along the horizontal plane and the effects of audio-visual spatial congruency in depth (i.e., along the depth axis) are relatively less well understood. In the following experiments we presented a visual (face) or auditory (voice) target stimulus in a location on a spatial array which was either spatially congruent or incongruent in depth (i.e., positioned directly in front or behind) with a crossmodal stimulus. The participant's task was to determine whether a visual (experiments 1 and 3) or auditory (experiment 2) target was located in the foreground or background of this array. We found that both visual and auditory targets were less accurately located when crossmodal stimuli were presented from different, compared to congruent, locations in depth. Moreover, this effect was particularly found for visual targets located in the periphery, although spatial incongruency affected the location of auditory targets across both locations. The relative distance of the array to the observer did not seem to modulate this congruency effect (experiment 3). Our results add to the growing evidence for multisensory influences on search performance and extend these findings to the localisation of targets in the depth plane.	\N	\N
23160796	Small songbirds have a difficult analysis problem: their head is small compared to the wavelengths of sounds used for communication providing only small interaural time and level differences. Klump and Larsen (1992) measured the physical binaural cues in the European starling (Sturnus vulgaris) that allow the comparison of acoustical cues and perception. We determined the starling's minimum audible angle (MAA) in an operant Go/NoGo procedure for different spectral and temporal stimulus conditions. The MAA for broadband noise with closed-loop localization reached 17°, while the starling's MAA for open-loop localization of broadband noise reached 29°. No substantial difference between open-loop and closed-loop localization was found in 2 kHz pure tones. The closed-loop MAA improved from 26° to 19° with an increase in pure tone frequency from 1 to 4 kHz. This finding is in line with the physical cues available. While the starlings can only make use of interaural time difference cues at lower frequencies (e.g., 1 and 2 kHz), additional interaural level difference cues become available at higher frequencies (e.g., 4 kHz or higher, Klump and Larsen 1992). An improvement of the starling's MAA with an increasing number of standard stimulus presentations prior to the test stimulus has important implications for determining relative (MAA) localization thresholds.	\N	\N
23163413	Music performance requires control of two sequential structures: the ordering of pitches and the temporal intervals between successive pitches. Whether pitch and temporal structures are processed as separate or integrated features remains unclear. A repetition suppression paradigm compared neural and behavioral correlates of mapping pitch sequences and temporal sequences to motor movements in music performance. Fourteen pianists listened to and performed novel melodies on an MR-compatible piano keyboard during fMRI scanning. The pitch or temporal patterns in the melodies either changed or repeated (remained the same) across consecutive trials. We expected decreased neural response to the patterns (pitch or temporal) that repeated across trials relative to patterns that changed. Pitch and temporal accuracy were high, and pitch accuracy improved when either pitch or temporal sequences repeated over trials. Repetition of either pitch or temporal sequences was associated with linear BOLD decrease in frontal-parietal brain regions including dorsal and ventral premotor cortex, pre-SMA, and superior parietal cortex. Pitch sequence repetition (in contrast to temporal sequence repetition) was associated with linear BOLD decrease in the intraparietal sulcus (IPS) while pianists listened to melodies they were about to perform. Decreased BOLD response in IPS also predicted increase in pitch accuracy only when pitch sequences repeated. Thus, behavioral performance and neural response in sensorimotor mapping networks were sensitive to both pitch and temporal structure, suggesting that pitch and temporal structure are largely integrated in auditory-motor transformations. IPS may be involved in transforming pitch sequences into spatial coordinates for accurate piano performance.	\N	\N
23169193	An estimated 36 million US citizens have impaired hearing, but nearly half of them have never had a hearing test. As noted by a recent National Institutes of Health/National Institute on Deafness and Other Communication Disorders (NIH/NIDCD) Working Group, "In the United States (in contrast to many other nations) there are no readily accessible low cost hearing screening programs…" (Donahue et al, 2010, p. 2). Since 2004, telephone administered screening tests utilizing three-digit sequences presented in noise have been developed, validated, and implemented in seven countries. Each of these tests has been based on a test protocol conceived by Smits and colleagues in The Netherlands. Investigators from Communication Disorders Technology, Inc., Indiana University, and VU University Medical Center of Amsterdam agreed to collaborate in the development and validation of a screening test for hearing impairment suitable for delivery over the telephone, for use in the United States. This test, utilizing spoken three-digit sequences (triplets), was to be based on the design of Smits and his colleagues. A version of the digits-in-noise test was developed utilizing digit triplets spoken in Middle American dialect. The stimuli were individually adjusted to speech-to-noise ratio (SNR) values yielding 50% correct identification, on the basis of data collected from a group of 10 young adult listeners with normal hearing. A final set of 64 homogeneous stimuli were selected from an original 160 recorded triplets. Each test consisted of a series of 40 triplets drawn at random, presented in a noise background. The SNR threshold for 50% correct identification of the triplets was determined by a one-down, one-up adaptive procedure. The test was implemented by telephone, and administered to listeners with varying levels of hearing impairment. The listeners were then evaluated with pure-tone tests and other audiometric measures as clinically appropriate. Ninety participants included 72 who were volunteers from the regular client population at the Indiana University Hearing Clinic, and 18 who were recruited with a newspaper ad offering a free hearing test. Of the 90 participants, 49 were later determined to have mean pure-tone thresholds greater than 20 dB hearing level (HL). The primary data analyses were correlations between telephone test thresholds and other measures, including pure-tone thresholds and speech recognition tests, collected for the same participants. The correlation between the telephone test and pure-tone thresholds (r = 0.74) was within the range of correlations observed with successful telephone screening tests in use in other countries. Thresholds based on the average of only 21 trials (trials five through 25 of the 40-trial tracking history) yielded sensitivity and specificity values of 0.80 and 0.83, respectively, using pure-tone average((0.5, 1.0, 2.0 kHz)) >20 dB HL as the criterion measure. This US version of the digits-in-noise telephone screening test is sufficiently valid to be implemented for use by the general public. Its properties are quite similar to those telephone screening tests currently in use in most European countries. Telephone tests provide efficient, easy to use, and valid screening for functional hearing impairment. The results of this test are a reasonable basis for advising those who fail to seek a comprehensive hearing evaluation by an audiologist.	\N	\N
23169195	Speech recognition in noise testing has been conducted at least since the 1940s (Dickson et al, 1946). The ability to recognize speech in noise is a distinct function of the auditory system (Plomp, 1978). According to Kochkin (2002), difficulty recognizing speech in noise is the primary complaint of hearing aid users. However, speech recognition in noise testing has not found widespread use in the field of audiology (Mueller, 2003; Strom, 2003; Tannenbaum and Rosenfeld, 1996). The audiogram has been used as the "gold standard" for hearing ability. However, the audiogram is a poor indicator of speech recognition in noise ability. This study investigates the relationship between pure-tone thresholds, the articulation index, and the ability to recognize speech in quiet and in noise. Pure-tone thresholds were measured for audiometric frequencies 250-6000 Hz. Pure-tone threshold groups were created. These included a normal threshold group and slight, mild, severe, and profound high-frequency pure-tone threshold groups. Speech recognition thresholds in quiet and in noise were obtained using the Hearing in Noise Test (HINT) (Nilsson et al, 1994; Vermiglio, 2008). The articulation index was determined by using Pavlovic's method with pure-tone thresholds (Pavlovic, 1989, 1991). Two hundred seventy-eight participants were tested. All participants were native speakers of American English. Sixty-three of the original participants were removed in order to create groups of participants with normal low-frequency pure-tone thresholds and relatively symmetrical high-frequency pure-tone threshold groups. The final set of 215 participants had a mean age of 33 yr with a range of 17-59 yr. Pure-tone threshold data were collected using the Hughson-Weslake procedure. Speech recognition data were collected using a Windows-based HINT software system. Statistical analyses were conducted using descriptive, correlational, and multivariate analysis of covariance (MANCOVA) statistics. The MANCOVA analysis (where the effect of age was statistically removed) indicated that there were no significant differences in HINT performances between groups of participants with normal audiograms and those groups with slight, mild, moderate, or severe high-frequency hearing losses. With all of the data combined across groups, correlational analyses revealed significant correlations between pure-tone averages and speech recognition in quiet performance. Nonsignificant or significant but weak correlations were found between pure-tone averages and HINT thresholds. The ability to recognize speech in steady-state noise cannot be predicted from the audiogram. A new classification scheme of hearing impairment based on the audiogram and the speech reception in noise thresholds, as measured with the HINT, may be useful for the characterization of the hearing ability in the global sense. This classification scheme is consistent with Plomp's two aspects of hearing ability (Plomp, 1978).	\N	\N
23173635	A 42-year-old man suffered damage to the left supra-sylvian areas due to a stroke and presented with verbal short-term memory (STM) deficits. He occasionally could not recall even a single syllable that he had heard one second before. A study of mismatch negativity using magnetoencephalography suggested that the duration of auditory sensory (echoic) memory traces was reduced on the affected side of the brain. His maximum digit span was four with auditory presentation (equivalent to the 1st percentile for normal subjects), whereas it was up to six with visual presentation (almost within the normal range). He simply showed partial recall in the digit span task, and there was no self correction or incorrect reproduction. From these findings, reduced echoic memory was thought to have affected his verbal short-term retention. Thus, the impairment of verbal short-term memory observed in this patient was "pure auditory" unlike previously reported patients with deficits of the phonological short-term store (STS), which is the next higher-order memory system. We report this case to present physiological and behavioral data suggesting impaired short-term storage of verbal information, and to demonstrate the influence of deterioration of echoic memory on verbal STM.	\N	\N
23177349	This research investigates how early learning about native language sound structure affects how infants associate sounds with meanings during word learning. Infants (19-month-olds) were presented with bisyllabic labels with high or low phonotactic probability (i.e., sequences of frequent or infrequent phonemes in English). The labels were produced with the predominant English trochaic (strong/weak) stress pattern or the less common iambic (weak/strong) pattern. Using the habituation-based Switch Task to test label learning, we found that infants readily learned high probability trochaic labels. However, they failed to learn low probability labels, regardless of stress, and failed to learn iambic labels, regardless of phonotactics. Thus, infants required support from both common phoneme sequences and a common stress pattern to map the labels to objects. These findings demonstrate that early word learning is shaped by prior knowledge of native language phonological regularities and provide support for the role of statistical learning in language acquisition.	\N	\N
23177756	A plethora of investigations have studied the acoustic characteristics of vibrato such as the rate, extent, onset (time from initiation of phonation until the first peak of vibrato), and periodicity. Despite extensive research, the degree to which various parameters of vibrato contribute to its acceptability remain unclear. The present study sought to determine the psychoacoustical relationship of mean fundamental frequency (f(0)), modulation frequency (f(f0m)), modulation depth (d(f0m)), and intensity to the appropriateness or inappropriateness of vibrato. Phonation samples of eight voice majors singing at low, middle, and high pitches were obtained. A high fidelity vocoder (STRAIGHT; Kawahara, 1997) was used to resynthesize these vowels with systematic manipulations of f(f0m) and d(f0m) of the f(0) contours resulting in a total of 600 stimuli (8 singers×3 pitches×5 f(f0m) levels×5 d(f0m) levels). Nine listeners (four experts and five students) evaluated these stimuli for appropriateness of vibrato at two different presentation levels (70 and 90 dB sound pressure level). Statistical analyses of the perceptual data suggest that appropriateness of vibrato tends to increase with mean f(0) and decrease with d(f0m.) Appropriateness of vibrato is greatest for f(f0m) value of 6 Hz, but decreases both above and below this frequency. perceived appropriateness of vibrato results from an interaction of mean f(0), f(f0m), and d(f0m) of the vowel waveform.	\N	\N
23202431	The investigation of brain activity using naturalistic, ecologically-valid stimuli is becoming an important challenge for neuroscience research. Several approaches have been proposed, primarily relying on data-driven methods (e.g. independent component analysis, ICA). However, data-driven methods often require some post-hoc interpretation of the imaging results to draw inferences about the underlying sensory, motor or cognitive functions. Here, we propose using a biologically-plausible computational model to extract (multi-)sensory stimulus statistics that can be used for standard hypothesis-driven analyses (general linear model, GLM). We ran two separate fMRI experiments, which both involved subjects watching an episode of a TV-series. In Exp 1, we manipulated the presentation by switching on-and-off color, motion and/or sound at variable intervals, whereas in Exp 2, the video was played in the original version, with all the consequent continuous changes of the different sensory features intact. Both for vision and audition, we extracted stimulus statistics corresponding to spatial and temporal discontinuities of low-level features, as well as a combined measure related to the overall stimulus saliency. Results showed that activity in occipital visual cortex and the superior temporal auditory cortex co-varied with changes of low-level features. Visual saliency was found to further boost activity in extra-striate visual cortex plus posterior parietal cortex, while auditory saliency was found to enhance activity in the superior temporal cortex. Data-driven ICA analyses of the same datasets also identified "sensory" networks comprising visual and auditory areas, but without providing specific information about the possible underlying processes, e.g., these processes could relate to modality, stimulus features and/or saliency. We conclude that the combination of computational modeling and GLM enables the tracking of the impact of bottom-up signals on brain activity during viewing of complex and dynamic multisensory stimuli, beyond the capability of purely data-driven approaches.	\N	\N
23205712	To estimate the prevalence of severe and profound hearing loss in a clinical population and to report the audiological and hearing-aid characteristics for this group, as well as outcome measures from use of hearing aids. A retrospective observational study initially, followed by a postal Glasgow health status inventory (GHSI) to establish the patients functional outcomes. A clinical database of 32 781 cases was interrogated from which 2199 cases of severe /profound hearing loss were identified. From these, an adult sample stratified in terms of age and gender of n = 302 was contacted. An estimated 6.7% of the local clinical population and 0.7% of the general population were found to have hearing > 70 dB averaged over 0.5, 1, and 2 kHz. Most patients were fitted with bilateral hearing aids, using a non-linear prescription, and as a group they reported a high level of social support. This study has estimated the prevalence of severe and profound hearing loss as 6.7% of the clinical population, and 0.7% of the general population. This is consistent with previous work, although it probably underestimates the prevalence. Further work is indicated to strengthen the estimate.	\N	\N
23207574	Synchronizing movements with auditory beats, compared to visual flashes, yields divergent activation in timing-related brain areas as well as more stable tapping synchronization. The differences in timing-related brain activation could reflect differences in tapping synchronization stability, rather than differences between modality (i.e., audio-motor vs. visuo-motor integration). In the current fMRI study, participants synchronized their finger taps with four types of visual and auditory pacing sequences: flashes and a moving bar, as well as beeps and a frequency-modulated 'siren'. Behavioral tapping results showed that visuo-motor synchronization improved with moving targets, whereas audio-motor synchronization degraded with frequency-modulated sirens. Consequently, a modality difference in synchronization occurred between the discrete beeps and flashes, but not between the novel continuous siren and moving bar. Imaging results showed that activation in the putamen, a key timing area, paralleled the behavioral results: putamen activation was highest for beeps, intermediate for the continuous siren and moving bar, and was lowest for the flashes. Putamen activation differed between modalities for beeps and flashes, but not for the novel moving bar and siren. By dissociating synchronization performance from modality, we show that activation in the basal ganglia is associated with sensorimotor synchronization stability rather than modality-specificity in this task. Synchronization stability is apparently contingent upon the modality's processing affinity: discrete auditory and moving visual signals are modality appropriate, and can be encoded reliably for integration with the motor system.	\N	\N
23216089	Results for speech recognition in noise tests when using a new research coding strategy designed to introduce the virtual channel effect provided no advantage over MP3(000™). Although statistically significant smaller just noticeable differences (JNDs) were obtained, the findings for pitch ranking proved to have little clinical impact. The aim of this study was to explore whether modifications to MP3000 by including sequential virtual channel stimulation would lead to further improvements in hearing, particularly for speech recognition in background noise and in competing-talker conditions, and to compare results for pitch perception and melody recognition, as well as informally collect subjective impressions on strategy preference. Nine experienced cochlear implant subjects were recruited for the prospective study. Two variants of the experimental strategy were compared to MP3000. The study design was a single-blinded ABCCBA cross-over trial paradigm with 3 weeks of take-home experience for each user condition. Comparing results of pitch-ranking, a significantly reduced JND was identified. No significant effect of coding strategy on speech understanding in noise or competing-talker materials was found. Melody recognition skills were the same under all user conditions.	\N	\N
23218176	The use of the stapes coupling technique, employed in the Vibrant Soundbridge system, is technically less demanding than the vibroplasty technique, and is more likely to generate a positive outcome without significantly changing residual hearing or resulting in medical or surgical complication. We report a patient with repeated left ossiculoplasty failure, who was successfully implanted with a Vibrant Soundbridge. We believe that the stapes coupling technique can provide natural stimulation to the inner ear, resulting in a better perceived sound quality.	\N	\N
23219981	Prior work with Wright and others demonstrated that rhesus monkeys recognized the relative relationships of notes in common melodies. As an extension of tests of pattern similarities, tamarins were habituated to 3-sound unit patterns in an AAB or ABB form that were human phonemes, piano notes, or monkey calls. The subjects were tested with novel sounds in each category constructed either to match the prior pattern or to violate the prior habituated pattern. The monkeys attended significantly more to a violation of their habituated pattern to a new pattern when human phonemes were used, and there was a trend difference in attention toward pattern violations with melodies. Monkey call patterns generated a variety of behavioral responses, were less likely to show habituation, and did not generate a strong attention reaction to changes in the patterns. Monkeys can extract abstract rules and patterns from auditory stimuli but the stimuli, by their nature, may generate competing responses which block processing of abstract regularities.	\N	\N
23220120	Normal-hearing listeners can perceptually segregate concurrent sound sources, but listeners with significant hearing loss or who wear a cochlear implant (CI) lag behind in this ability. Perceptual grouping mechanisms are essential to segregate concurrent sound sources and affect comodulation masking release (CMR). Thus, CMR measurements in CI users could shed light on segregation cues needed for forming and grouping of auditory objects. CMR illustrates the fact that detection of a target sound embedded in a fluctuating masker is improved by the addition of masker energy remote from the target frequency, provided the envelope fluctuations across masker components are coherent. We modified such a CMR experiment to electrically-induced hearing using direct stimulation and measured the effect in 21 CI users. Cluster analysis of our data revealed two groups: one showed no or only small CMR of 0.1 dB ± 2.7 (N = 14) and a second group achieved a CMR of 10.7 dB ± 3.2 (N = 7), a value that is close to the enhancement observed in a comparable acoustic experiment in normal-hearing listeners (12.9 dB ± 2.6, N = 6). Interestingly, we observed that CMR in CI users may relate to hearing etiology and duration of hearing loss pre-implantation. Our study demonstrates for the first time that a substantial minority of cochlear-implant listeners (about a third) can show significant CMR. This outcome motivates the development of physiologically inspired multi-band gain control and/or different coding strategies for these groups in order to better preserve coherent modulation and thus to take advantage of the individual remaining capabilities to analyze spectro-temporal patterns.	\N	\N
23224782	Past research has identified an event-related potential (ERP) marker for vocal emotional encoding and has highlighted vocal-processing differences between male and female listeners. We further investigated this ERP vocal-encoding effect in order to determine whether it predicts voice-related changes in listeners' memory for verbal interaction content. Additionally, we explored whether sex differences in vocal processing would affect such changes. To these ends, we presented participants with a series of neutral words spoken with a neutral or a sad voice. The participants subsequently encountered these words, together with new words, in a visual word recognition test. In addition to making old/new decisions, the participants rated the emotional valence of each test word. During the encoding of spoken words, sad voices elicited a greater P200 in the ERP than did neutral voices. While the P200 effect was unrelated to a subsequent recognition advantage for test words previously heard with a neutral as compared to a sad voice, the P200 did significantly predict differences between these words in a concurrent late positive ERP component. Additionally, the P200 effect predicted voice-related changes in word valence. As compared to words studied with a neutral voice, words studied with a sad voice were rated more negatively, and this rating difference was larger, the larger the P200 encoding effect was. While some of these results were comparable in male and female participants, the latter group showed a stronger P200 encoding effect and qualitatively different ERP responses during word retrieval. Estrogen measurements suggested the possibility that these sex differences have a genetic basis.	\N	\N
23231206	Earlier work using sine-wave and noise-vocoded signals suggests that dynamic spectral structure plays a greater role in speech recognition for children than adults [Nittrouer and Lowenstein. (2010). J. Acoust. Soc. Am. 127, 1624-1635], but questions arise concerning whether outcomes can be compared because sine waves and wide noise bands are different in nature. The current study addressed that question using narrow noise bands for both signals, and applying a difference ratio to index the contribution made by dynamic spectral structure. Results replicated earlier findings, supporting the idea that dynamic spectral structure plays a critical role in speech recognition, especially for children.	\N	\N
23241225	According to classical theories, automatic processes operate independently of attention. Recent evidence, however, shows that masked visuomotor priming, an example of an automatic process, depends on attention to visual form versus semantics. In a continuation of this approach, we probed feature-specific attention within the perceptual domain and tested in two event-related potential (ERP) studies whether masked visuomotor priming in a shape decision task specifically depends on attentional sensitization of visual pathways for shape in contrast to color. Prior to the masked priming procedure, a shape or a color decision task served to induce corresponding task sets. ERP analyses revealed visuomotor priming effects over the occipitoparietal scalp only after the shape, but not after the color induction task. Thus, top-down control coordinates automatic processing streams in congruency with higher-level goals even at a fine-grained level.	\N	\N
23246616	Speech recognition in a multi-talker situation poses high demands on attentional and other central resources. This study examines the relationship between age, cognition and speech recognition in tasks that require selective or divided attention in a multi-talker setting. Two groups of normal-hearing adults (one younger and one older group) were asked to repeat utterances from either one or two concurrent speakers. Cognitive abilities were then inspected by neuropsychological tests. Speech recognition scores approached its ceiling and did not significantly differ between age groups for tasks that demanded selective attention. However, when divided attention was required, performance in older listeners was reduced as compared to the younger group. When selective attention was required, speech recognition was strongly related to working memory skills, as determined by a regression model. In comparison, speech recognition for tests requiring divided attention could be more strongly determined by neuropsychological probes of fluid intelligence. The findings of this study indicate that - apart from hearing impairment - cognitive aspects account for the typical difficulties of older listeners in a multi-speaker setting. Our results are discussed in the context of evidence showing that frontal lobe functions in terms of working memory and fluid intelligence generally decline with age.	\N	\N
23269517	The most prominent models of numerical representation posit that numerical symbols are converted into a single internal, abstract representation prior to estimation and comparison processing. Here, we (1) provide a mathematical analysis of the predictions of the abstract-representation hypothesis, assuming the validity of the analog-representation hypothesis, (2) run a simulation to assess the patterns of data that result from our mathematical analysis, and (3) conduct two experiments to test the predictions of our model, using relative frequencies as inputs. We assess relative frequencies in a typical numerical distance task, whereby participants are presented with two relative frequencies and asked to identify the one that represents the larger quantity. Our data reveal that relative frequencies' numerical representations (1) are analog and (2) are scale-specific (i.e., nonabstract).	\N	\N
23275409	In this study, the authors explored whether French-learning infants use nonadjacent phonotactic regularities in their native language, which they learn between the ages of 7 and 10 months, to segment words from fluent speech. Two groups of 20 French-learning infants were tested using the head-turn preference procedure at 10 and 13 months of age. In Experiment 1, infants were familiarized with 2 passages: 1 containing a target word with a frequent nonadjacent phonotactic structure and the other containing a target word with an infrequent nonadjacent phonotactic structure in French. During the test phase, infants were presented with 4 word lists: 2 containing the target words presented during familiarization and 2 other control words with the same phonotactic structure. In Experiment 2, the authors retested infants' ability to segment words with the infrequent phonotactic structure. Ten- and 13-month-olds were able to segment words with the frequent phonotactic structure, but it is only by 13 months, and only under the circumstances of Experiment 2, that infants could segment words with the infrequent phonotactic structure. These results provide new evidence showing that infant word segmentation is influenced by prior nonadjacent phonotactic knowledge.	\N	\N
23275416	In this article, the authors describe the development of a new instrument, the Test of Child Speechreading (ToCS), which was specifically designed for use with deaf and hearing children. Speechreading is a skill that is required for deaf children to access the language of the hearing community. ToCS is a deaf-friendly, computer-based test that measures child speechreading (silent lipreading) at 3 psycholinguistic levels: (a) Words, (b) Sentences, and (c) Short Stories. The aims of the study were to standardize the ToCS with deaf and hearing children and to investigate the effects of hearing status, age, and linguistic complexity on speechreading ability. Eighty-six severely and profoundly deaf children and 91 hearing children participated. All children were between the ages of 5 and 14 years. The deaf children were from a range of language and communication backgrounds, and their preferred mode of communication varied. Speechreading skills significantly improved with age for both groups of children. There was no effect of hearing status on speechreading ability, and children from both groups showed similar performance across all subtests of the ToCS. The ToCS is a valid and reliable assessment of speechreading ability in school-age children that can be used to measure individual differences in performance in speechreading ability.	\N	\N
23275425	In this study, the authors aimed to investigate how differences in language ability relate to differences in processing talker information in the native language and an unfamiliar language by comparing performance for different ages and for groups with impaired language. Three groups of native English listeners with typical language development (TLD; ages 7-9, ages 10-12, adults) and 2 groups with specific language impairment (SLI; ages 7-9, ages 10-12) participated in the study. Listeners heard pairs of words in both English and German (unfamiliar language) and were asked to determine whether the words were produced by the same or different talkers. In English, talker discrimination improved with age. In German, performance improved with age for the school-age children but was worse for adult listeners. No differences were found between TLD and SLI children. These results show that as listeners' language skills develop, there is a trade-off between more general perceptual abilities useful for processing talker information in any language and those that are relevant to their everyday language experiences and, thus, tied to the phonology. The lack of differences between the children with and without language impairments suggests that general auditory processing may be intact in at least some children with SLI.	\N	\N
23275583	This study was designed to evaluate the effect of a pinna compensation (PC) algorithm on localization performance in the horizontal plane and speech intelligibility in noise. Nine and 18 experienced hearing aid users with bilaterally symmetrical sensorineural hearing loss participated in the localization study and the speech-in-noise study, respectively. Performance was evaluated unaided, aided with a behind-the-ear (BTE) hearing aid with an omnidirectional microphone (Omni), and aided with the same hearing aid with the PC algorithm (Omni+PC). Localization performance was measured using 12 loudspeakers spaced 30° apart on a horizontal plane. Speech-in-noise performance was measured with speech presented from 0° or 180°. A single-blinded, repeated measures design was used. Significant improvement in localization accuracy was found when comparing the Omni+PC condition to the Omni condition. Also, the Omni+PC condition improved the signal-to-noise ratio by 2.4 dB when compared to the Omni condition when speech was presented from the front in a diffuse noise background. Use of the PC algorithm improved localization on the horizontal plane and speech-in-noise performance. These results support use of the PC algorithm in BTE hearing aid fittings.	\N	\N
23276111	Recent research on eye movements during scene viewing has primarily focused on where the eyes fixate. But eye fixations also differ in their durations. Here we investigated whether fixation durations in scene viewing are under the direct and immediate control of the current visual input. Subjects freely viewed photographs of scenes in preparation for a later memory test while their eye movements were recorded. Using a novel scene degradation paradigm based on a saccade-contingent display change method, scenes were reduced in luminance during saccades ending in critical fixations. Results from two experiments showed that the durations of the critical fixations were immediately affected by scene luminance, with a monotonic relationship between luminance reduction and fixation duration. The results are the first to demonstrate that fixation durations in scene viewing are immediately influenced by the ease of processing of the image currently in view. These results are consistent with the CRISP (a timer-Controlled Random-Walk with Inhibition for Saccade Planning) computational model of saccade generation in scenes, proposing that difficulty in moment-by-moment visual and cognitive processing of the scene modulates fixation durations.	\N	\N
23281939	Recent human behavioral studies have shown semantic and/or lexical processing for stimuli presented below the auditory perception threshold. Here, we investigated electroencephalographic responses to words, pseudo-words and complex sounds, in conditions where phonological and lexical categorizations were behaviorally successful (categorized stimuli) or unsuccessful (uncategorized stimuli). Data showed a greater decrease in low-beta power at left-hemisphere temporal electrodes for categorized non-lexical sounds (complex sounds and pseudo-words) than for categorized lexical sounds (words), consistent with the signature of a failure in lexical access. Similar differences between lexical and non-lexical sounds were observed for uncategorized stimuli, although these stimuli did not yield evoked potentials or theta activity. The results of the present study suggest that behaviorally uncategorized stimuli were processed at the lexical level, and provide evidence of the neural bases of the results observed in previous behavioral studies investigating auditory perception in the absence of stimulus awareness.	\N	\N
23285949	To study the long-term rehabilitation effects for treating tinnitus by tinnitus masking combined with counseling. Complete the tinnitus handicap inventory(THI) for participants before treatment and after six months, 1 year, 2 years, 3 years. Eighty-six tinnitus patients participated. Nine participants and sixteen, twenty-six, sixteen participants drop-up during the follow up after half-year, 1 year, 2 years, 3 years separately. The percentage of participants whose THI score decreased more than or equal to 20 are 66%, 56%, 40%, 48% after half year, 1 year, 2 years, 3 years respectively. The tinnitus related handicap improved by tinnitus masking combined with counseling after 1 year. The drop-out rate was increase after follow-up 1 year. The long-term rehabilitation effects for tinnitus treatment is still needed.	\N	\N
23288656	Three experiments investigated whether extrinsic vowel normalization takes place largely at a categorical or a precategorical level of processing. Traditional vowel normalization effects in categorization were replicated in Experiment 1: Vowels taken from an [I]-[ε] continuum were more often interpreted as /I/ (which has a low first formant, F(1)) when the vowels were heard in contexts that had a raised F(1) than when the contexts had a lowered F(1). This was established with contexts that consisted of only two syllables. These short contexts were necessary for Experiment 2, a discrimination task that encouraged listeners to focus on the perceptual properties of vowels at a precategorical level. Vowel normalization was again found: Ambiguous vowels were more easily discriminated from an endpoint [ε] than from an endpoint [I] in a high-F(1) context, whereas the opposite was true in a low-F(1) context. Experiment 3 measured discriminability between pairs of steps along the [I]-[ε] continuum. Contextual influences were again found, but without discrimination peaks, contrary to what was predicted from the same participants' categorization behavior. Extrinsic vowel normalization therefore appears to be a process that takes place at least in part at a precategorical processing level.	\N	\N
23294198	Thirteen (5.4%) of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) had benign paroxysmal positional vertigo (BPPV). Most of the patients showed profound hearing loss and had BPPV of the lateral canal. BPPV in patients with ISSNHL may have no influence on hearing recovery. BPPV occurs in 8.6-12.7% of patients with ISSNHL; however, the role of BPPV in hearing recovery remains controversial. Therefore, we investigated hearing outcomes in the patients, including the distribution of initial hearing threshold, the type of canal involved, and the number of repositioning maneuvers performed. Of 241 patients with ISSNHL who presented to a dizziness clinic between March 2008 and May 2012, 13 with both ISSNHL and BPPV were recruited for this study. The patients were evaluated for their initial hearing threshold, type of canal involved, response to repositioning maneuvers, and hearing outcome. Age- and hearing threshold-matched patients with ISSNHL but without BPPV were randomly sampled and included for a hearing outcome comparison. Of 13 patients with ISSNHL and BPPV, 11 showed profound hearing loss. The lateral canal was involved in 11 patients, including 3 who had multi-canal involvement. Ten patients underwent a single repositioning maneuver. Those patients did not display a significant difference in hearing recovery compared with those patients having ISSNHL only.	\N	\N
23294284	Following cochlear implantation, hearing-impaired listeners must adapt to speech as heard through their prosthesis. Visual speech information (VSI; the lip and facial movements of speech) is typically available in everyday conversation. Here, we investigate whether learning to understand a popular auditory simulation of speech as transduced by a cochlear implant (noise-vocoded [NV] speech) is enhanced by the provision of VSI. Experiment 1 demonstrates that provision of VSI concurrently with a clear auditory form of an utterance as feedback after each NV utterance during training does not enhance learning over clear auditory feedback alone, suggesting that VSI does not play a special role in retuning of perceptual representations of speech. Experiment 2 demonstrates that provision of VSI concurrently with NV speech (a simulation of typical real-world experience) facilitates perceptual learning of NV speech, but only when an NV-only repetition of each utterance is presented after the composite NV/VSI form during training. Experiment 3 shows that this more efficient learning of NV speech is probably due to the additional listening effort required to comprehend the utterance when clear feedback is never provided and is not specifically due to the provision of VSI. Our results suggest that rehabilitation after cochlear implantation does not necessarily require naturalistic audiovisual input, but may be most effective when (a) training utterances are relatively intelligible (approximately 85% of words reported correctly during effortful listening), and (b) the individual has the opportunity to map what they know of an utterance's linguistic content onto the degraded form.	\N	\N
23294551	The aim of the present study was to examine patterns of neural activity in response to variations in scale notes and alterations from a scale note to a non-scale note. Event-related potentials (ERPs) were recorded in response to scale and non-scale violin notes using an odd-ball mismatch negativity (MMN) paradigm. Standard stimuli were set to the scale note A4 (440 Hz). Deviant stimuli included two scale notes (scale-B, B4 = 494 Hz; scale-C, C5 = 523 Hz) and a non-scale note halfway between them (non-scale, B4+42¢ = 506 Hz). MMN amplitude elicited by the non-scale was significantly larger than that elicited by the scale-B and scale-C, which did not differ significantly from one another. The current results suggest that the human brain may possess pre-attentive mechanisms for extracting relational aspects among sounds of the musical scale. The results indicate that non-scale notes may be processed in a different way even in the pre-attentive stage than scale notes.	\N	\N
23296187	Sounds can modulate visual perception as well as neural activity in retinotopic cortex. Most studies in this context investigated how sounds change neural amplitude and oscillatory phase reset in visual cortex. However, recent studies in macaque monkeys show that congruence of audio-visual stimuli also modulates the amount of stimulus information carried by spiking activity of primary auditory and visual neurons. Here, we used naturalistic video stimuli and recorded the spatial patterns of functional MRI signals in human retinotopic cortex to test whether the discriminability of such patterns varied with the presence and congruence of co-occurring sounds. We found that incongruent sounds significantly impaired stimulus decoding from area V2 and there was a similar trend for V3. This effect was associated with reduced inter-trial reliability of patterns (i.e. higher levels of noise), but was not accompanied by any detectable modulation of overall signal amplitude. We conclude that sounds modulate naturalistic stimulus encoding in early human retinotopic cortex without affecting overall signal amplitude. Subthreshold modulation, oscillatory phase reset and dynamic attentional modulation are candidate neural and cognitive mechanisms mediating these effects.	\N	\N
23297908	The relative contributions of within-channel and across-channel processes to perceptual comodulation masking release (CMR) were investigated in the framework of an auditory processing model. A generalized version of the computational auditory signal processing and perception model [CASP; Jepsen et al., J. Acoust. Soc. Am. 124, 422-438 (2008)] was used and extended by an across-channel modulation processing stage according to Piechowiak et al. [J. Acoust. Soc. Am. 121, 2111-2126 (2007)]. Five experimental paradigms were considered: CMR with a broadband noise masker as a function of the masker spectrum level; CMR with four widely spaced flanking bands (FBs) varying in overall level; CMR with one FB varying in frequency and level relative to the on-frequency band (OFB); CMR with one FB varying in frequency; and CMR as a function of the number of FBs. The predictions suggest that at least three different mechanisms contribute to overall CMR in the considered conditions: (1) a within-channel process based on changes in the envelope characteristic due to the addition of the signal to the masker; (2) a within-channel process based on nonlinear peripheral processing of the OFB's envelope caused by the FB(s); and (3) an across-channel process that is robust across presentation levels but relatively small (2-5 dB).	\N	\N
23297915	This study used the same methodology in Wong [J. Speech Lang. Hear. Res. 55, 1423-1437 (2012b)] to examine the perceived accuracy of monosyllabic Mandarin tones produced by 4- and 5-year-old Mandarin-speaking children growing up in Taiwan and combined the findings with those of 3-year-olds reported in Wong [J. Speech Lang. Hear. Res. 55, 1423-1437 (2012b)] to track the development of monosyllabic tone production in preschool children. Tone productions of adults and children were collected in a picture naming task and low-pass filtered to remove lexical information and reserve tone information. Five native-speakers categorized the target tones in the filtered productions. Children's tone accuracy was compared to adults' to determine mastery and developmental changes. The results showed that preschool children in Taiwan have not fully mastered the production of monosyllabic Mandarin tones. None of the tones produced by the children in the three age groups reached adult-like accuracy. Little developmental change was found in children's tone accuracy during the preschool years. A similar order of accuracy of the tones was observed across the three age groups and the order appeared to follow the order of articulatory complexity in producing the tones. The findings suggest a protracted course of development in children's acquisition of Mandarin tones and that tone development may be constrained by physiological factors.	\N	\N
23299125	Phantom electrode (PE) stimulation consists of out-of-phase stimulation of two electrodes. When presented at the apex of the electrode array, phantom stimulation is known to produce a lower pitch sensation than monopolar (MP) stimulation on the most apical electrode. The ratio of the current between the primary electrode (PEL) and the compensating electrode (CEL) is represented by the coefficient σ, which ranges from 0 (monopolar) to 1 (full bipolar). The exact mechanism by which PE stimulation produces a lower pitch sensation is unclear. In the present study, unmasked and masked thresholds were obtained using a forward masking paradigm to estimate the spread of current for MP and PE stimulation. Masked thresholds were measured for two phantom electrode configurations (1) PEL = 4, CEL = 5 (lower pitch phantom) and (2) PEL = 4, CEL = 3 (higher pitch phantom). The unmasked thresholds were subtracted from the masked thresholds to obtain masking patterns which were normalized to their peak. The masking patterns reveal (1) differences in the spread of excitation that are consistent with the direction of pitch shift produced by PE stimulation, and (2) narrower spread of electrical excitation for PE stimulation relative to MP stimulation.	\N	\N
23301659	The last decade has offered a multitude of instant fit coupling systems to be fitted with behind-the-ear (BTE) hearing aids. The impact of these designs on the reliability of real ear measurements (REMs) has not been reported. The purpose of this study was to obtain REM reliability data for instant fit coupling systems. REM reliability data was obtained for four different instant-fit coupling systems and for standard size 13 tubing and custom earmolds. REMs were performed for all five coupling systems two times and by two examiners. Ten normal-hearing individuals (20 ears) served as participants. The REM test-retest reliability is high for the four instant fit coupling systems as well as for the custom earmolds. The REM inter-examiner reliability is high for three of the four instant fit coupling systems. Carrying out REMs with instant fit coupling systems appears to be fundamentally no different than performing REMs with conventional hearing aids. For either, care should be taken in probe tube placement in terms of insertion depth and maintaining the probe tube placement, and other best practices regarding test environment and test setup should be observed.	\N	\N
23308266	Computational and experimental research has revealed that auditory sensory predictions are derived from regularities of the current environment by using internal generative models. However, so far, what has not been addressed is how the auditory system handles situations giving rise to redundant or even contradictory predictions derived from different sources of information. To this end, we measured error signals in the event-related brain potentials (ERPs) in response to violations of auditory predictions. Sounds could be predicted on the basis of overall probability, i.e., one sound was presented frequently and another sound rarely. Furthermore, each sound was predicted by an informative visual cue. Participants' task was to use the cue and to discriminate the two sounds as fast as possible. Violations of the probability based prediction (i.e., a rare sound) as well as violations of the visual-auditory prediction (i.e., an incongruent sound) elicited error signals in the ERPs (Mismatch Negativity [MMN] and Incongruency Response [IR]). Particular error signals were observed even in case the overall probability and the visual symbol predicted different sounds. That is, the auditory system concurrently maintains and tests contradictory predictions. Moreover, if the same sound was predicted, we observed an additive error signal (scalp potential and primary current density) equaling the sum of the specific error signals. Thus, the auditory system maintains and tolerates functionally independently represented redundant and contradictory predictions. We argue that the auditory system exploits all currently active regularities in order to optimally prepare for future events.	\N	\N
23317386	Non-word repetition (NWR) tasks have been found to correlate with language skills and to discriminate between groups of typically developing (TD) children and children with specific language impairment (SLI) across languages. The main aim was to develop an easily-administered NWR screening test that could discriminate between Slovak-speaking TD children and children with SLI. The second aim was to establish if the novel scoring methods for NWR tasks were equally effective at differentiating between the TD versus SLI groups. As Slovak vowels are not reduced in unstressed syllables, it was also sought to establish whether scoring vowels (in addition to the consonants usually assessed in English language tests) would be informative. The paper evaluated the performance of a new NWR task for Slovak-speaking children. Study 1 compared the performance of 60 TD children in three age groups: 3-year-olds (N = 20), 4-your-olds (N = 20) and 5-year-olds (N = 20). Five types of scoring methods were examined: whole-item, number of syllables, syllable structure, consonants, and vowels. Study 2 compared performance on the NWR task administered in Study 1 across three groups of child participants: an SLI group (N = 16), a TD age-matched group (N = 16), and a TD language-matched group (N = 14). Study 1 found an age effect in the TD sample for three out of five of the scoring methods tested (number of syllables, syllable structure, and consonants). Study 2 showed that all five of the scoring methods discriminated between: (1) the group of children with SLI and the TD language-matched (TDLM) sample and (2) the group of children with SLI and the TD age-matched (TDAM) group. The novel NWR tool reliably differentiated between children with SLI and TD children. Scoring cut-off points which demonstrated high rates of success at verifying true-positives (93.75%) and true-negatives (100%) are provided. The most informative scoring methods for Slavic languages (whole-item scoring and vowels correct) are identified and discussed.	\N	\N
23333667	Spontaneous beat gestures are an integral part of the paralinguistic context during face-to-face conversations. Here we investigated the time course of beat-speech integration in speech perception by measuring ERPs evoked by words pronounced with or without an accompanying beat gesture, while participants watched a spoken discourse. Words accompanied by beats elicited a positive shift in ERPs at an early sensory stage (before 100 ms) and at a later time window coinciding with the auditory component P2. The same word tokens produced no ERP differences when participants listened to the discourse without view of the speaker. We conclude that beat gestures are integrated with speech early on in time and modulate sensory/phonological levels of processing. The present results support the possible role of beats as a highlighter, helping the listener to direct the focus of attention to important information and modulate the parsing of the speech stream.	\N	\N
23333869	The present study investigates the status of rhythmic irregularities occurring in natural speech and the importance of rhythmic alternations in cognitive processing. Previous studies showed the relevance of rhythm for language processing, but there has been only little research using the method of event-related potentials to investigate this phenomenon in a natural metrical context. To this end, an experiment was conducted in which the so-called Rhythm Rule (alternation of stressed and unstressed syllables) was either met or violated by stress clashes or stress lapses which are known to occur in German. The comparison of rhythmic well-formed conditions with the conditions including rhythmic irregularities revealed biphasic EEG-patterns for rhythmically marked structures, i.e., stress clashes and lapses. The present results show that irregular but possible rhythmic variants are costly in language processing, reflected by an early negativity and an N400 in contrast to the well-formed control conditions. Supposedly, the early negativity reflects error detection in rhythmical structure and supports the view that the brain is sensitive to subtle violations of rhythmical structure. A late positive component reflects the evaluation process related to the task requirements. The study shows that subtle rhythmical deviations from the Rhythm Rule are perceived and treated differently from well-formed structures during processing, even if the deviation in question is permitted and can therefore occur in language production.	\N	\N
23335579	Recent work suggests that people predict how objects interact in a manner consistent with Newtonian physics, but with additional uncertainty. However, the sources of uncertainty have not been examined. In this study, we measure perceptual noise in initial conditions and stochasticity in the physical model used to make predictions. Participants predicted the trajectory of a moving object through occluded motion and bounces, and we compared their behavior to an ideal observer model. We found that human judgments cannot be captured by simple heuristics and must incorporate noisy dynamics. Moreover, these judgments are biased consistently with a prior expectation on object destinations, suggesting that people use simple expectations about outcomes to compensate for uncertainty about their physical models.	\N	\N
23337441	Here, we explore the sensitivity of different awareness scales in revealing conscious reports on visual emotion perception. Participants were exposed to a backward masking task involving fearful faces and asked to rate their conscious awareness in perceiving emotion in facial expression using three different subjective measures: confidence ratings (CRs), with the conventional taxonomy of certainty, the perceptual awareness scale (PAS), through which participants categorize "raw" visual experience, and post-decision wagering (PDW), which involves economic categorization. Our results show that the CR measure was the most exhaustive and the most graded. In contrast, the PAS and PDW measures suggested instead that consciousness of emotional stimuli is dichotomous. Possible explanations of the inconsistency were discussed. Finally, our results also indicate that PDW biases awareness ratings by enhancing first-order accuracy of emotion perception. This effect was possibly a result of higher motivation induced by monetary incentives.	\N	\N
23338560	Our study estimates detection thresholds for tones of different durations and frequencies in Great Tits (Parus major) with operant procedures. We employ signals covering the duration and frequency range of communication signals of this species (40-1,010 ms; 2, 4, 6.3 kHz), and we measure threshold level-duration (TLD) function (relating threshold level to signal duration) in silence as well as under behaviorally relevant environmental noise conditions (urban noise, woodland noise). Detection thresholds decreased with increasing signal duration. Thresholds at any given duration were a function of signal frequency and were elevated in background noise, but the shape of Great Tit TLD functions was independent of signal frequency and background condition. To enable comparisons of our Great Tit data to those from other species, TLD functions were first fitted with a traditional leaky-integrator model. We then applied a probabilistic model to interpret the trade-off between signal amplitude and duration at threshold. Great Tit TLD functions exhibit features that are similar across species. The current results, however, cannot explain why Great Tits in noisy urban environments produce shorter song elements or faster songs than those in quieter woodland environments, as detection thresholds are lower for longer elements also under noisy conditions.	\N	\N
23342146	This study investigated a theoretically challenging dissociation between good production and poor perception of tones among neurologically unimpaired native speakers of Cantonese. The dissociation is referred to as the near-merger phenomenon in sociolinguistic studies of sound change. In a passive oddball paradigm, lexical and nonlexical syllables of the T1/T6 and T4/T6 contrasts were presented to elicit the mismatch negativity (MMN) and P3a from two groups of participants, those who could produce and distinguish all tones in the language (Control) and those who could produce all tones but specifically failed to distinguish between T4 and T6 in perception (Dissociation). The presence of MMN to T1/T6 and null response to T4/T6 of lexical syllables in the dissociation group confirmed the near-merger phenomenon. The observation that the control participants exhibited a statistically reliable MMN to lexical syllables of T1/T6, weaker responses to nonlexical syllables of T1/T6 and lexical syllables of T4/T6, and finally null response to nonlexical syllables of T4/T6, suggests the involvement of top-down processing in speech perception. Furthermore, the stronger P3a response of the control group, compared with the dissociation group in the same experimental conditions, may be taken to indicate higher cognitive capability in attention switching, auditory attention or memory in the control participants. This cognitive difference, together with our speculation that constant top-down predictions without complete bottom-up analysis of acoustic signals in speech recognition may reduce one's sensitivity to small acoustic contrasts, account for the occurrence of dissociation in some individuals but not others.	\N	\N
23354998	Complex sounds vary along a number of acoustic dimensions. These dimensions may exhibit correlations that are familiar to listeners due to their frequent occurrence in natural sounds-namely, speech. However, the precise mechanisms that enable the integration of these dimensions are not well understood. In this study, we examined the categorization of novel auditory stimuli that differed in the correlations of their acoustic dimensions, using decision bound theory. Decision bound theory assumes that stimuli are categorized on the basis of either a single dimension (rule based) or the combination of more than one dimension (information integration) and provides tools for assessing successful integration across multiple acoustic dimensions. In two experiments, we manipulated the stimulus distributions such that in Experiment 1, optimal categorization could be accomplished by either a rule-based or an information integration strategy, while in Experiment 2, optimal categorization was possible only by using an information integration strategy. In both experiments, the pattern of results demonstrated that unidimensional strategies were strongly preferred. Listeners focused on the acoustic dimension most closely related to pitch, suggesting that pitch-based categorization was given preference over timbre-based categorization. Importantly, in Experiment 2, listeners also relied on a two-dimensional information integration strategy, if there was immediate feedback. Furthermore, this strategy was used more often for distributions defined by a negative spectral correlation between stimulus dimensions, as compared with distributions with a positive correlation. These results suggest that prior experience with such correlations might shape short-term auditory category learning.	\N	\N
23357804	Frequency-lowering signal processing in hearing aids has re-emerged as an option to improve audibility of the high frequencies by expanding the input bandwidth. Few studies have investigated the usefulness of the scheme as an option for bimodal users (i.e., combined use of a cochlear implant and a contralateral hearing aid). In this study, that question was posed. The purposes of this study were (1) to determine if frequency compression was a better bimodal option than conventional amplification and (2) to determine the impact of a frequency-compression hearing aid on speech recognition abilities. There were two separate experiments in this study. The first experiment investigated the contribution of a frequency-compression hearing aid to contralateral cochlear implant (CI) performance for localization and speech perception in noise. The second experiment assessed monaural consonant and vowel perception in quiet using the frequency-compression and conventional hearing aid without the use of a contralateral CI or hearing aid. Ten subjects fitted with a cochlear implant and hearing aid participated in the first experiment. Seventeen adult subjects with a cochlear implant and hearing aid or two hearing aids participated in the second experiment. To be included, subjects had to have a history of postlingual deafness, a moderate or moderate-to-severe hearing loss, and have not worn this type of frequency-lowering hearing aid previously. In the first experiment, performance using the frequency-compression and conventional hearing aids was assessed on tests of sound localization, speech perception in a background of noise, and two self-report questionnaires. In the second experiment, consonant and vowel perception in quiet was assessed monaurally for the two conditions. In both experiments, subjects alternated daily between a frequency-compression and conventional hearing aid for 2 mo. The parameters of frequency compression were set individually for each subject, and audibility was measured for the frequency compression and conventional hearing aid programs by comparing estimations of the Speech Intelligibility Index (SII) using a modified algorithm (Bentler et al, 2011). In both experiments, the outcome measures were administered following the hearing aid fitting to assess performance at baseline and after 2 mo of use. For this group of subjects, the results revealed no significant difference between the frequency-compression and conventional hearing aid on tests of localization and consonant recognition. Spondee-in-noise and vowel perception scores were significantly higher with the conventional hearing aid compared to the frequency-compression hearing aid after 2 mo of use. These results suggest that, for the subjects in this study, frequency compression is not a better bimodal option than conventional amplification. In addition, speech perception may be negatively influenced by frequency compression because formant frequencies are too severely compressed and can no longer be distinguished.	\N	\N
23357807	Johnson and Dillon (2011) provided a model-based comparison of current generic hearing aid prescriptive methods for adults with hearing loss based on the attributes of speech intelligibility, loudness, and bandwidth. This study compared the National Acoustic Laboratories-Non-linear 2 (NAL-NL2) and Cambridge Method for Loudness Equalization 2-High-Frequency (CAM2) prescriptive methods using adult participants with less high-frequency hearing loss than Johnson and Dillon (2011). Of study interest was quantification of prescribed audibility, speech intelligibility, and loudness. The preferences of participants for either NAL-NL2 or CAM2 and preferred deviations from prescribed settings are also reported. Using a single-blind, counter-balanced, randomized design, preference judgments for the prescriptive methods with regard to sound quality of speech and music stimuli were obtained. Preferred gain adjustments from the prescription within the 4-10 kHz frequency range were also obtained from each participant. Speech intelligibility and loudness model calculations were completed on the prescribed and adjusted amplification. Fourteen male Veterans, whose average age was 65 yr and whose hearing sensitivity averaged normal to borderline normal through 1000 Hz sloping to a moderately severe sensorineural loss, served as participants. Following a brief listening time (~10 min), typical of an initial fitting visit, the participants made paired comparison of sound quality between the NAL-NL2 and CAM2 prescriptive settings. Participants were also asked to modify each prescription in the range of 4-10 kHz using an overall gain control and make subsequent comparisons of sound quality preference between prescriptive and adjusted settings. Participant preferences were examined with respect to quantitative analysis of loudness modeling, speech intelligibility modeling, and measured high-frequency bandwidth audibility. Consistent with the lack of difference in predicted speech intelligibility between the two prescriptions, sound quality preferences on the basis of clarity were split across participants while some participants did not have a discernable preference. Considering sound quality judgments of pleasantness, the majority of participants preferred the sound quality of the NAL-NL2 (8 of 14) prescription instead of the CAM2 prescription (2 of 14). Four of the 14 participants showed no preference on the basis of pleasantness for either prescription. Individual subject preferences were supported by loudness modeling that indicated NAL-NL2 was the softer of the two prescriptions and CAM2 was the louder. CAM2 did provide more audibility to the higher frequencies (5-8 kHz) than NAL-NL2. Participants turned the 4-10 kHz gain recommendation of CAM2 lower, on average, by a significant amount of 4 dB when making adjustments while no significant adjustment was made to the initial NAL-NL2 recommendation. NAL-NL2 prescribed gains were more often preferred at the initial fitting by the majority of participating veterans. For those patients with preference for a louder fitting than NAL-NL2, CAM2 is a good alternative. When the participant adjustment from the prescription between 4 and 10 kHz exceeded 4 dB from either NAL-NL2 (2 of 14) or CAM2 (11 of 14), the participants demonstrated a later preference for that adjustment 69% of the time. These findings are viewed as limited evidence that some individuals may have a preference for high-frequency gain that differs from the starting prescription.	\N	\N
23363117	Recently introduced hearing devices allow dynamic-range compression to be coordinated at the two ears through a wireless link. This study investigates how linking compression across the ears might improve speech intelligibility in the presence of a spatially separated steady noise. An analysis of the compressors' behavior shows how linked compression can preserve interaural level differences (ILDs) and, compared to compression operating independently at each ear, improve the long-term apparent speech-to-noise ratio (SNR) at the ear with the better SNR. Speech intelligibility for normal-hearing listeners was significantly better with linked than with unlinked compression. The performance with linked compression was similar to that without any compression. The benefit of linked over unlinked compression was the same for binaural listening and for monaural listening to the ear with the better SNR, indicating that the benefit was due to changes to the signal at this ear and not to the preservation of ILDs. Differences in performance across experimental conditions were qualitatively consistent with changes in apparent SNR at the better ear. Predictions made using a speech intelligibility model suggest that linked compression could potentially provide a user of bilateral hearing aids with an improvement in intelligibility of up to approximately ten percentage points.	\N	\N
23374605	To date, the nature of the phonological deficit in developmental dyslexia is still debated. We concur with possible impairments in the representations of the universal phonological constraints that universally govern how phonemes co-occur as a source of this deficit. We were interested in whether-and how-dyslexic children have sensitivity to sonority-related markedness constraints. We tested 10 French dyslexic children compared with 20 typically developing chronological age-matched and reading level-matched controls. All were tested with two aurally administered syllable counting tasks that manipulated well-formedness of unattested consonant clusters, as determined by universal phonological sonority-related markedness constraints (onset clusters in Experiment 1; intervocalic clusters in Experiment 2). Surprisingly, dyslexic children's response patterns were similar to those in both control groups; as universal phonological sonority-related markedness increased, dyslexic children increasingly perceptually confused and phonologically repaired clusters with an illusory epenthetic vowel (e.g., /ʁəbal/). Although dyslexic children were systematically slower, like both control groups, they were influenced by universal sonority-related markedness constraints and hierarchically ranked constraints specific to French over evident acoustic-phonetic contrasts or sonority-unrelated cues. Our results are counterintuitive but innovative and compete to question an impaired universal phonological grammar because dyslexic children were found to have normal universal phonological constraints and were skilled to restore phonotactically legal syllable structures with a language-specific illusory epenthetic vowel (i.e., /ə/-like vowel). We discuss them regarding active phonological decoding and recoding processes within the framework of the optimality theory.	\N	\N
23384511	We tested whether incoming sounds are processed differently depending on how the preceding sound sequence has been interpreted by the brain. Sequences of a regularly repeating three-tone pattern, the perceived organization of which spontaneously switched back and forth between two alternative interpretations, were delivered to listeners. Occasionally, a regular tone was exchanged for a slightly or moderately lower one (deviants). The electroencephalogram (EEG) was recorded while listeners continuously marked their perception of the sound sequence. We found that for both the regular and the deviant tones, the early exogenous P1 and N1 amplitudes varied together with the perceived sound organization. Percept-dependent effects on the late endogenous N2 and P3a amplitudes were only found for deviant tones. These results suggest that the perceived sound organization affects sound processing both by modulating what information is extracted from incoming sounds as well as by influencing how deviant sound events are evaluated for further processing.	\N	\N
23384530	Prosodic aspects of speech such as pitch, duration and amplitude constitute nonverbal cues that supplement or modify the meaning of the spoken word, to provide valuable clues as to a speakers' state of mind. It can thus indicate what emotion a person is feeling (emotional prosody), or their attitude towards an event, person or object (attitudinal prosody). Whilst the study of emotional prosody has gathered pace, attitudinal prosody now deserves equal attention. In social cognition, understanding attitudinal prosody is important in its own right, since it can convey powerful constructs such as confidence, persuasion, sarcasm and superiority. In this review, it is examined what prosody is, how it conveys attitudes, and which attitudes prosody can convey. The review finishes by considering the neuroanatomy associated with attitudinal prosody, and put forward the hypothesis that this cognition is mediated by the right cerebral hemisphere, particularly posterior superior lateral temporal cortex, with an additional role for the basal ganglia, and limbic regions such as the medial prefrontal cortex and amygdala. It is suggested that further exploration of its functional neuroanatomy is greatly needed, since it could provide valuable clues about the value of current prosody nomenclature and its separability from other types of prosody at the behavioural level.	\N	\N
23386124	The sight of a speaker's facial movements during the perception of a spoken message can benefit speech processing through online predictive mechanisms. Recent evidence suggests that these predictive mechanisms can operate across sensory modalities, that is, vision and audition. However, to date, behavioral and electrophysiological demonstrations of cross-modal prediction in speech have considered only the speaker's native language. Here, we address a question of current debate, namely whether the level of representation involved in cross-modal prediction is phonological or pre-phonological. We do this by testing participants in an unfamiliar language. If cross-modal prediction is predominantly based on phonological representations tuned to the phonemic categories of the native language of the listener, then it should be more effective in the listener's native language than in an unfamiliar one. We tested Spanish and English native speakers in an audiovisual matching paradigm that allowed us to evaluate visual-to-auditory prediction, using sentences in the participant's native language and in an unfamiliar language. The benefits of cross-modal prediction were only seen in the native language, regardless of the particular language or participant's linguistic background. This pattern of results implies that cross-modal visual-to-auditory prediction during speech processing makes strong use of phonological representations, rather than low-level spatiotemporal correlations across facial movements and sounds.	\N	\N
23387878	Velopharyngeal incompetence is a contributing factor to speech disorders and implies the presence of hypernasality, inappropriate nasal escape, and decreased air pressure during speech. One prosthetic treatment is a rehabilitative procedure employing a palatal lift prosthesis (PLP), which reduces hypernasality by approximating the incompetent soft palate to the posterior pharyngeal wall and consists of two parts, the anterior denture base and the palatal lifting plate, which are connected with steel wires; however, it seems difficult to reproduce the mobility of the soft palate in speaking, and it is therefore likely that the palatal lifting plate stimulates or oppresses the tissue of the soft palate and hinders rather than assists articulatory function. To avoid these disturbances we devised an adjustable PLP with a flexible conjunction between the denture base and the palatal lifting plate to obtain the optimal vertical lifting angle. The palatal plate was adapted to conform in a passive manner to the soft palate with light-cured resin. The designed PLP simplified the procedure and reduced the number of adjustments and visits.	\N	\N
23389426	The human visual attention system is geared toward detecting the most salient and relevant events in an overwhelming stream of information. There has been great interest in measuring how many visual events can be processed at a time, and most of the work has suggested that the limit is three to four. However, attention to a visual stimulus can also be driven by a synchronous auditory event. The present work indicates that a fundamentally different limit applies to audiovisual processing, such that at most only a single audiovisual event can be processed at a time. This limited capacity is not due to a limitation in visual selection; participants were able to process about four visual objects simultaneously. Instead, we propose that audiovisual orienting is subject to a fundamentally different capacity limit than pure visual selection is.	\N	\N
23395711	In the current ERP study, an active oddball task was carried out, testing pure tones and auditory, visual and audiovisual syllables. For pure tones, an MMN, an N2b, and a P3 were found, confirming traditional findings. Auditory syllables evoked an N2 and a P3. We found that the amplitude of the P3 depended on the distance between standard and deviant. A smaller distance required more attention, which was reflected in a larger amplitude. An analysis of audiovisual material, after correction for visual activity, showed that McGurk type stimuli evoked brain responses that differed from both the standard and the congruent deviants. Finally, we found that congruent audiovisual stimuli elicited an N2 with a shorter latency and a P3 with a smaller amplitude than auditory stimuli. The current ERP study, thus, shows that for audiovisual processing the whole is more than the sum of its parts.	\N	\N
23395774	This paper examines the judgment of segmented temporal intervals, using short tone sequences as a convenient test case. In four experiments, we investigate how the relative lengths, arrangement, and pitches of the tones in a sequence affect judgments of sequence duration, and ask whether the data can be described by a simple weighted sum of segments model. The model incorporates three basic assumptions: (i) the judgment of each segment is a negatively accelerated function of its duration, (ii) the judgment of the overall interval is produced by summing the judgments of each segment, and (iii) more recent segments are weighted more heavily. We also assume that higher-pitched tones are judged to last longer. Empirically, sequences with equal-sized segments were consistently judged longer than those with accelerating or decelerating structures. Furthermore, temporal structure interacted with duration, such that accelerating sequences were judged longer than decelerating ones at short durations but the effect reversed at longer durations. These effects were modulated by the number of tones in the sequence, the rate of acceleration/deceleration, and whether the sequence had ascending or descending pitch, and were well-described by the weighted sum model. The data provide strong constraints on theories of temporal judgment, and the weighted sum of segments model offers a useful basis for future theoretical and empirical investigation.	\N	\N
23397035	We used a face-gender repetition priming paradigm to precisely map the spatial frequencies (SFs) that influence observers' responses under different prime awareness conditions. A visible prime condition was set up by presenting the stimulus sequence mask-blank-prime-blank-mask-target and an invisible prime condition by switching the order of the masks and the blanks (see also Dehaene et al., 2001). The prime faces (~4.6° × 3.1°) were randomly filtered trial-by-trial according to the SF bubbles technique (Willenbockel, Fiset et al., 2010). Classification vectors, derived by summing the SF filters from each trial weighted by observers' transformed response times, revealed that SFs around 12 cycles per face width modulated responses in both prime awareness conditions. The significant SFs closely matched those optimal for accurate performance in a direct face-gender classification paradigm. Surprisingly, the significant SFs facilitated observers' responses in the visible prime condition, whereas they slowed responses in the invisible prime condition. Our findings suggest that SF tuning per se remains robust under different prime awareness conditions but that diagnostic visual cues might be utilized in a qualitatively different fashion as a function of awareness.	\N	\N
23400826	In two experiments, we used an interruption-and-recall (IAR) task to explore listeners' ability to monitor the capacity of working memory as new information arrived in real time. In this task, listeners heard recorded word lists with instructions to interrupt the input at the maximum point that would still allow for perfect recall. Experiment 1 demonstrated that the most commonly selected segment size closely matched participants' memory span, as measured in a baseline span test. Experiment 2 showed that reducing the sound level of presented word lists to a suprathreshold but effortful listening level disrupted the accuracy of matching selected segment sizes with participants' memory spans. The results are discussed in terms of whether online capacity monitoring may be subsumed under other, already enumerated working memory executive functions (inhibition, set shifting, and memory updating).	\N	\N
23403808	The objective of this study was to examine the role of the acoustic stapedius reflex in the protection of speech recognition from the upward spread of masking arising from low-frequency background noise. Speech recognition scores were measured for nine control participants (19-34 years) and six patients with transected stapedius tendons poststapedotomy (39-57 years) as a function of the amplitude of a low-frequency masker, presented at nominal signal to noise ratios of +5 dB, -5 dB, and -15 dB. All participants had pure-tone hearing thresholds in the normal range. Continuous high-pass noise was present in all conditions to avoid ceiling effects; this reduced performance in quiet to approximately 85% for all participants. Scores were measured for soft and loud nonsense syllables (average third octave band levels of 35 and 65 dB SPL), so that a comparison of the low-frequency noise masking functions at the two levels would provide information about the effects of the reflex on speech intelligibility in noise. A third group of nine control participants (19-22 years) listened in the presence of a low-frequency masker gated to come on 1 sec before stimulus onset, to reduce the likelihood of reflex adaptation. The Speech-Intelligibility Index was used to quantify the amount of speech information available in each condition. Patients with transected tendons performed more poorly than control participants as a function of Speech-Intelligibility Index in all conditions, even at levels that were too soft for reflex activation. This could be because of postsurgical differences in sensitivity, the more advanced age of poststapedotomy group, or differences in medial olivocochlear inhibition. For loud speech, patient performance fell nearly linearly with increases in the low-frequency masker, but control participants' performance declined little as the signal to noise ratio declined from +5 to -5 dB, and then fell rapidly as the ratio declined to -15 dB. This plateau in the masking function did not occur for the patients. Masking functions obtained with the gated low-frequency masker were either highly similar or poorer to those obtained with a continuous masker, suggesting that the use of a continuous low frequency masker did not result in significant reflex adaptation. The stapedius reflex appears to offer some protection from the upward spread of masking of speech by background low-frequency noise at moderate levels, but not at high levels.	\N	\N
23406991	Around 10% of people experience subjective tinnitus (the perception of sound, only audible to the patient, in the absence of an external auditory stimulus).(1-3) It may be associated with hearing loss, anxiety, depression, sleep disturbance, concentration problems or reduced quality of life; for around 0.5% it is extremely disturbing.(1-4) Risk factors include aging, significant noise exposure, drug therapy (e.g. aminoglycosides, NSAIDs, diuretics), or disorders of the outer, middle or inner ear or auditory nerve (e.g. ear wax, infections, vestibular schwannoma, otosclerosis).(1,2,4) It may be due to excessive spontaneous activity in the auditory system and brain; if the signal (normally suppressed by the subconscious) becomes noticed it becomes more intrusive and annoying in a vicious cycle.(5) Here, we discuss symptomatic drug and non-drug treatments for subjective tinnitus in adults. We do not cover treatment of underlying causes of tinnitus.	\N	\N
23408389	Coding for the degree of disorder in a temporally unfolding sensory input allows for optimized encoding of these inputs via information compression and predictive processing. Prior neuroimaging work has examined sensitivity to statistical regularities within single sensory modalities and has associated this function with the hippocampus, anterior cingulate, and lateral temporal cortex. Here we investigated to what extent sensitivity to input disorder, quantified by Markov entropy, is subserved by modality-general or modality-specific neural systems when participants are not required to monitor the input. Participants were presented with rapid (3.3 Hz) auditory and visual series varying over four levels of entropy, while monitoring an infrequently changing fixation cross. For visual series, sensitivity to the magnitude of disorder was found in early visual cortex, the anterior cingulate, and the intraparietal sulcus. For auditory series, sensitivity was found in inferior frontal, lateral temporal, and supplementary motor regions implicated in speech perception and sequencing. Ventral premotor and central cingulate cortices were identified as possible candidates for modality-general uncertainty processing, exhibiting marginal sensitivity to disorder in both modalities. The right temporal pole differentiated the highest and lowest levels of disorder in both modalities, but did not show general sensitivity to the parametric manipulation of disorder. Our results indicate that neural sensitivity to input disorder relies largely on modality-specific systems embedded in extended sensory cortices, though uncertainty-related processing in frontal regions may be driven by both input modalities.	\N	\N
23413000	In the present experiments, participants had to verify properties of concepts but, depending on the trial condition, concept-property pairs were presented via headphones or on the screen. The results showed that participants took longer and were less accurate at verifying conceptual properties when the channel used to present the CONCEPT-property pair and the type of property matched in sensory modality (e.g., LEMON-yellow on screen; BLENDER-loud in headphones) compared to when properties and channel did not match (e.g., LEMON-yellow in headphones; BLENDER-loud on screen). Such interference is consistent with theories of embodied cognition holding that knowledge is grounded in modality-specific systems (Barsalou in Behav Brain Sci 22:577-660, 1999). When the resources of one modality are burdened during the task, processing costs are incurred in a conceptual task (Vermeulen et al. in Cognition 109:287-294, 2008).	\N	\N
23425567	Previous studies on the role of vowel harmony in word segmentation are based on artificial languages where harmonic cues reliably signal word boundaries. In this corpus study run on the data available at CHILDES, we investigated whether natural languages provide a learner with reliable segmentation cues similar to the ones created artificially. We observed that in harmonic languages (child-directed speech to thirty-five Turkish and three Hungarian children), but not in non-harmonic ones (child-directed speech to one Farsi and four Polish children), harmonic vowel sequences are more likely to appear within words, and non-harmonic ones mostly appear across word boundaries, suggesting that natural harmonic languages provide a learner with regular cues that could potentially be used for word segmentation along with other cues.	\N	\N
23432759	The time frame for infants' acquisition of language constancy was probed, using the phonetic variation in a rarely heard accent (South African English) or a frequently heard accent (American English). A total of 156 Australian infants were tested. Six-month-olds looked longer to Australian English than less commonly heard South African accent, but at 9 months, showed similar looking times. With the more frequently heard American accent, 3-month-olds looked longer to Australian and American English, whereas 6-month-olds looked equally. Together these results imply that in the 1st year, differential attention to native versus nonnative accents decreases as infants develop a sense of language constancy for the common native language. However, experience with the nonnative accent can expedite this process.	\N	\N
23433243	Patients with alien hand syndrome (AHS) experience making apparently deliberate and purposeful movements with their hand against their will. However, the mechanisms contributing to these involuntary actions remain poorly understood. Here, we describe two experimental investigations in a patient with corticobasal syndrome (CBS) with alien hand behaviour in her right hand. First, we show that responses with the alien hand are made significantly more quickly to images of objects which afford an action with that hand compared to objects which afford an action with the unaffected hand. This finding suggests that involuntary grasping behaviours in AHS might be due to exaggerated, automatic motor activation evoked by objects which afford actions with that limb. Second, using a backwards masked priming task, we found normal automatic inhibition of primed responses in the patient's unaffected hand, but importantly there was no evidence of such suppression in the alien limb. Taken together, these findings suggest that grasping behaviours in AHS may result from exaggerated object affordance effects, which might potentially arise from disrupted inhibition of automatically evoked responses.	\N	\N
23440517	Users of bilateral cochlear implants (CIs) experience difficulties localizing sounds in reverberant rooms, even in rooms where normal-hearing listeners would hardly notice the reverberation. We measured the localization ability of seven bilateral CI users listening with their own devices in anechoic space and in a simulated reverberant room. To determine factors affecting performance in reverberant space we measured the sensitivity to interaural time differences (ITDs), interaural level differences (ILDs), and forward masking in the same participants using direct computer control of the electric stimulation in their CIs. Localization performance, quantified by the coefficient of determination r(2) and the root mean squared error, was significantly worse in the reverberant room than in anechoic conditions. Localization performance in the anechoic room, expressed as r(2), was best predicted by subject's sensitivity to ILDs. However, the decrease in localization performance caused by reverberation was better predicted by the sensitivity to envelope ITDs measured on single electrode pairs, with a correlation coefficient of 0.92. The CI users who were highly sensitive to envelope ITDs also better maintained their localization ability in reverberant space. Results in the forward masking task added only marginally to the predictions of localization performance in both environments. The results indicate that envelope ITDs provided by CI processors support localization in reverberant space. Thus, methods that improve perceptual access to envelope ITDs could help improve localization with bilateral CIs in everyday listening situations.	\N	\N
23440859	Children with reading disability and normal reading development were compared in their ability to discriminate native (English) and novel language (Mandarin) from nonlinguistic sounds. Children's preference for native versus novel language sounds and for disyllables containing dominant trochaic versus non-dominant iambic stress patterns was also assessed. Participants included second and third grade monolingual native English speakers with reading disability (N = 18) and normal reading development (N = 18). Children selected from pairs of novel, native, and nonlinguistic sounds that was more like language. Both groups discriminated disyllabic linguistic sounds (native and novel) from nonlinguistic sounds. Both groups showed preference for the dominant English trochaic stress pattern over the non-dominant iambic stress pattern. Implications for development of prosodic sensitivity in relation to reading skills and future research are discussed.	\N	\N
23442569	The relative impact of early intervention approach on speech perception and language skills was examined in these 3 well-matched groups of children using cochlear implants. Eight children from an auditory verbal intervention program were identified. From a pediatric database, researchers blind to the outcome data, identified 23 children from auditory oral programs and 8 children from bilingual-bicultural programs with the same inclusion criteria and equivalent demographic factors. All child participants were male, had congenital profound hearing loss (pure tone average >80 dBHL), no additional disabilities, were within the normal IQ range, were monolingual English speakers, had no unusual findings on computed tomography/magnetic resonance imaging, and received hearing aids and cochlear implants at a similar age and before 4 years of age. Open-set speech perception (consonant-nucleus-consonant [CNC] words and Bamford-Kowal-Bench [BKB] sentences) and the Peabody Picture Vocabulary Test (PPVT) were administered. The mean age at cochlear implant was 1.7 years (range, 0.8-3.9; SD, 0.7), mean test age was 5.4 years (range, 2.5-10.1; SD, 1.7), and mean device experience was 3.7 years (range, 0.7-7.9; SD, 1.8). Results indicate mean CNC scores of 60%, 43%, and 24% and BKB scores of 77%, 77%, and 56% for the auditory-verbal (AV), aural-oral (AO), and bilingual-bicultural (BB) groups, respectively. The mean PPVT delay was 13, 19, and 26 months for AV, AO, and BB groups, respectively. Despite equivalent child demographic characteristics at the outset of this study, by 3 years postimplant, there were significant differences in AV, AO, and BB groups. Results support consistent emphasis on oral/aural input to achieve optimum spoken communication outcomes for children using cochlear implants.	\N	\N
23445327	Metabolic syndrome is a risk factor for age-related hearing impairment (ARHI). There are metabolic differences between abdominal adipose tissue present in subcutaneous and visceral areas. In this study, we investigated the association between abdominal fat composition, measured by computerized tomography (CT), and hearing thresholds. We recruited 662 adults aged 40-82 years with normal or symmetrical sensorineural hearing loss who underwent fat measurement by CT. Linear regression models were used to address the association between risk factors, including abdominal fat composition, and average hearing levels at low and high frequencies. After adjusting for age, systemic disease and other variables, a positive association between visceral adipose tissue (VAT) area and average hearing threshold was observed in women. In men, there was no significant association between abdominal fat composition and hearing threshold. Our findings show an association between VAT and hearing impairment in women. A reduction in visceral adiposity may help to prevent hearing loss in women.	\N	\N
23446225	The aim of this study was to assess the benefit of having preserved acoustic hearing in the implanted ear for speech recognition in complex listening environments. The present study included a within-subjects, repeated-measures design including 21 English-speaking and 17 Polish-speaking cochlear implant (CI) recipients with preserved acoustic hearing in the implanted ear. The patients were implanted with electrodes that varied in insertion depth from 10 to 31 mm. Mean preoperative low-frequency thresholds (average of 125, 250, and 500 Hz) in the implanted ear were 39.3 and 23.4 dB HL for the English- and Polish-speaking participants, respectively. In one condition, speech perception was assessed in an eight-loudspeaker environment in which the speech signals were presented from one loudspeaker and restaurant noise was presented from all loudspeakers. In another condition, the signals were presented in a simulation of a reverberant environment with a reverberation time of 0.6 sec. The response measures included speech reception thresholds (SRTs) and percent correct sentence understanding for two test conditions: CI plus low-frequency hearing in the contralateral ear (bimodal condition) and CI plus low-frequency hearing in both ears (best-aided condition). A subset of six English-speaking listeners were also assessed on measures of interaural time difference thresholds for a 250-Hz signal. Small, but significant, improvements in performance (1.7-2.1 dB and 6-10 percentage points) were found for the best-aided condition versus the bimodal condition. Postoperative thresholds in the implanted ear were correlated with the degree of electric and acoustic stimulation (EAS) benefit for speech recognition in diffuse noise. There was no reliable relationship among measures of audiometric threshold in the implanted ear nor elevation in threshold after surgery and improvement in speech understanding in reverberation. There was a significant correlation between interaural time difference threshold at 250 Hz and EAS-related benefit for the adaptive speech reception threshold. The findings of this study suggest that (1) preserved low-frequency hearing improves speech understanding for CI recipients, (2) testing in complex listening environments, in which binaural timing cues differ for signal and noise, may best demonstrate the value of having two ears with low-frequency acoustic hearing, and (3) preservation of binaural timing cues, although poorer than observed for individuals with normal hearing, is possible after unilateral cochlear implantation with hearing preservation and is associated with EAS benefit. The results of this study demonstrate significant communicative benefit for hearing preservation in the implanted ear and provide support for the expansion of CI criteria to include individuals with low-frequency thresholds in even the normal to near-normal range.	\N	\N
23446226	Understanding speech in acoustically degraded environments can place significant cognitive demands on school-age children who are developing the cognitive and linguistic skills needed to support this process. Previous studies suggest the speech understanding, word learning, and academic performance can be negatively impacted by background noise, but the effect of limited audibility on cognitive processes in children has not been directly studied. The aim of the present study was to evaluate the impact of limited audibility on speech understanding and working memory tasks in school-age children with normal hearing. Seventeen children with normal hearing between 6 and 12 years of age participated in the present study. Repetition of nonword consonant-vowel-consonant stimuli was measured under conditions with combinations of two different signal to noise ratios (SNRs; 3 and 9 dB) and two low-pass filter settings (3.2 and 5.6 kHz). Verbal processing time was calculated based on the time from the onset of the stimulus to the onset of the child's response. Monosyllabic word repetition and recall were also measured in conditions with a full bandwidth and 5.6 kHz low-pass cutoff. Nonword repetition scores decreased as audibility decreased. Verbal processing time increased as audibility decreased, consistent with predictions based on increased listening effort. Although monosyllabic word repetition did not vary between the full bandwidth and 5.6 kHz low-pass filter condition, recall was significantly poorer in the condition with limited bandwidth (low pass at 5.6 kHz). Age and expressive language scores predicted performance on word recall tasks, but did not predict nonword repetition accuracy or verbal processing time. Decreased audibility was associated with reduced accuracy for nonword repetition and increased verbal processing time in children with normal hearing. Deficits in free recall were observed even under conditions where word repetition was not affected. The negative effects of reduced audibility may occur even under conditions where speech repetition is not impacted. Limited stimulus audibility may result in greater cognitive effort for verbal rehearsal in working memory and may limit the availability of cognitive resources to allocate to working memory and other processes.	\N	\N
23464029	Aided consonant and vowel identification was measured in 13 listeners with high-frequency sloping hearing losses. To investigate the influence of compression-channel analysis bandwidth on identification performance independent of the number of channels, performance was compared for three 17-channel compression systems that differed only in terms of their channel bandwidths. One compressor had narrow channels, one had widely overlapping channels, and the third had level-dependent channels. Measurements were done in quiet, in speech-shaped noise, and in a three-talker background. The results showed no effect of channel bandwidth, neither on consonant nor on vowel identification scores. This suggests that channel bandwidth per se has little influence on speech intelligibility when individually prescribed, frequency-varying compressive gain is provided.	\N	\N
23466188	It is well established that individuals with schizophrenia demonstrate alterations in auditory perception beginning at the very earliest stages of information processing. However, it is not clear how these impairments in basic information processing translate into high-order cognitive deficits. Auditory scene analysis allows listeners to group auditory information into meaningful objects, and as such provides an important link between low-level auditory processing and higher cognitive abilities. In the present study we investigated whether low-level impairments in the processing of binaural temporal information impact upon auditory scene analysis ability. Binaural temporal processing ability was investigated in 19 individuals with schizophrenia and 19 matched controls. Individuals with schizophrenia showed impaired binaural temporal processing ability on an inter-aural time difference (ITD) discrimination task. In addition, patients demonstrated impairment in two measures of auditory scene analysis. Specifically, patients had reduced ability to use binaural temporal cues to extract signal from noise in a masking level difference paradigm, and to separate the location of a source sound in the presence of an echo in the precedence effect paradigm. These findings demonstrate that individuals with schizophrenia have impairments in the accuracy with which simple binaural temporal information is encoded in the auditory system, and furthermore, this impairment has functional consequences in terms of the use of these cues to extract information in complex auditory environments.	\N	\N
23467261	We tested whether congenital amusics, who exhibit pitch perception deficits, nevertheless adjust the pitch of their voice in response to a sudden pitch shift applied to vocal feedback. Nine amusics and matched controls imitated their own previously-recorded speech or singing, while the online feedback they received was shifted mid-utterance by 25 or 200 cents. While a few amusics failed to show pitch-shift effects, a majority showed a pitch-shift response and nearly half showed a normal response to both large and small shifts, with similar magnitudes and response times as controls. The size and presence of the shift response to small shifts were significantly predicted by participants' vocal pitch matching accuracy, rather than their ability to perceive small pitch changes. The observed dissociation between the ability to consciously perceive small pitch changes and to produce and monitor vocal pitch provides evidence for a dual-route model of pitch processing in the brain.	\N	\N
23472959	The more a novel word conforms to the phonotactics of the language, the more wordlike it is and the easier it is to learn. It is unknown to what extent children with hearing loss (CHL) take advantage of phonotactic cues to support word learning. This study investigated whether CHL had similar sensitivities to wordlikeness during a word-learning task as children with normal hearing (CNH). Sixteen CHL and 24 CNH participated in a novel word-learning task. Novel words varied by English wordlikeness. Recall was tested using a forced-choice identification task wherein foils for each trial related semantically, lexically or not at all. Receptive vocabulary and working memory were also assessed. All children were able to identify high wordlike novel words more accurately than low wordlike novel words. The number of errors on identification of words that were moderate in wordlikeness was inversely correlated to vocabulary size (not working memory) and CHL had smaller vocabularies than CNH. When in error, CHL were more likely than CNH to select a semantically related foil. Although they are sensitive to extremes in wordlikeness, compared with their peers with normal hearing, CHL present with subtle differences in word learning. Clinical implications for exploiting wordlikeness in service of word learning assessment and intervention are presented.	\N	\N
23473799	The Attention Network Test (ANT) assesses the networks of attention (alerting, orienting, and executive control). The utility of measuring attention network performances with the repeated administration of the ANT in clinical populations has not yet been explored. In the present study, we administered a variant of the ANT (ANT-I) to 11 multiple sclerosis (MS) patients and 11 controls over six monthly sessions to examine the stability, isolability, robustness, and reliability of the ANT-I. Participants responded through button presses to indicate the direction of a target arrow presented either above or below a fixation cross. The target was accompanied by distracting arrows, pointing either in the same or opposite direction of the target arrow. Target arrows were preceded in some trials by alerting auditory signals and/or by uninformative visual cues. Network scores were calculated using orthogonal subtractions of performance under selected conditions. The MS patients were slower than the controls, though group differences in network performance were rare. Even after five test sessions, the network scores remained stable, despite some practice effects that were the largest under conditions that tested the executive network. The reliabilities of the orienting and executive network effects were good in both groups and increased across sessions, especially with the MS patients. The alerting network was the least reliable, especially for MS patients, but it also became more reliable across sessions. The results suggest that the ANT-I can be used to measure the integrity of attention networks for MS patients in applications that require repeated testing.	\N	\N
23479475	The human visual system possesses the remarkable ability to pick out salient objects in images. Even more impressive is its ability to do the very same in the presence of disturbances. In particular, the ability persists despite the presence of noise, poor weather, and other impediments to perfect vision. Meanwhile, noise can significantly degrade the accuracy of automated computational saliency detection algorithms. In this article, we set out to remedy this shortcoming. Existing computational saliency models generally assume that the given image is clean, and a fundamental and explicit treatment of saliency in noisy images is missing from the literature. Here we propose a novel and statistically sound method for estimating saliency based on a nonparametric regression framework and investigate the stability of saliency models for noisy images and analyze how state-of-the-art computational models respond to noisy visual stimuli. The proposed model of saliency at a pixel of interest is a data-dependent weighted average of dissimilarities between a center patch around that pixel and other patches. To further enhance the degree of accuracy in predicting the human fixations and of stability to noise, we incorporate a global and multiscale approach by extending the local analysis window to the entire input image, even further to multiple scaled copies of the image. Our method consistently outperforms six other state-of-the-art models (Bruce & Tsotsos, 2009; Garcia-Diaz, Fdez-Vidal, Pardo, & Dosil, 2012; Goferman, Zelnik-Manor, & Tal, 2010; Hou & Zhang, 2007; Seo & Milanfar, 2009; Zhang, Tong, & Marks, 2008) for both noise-free and noisy cases.	\N	\N
23479544	The NIH Toolbox project has assembled measurement tools to assess a wide range of human perception and ability across the lifespan. As part of this initiative, a small but comprehensive battery of auditory tests has been assembled. The main tool of this battery, pure-tone thresholds, measures the ability of people to hear at specific frequencies. Pure-tone thresholds have long been considered the "gold standard" of auditory testing, and are normally obtained in a clinical setting by highly trained audiologists. For the purposes of the Toolbox project, an automated procedure (NIH Toolbox Threshold Hearing Test) was developed that allows nonspecialists to administer the test reliably. Three supplemental auditory tests are also included in the Toolbox auditory test battery: assessment of middle-ear function (tympanometry), speech perception in noise (the NIH Toolbox Words-in-Noise Test), and self-assessment of hearing impairment (the NIH Toolbox Hearing Handicap Inventory Ages 18-64 and the NIH Toolbox Hearing Handicap Inventory Ages 64+). Tympanometry can help differentiate conductive from sensorineural pathology. The NIH Toolbox Words-in-Noise Test measures a listener's ability to perceive words in noisy situations. This ability is not necessarily predicted by a person's pure-tone thresholds; some people with normal hearing have difficulty extracting meaning from speech sounds heard in a noisy context. The NIH Toolbox Hearing Handicap Inventory focuses on how a person's perceived hearing status affects daily life. The test was constructed to include emotional and social/situational subscales, with specific questions about how hearing impairment may affect one's emotional state or limit participation in specific activities. The 4 auditory tests included in the Toolbox auditory test battery cover a range of auditory abilities and provide a snapshot of a participant's auditory capacity.	\N	\N
23483527	We used the visual world paradigm to examine interlingual lexical competition when Dutch-English bilinguals listened to low-constraining sentences in their nonnative (L2; Experiment 1) and native (L1; Experiment 2) languages. Additionally, we investigated the influence of the degree of cross-lingual phonological similarity. When listening in L2, participants fixated more on competitor pictures of which the onset of the name was phonologically related to the onset of the name of the target in the nontarget language (e.g., fles, "bottle", given target flower) than on phonologically unrelated distractor pictures. Even when they listened in L1, this effect was also observed when the onsets of the names of the target picture (in L1) and the competitor picture (in L2) were phonologically very similar. These findings provide evidence for interlingual competition during the comprehension of spoken sentences, both in L2 and in L1.	\N	\N
23485447	With an incidence of 1:29 000 among Caucasians, Friedreich's ataxia (FRDA) is the most common inherited ataxia, leading to both sensory and motor degeneration. Despite many FRDA patients exhibiting normal or near normal sound detection thresholds, many individuals show abnormal neural conduction along their central auditory pathways. Electrophysiological testing can show abnormal or absent cochlear nerve and auditory brainstem recordings in the presence of normal pre-neural cochlear function (otoacoustic emissions or cochlear microphonics). This pattern of normal pre-neural cochlear function and disrupted neural conduction has been termed auditory neuropathy spectrum disorder (ANSD). Studies of FRDA patients with ANSD have shown that they exhibit severe deficits in temporal processing, impaired frequency discrimination, and deficits in speech perception. Rehabilitation of these auditory percept deficits remains difficult, as hearing aids may amplify sounds without adding clarity to the temporally disrupted or distorted signal that FRDA patients with ANSD may receive. There is limited data on the best intervention for patients with FRDA with ANSD, although personal radio aids (FM systems) have been shown to be beneficial. We report a case, where cochlear implantation has led to a dramatic improvement in speech perception in an individual with FRDA and ANSD. The majority of the literature on ANSD treatment has focused on paediatric patients with the 'dyssynchrony' type of ANSD, rather than the true neuropathy type underlying the hearing loss in FRDA patients.	\N	\N
23497238	Auditory feedback is important for accurate control of voice fundamental frequency (F(0)). The purpose of this study was to address whether task instructions could influence the compensatory responding and sensorimotor adaptation that has been previously found when participants are presented with a series of frequency-altered feedback (FAF) trials. Trained singers and musically untrained participants (nonsingers) were informed that their auditory feedback would be manipulated in pitch while they sang the target vowel [/α /]. Participants were instructed to either 'compensate' for, or 'ignore' the changes in auditory feedback. Whole utterance auditory feedback manipulations were either gradually presented ('ramp') in -2 cent increments down to -100 cents (1 semitone) or were suddenly ('constant') shifted down by 1 semitone. Results indicated that singers and nonsingers could not suppress their compensatory responses to FAF, nor could they reduce the sensorimotor adaptation observed during both the ramp and constant FAF trials. Compared to previous research, these data suggest that musical training is effective in suppressing compensatory responses only when FAF occurs after vocal onset (500-2500 ms). Moreover, our data suggest that compensation and adaptation are automatic and are influenced little by conscious control.	\N	\N
23506084	Although adults rapidly adjust to accented speakers' pronunciation of words, young children appear to struggle when confronted with unfamiliar variants of their native language (e.g., American English-learning 15-month-olds cannot recognize familiar words spoken in Jamaican English; Best et al., 2009). It is currently unclear, however, why this is the case, or how infants overcome this apparent inability. Here, we begin to address these crucial questions. Experiments 1 and 2 confirm with a new population that infants are initially unable to recognize familiar words produced in unfamiliar accents. That is, Canadian English-learning infants cannot recognize familiar words spoken in Australian English until they near their second birthday. However, Experiments 3 and 4 show that this early inability to recognize accented words can readily be overcome when infants are exposed to a story read in the unfamiliar accent prior to test. Importantly, this adaptation only occurs when the story is highly familiar, consistent with the idea that top-down lexical feedback may enable the adaptation process. We conclude that infants, like adults, have the cognitive capacity to rapidly deduce the mapping between their own and an unfamiliar variant of their native language. Thus, the essential machinery underlying spoken language communication is in place much earlier than previous studies have suggested.	\N	\N
23507048	Event related potentials (ERP) associated with early sensory information processing have been proposed as possible vulnerability markers for psychosis. Compared to other ERPs reported in schizophrenia research, like Mismatch Negativity (MMN), little is known about P3a, an ERP related to novelty detection. The aim of this study was to analyze the MMN-P3a complex in 20 antipsychotic naïve first-episode psychosis patients (FEP), 23 antipsychotic naïve individuals at clinical high-risk for psychosis (CHR) and 24 healthy controls. The MMN-P3a amplitudes and latencies were obtained during a passive auditory mismatch frequency deviant ERP paradigm and analyzed in frontal and central scalp regions. There were no significant differences in MMN amplitude between groups. There was a significant group difference in P3a due to reduced amplitude (F[2,64] = 3.7, p = 0.03) in both CHR and FEP groups (Mean difference (MD) = 0.39, p = 0.04 and MD = 0.49, p = 0.02, respectively) compared to the control group and this effect was most prominent on the right side (Group × laterality effect: MD = 0.57, p < 0.01 and MD = 0.58, p < 0.01, respectively). No significant differences were observed for MMN or P3a latencies between groups. Although a P3a decrement in chronic schizophrenia and FEP has been previously reported, our results suggest that this novelty detection impairment is present even in pre-psychosis stages in antipsychotic naïve subjects. This study supports the evidence that P3a could represent a neurophysiological vulnerability marker for the development of psychosis.	\N	\N
23510647	Rehabilitation success in cochlear implant patients is influenced by many factors. Influence of different etiologies of deafness on rehabilitation outcome is assessed. Retrospective survey of patients. University hospital. Secondary referral center. One hundred and sixty-three between 1996 and 2008 implanted children (0-18 years, mean 5.17 years). Evaluation of patients' data: origin of deafness, hearing and speech test results. Access Data Base; Wilcoxon and t-test. Mean follow-up: 65.4 months. Etiology of deafness in children found in 104 cases: 69 (51.9%) suffered from hereditary hearing loss. All children showed improvement in their auditory performance, children with connexin-26 mutation performed significantly best, Usher and CHARGE-syndrome children significantly worst. Post-meningitic and post-septic children developed slower but reached same levels later. Primary cause of deafness, among other factors, has a considerable impact on outcome of rehabilitation. This offers possibilities to influence the outcome by etiology-adjusted therapy modules.	\N	\N
23517653	Numerous cortical disorders affect language. We explore the connection between the observed language behavior and the underlying substrates by adopting a neurocomputational approach. To represent the observed trajectories of the discourse in patients with disorganized speech and in healthy participants, we design a graphical representation for the discourse as a trajectory that allows us to visualize and measure the degree of order in the discourse as a function of the disorder of the trajectories. Our work assumes that many of the properties of language production and comprehension can be understood in terms of the dynamics of modular networks of neural associative memories. Based upon this assumption, we connect three theoretical and empirical domains: (1) neural models of language processing and production, (2) statistical methods used in the construction of functional brain images, and (3) corpus linguistic tools, such as Latent Semantic Analysis (henceforth LSA), that are used to discover the topic organization of language. We show how the neurocomputational models intertwine with LSA and the mathematical basis of functional neuroimaging. Within this framework we describe the properties of a context-dependent neural model, based on matrix associative memories, that performs goal-oriented linguistic behavior. We link these matrix associative memory models with the mathematics that underlie functional neuroimaging techniques and present the "functional brain images" emerging from the model. This provides us with a completely "transparent box" with which to analyze the implication of some statistical images. Finally, we use these models to explore the possibility that functional synaptic disconnection can lead to an increase in connectivity between the representations of concepts that could explain some of the alterations in discourse displayed by patients with schizophrenia.	\N	\N
23522843	Aging usually affects the ability to focus attention on a given task and to ignore distractors. However, aging is also associated with increased between-subject variability, and it is unclear in which features of processing older high-performing and low-performing human beings may differ in goal-directed behavior. To study involuntary shifts in attention to task-irrelevant deviant stimuli and subsequent reorientation, we used an auditory distraction task and analyzed event-related potential measures (mismatch negativity), P3a and reorienting negativity) of 35 younger, 32 older high-performing, and 32 older low-performing participants. Although both high and low performing elderly individuals showed a delayed reorienting to the primary stimulus feature, relative to young participants, poor performance of the elderly participants in processing of deviant stimuli was associated with strong involuntary attention capture by task-irrelevant features. In contrast, high performance of the elderly group was associated with intensified attentional shifting toward the target features. Thus, it appears that performance deficits in aging are due to higher distractibility in combination with deficits in the orienting-reorienting mechanisms.	\N	\N
23526255	In this study, we present the normative values of the adaptation of the International Affective Digitized Sounds (IADS-2; Bradley & Lang, 2007a) for European Portuguese (EP). The IADS-2 is a standardized database of 167 naturally occurring sounds that is widely used in the study of emotions. The sounds were rated by 300 college students who were native speakers of EP, in the three affective dimensions of valence, arousal, and dominance, by using the Self-Assessment Manikin (SAM). The aims of this adaptation were threefold: (1) to provide researchers with standardized and normatively rated affective sounds to be used with an EP population; (2) to investigate sex and cultural differences in the ratings of affective dimensions of auditory stimuli between EP and the American (Bradley & Lang, 2007a) and Spanish (Fernández-Abascal et al., Psicothema 20:104-113 2008; Redondo, Fraga, Padrón, & Piñeiro, Behavior Research Methods 40:784-790 2008) standardizations; and (3) to promote research on auditory affective processing in Portugal. Our results indicated that the IADS-2 is a valid and useful database of digitized sounds for the study of emotions in a Portuguese context, allowing for comparisons of its results with those of other international studies that have used the same database for stimulus selection. The normative values of the EP adaptation of the IADS-2 database can be downloaded along with the online version of this article.	\N	\N
23528307	KCNA10 is a voltage gated potassium channel that is expressed in the inner ear. The localization and function of KCNA10 was studied in a mutant mouse, B6-Kcna10(TM45), in which the single protein coding exon of Kcna10 was replaced with a beta-galactosidase reporter cassette. Under the regulatory control of the endogenous Kcna10 promoter and enhancers, beta-galactosidase was expressed in hair cells of the vestibular organs and the organ of Corti. KCNA10 expression develops in opposite tonotopic gradients in the inner and outer hair cells. Kcna10(TM45) homozygotes display only a mild elevation in pure tone hearing thresholds as measured by auditory brainstem response (ABR), while heterozygotes are normal. However, Kcna10(TM45) homozygotes have absent vestibular evoked potentials (VsEPs) or elevated VsEP thresholds with prolonged peak latencies, indicating significant vestibular dysfunction despite the lack of any overt imbalance behaviors. Our results suggest that Kcna10 is expressed primarily in hair cells of the inner ear, with little evidence of expression in other organs. The Kcna10(TM45) targeted allele may be a model of human nonsyndromic vestibulopathy.	\N	\N
23534195	The author investigated the longitudinal relations between theory of mind (ToM) understanding and perceptions of self and social conversations in 17 school-aged children (12 girls, 5 boys, age 8-12 years). ToM was assessed at Time 1 (T1; M age = 8 years 5 months, SD = 8.7 months, and perceptions of self and conversational experiences assessed two years later at Time 2 (T2; M age = 10 years 4 months, SD = 7.9 months. Most importantly, longitudinal findings showed that children who scored relatively high on ToM at T1 reported relatively lower perceptions of self-worth and higher number of mental states verbs in their perceptions of peer and family conversations at T2. Significant negative longitudinal associations were found between children's number of siblings and their perceptions of self-worth (T1) and number of cognitive terms in their perceptions of peer and family conversations (T2). Frequency analysis suggested that girls' perceptions of conversations referred to more social and psychological aspects of self and relationships, whereas boys focused mainly on physical activities. Most children were more likely to prefer listening to talking during social conversations. The majority of children reported feelings of mixed or ambiguous emotions during experiences of silence. Implications for socioemotional and cognitive development in early adolescents are discussed.	\N	\N
23538131	A total of 64 loci for autosomal dominant non-syndromic hearing impairment have been described, and the causative genes have been identified for 24 of these. The present study reports on the clinical characteristics of an autosomal dominantly inherited hearing impairment that is linked to a region within the DFNA60 locus located on chromosome 2 in q22.1-24.1. A pedigree spanning four generations was established with 13 affected individuals. Linkage analysis demonstrated that the locus extended over a 2.96 Mb region flanked by markers D2S2335 and D2S2275. The audiograms mainly showed a distinctive U-shaped configuration. Deterioration of hearing started at a wide age range, from 12 to 40 years. Cross-sectional analysis showed rapid progression of hearing impairment from mild to severe, between the ages of 40 and 60 years, a phenomenon that is also observed in DFNA9 patients. The results of the individual longitudinal analyses were generally in line with those obtained by the cross-sectional analysis. Speech recognition scores related to the level of hearing impairment (PTA1,2,4 kHz) appeared to be fairly similar to those of presbyacusis patients. It is speculated that hearing impairment starting in mid-life, as shown by DFNA60 patients, could play a role in the development of presbyacusis. Furthermore, speech recognition did not deteriorate appreciably before the sixth decade of life. We conclude that DFNA60 should be considered in hearing impaired patients who undergo a rapid progression in middle age and are negative for DFNA9. Furthermore, cochlear implantation resulted in good rehabilitation in two DFNA60 patients.	\N	\N
23538912	Experiences of adversity in the early years of life alter the developing brain. However, evidence documenting this relationship often focuses on severe stressors and relies on peripheral measures of neurobiological functioning during infancy. In the present study, we employed functional MRI during natural sleep to examine associations between a more moderate environmental stressor (nonphysical interparental conflict) and 6- to 12-month-old infants' neural processing of emotional tone of voice. The primary question was whether interparental conflict experienced by infants is associated with neural responses to emotional tone of voice, particularly very angry speech. Results indicated that maternal report of higher interparental conflict was associated with infants' greater neural responses to very angry relative to neutral speech across several brain regions implicated in emotion and stress reactivity and regulation (including rostral anterior cingulate cortex, caudate, thalamus, and hypothalamus). These findings suggest that even moderate environmental stress may be associated with brain functioning during infancy.	\N	\N
23551061	The N1 and P2 event-related potentials (ERPs) are attenuated when the eliciting sounds coincide with our own actions. Although this ERP attenuation could be caused by central processes, it may also reflect a peripheral mechanism: the coactivation of the stapedius muscle with the task-relevant effector, which reduces signal transmission efficiency in the middle ear, reducing the effective intensity of concurrently presented tones, which, in turn, elicit lower amplitude auditory ERPs. Because stapedius muscle contraction attenuates frequencies below 2 kHz, no attenuation should occur at frequencies above 2 kHz. A self-induced tone paradigm was administered with 0.5, 2.0, and 8.0 kHz pure tones. Self-induced tones elicited attenuated N1 and P2 ERPs, but the magnitude of attenuation was not affected by tone frequency. This result does not support the hypothesis that ERP attenuation to self-induced tones are caused by stapedius muscle contractions.	\N	\N
23553325	Sound pressure level delivered through personal listening devices (PLDs) and reaching the ear drum might be affected by body size and jaw movements. This study aimed to investigate whether jaw movement and/or smaller body mass index (BMI) resulted in decrease of sound pressure level within the ear canals of PLD users via an earbud earphone. Case series. Forty-five normal-hearing subjects (16 males; mean age, 23.3 years) participated in this study. A probe-microphone system was used to measure sound pressure level in the external ear canal with music delivered from a media player via an earbud earphone. Test materials consisted of two 20-second excerpts from a heavy metal music piece. Subjects were instructed to adjust the volume of the media player to conform to three conditions for sound pressure measurement: comfortable, loud, and maximum. Measurements were then repeated while subjects mimicked chewing action under the same listening conditions. Sound pressure levels were significantly lower when measured with jaw movement than without jaw movement (P < .05). Sound pressure levels monitored with/without jaw movement were generally lower in subjects with a BMI<23 than those with a BMI ≥ 23 (P < .05). Jaw movement and low BMI (<23) reduced the overall sound level of PLDs at the ear canal. Sound pressure levels detected in the external ear canal of our subjects using earbud earphones were significantly lower under conditions of jaw movement/BMI <23. Our research invites further studies on a larger group of PLD users to correlate these variables with hearing threshold shifts over time.	\N	\N
23556595	Although bilateral cochlear implantation has the potential to improve sound localization and speech understanding in noise, obstacles exist in presenting maximally useful binaural information to bilateral cochlear-implant (CI) users. One obstacle is that electrode arrays may differ in cochlear position by several millimeters, thereby stimulating different neural populations. Effects of interaural frequency mismatch on binaural processing were studied in normal-hearing (NH) listeners using band-limited pulse trains, thereby avoiding confounding factors that may occur in CI users. In experiment 1, binaural image fusion was measured to capture perceptual number, location, and compactness. Subjects heard a single, compact image on 73% of the trials. In experiment 2, intracranial image location was measured for different interaural time differences (ITDs) and interaural level differences (ILDs). For larger mismatch, locations perceptually shifted towards the ear with the higher carrier frequency. In experiment 3, ITD and ILD just-noticeable differences (JNDs) were measured. JNDs increased with decreasing bandwidth and increasing mismatch, but were always measurable up to 3 mm of mismatch. If binaural-hearing mechanisms are similar between NH and CI subjects, these results may explain reduced sensitivity of ITDs and ILDs in CI users. Large mismatches may lead to distorted spatial maps and reduced binaural image fusion.	\N	\N
23556693	Talking silently to ourselves occupies much of our mental lives, yet the mechanisms underlying this experience remain unclear. The following experiments provide behavioral evidence that the auditory content of inner speech is provided by corollary discharge. Corollary discharge is the motor system's prediction of the sensory consequences of its actions. This prediction can bias perception of other sensations, pushing percepts to match with prediction. The two experiments below show this bias induced by inner speech, demonstrating that inner speech causes external sounds to be heard as similar to the imagined speech, and that this bias operates on subphonemic content.	\N	\N
23565267	Psychophysiological evidence suggests that music and language are intimately coupled such that experience/training in one domain can influence processing required in the other domain. While the influence of music on language processing is now well-documented, evidence of language-to-music effects have yet to be firmly established. Here, using a cross-sectional design, we compared the performance of musicians to that of tone-language (Cantonese) speakers on tasks of auditory pitch acuity, music perception, and general cognitive ability (e.g., fluid intelligence, working memory). While musicians demonstrated superior performance on all auditory measures, comparable perceptual enhancements were observed for Cantonese participants, relative to English-speaking nonmusicians. These results provide evidence that tone-language background is associated with higher auditory perceptual performance for music listening. Musicians and Cantonese speakers also showed superior working memory capacity relative to nonmusician controls, suggesting that in addition to basic perceptual enhancements, tone-language background and music training might also be associated with enhanced general cognitive abilities. Our findings support the notion that tone language speakers and musically trained individuals have higher performance than English-speaking listeners for the perceptual-cognitive processing necessary for basic auditory as well as complex music perception. These results illustrate bidirectional influences between the domains of music and language.	\N	\N
23571299	A variety of noises have been employed for decades in an effort to facilitate habituation, mask, or suppress tinnitus. Many of these sounds have reportedly provided benefit, but success has not been universal. More recently, musical stimuli have been added as a sound therapy component. The potential advantages of using such stimuli, in particular fractal tones, in combination with amplification are discussed in this paper.	\N	\N
23571301	The past decade has seen an escalating enthusiasm to comprehend chronic tinnitus from the perspective of both scientific understanding and clinical management. At the same time, there is a significant interest and commercial investment in providing targeted and individualized approaches to care, which incorporate novel sound-based technologies, with standard audiological and psychological strategies. Commercially produced sound-based devices for the tinnitus market include Co-ordinated Reset Neuromodulation ® , Neuromonics © , Serenade ® , and Widex ® Zen. Additionally, experimental interventions such as those based on frequency-discrimination training are of current interest. Many of these interventions overtly claim to target the underlying neurological causes of tinnitus. Here, we briefly summarize current perspectives on the pathophysiology of tinnitus and evaluate claims made by the device supporters from a critical point of view. We provide an opinion on how future research in the field of individualized sound-based interventions might best provide a reliable evidence-base in this growing area of translational medicine.	\N	\N
23577828	Mismatch negativity (MMN) overlaps with other auditory event-related potential (ERP) components. We examined the ERPs of 50 9- to 11-year-old children for vowels /i/, /y/ and equivalent complex tones. The goal was to separate MMN from obligatory ERP components using principal component analysis and equal probability control condition. In addition to the contrast of the deviant minus standard response, we employed the contrast of the deviant minus control response, to see whether the obligatory processing contributes to MMN in children. When looking for differences in speech deviant minus standard contrast, MMN starts around 112 ms. However, when both contrasts are examined, MMN emerges for speech at 160 ms whereas for nonspeech MMN is observed at 112 ms regardless of contrast. We argue that this discriminative response to speech stimuli at 112 ms is obligatory in nature rather than reflecting change detection processing.	\N	\N
23578016	Music is a cultural universal and a rich part of the human experience. However, little is known about common brain systems that support the processing and integration of extended, naturalistic 'real-world' music stimuli. We examined this question by presenting extended excerpts of symphonic music, and two pseudomusical stimuli in which the temporal and spectral structure of the Natural Music condition were disrupted, to non-musician participants undergoing functional brain imaging and analysing synchronized spatiotemporal activity patterns between listeners. We found that music synchronizes brain responses across listeners in bilateral auditory midbrain and thalamus, primary auditory and auditory association cortex, right-lateralized structures in frontal and parietal cortex, and motor planning regions of the brain. These effects were greater for natural music compared to the pseudo-musical control conditions. Remarkably, inter-subject synchronization in the inferior colliculus and medial geniculate nucleus was also greater for the natural music condition, indicating that synchronization at these early stages of auditory processing is not simply driven by spectro-temporal features of the stimulus. Increased synchronization during music listening was also evident in a right-hemisphere fronto-parietal attention network and bilateral cortical regions involved in motor planning. While these brain structures have previously been implicated in various aspects of musical processing, our results are the first to show that these regions track structural elements of a musical stimulus over extended time periods lasting minutes. Our results show that a hierarchical distributed network is synchronized between individuals during the processing of extended musical sequences, and provide new insight into the temporal integration of complex and biologically salient auditory sequences.	\N	\N
23580330	Schumacher et al. Psychological Science 12:101-108, (2001) demonstrated the elimination of most dual-task costs ("perfect time-sharing") after extensive dual-task practice of a visual and an auditory task in combination. For the present research, we used a transfer methodology to examine this practice effect in more detail, asking what task-processing stages were sped up by this dual-task practice. Such research will be essential to specify mechanisms associated with the practice-related elimination of dual-task costs. In three experiments, we introduced postpractice transfer probes focusing on the perception, central response-selection, and final motor-response stages. The results indicated that the major change achieved by dual-task practice was a speed-up in the central response-selection stages of both tasks. Additionally, perceptual-stage shortening of the auditory task was found to contribute to the improvements in time-sharing. For a better understanding of such time-sharing, we discuss the contributions of the present findings in relation to models of practiced dual-task performance.	\N	\N
23585888	To localize the neural generators of the musically elicited mismatch negativity with high temporal resolution we conducted a beamformer analysis (Synthetic Aperture Magnetometry, SAM) on magnetoencephalography (MEG) data from a previous musical mismatch study. The stimuli consisted of a six-tone melodic sequence comprising broken chords in C- and G-major. The musical sequence was presented within an oddball paradigm in which the last tone was lowered occasionally (20%) by a minor third. The beamforming analysis revealed significant right hemispheric neural activation in the superior temporal (STC), inferior frontal (IFC), superior frontal (SFC) and orbitofrontal (OFC) cortices within a time window of 100-200 ms after the occurrence of a deviant tone. IFC and SFC activation was also observed in the left hemisphere. The pronounced early right inferior frontal activation of the auditory mismatch negativity has not been shown in MEG studies so far. The activation in STC and IFC is consistent with earlier electroencephalography (EEG), optical imaging and functional magnetic resonance imaging (fMRI) studies that reveal the auditory and inferior frontal cortices as main generators of the auditory MMN. The observed right hemispheric IFC is also in line with some previous music studies showing similar activation patterns after harmonic syntactic violations. The results demonstrate that a deviant tone within a musical sequence recruits immediately a distributed neural network in frontal and prefrontal areas suggesting that top-down processes are involved when expectation violation occurs within well-known stimuli.	\N	\N
23586418	The neural dys-synchrony associated with auditory neuropathy spectrum disorder (ANSD) causes a temporal impairment that could degrade spatial hearing, particularly sound localization accuracy (SLA) and spatial release from masking (SRM). Unilateral cochlear implantation has become an accepted treatment for ANSD but treatment options for the contralateral ear remain controversial. We report spatial hearing measures in a child with ANSD before and after receiving a second cochlear implant (CI). An 11-year-7-month old boy with ANSD and expressive and receptive language delay received a second CI eight years after his first implant. The SLA and SRM were measured four months before sequential bilateral CIs (with the contralateral ear plugged and unplugged), and after nine months using both CIs. Testing done before the second CI, with the first CI alone, suggested that residual hearing in the contralateral ear contributed to sound localization accuracy, but not word recognition in quiet or noise. Nine-months after receiving a second CI, SLA improved by 12.76° and SRM increased to 3.8-4.2 dB relative to pre-operative performance. Results were compared to published outcomes for children with bilateral CIs. The addition of a second CI in this child with ANSD improved spatial hearing.	\N	\N
23587808	Whether visual subliminal processing involves semantic processing is still being debated. To examine this, we combined a passive electroencephalogram (EEG) study with an application of transcranial direct current stimulation (tDCS). In the masked-face priming paradigm, we presented a subliminal prime preceding the target stimulus. Participants were asked to determine whether the target face was a famous face, indicated by a button press. The prime and target pair were either the same person's face (congruent) or different person's faces (incongruent), and were always both famous or both non-famous faces. Experiments were performed over 2 days: 1 day for a real tDCS session and another for a sham session as a control condition. In the sham session, a priming effect, reflected in the difference in amplitude of the late positive component (250-500 ms to target onset), was observed only in the famous prime condition. According to a previous study, this effect might indicate a subliminal semantic process [10]. Alternatively, a priming effect toward famous primes disappeared after tDCS stimulation. Our results suggested that a subliminal process might not be limited to processes in the occipital and temporal areas, but may proceed to the semantic level processed in prefrontal cortex.	\N	\N
23616587	Congenital amusia is a lifelong disorder of music perception and production. The present study investigated the cerebral bases of impaired pitch perception and memory in congenital amusia using behavioural measures, magnetoencephalography and voxel-based morphometry. Congenital amusics and matched control subjects performed two melodic tasks (a melodic contour task and an easier transposition task); they had to indicate whether sequences of six tones (presented in pairs) were the same or different. Behavioural data indicated that in comparison with control participants, amusics' short-term memory was impaired for the melodic contour task, but not for the transposition task. The major finding was that pitch processing and short-term memory deficits can be traced down to amusics' early brain responses during encoding of the melodic information. Temporal and frontal generators of the N100m evoked by each note of the melody were abnormally recruited in the amusic brain. Dynamic causal modelling of the N100m further revealed decreased intrinsic connectivity in both auditory cortices, increased lateral connectivity between auditory cortices as well as a decreased right fronto-temporal backward connectivity in amusics relative to control subjects. Abnormal functioning of this fronto-temporal network was also shown during the retention interval and the retrieval of melodic information. In particular, induced gamma oscillations in right frontal areas were decreased in amusics during the retention interval. Using voxel-based morphometry, we confirmed morphological brain anomalies in terms of white and grey matter concentration in the right inferior frontal gyrus and the right superior temporal gyrus in the amusic brain. The convergence between functional and structural brain differences strengthens the hypothesis of abnormalities in the fronto-temporal pathway of the amusic brain. Our data provide first evidence of altered functioning of the auditory cortices during pitch perception and memory in congenital amusia. They further support the hypothesis that in neurodevelopmental disorders impacting high-level functions (here musical abilities), abnormalities in cerebral processing can be observed in early brain responses.	\N	\N
23621479	In some cochlear implant users, success is not achieved in spite of optimal clinical factors (including age at implantation, duration of rehabilitation and post-implant hearing level), which may be attributed to disorders at higher levels of the auditory pathway. We used cortical auditory evoked potentials to investigate the ability to perceive and discriminate auditory stimuli in 10 unsuccessful implant users aged 8-10 years (CI) and 10 healthy age-matched controls with normal hearing (NH). Pure tones (1 and 2 kHz) and double consonant-vowel syllables were applied. The stimuli were presented in an oddball paradigm that required the subjects to react consciously. The latencies and amplitudes of the P1, N1, P2, N2 and P3 waves were analyzed, in addition to reaction times and number of responses. Significant differences in the average response times and number of responses were observed between the CI and NH groups. The latencies also indicate that the CI group took longer to perceive and discriminate between tonal and speech auditory stimuli than the NH group.	\N	\N
23625644	In this study we provide evidence that unconscious priming can be obtained as a result of the processing of the salient region (SR) of illusory figures and without that of illusory contours (ICs). We used a metacontrast masking paradigm where illusory figures were masked by real figures. In Experiment 1 we found a clear priming effect when participants were asked to discriminate between square and diamond masks preceded by congruent or incongruent illusory square or diamond primes. It is likely that metacontrast impairs the processing of ICs but not of the SR; therefore the above result strongly suggests that the priming effect was specifically related to the processing of the SR. In Experiment 2 participants were tested in the same task as in Experiment 1 with additional primes in which the inducers were presented in the same locations but their shapes were changed so as to modify the global configuration. We termed these primes High, Low, and No Salient Region (HSR, LSR, and NSR, respectively). The HSR condition replicated Experiment 1, whereas in the LSR and NSR conditions the priming effect got progressively smaller. The results of Experiment 1 were replicated with the priming effect significantly larger in the HSR than in all other conditions. It was also larger in the HSR than in LSR condition and smallest but still present in the NSR condition. Taken together, these results indicate that the unconscious processing of only the SR yields a priming effect and that a reduction of the saliency of the SR leads to a reduction of the priming effect, while its elimination does not abolish it.	\N	\N
23627625	Fully auditory Brain-computer interfaces based on the dichotic listening task (DL-BCIs) are suited for users unable to do any muscular movement, which includes gazing, exploration or coordination of their eyes looking for inputs in form of feedback, stimulation or visual support. However, one of their disadvantages, in contrast with the visual BCIs, is their lower performance that makes them not adequate in applications that require a high accuracy. To overcome this disadvantage, we employed a Bayesian approach in which the DL-BCI was modeled as a Binary phase shift keying receiver for which the accuracy can be estimated a priori as a function of the signal-to-noise ratio. The results showed the measured accuracy to match the predefined target accuracy, thus validating this model that made possible to estimate in advance the classification accuracy on a trial-by-trial basis. This constitutes a novel methodology in the design of fully auditory DL-BCIs that let us first, define the target accuracy for a specific application and second, classify when the signal-to-noise ratio guarantees that target accuracy.	\N	\N
23633439	This study combines functional and structural magnetic resonance imaging to test the "asymmetric sampling in time" (AST) hypothesis, which makes assertions about the symmetrical and asymmetrical representation of speech in the primary and nonprimary auditory cortex. Twenty-three volunteers participated in this parametric clustered-sparse fMRI study. The availability of slowly changing acoustic cues in spoken sentences was systematically reduced over continuous segments with varying lengths (100, 150, 200, 250 ms) by utilizing local time-reversion. As predicted by the hypothesis, functional lateralization in Heschl's gyrus could not be observed. Lateralization in the planum temporale and posterior superior temporal gyrus shifted towards the right hemisphere with decreasing suprasegmental temporal integrity. Cortical thickness of the planum temporale was automatically measured. Participants with an L > R cortical thickness performed better on the in-scanner auditory pattern-matching task. Taken together, these findings support the AST hypothesis and provide substantial novel insight into the division of labor between left and right nonprimary auditory cortex functions during comprehension of spoken utterances. In addition, the present data yield support for a structural-behavioral relationship in the nonprimary auditory cortex.	\N	\N
23633643	The purpose of this study was to determine the effect of oral reading expressiveness on the comprehension of storybooks by 4- and 5-year-old prekindergarten children. The possible impact of prosody on listening comprehension was explored. Ninety-two prekindergarten children (M age = 57.26 months, SD = 3.89 months) listened to an expressive or inexpressive recording of 1 of 2 similar stories. Story comprehension was tested using assessments of both free recall and cued recall. Children showed statistically significantly better cued recall for the expressive readings of stories compared to the inexpressive readings of stories. This effect generalized across stories and when story length was controlled across both expressive and inexpressive versions. The effect of expressiveness on children's free recall was not significant. Highly expressive readings resulted in better comprehension of storybooks by prekindergarten children. Further, because recordings were used, this effect might be attributed to the facilitation of language processing rather than to enhanced social interaction between the reader and the child.	\N	\N
23645715	Even though language allows us to say exactly what we mean, we often use language to say things indirectly, in a way that depends on the specific communicative context. For example, we can use an apparently straightforward sentence like "It is hard to give a good presentation" to convey deeper meanings, like "Your talk was a mess!" One of the big puzzles in language science is how listeners work out what speakers really mean, which is a skill absolutely central to communication. However, most neuroimaging studies of language comprehension have focused on the arguably much simpler, context-independent process of understanding direct utterances. To examine the neural systems involved in getting at contextually constrained indirect meaning, we used functional magnetic resonance imaging as people listened to indirect replies in spoken dialog. Relative to direct control utterances, indirect replies engaged dorsomedial prefrontal cortex, right temporo-parietal junction and insula, as well as bilateral inferior frontal gyrus and right medial temporal gyrus. This suggests that listeners take the speaker's perspective on both cognitive (theory of mind) and affective (empathy-like) levels. In line with classic pragmatic theories, our results also indicate that currently popular "simulationist" accounts of language comprehension fail to explain how listeners understand the speaker's intended message.	\N	\N
23648960	Speech perception requires the effortless mapping from smooth, seemingly continuous changes in sound features into discrete perceptual units, a conversion exemplified in the phenomenon of categorical perception. Explaining how/when the human brain performs this acoustic-phonetic transformation remains an elusive problem in current models and theories of speech perception. In previous attempts to decipher the neural basis of speech perception, it is often unclear whether the alleged brain correlates reflect an underlying percept or merely changes in neural activity that covary with parameters of the stimulus. Here, we recorded neuroelectric activity generated at both cortical and subcortical levels of the auditory pathway elicited by a speech vowel continuum whose percept varied categorically from /u/ to /a/. This integrative approach allows us to characterize how various auditory structures code, transform, and ultimately render the perception of speech material as well as dissociate brain responses reflecting changes in stimulus acoustics from those that index true internalized percepts. We find that activity from the brainstem mirrors properties of the speech waveform with remarkable fidelity, reflecting progressive changes in speech acoustics but not the discrete phonetic classes reported behaviorally. In comparison, patterns of late cortical evoked activity contain information reflecting distinct perceptual categories and predict the abstract phonetic speech boundaries heard by listeners. Our findings demonstrate a critical transformation in neural speech representations between brainstem and early auditory cortex analogous to an acoustic-phonetic mapping necessary to generate categorical speech percepts. Analytic modeling demonstrates that a simple nonlinearity accounts for the transformation between early (subcortical) brain activity and subsequent cortical/behavioral responses to speech (>150-200 ms) thereby describing a plausible mechanism by which the brain achieves its acoustic-to-phonetic mapping. Results provide evidence that the neurophysiological underpinnings of categorical speech are present cortically by ~175 ms after sound enters the ear.	\N	\N
23651462	To develop and evaluate a 12-item version of the Speech, Spatial and Qualities of Hearing scale for use in clinical research and rehabilitation settings, and provide a formula for converting scores between the full (SSQ49) and abbreviated (SSQ12) versions. Items were selected independently at the three centres (Eriksholm Research Centre, MRC Institute of Hearing Research, University of New England) to be representative of the complete scale. A consensus was achieved after discussion. The data set (n = 1220) used for a factor analysis (Akeroyd et al, submitted) was re-analysed to compare original SSQ scores (SSQ49) with scores on the short version (SSQ12). A scatter-plot of SSQ12 scores against SSQ49 scores showed that SSQ12 score was about 0.6 of a scale point lower than the SSQ49 (0-10 scale) in the re-analysis of the Akeroyd et al data. SSQ12 scores lay on a slightly steeper slope than scores on the SSQ49. The SSQ12 provides similar results to SSQ49 in a large clinical research sample. The slightly lower average SSQ12 score and the slightly steeper slope reflect the composition of this short form relative to the SSQ49.	\N	\N
23652327	To compare speech understanding of the BAHA BP110 and BAHA Intenso sound processors. Prospective experimental study. Tertiary referral center. Twenty experienced user of osseointegrated auditory implants with conductive or mixed hearing loss. In a first session, half of the participants were fitted with an Intenso, the other half with a BP110. After 1 month of use, aided speech understanding in quiet and in noise was measured, and the other test processor was fitted. One month later, speech understanding with the second sound processor was assessed. Speech understanding in quiet and in noise, with noise arriving either from the front, the rear, or the side of the user with the osseointegrated bone conductor. Significant improvements were found for both processors for speech understanding in quiet (+9.6 to +34.8 percent points; p = 0.02 to 0.001) and in noise (+6.2 to +13.8 dB, p < 0.001). No significant differences were found between the 2 devices for speech in quiet. For noise from the rear, subjects were able to understand speech at signal-to-noise ratios which were lower (less favorable) by -5.1 dB (p < 0.001) when compared with the Intenso. Speech understanding is substantially improved by both devices, with no significant differences between the sound processors in quiet. In noise, speech understanding is significantly better with the BP110 when compared to the Intenso for noise from the rear.	\N	\N
23654396	Chen et al. [J. Acoust. Soc. Am. 131, 2987-2998 (2012)] evaluated the effectiveness of an algorithm for enhancing spectral changes over time in improving the intelligibility of speech in background sounds for hearing-impaired subjects. The processing improved intelligibility for speech in steady speech-spectrum noise (SSN) but tended to impair intelligibility in a background of two-talker speech (TTS). Large individual differences were found. The present study assessed whether the effectiveness of the algorithm was improved when the parameters that controlled the degree and type of enhancement were chosen individually for each subject, using a genetic algorithm based on subjective preferences for speech clarity. The parameter values selected by the genetic algorithm varied markedly across subjects. Speech intelligibility was measured for unprocessed stimuli and stimuli processed using the selected parameters, with SSN and TTS maskers and two signal-to-masker ratios (SMRs) for each subject. The intelligibility of speech in the SSN masker at the lower SMR was improved about 14 percentage points by the processing. The overall improvement produced by the processing was significantly larger than the improvement observed in the previous study when the parameter values were fixed across subjects, indicating that use of the genetic algorithm was beneficial.	\N	\N
23659894	Attentional problems are commonly reported as a feature of the behavioural profile in both Williams syndrome (WS) and Down's syndrome (DS). Recent studies have begun to investigate these impairments empirically, acknowledging the need for an approach that considers cross-syndrome comparisons and developmental changes across the different component functions of attention. The present study assessed children with WS and DS using a new preschool attention battery (ECAB: early childhood attention battery), designed to be suitable for mental age 3-6 years including groups with developmental disorders. The ECAB has the advantage of giving an individual profile of attentional abilities for each child, covering different components of attention. In relation to test norms for their mental age, both groups showed a profile of strengths and weaknesses in the attention domain. Both syndrome groups performed relatively well on tests of sustained attention and poorly on aspects of selective attention and attentional control (executive function). The DS group showed a specific strength in auditory sustained attention, whilst the WS group showed a particular deficit in visuo-spatial response control. There was also evidence for considerable differences in the developmental trajectory of these abilities across the two groups. The results provide evidence for syndrome-specific patterns of impairment, and distinct profiles of strengths and weaknesses that may be useful in understanding the nature of everyday attention difficulties in these groups and tailoring interventions to meet these needs.	\N	\N
23664833	Here, we applied a multi-feature mismatch negativity (MMN) paradigm in order to systematically investigate the neuronal representation of vowels and temporally manipulated CV syllables in a homogeneous sample of string players and non-musicians. Based on previous work indicating an increased sensitivity of the musicians' auditory system, we expected to find that musically trained subjects will elicit increased MMN amplitudes in response to temporal variations in CV syllables, namely voice-onset time (VOT) and duration. In addition, since different vowels are principally distinguished by means of frequency information and musicians are superior in extracting tonal (and thus frequency) information from an acoustic stream, we also expected to provide evidence for an increased auditory representation of vowels in the experts. In line with our hypothesis, we could show that musicians are not only advantaged in the pre-attentive encoding of temporal speech cues, but most notably also in processing vowels. Additional "just noticeable difference" measurements suggested that the musicians' perceptual advantage in encoding speech sounds was more likely driven by the generic constitutional properties of a highly trained auditory system, rather than by its specialisation for speech representations per se. These results shed light on the origin of the often reported advantage of musicians in processing a variety of speech sounds.	\N	\N
23683806	The present study aimed to investigate the vocal tract and glottal function during and after phonation into a tube and a stirring straw. A male classically trained singer was assessed. Computerized tomography (CT) was performed when the subject produced [a:] at comfortable speaking pitch, phonated into the resonance tube and when repeating [a:] after the exercise. Similar procedure was performed with a narrow straw after 15 minutes silence. Anatomic distances and area measures were obtained from CT midsagittal and transversal images. Acoustic, perceptual, electroglottographic (EGG), and subglottic pressure measures were also obtained. During and after phonation into the tube or straw, the velum closed the nasal passage better, the larynx position lowered, and hypopharynx area widened. Moreover, the ratio between the inlet of the lower pharynx and the outlet of the epilaryngeal tube became larger during and after tube/straw phonation. Acoustic results revealed a stronger spectral prominence in the singer/speaker's formant cluster region after exercising. Listening test demonstrated better voice quality after straw/tube than before. Contact quotient derived from EGG decreased during both tube and straw and remained lower after exercising. Subglottic pressure increased during straw and remained somewhat higher after it. CT and acoustic results indicated that vocal exercises with increased vocal tract impedance lead to increased vocal efficiency and economy. One of the major changes was the more prominent singer's/speaker's formant cluster. Vocal tract and glottal modifications were more prominent during and after straw exercising compared with tube phonation.	\N	\N
23684420	Bilateral cochlear implant (CI) users encounter difficulties in localizing sound sources in everyday environments, especially in the presence of background noise and reverberation. They tend to show large directional errors and front-back confusions compared to normal hearing (NH) subjects in the same conditions. In this study, the ability of bilateral CI users to use head movements to improve sound source localization was evaluated. Speech sentences of 0.5, 2, and 4.5 seconds were presented in noise to the listeners in conditions with and without head movements. The results show that for middle and long signal durations, the CI users could significantly reduce the number of front-back confusions. The angular accuracy, however, did not improve. Analysis of head trajectories showed that the CI users had great difficulties in moving their head towards the position of the source, whereas the NH listeners targeted the source loudspeaker correctly.	\N	\N
23686398	Morphology of the human brain predicts the speed at which individuals learn to distinguish novel foreign speech sounds after laboratory training. However, little is known about the neuroanatomical basis of individual differences in speech perception when a second language (L2) has been learned in natural environments for extended periods of time. In the present study, two samples of highly proficient bilinguals were selected according to their ability to distinguish between very similar L2 sounds, either isolated (prelexical) or within words (lexical). Structural MRI was acquired and processed to estimate vertex-wise indices of cortical thickness (CT) and surface area (CSA), and the association between cortical morphology and behavioral performance was inspected. Results revealed that performance in the lexical task was negatively associated with the thickness of the left temporal cortex and angular gyrus, as well as with the surface area of the left precuneus. Our findings, consistently with previous fMRI studies, demonstrate that morphology of the reported areas is relevant for word recognition based on phonological information. Further, we discuss the possibility that increased CT and CSA in sound-to-meaning mapping regions, found for poor non-native speech sounds perceivers, would have plastically arisen after extended periods of increased functional activity during L2 exposure.	\N	\N
23688330	A sequence of constant-frequency tones can promote streaming in a subsequent sequence of alternating-frequency tones, but why this effect occurs is not fully understood and its time course has not been investigated. Experiment 1 used a 2.0-s-long constant-frequency inducer (10 repetitions of a low-frequency pure tone) to promote segregation in a subsequent, 1.2-s test sequence of alternating low- and high-frequency tones. Replacing the final inducer tone with silence substantially reduced reported test-sequence segregation. This reduction did not occur when either the 4th or 7th inducer was replaced with silence. This suggests that a change at the induction/test-sequence boundary actively resets build-up, rather than less segregation occurring simply because fewer inducer tones were presented. Furthermore, Experiment 2 found that a constant-frequency inducer produced its maximum segregation-promoting effect after only three tones--this contrasts with the more gradual build-up typically observed for alternating-frequency sequences. Experiment 3 required listeners to judge continuously the grouping of 20-s test sequences. Constant-frequency inducers were considerably more effective at promoting segregation than alternating ones; this difference persisted for ∼10 s. In addition, resetting arising from a single deviant (longer tone) was associated only with constant-frequency inducers. Overall, the results suggest that constant-frequency inducers promote segregation by capturing one subset of test-sequence tones into an ongoing, preestablished stream, and that a deviant tone may reduce segregation by disrupting this capture. These findings offer new insight into the dynamics of stream segregation, and have implications for the neural basis of streaming and the role of attention in stream formation.	\N	\N
23689300	Evaluation of speech perception in noisy environments for normally hearing children was conducted in order to provide normal data for speech perception testing in children with hearing impairments thus improving early intervention alternatives for Mandarin-speaking children with hearing impairments. The speech perception abilities of 174 developmentally normal children ranging aged 2-5 years, in four age groups, were evaluated in environments that were quiet or with high levels of competing noise using the Mandarin pediatric speech intelligibility (MPSI) test. The mean score of MPSI between the four age groups showed notable statistical differences, including a variation in mean score between the four age groups, clearly indicating that the speech perception abilities of young children in noisy environments improved greatly with age, most notably between the ages of 3 and 4 years old. Speech perception ability in noisy environments was shown to be significantly, but weakly, related to age, implying the presence of other, possibly environment factors, in speech perception development. Furthermore, no statistically significant difference between boys and girls was noted in the experimental MPSI scores. The ability of children to increasingly perceive speech in environments containing high competing noise levels was shown to gradually and progressively increase with age. These results indicated that the developing Mandarin speech perception abilities in noisy environments in normal hearing children develops substantially after the age of 3-4 years, suggesting that similar age ranges may be even more critical intervention points for children with hearing impairments. More studies are still needed to confirm that.	\N	\N
23696279	The constituent elements and dynamics of the networks responsible for word production are a central issue to understanding human language. Of particular interest is their dependency on lexical category, particularly the possible segregation of nouns and verbs into separate processing streams. We applied a novel mixed-effects, multilevel analysis to electrocorticographic data collected from 19 patients (1942 electrodes) to examine the activity of broadly disseminated cortical networks during the retrieval of distinct lexical categories. This approach was designed to overcome the issues of sparse sampling and individual variability inherent to invasive electrophysiology. Both noun and verb generation evoked overlapping, yet distinct nonhierarchical processes favoring ventral and dorsal visual streams, respectively. Notable differences in activity patterns were noted in Broca's area and superior lateral temporo-occipital regions (verb > noun) and in parahippocampal and fusiform cortices (noun > verb). Comparisons with functional magnetic resonance imaging (fMRI) results yielded a strong correlation of blood oxygen level-dependent signal and gamma power and an independent estimate of group size needed for fMRI studies of cognition. Our findings imply parallel, lexical category-specific processes and reconcile discrepancies between lesional and functional imaging studies.	\N	\N
23700131	Recent research has reported that spatial modulation effects of audiotactile interactions tend to be limited to the space and body parts around the head. The present study investigated the generality of this finding by manipulating body parts stimulated and spatial relationships between the body parts and sounds. In Experiment 1, tactile stimuli were presented randomly to either left or right cheek, hand (palm or back) placed near the head, and knee while auditory stimuli were presented to either the same or opposite side from loudspeakers close to the head. Participants made speeded spatial discrimination responses regarding the side (left versus right) of the tactile stimulation. For any body part stimulated, the performance was worse when the auditory stimuli were presented from the opposite side rather than from the same side. Experiment 2 demonstrated that the spatial modulation effects for the palm or the back of the hand occurred irrespective of hand position (near or far from the head) and sound position (near or far from the head). The sounds delivered from near the head exerted a greater influence on tactile spatial discrimination performance as compared with the sound delivered from far from the head. Furthermore, the back of the hand was more influenced by the auditory stimuli than the palm when the hands were placed near the sounds. These results suggest that the spatial modulation effects of audiotactile interactions can occur beyond the space and body surface around the head.	\N	\N
23703134	To compare hearing performance relating to the peripheral and central auditory system between solvent-exposed and non-exposed workers. Forty-eight workers exposed to a mixture of solvents and 48 non-exposed control subjects of matched age, gender and educational level were selected to participate in the study. The evaluation procedures included: pure-tone audiometry (500 - 8,000 Hz), to investigate the peripheral auditory system; the Random Gap Detection test, to assess the central auditory system; and the Amsterdam Inventory for Auditory Disability and Handicap, to investigate subjects' self-reported hearing performance in daily-life activities. A Student t test and analyses of covariance (ANCOVA) were computed to determine possible significant differences between solvent-exposed and non-exposed subjects for the hearing level, Random Gap Detection test and Amsterdam Inventory for Auditory Disability and Handicap. Pearson correlations among the three measures were also calculated. Solvent-exposed subjects exhibited significantly poorer hearing thresholds for the right ear than non-exposed subjects. Also, solvent-exposed subjects exhibited poorer results for the Random Gap Detection test and self-reported poorer listening performance than non-exposed subjects. Results of the Amsterdam Inventory for Auditory Disability and Handicap were significantly correlated with the binaural average of subject pure-tone thresholds and Random Gap Detection test performance. Solvent exposure is associated with poorer hearing performance in daily life activities that relate to the function of the peripheral and central auditory system.	\N	\N
23705636	This article explores enhancing sincerity, honesty, or truthfulness in computer-generated synthetic speech by accompanying it with music. Sincerity is important if we are to respond positively to any voice, whether human or artificial. What is sincerity in the artificial disembodied voice? Studies in musical expression and performance may illuminate aspects of the 'musically spoken' or sung voice in rendering deeper levels of expression that may include sincerity. We consider one response to this notion in an especially composed melodrama (music accompanying a (synthetic) spoken voice) designed to convey sincerity.	\N	\N
23709064	Spatial ventriloquism refers to the phenomenon that a visual stimulus such as a flash can attract the perceived location of a spatially discordant but temporally synchronous sound. An analogous example of mutual attraction between audition and vision has been found in the temporal domain, where temporal aspects of a visual event, such as its onset, frequency, or duration, can be biased by a slightly asynchronous sound. In this review, we examine various manifestations of spatial and temporal attraction between the senses (both direct effects and aftereffects), and we discuss important constraints on the occurrence of these effects. Factors that potentially modulate ventriloquism-such as attention, synesthetic correspondence, and other cognitive factors-are described. We trace theories and models of spatial and temporal ventriloquism, from the traditional unity assumption and modality appropriateness hypothesis to more recent Bayesian and neural network approaches. Finally, we summarize recent evidence probing the underlying neural mechanisms of spatial and temporal ventriloquism.	\N	\N
23711533	Auditory cortices can be separated into dissociable processing pathways similar to those observed in the visual domain. Emotional stimuli elicit enhanced neural activation within sensory cortices when compared to neutral stimuli. This effect is particularly notable in the ventral visual stream. Little is known, however, about how emotion interacts with dorsal processing streams, and essentially nothing is known about the impact of emotion on auditory stimulus localization. In the current study, we used fMRI in concert with individualized auditory virtual environments to investigate the effect of emotion during an auditory stimulus localization task. Surprisingly, participants were significantly slower to localize emotional relative to neutral sounds. A separate localizer scan was performed to isolate neural regions sensitive to stimulus location independent of emotion. When applied to the main experimental task, a significant main effect of location, but not emotion, was found in this ROI. A whole-brain analysis of the data revealed that posterior-medial regions of auditory cortex were modulated by sound location; however, additional anterior-lateral areas of auditory cortex demonstrated enhanced neural activity to emotional compared to neutral stimuli. The latter region resembled areas described in dual pathway models of auditory processing as the 'what' processing stream, prompting a follow-up task to generate an identity-sensitive ROI (the 'what' pathway) independent of location and emotion. Within this region, significant main effects of location and emotion were identified, as well as a significant interaction. These results suggest that emotion modulates activity in the 'what,' but not the 'where,' auditory processing pathway.	\N	\N
23716219	The purpose of this study is to investigate the sufficient "similarity" between consecutive auditory events for the auditory system to define the fundamental period for pitch perception. It is possible to contaminate the periodicity of harmonic complex tones by scaling the impulse response in the time domain at every other cycle. Scale-alternating wavelet sequences (SAWS) in which two impulse responses with different scaling factors alternated were generated based on impulse responses obtained from Japanese vowels spoken by a male speaker. Preliminary listening to such signals indicated that the perceived pitch went down an octave relative to the original when the scaling factor exceeded a certain degree. In the first experiment, pitch matching was measured as a function of the scaling factor by the method of adjustment where the comparison stimuli were completely periodic with adjustable base periods. The pitch shift was discontinuous against the base period, chromatic continuum. In the second experiment, pitch matching was investigated with comparison stimuli whose odd harmonics were attenuated. This procedure provides a stimulus continuum where the pitch moved up an octave without changing its pitch chroma. The attenuation of the odd harmonics needed to match the SAWS varied systematically as a function of the degree of scaling. The relation between pitch matching and the peak height along the time interval axis of the stabilized auditory image is discussed.	\N	\N
23716244	This study investigated monaural envelope correlation perception (Richards 1987) for noise bandwidths ranging from 25 to 1,600 Hz. The high-frequency side of the low band was fixed at 3,000 Hz and the low-frequency side of the high band was fixed at 3,500 Hz. When comodulated, the magnitude spectra of the pair of noise bands were either identical or reflected around the midpoint. Six listeners with normal hearing participated. Listeners showed similar performance for identical and reflected-spectrum conditions, with best performance usually occurring for bandwidths between 200 and 800 Hz. Results were considered in terms of envelope comparisons of waveforms at the outputs of multiple peripheral filters or envelope comparisons of waveforms at the outputs of central filters set to the bandwidths of the noise stimuli. Some aspects of the results were incompatible with the account based on multiple peripheral filters. However, the results of a supplementary condition involving the gating of band subregions indicated that this incompatibility could be accounted for by nonoptimal weighting of peripheral filter outputs.	\N	\N
23716245	Envelope fluctuations of complex sounds carry information that is -essential for many types of discrimination and for detection in noise. To study the neural representation of envelope information and mechanisms for processing of this temporal aspect of sounds, it is useful to identify an animal model that can -sensitively detect amplitude modulations (AM). Low modulation frequencies, which dominate speech sounds, are of particular interest. Yet, most animal -models studied previously are relatively insensitive to AM at low modulation -frequencies. Rabbits have high thresholds for low-frequency modulations, -especially for tone carriers. Rhesus macaques are less sensitive than humans to low-frequency -modulations of wideband noise (O'Conner et al. Hear Res 277, 37-43, 2011). Rats and -chinchilla also have higher thresholds than humans for amplitude -modulations of noise (Kelly et al. J Comp Psychol 120, 98-105, 2006; Henderson et al. J Acoust Soc Am 75, -1177-1183, 1984). In contrast, the budgerigar has thresholds for AM detection of wideband noise similar to those of human listeners at low -modulation frequencies (Dooling and Searcy. Percept Psychophys 46, 65-71, 1981). A -one-interval, two-alternative operant conditioning procedure was used to estimate AM -detection thresholds for 4-kHz tone carriers at low modulation -frequencies (4-256 Hz). Budgerigar thresholds are comparable to those of human subjects in a comparable task. Implications of these comparative results for temporal coding of complex sounds are discussed. Comparative results for masked AM detection are also presented.	\N	\N
23716246	Compared to humans, Mongolian gerbils (Meriones unguiculatus) are much more sensitive at detecting mistuning of frequency components of a harmonic complex (Klinge and Klump. J Acoust Soc Am 128:280-290, 2010). One processing mechanism suggested to result in the high sensitivity involves evaluating the phase shift that gradually develops between the mistuned and the remaining components in the same or separate auditory filters. To investigate if this processing mechanism may explain the observed sensitivity, we determined the gerbils' thresholds to detect a constant phase shift in a component of a harmonic complex that is introduced without a frequency shift. The gerbils' detection thresholds for constant phase shifts were considerably lower for a high-frequency component (6,400 Hz) than for a low-frequency component (400 Hz) of a 200-Hz harmonic complex and increased with decreasing stimulus duration. Compared to the phase shifts calculated from the mistuning detection thresholds, the detection thresholds for constant phase shifts were similar to those for gradual phase shifts for the low-frequency harmonic but considerably lower for the high-frequency harmonic. A simulation of the processing of harmonic complexes by the gerbil's peripheral auditory filters when components are phase shifted shows waveform changes comparable to those assessed for mistuning detection Klinge and Klump (J Acoust Soc Am 128:280-290, 2010) and provides evidence that detection of the gradual phase shifts may underlie mistuning detection.	\N	\N
23716247	Detecting rare and surprising events is a useful strategy for sensory -systems. In the human auditory system, deviance detection is indexed by an important component of the auditory event-related potentials, the mismatch negativity (MMN). Responses of single neurons in the inferior colliculus, medial geniculate body, and auditory cortex of mammals (cats, rats, and mice) show responses that share some properties with MMN: they are evoked by rare events, are preattentive (in as much as they occur in anesthetized animals), and, at least at the level of primary auditory cortex, cannot be accounted for by simple fatigue of the incoming sensory information. Here we extend these results to deviations beyond tone frequency. Recording in rat primary auditory cortex and using oddball sequences consisting of two frozen tokens of broadband noise samples, we found differences between the responses to the same token when used as the common and when used as the deviant, showing an exquisite sensitivity to the small differences between two spectro-temporally similar sounds. Similarly, differential adaptation can be demonstrated when using two word-like stimuli that have been derived from human speech but adapted to the rat auditory system. Thus, differential adaptation to common and rare sounds is present also with sounds whose complexity mirrors that of natural environments.	\N	\N
23716255	Many previous studies have shown that a tone that is momentarily -interrupted can be perceived as continuous if the interruption is completely masked by noise. It has been suggested this "continuity illusion" occurs only when peripheral neural responses contain no evidence that the signal was interrupted. In this study, we used a combination of psychophysical measures and computational simulations of peripheral auditory responses to examine whether the continuity illusion can be experienced under conditions where peripheral neural responses contain evidence that the signal did not continue through the masker. Our results provide an example of a salient continuity illusion despite evidence of an interruption in the peripheral representation, indicating that the illusion may depend more on global features of the interrupting sound, such as its long-term specific loudness, than on its fine-grained temporal structure.	\N	\N
23717403	The present study of KCNQ4 mutations was carried out to 1) determine the prevalence by unbiased population-based genetic screening, 2) clarify the mutation spectrum and genotype/phenotype correlations, and 3) summarize clinical characteristics. In addition, a review of the reported mutations was performed for better understanding of this deafness gene. The screening using 287 probands from unbiased Japanese autosomal dominant nonsyndromic hearing loss (ADNSHL) families identified 19 families with 7 different disease causing mutations, indicating that the frequency is 6.62% (19/287). While the majority were private mutations, one particular recurrent mutation, c.211delC, was observed in 13 unrelated families. Haplotype analysis in the vicinity of c.211delC suggests existence of a common ancestor. The majority of the patients showed all frequency, but high-frequency predominant, sensorineural hearing loss. The present study adds a new typical audiogram configuration characterized by mid-frequency predominant hearing loss caused by the p.V230E mutation. A variant at the N-terminal site (c. 211delC) showed typical ski-slope type audiogram configuration. Concerning clinical features, onset age was from 3 to 40 years old, and mostly in the teens, and hearing loss was gradually progressive. Progressive nature is a common feature of patients with KCNQ4 mutations regardless of the mutation type. In conclusion, KCNQ4 mutations are frequent among ADNSHL patients, and therefore screening of the gene and molecular confirmation of these mutations have become important in the diagnosis of these conditions.	\N	\N
23727883	Visual motion aftereffects can occur contingent on arbitrary sounds. Two circles, placed side by side, were alternately presented, and the onsets were accompanied by tone bursts of high and low frequencies, respectively. After a few minutes of exposure to the visual apparent motion with the tones, a circle blinking at a fixed location was perceived as a lateral motion in the same direction as the previously exposed apparent motion (Teramoto et al. in PLoS One 5:e12255, 2010). In the present study, we attempted to reverse this contingency (pitch aftereffects contingent on visual information). Results showed that after prolonged exposure to the audio-visual stimuli, the apparent visual motion systematically affected the perceived pitch of the auditory stimuli. When the leftward apparent visual motion was paired with the high-low-frequency sequence during the adaptation phase, a test tone sequence was more frequently perceived as a high-low-pitch sequence when the leftward apparent visual motion was presented and vice versa. Furthermore, the effect was specific for the exposed visual field and did not transfer to the other side, thus ruling out an explanation in terms of simple response bias. These results suggest that new audiovisual associations can be established within a short time, and visual information processing and auditory processing can mutually influence each other.	\N	\N
23740184	Age-related hearing loss (presbyacusis) has a complex etiology. Results from animal models detailing the effects of specific cochlear injuries on audiometric profiles may be used to understand the mechanisms underlying hearing loss in older humans and predict cochlear pathologies associated with certain audiometric configurations ("audiometric phenotypes"). Patterns of hearing loss associated with cochlear pathology in animal models were used to define schematic boundaries of human audiograms. Pathologies included evidence for metabolic, sensory, and a mixed metabolic + sensory phenotype; an older normal phenotype without threshold elevation was also defined. Audiograms from a large sample of older adults were then searched by a human expert for "exemplars" (best examples) of these phenotypes, without knowledge of the human subject demographic information. Mean thresholds and slopes of higher frequency thresholds of the audiograms assigned to the four phenotypes were consistent with the predefined schematic boundaries and differed significantly from each other. Significant differences in age, gender, and noise exposure history provided external validity for the four phenotypes. Three supervised machine learning classifiers were then used to assess reliability of the exemplar training set to estimate the probability that newly obtained audiograms exhibited one of the four phenotypes. These procedures classified the exemplars with a high degree of accuracy; classifications of the remaining cases were consistent with the exemplars with respect to average thresholds and demographic information. These results suggest that animal models of age-related hearing loss can be used to predict human cochlear pathology by classifying audiograms into phenotypic classifications that reflect probable etiologies for hearing loss in older humans.	\N	\N
23741046	Many manual tasks involve object manipulation and are achieved by an evolving series of actions, or action phases, recruited to achieve task subgoals. The ability to effectively link action phases is an important component of manual dexterity. However, our understanding of how the effective linking of sequential action phases develops with skill learning is limited. Here, we addressed this issue using a task in which participants applied forces to a handle to move a cursor on a computer screen to successively acquire visual targets. Target acquisition required actively holding the cursor within the target zone (hold phase) for a required duration before moving to the next target (transport phase). If the transport phase was initiated prematurely, before the end of the required hold duration, participants had to return to the target to acquire it. The goal was to acquire targets as quickly as possible. Distinct visual and auditory sensory events marked goal completion of each action phase. During initial task performance, the transport phase was reactively triggered by sensory events signaling hold phase completion. However, with practice, participants learned to initiate the transport phase based on a prediction of the time of hold phase completion. Simulations revealed that participants learned to near-optimally compensate for temporal uncertainty, presumably related to estimation of time intervals and execution of motor commands, so as to reduce the average latency between the end of the required hold phase duration and the start of the transport phase, while avoiding an excess of premature exits.	\N	\N
23742366	Estimates of human basilar membrane gain and compression obtained using temporal masking curve (TMC) and additivity of forward masking (AFM) methods with long-duration maskers or long masker-signal silent intervals may be affected by olivocochlear efferent activation, which reduces basilar membrane gain. The present study introduces a fixed-duration masking curve (FDMC) method, which involves a comparison of off- and on-frequency forward masker levels at threshold as a function of masker and signal duration, with the total masker-signal duration fixed at 25 ms to minimize efferent effects. Gain and compression estimates from the FDMC technique were compared with those from TMC (104-ms maskers) and AFM (10- and 200-ms maskers) methods. Compression estimates over an input-masker range of 40-60 dB sound pressure level were similar for the four methods. Maximum compression occurred at a lower input level for the FDMC compared to the TMC method. Estimates of gain were similar for TMC and FDMC methods. The FDMC method may provide a more reliable estimate of BM gain and compression in the absence of efferent activation and could be a useful method for estimating effects of efferent activity when used with a precursor sound (to trigger efferent activation), presented prior to the combined masker-signal stimulus.	\N	\N
23742368	Masking functions and fixed-signal functions were constructed using a narrow range of pedestal intensities for 10-ms, 1000-Hz gated tones. Data from three experiments agreed with previously reported data, clearly demonstrating negative masking and the pedestal effect. The data extend earlier findings by showing (1) the resilience of the pedestal effect when a background noise masker is introduced; (2) a possible indifference of the fixed-signal function to stimulus duration; (3) the ability of a set of psychometric functions to produce both masking and fixed-signal functions; (4) depending on method, the impact of unit choice on the interpretation of both the pedestal effect and negative masking data. Results are discussed in relation to current psychophysical models, and suggest that accounting for the auditory system's sensitivity to differences in low-level sounds remains a challenge.	\N	\N
23745759	This study investigates the influence of stress grouping on verbal short-term memory (STM). English speakers show a preference to combine syllables into trochaic groups, both lexically and in continuous speech. In two serial recall experiments, auditory lists of nonsense syllables were presented with either trochaic (STRONG-weak) or iambic (weak-STRONG) stress patterns, or in monotone. The acoustic correlates that carry stress were also manipulated in order to examine the relationship between input and output processes during recall. In Experiment 1, stressed and unstressed syllables differed in intensity and pitch but were matched for spoken duration. Significantly more syllables were recalled in the trochaic stress pattern condition than in the iambic and monotone conditions, which did not differ. In Experiment 2, spoken duration and pitch were manipulated but intensity was held constant. No effects of stress grouping were observed, suggesting that intensity is a critical acoustic factor for trochaic grouping. Acoustic analyses demonstrated that speech output was not identical to the auditory input, but that participants generated correct stress patterns by manipulating acoustic correlates in the same way in both experiments. These data challenge the idea of a language-independent STM store and support the notion of separable phonological input and output processes.	\N	\N
23751011	Cognitive theories on consciousness propose a strong link between consciousness and working memory (WM). This link is also present at the neural level: Both consciousness and WM have been implicated in a prefrontal parietal network. However, the link remains empirically unexplored. The present study investigates the relation between consciousness and WM by studying the impact of WM load on one aspect of consciousness, the threshold for subjective visibility. At the same time, we investigated how WM affects cognitive control, a function that has been implicated to consciousness. Results showed an increase in the threshold of subjective visibility when WM load increased. Furthermore, the impact of a prime stimulus on the response to the target was also modulated by WM load. We propose that the observed interference is caused by the functional and neural overlap of these functions.	\N	\N
23751171	The extent of visual perceptual processing that occurs in the absence of awareness is as yet unclear. Here we examined event-related-potential (ERP) indices of visual and cognitive processes as awareness was manipulated through object-substitution masking (OSM), an awareness-disrupting effect that has been hypothesized to result from the disruption of reentrant signaling to low-level visual cortical areas. In OSM, a visual stimulus array is briefly presented that includes a parafoveal visual target denoted by a cue, typically consisting of several surrounding dots. When the offset of the target-surrounding cue dots is delayed relative to the rest of the array, a striking reduction in the perception of the target image surrounded by the dots is observed. Using faces and houses as the target stimuli, we found that successful OSM reduced or eliminated all the measured electrophysiological indices of visual processing stages after 130ms post-stimulus. More specifically, when targets were missed within the masked condition (i.e., on trials with effective OSM that disrupted awareness), we observed fully intact early feed-forward processing up through the visual extrastriate P1 ERP component peaking at 100ms, followed by reduced low-level activity over the occipital pole 130-170ms post-stimulus, reduced ERP indices of lateralized shifts of attention toward the parafoveal target, reduced object-generic visual processing, abolished object-category-specific (face-specific) processing, and reduced late visual short-term-memory processing activity. The results provide a comprehensive electrophysiological account of the neurocognitive underpinnings of effective OSM of visual-object images, including evidence for central roles of early reentrant signal disruption and insufficient visual attentional deployment.	\N	\N
23757308	Most people cannot name the musical note that corresponds to a particular pitch without being provided a reference note, but those people with absolute pitch (AP) can do this accurately. Early experience during a developmental period is often thought to convey identity and stability of the note categories in people with AP, but the plasticity of these categories has not been investigated. Here we provide the first evidence that the note categories of adults with AP can change with listening experience. Participants with AP showed shifts in perception in direct accord with prior exposure to music detuned by a fraction of a semitone. This suggests that the apparent stability of AP categories is conferred not by early experience but rather by the cultural norms adopted for tuning music.	\N	\N
23758506	Levitin's findings that nonmusicians could produce from memory the absolute pitches of self-selected pop songs have been widely cited in the music psychology literature. These findings suggest that latent absolute pitch (AP) memory may be a more widespread trait within the population than traditional AP labelling ability. However, it has been left unclear what factors may facilitate absolute pitch retention for familiar pieces of music. The aim of the present paper was to investigate factors that may contribute to latent AP memory using Levitin's sung production paradigm for AP memory and comparing results to the outcomes of a pitch labelling task, a relative pitch memory test, measures of music-induced emotions, and various measures of participants' musical backgrounds. Our results suggest that relative pitch memory and the quality and degree of music-elicited emotions impact on latent AP memory.	\N	\N
23774001	Auditory alarm misperception is one of the critical events that lead aircraft pilots to an erroneous flying decision. The rarity of these alarms associated with their possible unreliability may play a role in this misperception. In order to investigate this hypothesis, we manipulated both audiovisual conflict and sound rarity in a simplified landing task. Behavioral data and event related potentials (ERPs) of thirteen healthy participants were analyzed. We found that the presentation of a rare auditory signal (i.e., an alarm), incongruent with visual information, led to a smaller amplitude of the auditory N100 (i.e., less negative) compared to the condition in which both signals were congruent. Moreover, the incongruity between the visual information and the rare sound did not significantly affect reaction times, suggesting that the rare sound was neglected. We propose that the lower N100 amplitude reflects an early visual-to-auditory gating that depends on the rarity of the sound. In complex aircraft environments, this early effect might be partly responsible for auditory alarm insensitivity. Our results provide a new basis for future aeronautic studies and the development of countermeasures.	\N	\N
23776244	Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.	\N	\N
23778471	The audibility thresholds for the sound frequency of 137 upward- and downward-sloping audiograms showing sensorineural hearing loss were selected and analyzed in conjunction with speech recognition thresholds obtained from individuals seen at a public otolaryngology clinic to determine which frequencies in slope audiograms best represent speech recognition thresholds. The linear regression model and mean square error were used to determine the associations between the threshold values. The mean square error identified larger errors when using thresholds of 500, 1000, and 2000 Hz than when using audibility thresholds of 500, 1000, 2000, and 4000 Hz. The linear regression model showed a higher correlation (91%) between the audiogram thresholds for frequencies of 500, 1000, 2000, and 4000 Hz than for the frequencies of 500, 1000, and 2000 Hz (88%). Frequencies of 500, 1000, 2000, and 4000 Hz were the most significant in predicting the speech recognition threshold.	\N	\N
23784072	Several sources of evidence point toward a link between asymmetry of prefrontal brain activity and approach-withdrawal tendencies. Here, we tested the causal nature of this link and examined if the categorization of an ambiguous approach- or withdrawal-related vocal signal can be biased by manipulating left and right frontal neural activity. We used voice morphing of affective non-verbal vocalizations to create individually tailored affectively ambiguous stimuli on an Anger-Fear continuum-two emotions that represent extremes on the approach-withdrawal dimension. We tested perception of these stimuli after 10 min of low-frequency repetitive transcranial magnetic stimulation over left or right dorsolateral prefrontal cortex or over the vertex (control), a technique that has transient inhibitory effects on the targeted brain region. As expected, ambiguous stimuli were more likely perceived as expressing Anger (approach) than Fear (withdrawal) after right prefrontal compared with left prefrontal or control stimulation. These results provide the first evidence that the manipulation of asymmetrical activity in prefrontal cortex can change the explicit categorization of ambiguous emotional signals.	\N	\N
23785181	To evaluate child-adult differences for consonant identification in a noise or a 2-talker masker. Error patterns were compared across age and masker type to test the hypothesis that errors with the noise masker reflect limitations in the peripheral encoding of speech, whereas errors with the 2-talker masker reflect target-masker confusions within the central auditory system. A repeated-measures design compared the performance of children (5-13 years) and adults in continuous speech-shaped noise or a 2-talker masker. Consonants were identified from a closed set of 12 using a picture-pointing response. In speech-shaped noise, children under age 10 years performed more poorly than adults, but performance was adultlike for 11- to 13-year-olds. In the 2-talker masker, significant child-adult differences were observed in even the oldest group of children. Systematic clusters of consonant errors were observed for children in the noise masker and for adults in both maskers, but not for children in the 2-talker masker. These results suggest a more prolonged time course of development for consonant identification in a 2-talker masker than in a noise masker. Differences in error patterns between the maskers support the hypothesis that errors with the 2-talker masker reflect failures of sound segregation.	\N	\N
23785182	In this study, the authors assessed the influence of masking level (29% or 71% sentence perception) and test modality on the processing load during language perception as reflected by the pupil response. In addition, the authors administered a delayed cued stimulus recall test to examine whether processing load affected the encoding of the stimuli in memory. Participants performed speech and text reception threshold tests, during which the pupil response was measured. In the cued recall test, the first half of correctly perceived sentences was presented, and participants were asked to complete the sentences. Reading and listening span tests of working memory capacity were presented as well. Regardless of test modality, the pupil response indicated higher processing load in the 29% condition than in the 71% correct condition. Cued recall was better for the 29% condition. The consistent effect of masking level on the pupil response during listening and reading support the validity of the pupil response as a measure of processing load during language perception. The absent relation between pupil response and cued recall may suggest that cued recall is not directly related to processing load, as reflected by the pupil response.	\N	\N
23786392	Exposure to loud noise can impair cochlear microcirculation and cause noise-induced hearing loss (NIHL). TNF-α signaling has been shown to be activated in NIHL and to control spiral modiolar artery vasoconstriction that regulates cochlear microcirculation. It was the aim of this experimental study to analyse the effects of the TNF-α inhibitor etanercept on cochlear microcirculation and hearing threshold shift in NIHL in vivo. After assessment of normacusis using ABR, loud noise (106 dB SPL, 30 minutes) was applied on both ears in guinea pigs. Etanercept was administered systemically after loud noise exposure while control animals received a saline solution. In vivo fluorescence microscopy of strial capillaries was performed after surgical exposure of the cochlea for microcirculatory analysis. ABR measurements were derived from the contralateral ear. Guinea pigs (n = 6, per group). Compared to controls, cochlear blood flow in strial capillary segments was significantly increased in etanercept-treated animals. Additionally, hearing threshold was preserved in animals receiving the TNF-α inhibitor in contrast to a significant threshold raising in controls. TNF-α inhibition using etanercept improves cochlear microcirculation and protects hearing levels after loud noise exposure and appears as a promising treatment strategy for human NIHL.	\N	\N
23786395	This study investigates the relation between diagnosis of dead regions based on the off-frequency psychophysical tuning curve (PTC) tip and the frequency and level of the probe tone. A previously developed functional model of auditory processing was used to simulate the complete loss of inner hair cells (IHC), dysfunction of outer hair cells (OHC), complete loss of IHCs in combination with OHC dysfunction, and IHC insensitivity. The model predictions were verified through comparison with experimental data. This study compares PTC data of five normal-hearing listeners and six hearing-impaired listeners with model-simulated PTC data. It was shown that OHC activity and IHC insensitivity may significantly alter the shift of PTC tips with increasing probe level. Model results suggest that OHC activity and IHC insensitivity can change the outcome of dead region diagnosis using PTCs. Supplementary to PTC dead region diagnostic information, model results may provide additional information regarding the edge frequency of a dead region and OHC function.	\N	\N
23789623	Pickering & Garrod's (P&G's) integrated model of production and comprehension includes no explicit role for nonlinguistic cognitive processes. Yet, how domain-general cognitive functions contribute to language processing has become clearer with well-specified theories and supporting data. We therefore believe that their account can benefit by incorporating functions like working memory and cognitive control into a unified model of language processing.	\N	\N
23789938	Pickering & Garrod (P&G) consider the possibility that inner speech might be a product of forward production models. Here I consider the idea of inner speech as a forward model in light of empirical work from the past few decades, concluding that, while forward models could contribute to it, inner speech nonetheless requires activity from the implementers.	\N	\N
23790092	The purpose of this study was to evaluate the effect of lengthening of voice onset time and burst duration of selected speech stimuli on perception by individuals with auditory dys-synchrony. This is the second of a series of articles reporting the effect of signal enhancing strategies on speech perception by such individuals. Two experiments were conducted: (1) assessment of the 'just-noticeable difference' for voice onset time and burst duration of speech sounds; and (2) assessment of speech identification scores when speech sounds were modified by lengthening the voice onset time and the burst duration in units of one just-noticeable difference, both in isolation and in combination with each other plus transition duration modification. Lengthening of voice onset time as well as burst duration improved perception of voicing. However, the effect of voice onset time modification was greater than that of burst duration modification. Although combined lengthening of voice onset time, burst duration and transition duration resulted in improved speech perception, the improvement was less than that due to lengthening of transition duration alone. These results suggest that innovative speech processing strategies that enhance temporal cues may benefit individuals with auditory dys-synchrony.	\N	\N
23790958	To determine the prevalence of otitis media with effusion (OME) in children with Down syndrome (DS), and the associated to hearing loss at the age of 8 years. A national population based clinical study of all children with DS born in Norway in 2002. OME was found in 20 out of 52 (38%) children. Those with OME had a significant lower hearing level with a mean pure tone average (PTA) of 33.4 dB HL compared to children with no OME whose mean PTA was 21.7 dB HL (p < 0.0001). Verified hearing loss above 25 dB HL in the better hearing ear was found in 12 out of the 20 with OME, compared to 5 out 31 without OME. The findings of this present study uncover the increased risk of OME in eight year old children with DS as current otitis media was found in one of three. This reduced hearing ability in children with DS due to OME at age of 8 strongly emphasizes the need for optimal treatment and follow up to optimize hearing rehabilitation. The findings are further supported by the population based study design, the focus on the narrow age band and the high response rate.	\N	\N
23801322	When a deviant (oddball) stimulus is presented within a series of otherwise identical (standard) stimuli, the duration of the oddball tends to be overestimated. Two experiments investigated factors affecting systematic distortions in the perceived duration of oddball stimuli. Both experiments used an auditory oddball paradigm where oddball tones varied in both their pitch distance from the pitch of a standard tone and their likelihood of occurrence. Experiment 1 revealed that (1) far-pitch oddballs were perceived to be longer than near-pitch oddballs, (2) effects of pitch distance were greater in low-likelihood conditions, and (3) oddballs in later serial positions were perceived to be longer than oddballs in earlier serial positions. The above effects held regardless of whether oddballs were higher or lower in pitch than the standard. Experiment 2 revealed a pattern of response times in an oddball detection task that generally paralleled the pattern of data observed in Experiment 1; across conditions, there was a negative correlation between detection times and perceived duration. Taken together, the results suggest that the observed effects of oddball pitch, likelihood, and position on perceived duration are at least partly driven by how quickly individuals are able to initiate timing the oddball following its onset. Implications for different theoretical accounts of the oddball effect are discussed.	\N	\N
23817922	For this research, we used a dual-task approach to investigate the involvement of working memory in following written instructions. In two experiments, participants read instructions to perform a series of actions on objects and then recalled the instructions either by spoken repetition or performance of the action sequence. Participants engaged in concurrent articulatory suppression, backward-counting, and spatial-tapping tasks during the presentation of the instructions, in order to disrupt the phonological-loop, central-executive, and visuospatial-sketchpad components of working memory, respectively. Recall accuracy was substantially disrupted by all three concurrent tasks, indicating that encoding and retaining verbal instructions depends on multiple components of working memory. The accuracy of recalling the instructions was greater when the actions were performed than when the instructions were repeated, and this advantage was unaffected by the concurrent tasks, suggesting that the benefit of enactment over oral repetition does not cost additional working memory resources.	\N	\N
23831479	Mismatch negativity (MMN) is a promising window on how the functional integrity of auditory sensory memory and change discrimination is modulated by age and relevant clinical conditions. However, the effects of aging on MMN have remained somewhat elusive, particularly at short interstimulus intervals (ISIs). We performed a meta-analysis of peer-reviewed MMN studies that had targeted both young and elderly adults to estimate the mean effect size. Nine studies, consisting of 29 individual investigations, were included and the final total study population consisted of 182 young and 165 elderly subjects. The effects of different deviant types and duration of ISIs on the effect size were assessed. The overall mean effect size was 0.63 (95% CI at 0.43-0.82). The effect sizes for long ISI (>2s, effect size 0.68, 95% CI at 0.31-1.06) and short ISI (<2s, effect size 0.61, 95% CI at 0.39-0.84) were both considered moderate. A further analysis showed a prominent aging-related decrease in MMN responses to duration and frequency changes at short ISIs. It was also interesting to note that the effect size was about 25% larger for duration deviant condition compared to the frequency deviant condition. In conclusion, a reduced MMN response to duration and frequency deviants is a robust feature among the aged adults, which suggests that there has been a decline in the functional integrity of central auditory processing in this population.	\N	\N
23842602	The aim of this study was to investigate the influence of impulse noise on age-related hearing loss. The study consisted of two groups. Each group contained 109 men. Group I comprised veterans with normal hearing at the end of 1979 sino-vietnamese war. All these veterans were randomly selected from Guangzhou Military Command. Group II were men with no military experience randomly chosen from the health examination center of Guangzhou General Hospital of Guangzhou Military Command. Pure-tone thresholds of these two groups were measured and compared. The pure-tone thresholds of Group I were poorer than those of Group II at the frequencies of 4, 6 and 8 kHz. Thus, impulse noise accelerates age-related hearing loss.	\N	\N
23855495	Recent evidence suggests that humans can become fearful after exposure to olfactory fear signals, yet these studies have reported the effects of fear chemosignals without examining emotion-relevant input from traditional communication modalities (i.e., vision, audition). The question that we pursued here was therefore: How significant is an olfactory fear signal in the broader context of audiovisual input that either confirms or contradicts olfactory information? To test this, we manipulated olfactory (fear, no fear) and audiovisual (fear, no fear) information and demonstrated that olfactory fear signals were as potent as audiovisual fear signals in eliciting a fearful facial expression. Irrespective of confirmatory or contradictory audiovisual information, olfactory fear signals produced by senders induced fear in receivers outside of conscious access. These findings run counter to traditional views that emotions are communicated exclusively via visual and linguistic channels.	\N	\N
23864263	Similarities have been observed in the localization of the final position of moving visual and moving auditory stimuli: Perceived endpoints that are judged to be farther in the direction of motion in both modalities likely reflect extrapolation of the trajectory, mediated by predictive mechanisms at higher cognitive levels. However, actual comparisons of the magnitudes of displacement between visual tasks and auditory tasks using the same experimental setup are rare. As such, the purpose of the present free-field study was to investigate the influences of the spatial location of motion offset, stimulus velocity, and motion direction on the localization of the final positions of moving auditory stimuli (Experiment 1 and 2) and moving visual stimuli (Experiment 3). To assess whether auditory performance is affected by dynamically changing binaural cues that are used for the localization of moving auditory stimuli (interaural time differences for low-frequency sounds and interaural intensity differences for high-frequency sounds), two distinct noise bands were employed in Experiments 1 and 2. In all three experiments, less precise encoding of spatial coordinates in paralateral space resulted in larger forward displacements, but this effect was drowned out by the underestimation of target eccentricity in the extreme periphery. Furthermore, our results revealed clear differences between visual and auditory tasks. Displacements in the visual task were dependent on velocity and the spatial location of the final position, but an additional influence of motion direction was observed in the auditory tasks. Together, these findings indicate that the modality-specific processing of motion parameters affects the extrapolation of the trajectory.	\N	\N
23866207	Although much research has been done to study the working memory structure in children in their first school years, the relation of cognitive constructs involved in this process remains uncertain. In particular, it is unclear whether working memory is a domain general construct that coordinates separate codes of verbal and visuospatial storage or whether it is a domain-specific construct with distinct resources of verbal and visuospatial information. This paper investigates the structure of working memory, by using the Working Memory Test Battery for Children (WMTB-C) and by doing confirmatory factor analyses (CFAs) on a sample of Portuguese children (n = 103) between 8 and 9 years of age. The results of the confirmatory factor analyses that provide the best fit of the data correspond to the model that includes Central Executive and Visuospatial Sketchpad in the same factor, co-varying with a Phonological Loop factor. Moreover, the traditional working memory tripartite structure--based on the Baddeley and Hitch Model--revealed good fit to the data.	\N	\N
23871868	Accounts of the functional role of the frontal cortex in pre-attentive auditory change detection include attention switching, response inhibition, contrast enhancement, and activation of a predictive model. These accounts assume different sequential activation patterns between the temporal and frontal cortices: Change detection in the auditory areas of the superior temporal cortex (STC) followed by inferior frontal cortex (IFC) activation for attention switching and response inhibition; STC preceded by IFC activation for contrast enhancement; and an IFC-STC-IFC activation sequence for the predictive model. We used the event-related optical signal (EROS), which provides a temporal resolution of milliseconds and a spatial resolution of 5 to 10mm, combined with lagged correlation path modeling to examine the response of the right frontal and temporal cortices to auditory duration deviants of varying magnitude. Event-related potentials (ERPs) were also recorded, as was the slow optical (hemodynamic) brain response. The data analyses revealed temporal-frontal, frontal-temporal-frontal, and temporal-frontal activation patterns when the deviants represented relatively large, medium, and small changes from the standard stimulus, respectively. These results indicate that the degree of deviance modulates spatio-temporal dynamics within the STC-IFC auditory change detection network.	\N	\N
23874705	Besides the influence of dopaminergic neurotransmission on negative symptoms in schizophrenia, there is evidence that alterations of serotonin (5-HT) system functioning also play a crucial role in the pathophysiology of these disabling symptoms. From post mortem and genetic studies on patients with negative symptoms a 5-HT dysfunction is documented. In addition atypical neuroleptics and some antidepressants improve negative symptoms via serotonergic action. So far no research has been done to directly clarify the association between the serotonergic functioning and the extent of negative symptoms. Therefore, we examined the status of brain 5-HT level in negative symptoms in schizophrenia by means of the loudness dependence of auditory evoked potentials (LDAEP). The LDAEP provides a well established and non-invasive in vivo marker of the central 5-HT activity. We investigated 13 patients with schizophrenia with predominant negative symptoms treated with atypical neuroleptics and 13 healthy age and gender matched controls with a 32-channel EEG. The LDAEP of the N1/P2 component was evaluated by dipole source analysis and single electrode estimation at Cz. Psychopathological parameters, nicotine use and medication were assessed to control for additional influencing factors. Schizophrenic patients showed significantly higher LDAEP in both hemispheres than controls. Furthermore, the LDAEP in the right hemisphere in patients was related to higher scores in scales assessing negative symptoms. A relationship with positive symptoms was not found. These data might suggest a diminished central serotonergic neurotransmission in patients with predominant negative symptoms.	\N	\N
23876942	The goal of the present study was to determine if students can be trained to reliably perceive dysphonia using the Dysphonic Severity Percentage (DSP) scale, a perceptual measure shown to have high interrater reliability when used by speech-language pathologists experienced with voice disorders. Because the DSP scale was found to be useful as a research tool in the measurement of dysphonia, using it to train students to recognize dysphonia can enhance their education as future clinicians and researchers. This method involved having five inexperienced speech-language pathology students listen to voice samples in two conditions (spontaneous speech and paragraph reading) of 10 clients with moderate to severe dysphonia (phonotrauma); the students simultaneously tallied the nondysphonic syllables on written content of the samples to obtain a DSP for both conditions. Because the clients' dysphonias were moderate to severe, and there were many dysphonic syllables, it was more efficient and advantageous for the students' perception and training to tally the nondysphonic syllables, leaving the dysphonic syllables to calculate the DSP. By tallying the nondysphonic syllables, the students were still recognizing which syllables were dysphonic by not choosing them, thus increasing their perception of both normal and disordered syllables. Statistical analysis using the intraclass correlation coefficient revealed high interrater reliability and high correlations among the trained students for both spontaneous speech and paragraph reading, thus indicating similar training experiences and perceptions. This method appeared to be a more quantitative measure of perceptual ratings than current scales, which use general gradations of dysphonic severity. Moreover, the DSPs were similar between the newly trained students and experienced raters for spontaneous speech, indicating that the students could be trained in the direction experienced by voice clinicians. There was, however, a significant difference between the two groups for paragraph reading, which will be discussed. It was concluded that the DSP method was an effective technique to train students to recognize dysphonia.	\N	\N
23882007	In this article, the authors examine (a) the effect of semantic context on accentedness, comprehensibility, and intelligibility of Spanish-accented American English (AE) as judged by monolingual AE listeners and (b) the interaction of semantic context and accentedness on comprehensibility and intelligibility. Twenty adult native (L1) Spanish speakers proficient in AE and 4 L1 AE speakers (controls) read 48 statements consisting of true-false, semantically meaningful, and semantically anomalous sentences. Eighty monolingual AE listeners assessed accentedness, comprehensibility, and intelligibility of the statements. A significant main effect was found for semantic category on all 3 dependent variables. Accents were perceived to be stronger, and both comprehensibility and intelligibility were worse, in semantically anomalous contexts. Speaker data were grouped into strong, mid-level, and mild accents. The interaction between semantic category and accent was significant for both comprehensibility and intelligibility. The effect of semantic context was strongest for strong accents. Intelligibility was excellent for speakers with mid-level accents in true-false and semantically meaningful contexts, and it was excellent for mild accents in all contexts. Listeners access semantic information, in addition to phonetic and phonotactic features, in the perception of nonnative speech. Both accent level and semantic context are important in research on foreign-accented speech.	\N	\N
23883307	The irrelevant sound effect (ISE) is the finding that serial recall performance is impaired under complex auditory backgrounds such as speech as compared to white noise or silence. Several findings have demonstrated that ISE occurs with nonspeech backgrounds and that the changing-state complexity of the background stimuli is critical to ISE. In a pair of experiments, we investigate whether speech-like qualities of the irrelevant background have an effect beyond their changing-state complexity. We do so by using two kinds of transformations of speech with identical changing-state complexity: one kind that preserved speech-like information (sinewave speech and fully reversed sinewave speech) and others in which this information was distorted (two selectively reversed sinewave speech conditions). Our results indicate that even when changing-state complexity is held constant, sinewave speech conditions in which speech-like interformant relationships are disrupted, produce less ISE than those in which these relationships are preserved. This indicates that speech-like properties of the background are important beyond their changing-state complexity for ISE.	\N	\N
23885549	In patients with epileptic lesions in the hippocampus as well as in the temporal lobe and hippocampus simultaneously, studies were made on the perception of sound signals imitating sound source movement. It was established that hippocampal lesion results in disturbance of estimation of sound spatial characteristics which manifests in a change accuracy of localization and shortening of subjective sound image movement trajectory. Maximum disturbances of localization function are observed during lesions of hippocampus and temporal lobe. Possible neurophysiological mechanism underling observed disturbances are considered.	\N	\N
23886425	Communication while traveling in an automobile often is very difficult for hearing aid users. This is because the automobile/road noise level is usually high, and listeners/drivers often do not have access to visual cues. Since the talker of interest usually is not located in front of the listener/driver, conventional directional processing that places the directivity beam toward the listener's front may not be helpful and, in fact, could have a negative impact on speech recognition (when compared to omnidirectional processing). Recently, technologies have become available in commercial hearing aids that are designed to improve speech recognition and/or listening effort in noisy conditions where talkers are located behind or beside the listener. These technologies include (1) a directional microphone system that uses a backward-facing directivity pattern (Back-DIR processing), (2) a technology that transmits audio signals from the ear with the better signal-to-noise ratio (SNR) to the ear with the poorer SNR (Side-Transmission processing), and (3) a signal processing scheme that suppresses the noise at the ear with the poorer SNR (Side-Suppression processing). The purpose of the current study was to determine the effect of (1) conventional directional microphones and (2) newer signal processing schemes (Back-DIR, Side-Transmission, and Side-Suppression) on listener's speech recognition performance and preference for communication in a traveling automobile. A single-blinded, repeated-measures design was used. Twenty-five adults with bilateral symmetrical sensorineural hearing loss aged 44 through 84 yr participated in the study. The automobile/road noise and sentences of the Connected Speech Test (CST) were recorded through hearing aids in a standard van moving at a speed of 70 mph on a paved highway. The hearing aids were programmed to omnidirectional microphone, conventional adaptive directional microphone, and the three newer schemes. CST sentences were presented from the side and back of the hearing aids, which were placed on the ears of a manikin. The recorded stimuli were presented to listeners via earphones in a sound-treated booth to assess speech recognition performance and preference with each programmed condition. Compared to omnidirectional microphones, conventional adaptive directional processing had a detrimental effect on speech recognition when speech was presented from the back or side of the listener. Back-DIR and Side-Transmission processing improved speech recognition performance (relative to both omnidirectional and adaptive directional processing) when speech was from the back and side, respectively. The performance with Side-Suppression processing was better than with adaptive directional processing when speech was from the side. The participants' preferences for a given processing scheme were generally consistent with speech recognition results. The finding that performance with adaptive directional processing was poorer than with omnidirectional microphones demonstrates the importance of selecting the correct microphone technology for different listening situations. The results also suggest the feasibility of using hearing aid technologies to provide a better listening experience for hearing aid users in automobiles.	\N	\N
23888869	Binding is key in multisensory perception. This study investigated the audio-visual (A-V) temporal binding window in 4-, 5-, and 6-year-old children (total N = 120). Children watched a person uttering a syllable whose auditory and visual components were either temporally synchronized or desynchronized by 366, 500, or 666 ms. They were asked whether the voice and face went together (Experiment 1) or whether the desynchronized videos differed from the synchronized one (Experiment 2). Four-year-olds detected the 666-ms asynchrony, 5-year-olds detected the 666- and 500-ms asynchrony, and 6-year-olds detected all asynchronies. These results show that the A-V temporal binding window narrows slowly during early childhood and that it is still wider at 6 years of age than in older children and adults.	\N	\N
23891107	Biologically salient sounds, including speech, are rarely heard in isolation. Our brains must therefore organize the input arising from multiple sources into separate "streams" and, in the case of speech, map the acoustic components of the target signal onto meaning. These auditory and linguistic processes have traditionally been considered to occur sequentially and are typically studied independently [1, 2]. However, evidence that streaming is modified or reset by attention [3], and that lexical knowledge can affect reports of speech sound identity [4, 5], suggests that higher-level factors may influence perceptual organization. In two experiments, listeners heard sequences of repeated words or acoustically matched nonwords. After several presentations, they reported that the initial /s/ sound in each syllable formed a separate stream; the percept then fluctuated between the streamed and fused states in a bistable manner. In addition to measuring these verbal transformations, we assessed streaming objectively by requiring listeners to detect occasional targets-syllables containing a gap after the initial /s/. Performance was better when streaming caused the syllables preceding the target to transform from words into nonwords, rather than from nonwords into words. Our results show that auditory stream formation is influenced not only by the acoustic properties of speech sounds, but also by higher-level processes involved in recognizing familiar words.	\N	\N
23893201	Mimicking the human ear on the basis of auditory models has become a viable approach in many applications by now. However, only a few attempts have been made to extend the scope of physiological ear models to be employed in cochlear implants (CI). Contemporary CI systems rely on much simpler filter banks and simulate the natural signal processing of a healthy cochlea to only a very limited extent. When looking at rehabilitation outcomes, current systems seem to have reached their peak potential, which signals the need for better algorithms and/or technologies. In this paper, we present a novel sound processing strategy, SAM (Stimulation based on Auditory Modeling), that is based on neurophysiological models of the human ear and can be employed in auditory prostheses. It incorporates active cochlear filtering (basilar membrane and outer hair cells) along with the mechanoelectrical transduction of the inner hair cells, so that several psychoacoustic phenomena are accounted for inherently. Although possible, current implementation does not make use of parallel stimulation of the electrodes, which matches state-of-the-art CI hardware. This paper elaborates on SAM's signal processing and provides a computational evaluation of the strategy. Results show that aspects of normal cochlear processing that are missing in common strategies can be replicated by SAM. This is supposed to improve overall CI user performance, which we have at least partly proven in a pilot study with implantees.	\N	\N
23893677	Several studies suggest that auditory perception in general and the perception of speech in noise in particular continue to develop until late childhood or early adolescence. It remains unclear, however, whether this prolonged development results from the maturation of the cognitive factors associated with the performance of auditory tasks or from the slow development of auditory sensory processing. We investigated the perception of monosyllabic words embedded in white noise in Hebrew-speaking school-age children and adults. Although identification thresholds did not become adult-like until 11 years of age, we found no evidence linking this prolonged development to non-sensory factors associated with performance consistency. Therefore, we suggest that similar to the development of amplitude and frequency modulation detection thresholds, this protracted development is related to the maturation of auditory sensory processing.	\N	\N
23893940	Videos can be used as didactic tools for self-learning under several circumstances, including those cases in which students are responsible for the development of this resource as an audiovisual notebook. We compared students' and teachers' perceptions regarding the main features that an audiovisual notebook should include. Four questionnaires with items about information, images, text and music, and filmmaking were used to investigate students' (n = 115) and teachers' perceptions (n = 28) regarding the development of a video focused on a histological technique. The results show that both students and teachers significantly prioritize informative components, images and filmmaking more than text and music. The scores were significantly higher for teachers than for students for all four components analyzed. The highest scores were given to items related to practical and medically oriented elements, and the lowest values were given to theoretical and complementary elements. For most items, there were no differences between genders. A strong positive correlation was found between the scores given to each item by teachers and students. These results show that both students' and teachers' perceptions tend to coincide for most items, and suggest that audiovisual notebooks developed by students would emphasize the same items as those perceived by teachers to be the most relevant. Further, these findings suggest that the use of video as an audiovisual learning notebook would not only preserve the curricular objectives but would also offer the advantages of self-learning processes.	\N	\N
23905279	Recent studies in the field of intonational phonology have shown that information-seeking questions can be distinguished from confirmation-seeking questions by prosodic means in a variety of languages (Armstrong, 2010, for Puerto Rican Spanish; Grice & Savino, 1997, for Bari Italian; Kügler, 2003, for Leipzig German; Mata & Santos, 2010, for European Portuguese; Vanrell, Mascaró, Prieto, & Torres-Tamarit, 2010, for Catalan). However, all these studies have relied on production experiments and little is known about the perceptual relevance of these intonational cues. This paper explores whether Majorcan Catalan listeners distinguish information- and confirmation-seeking questions by means of two distinct nuclear falling pitch accents. Three behavioral tasks were conducted with 20 Majorcan Catalan subjects, namely a semantic congruity test, a rating test, and a classical categorical perception identification/discrimination test. The results show that a difference in pitch scaling on the leading H tone of the H+L* nuclear pitch accent is the main cue used by Majorcan Catalan listeners to distinguish confirmation questions from information-seeking questions. Thus, while a iH+L* pitch accent signals an information-seeking question (i.e., the speaker has no expectation about the nature of the answer), the H+L* pitch accent indicates that the speaker is asking about mutually shared information. We argue that these results have implications in representing the distinctions of tonal height in Catalan. The results also support the claim that phonological contrasts in intonation, together with other linguistic strategies, can signal the speakers' beliefs about the certainty of the proposition expressed.	\N	\N
23906967	Training people on temporal discrimination can substantially improve performance in the trained modality but also in untrained modalities. A pretest-training-posttest design was used to investigate whether consolidation plays a crucial role for training effects within the trained modality and its transfer to another modality. In the pretest, both auditory and visual discrimination performance was assessed. In the training phase, participants performed only the auditory task. After a consolidation interval of either 5 min or 24h, participants were again tested in both the auditory and visual tasks. Irrespective of the consolidation interval, performance improved from the pretest to the posttest in both modalities. Most importantly, the training effect for the trained auditory modality was independent of the consolidation interval whereas the transfer effect to the visual modality was larger after 24h than after 5 min. This finding shows that transfer effects benefit from extended consolidation.	\N	\N
23921930	To confirm the clinical efficacy and safety of a direct acoustic cochlear implant. Prospective multicenter study. The study was performed at 3 university hospitals in Europe (Germany, The Netherlands, and Switzerland). Fifteen patients with severe-to-profound mixed hearing loss because of otosclerosis or previous failed stapes surgery. Implantation with a Codacs direct acoustic cochlear implant investigational device (ID) combined with a stapedotomy with a conventional stapes prosthesis Preoperative and postoperative (3 months after activation of the investigational direct acoustic cochlear implant) audiometric evaluation measuring conventional pure tone and speech audiometry, tympanometry, aided thresholds in sound field and hearing difficulty by the Abbreviated Profile of Hearing Aid Benefit questionnaire. The preoperative and postoperative air and bone conduction thresholds did not change significantly by the implantation with the investigational Direct Acoustic Cochlear Implant. The mean sound field thresholds (0.25-8 kHz) improved significantly by 48 dB. The word recognition scores (WRS) at 50, 65, and 80 dB SPL improved significantly by 30.4%, 75%, and 78.2%, respectively, after implantation with the investigational direct acoustic cochlear implant compared with the preoperative unaided condition. The difficulty in hearing, measured by the Abbreviated Profile of Hearing Aid Benefit, decreased by 27% after implantation with the investigational direct acoustic cochlear implant. Patients with moderate-to-severe mixed hearing loss because of otosclerosis can benefit substantially using the Codacs investigational device.	\N	\N
23927112	The present study evaluated the influence of suppressor frequency (fs) and level (Ls) on stimulus-frequency otoacoustic emissions (SFOAEs) recorded using the amplitude-modulated (AM) suppressor technique described by Neely et al. [J. Acoust. Soc. Am. 118, 2124-2127 (2005a)]. Data were collected in normal-hearing subjects, with data collection occurring in two phases. In phase 1, SFOAEs were recorded with probe frequency (fp) = 1, 2, and 4 kHz and probe levels (Lp) ranging from 0 to 60 dB sound pressure level (SPL). At each fp, Ls ranged from Ls = Lp to Ls = Lp + 30 dB. Additionally, nine relationships between fs and fp were evaluated, ranging from fs/fp = 0.80 to fs/fp = 1.16. Results indicated that for low suppressor levels, suppressors higher in frequency than fp (fs > fp) resulted in higher AM-SFOAE levels than suppressors lower in frequency than fp (fs < fp). At higher suppressor levels, suppressors both higher and lower in frequency than fp produced similar AM-SFOAE levels, and, in many cases, low-frequency suppressors produced the largest response. Recommendations for stimulus parameters that maximize AM-SFOAE level were derived from these data. In phase 2, AM-SFOAEs were recorded using these parameters for fp = 0.7-8 kHz and Lp = 20-60 dB SPL. Robust AM-SFOAE responses were recorded in this group of subjects using the parameters developed in phase 1.	\N	\N
23927121	Real-world sound sources are usually perceived as externalized and thus properly localized in both direction and distance. This is largely due to (1) the acoustic filtering by the head, torso, and pinna, resulting in modifications of the signal spectrum and thereby a frequency-dependent shaping of interaural cues and (2) interaural cues provided by the reverberation inside an enclosed space. This study first investigated the effect of room reverberation on the spectro-temporal behavior of interaural level differences (ILDs) by analyzing dummy-head recordings of speech played at different distances in a standard listening room. Next, the effect of ILD fluctuations on the degree of externalization was investigated in a psychoacoustic experiment performed in the same listening room. Individual binaural impulse responses were used to simulate a distant sound source delivered via headphones. The ILDs were altered using a gammatone filterbank for analysis and resynthesis, where the envelopes of the left and right-ear signals were modified such that the naturally occurring fluctuations of the ILDs were restricted. This manipulation reduced the perceived degree of externalization. This was consistent with the analysis of short-term ILDs at different distances showing that a decreased distance to the sound source also reduced the ILD fluctuations.	\N	\N
23927128	The perturbation of acoustic features in a speaker's auditory feedback elicits rapid compensatory responses that demonstrate the importance of auditory feedback for control of speech output. The current study investigated whether responses to a perturbation of speech auditory feedback vary depending on the importance of the perturbed feature to perception of the vowel being produced. Auditory feedback of speakers' first formant frequency (F1) was shifted upward by 130 mels in randomly selected trials during the speakers' production of consonant-vowel-consonant words containing either the vowel /Λ/ or the vowel /ɝ/. Although these vowels exhibit comparable F1 frequencies, the contribution of F1 to perception of /Λ/ is greater than its contribution to perception of /ɝ/. Compensation to the F1 perturbation was observed during production of both vowels, but compensatory responses during /Λ/ occurred at significantly shorter latencies and exhibited significantly larger magnitudes than compensatory responses during /ɝ/. The finding that perturbation of vowel F1 during /Λ/ and /ɝ/ yielded compensatory differences that mirrored the contributions of F1 to perception of these vowels indicates that some portion of feedback control is weighted toward monitoring and preservation of acoustic cues for speech perception.	\N	\N
23933139	A series of five experiments investigated the extent of subliminal processing of negation. Participants were presented with a subliminal instruction to either pick or not pick an accompanying noun, followed by a choice of two nouns. By employing subjective measures to determine individual thresholds of subliminal priming, the results of these studies indicated that participants were able to identify the correct noun of the pair--even when the correct noun was specified by negation. Furthermore, using a grey-scale contrast method of masking, Experiment 5 confirmed that these priming effects were evidenced in the absence of partial awareness, and without the effect being attributed to the retrieval of stimulus-response links established during conscious rehearsal.	\N	\N
23937006	To analyse the impact of tinnitus loudness, tinnitus frequency, hearing loss, tinnitus subjective loudness on the life of tinnitus patient. To inspect the 154 tinnitus patients with pure tone audiometry, tinnitus matching, tinnitus classification questionnaire and THI scale. This study applies THI scale to evaluate the impact of tinnitus on the life of tinnitus patient. Using statistical methods to analyse the relationship between tinnitus loudness, tinnitus frequency, hearing loss, tinnitus subjective loudness and the impact of tinnitus on the life of tinnitus patient. (1) Tinnitus frequency is closed with the frequency of hearing loss. (2) There is no significant correlation between tinnitus loudness and the impact of tinnitus on the life of tinnitus patient. (3) There is no distinction between hearing loss and the THI scores. (4) The patient gets more scores in subgroup of THI with the increase of tinnitus subjective loudness classification. The impact of tinnitus loudness, hearing loss on the life of tinnitus patient is not very clearly, while the impact of tinnitus subjective loudness classification on the life of tinnitus patient is significant. In clinical, we can not evaluate the effect of the tinnitus treatment relying on tinnitus loudness and hearing loss simply.The finding provides us individual treatment to tinnitus patients.	\N	\N
23937689	Several accounts of speech perception propose that the areas involved in producing language are also involved in perceiving it. In line with this view, neuroimaging studies show activation of premotor cortex (PMC) during phoneme judgment tasks; however, there is debate about whether speech perception necessarily involves motor processes, across all task contexts, or whether the contribution of PMC is restricted to tasks requiring explicit phoneme awareness. Some aspects of speech processing, such as mapping sounds onto meaning, may proceed without the involvement of motor speech areas if PMC specifically contributes to the manipulation and categorical perception of phonemes. We applied TMS to three sites-PMC, posterior superior temporal gyrus, and occipital pole-and for the first time within the TMS literature, directly contrasted two speech perception tasks that required explicit phoneme decisions and mapping of speech sounds onto semantic categories, respectively. TMS to PMC disrupted explicit phonological judgments but not access to meaning for the same speech stimuli. TMS to two further sites confirmed that this pattern was site specific and did not reflect a generic difference in the susceptibility of our experimental tasks to TMS: stimulation of pSTG, a site involved in auditory processing, disrupted performance in both language tasks, whereas stimulation of occipital pole had no effect on performance in either task. These findings demonstrate that, although PMC is important for explicit phonological judgments, crucially, PMC is not necessary for mapping speech onto meanings.	\N	\N
23943499	To investigate the effect of semantic congruity on audiovisual target responses, participants detected a semantic concept that was embedded in a series of rapidly presented stimuli. The target concept appeared as a picture, an environmental sound, or both; and in bimodal trials, the audiovisual events were either consistent or inconsistent in their representation of a semantic concept. The results showed faster detection latencies to bimodal than to unimodal targets and a higher rate of missed targets when visual distractors were presented together with auditory targets, in comparison to auditory targets presented alone. The findings of Experiment 2 showed a cross-modal asymmetry, such that visual distractors were found to interfere with the accuracy of auditory target detection, but auditory distractors had no effect on either the speed or the accuracy of visual target detection. The biased-competition theory of attention (Desimone & Duncan Annual Review of Neuroscience 18: 1995; Duncan, Humphreys, & Ward Current Opinion in Neurobiology 7: 255-261 1997) was used to explain the findings because, when the saliency of the visual stimuli was reduced by the addition of a noise filter in Experiment 4, visual interference on auditory target detection was diminished. Additionally, the results showed faster and more accurate target detection when semantic concepts were represented in a visual rather than an auditory format.	\N	\N
23966690	Aging listeners experience greater difficulty understanding speech in adverse listening conditions and exhibit degraded temporal resolution, even when audiometric thresholds are normal. When threshold evidence for peripheral involvement is lacking, central and cognitive factors are often cited as underlying performance declines. However, previous work has uncovered widespread loss of cochlear afferent synapses and progressive cochlear nerve degeneration in noise-exposed ears with recovered thresholds and no hair cell loss (Kujawa and Liberman 2009). Here, we characterize age-related cochlear synaptic and neural degeneration in CBA/CaJ mice never exposed to high-level noise. Cochlear hair cell and neuronal function was assessed via distortion product otoacoustic emissions and auditory brainstem responses, respectively. Immunostained cochlear whole mounts and plastic-embedded sections were studied by confocal and conventional light microscopy to quantify hair cells, cochlear neurons, and synaptic structures, i.e., presynaptic ribbons and postsynaptic glutamate receptors. Cochlear synaptic loss progresses from youth (4 weeks) to old age (144 weeks) and is seen throughout the cochlea long before age-related changes in thresholds or hair cell counts. Cochlear nerve loss parallels the synaptic loss, after a delay of several months. Key functional clues to the synaptopathy are available in the neural response; these can be accessed noninvasively, enhancing the possibilities for translation to human clinical characterization.	\N	\N
23966965	Williams syndrome (WS), a genetic, neurodevelopmental disorder, is of keen interest to music cognition researchers because of its characteristic auditory sensitivities and emotional responsiveness to music. However, actual musical perception and production abilities are more variable. We examined musicality in WS through the lens of amusia and explored how their musical perception abilities related to their auditory sensitivities, musical production skills, and emotional responsiveness to music. In our sample of 73 adolescents and adults with WS, 11% met criteria for amusia, which is higher than the 4% prevalence rate reported in the typically developing (TD) population. Amusia was not related to auditory sensitivities but was related to musical training. Performance on the amusia measure strongly predicted musical skill but not emotional responsiveness to music, which was better predicted by general auditory sensitivities. This study represents the first time amusia has been examined in a population with a known neurodevelopmental genetic disorder with a range of cognitive abilities. Results have implications for the relationships across different levels of auditory processing, musical skill development, and emotional responsiveness to music, as well as the understanding of gene-brain-behavior relationships in individuals with WS and TD individuals with and without amusia.	\N	\N
23967947	The purpose of this study was to analyze vowel articulation across various speaking tasks in a group of 20 early Parkinson's disease (PD) individuals prior to pharmacotherapy. Vowels were extracted from sustained phonation, sentence repetition, reading passage, and monologue. Acoustic analysis was based upon measures of the first (F1) and second (F2) formant of the vowels /a/, /i/, and /u/, vowel space area (VSA), F2i/F2u and vowel articulation index (VAI). Parkinsonian speakers manifested abnormalities in vowel articulation across F2u, VSA, F2i/F2u, and VAI in all speaking tasks except sustained phonation, compared to 15 age-matched healthy control participants. Findings suggest that sustained phonation is an inappropriate task to investigate vowel articulation in early PD. In contrast, monologue was the most sensitive in differentiating between controls and PD patients, with classification accuracy up to 80%. Measurements of vowel articulation were able to capture even minor abnormalities in speech of PD patients with no perceptible dysarthria. In conclusion, impaired vowel articulation may be considered as a possible early marker of PD. A certain type of speaking task can exert significant influence on vowel articulation. Specifically, complex tasks such as monologue are more likely to elicit articulatory deficits in parkinsonian speech, compared to other speaking tasks.	\N	\N
23977030	Mechanisms of propofol-induced loss of consciousness remain poorly understood. Recent fMRI studies have shown decreases in functional connectivity during unconsciousness induced by this anesthetic agent. Functional connectivity does not provide information of directional changes in the dynamics observed during unconsciousness. The aim of the present study was to investigate, in healthy humans during an auditory task, the changes in effective connectivity resulting from propofol induced loss of consciousness. We used Dynamic Causal Modeling for fMRI (fMRI-DCM) to assess how causal connectivity is influenced by the anesthetic agent in the auditory system. Our results suggest that the dynamic observed in the auditory system during unconsciousness induced by propofol, can result in a mixture of two effects: a local inhibitory connectivity increase and a decrease in the effective connectivity in sensory cortices.	\N	\N
23978930	Faces presented upside-down are harder to recognize than presented right-side up, an effect known as the face inversion effect. With inversion the perceptual processing of the spatial relationship among facial parts is disrupted. Previous literature indicates a face inversion effect in chimpanzees toward familiar and conspecific faces. Although these results are not inconsistent with findings from humans they have some controversy in their methodology. Here, we employed a delayed matching-to-sample task to test captive chimpanzees on discriminating chimpanzee and human faces. Their performances were deteriorated by inversion. More importantly, the discrimination deterioration was systematically different between the two age groups of chimpanzee participants, i.e. young chimpanzees showed a stronger inversion effect for chimpanzee than for human faces, while old chimpanzees showed a stronger inversion effect for human than for chimpanzee faces. We conclude that the face inversion effect in chimpanzees is modulated by the level of expertise of face processing.	\N	\N
23980148	Learning, the foundation of adaptive and intelligent behavior, is based on plastic changes in neural assemblies, reflected by the modulation of electric brain responses. In infancy, auditory learning implicates the formation and strengthening of neural long-term memory traces, improving discrimination skills, in particular those forming the prerequisites for speech perception and understanding. Although previous behavioral observations show that newborns react differentially to unfamiliar sounds vs. familiar sound material that they were exposed to as fetuses, the neural basis of fetal learning has not thus far been investigated. Here we demonstrate direct neural correlates of human fetal learning of speech-like auditory stimuli. We presented variants of words to fetuses; unlike infants with no exposure to these stimuli, the exposed fetuses showed enhanced brain activity (mismatch responses) in response to pitch changes for the trained variants after birth. Furthermore, a significant correlation existed between the amount of prenatal exposure and brain activity, with greater activity being associated with a higher amount of prenatal speech exposure. Moreover, the learning effect was generalized to other types of similar speech sounds not included in the training material. Consequently, our results indicate neural commitment specifically tuned to the speech features heard before birth and their memory representations.	\N	\N
23992232	The detection of auditory stimuli that deviate from a simple or complex auditory regularity is reflected by the mismatch negativity component of the human auditory evoked potential. Moreover, simple deviants of an oddball paradigm modulate the preceding middle-latency response of the auditory evoked potential. For the frequency oddball paradigms it has been shown that the Nb wave, at approximately 40 ms from stimulus onset, is enhanced in response to deviant compared with standard stimuli. In this study we tested whether the detection of auditory deviants in a (frequency-location) feature-conjunction paradigm is reflected by modulations of the Na, Pa or Nb wave of healthy human participants. In addition, a frequency oddball paradigm was applied to directly contrast the results of a simple and a complex invariance. Feature-conjunction deviants did not elicit any modulations of the tested middle-latency waves. Deviants of the frequency oddball paradigm, by contrast, elicited an enhancement of the Nb wave, confirming the outcome of precedent studies. In both conditions a significant mismatch negativity component was elicited, which showed larger amplitudes and shorter latencies in the oddball condition than in the feature-conjunction condition. These findings corroborate the idea that simple auditory regularities are encoded upstream of those of more complex auditory features and are in line with the idea of a hierarchically working auditory novelty system.	\N	\N
24003981	This study explores if increasing number of repetitions might improve the precision of the acceptable noise level (ANL) test. We measured twelve ANL repetitions, i.e. four complete ANL tests (4 × 3 repetitions), at one session using diotic presentation and a non-semantic ANL version. Thirty-two normal-hearing adults. Small order and fatigue effects were seen. We used the coefficient of repeatability (CR) to assess the repeatability; CRs ranged between 3.9 and 7.6 dB for the four ANL tests. Using the twelve ANL repetitions we removed the variability of the ANL across subjects by normalizing the data to the individual mean ANL for the twelve repetitions. The mean normalized ANL across the subjects rapidly approached the ANL normalized to the individual mean for the 12 repetitions (0 dB), and after three repetitions the SD seemed to be stable at about 3 dB. The findings suggest that both order and fatigue affect the ANL. The findings also suggest that it may be more accurate to speak of an acceptable noise range than ANL. These findings have large implications for how we understand acceptable noise and it would explain a large part of the variability seen among normal-hearing and perhaps hearing-impaired subjects.	\N	\N
24005271	The objective of the present study was to evaluate the hearing function in the airport technical personnel and estimate the effectiveness of multicomponent anti-noise hearing protectors used by the specialists engaged in the aircraft maintenance. The tonal threshold audiometry was carried out before and after a shiftwork. The extra-aural effect of noise was assessed from the characteristics of cardiac rhythm variability. The study included two groups of subjects: in one of them (n=8) they used ordinary flight headsets (control) in the other the protection was ensured with the help of multi-insert hearing protectors (n=16). The initial hearing thresholds were found to be increased up to 70 and 60 dB at the frequencies of 4 and 8 kHz respectively. The regression analysis revealed the relationship between these parameters and the duration of aerodrome work experience. Temporary threshold shifts were observed only in the control group. An increase in the tone of the sympathetic nervous system was observed in the control subjects but was absent in the study group. It is concluded that the multi-component hearing protectors employed in the present study are highly efficacious anti-noise devices. The mechanisms of noise-induced hearing loss are discussed.	\N	\N
24007920	Many previous studies have shown that the human language processor is capable of rapidly integrating information from different sources during reading or listening. Yet, little is known about how this ability develops from child to adulthood. To gain insight into how children (in comparison to adults) handle different kinds of linguistic information during on-line language comprehension, the current study investigates a well-known morphological phenomenon that is subject to both structural and semantic constraints, the plurals-in-compounds effect, i.e. the dislike of plural (specifically regular plural) modifiers inside compounds (e.g. rats eater). We examined 96 seven-to-twelve-year-old children and a control group of 32 adults measuring their eye-gaze changes in response to compound-internal plural and singular forms. Our results indicate that children rely more upon structural properties of language (in the present case, morphological cues) early in development and that the ability to efficiently integrate information from multiple sources takes time for children to reach adult-like levels.	\N	\N
24012681	It was recently shown that brain activity can be represented as a stimulation-specific vector field. Since the vector field of brain activity is specifically transformed by sensory input, we suggested that a tensor field that transforms brain activity reflects sensory input. We calculated the tensor fields that transform brain activity between visual baseline and auditory word processing in PET data and between environmental sounds and auditory word processing in fMRI data. In the first comparison, significant clusters formed a distributed network over the brain cortex. In the second comparison, clusters were more localised in the temporo-frontal network of speech processing. Our study therefore demonstrated that tensor fields reflect the sensory input that specifically transforms brain activity.	\N	\N
24016155	For studying multistable auditory perception, we propose a paradigm that evokes integrated or segregated perception of a sound sequence, and permits decomposition of the segregated grouping into foreground and background sounds. The paradigm combines 3-tone pitch patterns with alternating timbres, resulting in a repeating 6-tone structure that can be perceived as rising based on temporal proximity, or as falling based on timbre similarity. Listeners continuously report their percept while EEG is recorded. Results show an ERP modulation starting at ∼70 ms after sound onset that can be explained by whether a sound belongs to perceived foreground or background, with no additional effect of integrated versus segregated grouping. Auditory grouping as indexed by the mismatch negativity did not correspond with reported sound grouping. The paradigm offers a new possibility for investigating effects of conscious perceptual organization on sound processing.	\N	\N
24018572	The purpose of this study was to determine the effects of hearing instruments set to Desired Sensation Level version 5 (DSL v5) hearing instrument prescription algorithm targets and equipped with directional microphones and digital noise reduction (DNR) on children's sentence recognition in noise performance and loudness perception in a classroom environment. Ten children (ages 8-17 years) with stable, congenital sensorineural hearing losses participated in the study. Participants were fitted bilaterally with behind-the-ear hearing instruments set to DSL v5 prescriptive targets. Sentence recognition in noise was evaluated using the Bamford-Kowal-Bench Speech in Noise Test (Niquette et al., 2003). Loudness perception was evaluated using a modified version of the Contour Test of Loudness Perception (Cox, Alexander, Taylor, & Gray, 1997). Children's sentence recognition in noise performance was significantly better when using directional microphones alone or in combination with DNR than when using omnidirectional microphones alone or in combination with DNR. Children's loudness ratings for sounds above 72 dB SPL were lowest when fitted with the DSL v5 Noise prescription combined with directional microphones. DNR use showed no effect on loudness ratings. Use of the DSL v5 Noise prescription with a directional microphone improved sentence recognition in noise performance and reduced loudness perception ratings for loud sounds relative to a typical clinical reference fitting with the DSL v5 Quiet prescription with no digital signal processing features enabled. Potential clinical strategies are discussed.	\N	\N
24021849	Dehaene et al. (2003) showed an absence of conscious, but not masked, conflict effects when patients with schizophrenia performed a number-categorisation priming task. We aimed to replicate these influential results using a different word-categorisation priming task. Counter to Dehaene et al.'s findings, 21 patients and 20 healthy controls showed similar congruence effects for both masked and visible primes. Within patients, a reduced congruence effect for visible primes associated with longer duration of illness and more severe behavioural disorganisation. Patients, unlike controls, were no slower to respond to targets that followed visible compared to masked primes. Conscious conflict effects on priming tasks are not universally reduced in schizophrenia but may associate with chronicity and behavioural disorganisation. That patients were no slower when the preceding primes were clearly visible accords with evidence elsewhere that information processing in schizophrenia is driven more by immediate conscious experience and constrained less by prior events.	\N	\N
24024543	Emotion in audio-voice signals, as synthesized by text-to-speech (TTS) technologies, was investigated to formulate a theory of expression for user interface design. Emotional parameters were specified with markup tags, and the resulting audio was further modulated with post-processing techniques. Software was then developed to link a selected TTS synthesizer with an automatic speech recognition (ASR) engine, producing a chatbot that could speak and listen. Using these two artificial voice subsystems, investigators explored both artistic and psychological implications of artificial speech emotion. Goals of the investigation were interdisciplinary, with interest in musical composition, augmentative and alternative communication (AAC), commercial voice announcement applications, human-computer interaction (HCI), and artificial intelligence (AI). The work-in-progress points towards an emerging interdisciplinary ontology for artificial voices. As one study output, HCI tools are proposed for future collaboration.	\N	\N
24028995	Recent theory of physiology of language suggests a dual stream dorsal/ventral organization of speech perception. Using intra-cerebral Event-related potentials (ERPs) during pre-surgical assessment of twelve drug-resistant epileptic patients, we aimed to single out electrophysiological patterns during both lexical-semantic and phonological monitoring tasks involving ventral and dorsal regions respectively. Phonological information processing predominantly occurred in the left supra-marginal gyrus (dorsal stream) and lexico-semantic information occurred in anterior/middle temporal and fusiform gyri (ventral stream). Similar latencies were identified in response to phonological and lexico-semantic tasks, suggesting parallel processing. Typical ERP components were strongly left lateralized since no evoked responses were recorded in homologous right structures. Finally, ERP patterns suggested the inferior frontal gyrus as the likely final common pathway of both dorsal and ventral streams. These results brought out detailed evidence of the spatial-temporal information processing in the dual pathways involved in speech perception.	\N	\N
24032320	The purpose was the develop a questionnaire to identify the specific listening difficulties of second language (L2) learners. Based on previous research, a questionnaire containing 31 items was developed and administered to 1,056 college freshmen. The whole sample was split randomly into two subsamples, each containing 528 cases. Exploratory factor analysis was performed to analyse the first subsample, and six factors were extracted, explaining a total of 57.1% of variance. To test the factor model, confirmatory factor analysis was conducted with the second subsample. Various fit indices were examined. The best fitting model for the data was a 23-item, six-factor model representing text, input channel and surroundings, relevance, listener, speaker, and task. Apart from the listener factor, all components are external ones and deemed to be uncontrollable by listeners. L2 learners must take an active role in listening practice to overcome L2 listening difficulties.	\N	\N
24034879	This paper presents an analytic procedure to assist safety practitioners in evaluating the audibility of an existing auditory warning system in their workplaces. Two alarm location models are described: (a) a model with an unknown signal sound level, and (b) a model with a known signal sound level. A heuristic algorithm to determine a minimum number of alarm devices and their locations so that the warning signals can be clearly heard by workers is also proposed. The algorithm considers the ambient noise level, noise levels generated by individual machines, locations where workers are likely to be present, and noise levels at worker locations. From the numerical examples and the computation experiment, both the optimization and heuristic approaches yield solutions that satisfy the 15-dBA constraints. The heuristic approach is efficient in solving large alarm location problems due its capability to find near-optimal solutions within reasonable computation time.	\N	\N
24035819	Given recent interest in syllabic rates (∼2-5 Hz) for speech processing, we review the perception of "fluctuation" range (∼1-10 Hz) modulations during listening to speech and technical auditory stimuli (AM and FM tones and noises, and ripple sounds). We find evidence that the temporal modulation transfer function (TMTF) of human auditory perception is not simply low-pass in nature, but rather exhibits a peak in sensitivity in the syllabic range (∼2-5 Hz). We also address human and animal neurophysiological evidence, and argue that this bandpass tuning arises at the thalamocortical level and is more associated with non-primary regions than primary regions of cortex. The bandpass rather than low-pass TMTF has implications for modeling auditory central physiology and speech processing: this implicates temporal contrast rather than simple temporal integration, with contrast enhancement for dynamic stimuli in the fluctuation range. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives".	\N	\N
24042339	Behavioral improvement within the first hour of training is commonly explained as procedural learning (i.e., strategy changes resulting from task familiarization). However, it may additionally reflect a rapid adjustment of the perceptual and/or attentional system in a goal-directed task. In support of this latter hypothesis, we show feature-specific gains in performance for groups of participants briefly trained to use either a spectral or spatial difference between 2 vowels presented simultaneously during a vowel identification task. In both groups, the neuromagnetic activity measured during the vowel identification task following training revealed source activity in auditory cortices, prefrontal, inferior parietal, and motor areas. More importantly, the contrast between the 2 groups revealed a striking double dissociation in which listeners trained on spectral or spatial cues showed higher source activity in ventral ("what") and dorsal ("where") brain areas, respectively. These feature-specific effects indicate that brief training can implicitly bias top-down processing to a trained acoustic cue and induce a rapid recalibration of the ventral and dorsal auditory streams during speech segregation and identification.	\N	\N
24047945	Tests of auditory perception, such as those used in the assessment of central auditory processing disorders ([C]APDs), represent a domain in audiological assessment where measurement of this theoretical construct is often confounded by nonauditory abilities due to methodological shortcomings. These confounds include the effects of cognitive variables such as memory and attention and suboptimal testing paradigms, including the use of verbal reproduction as a form of response selection. We argue that these factors need to be controlled more carefully and/or modified so that their impact on tests of auditory and visual perception is only minimal. To advocate for a stronger theoretical framework than currently exists and to suggest better methodological strategies to improve assessment of auditory processing disorders (APDs). Emphasis is placed on adaptive forced-choice psychophysical methods and the use of matched tasks in multiple sensory modalities to achieve these goals. Together, this approach has potential to improve the construct validity of the diagnosis, enhance and develop theory, and evolve into a preferred method of testing. Examination of methods commonly used in studies of APDs. Where possible, currently used methodology is compared to contemporary psychophysical methods that emphasize computer-controlled forced-choice paradigms. In many cases, the procedures used in studies of APD introduce confounding factors that could be minimized if computer-controlled forced-choice psychophysical methods were utilized. Ambiguities of interpretation, indeterminate diagnoses, and unwanted confounds can be avoided by minimizing memory and attentional demands on the input end and precluding the use of response-selection strategies that use complex motor processes on the output end. Advocated are the use of computer-controlled forced-choice psychophysical paradigms in combination with matched tasks in multiple sensory modalities to enhance the prospect of obtaining a valid diagnosis.	\N	\N
24048514	We studied autistics by quantitative EEG spectral and coherence analysis during three experimental conditions: basal, watching a cartoon with audio (V-A), and with muted audio band (VwA). Significant reductions were found for the absolute power spectral density (PSD) in the central region for delta and theta, and in the posterior region for sigma and beta bands, lateralized to the right hemisphere. When comparing VwA versus the V-A in the midline regions, we found significant decrements of absolute PSD for delta, theta and alpha, and increments for the beta and gamma bands. In autistics, VwA versus V-A tended to show lower coherence values in the right hemisphere. An impairment of visual and auditory sensory integration in autistics might explain our results.	\N	\N
24059595	The frequency-following response (FFR) is the compound phase-locked brainstem response to periodic components of sound stimuli, and is closely related to pitch perception. Its weak amplitude often prevents its measurement with a high signal-to-noise ratio (SNR). Recording of FFR using multichannel EEG is possible but expensive and it involves the manual screening of raw data. We describe a new method to extract FFR features by prescreening the raw data using automatic monitoring of sound pressure in the ear canal. Removal of stimulus artifacts, noise reduction, and data selection were systematically studied. The reliability of our new method was tested by comparing FFRs tracking accuracy and pitch perception in fifteen individuals with normal hearing. The extracted FFRs tracking accuracy was significantly correlated with behavioral measures of pitch perception, indicating that FFR could be used to represent individual differences in pitch perception ability among a population with similar hearing characteristics. The designed system could extract FFR signals more accurately with high SNR after signal prescreen and noise reduction.	\N	\N
24060845	The present study investigated whether and how beat gesture (small baton-like hand movements used to emphasize information in speech) influences semantic processing as well as its interaction with pitch accent during speech comprehension. Event-related potentials were recorded as participants watched videos of a person gesturing and speaking simultaneously. The critical words in the spoken sentences were accompanied by a beat gesture, a control hand movement, or no hand movement, and were expressed either with or without pitch accent. We found that both beat gesture and control hand movement induced smaller negativities in the N400 time window than when no hand movement was presented. The reduced N400s indicate that both beat gesture and control movement facilitated the semantic integration of the critical word into the sentence context. In addition, the words accompanied by beat gesture elicited smaller negativities in the N400 time window than those accompanied by control hand movement over right posterior electrodes, suggesting that beat gesture has a unique role for enhancing semantic processing during speech comprehension. Finally, no interaction was observed between beat gesture and pitch accent, indicating that they affect semantic processing independently.	\N	\N
24060967	Some dialogues are perceived as running more smoothly than others. To some extent that impression could be related to how well speakers adapt their prosody to each other. Adaptation in prosody can be signaled by the use of pitch accents that indicate how utterances are structurally related to those of the interlocutor (prosodic function) or by copying the interlocutor's prosodic features (prosodic form). The same acoustic features, such as pitch, are involved in both ways of adaptation. Further, function and form may require a different prosody for successful adaptation in certain discourse contexts. In this study we investigate to what extent interlocutors are perceived as good adapters, depending on whether the prosody of both speakers is functionally coherent or similar in form. This is done in two perception tests using prosodically manipulated dialogues. Results show that coherent functional prosody can be a cue for speaker adaptation and that this cue is more powerful than similarity in prosodic form.	\N	\N
24066179	We tested non-musicians and musicians in an auditory psychophysical experiment to assess the effects of timbre manipulation on pitch-interval discrimination. Both groups were asked to indicate the larger of two presented intervals, comprised of four sequentially presented pitches; the second or fourth stimulus within a trial was either a sinusoidal (or "pure"), flute, piano, or synthetic voice tone, while the remaining three stimuli were all pure tones. The interval-discrimination tasks were administered parametrically to assess performance across varying pitch distances between intervals ("interval-differences"). Irrespective of timbre, musicians displayed a steady improvement across interval-differences, while non-musicians only demonstrated enhanced interval discrimination at an interval-difference of 100 cents (one semitone in Western music). Surprisingly, the best discrimination performance across both groups was observed with pure-tone intervals, followed by intervals containing a piano tone. More specifically, we observed that: 1) timbre changes within a trial affect interval discrimination; and 2) the broad spectral characteristics of an instrumental timbre may influence perceived pitch or interval magnitude and make interval discrimination more difficult.	\N	\N
24073580	To establish music reference values for normal-hearing (NH) person in China, in order to give convenience in clinical application. The NH participant group included 39 subjects, of which 21 females and 18 males. Musical Sounds in Cochlear Implants test battery was used to assess the music perception ability for normal-hearing participants. The median pitch difference NH participants could discriminate for string was 2.5 semitones and 0.5 for flute. The average scores of rhythm discrimination, melody discrimination, chord discrimination, instrument identification and instrument number detection test were 86.1% (SD = 11.2), 76.5% (SD = 11.1), 75.6% (SD = 11.4), 89.9% (SD = 13.0) and 74.1% (SD = 20.7), respectively. The MuSIC test could be a test for music perception ability for China users and in further study the material that more suited for our culture should be added into it.	\N	\N
24073684	Work on the perception of urban soundscapes has generated a number of perceptual models which are proposed as tools to test and evaluate soundscape interventions. However, despite the excessive sound levels and noise within hospital environments, perceptual models have not been developed for these spaces. To address this, a two-stage approach was developed by the authors to create such a model. First, semantics were obtained from listening evaluations which captured the feelings of individuals from hearing hospital sounds. Then, 30 participants rated a range of sound clips representative of a ward soundscape based on these semantics. Principal component analysis extracted a two-dimensional space representing an emotional-cognitive response. The framework enables soundscape interventions to be tested which may improve the perception of these hospital environments.	\N	\N
24080979	Cochlear implantation (CI) is currently the main device option for children with auditory neuropathy spectrum disorder (ANSD) who receive minimal benefit from conventional amplification. This study examines potential prognostic factors associated with post-CI speech performance in this population. Retrospective chart review. Academic center. ANSD patients without inner ear abnormalities implanted with unilateral or bilateral CI between 1998 and 2010. CI and speech perception testing. Post-CI speech perception testing at 50 dBHL. "Good" performers were defined as patients with greater than 70% speech perception and "poor" performers less than 70%. Medical comorbidity, educational information, and social history were gathered. Twenty-seven patients met inclusion criteria. Mean age at diagnosis, first CI, and second CI in good performers were 2.5 ± 3.4, 3.4 ± 3.6, and 3.8 ± 1.6 years, respectively, compared with 9.7 ± 7.8, 14.8 ± 12.9, and 8.9 ± 3.5 in poor performers. Mean speech perception after first and second implantation for good performers trended at 85% and 90%, respectively, compared with 36% and 73% in poor performers. Better pre-CI PTA correlated with better post-CI speech perception. Patients with bilateral CI demonstrated better speech perception outcomes compared with unilateral CI use. Poor performers had later age of implantation, lower socioeconomic status, and lack of family support compared with good performers. ANSD patients who do not benefit from conventional amplification do well when implanted at a young age with proper access to education and habilitation training. Medical, social, and economic information may be helpful in predicting positive outcomes.	\N	\N
24083896	In this cross-language study, six Italian and six French voice experts evaluated perceptually the speech of 27 Italian and 40 French patients with dysphonia to determine if there were differences based on native language. French and Italian voice specialists agreed substantially in their evaluations of the overall grade of dysphonia and moderately concerning roughness and breathiness. No statistically significant effects were found related to the language of the speakers with the exception of breathiness, a finding that was interpreted as being due to different voice pathologies in the patient groups. It was concluded that the perception of the overall grade of dysphonia and breathiness is not language-dependent, whereas the significant difference in the perception of roughness may be related to a perception/adaption process.	\N	\N
24089502	Linguistic content can be conveyed both in speech and in writing. But how similar is the neural processing when the same real-life information is presented in spoken and written form? Using functional magnetic resonance imaging, we recorded neural responses from human subjects who either listened to a 7 min spoken narrative or read a time-locked presentation of its transcript. Next, within each brain area, we directly compared the response time courses elicited by the written and spoken narrative. Early visual areas responded selectively to the written version, and early auditory areas to the spoken version of the narrative. In addition, many higher-order parietal and frontal areas demonstrated strong selectivity, responding far more reliably to either the spoken or written form of the narrative. By contrast, the response time courses along the superior temporal gyrus and inferior frontal gyrus were remarkably similar for spoken and written narratives, indicating strong modality-invariance of linguistic processing in these circuits. These results suggest that our ability to extract the same information from spoken and written forms arises from a mixture of selective neural processes in early (perceptual) and high-order (control) areas, and modality-invariant responses in linguistic and extra-linguistic areas.	\N	\N
24091182	The auditory nervous system is highly nonlinear. Some nonlinear responses arise through active processes in the cochlea, while others may arise in neural populations of the cochlear nucleus, inferior colliculus and higher auditory areas. In humans, auditory brainstem recordings reveal nonlinear population responses to combinations of pure tones, and to musical intervals composed of complex tones. Yet the biophysical origin of central auditory nonlinearities, their signal processing properties, and their relationship to auditory perception remain largely unknown. Both stimulus components and nonlinear resonances are well represented in auditory brainstem nuclei due to neural phase-locking. Recently mode-locking, a generalization of phase-locking that implies an intrinsically nonlinear processing of sound, has been observed in mammalian auditory brainstem nuclei. Here we show that a canonical model of mode-locked neural oscillation predicts the complex nonlinear population responses to musical intervals that have been observed in the human brainstem. The model makes predictions about auditory signal processing and perception that are different from traditional delay-based models, and may provide insight into the nature of auditory population responses. We anticipate that the application of dynamical systems analysis will provide the starting point for generic models of auditory population dynamics, and lead to a deeper understanding of nonlinear auditory signal processing possibly arising in excitatory-inhibitory networks of the central auditory nervous system. This approach has the potential to link neural dynamics with the perception of pitch, music, and speech, and lead to dynamical models of auditory system development.	\N	\N
24094802	Although reduced stress is thought to be one of the most deviant speech dimensions in hypokinetic dysarthria associated with Parkinson's disease (PD), the mechanisms of stress production in PD have not been thoroughly explored by objective methods. The aim of the present study was to quantify the effect of PD on prosodic characteristics and to describe contrastive stress patterns in parkinsonian speech. The ability of 20 male speakers with early PD and 16 age- and gender-matched healthy controls (HCs) to signal contrastive stress was investigated. Each participant was instructed to unnaturally emphasize five key words while reading a short block of text. Acoustic analyses were based on the measurement of pitch, intensity, and duration. In addition, an innovative measurement termed the stress pattern index (SPI) was designed to mirror the effect of all distinct acoustic cues exploited during stress production. Although PD patients demonstrated a reduced ability to convey contrastive stress, they could still notably increase pitch, intensity, and duration to emphasize a word within a sentence. No differences were revealed between PD and HC stress productions using the measurements of pitch, intensity, duration, and intensity range. However, restricted SPI and pitch range were evident in the PD group. A reduced ability to express stress seems to be the distinctive pattern of hypokinetic dysarthria, even in the early stages of PD. Because PD patients were able to consciously improve their speech performance using multiple acoustic cues, the introduction of speech therapy may be rewarding.	\N	\N
24098565	In the present study, we investigated brain morphological signatures of dyslexia by using a voxel-based asymmetry analysis. Dyslexia is a developmental disorder that affects the acquisition of reading and spelling abilities and is associated with a phonological deficit. Speech perception disabilities have been associated with this deficit, particularly when listening conditions are challenging, such as in noisy environments. These deficits are associated with known neurophysiological correlates, such as a reduction in the functional activation or a modification of functional asymmetry in the cortical regions involved in speech processing, such as the bilateral superior temporal areas. These functional deficits have been associated with macroscopic morphological abnormalities, which potentially include a reduction in gray and white matter volumes, combined with modifications of the leftward asymmetry along the perisylvian areas. The purpose of this study was to investigate gray/white matter distribution asymmetries in dyslexic adults using automated image processing derived from the voxel-based morphometry technique. Correlations with speech-in-noise perception abilities were also investigated. The results confirmed the presence of gray matter distribution abnormalities in the superior temporal gyrus (STG) and the superior temporal Sulcus (STS) in individuals with dyslexia. Specifically, the gray matter of adults with dyslexia was symmetrically distributed over one particular region of the STS, the temporal voice area, whereas normal readers showed a clear rightward gray matter asymmetry in this area. We also identified a region in the left posterior STG in which the white matter distribution asymmetry was correlated to speech-in-noise comprehension abilities in dyslexic adults. These results provide further information concerning the morphological alterations observed in dyslexia, revealing the presence of both gray and white matter distribution anomalies and the potential involvement of these defects in speech-in-noise deficits.	\N	\N
24098665	Numerous studies have documented the phenomenon of phonetic imitation: the process by which the production patterns of an individual become more similar on some phonetic or acoustic dimension to those of her interlocutor. Though social factors have been suggested as a motivator for imitation, few studies has established a tight connection between language-external factors and a speaker's likelihood to imitate. The present study investigated the phenomenon of phonetic imitation using a within-subject design embedded in an individual-differences framework. Participants were administered a phonetic imitation task, which included two speech production tasks separated by a perceptual learning task, and a battery of measures assessing traits associated with Autism-Spectrum Condition, working memory, and personality. To examine the effects of subjective attitude on phonetic imitation, participants were randomly assigned to four experimental conditions, where the perceived sexual orientation of the narrator (homosexual vs. heterosexual) and the outcome (positive vs. negative) of the story depicted in the exposure materials differed. The extent of phonetic imitation by an individual is significantly modulated by the story outcome, as well as by the participant's subjective attitude toward the model talker, the participant's personality trait of openness and the autistic-like trait associated with attention switching.	\N	\N
24099584	The objective of this prospective study was to investigate the relationship between acceptable noise level (ANL), which was measured using Taiwanese and the international speech test signal (ISTS), and real-world hearing-aid success for listeners who were representative of the population commonly seen in clinics. Unaided ANLs were measured pre-hearing-aid fitting. Hearing-aid success was assessed three months post-fitting using the international outcome inventory for hearing aids (IOI-HA) and a hearing-aid use questionnaire. Eighty adults with hearing impairment completed the study. Both Taiwanese and ISTS ANLs were significantly associated with hearing-aid success, with higher ANLs suggesting poorer outcomes. However, the ANL's prediction accuracy for the probability of hearing-aid success was either much lower than that suggested by some literature, or was not much different from that of simply predicting all listeners as successful users. The current study suggested the possibility of using ANL to predict hearing-aid success. However, the usefulness of ANL as a clinical tool is unlikely to be as great as indicated by the literature.	\N	\N
24101343	In a series of three experiments, we used an ambiguous plaid motion stimulus to explore the behavioral and electrophysiological effects of prior stimulus exposures and perceptual states on current awareness. The results showed that prior exposure to a stimulus biased toward one percept led to subsequent suppression of that percept. In contrast, in the absence of stimulus bias, prior perceptual experience can have a facilitative influence. The suppressive effects caused by the prior stimulus were found to transfer to an ambiguous plaid test stimulus rotated 180º relative to the adaptation stimulus, but were abolished if (1) the ambiguous test stimulus was only rotated 90º relative to the adaptation stimulus or (2) the adaptation stimulus was heavily biased toward the component grating percept. Event-related potential recordings were consistent with the involvement of visual cortical areas and suggested that the influence of recent stimulus exposure may involve recruitment of additional brain processes beyond those responsible for initial stimulus encoding. In contrast, the effects of prior and current perceptual experience appeared to depend on similar brain processes. Although the data presented here focus on vision, the work is discussed within the context of data from a parallel series of experiments in audition.	\N	\N
24110307	The cocktail party problem is a multi-faceted challenge which encompasses various aspects of auditory perception. Its processes underlie the brain's ability to detect, identify and classify sound objects; to robustly represent and maintain speech intelligibility amidst severe distortions; and to guide actions and behaviors in line with complex goals and shifting acoustic soundscapes. Here, we present a perspective that considers the powerful Bayesian inference as a unifying framework to integrate the role of sensory cues as well as stimulus-driven priors and top-down schemas including attention.	\N	\N
24110658	Temporal fine structure (TFS) carries important information for the speech perception of hearing-impaired listeners and for the design of novel prosthetic hearing devices. This study assessed the performance of present intelligibility indices for predicting the intelligibility of speech containing different amount of TFS information. Speech intelligibility data was collected from vocoded and wideband Mandarin sentences containing little/partial and intact TFS information, respectively, and was then subjected to the correlation analysis with existing intelligibility indices. It was found that, though performing well in predicting the intelligibility of vocoded or wideband speech separately, present intelligibility indices were not highly correlated with the intelligibility scores when a general function was used to map all intelligibility measures to intelligibility scores. Analysis further showed that the intelligibility prediction power could be significantly improved when multiple condition-dependent functions were used for mapping intelligibility measures to intelligibility scores.	\N	\N
24116428	Bilateral cochlear implants (CIs) have provided some success in improving spatial hearing abilities to patients, but with large variability in performance. One reason for the variability is that there may be a mismatch in the place-of-stimulation arising from electrode arrays being inserted at different depths in each cochlea. Goupell et al. [(2013b). J. Acoust. Soc. Am. 133(4), 2272-2287] showed that increasing interaural mismatch led to non-fused auditory images and poor lateralization of interaural time differences in normal hearing subjects listening to a vocoder. However, a greater bandwidth of activation helped mitigate these effects. In the present study, the same experiments were conducted in post-lingually deafened bilateral CI users with deliberate and controlled interaural mismatch of single electrode pairs. Results show that lateralization was still possible with up to 3 mm of interaural mismatch, even when off-center, or multiple, auditory images were perceived. However, mismatched inputs are not ideal since it leads to a distorted auditory spatial map. Comparison of CI and normal hearing listeners showed that the CI data were best modeled by a vocoder using Gaussian-pulsed tones with 1.5 mm bandwidth. These results suggest that interaural matching of electrodes is important for binaural cues to be maximally effective.	\N	\N
24116537	Using molecular psychophysics, temporal loudness weights were measured for 2-s, 1-kHz tones with flat, increasing and decreasing time-intensity profiles. While primacy and recency effects were observed for flat profile stimuli, the so-called "level dominance" effect was observed for both increasing and decreasing profile stimuli, fully determining their temporal weights. The weighs obtained for these profiles were basically zero for all but the most intense parts of these sounds. This supports the view that the "level dominance" effect is prominent with intensity-varying sounds and that it persists over time since temporal weights are not affected by the direction of intensity change.	\N	\N
24124356	To assess the benefits of cochlear implantation in the elderly. A retrospective analysis of 31 postlingually deafened elderly (≥60 years of age) with unilateral cochlear implants was conducted. Audiological testing included preoperative and postoperative pure-tone audiometry and a monosyllabic word recognition test presented from recorded material in free field. Speech perception tests included Ling's six sound test (sound detection, discrimination, and identification), syllable discrimination, and monosyllabic and multisyllabic word recognition (open set) without lip-reading. Everyday life benefits from cochlear implantation were also evaluated. The mean age at the time of cochlear implantation was 72.4 years old. The mean postimplantation follow-up time was 2.34 years. All patients significantly improved their audiological and speech understanding performances. The preoperative mean pure-tone average threshold for 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz was 110.17 dB HL. Before cochlear implantation, all patients scored 0% on the monosyllabic word recognition test in free field at 70 dB SPL intensity level. The postoperative pure-tone average was 37.14 dB HL (the best mean threshold was 17.50 dB HL, the worst was 58.75 dB HL). After the surgery, mean monosyllabic word recognition reached 47.25%. Speech perception tests showed statistically significant improvement in speech recognition. The results of this study showed that cochlear implantation is indeed a successful treatment for improving speech recognition and offers a great help in everyday life to deafened elderly patients. Therefore, they can be good candidates for cochlear implantation and their age alone should not be a relevant or excluding factor when choosing candidates for cochlear implantation.	\N	\N
24129008	PURPOSE Previous work has shown that monolingual French and English speakers use distinct articulatory settings, the underlying articulatory posture of a language. In the present article, the authors report on an experiment in which they investigated articulatory settings in bilingual speakers. The authors first tested the hypothesis that in order to sound native-like, bilinguals must use distinct, language-specific articulatory settings in monolingual mode. The authors then tested the hypothesis that in bilingual mode, a bilingual individual's articulatory setting is identical to the monolingual-mode setting of 1 of his or her languages. METHOD Eight French-English bilinguals each read 90 English and 90 French sentences, and the authors measured their interspeech posture (ISP) using optical tracking of the lips and jaw and ultrasound imaging of the tongue. RESULTS Results show that bilingual speakers who are perceived as native in both languages exhibit distinct, language-specific ISPs, and those who are not perceived as native in one or more languages do not. In bilingual mode, bilinguals use an ISP that is equivalent to the monolingual-mode ISP of their currently most used language. The most balanced bilingual used a French lip ISP but an English tongue-tip ISP. CONCLUSION Results support the claim that bilinguals who sound native in each of their languages have distinct articulatory settings for each language.	\N	\N
24130256	Biological motion research is an increasingly active field, with a great potential to contribute to a wide range of applications, such as behavioral monitoring/motion detection in surveillance situations, intention inference in social interactions, and diagnostic tools in autism research. In recent years, a large amount of motion capture data has become freely available online, potentially providing rich stimulus sets for biological motion research. However, there currently does not exist an easy-to-use tool to extract, present and manipulate motion capture data in the MATLAB environment, which many researchers use to program their experiments. We have developed the Biomotion Toolbox, which allows researchers to import motion capture data in a variety of formats, to display actions using Psychtoolbox 3, and to manipulate action displays in specific ways (e.g., inversion, three-dimensional rotation, spatial scrambling, phase-scrambling, and limited lifetime). The toolbox was designed to allow researchers with a minimal level of MATLAB programming skills to code experiments using biological motion stimuli.	\N	\N
24130865	Temporal processing underlies both music and language skills. There is increasing evidence that rhythm abilities track with reading performance and that language disorders such as dyslexia are associated with poor rhythm abilities. However, little is known about how basic time-keeping skills can be shaped by musical training, particularly during critical literacy development years. This study was carried out in collaboration with Harmony Project, a non-profit organization providing free music education to children in the gang reduction zones of Los Angeles. Our findings reveal that elementary school children with just one year of classroom music instruction perform more accurately in a basic finger-tapping task than their untrained peers, providing important evidence that fundamental time-keeping skills may be strengthened by short-term music training. This sets the stage for further examination of how music programs may be used to support the development of basic skills underlying learning and literacy, particularly in at-risk populations which may benefit the most.	\N	\N
24131604	The Dichotic Verbal Memory Test (DVMT) is useful in detecting verbal memory deficits and differences in memory function between the brain hemispheres. The purpose of this study was to prepare the Persian version of DVMT, to obtain its results in 18- to 25-yr-old Iranian individuals, and to examine the ear, gender, and serial position effect. The Persian version of DVMT consisted of 18 10-word lists. After preparing the 18 lists, content validity was assessed by a panel of eight experts and the equivalency of the lists was evaluated. Then the words were recorded on CD in a dichotic mode such that 10 words were presented to one ear, with the same words reversed simultaneously presented to the other ear. Thereafter, it was performed on a sample of young, normal, Iranian individuals. Thirty normal individuals (no history of neurological, ontological, or psychological diseases) with ages ranging from 18 to 25 yr were examined for evaluating the equivalency of the lists, and 110 subjects within the same age range participated in the final stage of the study to obtain the normative data on the developed test. There was no significant difference between the mean scores of the 18 developed lists (p > 0.05). The mean content validity index (CVI) score was .96. A significant difference was found between the mean score of the two ears (p < 0.05) and between female and male participants (p < 0.05). The Persian version of DVMT has good content validity and can be used for verbal memory assessment in Iranian young adults.	\N	\N
24131606	Current bone anchored hearing solutions (BAHSs) have incorporated automatic adaptive multichannel directional microphones (DMs). Previous fixed single-channel hypercardioid DMs in BAHSs have provided benefit in a diffuse listening environment, but little data are available on the performance of adaptive multichannel DMs in BAHSs for persons with unilateral sensorineural hearing loss (USNHL). The primary goal was to determine if statistically significant differences existed in the mean Reception Threshold for Sentences (RTS in dB) in diffuse uncorrelated restaurant noise between unaided, an omnidirectional microphone (OM), split DM (SDM), and full DM (FDM) in the Oticon Medical Ponto Pro. A second goal was to assess subjective benefit using the Abbreviated Profile of Hearing Aid Benefit (APHAB) comparing the Ponto Pro to the participant's current BAHS, and the Ponto Pro and participant's own BAHS to unaided. The third goal was to compare RTS data of the Ponto Pro to data from an identical study examining Cochlear Americas' Divino. A randomized repeated measures, single blind design was used to measure an RTS for each participant for unaided, OM, SDM, and FDM. Fifteen BAHS users with USNHL were recruited from Washington University in St. Louis and the surrounding area. The Ponto Pro was fit by measuring in-situ bone conduction thresholds and was worn for 4 wk. An RTS was obtained utilizing Hearing in Noise Test (HINT) sentences in uncorrelated restaurant noise from an eight loudspeaker array, and subjective benefit was determined utilizing the APHAB. Analysis of variance (ANOVA) was used to analyze the results of the Ponto Pro HINT and APHAB data, and comparisons between the Ponto Pro and previous Divino data. No statistically significant differences existed in mean RTS between unaided, the Ponto Pro's OM, SDM, or FDM (p = 0.10). The Ponto Pro provided statistically significant benefit for the Background Noise (BN) (p < 0.01) and Reverberation (RV) (p < 0.05) subscales compared to the participant's own BAHS. The Ponto Pro (Ease of Communication [EC] [p < 0.01], BN [p < 0.001], and RV [p < 0.01] subscales) and participant's own BAHS (BN [p < 0.01] and RV [p < 0.01] subscales) overall provided statistically significant benefit compared to unaided. Clinically significant benefit of 5% was present for the Ponto Pro compared to the participant's own BAHS and 10% for the Ponto Pro and the participant's own BAHS compared to unaided. The Ponto Pro's OM (p = 0.05), SDM (p = 0.05), and FDM (p < 0.01) were statistically significantly better than the Divino's OM. No significant differences existed between the Ponto Pro's OM, SDM, and FDM compared to the Divino's DM. No statistically significant differences existed between unaided, OM, SDM, or FDM. Participants preferred the Ponto Pro compared to the participant's own BAHS and the Ponto Pro and participant's own BAHS compared to unaided. The RTS of the Ponto Pro's adaptive multichannel DM was similar to the Divino's fixed hypercardioid DM, but the Ponto Pro's OM was statistically significantly better than the Divino's OM.	\N	\N
24136318	Hearing loss resulting from bilateral vestibular schwannomas (VSs) has a significant effect on the quality of life of patients with neurofibromatosis Type 2 (NF2). A national consensus protocol was produced in England as a guide for cochlear implantation (CI) and auditory brainstem implantation (ABI) in these patients. Consensus statement. English NF2 Service. Clinicians from all 4 lead NF2 units in England. A protocol for the assessment, insertion and rehabilitation of CI and ABI in NF2 patients. Patients should undergo more detailed hearing assessment once their maximum aided speech discrimination score falls below 50% in the better hearing ear. Bamford-Kowal-Bench sentence testing scores below 50% should trigger assessment for auditory implantation, as recommended by the National Institute for Clinical Excellence guidelines on CI. Where this occurs in patients with bilateral stable VS or a unilateral stable VS where the contralateral cochlear nerve was lost at previous surgery, CI should be considered. Where VS surgery is planned, CI should be considered where cochlear nerve preservation is thought possible, otherwise an ABI should be considered. Intraoperative testing using electrically evoked auditory brainstem responses or cochlear nerve action potentials may be used to determine whether a CI or ABI is inserted. The NF2 centers in England agreed on this protocol. Multisite, prospective assessments of standardized protocols for auditory implantation in NF2 provide an essential model for evaluating candidacy and outcomes in this challenging patient population.	\N	\N
24139706	Language experience can alter perceptual abilities and the neural specialization for phonological contrasts. Here we investigated whether dialectal differences in the lexical use of pitch information lead to differences in functional lateralization for pitch processing. We measured cortical hemodynamic responses to pitch pattern changes in native speakers of Standard (Tokyo) Japanese, which has a lexical pitch accent system, and native speakers of 'accentless' dialects, which do not have any lexical tonal phenomena. While the Standard Japanese speakers showed left-dominant responses in temporal regions to pitch pattern changes within words, the accentless dialects speakers did not show such left-dominance. Pitch pattern changes within harmonic-complex tones also elicited different brain activation patterns between the two groups. These results indicate that the neural processing of pitch information differs depending on the listener's native dialect, and that listeners' linguistic experiences may further affect the processing of pitch changes even for non-linguistic sounds.	\N	\N
24141311	Across all sensory modalities, the effect of context-dependent neural adaptation can be observed at every level, from receptors to perception. Nonetheless, it has long been assumed that the processing of interaural time differences, which is the primary cue for sound localization, is nonadaptive, as its outputs are mapped directly onto a hard-wired representation of space. Here we present evidence derived from in vitro and in vivo experiments in gerbils indicating that the coincidence-detector neurons in the medial superior olive modulate their sensitivity to interaural time differences through a rapid, GABA(B) receptor-mediated feedback mechanism. We show that this mechanism provides a gain control in the form of output normalization, which influences the neuronal population code of auditory space. Furthermore, psychophysical tests showed that the paradigm used to evoke neuronal GABA(B) receptor-mediated adaptation causes the perceptual shift in sound localization in humans that was expected on the basis of our physiological results in gerbils.	\N	\N
24141681	The signal processing strategy is a parameter that may influence the auditory performance of cochlear implant and is important to optimize this parameter to provide better speech perception, especially in difficult listening situations. To evaluate the individual's auditory performance using two different signal processing strategy. Prospective study with 11 prelingually deafened children with open-set speech recognition. A within-subjects design was used to compare performance with standard HiRes and HiRes 120 in three different moments. During test sessions, subject's performance was evaluated by warble-tone sound-field thresholds, speech perception evaluation, in quiet and in noise. In the silence, children S1, S4, S5, S7 showed better performance with the HiRes 120 strategy and children S2, S9, S11 showed better performance with the HiRes strategy. In the noise was also observed that some children performed better using the HiRes 120 strategy and other with HiRes. Not all children presented the same pattern of response to the different strategies used in this study, which reinforces the need to look at optimizing cochlear implant clinical programming.	\N	\N
24148845	Autism spectrum disorders (ASDs) are associated with auditory hyper- or hyposensitivity; atypicalities in central auditory processes, such as speech-processing and selective auditory attention; and neural connectivity deficits. We sought to investigate whether the low-level integrative processes underlying sound localization and spatial discrimination are affected in ASDs. We performed 3 behavioural experiments to probe different connecting neural pathways: 1) horizontal and vertical localization of auditory stimuli in a noisy background, 2) vertical localization of repetitive frequency sweeps and 3) discrimination of horizontally separated sound stimuli with a short onset difference (precedence effect). Ten adult participants with ASDs and 10 healthy control listeners participated in experiments 1 and 3; sample sizes for experiment 2 were 18 adults with ASDs and 19 controls. Horizontal localization was unaffected, but vertical localization performance was significantly worse in participants with ASDs. The temporal window for the precedence effect was shorter in participants with ASDs than in controls. The study was performed with adult participants and hence does not provide insight into the developmental aspects of auditory processing in individuals with ASDs. Changes in low-level auditory processing could underlie degraded performance in vertical localization, which would be in agreement with recently reported changes in the neuroanatomy of the auditory brainstem in individuals with ASDs. The results are further discussed in the context of theories about abnormal brain connectivity in individuals with ASDs.	\N	\N
24150886	Facilitatory effects have been noted between tools and the objects that they act upon (their "action recipients") across several paradigms. However, it has not been convincingly established that the motor system is directly involved in the joint visual processing of these object pairings. Here, we used the attentional blink (AB) paradigm to demonstrate privileged access to perceptual awareness for tool-action recipient object pairs and to investigate how motor affordances modulate their joint processing. We demonstrated a reduction in the size of the AB that was greater for congruent tool-action recipient pairings (e.g., hammer-nail) than for incongruent pairings (e.g., scissors-nail). Moreover, the AB was reduced only when action recipients followed their associated tool in the temporal sequence, but not when this order was reversed. Importantly, we also found that the effect was sensitive to manipulations of the motor congruence between the tool and the action recipient. First, we observed a greater reduction in the AB when the tool and action recipient were correctly aligned for action than when the tool was rotated to face away from the action recipient. Second, presenting a different tool as a distractor between the tool and action recipient target objects removed any benefit seen for congruent pairings. This was likely due to interference from the motor properties of the distractor tool that disrupted the motor synergy between the congruent tool and action recipient targets. Overall, these findings demonstrate that the contextual motoric relationship between tools and their action recipients facilitates their visual encoding and access to perceptual awareness.	\N	\N
24157488	The aim of this study was to evaluate electrode array position in relation to cochlear anatomy and its influence on hearing performance in cochlear implantees. Twenty-two patients (25 ears) with Med-El cochlear implants were included in this retrospective study. A negative correlation was observed between electrode-modiolus distance (EMD) at the cochlear base and monosyllabic word discrimination 6 months after implantation. We found no correlation between EMD and hearing outcome at 12 months. The insertion depth/cochlear perimeter ratio appeared to negatively influence the EMD at the base. Indeed, deep insertions in small cochleae appeared to yield smaller EMD and better hearing performance. This observation supports the idea of preplanning the surgery by adapting the electrode array to the length of the available scala tympani.	\N	\N
24157596	Rhythmic disturbances are a hallmark of motor speech disorders, in which the motor control deficits interfere with the outward flow of speech and by extension speech understanding. As the functions of rhythm are language-specific, breakdowns in rhythm should have language-specific consequences for communication. The goals of this paper are to (i) provide a review of the cognitive-linguistic role of rhythm in speech perception in a general sense and crosslinguistically; (ii) present new results of lexical segmentation challenges posed by different types of dysarthria in American English, and (iii) offer a framework for crosslinguistic considerations for speech rhythm disturbances in the diagnosis and treatment of communication disorders associated with motor speech disorders. This review presents theoretical and empirical reasons for considering speech rhythm as a critical component of communication deficits in motor speech disorders, and addresses the need for crosslinguistic research to explore language-universal versus language-specific aspects of motor speech disorders.	\N	\N
24157638	This study sought to determine if a monolingual English listener could rate nasality in English and in Spanish with the same proficiency as a bilingual English-Spanish listener, and to compare nasalance scores with nasality ratings. Speakers for this study were 26 bilingual English-Spanish-speaking children. Speech samples and nasalance scores were obtained simultaneously as each speaker recited one English sentence and one Spanish sentence. A monolingual listener and a bilingual listener rated nasality. For the English sentences, the intrajudge correlation coefficient was r = 0.89 for the monolingual listener and r = 0.89 for the bilingual listener. For the Spanish sentences, the intrajudge correlation coefficient was r = 0.91 for the monolingual listener and r = 0.92 for the bilingual listener. Interjudge agreement was r = 0.86 for rating English sentences and r = 0.78 for rating Spanish sentences. All correlation coefficients were significant (p < 0.001). The correlation coefficients between nasality ratings and nasalance scores were essentially the same for both listeners and both languages. A monolingual and a bilingual judge had high agreement on ratings of nasality for English and Spanish speech. The relationship between nasalance and nasality was not different across languages.	\N	\N
24157861	Quite often, magnetoencephalography (MEG) measurements are contaminated by a series of artifacts that degrade the quality of the various source localization methods applied to them. In particular, eye blinking, minor head movement and related activities are a constant source of measurement contamination. In order to solve this problem, trial selection and rejection is applied, a task that is usually performed manually. The present work shows an automatic trial selection and rejection algorithm based on clustering techniques. These techniques employ a measurement of the dissimilarity of the items belonging to a set. This measure, based on the projection of the eigenvector corresponding to the largest eigenvalue of the covariance matrix, is provided and its rationale is explained. Subsequently, covariance matrices belonging to the selected cluster are averaged and used in the well-known Linearly Constrained Minimum Variance (LCMV) Beamformer. The results show a marked improvement of the specificity of the localization algorithm compared to the application of the LCMV without clustering. The method shows a marked reduction in computational cost compared with other data cleaning procedure widely used: Independent Component Analysis (ICA). Thus, we propose clustering techniques to be used in brain localization activity algorithms.	\N	\N
24161466	A current view proposes that the right inferior frontal cortex (IFC) is particularly responsible for attentive decoding and cognitive evaluation of emotional cues in human vocalizations. Although some studies seem to support this view, an exhaustive review of all recent imaging studies points to an important functional role of both the right and the left IFC in processing vocal emotions. Second, besides a supposed predominant role of the IFC for an attentive processing and evaluation of emotional voices in IFC, these recent studies also point to a possible role of the IFC in preattentive and implicit processing of vocal emotions. The studies specifically provide evidence that both the right and the left IFC show a similar anterior-to-posterior gradient of functional activity in response to emotional vocalizations. This bilateral IFC gradient depends both on the nature or medium of emotional vocalizations (emotional prosody versus nonverbal expressions) and on the level of attentive processing (explicit versus implicit processing), closely resembling the distribution of terminal regions of distinct auditory pathways, which provide either global or dynamic acoustic information. Here we suggest a functional distribution in which several IFC subregions process different acoustic information conveyed by emotional vocalizations. Although the rostro-ventral IFC might categorize emotional vocalizations, the caudo-dorsal IFC might be specifically sensitive to their temporal features.	\N	\N
24163248	Aphasic deficits are usually only interpreted in terms of domain-specific language processes. However, effective human communication and tests that probe this complex cognitive skill are also dependent on domain-general processes. In the clinical context, it is a pragmatic observation that impaired attention and executive functions interfere with the rehabilitation of aphasia. One system that is important in cognitive control is the salience network, which includes dorsal anterior cingulate cortex and adjacent cortex in the superior frontal gyrus (midline frontal cortex). This functional imaging study assessed domain-general activity in the midline frontal cortex, which was remote from the infarct, in relation to performance on a standard test of spoken language in 16 chronic aphasic patients both before and after a rehabilitation programme. During scanning, participants heard simple sentences, with each listening trial followed immediately by a trial in which they repeated back the previous sentence. Listening to sentences in the context of a listen-repeat task was expected to activate regions involved in both language-specific processes (speech perception and comprehension, verbal working memory and pre-articulatory rehearsal) and a number of task-specific processes (including attention to utterances and attempts to overcome pre-response conflict and decision uncertainty during impaired speech perception). To visualize the same system in healthy participants, sentences were presented to them as three-channel noise-vocoded speech, thereby impairing speech perception and assessing whether this evokes domain general cognitive systems. As expected, contrasting the more difficult task of perceiving and preparing to repeat noise-vocoded speech with the same task on clear speech demonstrated increased activity in the midline frontal cortex in the healthy participants. The same region was activated in the aphasic patients as they listened to standard (undistorted) sentences. Using a region of interest defined from the data on the healthy participants, data from the midline frontal cortex was obtained from the patients. Across the group and across different scanning sessions, activity correlated significantly with the patients' communicative abilities. This correlation was not influenced by the sizes of the lesion or the patients' chronological ages. This is the first study that has directly correlated activity in a domain general system, specifically the salience network, with residual language performance in post-stroke aphasia. It provides direct evidence in support of the clinical intuition that domain-general cognitive control is an essential factor contributing to the potential for recovery from aphasic stroke.	\N	\N
24183205	To evaluate both monaural and binaural processing skills in a group of children with autism spectrum disorder (ASD) and to determine the degree to which personal frequency modulation (radio transmission) (FM) listening systems could ameliorate their listening difficulties. Auditory temporal processing (amplitude modulation detection), spatial listening (integration of binaural difference cues), and functional hearing (speech perception in background noise) were evaluated in 20 children with ASD. Ten of these subsequently underwent a 6-week device trial in which they wore the FM system for up to 7 hours per day. Auditory temporal processing and spatial listening ability were poorer in subjects with ASD than in matched controls (temporal: P = .014 [95% CI -6.4 to -0.8 dB], spatial: P = .003 [1.0 to 4.4 dB]), and performance on both of these basic processing measures was correlated with speech perception ability (temporal: r = -0.44, P = .022; spatial: r = -0.50, P = .015). The provision of FM listening systems resulted in improved discrimination of speech in noise (P < .001 [11.6% to 21.7%]). Furthermore, both participant and teacher questionnaire data revealed device-related benefits across a range of evaluation categories including Effect of Background Noise (P = .036 [-60.7% to -2.8%]) and Ease of Communication (P = .019 [-40.1% to -5.0%]). Eight of the 10 participants who undertook the 6-week device trial remained consistent FM users at study completion. Sustained use of FM listening devices can enhance speech perception in noise, aid social interaction, and improve educational outcomes in children with ASD.	\N	\N
24216384	To investigate automatic event-related potentials (ERPs) to an auditory change in migraine patients. Auditory ERPs were recorded in 22 female patients suffering from menstrually-related migraine and in 20 age-matched control subjects, in three sessions: in the middle of the menstrual cycle, before and during menses. In each session, 200 trains of tone-bursts each including two duration deviants were presented in a passive listening condition. In all sessions, duration deviance elicited a mismatch negativity (MMN) showing no difference between the two groups. However, migraine patients showed an increased N1 orienting component to all incoming stimuli and a prolonged N2b to deviance. They also presented a different modulation of P3a amplitude along the menstrual cycle, which tended to normalise during migraine attacks. None of the studied ERP components showed a default of habituation. This passive paradigm highlighted increased automatic attention orienting to auditory changes but normal auditory sensory processing in migraineurs. Our observations suggest normal auditory processing up to attention triggering but enhanced activation of attention-related frontal networks in migraineurs.	\N	\N
24219698	In Williams Syndrome (WS), a known genetic deletion results in atypical brain function with strengths in face and language processing. We examined how genetic influences on brain activity change with development. In three studies, event-related potentials (ERPs) from large samples of children, adolescents, and adults with the full genetic deletion for WS were compared to typically developing controls, and two adults with partial deletions for WS. Studies 1 and 2 identified ERP markers of brain plasticity in WS across development. Study 3 suggested that, in adults with partial deletions for WS, specific genes may be differentially implicated in face and language processing.	\N	\N
24231421	A technology of backup alarms based on the use of a broadband signal has recently gained popularity in many countries. In this study, the performance of this broadband technology is compared to that of a conventional tonal alarm and a multi-tone alarm from a worker-safety standpoint. Field measurements of sound pressure level patterns behind heavy vehicles were performed in real work environments and psychoacoustic measurements (sound detection thresholds, equal loudness, perceived urgency and sound localization) were carried out in the laboratory with human subjects. Compared with the conventional tonal alarm, the broadband alarm generates a much more uniform sound field behind vehicles, is easier to localize in space and is judged slighter louder at representative alarm levels. Slight advantages were found with the tonal alarm for sound detection and for perceived urgency at low levels, but these benefits observed in laboratory conditions would not overcome the detrimental effects associated with the large and abrupt variations in sound pressure levels (up to 15-20 dB within short distances) observed in the field behind vehicles for this alarm, which are significantly higher than those obtained with the broadband alarm. Performance with the multi-tone alarm generally fell between that of the tonal and broadband alarms on most measures.	\N	\N
24231629	This study aimed to (1) determine the sensitivity of the electrically evoked auditory change complex (eACC) to changes in stimulating electrode position; and (2) investigate the association between results of eACC measures and behavioral electrode discrimination and their association with speech-perception performance in pediatric cochlear implant (CI) users who have auditory neuropathy spectrum disorder (ANSD). Fifteen children with ANSD ranging in age between 5.4 and 18.6 years participated in this study. All subjects used Cochlear Nucleus devices. For each subject, open-set speech-perception ability was assessed using the Phonetically Balanced Kindergarten word lists presented at 60 dB SPL, using monitored live voice in a sound booth. Behavioral and objective measures of electrode discrimination were assessed in a nonclinical test environment. The stimuli used to elicit these measures were 800 msec biphasic pulse trains delivered by a direct interface to the CI. Data were collected from two basic stimulation conditions. In the standard condition, the entire pulse train was delivered to a mid-array electrode (electrode 11 or 12) at the maximum comfortable level (C level). In the change condition, the stimulus was split into two 400 msec pulse train segments presented sequentially on two different electrodes. The stimulation level of the second 400 msec pulse train was loudness balanced to the C level of the mid-array electrode used in the standard condition. The separation between the pair of stimulating electrodes was systematically varied. For behavioral electrode-discrimination measures, each subject was required to determine whether he or she heard one or two sounds for stimuli presented in different stimulation conditions. For the eACC measures, two replicates of 100 artifact-free sweeps were recorded for each stimulation condition. The eACC in response to changes in stimulating electrode position was recorded from all subjects with ANSD using direct electrical stimulation. Electrode-discrimination thresholds determined with the eACC and behavioral measures were consistent. Children with ANSD using CIs who showed poorer speech performance also required larger separations between the stimulating electrode pair to reliably elicit the eACC than subjects with better speech-perception performance. There was a robust correlation between electrode-discrimination capacities and speech-perception performances in subjects tested in this study. The effect of electrode separation on eACC amplitudes was not monotonic. These results demonstrate the feasibility of using eACC to evaluate electrode-discrimination capacities in children with ANSD. These results suggest that the eACC elicited by changes in stimulating electrode position holds great promise as an objective tool for evaluating spectral-pattern detection in such subjects, which may be predictive of their potential speech-perception performance.	\N	\N
24232062	Children with auditory neuropathy (AN) have variable hearing on pure tone testing, and the presence of speech and language delays often play a major role in the decision to offer cochlear implantation (CI) in this population. Despite this fact, the speech and language outcomes in this group after CI are not well described. This study compares speech and language outcomes after CI in a subset of the pediatric AN population that does not have a confounding cognitive disorder with those of their peers with cochlear hearing loss (CoHL). Retrospective chart review. Tertiary referral center. Seventeen pediatric patients with AN who received a CI and a group of children with CoHL who received a CI were the subjects of this study. The 2 groups demonstrated similar ages at implant. Children with cognitive delays were excluded from each group. Cochlear implantation. All subjects were evaluated preoperatively and postoperatively with standardized age appropriate speech and language measures, including the Expressive Vocabulary Test (EVT), Peabody Picture Vocabulary Test (PPVT), and Preschool Language Scale (PLS). There was no significant difference between the groups on age of activation of the CI. Children with a diagnosis of AN had a significantly lower unaided pure tone average preoperatively as compared with children with cochlear hearing loss; however, there was no significant difference between the groups on either their preimplantation or postimplantation speech and language scores. Children with a diagnosis of AN without associated cognitive or developmental disorders have speech and language outcomes comparable to other children who received a CI.	\N	\N
24236696	Evidence in animals and humans indicates that there are sensitive periods during development, times when experience or stimulation has a greater influence on behavior and brain structure. Sensitive periods are the result of an interaction between maturational processes and experience-dependent plasticity mechanisms. Previous work from our laboratory has shown that adult musicians who begin training before the age of 7 show enhancements in behavior and white matter structure compared with those who begin later. Plastic changes in white matter and gray matter are hypothesized to co-occur; therefore, the current study investigated possible differences in gray matter structure between early-trained (ET; <7) and late-trained (LT; >7) musicians, matched for years of experience. Gray matter structure was assessed using voxel-wise analysis techniques (optimized voxel-based morphometry, traditional voxel-based morphometry, and deformation-based morphometry) and surface-based measures (cortical thickness, surface area and mean curvature). Deformation-based morphometry analyses identified group differences between ET and LT musicians in right ventral premotor cortex (vPMC), which correlated with performance on an auditory motor synchronization task and with age of onset of musical training. In addition, cortical surface area in vPMC was greater for ET musicians. These results are consistent with evidence that premotor cortex shows greatest maturational change between the ages of 6-9 years and that this region is important for integrating auditory and motor information. We propose that the auditory and motor interactions required by musical practice drive plasticity in vPMC and that this plasticity is greatest when maturation is near its peak.	\N	\N
24236753	Does temporal regularity facilitate prediction in audition? To test this, we recorded human event-related potentials to frequent standard tones and infrequent pitch deviant tones, pre-attentively delivered within isochronous and anisochronous (20% onset jitter) rapid sequences. Deviant tones were repeated, either with high or low probability. Standard tone repetition sets a first-order prediction, which is violated by deviant tone onset, leading to a first-order prediction error response (Mismatch Negativity). The response to highly probable deviant repetitions is, however, attenuated relative to less probable repetitions, reflecting the formation of higher-order sensory predictions. Results show that temporal regularity is required for higher-order predictions, but does not modulate first-order prediction error responses. Inverse solution analyses (Variable Resolution Electrical Tomography; VARETA) localized the error response attenuation to posterior regions of the left superior temporal gyrus. In a control experiment with a slower stimulus rate, we found no evidence for higher-order predictions, and again no effect of temporal information on first-order prediction error. We conclude that: (i) temporal regularity facilitates the establishing of higher-order sensory predictions, i.e. 'knowing what next', in fast auditory sequences; (ii) first-order prediction error relies predominantly on stimulus feature mismatch, reflecting the adaptive fit of fast deviance detection processes.	\N	\N
24244617	Due to their different propagation times, visual and auditory signals from external events arrive at the human sensory receptors with a disparate delay. This delay consistently varies with distance, but, despite such variability, most events are perceived as synchronic. There is, however, contradictory data and claims regarding the existence of compensatory mechanisms for distance in simultaneity judgments. In this paper we have used familiar audiovisual events--a visual walker and footstep sounds--and manipulated the number of depth cues. In a simultaneity judgment task we presented a large range of stimulus onset asynchronies corresponding to distances of up to 35 meters. We found an effect of distance over the simultaneity estimates, with greater distances requiring larger stimulus onset asynchronies, and vision always leading. This effect was stronger when both visual and auditory cues were present but was interestingly not found when depth cues were impoverished. These findings reveal that there should be an internal mechanism to compensate for audiovisual delays, which critically depends on the depth information available.	\N	\N
24257810	Remifentanil (Ultiva(®)) is a potent ultra-short acting mu-opioid receptor agonist used for perioperative pain treatment and anaesthesia. So far, it is not known how sensitive the cognitive processing of auditory perception elicited by the mismatch negativity (MMN) paradigm is to opioids. The present exploratory study investigated how the opioid remifentanil modulates different stages of auditory processing as reflected in the MMN(m) and P3a(m). We recorded electroencephalography (EEG) and magnetoencephalography (MEG) during auditory stimulation under remifentanil or placebo infusion in 20 healthy participants. For the MMN, a gender effect was found for tones deviating in frequency (± 10%) from the standard tone. Remifentanil increased the amplitude of the frequency MMN at F3 in females but not in males. No effect of treatment was found for the MMN(m) or the novel P3a(m). These results suggest that while the bottom-up stimulus change detection system for auditory stimuli appears to be relatively insensitive to opioids, the automatic attention switch caused by the change detection seems to be modulated by the opioid system in females. The multiple deviant paradigm including novel sounds is a promising tool for investigating pharmacological manipulation of different stages of auditory processing. Furthermore, combining the two techniques will yield more specific information about the drug effects on MMN(m).	\N	\N
24259564	One of the more enduring mysteries of neuroscience is how the visual system constructs robust maps of the world that remain stable in the face of frequent eye movements. Here we show that encoding the position of objects in external space is a relatively slow process, building up over hundreds of milliseconds. We display targets to which human subjects saccade after a variable preview duration. As they saccade, the target is displaced leftwards or rightwards, and subjects report the displacement direction. When subjects saccade to targets without delay, sensitivity is poor; but if the target is viewed for 300-500 ms before saccading, sensitivity is similar to that during fixation with a strong visual mask to dampen transients. These results suggest that the poor displacement thresholds usually observed in the "saccadic suppression of displacement" paradigm are a result of the fact that the target has had insufficient time to be encoded in memory, and not a result of the action of special mechanisms conferring saccadic stability. Under more natural conditions, trans-saccadic displacement detection is as good as in fixation, when the displacement transients are masked.	\N	\N
24259673	Viewers can recognize the gist of a scene (i.e., its holistic semantic representation, such as its category) in less time than a single fixation, and backward masking has traditionally been employed as a means to determine that time course. The masks used in those paradigms are often characterized by either specific amplitude spectra only, or amplitude and phase spectra-defined structural properties. However, it remains unclear whether there would be a differential contribution of amplitude only or amplitude + phase defined image statistics to the effective backward masking of rapid scene categorization. The current study addresses this issue. Experiments 1-3 explored amplitude spectra defined contributions to category masking and revealed that the slope of the amplitude spectrum was more important for modulating scene category masking strength than amplitude orientation. Further, the masking effects followed an "amplitude spectrum slope similarity principle" whereby the more similar the amplitude spectrum slope of the mask was to the target's amplitude spectrum slope, the stronger the masking. Experiment 5 showed that, when holding mask amplitude spectrum slope approximately constant, both categorically specific unrecognizable amplitude only and amplitude + phase statistical regularities disrupted rapid scene categorization. Specifically, the masking effects observed in Experiment 5 followed a target-mask categorical dissimilarity principle whereby the more dissimilar the mask category is to the target image category, the stronger the masking. Overall, the results support the notion that amplitude only or amplitude + phase-defined image statistics differentially contribute to the effective backward masking of rapid scene gist recognition.	\N	\N
24265213	This study assesses the effects of adding low- or high-frequency information to the band-limited telephone-processed speech on bimodal listeners' telephone speech perception in quiet environments. In the proposed experiments, bimodal users were presented under quiet listening conditions with wideband speech (WB), bandpass-filtered telephone speech (300-3,400 Hz, BP), high-pass filtered speech (f > 300 Hz, HP, i.e., distorted frequency components above 3,400 Hz in telephone speech were restored), and low-pass filtered speech (f < 3,400 Hz, LP, i.e., distorted frequency components below 300 Hz in telephone speech were restored). Results indicated that in quiet environments, for all four types of stimuli, listening with both hearing aid (HA) and cochlear implant (CI) was significantly better than listening with CI alone. For both bimodal and CI-alone modes, there were no statistically significant differences between the LP and BP scores and between the WB and HP scores. However, the HP scores were significantly better than the BP scores. In quiet conditions, both CI alone and bimodal listening achieved the largest benefits when telephone speech was augmented with high rather than low-frequency information. These findings provide support for the design of algorithms that would extend higher frequency information, at least in quiet environments.	\N	\N
24268879	Timing performance becomes less precise for longer intervals, which makes it difficult to achieve simultaneity in synchronisation with a rhythm. The metrical structure of music, characterised by hierarchical levels of binary or ternary subdivisions of time, may function to increase precision by providing additional timing information when the subdivisions are explicit. This hypothesis was tested by comparing synchronisation performance across different numbers of metrical levels conveyed by loudness of sounds, such that the slowest level was loudest and the fastest was softest. Fifteen participants moved their hand with one of 9 inter-beat intervals (IBIs) ranging from 524 to 3,125 ms in 4 metrical level (ML) conditions ranging from 1 (one movement for each sound) to 4 (one movement for every 8th sound). The lowest relative variability (SD/IBI<1.5%) was obtained for the 3 longest IBIs (1600-3,125 ms) and MLs 3-4, significantly less than the smallest value (4-5% at 524-1024 ms) for any ML 1 condition in which all sounds are identical. Asynchronies were also more negative with higher ML. In conclusion, metrical subdivision provides information that facilitates temporal performance, which suggests an underlying neural multi-level mechanism capable of integrating information across levels.	\N	\N
24270967	An important parameter for characterization of the acoustic quality of closed rooms is reverberation. There is a rising interest in evaluating the ability of cochlear implant (CI) users to understand speech in real-world environments. Whereas the influence of noise on speech perception has been widely investigated, much less is known about the detrimental effect of reverberation. The present study aimed to investigate the influence of reverberation time on the speech perception of CI users and subjects with normal hearing. A reverberated version of the sentences of the Oldenburg sentence test (OLSA) which is a widely used German test to measure speech reception thresholds (SRT) in cochlear implant users was generated using professional audio processing software. The reverberation times used were 0.7, 1.0, 1.5 and 2.0 s. For these four reverberation times and for a non-reverberated control condition, the SRT was measured in eight adult CI users and in eight subjects with normal hearing. To characterize the detrimental effect of reverberation the SRT differences between the reverberated and non-reverberated conditions were calculated. These SRT differences revealed a significant effect of reverberation in CI users with, e.g. a mean SRT increase of 2.9 dB in CI users and 0.9 dB in subjects with normal hearing for a reverberation time of 0.7 s. A strong correlation was found between the SRT increase and the SRT in the non-reverberated condition, highlighting the problems of poor performers in reverberant environments. The results of the current investigation indicated that reverberation results in decreased speech understanding of CI users.	\N	\N
24274362	Infant vocalizations and "looming sounds" are classes of environmental stimuli that are critically important to survival but can have dramatically different emotional valences. Here, we simultaneously presented listeners with a stationary infant vocalization and a 3D virtual looming tone for which listeners made auditory time-to-arrival judgments. Negatively valenced infant cries produced more cautious (anticipatory) estimates of auditory arrival time of the tone over a no-vocalization control. Positively valenced laughs had the opposite effect, and across all conditions, men showed smaller anticipatory biases than women. In Experiment 2, vocalization-matched vocoded noise stimuli did not influence concurrent auditory time-to-arrival estimates compared with a control condition. In Experiment 3, listeners estimated the egocentric distance of a looming tone that stopped before arriving. For distant stopping points, women estimated the stopping point as closer when the tone was presented with an infant cry than when it was presented with a laugh. For near stopping points, women showed no differential effect of vocalization type. Men did not show differential effects of vocalization type at either distance. Our results support the idea that both the sex of the listener and the emotional valence of infant vocalizations can influence auditory motion perception and can modulate motor responses to other behaviorally relevant environmental sounds. We also find support for previous work that shows sex differences in emotion processing are diminished under conditions of higher stress.	\N	\N
24293020	Multisensory enhancement, as a facilitation phenomenon, is responsible for superior behavioral performance when an individual is responding to cross-modal versus modality-specific stimuli. However, the event-related potential (ERP) counterparts of behavioral multisensory enhancement are not well known. We recorded ERPs and behavioral data from 14 healthy volunteers with three types of target stimuli (modality-specific, bimodal, and trimodal) to examine the spatio-temporal electrophysiological characteristics of multisensory enhancement by comparing behavioral data with ERPs. We found a strong correlation between P3 latency and behavioral performance in terms of reaction time (RT) (R = 0.98, P <0.001), suggesting that P3 latency constitutes a temporal measure of behavioral multisensory enhancement. In addition, a fast RT and short P3 latency were found when comparing the modality-specific visual target with the modality-specific auditory and somatosensory targets. Our results indicate that behavioral multisensory enhancement can be identified by the latency and source distribution of the P3 component. These findings may advance our understanding of the neuronal mechanisms of multisensory enhancement.	\N	\N
24306440	Vection is the illusion of self-motion in the absence of real physical movement. The aim of the present study was to analyze how multisensory inputs (visual and auditory) contribute to the perception of vection. Participants were seated in a stationary position in front of a large, curved projection display and were exposed to a virtual scene that constantly rotated around the yaw-axis, simulating a 360° rotation. The virtual scene contained either only visual, only auditory, or a combination of visual and auditory cues. Additionally, simulated rotation speed (90°/s vs. 60°/s) and the number of sound sources (1 vs. 3) were varied for all three stimulus conditions. All participants were exposed to every condition in a randomized order. Data specific to vection latency, vection strength, the severity of motion sickness (MS), and postural steadiness were collected. Results revealed reduced vection onset latencies and increased vection strength when auditory cues were added to the visual stimuli, whereas MS and postural steadiness were not affected by the presence of auditory cues. Half of the participants reported experiencing auditorily induced vection, although the sensation was rather weak and less robust than visually induced vection. Results demonstrate that the combination of visual and auditory cues can enhance the sensation of vection.	\N	\N
24313638	This study examined the time-course of reading single words in children and adults using masked repetition priming and the recording of event-related potentials. The N250 and N400 repetition priming effects were used to characterize form- and meaning-level processing, respectively. Children had larger amplitude N250 effects than adults for both shorter and longer duration primes. Children did not differ from adults on the N400 effect. The difference on the N250 suggests that automaticity for form processing is still maturing in children relative to adults, while the lack of differentiation on the N400 effect suggests that meaning processing is relatively mature by late childhood. The overall similarity in the children's repetition priming effects to adults' effects is in line with theories of reading acquisition, according to which children rapidly transition to an orthographic strategy for fast access to semantic information from print.	\N	\N
24315729	Goal-directed behavior is well-known to show declines in elderly individuals, possibly because of alterations in dopaminergic neural transmission. The dopaminergic system is modulated by a number of other different factors. One of these factors, which has attracted a considerable amount of interest in neurobiology, but has only rarely been examined with respect to its possible modulatory role for cognitive functions in elderly individuals, is latent Toxoplasma gondii (T. gondii) infection. Latent T. gondii infection may be of relevance to goal-directed behavior as it alters dopaminergic neural transmission. We examine goal-directed behavior in T. gondii IgG positive and negative elderly subjects in auditory distraction paradigm. We apply event-related potentials to examine which cognitive subprocesses are affected by latent T. gondii infection on a neurophysiological level. We show that latent T. gondii infection compromises the management of auditory distraction in elderly by specifically delaying processes of attentional allocation and disengagement. The results show that latent T. gondii infection is neglected but an important neurobiological modulator of cognitive functions in elderly individuals.	\N	\N
24320112	There are increasing reports that individual variation in behavioral and neurophysiological measures of infant speech processing predicts later language outcomes, and specifically concurrent or subsequent vocabulary size. If such findings are held up under scrutiny, they could both illuminate theoretical models of language development and contribute to the prediction of communicative disorders. A qualitative, systematic review of this emergent literature illustrated the variety of approaches that have been used and highlighted some conceptual problems regarding the measurements. A quantitative analysis of the same data established that the bivariate relation was significant, with correlations of similar strength to those found for well-established nonlinguistic predictors of language. Further exploration of infant speech perception predictors, particularly from a methodological perspective, is recommended.	\N	\N
24321583	The voice is a primary work tool for call center operators, but the main risk factors for voice disorders in this category have not yet been clarified. This study aimed to analyze the vocal behavior in call center operators and search for correlations between the daily voice dose and the self-perceived voice-related handicap. Prospective. Ninety-two call center operators (aged 24-50 years) underwent ambulatory phonation monitoring during a working day and were administered the Voice Handicap Index (VHI) questionnaire and a questionnaire concerning smoking habits, symptoms, and extrawork activities requiring intensive voice use. Mean percentage phonation time (PT) during work was 14.74% and ranged from 4% to 31%. There was a significant difference between the percentage PT in working time and in extrawork time; however, subjects with high percentage PT in working time maintained a high value also in extrawork time. The mean PT was 87.5 ± 35.8 minutes and was not correlated with age, gender, number of work hours, symptoms, extraprofessional voice use, and VHI scores. The mean amplitude was significantly higher in subjects with longer PT and higher pitch (P < 0.001). VHI score (median = 9) was slightly higher than in the general population but not related to the number of work hours, indicating that work time was not a critical factor in causing the perception of voice problems. Our study provides data about the voice behavior of a large cohort of call center operators and demonstrates that the number of work hours and the percentage PT are not statistically related to the perception of voice disturbances in this working category.	\N	\N
24323099	In the study of the spatial characteristics of the visual channels, the power spectrum model of visual masking is one of the most widely used. When the task is to detect a signal masked by visual noise, this classical model assumes that the signal and the noise are previously processed by a bank of linear channels and that the power of the signal at threshold is proportional to the power of the noise passing through the visual channel that mediates detection. The model also assumes that this visual channel will have the highest ratio of signal power to noise power at its output. According to this, there are masking conditions where the highest signal-to-noise ratio (SNR) occurs in a channel centered in a spatial frequency different from the spatial frequency of the signal (off-frequency looking). Under these conditions the channel mediating detection could vary with the type of noise used in the masking experiment and this could affect the estimation of the shape and the bandwidth of the visual channels. It is generally believed that notched noise, white noise and double bandpass noise prevent off-frequency looking, and high-pass, low-pass and bandpass noises can promote it independently of the channel's shape. In this study, by means of a procedure that finds the channel that maximizes the SNR at its output, we performed numerical simulations using the power spectrum model to study the characteristics of masking caused by six types of one-dimensional noise (white, high-pass, low-pass, bandpass, notched, and double bandpass) for two types of channel's shape (symmetric and asymmetric). Our simulations confirm that (1) high-pass, low-pass, and bandpass noises do not prevent the off-frequency looking, (2) white noise satisfactorily prevents the off-frequency looking independently of the shape and bandwidth of the visual channel, and interestingly we proved for the first time that (3) notched and double bandpass noises prevent off-frequency looking only when the noise cutoffs around the spatial frequency of the signal match the shape of the visual channel (symmetric or asymmetric) involved in the detection. In order to test the explanatory power of the model with empirical data, we performed six visual masking experiments. We show that this model, with only two free parameters, fits the empirical masking data with high precision. Finally, we provide equations of the power spectrum model for six masking noises used in the simulations and in the experiments.	\N	\N
24336606	Sensory-specific cortices appear to be sensitive to information from another modality. Here we investigate whether the human brain automatically extracts the phonological information in visual words in early visual processing. We continuously presented native Chinese speakers peripherally with Chinese homophone characters in an oddball paradigm, while they performed a visual detection task presented in the centre of the visual field. We found the lexical tone phonology embedded in the characters is processed automatically by the brain of native speakers, as revealed by whole-head electrical recordings of the mismatch negativity (MMN). Source solution further revealed the MMN involved the neural activations from the visual cortex to the auditory cortex (130-460 ms). The spatial-temporal dynamics indicate a visual-auditory interaction in the early, automatic processing of phonological information in visual words.	\N	\N
24349800	Perceptual learning can be specific to a trained stimulus or optimally generalized to novel stimuli with the breadth of generalization being imperative for how we structure perceptual training programs. Adapting an established auditory interval discrimination paradigm to utilise complex signals, we trained human adults on a standard interval for either 2, 4, or 10 days. We then tested the standard, alternate frequency, interval, and stereo input conditions to evaluate the rapidity of specific learning and breadth of generalization over the time course. In comparison with previous research using simple stimuli, the speed of perceptual learning and breadth of generalization were more rapid and greater in magnitude, including novel generalization to an alternate temporal interval within stimulus type. We also investigated the long term maintenance of learning and found that specific and generalized learning was maintained over 3 and 6 months. We discuss these findings regarding stimulus complexity in perceptual learning and how they can inform the development of effective training protocols.	\N	\N
24361298	Prestin, the motor protein of cochlear outer hair cells, was identified 14 years ago. Prestin-based outer hair cell motility is responsible for the exquisite sensitivity and frequency selectivity seen in the mammalian cochlea. Prestin is the 5th member of an eleven-member membrane transporter superfamily of SLC26A proteins. Unlike its paralogs, which are capable of transporting anions across the cell membrane, prestin primarily functions as a motor protein with unique capability of performing direct and reciprocal electromechanical conversion on microsecond time scale. Significant progress in the understanding of its structure and the molecular mechanism has been made in recent years using electrophysiological, biochemical, comparative genomics, structural bioinformatics, molecular dynamics simulation, site-directed mutagenesis and domain-swapping techniques. This article reviews recent advances of the structural and functional properties of prestin with focus on the areas that are critical but still controversial in understanding the molecular mechanism of how prestin works: The structural domains for voltage sensing and interaction with anions and for conformational change. Future research directions and potential application of prestin are also discussed. This article is part of a Special Issue entitled <Annual Reviews 2014>.	\N	\N
24365660	SIRT1 is a highly conserved NAD(+)-dependent protein deacetylase known to have protective effects against a variety of age-related diseases. However, there is a lack of information concerning SIRT1 expression in the cochlea and auditory cortex of C57BL/6 mice, a mouse model of age-related hearing loss. Using RT-PCR and immunohistochemistry, we show that SIRT1 is abundantly expressed in the inner hair cells, strial marginal cells, strial intermediate cells, type I and type IV fibrocytes of the spiral ligament and spiral ganglion neurons. In addition, moderate SIRT1 is also detected in the outer hair cells and neurons of the auditory cortex. Associated with elevated hearing thresholds and hair cells loss during aging, there is also a significant reduction of SIRT1 expression in the cochlea and auditory cortex. The expression pattern of SIRT1 in the peripheral and central auditory system suggests that SIRT1 may play an important role in auditory function and therefore may serve as a protective molecule against age-related hearing loss.	\N	\N
24383225	In current terminology, auditory neuropathy spectrum disorder (ANSD) is a disease involving the disruption of the temporal coding of acoustic signals in auditory nerve fibres, resulting in the impairment of auditory perceptions that rely on temporal cues. There is debate about almost every aspect of the disorder, including aetiology, lesion sites, and the terminology used to describe it. ANSD is a heterogeneous disease despite similar audiological findings. The absence of an auditory brainstem response (ABR) and the presence of otoacoustic emissions (OAE) suggest an ANSD profile. However, to determine the exact anatomical site of the disorder, more in-depth audiological and electrophysiological tests must be combined with imaging, genetics and neurological examinations. Greater diagnostic specificity is therefore needed to provide these patients with more adequate treatment.	\N	\N
24384079	Previous research has suggested that electrically coupled frequency modulation (FM) systems substantially improved speech-recognition performance in noise in individuals with cochlear implants (CIs). However, there is limited evidence to support the use of electromagnetically coupled (neck loop) FM receivers with contemporary CI sound processors containing telecoils. The primary goal of this study was to compare speech-recognition performance in noise and subjective ratings of adolescents and adults using one of three contemporary CI sound processors coupled to electromagnetically and electrically coupled FM receivers from Oticon. A repeated-measures design was used to compare speech-recognition performance in noise and subjective ratings without and with the FM systems across three test sessions (Experiment 1) and to compare performance at different FM-gain settings (Experiment 2). Descriptive statistics were used in Experiment 3 to describe output differences measured through a CI sound processor. Experiment 1 included nine adolescents or adults with unilateral or bilateral Advanced Bionics Harmony (n = 3), Cochlear Nucleus 5 (n = 3), and MED-EL OPUS 2 (n = 3) CI sound processors. In Experiment 2, seven of the original nine participants were tested. In Experiment 3, electroacoustic output was measured from a Nucleus 5 sound processor when coupled to the electromagnetically coupled Oticon Arc neck loop and electrically coupled Oticon R2. In Experiment 1, participants completed a field trial with each FM receiver and three test sessions that included speech-recognition performance in noise and a subjective rating scale. In Experiment 2, participants were tested in three receiver-gain conditions. Results in both experiments were analyzed using repeated-measures analysis of variance. Experiment 3 involved electroacoustic-test measures to determine the monitor-earphone output of the CI alone and CI coupled to the two FM receivers. The results in Experiment 1 suggested that both FM receivers provided significantly better speech-recognition performance in noise than the CI alone; however, the electromagnetically coupled receiver provided significantly better speech-recognition performance in noise and better ratings in some situations than the electrically coupled receiver when set to the same gain. In Experiment 2, the primary analysis suggested significantly better speech-recognition performance in noise for the neck-loop versus electrically coupled receiver, but a second analysis, using the best performance across gain settings for each device, revealed no significant differences between the two FM receivers. Experiment 3 revealed monitor-earphone output differences in the Nucleus 5 sound processor for the two FM receivers when set to the +8 setting used in Experiment 1 but equal output when the electrically coupled device was set to a +16 gain setting and the electromagnetically coupled device was set to the +8 gain setting. Individuals with contemporary sound processors may show more favorable speech-recognition performance in noise electromagnetically coupled FM systems (i.e., Oticon Arc), which is most likely related to the input processing and signal processing pathway within the CI sound processor for direct input versus telecoil input. Further research is warranted to replicate these findings with a larger sample size and to develop and validate a more objective approach to fitting FM systems to CI sound processors.	\N	\N
24384084	To validate diagnostic pure-tone audiometry in schools without a sound-treated environment using an audiometer that incorporates insert earphones covered by circumaural earcups and real-time environmental noise monitoring. A within-subject repeated measures design was employed to compare air (250 to 8000 Hz) and bone (250 to 4000 Hz) conduction pure-tone thresholds measured in natural school environments with thresholds measured in a sound-treated booth. 149 children (54% female) with an average age of 6.9 yr (SD = 0.6; range = 5-8). Average difference between the booth and natural environment thresholds was 0.0 dB (SD = 3.6) for air conduction and 0.1 dB (SD = 3.1) for bone conduction. Average absolute difference between the booth and natural environment was 2.1 dB (SD = 2.9) for air conduction and 1.6 dB (SD = 2.7) for bone conduction. Almost all air- (96%) and bone-conduction (97%) threshold comparisons between the natural and booth test environments were within 0 to 5 dB. No statistically significant differences between thresholds recorded in the natural and booth environments for air- and bone-conduction audiometry were found (p > 0.01). Diagnostic air- and bone-conduction audiometry in schools, without a sound-treated room, is possible with sufficient earphone attenuation and real-time monitoring of environmental noise. Audiological diagnosis on-site for school screening may address concerns of false-positive referrals and poor follow-up compliance and allow for direct referral to audiological and/or medical intervention.	\N	\N
24386403	The objective was to determine if one of the neural temporal features, neural adaptation, can account for the across-subject variability in behavioral measures of temporal processing and speech perception performance in cochlear implant (CI) recipients. Neural adaptation is the phenomenon in which neural responses are the strongest at the beginning of the stimulus and decline following stimulus repetition (e.g., stimulus trains). It is unclear how this temporal property of neural responses relates to psychophysical measures of temporal processing (e.g., gap detection) or speech perception. The adaptation of the electrical compound action potential (ECAP) was obtained using 1000 pulses per second (pps) biphasic pulse trains presented directly to the electrode. The adaptation of the late auditory evoked potential (LAEP) was obtained using a sequence of 1-kHz tone bursts presented acoustically, through the cochlear implant. Behavioral temporal processing was measured using the Random Gap Detection Test at the most comfortable listening level. Consonant nucleus consonant (CNC) word and AzBio sentences were also tested. The results showed that both ECAP and LAEP display adaptive patterns, with a substantial across-subject variability in the amount of adaptation. No correlations between the amount of neural adaptation and gap detection thresholds (GDTs) or speech perception scores were found. The correlations between the degree of neural adaptation and demographic factors showed that CI users having more LAEP adaptation were likely to be those implanted at a younger age than CI users with less LAEP adaptation. The results suggested that neural adaptation, at least this feature alone, cannot account for the across-subject variability in temporal processing ability in the CI users. However, the finding that the LAEP adaptive pattern was less prominent in the CI group compared to the normal hearing group may suggest the important role of normal adaptation pattern at the cortical level in speech perception.	\N	\N
24389260	The left temporal pole (LTP) has been posited to be a heteromodal hub for retrieving proper names for semantically unique entities. Previous investigations have demonstrated that LTP is important for retrieving names for famous faces and unique landmarks. However, whether such a relationship would hold for unique entities apprehended through stimulus modalities other than vision has not been well established, and such evidence is critical to adjudicate claims about the "heteromodal" nature of the LTP. Here, we tested the hypothesis that the LTP would be important for naming famous voices. Individuals with LTP lesions were asked to recognize and name famous persons speaking in audio clips. Relative to neurologically normal and brain damaged comparison participants, patients with LTP lesions were able to recognize famous persons from their voices normally, but were selectively impaired in naming famous persons from their voices. The current results extend previous research and provide further support for the notion that the LTP is a convergence region serving as a heteromodal hub for retrieving the names of semantically unique entities.	\N	\N
24391928	The brain is able to realign asynchronous signals that approximately coincide in both space and time. Given that many experience-based links between visual and auditory stimuli are established in the absence of spatiotemporal proximity, we investigated whether or not temporal realignment arises in these conditions. Participants received a 3-min exposure to visual and auditory stimuli that were separated by 706 ms and appeared either from the same (Experiment 1) or from different spatial positions (Experiment 2). A simultaneity judgment task (SJ) was administered right afterwards. Temporal realignment between vision and audition was observed, in both Experiment 1 and 2, when comparing the participants' SJs after this exposure phase with those obtained after a baseline exposure to audiovisual synchrony. However, this effect was present only when the visual stimuli preceded the auditory stimuli during the exposure to asynchrony. A similar pattern of results (temporal realignment after exposure to visual-leading asynchrony but not after exposure to auditory-leading asynchrony) was obtained using temporal order judgments (TOJs) instead of SJs (Experiment 3). Taken together, these results suggest that temporal recalibration still occurs for visual and auditory stimuli that fall clearly outside the so-called temporal window for multisensory integration and appear from different spatial positions. This temporal realignment may be modulated by long-term experience with the kind of asynchrony (vision-leading) that we most frequently encounter in the outside world (e.g., while perceiving distant events).	\N	\N
24398259	There is currently no consensus regarding what measures are most valid to demonstrate perceptual processing without awareness. Likewise, whether conscious perception and unconscious processing rely on independent mechanisms or lie on a continuum remains a matter of debate. Here, we addressed these issues by comparing the time courses of subjective reports, objective discrimination performance and response priming during meta-contrast masking, under similar attentional demands. We found these to be strikingly similar, suggesting that conscious perception and unconscious processing cannot be dissociated by their time course. Our results also demonstrate that unconscious processing, indexed by response priming, occurs, and that objective discrimination performance indexes the same conscious processes as subjective visibility reports. Finally, our results underscore the role of attention by showing that how much attention the stimulus receives relative to the mask, rather than whether processing is measured by conscious discrimination or by priming, determines the time course of meta-contrast masking.	\N	\N
24402676	While deafness-induced plasticity has been investigated in the visual and auditory domains, not much is known about language processing in audiovisual multimodal environments for patients with restored hearing via cochlear implant (CI) devices. Here, we examined the effect of agreeing or conflicting visual inputs on auditory processing in deaf patients equipped with degraded artificial hearing. Ten post-lingually deafened CI users with good performance, along with matched control subjects, underwent H 2 (15) O-positron emission tomography scans while carrying out a behavioral task requiring the extraction of speech information from unimodal auditory stimuli, bimodal audiovisual congruent stimuli, and incongruent stimuli. Regardless of congruency, the control subjects demonstrated activation of the auditory and visual sensory cortices, as well as the superior temporal sulcus, the classical multisensory integration area, indicating a bottom-up multisensory processing strategy. Compared to CI users, the control subjects exhibited activation of the right ventral premotor-supramarginal pathway. In contrast, CI users activated primarily the visual cortices more in the congruent audiovisual condition than in the null condition. In addition, compared to controls, CI users displayed an activation focus in the right amygdala for congruent audiovisual stimuli. The most notable difference between the two groups was an activation focus in the left inferior frontal gyrus in CI users confronted with incongruent audiovisual stimuli, suggesting top-down cognitive modulation for audiovisual conflict. Correlation analysis revealed that good speech performance was positively correlated with right amygdala activity for the congruent condition, but negatively correlated with bilateral visual cortices regardless of congruency. Taken together these results suggest that for multimodal inputs, cochlear implant users are more vision-reliant when processing congruent stimuli and are disturbed more by visual distractors when confronted with incongruent audiovisual stimuli. To cope with this multimodal conflict, CI users activate the left inferior frontal gyrus to adopt a top-down cognitive modulation pathway, whereas normal hearing individuals primarily adopt a bottom-up strategy.	\N	\N
24405904	Although HIV is associated with decreased emotional and cognitive functioning, the mechanisms through which affective changes can alter cognitive processes in HIV-infected individuals are unknown. We aimed to clarify this question through testing the extent to which emotionally negative stimuli prime attention to a subsequent infrequently occurring auditory tone in HIV+ compared to HIV- females. Attention to emotional compared to non-emotional pictures was measured via the LPP ERP. Subsequent attention was indexed through the N1 and late processing negativity ERP. We also assessed mood and cognitive functioning in both groups. In HIV- females, emotionally negative pictures, compared to neutral pictures, resulted in an enhanced LPP to the pictures and an enhanced N1 to subsequent tones. The HIV+ group did not show a difference in the LPP measure between picture categories, and accordingly, did not show a priming effect to the subsequent infrequent tones. The ERP findings, combined with neuropsychological deficits, suggest that HIV+ females show impairments in attention to emotionally-laden stimuli and that this impairment might be related to a loss of affective priming. This study is the first to provide physiological evidence that the LPP, a measure of attention to emotionally-charged visual stimuli, is reduced in HIV-infected individuals. These results set the stage for future work aimed at localizing brain activation to emotional stimuli in HIV+ individuals.	\N	\N
24414279	Speech production, both overt and covert, down-regulates the activation of auditory cortex. This is thought to be due to forward prediction of the sensory consequences of speech, contributing to a feedback control mechanism for speech production. Critically, however, these regulatory effects should be specific to speech content to enable accurate speech monitoring. To determine the extent to which such forward prediction is content-specific, we recorded the brain's neuromagnetic responses to heard multisyllabic pseudowords during covert rehearsal in working memory, contrasted with a control task. The cortical auditory processing of target syllables was significantly suppressed during rehearsal compared with control, but only when they matched the rehearsed items. This critical specificity to speech content enables accurate speech monitoring by forward prediction, as proposed by current models of speech production. The one-to-one phonological motor-to-auditory mappings also appear to serve the maintenance of information in phonological working memory. Further findings of right-hemispheric suppression in the case of whole-item matches and left-hemispheric enhancement for last-syllable mismatches suggest that speech production is monitored by 2 auditory-motor circuits operating on different timescales: Finer grain in the left versus coarser grain in the right hemisphere. Taken together, our findings provide hemisphere-specific evidence of the interface between inner and heard speech.	\N	\N
24423729	Across the animal kingdom, sensations resulting from an animal's own actions are processed differently from sensations resulting from external sources, with self-generated sensations being suppressed. A forward model has been proposed to explain this process across sensorimotor domains. During vocalization, reduced processing of one's own speech is believed to result from a comparison of speech sounds to corollary discharges of intended speech production generated from efference copies of commands to speak. Until now, anatomical and functional evidence validating this model in humans has been indirect. Using EEG with anatomical MRI to facilitate source localization, we demonstrate that inferior frontal gyrus activity during the 300ms before speaking was associated with suppressed processing of speech sounds in auditory cortex around 100ms after speech onset (N1). These findings indicate that an efference copy from speech areas in prefrontal cortex is transmitted to auditory cortex, where it is used to suppress processing of anticipated speech sounds. About 100ms after N1, a subsequent auditory cortical component (P2) was not suppressed during talking. The combined N1 and P2 effects suggest that although sensory processing is suppressed as reflected in N1, perceptual gaps may be filled as reflected in the lack of P2 suppression, explaining the discrepancy between sensory suppression and preserved sensory experiences. These findings, coupled with the coherence between relevant brain regions before and during speech, provide new mechanistic understanding of the complex interactions between action planning and sensory processing that provide for differentiated tagging and monitoring of one's own speech, processes disrupted in neuropsychiatric disorders.	\N	\N
24424293	To assess the role of the efferent auditory system by inhibition of contralateral otoacoustic emission in dyslexic children with auditory processing disorders. The study sample was 34 children: 17 with dyslexia and 17 age-matched controls. Sensitive speech tests (low-pass filtered, time-compressed, distorted and dichotic) were performed to assess coexisting auditory processing disorder. Distortion-product otoacoustic emission (DPOAE) values were measured in basal condition and with contralateral broadband noise signal delivered via an earphone transducer at 60 dB SPL. The lower scores at sensitive speech testing confirmed the association of an auditory processing disorder in the dyslexic children. DPOAE values were significantly attenuated by contralateral inhibition only in the control group (p=0.001; dyslexics, p=0.19); attenuation was not significant at any frequency in the dyslexic group. The differences in DPOAE attenuation between the groups, although not statistically significant, suggest alterations in the auditory efferent system in the dyslexic population. These alterations may affect language perception. If confirmed in further studies with larger samples, these results could provide insight into a possible pathophysiological background of dyslexia.	\N	\N
24434131	Cochlear implantation provides children with a significant hearing loss the potential to engage in phonological processing via audition; however these children can still have poor or inadequately detailed mental (phonological) representations of speech and as such phonological awareness and reading difficulties. Heterogeneous participant profiles, particularly varying modes of communication have clouded the research regarding reading outcomes of children using a cochlear implant. The objective of this study was to explore the relationships between word reading and reading comprehension outcomes, and a range of variables of a relatively homogenous group of children using cochlear implants. Forty-seven oral communicating children using a cochlear implant and who had attended auditory-verbal therapy served as participants. They were administered a comprehensive battery of 10 different assessments covering 22 different tasks across the domains of speech perception, speech production, language, phonological processing and reading. Correlation and principal component analyses were used to examine the relationships between outcome areas. Audiologic and demographic variables were not significantly related to reading outcomes, with the exception of family size. Language and word reading were most strongly related to reading comprehension, while phonological awareness and language were most strongly related to word reading. It is proposed that the development of well-specified phonological representations might underlie these relationships. For oral communicating children using a cochlear implant, good reading outcomes are linked to better language and phonological processing abilities.	\N	\N
24437764	Preferences of concert hall acoustics are explored with preference mapping. The investigation is performed on previously gathered data from individual vocabulary profiling of nine concert halls and three pieces of symphonic music, namely, excerpts of compositions by Beethoven, Bruckner, and Mozart. Individual preferences are regressed onto a latent three-dimensional sensory space obtained by multiple factor analysis of descriptive sensory data. Overlaying individually estimated preference surfaces onto one another produces preference maps which illustrates both the overall preference of the stimuli as well as differences between individual listeners. A comparison of the maps between music motifs illustrates how each music signal affects the weighting of different acoustical qualities in preference judgments. Differences in preferences between individuals are pronounced in the excerpts of Beethoven and Bruckner, while the responses are more homogeneous for Mozart music motif. Overall, proximity is identified as the main aspect associated with preference, but also loudness, envelopment, and bass are important. A correlation analysis of objective parameters and subjective perceptions substantiates the importance of lateral sound energy for good concert hall acoustics. Particularly, the lateral early energy fraction at high frequencies is found to be associated with the perception of proximity, and hence, also with preference.	\N	\N
24437852	The purpose of this study was to determine the overall impact of early and late reflections on the intelligibility of reverberated speech by cochlear implant listeners. Two specific reverberation times were assessed. For each reverberation time, sentences were presented in three different conditions wherein the target signal was filtered through the early, late or entire part of the acoustic impulse response. Results obtained with seven cochlear implant listeners indicated that while early reflections neither enhanced nor reduced overall speech perception performance, late reflections severely reduced speech intelligibility in both reverberant conditions tested.	\N	\N
24453339	The temporal envelope of speech is an important cue contributing to speech intelligibility. Theories about the neural foundations of speech perception postulate that the left and right auditory cortices are functionally specialized in analyzing speech envelope information at different time scales: the right hemisphere is thought to be specialized in processing syllable rate modulations, whereas a bilateral or left hemispheric specialization is assumed for phoneme rate modulations. Recently, it has been found that this functional hemispheric asymmetry is different in individuals with language-related disorders such as dyslexia. Most studies were, however, performed in adults and school-aged children, and only a little is known about how neural auditory processing at these specific rates manifests and develops in very young children before reading acquisition. Yet, studying hemispheric specialization for processing syllable and phoneme rate modulations in preliterate children may reveal early neural markers for dyslexia. In the present study, human cortical evoked potentials to syllable and phoneme rate modulations were measured in 5-year-old children at high and low hereditary risk for dyslexia. The results demonstrate a right hemispheric preference for processing syllable rate modulations and a symmetric pattern for phoneme rate modulations, regardless of hereditary risk for dyslexia. These results suggest that, while hemispheric specialization for processing syllable rate modulations seems to be mature in prereading children, hemispheric specialization for phoneme rate modulation processing may still be developing. These findings could have important implications for the development of phonological and reading skills.	\N	\N
24456178	Spectral modulation detection (SMD) provides a psychoacoustic estimate of spectral resolution. The SMD threshold for an implanted ear is highly correlated with speech understanding and is thus a non-linguistic, psychoacoustic index of speech understanding. This measure, however, is time and equipment intensive and thus not practical for clinical use. Thus the purpose of the current study was to investigate the efficacy of a quick SMD task with the following three study aims: (1) to investigate the correlation between the long psychoacoustic, and quick SMD tasks, (2) to determine the test/retest variability of the quick SMD task, and (3) to evaluate the relationship between the quick SMD task and speech understanding. This study included a within-subjects, repeated-measures design. Seventy-six adult cochlear implant recipients participated. The results were as follows: (1) there was a significant correlation between the long psychoacoustic, and quick SMD tasks, (2) the test-retest variability of the quick SMD task was highly significant and, (3) there was a significant positive correlation between the quick SMD task and monosyllabic word recognition. The results of this study represent the direct clinical translation of a research-proven task of SMD into a quick, clinically feasible format.	\N	\N
24457086	Due to extensive variability in the phonetic realizations of words, there may be few or no proximal spectro-temporal cues that identify a word's onset or even its presence. Dilley and Pitt (2010) showed that the rate of context speech, distal from a to-be-recognized word, can have a sizeable effect on whether or not a word is perceived. This investigation considered whether there is a distinct role for distal rhythm in the disappearing word effect. Listeners heard sentences that had a grammatical interpretation with or without a critical function word (FW) and transcribed what they heard (e.g., are in Jill got quite mad when she heard there are birds can be removed and Jill got quite mad when she heard their birds is still grammatical). Consistent with a perceptual grouping hypothesis, participants were more likely to report critical FWs when distal rhythm (repeating ternary or binary pitch patterns) matched the rhythm in the FW-containing region than when it did not. Notably, effects of distal rhythm and distal rate were additive. Results demonstrate a novel effect of distal rhythm on the amount of lexical material listeners hear, highlighting the importance of distal timing information and providing new constraints for models of spoken word recognition.	\N	\N
24464088	Bimodal stimulation, or stimulation of a cochlear implant (CI) together with a contralateral hearing aid (HA), can improve speech perception in noise However, this benefit is variable, and some individuals even experience interference with bimodal stimulation. One contributing factor to this variability may be differences in binaural spectral integration (BSI) due to abnormal auditory experience. CI programming introduces interaural pitch mismatches, in which the frequencies allocated to the electrodes (and contralateral HA) differ from the electrically stimulated cochlear frequencies. Previous studies have shown that some, but not all, CI users adapt pitch perception to reduce this mismatch. The purpose of this study was to determine whether broadened BSI may also reduce the perception of mismatch. Interaural pitch mismatches and dichotic pitch fusion ranges were measured in 21 bimodal CI users. Seventeen subjects with wide fusion ranges also conducted a task to pitch match various fused electrode-tone pairs. All subjects showed abnormally wide dichotic fusion frequency ranges of 1-4 octaves. The fusion range size was weakly correlated with the interaural pitch mismatch, suggesting a link between broad binaural pitch fusion and large interaural pitch mismatch. Dichotic pitch averaging was also observed, in which a new binaural pitch resulted from the fusion of the original monaural pitches, even when the pitches differed by as much as 3-4 octaves. These findings suggest that abnormal BSI, indicated by broadened fusion ranges and spectral averaging between ears, may account for speech perception interference and nonoptimal integration observed with bimodal compared with monaural hearing device use.	\N	\N
24465675	Perception of our environment is a multisensory experience; information from different sensory systems like the auditory, visual and tactile is constantly integrated. Complex tasks that require high temporal and spatial precision of multisensory integration put strong demands on the underlying networks but it is largely unknown how task experience shapes multisensory processing. Long-term musical training is an excellent model for brain plasticity because it shapes the human brain at functional and structural levels, affecting a network of brain areas. In the present study we used magnetoencephalography (MEG) to investigate how audio-tactile perception is integrated in the human brain and if musicians show enhancement of the corresponding activation compared to non-musicians. Using a paradigm that allowed the investigation of combined and separate auditory and tactile processing, we found a multisensory incongruency response, generated in frontal, cingulate and cerebellar regions, an auditory mismatch response generated mainly in the auditory cortex and a tactile mismatch response generated in frontal and cerebellar regions. The influence of musical training was seen in the audio-tactile as well as in the auditory condition, indicating enhanced higher-order processing in musicians, while the sources of the tactile MMN were not influenced by long-term musical training. Consistent with the predictive coding model, more basic, bottom-up sensory processing was relatively stable and less affected by expertise, whereas areas for top-down models of multisensory expectancies were modulated by training.	\N	\N
24482186	Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. In the current absence of a cure for tinnitus, clinical management typically focuses on reducing the effects of co-morbid symptoms such as distress or hearing loss. Hearing loss is commonly co-morbid with tinnitus and so logic implies that amplification of external sounds by hearing aids will reduce perception of the tinnitus sound and the distress associated with it. To assess the effects of hearing aids specifically in terms of tinnitus benefit in patients with tinnitus and co-existing hearing loss. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 19 August 2013. Randomised controlled trials and non-randomised controlled trials recruiting adults with subjective tinnitus and some degree of hearing loss, where the intervention involves amplification with hearing aids and this is compared to interventions involving other medical devices, other forms of standard or complementary therapy, or combinations of therapies, no intervention or placebo interventions. Three authors independently screened all selected abstracts. Two authors independently extracted data and assessed those potentially suitable studies for risk of bias. For studies meeting the inclusion criteria, we used the mean difference (MD) to compare hearing aids with other interventions and controls. One randomised controlled trial (91 participants) was included in this review. We judged the trial to have a low risk of bias for method of randomisation and outcome reporting, and an unclear risk of bias for other criteria. No non-randomised controlled trials meeting our inclusion criteria were identified. The included study measured change in tinnitus severity (primary measure of interest) using a tinnitus questionnaire measure, and change in tinnitus loudness (secondary measure of interest) on a visual analogue scale. Other secondary outcome measures of interest, namely change in the psychoacoustic characteristics of tinnitus, change in self reported anxiety, depression and quality of life, and change in neurophysiological measures, were not investigated in this study. The included study compared hearing aid use to sound generator use. The estimated effect on change in tinnitus loudness or severity as measured by the Tinnitus Handicap Inventory score was compatible with benefits for both hearing aids or sound generators but no difference was found between the two alternative treatments (MD -0.90, 95% confidence interval (CI) -7.92 to 6.12) (100-point scale); moderate quality evidence. No negative or adverse events were reported. The current evidence base for hearing aid prescription for tinnitus is limited. To be useful, future studies should make appropriate use of blinding and be consistent in their use of outcome measures. Whilst hearing aids are sometimes prescribed as part of tinnitus management, there is currently no evidence to support or refute their use as a more routine intervention for tinnitus.	\N	\N
24486809	Novel stimuli reliably attract attention, suggesting that novelty may disrupt performance when it is task-irrelevant. However, under certain circumstances novel stimuli can also elicit a general alerting response having beneficial effects on performance. In a series of experiments we investigated whether different aspects of novelty--stimulus novelty, contextual novelty, surprise, deviance, and relative complexity--lead to distraction or facilitation. We used a version of the visual oddball paradigm in which participants responded to an occasional auditory target. Participants responded faster to this auditory target when it occurred during the presentation of novel visual stimuli than of standard stimuli, especially at SOAs of 0 and 200 ms (Experiment 1). Facilitation was absent for both infrequent simple deviants and frequent complex images (Experiment 2). However, repeated complex deviant images did facilitate responses to the auditory target at the 200 ms SOA (Experiment 3). These findings suggest that task-irrelevant deviant visual stimuli can facilitate responses to an unrelated auditory target in a short 0-200 millisecond time-window after presentation. This only occurs when the deviant stimuli are complex relative to standard stimuli. We link our findings to the novelty P3, which is generated under the same circumstances, and to the adaptive gain theory of the locus coeruleus-norepinephrine system (Aston-Jones and Cohen, 2005), which may explain the timing of the effects.	\N	\N
24496290	Growing evidence suggests that children who are deaf and use cochlear implants (CIs) can communicate effectively using spoken language. Research has reported that age of implantation and length of experience with the CI play an important role in a predicting a child's linguistic development. In recent years, the increase in the number of children receiving bilateral CIs (BiCIs) has led to interest in new variables that may also influence the development of hearing, speech, and language abilities, such as length of bilateral listening experience and the length of time between the implantation of the two CIs. One goal of the present study was to determine how a cohort of children with BiCIs performed on standardized measures of language and nonverbal cognition. This study examined the relationship between performance on language and nonverbal intelligence quotient (IQ) tests and the ages at implantation of the first CI and second CI. This study also examined whether early bilateral activation is related to better language scores. Children with BiCIs (n = 39; ages 4 to 9 years) were tested on two standardized measures, the Test of Language Development and the Leiter International Performance Scale-Revised, to evaluate their expressive/receptive language skills and nonverbal IQ/memory. Hierarchical regression analyses were used to evaluate whether BiCI hearing experience predicts language performance. While large intersubject variability existed, on average, almost all the children with BiCIs scored within or above normal limits on measures of nonverbal cognition. Expressive and receptive language scores were highly variable, less likely to be above the normative mean, and did not correlate with Length of first CI Use, defined as length of auditory experience with one cochlear implant, or Length of second CI Use, defined as length of auditory experience with two cochlear implants. All children in the present study had BiCIs. Most IQ scores were either at or above that found in the general population of typically hearing children. However, there was greater variability in their performance on a standardized test of expressive and receptive language. This cohort of children, who are mainstreamed in schools at age-appropriate grades, whose mothers' education is high, and whose families' socioecononomic status is high, had, as a group, on average, language scores within the same range as the normative sample of hearing children. Further research identifying the predictors that contribute to the high variability in both expressive and receptive language scores in children with BiCIs will provide useful information that can aid in clinical management and decision making.	\N	\N
24497938	The vast majority of people experience involuntary musical imagery (INMI) or 'earworms'; perceptions of spontaneous, repetitive musical sound in the absence of an external source. The majority of INMI episodes are not bothersome, while some cause disruption ranging from distraction to anxiety and distress. To date, little is known about how the majority of people react to INMI, in particular whether evaluation of the experience impacts on chosen response behaviours or if attempts at controlling INMI are successful or not. The present study classified 1046 reports of how people react to INMI episodes. Two laboratories in Finland and the UK conducted an identical qualitative analysis protocol on reports of INMI reactions and derived visual descriptive models of the outcomes using grounded theory techniques. Combined analysis carried out across the two studies confirmed that many INMI episodes were considered neutral or pleasant, with passive acceptance and enjoyment being among the most popular response behaviours. A significant number of people, however, reported on attempts to cope with unwanted INMI. The most popular and effective behaviours in response to INMI were seeking out the tune in question, and musical or verbal distraction. The outcomes of this study contribute to our understanding of the aetiology of INMI, in particular within the framework of memory theory, and present testable hypotheses for future research on successful INMI coping strategies.	\N	\N
24506533	We examined infants' oscillatory brain activity during a live interaction with an adult who showed them novel objects. Activation in the alpha frequency range was assessed. Nine-month-old infants responded with desynchronization of alpha-band activity when looking at an object together with an adult during a social interaction involving eye contact. When infant and experimenter only looked at the object without engaging in eye contact, no such effect was observed. Results are interpreted in terms of activation of a generic semantic knowledge system induced by eye contact during a social interaction.	\N	\N
24518404	It was hypothesized that cochlear implant (CI) subjects would be able to correctly identify 1, 2, and 3 simultaneous pitches through direct electrical stimulation. We further hypothesized that the location on the implant array and the fundamental frequency of the pitches would have an impact on the performance. "They gave me back speech but not music" is a sentence commonly heard by CI subjects. One of the reasons is that in music, multiple streams are frequently played at the same time, which is an essential feature of harmony. Current CI speech processors do not allow CI users to perceive such complex polyphonic sounds. In the present study, the authors assessed the ability of CI subjects to perceive simultaneous modulation frequencies based on direct electrical stimulation. Ten CI subjects were asked to identify 1, 2, and 3 simultaneous pitches applied on different electrodes using sinusoidal amplitude modulation. All stimuli were loudness balanced before the actual identification task. Subjects were able to identify 1, 2, and 3 simultaneous pitches. The further the distance between the 2 electrodes, the better was the performance in the 2-pitch condition. The distance between the modulation frequencies had a significant effect on the performance in the 2-and 3-pitch condition. Subjects are able to identify complex polyphonic stimuli based on the number of active electrodes. The additional polyphonic rate pitch cue improves performance in some conditions.	\N	\N
24553776	Sounds emitted by different sources arrive at our ears as a mixture that must be disentangled before meaningful information can be retrieved. It is still a matter of debate whether this decomposition happens automatically or requires the listener's attention. These opposite positions partly stem from different methodological approaches to the problem. We propose an integrative approach that combines the logic of previous measurements targeting either auditory stream segregation (interpreting a mixture as coming from two separate sources) or integration (interpreting a mixture as originating from only one source). By means of combined behavioral and event-related potential (ERP) measures, our paradigm has the potential to measure stream segregation and integration at the same time, providing the opportunity to obtain positive evidence of either one. This reduces the reliance on zero findings (i.e., the occurrence of stream integration in a given condition can be demonstrated directly, rather than indirectly based on the absence of empirical evidence for stream segregation, and vice versa). With this two-way approach, we systematically manipulate attention devoted to the auditory stimuli (by varying their task relevance) and to their underlying structure (by delivering perceptual tasks that require segregated or integrated percepts). ERP results based on the mismatch negativity (MMN) show no evidence for a modulation of stream integration by attention, while stream segregation results were less clear due to overlapping attention-related components in the MMN latency range. We suggest future studies combining the proposed two-way approach with some improvements in the ERP measurement of sequential stream segregation.	\N	\N
24556905	The aim of this study was to investigate the efficacy of a direct acoustic cochlear implant (DACI) for speech understanding in noise in patients suffering from severe to profound mixed hearing loss (MHL) due to various etiologies compared to the preoperative best-aided condition. The study was performed at five tertiary referral centers in Europe (Belgium, Germany, Poland and Spain). Nineteen adult subjects with severe to profound MHL due to (advanced) otosclerosis, ear canal fibrosis, chronic otitis media, tympanosclerosis or previous cholesteatoma were implanted with a DACI (Codacs™ Investigational Device) combined with a conventional stapes prosthesis. Unaided and aided speech reception scores in quiet and in noise, preoperative and postoperative air and bone conduction thresholds and aided and unaided sound field thresholds were measured prospectively during the study. Subjective benefit analysis was determined through the Abbreviated Profile of Hearing Aid Benefit questionnaire. Quality of life was measured by the Health Utilities Index. All subjects were fitted preoperatively with hearing aids and/or a bone conduction implant on a headband before DACI implantation. This allows direct comparison between different hearing rehabilitation solutions. The mean speech reception threshold in noise improved significantly by 7.9 dB signal-to-noise ratio (SNR) after activation of the DACI compared to the preoperative best-aided condition. For all 19 subjects, a mean postoperative aided speech reception threshold of 2.6 dB SNR (standard deviation: 8.3 dB) was measured. On average, no significant shift in the bone conduction thresholds was noted 4-5 months after implantation. A mean sound field threshold improvement of 46 and 16 dB was measured compared to the preoperative unaided and best-aided condition, respectively. Speech perception tests in quiet showed a mean improvement of the word recognition scores by 65 and 48% at 65 dB SPL compared to the preoperative unaided and best-aided condition, respectively. In summary, DACI provides an effective improvement of the speech perception in noise compared to the best-aided condition in subjects suffering from severe to profound MHL.	\N	\N
24559662	The minimum time interval between two stimuli that can be reliably detected is called the gap detection threshold. The present study examines whether an unconscious state, natural sleep affects the gap detection threshold. Event-related potentials were recorded in 10 young adults while awake and during all-night sleep to provide an objective estimate of this threshold. These subjects were presented with 2, 4, 8 or 16ms gaps occurring in 1.5 duration white noise. During wakefulness, a significant N1 was elicited for the 8 and 16ms gaps. N1 was difficult to observe during stage N2 sleep, even for the longest gap. A large P2 was however elicited and was significant for the 8 and 16ms gaps. Also, a later, very large N350 was elicited by the 16ms gap. An N1 and P2 was significant only for the 16ms gap during REM sleep. ERPs to gaps occurring in noise segments can therefore be successfully elicited during natural sleep. The gap detection threshold is similar in the waking and sleeping states.	\N	\N
24561213	The present study investigated the joint impact of target-flanker similarity and of spatial frequency content on the crowding effect in letter identification. We presented spatial frequency filtered letters to neurologically intact non-dyslexic readers while manipulating target-flanker distance, target eccentricity and target-flanker confusability (letter similarity metric based on published letter confusion matrices). The results show that high target-flanker confusability magnifies crowding. They also reveal an intricate pattern of interactions of the spatial frequency content of the stimuli with target eccentricity, flanker distance and similarity. The findings are congruent with the notion that crowding results from the inappropriate pooling of target and flanker features and that this integration is more likely to match a response template at a subsequent decision stage with similar than dissimilar flankers. In addition, the evidence suggests that crowding from similar flankers is biased towards relatively high spatial frequencies and that crowding shifts towards lower spatial frequencies as target eccentricity is increased.	\N	\N
24566800	Learning in perceptual tasks is typically highly specific to the trained stimulus parameters. However, can learning be specific to a stimulus parameter that is perceptually indistinguishable from another? We assessed this question using a perceived sound location task in which the perceived sound location was created through either an interaural time difference (ITD) cue or an interaural level difference (ILD) cue. We used the same transient, broadband sound (clicks) for both cues, and after training on one of the cues, listeners switched cue mid-session. This allowed us to assess cue specificity or transfer when the subjectively unnoticed cue switch occurred. One group of listeners improved their ITD performance as a function of training, but deteriorated in performance when switching to ILD in mid training session. Another group of listeners started with ILD training; their improved performance level did not deteriorate as they switched to the ITD cue. This transfer asymmetry was not hypothesized, and we therefore extended our study with a second data collection. Both the training effect and the transfer asymmetry remained after the second data collection. Our results indicate (a) listeners can improve both their ITD and ILD performance for click sounds, extending previous findings on tones; (b) learning can be specific to a stimulus parameter that is indistinguishable from another, as ITD learning did not transfer to ILD performance; but (c) ILD learning can transfer to ITD performance. This transfer asymmetry may have occurred because of how ITD and ILD are coded in early brainstem areas.	\N	\N
24568205	The melodic contour of speech forms an important perceptual aspect of tonal and nontonal languages and an important limiting factor on the intelligibility of speech heard through a cochlear implant. Previous work exploring the neural correlates of speech comprehension identified a left-dominant pathway in the temporal lobes supporting the extraction of an intelligible linguistic message, whereas the right anterior temporal lobe showed an overall preference for signals clearly conveying dynamic pitch information [Johnsrude, I. S., Penhune, V. B., & Zatorre, R. J. Functional specificity in the right human auditory cortex for perceiving pitch direction. Brain, 123, 155-163, 2000; Scott, S. K., Blank, C. C., Rosen, S., & Wise, R. J. Identification of a pathway for intelligible speech in the left temporal lobe. Brain, 123, 2400-2406, 2000]. The current study combined modulations of overall intelligibility (through vocoding and spectral inversion) with a manipulation of pitch contour (normal vs. falling) to investigate the processing of spoken sentences in functional MRI. Our overall findings replicate and extend those of Scott et al. [Scott, S. K., Blank, C. C., Rosen, S., & Wise, R. J. Identification of a pathway for intelligible speech in the left temporal lobe. Brain, 123, 2400-2406, 2000], where greater sentence intelligibility was predominately associated with increased activity in the left STS, and the greatest response to normal sentence melody was found in right superior temporal gyrus. These data suggest a spatial distinction between brain areas associated with intelligibility and those involved in the processing of dynamic pitch information in speech. By including a set of complexity-matched unintelligible conditions created by spectral inversion, this is additionally the first study reporting a fully factorial exploration of spectrotemporal complexity and spectral inversion as they relate to the neural processing of speech intelligibility. Perhaps surprisingly, there was little evidence for an interaction between the two factors-we discuss the implications for the processing of sound and speech in the dorsolateral temporal lobes.	\N	\N
24576508	We investigated the effects of linguistic experience and language familiarity on the perception of audio-visual (A-V) synchrony in fluent speech. In Experiment 1, we tested a group of monolingual Spanish- and Catalan-learning 8-month-old infants to a video clip of a person speaking Spanish. Following habituation to the audiovisually synchronous video, infants saw and heard desynchronized clips of the same video where the audio stream now preceded the video stream by 366, 500, or 666 ms. In Experiment 2, monolingual Catalan and Spanish infants were tested with a video clip of a person speaking English. Results indicated that in both experiments, infants detected a 666 and a 500 ms asynchrony. That is, their responsiveness to A-V synchrony was the same regardless of their specific linguistic experience or familiarity with the tested language. Compared to previous results from infant studies with isolated audiovisual syllables, these results show that infants are more sensitive to A-V temporal relations inherent in fluent speech. Furthermore, the absence of a language familiarity effect on the detection of A-V speech asynchrony at eight months of age is consistent with the broad perceptual tuning usually observed in infant response to linguistic input at this age.	\N	\N
24581119	Music conveys emotion by manipulating musical structures, particularly musical mode- and tempo-impact. The neural correlates of musical mode and tempo perception revealed by electroencephalography (EEG) have not been adequately addressed in the literature. This study used independent component analysis (ICA) to systematically assess spatio-spectral EEG dynamics associated with the changes of musical mode and tempo. Empirical results showed that music with major mode augmented delta-band activity over the right sensorimotor cortex, suppressed theta activity over the superior parietal cortex, and moderately suppressed beta activity over the medial frontal cortex, compared to minor-mode music, whereas fast-tempo music engaged significant alpha suppression over the right sensorimotor cortex. The resultant EEG brain sources were comparable with previous studies obtained by other neuroimaging modalities, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). In conjunction with advanced dry and mobile EEG technology, the EEG results might facilitate the translation from laboratory-oriented research to real-life applications for music therapy, training and entertainment in naturalistic environments.	\N	\N
24581190	The use of adequate assessment tools in health care is crucial for the management of care. The lack of specific tools in Portugal for assessing the performance of children who use cochlear implants motivated the translation and adaptation of the EARS (Evaluation of Auditory Responses to Speech) test battery into European Portuguese. This test battery is today one of the most commonly used by (re)habilitation teams of deaf children who use cochlear implants worldwide. The goal to be achieved with the validation of EARS was to provide (re)habilitation teams an instrument that enables: (i) monitoring the progress of individual (re)habilitation, (ii) managing a (re)habilitation program according to objective results, comparable between different (re)habilitation teams, (iii) obtaining data that can be compared with the results of international teams, and (iv) improving engagement and motivation of the family and other professionals from local teams. For the test battery translation and adaptation process, the adopted procedures were the following: (i) translation of the English version into European Portuguese by a professional translator, (ii) revision of the translation performed by an expert panel, including doctors, speech-language pathologists and audiologists, (iii) adaptation of the test stimuli by the team's speechlanguage pathologist, and (iv) further review by the expert panel. For each of the tests that belong to the EARS battery, the introduced adaptations and adjustments are presented, combining the characteristics and objectives of the original tests with the linguistic and cultural specificities of the Portuguese population. The difficulties that have been encountered during the translation and adaptation process and the adopted solutions are discussed. Comparisons are made with other versions of the EARS battery. We defend that the translation and the adaptation process followed for the EARS test battery into European Portuguese was correctly conducted, respecting the characteristics of the original instruments and adapting the test stimuli to the linguistic and cultural reality of the Portuguese population, thus meeting the goals that have been set.	\N	\N
24581551	There is evidence that people with psychosis display a "jump-to-conclusions" (JTC) reasoning style, and that this bias may be specific to delusions. A "jump-to-perceptions" (JTP) cognitive bias has also been found and is typically linked to hallucinations. However, there is some evidence for an association between JTP and delusions, and its specificity to hallucinations remains unclear. It has been suggested that these biases are related and products of shared cognitive processes. This study examined the symptom specificity of JTC and JTP, and the relationship between them, in a sample of 98 individuals with delusions divided into 'hallucinators' (n=51) and 'non-hallucinators' (n=47). Biases were assessed using the beads task and visual and auditory perceptual tasks. As predicted, both groups demonstrated a JTC bias, but the 'hallucinators' showed a more pronounced JTP style in both modalities. The presence of JTC and JTP biases did not co-occur: making a decision on the beads task after two or fewer draws was not related to visual JTP, and was associated with a less marked JTP bias in the auditory perceptual task. No differences were found in JTP or JTC between participants with and without a schizophrenia diagnosis. JTP, but not JTC, was associated with the presence of hallucinations. These findings suggest that the JTC and JTP biases show specificity to delusions and hallucinations, respectively, and not to diagnosis. There was no evidence that they are the product of shared cognitive processes, further supporting their specificity.	\N	\N
24597272	Listeners find it relatively difficult to recognize words that are similar-sounding to other known words. In contrast, when asked to identify spoken nonwords, listeners perform better when the nonwords are similar to many words in their language. These effects of sound similarity have been assessed in multiple ways, and both sublexical (phonotactic probability) and lexical (neighborhood) effects have been reported, leading to models that incorporate multiple stages of processing. One prediction that can be derived from these models is that there may be differences among individuals in the size of these similarity effects as a function of working memory abilities. This study investigates how item-individual characteristics of nonwords (both phonotactic probability and neighborhood density) interact with listener-individual characteristics (such as cognitive abilities and hearing sensitivity) in the perceptual identification of nonwords. A set of nonwords was used in which neighborhood density and phonotactic probability were not correlated. In our data, neighborhood density affected identification more reliably than did phonotactic probability. The first study, with young adults, showed that higher neighborhood density particularly benefits nonword identification for those with poorer attention-switching control. This suggests that it may be easier to focus attention on a novel item if it activates and receives support from more similar-sounding neighbors. A similar study on nonword identification with older adults showed increased neighborhood density effects for those with poorer hearing, suggesting that activation of long-term linguistic knowledge is particularly important to back up auditory representations that are degraded as a result of hearing loss.	\N	\N
24603717	Objective identification and description of mimicked calls is a primary component of any study on avian vocal mimicry but few studies have adopted a quantitative approach. We used spectral feature representations commonly used in human speech analysis in combination with various distance metrics to distinguish between mimicked and non-mimicked calls of the greater racket-tailed drongo, Dicrurus paradiseus and cross-validated the results with human assessment of spectral similarity. We found that the automated method and human subjects performed similarly in terms of the overall number of correct matches of mimicked calls to putative model calls. However, the two methods also misclassified different subsets of calls and we achieved a maximum accuracy of ninety five per cent only when we combined the results of both the methods. This study is the first to use Mel-frequency Cepstral Coefficients and Relative Spectral Amplitude - filtered Linear Predictive Coding coefficients to quantify vocal mimicry. Our findings also suggest that in spite of several advances in automated methods of song analysis, corresponding cross-validation by humans remains essential.	\N	\N
24604542	Two experiments were conducted to study effects of modality, temporal position, and their interaction on comparisons of successive stimuli. In Experiment 1, intramodal (tone-tone and line-line) and crossmodal (tone-line and line-tone) stimulus pairs, with two interstimulus intervals (ISIs), 400 and 2,000 ms, were presented. Participants indicated which stimulus was the "stronger." Time-order errors (TOEs) were assessed using the D% measure and were found in all types of pairs. Variation in TOEs across conditions was well accounted for by changes in parameters (stimulus weights, reference levels) in an extended version of Hellström's sensation weighting (SW) model. With an ISI of 2,000 ms, the first stimulus had a lower weight (less impact on the response) than did the second stimulus. More negative TOEs were found with the longer ISI in all pair types except tone-line. In Experiment 2, participants indicated which of two lines was the longer or which of two tones was the louder. An intra- or crossmodal anchor, or no anchor, was interpolated between the stimuli. Anchoring tended to reduce the weight of the first stimulus, suggesting interference with memory, and to yield negative TOEs. Intramodal anchors yielded reduced weights of both stimuli, most dramatically for tones, suggesting an additional effect of stimulus interference. Response times decreased with crossmodal anchors. For line-line pairs, strong negative TOEs were found. In both experiments, the variation in TOE across conditions was well accounted for by the SW model.	\N	\N
24606282	An experiment was carried out to determine whether the level of the speech fluency disorder can be estimated by means of automatic acoustic measurements. These measures analyze, for example, the amount of silence in a recording or the number of abrupt spectral changes in a speech signal. All the measures were designed to take into account symptoms of stuttering. In the experiment, 118 audio recordings of read speech by Czech native speakers were employed. The results indicate that the human-made rating of the speech fluency disorder in read speech can be predicted on the basis of automatic measurements. The number of abrupt spectral changes in the speech segments turns out to be the most appropriate measure to describe the overall speech performance. The results also imply that there are measures with good results describing partial symptoms (especially fixed postures without audible airflow).	\N	\N
24611258	Previous researchers have found that participants associate higher frequencies with locations that are higher in space and lower frequencies with lower locations, creating a phenomenological-spatial association for the frequency of auditory tones. With such an association, the frequency of an auditory tone could potentially bias movements along multiple axes. This hypothesis was tested. In four experiments, nine frequencies (250-1,250 Hz) were binaurally presented to blindfolded participants (n = 10, 12, 20, & 9; M age = 22 yr.) who indicated the perceived location of the stimuli on a measurement scale oriented in the vertical, the horizontal (Experiment 1), or depth dimension (Experiment 2). In Experiment 3, participants were asked to indicate the perceived location of the frequencies on a two-dimensional vertical board located in front of them. In Experiment 4, participants indicated the perceived location in three-dimensional space. An optoelectronic device recorded at all locations. Analyses of constant error indicated a spatial association in the vertical, horizontal, and depth dimensions when responses were restricted to only one dimension (Experiments 1 & 2). Higher frequencies were perceived to be located higher, farther to the right, and farther away from the body than lower frequencies. However, this spatial association was only exhibited in the vertical dimension when the responses were unconstrained in two dimensions (vertical and horizontal; Experiment 3) and all three dimensions (Experiment 4). Although this spatial association is a robust phenomenon, it appears that the association only biases actions when indicating perceived locations in the vertical dimension during unconstrained responses.	\N	\N
24616980	To investigate the changes of electrode impedance, THR/MCL values, and dynamic range (DR) in Combi 40+ cochlear implant after implantation. A respective study was carried out collecting 20 consecutively implanted children's electrode impedances, THR/MCL values, and DR at seven time point during the first three years after implantation. Their variation and correlations were analyzed. Overall, electrode impedances were lowest during the operation, and significantly rise to the highest at the first stimulation, then followed by a gradual decrease. After three months, electrode impedance of apical and medial cochlear segment were basically stable, while that of the basal segment was gradually increased. Dynamic range (DR) of apical and medial group electrode increased early after the operation and showed a stabilization from the second year, whereas that of basal group have a downward trend since the first year. However, the electric charge of each group increased significantly after three months, and then become stable after first year. Otherwise, a stronger negative rectilinear correlation was found between impedance changes with DR than with THR/MCL level. The electrode impedances vary clue to different electrode position. Measuring the electrode impedance can effectively evaluate the working status of Combi C40+ cochlear implant. The dynamic range of the electrode was negatively correlated with the impedances, which made it possible to predict the width of the dynamic range by measuring the impedance 3 or 6 months after operation.	\N	\N
24622027	The safety of implanting a titanium microactuator into the lateral wall of cat scala tympani was assessed by comparing preoperative and postoperative auditory brainstem response (ABR) thresholds for 1 to 3 months. The safety of directly stimulating cochlear perilymph with an implantable hearing system requires maintaining preoperative hearing levels. This cat study is an essential step in the development of the next generation of fully implantable hearing devices for humans. Following GLP surgical standards, a 1-mm cochleostomy was drilled into the lateral wall of the scala tympani, and a nonfunctioning titanium anchor/microactuator assembly was inserted in 8 cats. The scala media was damaged in the 1 cat. ABR thresholds with click and 4- and 8-kHz stimuli were measured preoperatively and compared with postoperative thresholds at 1, 2, and 3 months. Nonimplanted ear thresholds were also measured to establish statistical significance for threshold shifts (>28.4 dB). Two audiologists independently interpreted thresholds. Postoperatively, 7 cats implanted in the scala tympani demonstrated no significant ABR threshold shift for click stimulus; one shifted ABR thresholds to 4- and 8-kHz stimuli. The eighth cat, with surgical damage to the scala media, maintained stable click threshold but had a significant shift to 4- and 8-kHz stimuli. This cat study provides no evidence of worsening hearing thresholds after fenestration of the scala tympani and insertion of a titanium anchor/microactuator, provided there is no surgical trauma to the scala media and the implanted device is securely anchored in the cochleostomy. These 2 issues have been resolved in the development of a fully implantable hearing system for humans. The long-term hearing stability (combined with histologic studies) reaffirm that the microactuator is well tolerated by the cat cochlea.	\N	\N
24622351	Pure-tone auditory thresholds in children are below the standardized hearing threshold levels described by ). The development of hearing ability in Chinese and German children at different ages is analyzed and compared with data in the literature. Extended high frequencies above 8 kHz are included due to their vulnerability to noise. Ninety-one children in China and 197 children at a typical primary school in Germany underwent audiometric tests at 17 frequencies ranging from 125 Hz to 16 kHz. To analyze effects of age the children were assessed in age groups of 6 to 9, 9 to 12, and 13 to 16 years of age. Children in China and Germany have the poorest hearing sensitivity at low frequencies (below 1 kHz) and the best sensitivity at the extended high frequencies above 8 kHz. The mean deviations (both ears) from the standard thresholds for adults 18 to 25 years of age, averaged over all frequencies, are 6.7 dB for Chinese and 7.1 dB for German children in the youngest age groups. In the Chinese age group of 9- to 12-year olds the averaged threshold is 4.5 dB and for the same German age group 3.6 dB. For the Chinese age group of 13- to 16-year olds the averaged threshold is 3.3 dB. The improvements of the older German age group compared with the younger are significant at p < 0.05 and are nearly twice as high compared with the comparable Chinese age groups. Age-dependent improvements of hearing ability are evident in children and should be considered in evaluating audiometric test results. Audiometric tests in the extended high-frequency range could be used as an early warning system for future degeneration of hearing ability.	\N	\N
24623783	The earliest stages of cortical processing of speech sounds take place in the auditory cortex. Transcranial magnetic stimulation (TMS) studies have provided evidence that the human articulatory motor cortex contributes also to speech processing. For example, stimulation of the motor lip representation influences specifically discrimination of lip-articulated speech sounds. However, the timing of the neural mechanisms underlying these articulator-specific motor contributions to speech processing is unknown. Furthermore, it is unclear whether they depend on attention. Here, we used magnetoencephalography and TMS to investigate the effect of attention on specificity and timing of interactions between the auditory and motor cortex during processing of speech sounds. We found that TMS-induced disruption of the motor lip representation modulated specifically the early auditory-cortex responses to lip-articulated speech sounds when they were attended. These articulator-specific modulations were left-lateralized and remarkably early, occurring 60-100 ms after sound onset. When speech sounds were ignored, the effect of this motor disruption on auditory-cortex responses was nonspecific and bilateral, and it started later, 170 ms after sound onset. The findings indicate that articulatory motor cortex can contribute to auditory processing of speech sounds even in the absence of behavioral tasks and when the sounds are not in the focus of attention. Importantly, the findings also show that attention can selectively facilitate the interaction of the auditory cortex with specific articulator representations during speech processing.	\N	\N
24627167	In research investigating Stroop or Simon effects, data are typically analyzed at the level of mean response time (RT), with results showing faster responses for compatible than for incompatible trials. However, this analysis provides only limited information as it glosses over the shape of the RT distributions and how they may differ across tasks and experimental conditions. These limitations have encouraged the analysis of RT distributions using delta plots. In the present review, we aim to bring together research on distributional properties of auditory and visual interference effects. Extending previous reviews on distributional properties of the Simon effect, we additionally review studies reporting distributional analyses of Stroop effects. We show that distributional analyses of sequential effects (i.e., taking into account congruency of the previous trial) capture important similarities and differences of interference effects across tasks (Simon, Stroop) as well as across sensory modalities, despite some challenges associated to this approach.	\N	\N
24627209	In multisensory research, faster responses are commonly observed when multimodal stimuli are presented, as compared to unimodal target presentations. This so-called redundant-signals effect can be explained by several frameworks, including separate-activation and coactivation models. The redundant-signals effect has been investigated in a large number of studies; however, most of those studies have been limited to the rejection of separate-activation models. Coactivation models have been analyzed in only a few studies, primarily using simple response tasks. Here, we investigated the mechanism of multisensory integration underlying go/no-go and choice responses to redundant auditory-visual stimuli. In the present study, the mean and variance of response times, as well as the accuracy rates of go/no-go and choice responses, were used to test a coactivation model based on the linear superposition of diffusion processes (Schwarz, 1994) within two absorbing barriers. The diffusion superposition model accurately describes the means and variances of response times as well as the proportions of correct responses observed in the two tasks. Linear superposition thus seems to be a general principle in the integration of redundant information provided by different sensory channels, and is not restricted to simple responses. The results connect existing theories of multisensory integration with theories on choice behavior.	\N	\N
24632322	Two experiments investigated the cognitive skills that underlie children's susceptibility to semantic and phonological false memories in the Deese/Roediger-McDermott procedure (Deese, 1959; Roediger & McDermott, 1995). In Experiment 1, performance on the Verbal Similarities subtest of the British Ability Scales (BAS) II (Elliott, Smith, & McCulloch, 1997) predicted correct and false recall of semantic lures. In Experiment 2, performance on the Yopp-Singer Test of Phonemic Segmentation (Yopp, 1988) did not predict correct recall, but inversely predicted the false recall of phonological lures. Auditory short-term memory was a negative predictor of false recall in Experiment 1, but not in Experiment 2. The findings are discussed in terms of the formation of gist and verbatim traces as proposed by fuzzy trace theory (Reyna & Brainerd, 1998) and the increasing automaticity of associations as proposed by associative activation theory (Howe, Wimmer, Gagnon, & Plumpton, 2009).	\N	\N
24633379	In order to acquire language, children require speech input. The prosody of the speech input plays an important role. In most cultures adults modify their code when communicating with children. Compared to normal speech this code differs especially with regard to prosody. For this review a selective literature search in PubMed and Scopus was performed. Prosodic characteristics are a key feature of spoken language. By analysing prosodic features, children gain knowledge about underlying grammatical structures. Child-directed speech (CDS) is modified in a way that meaningful sequences are highlighted acoustically so that important information can be extracted from the continuous speech flow more easily. CDS is said to enhance the representation of linguistic signs. Taking into consideration what has previously been described in the literature regarding the perception of suprasegmentals, CDS seems to be able to support language acquisition due to the correspondence of prosodic and syntactic units. However, no findings have been reported, stating that the linguistically reduced CDS could hinder first language acquisition.	\N	\N
24635583	The attentional blink (AB) refers to the decline in report accuracy of a second target (T2) when presented shortly after a first target (T1) in a rapid serial visual presentation (RSVP) of distractors. It is known that masking T1 increases the magnitude of the AB, and masking a single target (equivalent to T1) in a RSVP stream attenuates the P3 to the target in correct trials. The major purpose of the present study was to clarify how these two effects may be integrated. An intervening distractor was presented at lag 1 (T1+1), at lag 2 (T1+2), or at neither of these two lags (no distractor). T2 was always presented at lag 3, as the last item in the stream. The P3 to T1 was attenuated and the P3 to T2 delayed in the T1+1 condition compared to the two other distractor conditions. These results clearly show that masking T1 attenuates the P3 to T1 and delays the P3 to T2 in the AB. Implications for extant theories of the AB are discussed.	\N	\N
24637103	Processing local elements of hierarchical patterns at a superior level and independently from an intact global influence is a well-established characteristic of autistic visual perception. However, whether this confirmed finding has an equivalent in the auditory modality is still unknown. To fill this gap, 18 autistics and 18 typical participants completed a melodic decision task where global and local level information can be congruent or incongruent. While focusing either on the global (melody) or local level (group of notes) of hierarchical auditory stimuli, participants have to decide whether the focused level is rising or falling. Autistics showed intact global processing, a superior performance when processing local elements and a reduced global-to-local interference compared to typical participants. These results are the first to demonstrate that autistic processing of auditory hierarchical stimuli closely parallels processing of visual hierarchical stimuli. When analyzing complex auditory information, autistic participants present a local bias and a more autonomous local processing, but not to the detriment of global processing.	\N	\N
24639401	Blind people rely more on vocal cues when they recognize a person's identity than sighted people. Indeed, a number of studies have reported better voice recognition skills in blind than in sighted adults. The present functional magnetic resonance imaging study investigated changes in the functional organization of neural systems involved in voice identity processing following congenital blindness. A group of congenitally blind individuals and matched sighted control participants were tested in a priming paradigm, in which two voice stimuli (S1, S2) were subsequently presented. The prime (S1) and the target (S2) were either from the same speaker (person-congruent voices) or from two different speakers (person-incongruent voices). Participants had to classify the S2 as either a old or a young person. Person-incongruent voices (S2) compared with person-congruent voices elicited an increased activation in the right anterior fusiform gyrus in congenitally blind individuals but not in matched sighted control participants. In contrast, only matched sighted controls showed a higher activation in response to person-incongruent compared with person-congruent voices (S2) in the right posterior superior temporal sulcus. These results provide evidence for crossmodal plastic changes of the person identification system in the brain after visual deprivation.	\N	\N
24642285	We used magnetoencephalography (MEG) to examine brain activity related to the maintenance of non-verbal pitch information in auditory short-term memory (ASTM). We focused on brain activity that increased with the number of items effectively held in memory by the participants during the retention interval of an auditory memory task. We used very simple acoustic materials (i.e., pure tones that varied in pitch) that minimized activation from non-ASTM related systems. MEG revealed neural activity in frontal, temporal, and parietal cortices that increased with a greater number of items effectively held in memory by the participants during the maintenance of pitch representations in ASTM. The present results reinforce the functional role of frontal and temporal cortices in the retention of pitch information in ASTM. This is the first MEG study to provide both fine spatial localization and temporal resolution on the neural mechanisms of non-verbal ASTM for pitch in relation to individual differences in the capacity of ASTM. This research contributes to a comprehensive understanding of the mechanisms mediating the representation and maintenance of basic non-verbal auditory features in the human brain.	\N	\N
24655365	Previous studies have shown that in semi-spontaneous speech, individuals with Broca's and anomic aphasia produce relatively many direct speech constructions. It has been claimed that in 'healthy' communication direct speech constructions contribute to the liveliness, and indirectly to the comprehensibility, of speech. To examine the effects of the occurrence of direct speech constructions on the perceived liveliness and speech comprehensibility of narratives produced by individuals with and without aphasia. Thirty-seven naive listeners rated 30 speech fragments with and without direct speech from ten speakers with and ten speakers without aphasia. The fragments originated from semi-structured interviews. The raters scored the perceived liveliness and the perceived comprehensibility of these fragments. For both groups of speakers, fragments containing direct speech constructions received higher scores for liveliness than fragments without direct speech constructions. However, no effect of direct speech was found on perceived comprehensibility. This is the first research to demonstrate that communication is perceived as more lively when it contains direct speech than when it does not, but yet is not more comprehensible. Individuals with Broca's and anomic aphasia are known to produce regularly direct speech constructions in elicited narratives. Given that liveliness is known to increase listeners' involvement and to help listeners stay focused, we suggest that this relative increase in direct speech by aphasic speakers may reflect a strategy to increase not only the liveliness of their discourse, but also listener focus and involvement.	\N	\N
24658600	Extended stabilization of gaze leads to disappearance of dim visual targets presented peripherally. This phenomenon, known as Troxler fading, is thought to result from neuronal adaptation. Intense targets also disappear intermittently when surrounded by a moving pattern (the "mask"), a phenomenon known as motion-induced blindness (MIB). The similar phenomenology and dynamics of these disappearances may suggest that also MIB is, likewise, solely due to adaptation, which may be amplified by the presence of the mask. Here we directly compared the dependence of both phenomena on target contrast. Observers reported the disappearance and reappearance of a target of varying intensity (contrast levels: 8%-80%). MIB was induced by adding a mask that moved at one of various different speeds. The results revealed a lawful effect of contrast in both MIB and Troxler fading, but with opposite trends. Increasing target contrast increased (doubled) the rate of disappearance events for MIB, but decreased the disappearance rate to half in Troxler fading. The target mean invisible period decreased equally strongly with target contrast in MIB and in Troxler fading. The results suggest that both MIB and Troxler are equally affected by contrast adaptation, but that the rate of MIB is governed by an additional mechanism, possibly involving antagonistic processes between neuronal populations processing target and mask. Our results link MIB to other bi-stable visual phenomena that involve neuronal competition (such as binocular rivalry), which exhibit an analogous dependency on the strength of the competing stimulus components.	\N	\N
24658601	The goal of this study was to create and validate a new set of sentence lists that could be used to evaluate the speech-perception abilities of listeners with hearing loss in cases where adult materials are inappropriate due to difficulty level or content. The authors aimed to generate a large number of sentence lists with an equivalent level of difficulty for the evaluation of performance over time and across conditions. The original Pediatric AzBio sentence corpus included 450 sentences recorded from one female talker. All sentences included in the corpus were successfully repeated by kindergarten and first-grade students with normal hearing. The mean intelligibility of each sentence was estimated by processing each sentence through a cochlear implant simulation and calculating the mean percent correct score achieved by 15 normal-hearing listeners. After sorting sentences by mean percent correct scores, 320 sentences were assigned to 16 lists of equivalent difficulty. List equivalency was then validated by presenting all sentence lists, in a novel random order, to adults and children with hearing loss. A final-validation stage examined single-list comparisons from adult and pediatric listeners tested in research or clinical settings. The results of the simulation study allowed for the creation of 16 lists of 20 sentences. The average intelligibility of each list ranged from 78.4 to 78.7%. List equivalency was then validated, when the results of 16 adult cochlear implant users and 9 pediatric hearing aid and cochlear implant users revealed no significant differences across lists. The binomial distribution model was used to account for the inherent variability observed in the lists. This model was also used to generate 95% confidence intervals for one and two list comparisons. A retrospective analysis of 361 instances from 78 adult cochlear implant users and 48 instances from 36 pediatric cochlear implant users revealed that the 95% confidence intervals derived from the model captured 94% of all responses (385 of 409). The cochlear implant simulation was shown to be an effective method for estimating the intelligibility of individual sentences for use in the evaluation of cochlear implant users. Furthermore, the method used for constructing equivalent sentence lists and estimating the inherent variability of the materials has also been validated. Thus, the AzBio Pediatric Sentence Lists are equivalent and appropriate for the assessment of speech-understanding abilities of children with hearing loss as well as adults for whom performance on AzBio sentences is near the floor.	\N	\N
24671776	Learning about objects often requires making arbitrary associations among multisensory properties, such as the taste and appearance of a food or the face and voice of a person. However, the multisensory properties of individual objects usually are statistically constrained, such that some properties are more likely to co-occur than others, on the basis of their category. For example, male faces are more likely to co-occur with characteristically male voices than with female voices. Here, we report evidence that these natural multisensory statistics play a critical role in the learning of novel, arbitrary associative pairs. In Experiment 1, we found that learning of pairs consisting of human voices and gender-congruent faces was superior to learning of pairs consisting of human voices and gender-incongruent faces or of pairs consisting of human voices and pictures of inanimate objects (plants and rocks). In Experiment 2, we found that this "categorical congruency" advantage extended to nonhuman stimuli, as well-namely, to pairs of class-congruent animal pictures and vocalizations (e.g., dogs and barks) versus class-incongruent pairs (e.g., dogs and bird chirps). These findings suggest that associating multisensory properties that are statistically consistent with the various objects that we encounter in our daily lives is a privileged form of learning.	\N	\N
24686722	PURPOSE Several acoustic cues specify any single phonemic contrast. Nonetheless, adult, native speakers of a language share weighting strategies, showing preferential attention to some properties over others. Cochlear implant (CI) signal processing disrupts the salience of some cues: In general, amplitude structure remains readily available, but spectral structure less so. This study asked how well speech recognition is supported if CI users shift attention to salient cues not weighted strongly by native speakers. METHOD Twenty adults with CIs participated. The /bɑ/-/wɑ/ contrast was used because spectral and amplitude structure varies in correlated fashion for this contrast. Adults with normal hearing weight the spectral cue strongly but the amplitude cue negligibly. Three measurements were made: labeling decisions, spectral and amplitude discrimination, and word recognition. RESULTS Outcomes varied across listeners: Some weighted the spectral cue strongly, some weighted the amplitude cue, and some weighted neither. Spectral discrimination predicted spectral weighting. Spectral weighting explained the most variance in word recognition. Age of onset of hearing loss predicted spectral weighting but not unique variance in word recognition. CONCLUSION The weighting strategies of listeners with normal hearing likely support speech recognition best, so efforts in implant design, fitting, and training should focus on developing those strategies.	\N	\N
24687127	The purpose of this research was to compare the perception of Japanese vowel length contrasts by 4 groups of listeners who differed in their familiarity with length contrasts in their first language (L1; i.e., American English, Italian, Japanese, and Thai). Of the 3 nonnative groups, native Thai listeners were expected to outperform American English and Italian listeners, because vowel length is contrastive in their L1. Native Italian listeners were expected to demonstrate a higher level of accuracy for length contrasts than American English listeners, because the former are familiar with consonant (but not vowel) length contrasts (i.e., singleton vs. geminate) in their L1. A 2-alternative forced-choice AXB discrimination test that included 125 trials was administered to all the participants, and the listeners' discrimination accuracy (d') was reported. As expected, Japanese listeners were more accurate than all 3 nonnative groups in their discrimination of Japanese vowel length contrasts. The 3 nonnative groups did not differ from one another in their discrimination accuracy despite varying experience with length contrasts in their L1. Only Thai listeners were more accurate in their length discrimination when the target vowel was long than when it was short. Being familiar with vowel length contrasts in L1 may affect the listeners' cross-language perception, but it does not guarantee that their L1 experience automatically results in efficient processing of length contrasts in unfamiliar languages. The extent of success may be related to how length contrasts are phonetically implemented in listeners' L1.	\N	\N
24690415	When musical notes are combined to make a chord, the closeness of fit of the combined spectrum to a single harmonic series (the 'harmonicity' of the chord) predicts the perceived consonance (how pleasant and stable the chord sounds; McDermott, Lehr, & Oxenham, 2010). The distinction between consonance and dissonance is central to Western musical form. Harmonicity is represented in the temporal firing patterns of populations of brainstem neurons. The current study investigates the role of brainstem temporal coding of harmonicity in the perception of consonance. Individual preference for consonant over dissonant chords was measured using a rating scale for pairs of simultaneous notes. In order to investigate the effects of cochlear interactions, notes were presented in two ways: both notes to both ears or each note to different ears. The electrophysiological frequency following response (FFR), reflecting sustained neural activity in the brainstem synchronised to the stimulus, was also measured. When both notes were presented to both ears the perceptual distinction between consonant and dissonant chords was stronger than when the notes were presented to different ears. In the condition in which both notes were presented to the both ears additional low-frequency components, corresponding to difference tones resulting from nonlinear cochlear processing, were observable in the FFR effectively enhancing the neural harmonicity of consonant chords but not dissonant chords. Suppressing the cochlear envelope component of the FFR also suppressed the additional frequency components. This suggests that, in the case of consonant chords, difference tones generated by interactions between notes in the cochlea enhance the perception of consonance. Furthermore, individuals with a greater distinction between consonant and dissonant chords in the FFR to individual harmonics had a stronger preference for consonant over dissonant chords. Overall, the results provide compelling evidence for the role of neural temporal coding in the perception of consonance, and suggest that the representation of harmonicity in phase locked neural firing drives the perception of consonance.	\N	\N
24701988	Studies of facial affect recognition by people with traumatic brain injury (TBI) have shown this to be a significant problem. Vocal affect recognition also appears to be challenging for this population, but little is known about the degree to which one modality is impaired compared to the other. This study compared facial and vocal affect recognition of high and low intensity emotion expressions in people with moderate-to-severe TBI. The Diagnostic Analysis of Nonverbal Accuracy-2 (Adult Faces; Voices) was administered to 203 participants with TBI. Adults with TBI identified vocal emotion expressions with greater accuracy than facial emotion expressions. Facial affect recognition impairment was identified in 34% of participants, 22% were classified as having vocal affect recognition impairment and 15% showed impairment in both modalities. Participants were significantly less accurate at identifying low vs high intensity emotion expressions in both modalities. Happy facial expressions were significantly better identified than all other emotions. Errors were distributed across the emotion categories for vocal expressions. The degree of facial affect impairment was significantly greater than vocal affect impairment in this sample of people with moderate-to-severe TBI. Low intensity emotion expressions were particularly problematic and an advantage for positively valenced facial emotion expressions was indicated.	\N	\N
24702433	In this paper, the authors analyze the auditory rehabilitation after cochlear implantation in adults with hearing impairment after head trauma, comparing their performance with that of other cochlear implant (CI) adult users who have post-lingual hearing impairment with other etiologies. The participants were divided into two groups: group 1 (N = 14) composed of CI adult users who have acquired severe to profound hearing loss after head trauma; group 2 (N = 231) composed of CI adult users who have severe to profound hearing loss from other etiologies. Performance was assessed using the following tests: tonal audiometry, speech audiometry, consonantal phonemes identification test, 100 words test, 100 words through the telephone test, monosyllables test, numbers test, sentences test, and sentences through the telephone test. Average results from group 1 were lower when compared with those of group 2 in all the tests used. No statistically significant difference was found for most tests. Statistically significant difference was found for consonantal phonemes identification test, 100 words through the telephone test, monosyllables test (when analyzed regarding the phonemes correctly repeated), and sentences through the telephone test. The performance of the group of CI adult users who have acquired hearing impairment after head trauma was globally lower than that observed on the group of hearing impairment with other etiologies. However, the difference was not statistically significant for most tests. Despite this difference in performance, the results from the group of CI adult users who have acquired hearing impairment after head trauma show the effectiveness of auditory rehabilitation through cochlear implantation in these situations.	\N	\N
24703829	Exploding head syndrome is characterized by the perception of abrupt, loud noises when going to sleep or waking up. They are usually painless, but associated with fear and distress. In spite of the fact that its characteristic symptomatology was first described approximately 150 y ago, exploding head syndrome has received relatively little empirical and clinical attention. Therefore, a comprehensive review of the scientific literature using Medline, PsycINFO, Google Scholar, and PubMed was undertaken. After first discussing the history, prevalence, and associated features, the available polysomnography data and five main etiological theories for exploding head syndrome are summarized. None of these theories has yet reached dominance in the field. Next, the various methods used to assess and treat exploding head syndrome are discussed, as well as the limited outcome data. Finally, recommendations for future measure construction, treatment options, and differential diagnosis are provided.	\N	\N
24707789	Syntactic priming occurs when structural information from one sentence influences processing of a subsequently encountered sentence (Bock, 1986; Ledoux et al., 2007). This article reports 2 eye-tracking experiments investigating the effects of a prime sentence on the processing of a target sentence that shared aspects of syntactic form. The experiments were designed to determine the degree to which lexical overlap between prime and target sentences produced larger effects, comparable to the widely observed "lexical boost" in production experiments (Pickering & Branigan, 1998; Pickering & Ferreira, 2008). The current experiments showed that priming effects during online comprehension were in fact larger when a verb was repeated across the prime and target sentences (see also Tooley et al., 2009). The finding of larger priming effects with lexical repetition supports accounts under which syntactic form representations are connected to individual lexical items (e.g., Tomasello, 2003; Vosse & Kempen, 2000, 2009).	\N	\N
24708425	Visual illusions can reveal unconscious representations and processes at work in perception. Here we report a robust illusion that involves the misperception of moving, partially occluded objects. When a dynamically occluded object is seen through 2 misaligned apertures, the object appears misaligned in the direction of the apertures, creating the Aperture Capture Illusion. Specifically, when part of a dynamically occluded object disappears behind an occluding surface and then another part of the object comes into view immediately afterward, the 2 parts appear misaligned in the direction of the offset of the apertures through which they were seen. This illusion can be nulled: Separating the 2 object parts to increase the time interval between their appearance produced the percept of alignment. The ability to null the illusion in this manner demonstrates that dynamically occluded regions of moving objects continue to persist in perceptual awareness but, we argue, are perceived to move at a slower velocity than visible regions. We report 7 experiments establishing the existence of the illusion and ruling out several classes of explanation for it. We interpret the illusion and the ability to nullify it within the context of Palmer, Kellman, and Shipley's (2006) theory of spatiotemporal object formation.	\N	\N
24719237	A briefly flashed target stimulus can become "invisible" when immediately followed by a mask-a phenomenon known as backward masking, which constitutes a major tool in the cognitive sciences. One form of backward masking is termed metacontrast masking. It is generally assumed that in metacontrast masking, the mask suppresses activity on which the conscious perception of the target relies. This assumption biases conclusions when masking is used as a tool-for example, to study the independence between perceptual detection and motor reaction. This is because other models can account for reduced perceptual performance without requiring suppression mechanisms. In this study, we used signal detection theory to test the suppression model against an alternative view of metacontrast masking, referred to as the summation model. This model claims that target- and mask-related activations fuse and that the difficulty in detecting the target results from the difficulty to discriminate this fused response from the response produced by the mask alone. Our data support this alternative view. This study is not a thorough investigation of metacontrast masking. Instead, we wanted to point out that when a different model is used to account for the reduced perceptual performance in metacontrast masking, there is no need to postulate a dissociation between perceptual and motor responses to account for the data. Metacontrast masking, as implemented in the Fehrer-Raab situation, therefore is not a valid method to assess perceptual-motor dissociations.	\N	\N
24728649	Recent findings have suggested that transient attention can be triggered at two locations simultaneously. However, it is unclear whether doing so reduces the effect of attention at each attended location. In two experiments, we explored the consequences of dividing attention. In the first experiment, we compared the effects of one or two cues against an uncued baseline to determine the consequences of dividing attention in a paradigm with four rapid serial visual presentation (RSVP) streams. The results indicated that two simultaneous cues increase the accuracy of reporting two targets by almost the same amount as a single cue increases the report of a single target. These results suggest that when attention is divided between multiple locations, the attentional benefit at each location is not reduced in proportion to the total number of cues. A consequent prediction of this finding is that the identification of two RSVP targets should be better when they are presented simultaneously rather than sequentially. In a second experiment, we verified this prediction by finding evidence of lag-0 sparing: Two targets presented simultaneously in different locations were reported more easily than two targets separated by 100 ms. These findings argue against a biased-competition theory of attention. We suggest that visual attention, as triggered by a cue or target, is better described by a convergent gradient-field attention model.	\N	\N
24728874	In autism spectrum disorders (ASD), social motivation theories suggest that the core social communication problems seen in children with ASD arise from diminished responsiveness to social reward. Although clinical and experimental data support these theories, the extent to which the reward deficit in ASD is unique for social rewards remains unclear. With the present investigation, we aimed to provide insight into the degree to which sociality as well as familiarity of reward incentives impact motivated goal-directed behavior in children with ASD. To do so, we directly compared the influence of familiar versus unfamiliar social reward relative to nonsocial, monetary reward in children with ASD relative to age- and IQ-matched typically developing controls (TDC) using a visual and auditory incentive go/nogo task with reward contingencies for successful response inhibitions. We found that children with ASD responded stronger to visual familiar and unfamiliar social reward as well as to nonsocial, monetary reward than TDC. While the present data are at odds with predictions made by social motivation theories, individual variations beyond clinical diagnosis, such as reward exposure across various social settings, help explain the pattern of results. The findings of this study stress the necessity for additional research on intra-individual as well as environmental factors that contribute to social reward responsiveness in individuals with ASD versus other neuropsychiatric disorders such as ADHD or conduct disorder.	\N	\N
24732070	Human subjects performed in several behavioral conditions requiring, or not requiring, selective attention to visual stimuli. Specifically, the attentional task was to recognize strings of digits that had been presented visually. A nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE), called the nSFOAE, was collected during the visual presentation of the digits. The segment of the physiological response discussed here occurred during brief silent periods immediately following the SFOAE-evoking stimuli. For all subjects tested, the physiological-noise magnitudes were substantially weaker (less noisy) during the tasks requiring the most visual attention. Effect sizes for the differences were >2.0. Our interpretation is that cortico-olivo influences adjusted the magnitude of efferent activation during the SFOAE-evoking stimulation depending upon the attention task in effect, and then that magnitude of efferent activation persisted throughout the silent period where it also modulated the physiological noise present. Because the results were highly similar to those obtained when the behavioral conditions involved auditory attention, similar mechanisms appear to operate both across modalities and within modalities. Supplementary measurements revealed that the efferent activation was spectrally global, as it was for auditory attention.	\N	\N
24746946	Action representations associated with object use may be incidentally activated during visual object processing, and the time course of such activations may be influenced by lexical-semantic context (e.g., Lee, Middleton, Mirman, Kalénine, & Buxbaum (2012). Journal of Experimental Psychology: Human Perception and Performance, 39(1), 257-270). In this study we used the "visual world" eye-tracking paradigm to examine whether a deficit in producing skilled object-use actions (apraxia) is associated with abnormalities in incidental activation of action information, and assessed the neuroanatomical substrates of any such deficits. Twenty left hemisphere stroke patients, ten of whom were apraxic, performed a task requiring identification of a named object in a visual display containing manipulation-related and unrelated distractor objects. Manipulation relationships among objects were not relevant to the identification task. Objects were cued with neutral ("S/he saw the…."), or action-relevant ("S/he used the….") sentences. Non-apraxic participants looked at use-related non-target objects significantly more than at unrelated non-target objects when cued both by neutral and action-relevant sentences, indicating that action information is incidentally activated. In contrast, apraxic participants showed delayed activation of manipulation-based action information during object identification when cued by neutral sentences. The magnitude of delayed activation in the neutral sentence condition was reliably predicted by lower scores on a test of gesture production to viewed objects, as well as by lesion loci in the inferior parietal and posterior temporal lobes. However, when cued by a sentence containing an action verb, apraxic participants showed fixation patterns that were statistically indistinguishable from non-apraxic controls. In support of grounded theories of cognition, these results suggest that apraxia and temporal-parietal lesions may be associated with abnormalities in incidental activation of action information from objects. Further, they suggest that the previously-observed facilitative role of action verbs in the retrieval of object-related action information extends to participants with apraxia.	\N	\N
24746955	Selective attention to phonology, i.e., the ability to attend to sub-syllabic units within spoken words, is a critical precursor to literacy acquisition. Recent functional magnetic resonance imaging evidence has demonstrated that a left-lateralized network of frontal, temporal, and posterior language regions, including the visual word form area, supports this skill. The current event-related potential (ERP) study investigated the temporal dynamics of selective attention to phonology during spoken word perception. We tested the hypothesis that selective attention to phonology dynamically modulates stimulus encoding by recruiting left-lateralized processes specifically while the information critical for performance is unfolding. Selective attention to phonology was captured by manipulating listening goals: skilled adult readers attended to either rhyme or melody within auditory stimulus pairs. Each pair superimposed rhyming and melodic information ensuring identical sensory stimulation. Selective attention to phonology produced distinct early and late topographic ERP effects during stimulus encoding. Data-driven source localization analyses revealed that selective attention to phonology led to significantly greater recruitment of left-lateralized posterior and extensive temporal regions, which was notably concurrent with the rhyme-relevant information within the word. Furthermore, selective attention effects were specific to auditory stimulus encoding and not observed in response to cues, arguing against the notion that they reflect sustained task setting. Collectively, these results demonstrate that selective attention to phonology dynamically engages a left-lateralized network during the critical time-period of perception for achieving phonological analysis goals. These findings suggest a key role for selective attention in on-line phonological computations. Furthermore, these findings motivate future research on the role that neural mechanisms of attention may play in phonological awareness impairments thought to underlie developmental reading disabilities.	\N	\N
24751993	Voice pitch is an important information-bearing component of language that is subject to experience dependent plasticity at both early cortical and subcortical stages of processing. We have already demonstrated that pitch onset component (Na) of the cortical pitch response (CPR) is sensitive to flat pitch and its salience … CPR responses from Chinese listeners were elicited by three citation forms varying in pitch acceleration and duration. Results showed that the pitch onset component (Na) was invariant to changes in acceleration. In contrast, Na–Pb and Pb–Nb showed a systematic decrease in the interpeak latency and decrease in amplitude with increase in pitch acceleration that followed the time course of pitch change across the three stimuli. A strong correlation with pitch acceleration was observed for these two components only – a putative index of pitch-relevant neural activity associated with the more rapidly-changing portions of the pitch contour. Pc–Nc marks unambiguously the stimulus offset … and their functional roles as related to sensory and cognitive properties of the stimulus. [Corrected]	\N	\N
24754984	To retrospectively analyze the auditory and speech development of young children with bilateral congenital aural atresia after using bone-anchored hearing aid (BAHA) softband. From August 2010 to January 2013, a total of 12 patients aged at a range of 3 months to 6 years with bilateral aural atresia using BAHA softband were divided into under 4-year-old group (n = 7, an average age of 14 months) and over 4-year-old group (n = 5, an average age of 77 months). The air and bone auditory thresholds of the under 4-year-old group were assessed by auditory brainstem response (ABR). The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) was used to evaluate early auditory development.Soundfield pure tone audiometry (PTA) was applied in the over 4-year-old group. The Standard Chinese lexical neighborhood test (LNT) was conducted to evaluate the speech discrimination scores unaided and aided for 6, 12 and 24 months. For the under 4-year-old group, the unaided air and bone conduction hearing thresholds were 70-90(73 ± 12) and 15-25(21 ± 4) dB nHL respectively.IT-MAIS score improved significantly after using softband for 6 months in comparisons with unaided situations. The average hearing threshold of patients in the over 4-year-old group was (63 ± 6) dB HL unaided versus (31 ± 4)dB HL aided. The average decline in pure-tone threshold was (32 ± 3)dB HL with BAHA softbands and LNT demonstrated improvements in the speech discrimination score. The differences of paired comparison were significant (all P < 0.05). The hearing ability of children with bilateral congenital aural atresia improves significantly after using BAHA softband. And its application at a young age can guarantee a relatively normal hearing development and avoid oral communication impairment.	\N	\N
24764068	The effects on multisensory integration have rarely been examined in amblyopia. The McGurk effect is a well-established audiovisual illusion that is manifested when an auditory phoneme is presented concurrently with an incongruent visual phoneme. Visually healthy viewers will hear a phoneme that does not match the actual auditory stimulus, having been perceptually influenced by the visual phoneme. This study examines audiovisual integration in adults with amblyopia. Twenty-two subjects with amblyopia and 25 visually healthy controls participated. Participants viewed videos of combinations of visual and auditory phonemes, and were asked to report what they heard. Some videos had congruent video and audio (control), whereas others had incongruent video and audio (McGurk). The McGurk effect is strongest when the visual phoneme dominates over the audio phoneme, resulting in low auditory accuracy on the task. Adults with amblyopia demonstrated a weaker McGurk effect than visually healthy controls (P = 0.01). The difference was greatest when viewing monocularly with the amblyopic eye, and it was also evident when viewing binocularly or monocularly with the fellow eye. No correlations were found between the strength of the McGurk effect and either visual acuity or stereoacuity in subjects with amblyopia. Subjects with amblyopia and controls showed a similar response pattern to different speakers and syllables, and subjects with amblyopia consistently demonstrated a weaker effect than controls. Abnormal visual experience early in life can have negative consequences for audiovisual integration that persists into adulthood in people with amblyopia.	\N	\N
24770403	To clarify the responsible gene for a family associated with hearing loss but having no well-known mitochondrial mutations. A Japanese family showing late-onset, progressive, and ski-sloping sensorineural hearing loss. Whole mitochondrial genome sequencing identified the 1673T>C mutation, a novel mitochondrial DNA mutation in the 16S ribosomal RNA gene. Whole mitochondrial genome sequencing is a powerful tool to identify the responsible gene for plausible mitochondrially inherited families. This is additional evidence that mitochondrial gene mutations may cause late-onset, progressive, and ski-sloping sensorineural hearing loss.	\N	\N
24778251	Although it is well accepted that the speech motor system (SMS) is activated during speech perception, the functional role of this activation remains unclear. Here we test the hypothesis that the redundant motor activation contributes to categorical speech perception under adverse listening conditions. In this functional magnetic resonance imaging study, participants identified one of four phoneme tokens (/ba/, /ma/, /da/, or /ta/) under one of six signal-to-noise ratio (SNR) levels (-12, -9, -6, -2, 8 dB, and no noise). Univariate and multivariate pattern analyses were used to determine the role of the SMS during perception of noise-impoverished phonemes. Results revealed a negative correlation between neural activity and perceptual accuracy in the left ventral premotor cortex and Broca's area. More importantly, multivoxel patterns of activity in the left ventral premotor cortex and Broca's area exhibited effective phoneme categorization when SNR ≥ -6 dB. This is in sharp contrast with phoneme discriminability in bilateral auditory cortices and sensorimotor interface areas (e.g., left posterior superior temporal gyrus), which was reliable only when the noise was extremely weak (SNR > 8 dB). Our findings provide strong neuroimaging evidence for a greater robustness of the SMS than auditory regions for categorical speech perception in noise. Under adverse listening conditions, better discriminative activity in the SMS may compensate for loss of specificity in the auditory system via sensorimotor integration.	\N	\N
24778384	The activation of listener's motor system during speech processing was first demonstrated by the enhancement of electromyographic tongue potentials as evoked by single-pulse transcranial magnetic stimulation (TMS) over tongue motor cortex. This technique is, however, technically challenging and enables only a rather coarse measurement of this motor mirroring. Here, we applied TMS to listeners' tongue motor area in association with ultrasound tissue Doppler imaging to describe fine-grained tongue kinematic synergies evoked by passive listening to speech. Subjects listened to syllables requiring different patterns of dorso-ventral and antero-posterior movements (/ki/, /ko/, /ti/, /to/). Results show that passive listening to speech sounds evokes a pattern of motor synergies mirroring those occurring during speech production. Moreover, mirror motor synergies were more evident in those subjects showing good performances in discriminating speech in noise demonstrating a role of the speech-related mirror system in feed-forward processing the speaker's ongoing motor plan.	\N	\N
24779648	This study used event-related potentials (ERPs) to investigate discourse-coherence processing. Because there are scant data on ERP indices of discourse coherence in typical adults, it is important to study a non-clinical population before examining clinical populations. Twelve adults listened to a story with sentences in a coherent versus incoherent order. Sequences of nonsense syllables served as a control. ERPs in the 200-400 ms time window, reflecting phonological and lexical processing, and in the 600-900 ms time window, reflecting later discourse processing for integration, were investigated. Results revealed a right anterior and posterior positivity that was greater for coherent than for incoherent discourse during the 600-900 ms time window. These findings point to an index of discourse coherence and further suggest that ERPs can be used as a clinical tool to study discourse-processing disorders in populations with brain damage, such as aphasia and traumatic brain injury.	\N	\N
24793771	Auditory filter theory dictates a physiological compromise between frequency and temporal resolution of cochlear signal processing. We examined neurophysiological correlates of these spectrotemporal tradeoffs in the human auditory system using auditory evoked brain potentials and psychophysical responses. Temporal resolution was assessed using scalp-recorded auditory brainstem responses (ABRs) elicited by paired clicks. The inter-click interval (ICI) between successive pulses was parameterized from 0.7 to 25 ms to map ABR amplitude recovery as a function of stimulus spacing. Behavioral frequency difference limens (FDLs) and auditory filter selectivity (Q10 of psychophysical tuning curves) were obtained to assess relations between behavioral spectral acuity and electrophysiological estimates of temporal resolvability. Neural responses increased monotonically in amplitude with increasing ICI, ranging from total suppression (0.7 ms) to full recovery (25 ms) with a temporal resolution of ∼3-4 ms. ABR temporal thresholds were correlated with behavioral Q10 (frequency selectivity) but not FDLs (frequency discrimination); no correspondence was observed between Q10 and FDLs. Results suggest that finer frequency selectivity, but not discrimination, is associated with poorer temporal resolution. The inverse relation between ABR recovery and perceptual frequency tuning demonstrates a time-frequency tradeoff between the temporal and spectral resolving power of the human auditory system.	\N	\N
24795958	This study investigates how speed of motion is processed in language. In three eye-tracking experiments, participants were presented with visual scenes and spoken sentences describing fast or slow events (e.g., The lion ambled/dashed to the balloon). Results showed that looking time to relevant objects in the visual scene was affected by the speed of verb of the sentence, speaking rate, and configuration of a supporting visual scene. The results provide novel evidence for the mental simulation of speed in language and show that internal dynamic simulations can be played out via eye movements toward a static visual scene.	\N	\N
24801737	Two experiments used the progressive demasking (PD) task to examine age differences in the ability to inhibit higher frequency competitors during the process of identifying a visually degraded word. In Experiment 1, older adults exhibited a larger inhibitory neighborhood frequency effect (i.e., slower identification of words with many higher frequency competitors) than younger adults, but additional analyses indicated that this difference could be explained by general slowing rather than a deficit in inhibitory abilities. In Experiment 2, a primed version of the PD task was used to promote hypothesis testing by semantically priming the target word (e.g., cry-weep) or a higher frequency competitor of the target (e.g, day-weep) prior to the onset of the demasking sequence. Although older adults were more likely to make identification errors consistent with an inhibitory deficit (e.g., identifying weep as week), these errors were infrequent overall and there was no corresponding evidence of a larger interference effect in the older adults' identification latencies. Taken together, performance in these two tasks provides little evidence of reduced inhibitory functioning in older adults. The implications for the inhibitory deficit hypothesis of cognitive aging and directions for future are discussed.	\N	\N
24807850	The Finnish Matrix Test is the first sentence test in noise for the Finnish language. It was developed according to the HearCom standards and provides reliable speech intelligibility measurements with highly comparable results with the other international matrix tests. The aim of the study was to develop an accurate speech intelligibility test in noise for the Finnish language that is comparable across different languages. We chose a matrix sentence test, which comprises a base matrix of 10 names, verbs, numerals, adjectives and nouns. Test lists were formed from this matrix quasi randomly, providing test sentences of the same syntactical structure. The speech material corresponds to everyday spoken language and the phoneme distribution is representative of the Finnish language. The test was optimized by determining the speech recognition thresholds of the individual words and subsequently by applying level corrections of up to ±3 dB. Evaluation measurements were performed to check the equivalence of the different test lists with respect to speech intelligibility and to provide reference values for further clinical applications. After training, the mean speech recognition threshold (SRT) and the slope of the final test lists were -10.1 ± 0.1 dB signal-to-noise-ratio (SNR)and 16.7 ± 1.2%/dB, respectively (measurements at constant level; inter-list variability). The mean SRT and the slope of the test subjects were -10.1 ± 0.7 dB SNR and 17.5 ± 2.2%/dB (measurements at constant level; inter-subject variability). The expected SRT range for normal-hearing young adults for adaptive measurements is -9.7 ± 0.7 dB SNR.	\N	\N
24814580	The goal of the present research was to provide direct evidence for the cross-language interaction of phonologies at the sub-lexical level by using the masked onset priming paradigm. More specifically, we investigated whether there is a cross-language masked onset priming effect (MOPE) with L2 (English) primes and L1 (Russian) targets and whether it is modulated by the orthographic similarity of primes and targets. Primes and targets had onsets that overlapped either only phonologically, only orthographically, both phonologically and orthographically, or did not have any overlap. Phonological overlap, but not orthographic overlap, between primes and targets led to faster naming latencies. In contrast, the ERP data provided evidence for effects of both phonological and orthographic overlap. Finally, the time-course of phonological and orthographic processing for our bilinguals mirrored the time-course previously reported for monolinguals in the ERP data. These results provide evidence for shared representations at the sub-lexical level for a bilingual's two languages.	\N	\N
24815281	Reduced spectral resolution negatively impacts speech perception, particularly perception of vowels and consonant place. This study assessed impact of number of spectral channels on vowel discrimination by 6-month-old infants with normal hearing by comparing three listening conditions: Unprocessed speech, 32 channels, and 16 channels. Auditory stimuli (/ti/ and /ta/) were spectrally reduced using a noiseband vocoder and presented to infants with normal hearing via visual habituation. Results supported a significant effect of number of channels on vowel discrimination by 6-month-old infants. No differences emerged between unprocessed and 32-channel conditions in which infants looked longer during novel stimulus trials (i.e., discrimination). The 16-channel condition yielded a significantly different pattern: Infants demonstrated no significant difference in looking time to familiar vs novel stimulus trials, suggesting infants cannot discriminate /ti/ and /ta/ with only 16 channels. Results support effects of spectral resolution on vowel discrimination. Relative to published reports, young infants need more spectral detail than older children and adults to perceive spectrally degraded speech. Results have implications for development of perception by infants with hearing loss who receive auditory prostheses.	\N	\N
24828221	There are many clinically available tests for the assessment of auditory processing skills in children and adults. However, there is limited data available on the maturational effects on the performance on these tests. The current study investigated maturational effects on auditory processing abilities using three psychophysical measures: temporal modulation transfer function (TMTF), iterated ripple noise (IRN) perception, and spectral ripple discrimination (SRD). A cross-sectional study. Three groups of subjects were tested: 10 adults (18-30 yr), 10 older children (12-18 yr), and 10 young children (8-11 yr) Temporal envelope processing was measured by obtaining thresholds for amplitude modulation detection as a function of modulation frequency (TMTF; 4, 8, 16, 32, 64, and 128 Hz). Temporal fine structure processing was measured using IRN, and spectral processing was measured using SRD. The results showed that young children had significantly higher modulation thresholds at 4 Hz (TMTF) compared to the other two groups and poorer SRD scores compared to adults. The results on IRN did not differ across groups. The results suggest that different aspects of auditory processing mature at different age periods and these maturational effects need to be considered while assessing auditory processing in children.	\N	\N
24838018	The multisensory response enhancement (MRE), occurring when the response to a visual target integrated with a spatially congruent sound is stronger than the response to the visual target alone, is believed to be mediated by the superior colliculus (SC) (Stein & Meredith, 1993). Here, we used a focused attention paradigm to show that the spatial congruency effect occurs with red (SC-effective) but not blue (SC-ineffective) visual stimuli, when presented with spatially congruent sounds. To isolate the chromatic component of SC-ineffective targets and to demonstrate the selectivity of the spatial congruency effect we used the random luminance modulation technique (Experiment 1) and the tritanopic technique (Experiment 2). Our results indicate that the spatial congruency effect does not require the distribution of attention over different sensory modalities and provide correlational evidence that the SC mediates the effect.	\N	\N
24842067	Auditory feedback plays an important role in children's speech development by providing the child with information about speech outcomes that is used to learn and fine-tune speech motor plans. The use of auditory feedback in speech motor learning has been extensively studied in adults by examining oral motor responses to manipulations of auditory feedback during speech production. Children are also capable of adapting speech motor patterns to perceived changes in auditory feedback; however, it is not known whether their capacity for motor learning is limited by immature auditory-perceptual abilities. Here, the link between speech perceptual ability and the capacity for motor learning was explored in two groups of 5- to 7-year-old children who underwent a period of auditory perceptual training followed by tests of speech motor adaptation to altered auditory feedback. One group received perceptual training on a speech acoustic property relevant to the motor task while a control group received perceptual training on an irrelevant speech contrast. Learned perceptual improvements led to an enhancement in speech motor adaptation (proportional to the perceptual change) only for the experimental group. The results indicate that children's ability to perceive relevant speech acoustic properties has a direct influence on their capacity for sensory-based speech motor adaptation.	\N	\N
24850915	Many everyday skilled actions depend on moving in time with signals that are embedded in complex auditory streams (e.g. musical performance, dancing or simply holding a conversation). Such behaviour is apparently effortless; however, it is not known how humans combine auditory signals to support movement production and coordination. Here, we test how participants synchronize their movements when there are potentially conflicting auditory targets to guide their actions. Participants tapped their fingers in time with two simultaneously presented metronomes of equal tempo, but differing in phase and temporal regularity. Synchronization therefore depended on integrating the two timing cues into a single-event estimate or treating the cues as independent and thereby selecting one signal over the other. We show that a Bayesian inference process explains the situations in which participants choose to integrate or separate signals, and predicts motor timing errors. Simulations of this causal inference process demonstrate that this model provides a better description of the data than other plausible models. Our findings suggest that humans exploit a Bayesian inference process to control movement timing in situations where the origin of auditory signals needs to be resolved.	\N	\N
24851348	Learning and discovery seem often to begin with noting patterns. Human infants are skilled at pattern detection, even patterns only definable at an abstract level, which is key to their acquisition of complex knowledge systems such as language and music. However, research examining infants' abstract rule learning has generated inconsistent results. We propose that apparent domain differences in infants' abstract rule learning may be the result of extraneous stimulus variation and discrepancies in the methodologies employed across studies probing this skill. We discuss how a behavioral methodology indexing infants' online learning would be valuable in furthering understanding of infants' (as well as adults') abstract rule learning and its neurophysiological concomitants. We outline current research aimed at developing such an index, and we propose future research, pairing such techniques with neurophysiological methods, aimed at shining more light on human skill at discovering structure.	\N	\N
24856208	Human early visual cortex was traditionally thought to process simple visual features such as orientation, contrast, and spatial frequency via feedforward input from the lateral geniculate nucleus (e.g., [1]). However, the role of nonretinal influence on early visual cortex is so far insufficiently investigated despite much evidence that feedback connections greatly outnumber feedforward connections [2-5]. Here, we explored in five fMRI experiments how information originating from audition and imagery affects the brain activity patterns in early visual cortex in the absence of any feedforward visual stimulation. We show that category-specific information from both complex natural sounds and imagery can be read out from early visual cortex activity in blindfolded participants. The coding of nonretinal information in the activity patterns of early visual cortex is common across actual auditory perception and imagery and may be mediated by higher-level multisensory areas. Furthermore, this coding is robust to mild manipulations of attention and working memory but affected by orthogonal, cognitively demanding visuospatial processing. Crucially, the information fed down to early visual cortex is category specific and generalizes to sound exemplars of the same category, providing evidence for abstract information feedback rather than precise pictorial feedback. Our results suggest that early visual cortex receives nonretinal input from other brain areas when it is generated by auditory perception and/or imagery, and this input carries common abstract information. Our findings are compatible with feedback of predictive information to the earliest visual input level (e.g., [6]), in line with predictive coding models [7-10].	\N	\N
24858108	Rapidly approaching (looming) sounds are ecologically salient stimuli that are perceived as nearer than they are due to overestimation of their loudness change and underestimation of their distance (Neuhoff, 1998; Seifritz et al., 2002). Despite evidence for crossmodal influence by looming sounds onto visual areas (Romei, Murray, Cappe, & Thut, 2009, 2013; Tyll et al., 2013), it is unknown whether such sounds bias visual percepts in similar ways. Nearer objects appear to be larger and brighter than distant objects. If looming sounds impact visual processing, then visual stimuli paired with looming sounds should be perceived as brighter and larger, even when the visual stimuli do not provide motion cues, i.e. are static. In Experiment 1 we found that static visual objects paired with looming tones (but not static or receding tones) were perceived as larger and brighter than their actual physical properties, as if they appear closer to the observer. In a second experiment, we replicate and extend the findings of Experiment 1. Crucially, we did not find evidence of such bias by looming sounds when visual processing was disrupted via masking or when catch trials were presented, ruling out simple response bias. Finally, in a third experiment we found that looming tones do not bias visual stimulus characteristics that do not carry visual depth information such as shape, providing further evidence that they specifically impact in-depth visual processing. We conclude that looming sounds impact visual perception through a mechanism transferring in-depth sound motion information onto the relevant in-depth visual dimensions (such as size and luminance but not shape) in a crossmodal remapping of information for a genuine, evolutionary advantage in stimulus detection.	\N	\N
24869445	Two studies examined adult cochlear implant (CI) users' ability to match auditory rhythms occurring in music to visual rhythms occurring in dance (Cha Cha, Slow Swing, Tango and Jive). In Experiment 1, adults CI users (n = 10) and hearing controls matched a music excerpt to choreographed dance sequences presented as silent videos. In Experiment 2, participants matched a silent video of a dance sequence to music excerpts. CI users were successful in detecting timing congruencies across music and dance at well above-chance levels suggesting that they were able to process distinctive auditory and visual rhythm patterns that characterized each style. However, they were better able to detect cross-modal timing congruencies when the reference was an auditory rhythm than when the reference was a visual rhythm. Learning strategies that encourage cross-modal learning of musical rhythms may have applications in developing novel rehabilitative strategies to enhance music perception and appreciation outcomes of child implant users.	\N	\N
24872325	In the present study we investigate the rules governing the perception of audiovisual synchrony within spatio-temporally cluttered visual environments. Participants viewed a ring of 19 discs modulating in luminance while hearing an amplitude modulating tone. Each disc modulated with a unique temporal phase (40 ms intervals), with only one synchronized to the tone. Participants searched for the synchronised disc whose spatial location varied randomly across trials. Square-wave modulation facilitated search: the synchronized disc was frequently chosen, with tight response distributions centred near zero-phase lag. In the sinusoidal condition responses were equally distributed over the 19 discs regardless of phase. To investigate whether subjective synchrony in the square-wave condition was limited by spatial or temporal factors we repeated the experiment with either reduced spatial density (9 discs) or temporal density (80 ms phase intervals). Reduced temporal density greatly facilitated synchrony perception but left the synchrony bandwidth unchanged, while no influence of spatial density was found. We conclude that audio-visual synchrony is not strongly constrained by the spatial or temporal density of the visual display, but by a temporal window within which audio-visual events are perceived as synchronous, with a full bandwidth of ~185 ms.	\N	\N
24878593	One of the main issues within the field of social robotics is to endow robots with the ability to direct attention to people with whom they are interacting. Different approaches follow bio-inspired mechanisms, merging audio and visual cues to localize a person using multiple sensors. However, most of these fusion mechanisms have been used in fixed systems, such as those used in video-conference rooms, and thus, they may incur difficulties when constrained to the sensors with which a robot can be equipped. Besides, within the scope of interactive autonomous robots, there is a lack in terms of evaluating the benefits of audio-visual attention mechanisms, compared to only audio or visual approaches, in real scenarios. Most of the tests conducted have been within controlled environments, at short distances and/or with off-line performance measurements. With the goal of demonstrating the benefit of fusing sensory information with a Bayes inference for interactive robotics, this paper presents a system for localizing a person by processing visual and audio data. Moreover, the performance of this system is evaluated and compared via considering the technical limitations of unimodal systems. The experiments show the promise of the proposed approach for the proactive detection and tracking of speakers in a human-robot interactive framework.	\N	\N
24880672	To assess treatment outcomes via acoustic voice laboratory measurements before and after intervention in patients with common voice problems and Determine if outcome sensitivity of certain voice laboratory measures varies with disorder type. Retrospective and single-blinded. In this study, 40 patients with a single voice disorder diagnosis of either benign vocal fold lesions (lesions), primary muscle tension dysphonia (MTD-1), vocal fold atrophy (atrophy) or unilateral vocal fold paralysis (UVFP) underwent baseline testing, a single intervention-type (phonosurgery/voice therapy), and follow-up testing at uniform time points. Ten patients per diagnosis group were analyzed before and after treatment. Time- and frequency-based acoustic measures taken from vowels and sentences as well as patient-perceptual analysis (Voice Handicap Index-10) were reviewed. Statistically significant improvements were observed for three of four groups. Patients with muscle tension dysphonia displayed an improvement in Cepstral Spectral Index of Dysphonia speech (CSID) (P < 0.05). Patients with lesions had improved Voice Handicap Index-10 (P < 0.05), cepstral peak prominence (CPP) vowel standard deviation (P < 0.05), and CPP speech (P < 0.05). Patients with atrophy did not demonstrate significant improvement in any measure. Patients with unilateral vocal fold paralysis showed an improvement in CSID speech (P < 0.05) and CPP speech (P < 0.05). In addition, strong effect sizes were observed for many of the acoustic parameters studied. For all groups except atrophy, treatment was successful in improving patient perception of voice handicap and/or some acoustic voice parameters. A disorder-specific response to frequency-based acoustic measures was found.	\N	\N
24887110	Age-related hearing loss (presbycusis) is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1-3 month-old) and aged (2-2.5 year-old) mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10(+) cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells) in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10(+) marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10(+) cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10(+) cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10(+) cells may also be associated with a decline in the repair capabilities of non-sensory cells in the aged ear.	\N	\N
24893743	RTs in conversation, with average gaps of 200 msec and often less, beat standard RTs, despite the complexity of response and the lag in speech production (600 msec or more). This can only be achieved by anticipation of timing and content of turns in conversation, about which little is known. Using EEG and an experimental task with conversational stimuli, we show that estimation of turn durations are based on anticipating the way the turn would be completed. We found a neuronal correlate of turn-end anticipation localized in ACC and inferior parietal lobule, namely a beta-frequency desynchronization as early as 1250 msec, before the end of the turn. We suggest that anticipation of the other's utterance leads to accurately timed transitions in everyday conversations.	\N	\N
24897885	Twenty-four Japanese undergraduate pairs (12 male and 12 female pairs) participated as witnesses to a simulated criminal event. Although the witness pairs watched the same video together, through wireless headphones they experienced two different auditory versions with four differing items without being aware of the discrepancies. After the presentation, the witnesses were led to discuss six items, including two critical ones they had heard differently and another four they had heard in common. Witness memory performance was assessed individually with multiple-choice questionnaires in three sessions: before the discussion, after the discussion, and 1 week later. The results showed that participants tended to conform to their co-witness more often on the discussed items than on the not-discussed items. Source monitoring analyses on the four critical items revealed that even those participants who conformed were mostly cognizant of the source of their information just after the discussion, but they were prone to source-monitoring errors a week later.	\N	\N
24904404	Auditory perception and auditory imagery have been shown to activate overlapping brain regions. We hypothesized that these phenomena also share a common underlying neural representation. To assess this, we used electrocorticography intracranial recordings from epileptic patients performing an out loud or a silent reading task. In these tasks, short stories scrolled across a video screen in two conditions: subjects read the same stories both aloud (overt) and silently (covert). In a control condition the subject remained in a resting state. We first built a high gamma (70-150 Hz) neural decoding model to reconstruct spectrotemporal auditory features of self-generated overt speech. We then evaluated whether this same model could reconstruct auditory speech features in the covert speech condition. Two speech models were tested: a spectrogram and a modulation-based feature space. For the overt condition, reconstruction accuracy was evaluated as the correlation between original and predicted speech features, and was significant in each subject (p < 10(-5); paired two-sample t-test). For the covert speech condition, dynamic time warping was first used to realign the covert speech reconstruction with the corresponding original speech from the overt condition. Reconstruction accuracy was then evaluated as the correlation between original and reconstructed speech features. Covert reconstruction accuracy was compared to the accuracy obtained from reconstructions in the baseline control condition. Reconstruction accuracy for the covert condition was significantly better than for the control condition (p < 0.005; paired two-sample t-test). The superior temporal gyrus, pre- and post-central gyrus provided the highest reconstruction information. The relationship between overt and covert speech reconstruction depended on anatomy. These results provide evidence that auditory representations of covert speech can be reconstructed from models that are built from an overt speech data set, supporting a partially shared neural substrate.	\N	\N
24908166	Aging is associated with declines in auditory processing including speech comprehension abilities. Here, we evaluated both brainstem and cortical speech-evoked brain responses to elucidate how aging impacts the neural transcription and transfer of speech information between functional levels of the auditory nervous system. Behaviorally, older adults showed slower, more variable speech classification performance than younger listeners, which coincided with reduced brainstem amplitude and increased, but delayed, cortical speech-evoked responses. Mild age-related hearing loss showed differential correspondence with neurophysiological responses showing negative (brainstem) and positive (cortical) correlations with brain activity. Spontaneous brain activity, that is, "neural noise," did not differ between older and younger adults. Yet, mutual information and correlations computed between brainstem and cortex revealed higher redundancy (i.e., lower interdependence) in speech information transferred along the auditory pathway implying less neural flexibility in older adults. Results are consistent with the notion that weakened speech encoding in brainstem is overcompensated by increased cortical dysinhibition in the aging brain. Findings suggest aging negatively impacts speech listening abilities by distorting the hierarchy of speech representations, reducing neural flexibility through increased neural redundancy, and ultimately impairing the acoustic-phonetic mapping necessary for robust speech understanding.	\N	\N
24931795	Alpha oscillations are a prominent electrophysiological signal measured across a wide range of species and cortical and subcortical sites. Alpha oscillations have been viewed for a long time as an "idling" rhythm, purely reflecting inactive sites. Despite earlier evidence from neurophysiology, awareness that alpha oscillations can substantially influence perception and behavior has grown only recently in cognitive neuroscience. Evidence for an active role of alpha for perception comes mainly from several visual, near-threshold experiments. In the current review, we extend this view by summarizing studies showing how alpha-defined brain states relate to illusory perception, i.e. cases of perceptual reports that are not "objectively" verifiable by distinct stimuli or stimulus features. These studies demonstrate that ongoing or prestimulus alpha oscillations substantially influence the perception of auditory, visual or multisensory illusions.	\N	\N
24935820	Action perception and recognition are core abilities fundamental for human social interaction. A parieto-frontal network (the mirror neuron system) matches visually presented biological motion information onto observers' motor representations. This process of matching the actions of others onto our own sensorimotor repertoire is thought to be important for action recognition, providing a non-mediated "motor perception" based on a bidirectional flow of information along the mirror parieto-frontal circuits. State-of-the-art machine learning strategies for hand action identification have shown better performances when sensorimotor data, as opposed to visual information only, are available during learning. As speech is a particular type of action (with acoustic targets), it is expected to activate a mirror neuron mechanism. Indeed, in speech perception, motor centers have been shown to be causally involved in the discrimination of speech sounds. In this paper, we review recent neurophysiological and machine learning-based studies showing (a) the specific contribution of the motor system to speech perception and (b) that automatic phone recognition is significantly improved when motor data are used during training of classifiers (as opposed to learning from purely auditory data).	\N	\N
24936610	All languages employ certain phonetic contrasts when distinguishing words. Infant speech perception is rapidly attuned to these contrasts before many words are learned, thus phonetic attunement is thought to proceed independently of lexical and referential knowledge. Here, evidence to the contrary is provided. Ninety-eight 9-month-old English-learning infants were trained to perceive a non-native Cantonese tone contrast.Two object–tone audiovisual pairings were consistently presented, which highlighted the target contrast (Object A with Tone X; Object B with Tone Y). Tone discrimination was then assessed. Results showed improved tone discrimination if object–tone pairings were perceived as being referential word labels, although this effect was modulated by vocabulary size. Results suggest how lexical and referential knowledge could play a role in phonetic attunement.	\N	\N
24945666	Naturalistic stimuli, such as normal speech and narratives, are opening up intriguing prospects in neuroscience, especially when merging neuroimaging with machine learning methodology. Here we propose a task-optimized spatial filtering strategy for uncovering individual magnetoencephalographic (MEG) responses to audiobook stories. Ten subjects listened to 1-h-long recording once, as well as to 48 repetitions of a 1-min-long speech passage. Employing response replicability as statistical validity and utilizing unsupervised learning methods, we trained spatial filters that were able to generalize over datasets of an individual. For this blind-signal-separation (BSS) task, we derived a version of multi-set similarity-constrained canonical correlation analysis (SimCCA) that theoretically provides maximal signal-to-noise ratio (SNR) in this setting. Irrespective of significant noise in unaveraged MEG traces, the method successfully uncovered feasible time courses up to ~120 Hz, with the most prominent signals below 20 Hz. Individual trial-to-trial correlations of such time courses reached the level of 0.55 (median 0.33 in the group) at ~0.5 Hz, with considerable variation between subjects. By this filtering, the SNR increased up to 20 times. In comparison, independent component analysis (ICA) or principal component analysis (PCA) did not improve SNR notably. The validity of the extracted brain signals was further assessed by inspecting their associations with the stimulus, as well as by mapping the contributing cortical signal sources. The results indicate that the proposed methodology effectively reduces noise in MEG recordings to that extent that brain responses can be seen to nonrecurring audiobook stories. The study paves the way for applications aiming at accurately modeling the stimulus-response-relationship by tackling the response variability, as well as for real-time monitoring of brain signals of individuals in naturalistic experimental conditions.	\N	\N
24946201	To examine active inhibition of irrelevant stimuli and evaluate its neural basis using functional near infrared spectroscopy in patients with attention deficits after traumatic brain injury (TBI). Case control study. Ten patients with TBI and 10 healthy control subjects participated in this study. The Paced Auditory Serial Addition Test (PASAT) was performed with (distracting PASAT) and without (PASAT) distracting Japanese kana phonetic characters presented between each number. A block design was used. Subjects alternately performed each task three times. Healthy controls performed better than patients with TBI on both the tasks. When performing the PASAT, healthy controls showed significant activity in every region of interest except the right lateral prefrontal cortex (PFC), but patients with TBI showed significant activity only in the left anterior PFC and left lateral PFC. When performing the distracting PASAT, the right lateral PFC was active in healthy controls, but not in patients with TBI. These results confirm that patients with moderate-to-severe TBI were affected by distractors that influenced order processing. It is suggested that the working memory of patients with TBI was affected by distracting stimuli, whereas that of healthy individuals was not.	\N	\N
24963624	Recent experimental evidence suggests that the perception of temporal intervals is influenced by the temporal context in which they are presented. A longstanding example is the time-order-error, wherein the perception of two intervals relative to one another is influenced by the order in which they are presented. Here, we test whether the perception of temporal intervals in an absolute judgment task is influenced by the preceding temporal context. Human subjects participated in a temporal bisection task with no anchor durations (partition method). Intervals were demarcated by a Gaussian blob (visual condition) or burst of white noise (auditory condition) that persisted for one of seven logarithmically spaced sub-second intervals. Crucially, the order in which stimuli were presented was first-order counterbalanced, allowing us to measure the carryover effect of every successive combination of intervals. The results demonstrated a number of distinct findings. First, the perception of each interval was biased by the prior response, such that each interval was judged similarly to the preceding trial. Second, the perception of each interval was also influenced by the prior interval, such that perceived duration shifted away from the preceding interval. Additionally, the effect of decision bias was larger for visual intervals, whereas auditory intervals engendered greater perceptual carryover. We quantified these effects by designing a biologically-inspired computational model that measures noisy representations of time against an adaptive memory prior while simultaneously accounting for uncertainty, consistent with a Bayesian heuristic. We found that our model could account for all of the effects observed in human data. Additionally, our model could only accommodate both carryover effects when uncertainty and memory were calculated separately, suggesting separate neural representations for each. These findings demonstrate that time is susceptible to similar carryover effects as other basic stimulus attributes, and that the brain rapidly adapts to temporal context.	\N	\N
24975235	Matrix sentence tests use words from a fixed word matrix to compose syntactically equivalent, but semantically unpredictable sentences. These tests are suitable for monitoring performance of cochlear implant (CI) users by repeated speech intelligibility testing. This study evaluates the Dutch matrix sentence test in CI users in quiet and in noise. It then investigates the possibility to improve the test-retest reliability for CI users by selecting subsets of sentences. Repeated speech intelligibility testing was performed in quiet and in noise. The effect of sentence selection on the test-retest reliability was predicted by computer simulations and experimentally evaluated using a cross-over design. Fifteen post-lingually deafened CI users, of which eleven participated in the cross-over study. The test-retest reliability equaled 2.3 dB in quiet and 1.3 dB in noise. The simulations predicted an improvement in test-retest reliability, especially in quiet. The cross-over study did not confirm the predictions. The results of the study suggest that the homogeneity of the sentences is not the prime component underlying the test-retest reliability. The Dutch matrix speech material and the selected subsets of sentences were equally suitable for speech intelligibility testing in CI users.	\N	\N
24993019	Conversation scenes are a typical example in which classical models of visual attention dramatically fail to predict eye positions. Indeed, these models rarely consider faces as particular gaze attractors and never take into account the important auditory information that always accompanies dynamic social scenes. We recorded the eye movements of participants viewing dynamic conversations taking place in various contexts. Conversations were seen either with their original soundtracks or with unrelated soundtracks (unrelated speech and abrupt or continuous natural sounds). First, we analyze how auditory conditions influence the eye movement parameters of participants. Then, we model the probability distribution of eye positions across each video frame with a statistical method (Expectation-Maximization), allowing the relative contribution of different visual features such as static low-level visual saliency (based on luminance contrast), dynamic low level visual saliency (based on motion amplitude), faces, and center bias to be quantified. Through experimental and modeling results, we show that regardless of the auditory condition, participants look more at faces, and especially at talking faces. Hearing the original soundtrack makes participants follow the speech turn-taking more closely. However, we do not find any difference between the different types of unrelated soundtracks. These eyetracking results are confirmed by our model that shows that faces, and particularly talking faces, are the features that best explain the gazes recorded, especially in the original soundtrack condition. Low-level saliency is not a relevant feature to explain eye positions made on social scenes, even dynamic ones. Finally, we propose groundwork for an audiovisual saliency model.	\N	\N
24993189	Multiple sound reflections from room materials and a listener's head induce slight spectral modifications of sounds. This coloration depends on the listener and source positions, and on the room itself. This study investigated whether coloration could help segregate competing sources. Obligatory streaming was evaluated for diotic speech-shaped noises using a rhythmic discrimination task. Thresholds for detecting anisochrony were always significantly higher when stimuli differed in spectrum. The tested differences corresponded to three spatial configurations involving different levels of head and room coloration. These results suggest that, despite the generally deleterious effects of reverberation on speech intelligibility, coloration could favor source segregation.	\N	\N
24993221	Prosodic rhythm in speech [the alternation of "Strong" (S) and "weak" (w) syllables] is cued, among others, by slow rates of amplitude modulation (AM) within the speech envelope. However, it is unclear exactly which envelope modulation rates and statistics are the most important for the rhythm percept. Here, the hypothesis that the phase relationship between "Stress" rate (∼2 Hz) and "Syllable" rate (∼4 Hz) AMs provides a perceptual cue for speech rhythm is tested. In a rhythm judgment task, adult listeners identified AM tone-vocoded nursery rhyme sentences that carried either trochaic (S-w) or iambic patterning (w-S). Manipulation of listeners' rhythm perception was attempted by parametrically phase-shifting the Stress AM and Syllable AM in the vocoder. It was expected that a 1π radian phase-shift (half a cycle) would reverse the perceived rhythm pattern (i.e., trochaic → iambic) whereas a 2π radian shift (full cycle) would retain the perceived rhythm pattern (i.e., trochaic → trochaic). The results confirmed these predictions. Listeners judgments of rhythm systematically followed Stress-Syllable AM phase-shifts, but were unaffected by phase-shifts between the Syllable AM and the Sub-beat AM (∼14 Hz) in a control condition. It is concluded that the Stress-Syllable AM phase relationship is an envelope-based modulation statistic that supports speech rhythm perception.	\N	\N
24993222	Perceptual compensation for coarticulation (PCCA) refers to listener responses consistent with perceptual reduction of the acoustic effects of the coarticulatory context on a target sound. The robustness of PCCA across individuals and across tasks have not been studied together previously. This study reports the results of two experiments designed to determine the robustness of perceptual compensation for vocalic influence on sibilant perception across tasks and the stability of such compensatory response within an individual. Identification and discrimination data, collected in the laboratory and on Amazon's Mechanical Turk, showed that individuals are moderately stable in their PCCA responses across tasks and the level of stability is consistent across both the lab-based and the internet-based cohorts, although some differences are observed.	\N	\N
24995901	Residual inhibition (RI) is the temporary inhibition of tinnitus by use of masking stimuli when the device is turned off. The main aim of this study was to evaluate the effects of RI induced by auditory electrical stimulation (AES) in the primary auditory pathways using early auditory-evoked potentials (AEPs) in subjective idiopathic tinnitus (SIT) subjects. A randomized placebo-controlled study was conducted on forty-four tinnitus subjects. All enrolled subjects based on the responses to AES, were divided into two groups of RI and Non-RI (NRI). The results of the electrocochleography (ECochG), auditory brain stem response (ABR) and brain stem transmission time (BTT) were determined and compared pre- and post-AES in the studied groups. The mean differences in the compound action potential (CAP) amplitudes and III/V and I/V amplitude ratios were significantly different between the RI, NRI and PES controls. BTT was significantly decreased associated with RI. The observed changes in AEP associated with RI suggested some peripheral and central auditory alterations. Synchronized discharges of the auditory nerve fibers and inhibition of the abnormal activity of the cochlear nerve by AES may play important roles associated with RI. Further comprehensive studies are required to determine the mechanisms of RI more precisely.	\N	\N
25000379	The purpose of this study was to determine the influence of dialect upon the perception of dysarthric speech. Speakers and listeners were self-identifying as either Caucasian American or African American. Three speakers were Caucasian American, three were African American. Four speakers had experienced a CVA and were dysarthric. Listeners were age matched and were equally divided for gender. Readers recorded 14 word sentences from the Assessment of Intelligibility of Dysarthric Speech. Listeners provided ratings of intelligibility, comprehensibility, and acceptability. Own-race biases were found for all measures; however, significant findings were found for intelligibility and comprehensibility in that the Caucasian Americans provided significantly higher scores for Caucasian American speakers. Clinical implications are discussed.	\N	\N
25003309	The idea that the human mind can be divided into distinct (but interacting) functional modules is an important presupposition in many theories of cognition. While previous research on modularity predominantly studied input domains (e.g., vision) or central processes, the present study focused on cognitive representations of output domains. Specifically, we asked to what extent output domain representations are encapsulated (i.e., immune to influence from other domains, representing a key feature of modularity) by studying determinants of interference between simultaneous action demands (oculomotor and vocal responses). To examine the degree of encapsulation, we compared single- vs. dual-response performance triggered by single stimuli. Experiment 1 addressed the role of stimulus modality under dimensionally overlapping response requirements (stimuli and responses were spatial and compatible throughout). In Experiment 2, we manipulated the presence of dimensional overlap across responses. Substantial performance costs associated with dual-response (vs. single-response) demands were observed across response modalities, conditions, and experiments. Dimensional overlap combined with shared spatial codes across responses enabled response-code priming (i.e., beneficial crosstalk between output domains). Overall, the results are at odds with the idea of strong encapsulation of output system representations and show how processing content determines the extent of interdependency between output domains in cognition.	\N	\N
25018691	In schizophrenia, evoked 40-Hz auditory steady-state responses (ASSRs) are impaired, which reflects the sensory deficits in this disorder, and baseline spontaneous oscillatory activity also appears to be abnormal. It has been debated whether the evoked ASSR impairments are due to the possible increase in baseline power. GABAergic interneuron-specific NMDA receptor (NMDAR) hypofunction mutant mice mimic some behavioral and pathophysiological aspects of schizophrenia. To determine the presence and extent of sensory deficits in these mutant mice, we recorded spontaneous local field potential (LFP) activity and its click-train evoked ASSRs from primary auditory cortex of awake, head-restrained mice. Baseline spontaneous LFP power in the pre-stimulus period before application of the first click trains was augmented at a wide range of frequencies. However, when repetitive ASSR stimuli were presented every 20 s, averaged spontaneous LFP power amplitudes during the inter-ASSR stimulus intervals in the mutant mice became indistinguishable from the levels of control mice. Nonetheless, the evoked 40-Hz ASSR power and their phase locking to click trains were robustly impaired in the mutants, although the evoked 20-Hz ASSRs were also somewhat diminished. These results suggested that NMDAR hypofunction in cortical GABAergic neurons confers two brain state-dependent LFP abnormalities in the auditory cortex; (1) a broadband increase in spontaneous LFP power in the absence of external inputs, and (2) a robust deficit in the evoked ASSR power and its phase-locking despite of normal baseline LFP power magnitude during the repetitive auditory stimuli. The "paradoxically" high spontaneous LFP activity of the primary auditory cortex in the absence of external stimuli may possibly contribute to the emergence of schizophrenia-related aberrant auditory perception.	\N	\N
25036146	The objective of this study was to examine how the level of current required for cochlear implant listeners to detect single-channel electrical pulse trains relates to loudness perception on the same channel. The working hypothesis was that channels with relatively high thresholds, when measured with a focused current pattern, interface poorly to the auditory nerve. For such channels, a smaller dynamic range between perceptual threshold and the most comfortable loudness would result, in part, from a greater sensitivity to changes in electrical field spread compared to low-threshold channels. The narrower range of comfortable listening levels may have important implications for speech perception. Data were collected from eight, adult cochlear implant listeners implanted with the HiRes90k cochlear implant (Advanced Bionics Corp.). The partial tripolar (pTP) electrode configuration, consisting of one intracochlear active electrode, two flanking electrodes carrying a fraction (σ) of the return current, and an extracochlear ground, was used for stimulation. Single-channel detection thresholds and most comfortable listening levels were acquired using the most focused pTP configuration possible (σ ≥ 0.8) to identify three channels for further testing-those with the highest, median, and lowest thresholds-for each subject. Threshold, equal-loudness contours (at 50% of the monopolar dynamic range), and loudness growth functions were measured for each of these three test channels using various pTP fractions. For all test channels, thresholds increased as the electrode configuration became more focused. The rate of increase with the focusing parameter σ was greatest for the high-threshold channel compared to the median- and low-threshold channels. The 50% equal-loudness contours exhibited similar rates of increase in level across test channels and subjects. Additionally, test channels with the highest thresholds had the narrowest dynamic ranges (for σ ≥ 0.5) and steepest growth of loudness functions for all electrode configurations. Together with previous studies using focused stimulation, the results suggest that auditory responses to electrical stimuli at both threshold and suprathreshold current levels are not uniform across the electrode array of individual cochlear implant listeners. Specifically, the steeper growth of loudness and thus smaller dynamic ranges observed for high-threshold channels are consistent with a degraded electrode-neuron interface, which could stem from lower numbers of functioning auditory neurons or a relatively large distance between the neurons and electrodes. These findings may have potential implications for how stimulation levels are set during the clinical mapping procedure, particularly for speech-processing strategies that use focused electrical fields.	\N	\N
25041936	In vision an extensive literature supports the existence of competitive dual-processing systems of category learning that are grounded in neuroscience and are partially-dissociable. The reflective system is prefrontally-mediated and uses working memory and executive attention to develop and test rules for classifying in an explicit fashion. The reflexive system is striatally-mediated and operates by implicitly associating perception with actions that lead to reinforcement. Although categorization is fundamental to auditory processing, little is known about the learning systems that mediate auditory categorization and even less is known about the effects of individual difference in the relative efficiency of the two learning systems. Previous studies have shown that individuals with elevated depressive symptoms show deficits in reflective processing. We exploit this finding to test critical predictions of the dual-learning systems model in audition. Specifically, we examine the extent to which the two systems are dissociable and competitive. We predicted that elevated depressive symptoms would lead to reflective-optimal learning deficits but reflexive-optimal learning advantages. Because natural speech category learning is reflexive in nature, we made the prediction that elevated depressive symptoms would lead to superior speech learning. In support of our predictions, individuals with elevated depressive symptoms showed a deficit in reflective-optimal auditory category learning, but an advantage in reflexive-optimal auditory category learning. In addition, individuals with elevated depressive symptoms showed an advantage in learning a non-native speech category structure. Computational modeling suggested that the elevated depressive symptom advantage was due to faster, more accurate, and more frequent use of reflexive category learning strategies in individuals with elevated depressive symptoms. The implications of this work for dual-process approach to auditory learning and depression are discussed.	\N	\N
25059267	Chronic tinnitus affects 5-15% of the general population; in 1% of individuals with tinnitus this condition severely affects their quality of life. Pharmacological treatment is one of the options for the management of tinnitus patients, but their efficacy remains controversial. AIM. To evaluate the level of evidence to support the use of different drugs in reducing the severity of tinnitus. The pharmacological groups that have been investigated for the treatment of tinnitus include anesthetics, anticonvulsants, antidepressants, antihistamines, benzodiazepines, diuretics, corticosteroids, and of other substances. Intravenous lidocaine seems to be effective, but the short duration of the effect and the adverse reactions prevent its use. Compared with placebo, carbamazepine and gabapentine have not demonstrated effectiveness although they may be effective in some patients with auditory nerve vascular compression or myoclonus. Tricyclic antidepressants are no more effective than placebo at reducing tinnitus severity although they may improve comorbid depression. There is insufficient evidence to evaluate the effectiveness of selective serotonin reuptake inhibitors and benzodiazepines. Acamprosate may decrease the severity of tinnitus, but the level of evidence is low. There are no consistent results in the studies with intratympanic gentamicin or steroids in tinnitus associated with Meniere's disease. The use of pharmacotherapy in reducing the severity of tinnitus is not well supported by prospective, randomized, placebo-controlled clinical trials. Various drugs have been shown to be effective in some studies, but the clinical evidence is limited. Large randomized clinical trials are needed.	\N	\N
25085738	We establish a new dissociation between the roles of working memory (WM) cognitive control and visual maintenance in selective attention as measured by the efficiency of distractor rejection. The extent to which focused selective attention can prevent distraction has been shown to critically depend on the level and type of load involved in the task. High perceptual load that consumes perceptual capacity leads to reduced distractor processing, whereas high WM load that reduces WM ability to exert priority-based executive cognitive control over the task results in increased distractor processing (e.g., Lavie, Trends in Cognitive Sciences, 9(2), 75-82, 2005). WM also serves to maintain task-relevant visual representations, and such visual maintenance is known to recruit the same sensory cortices as those involved in perception (e.g., Pasternak & Greenlee, Nature Reviews Neuroscience, 6(2), 97-107, 2005). These findings led us to hypothesize that loading WM with visual maintenance would reduce visual capacity involved in perception, thus resulting in reduced distractor processing-similar to perceptual load and opposite to WM cognitive control load. Distractor processing was assessed in a response competition task, presented during the memory interval (or during encoding; Experiment 1a) of a WM task. Loading visual maintenance or encoding by increased set size for a memory sample of shapes, colors, and locations led to reduced distractor response competition effects. In contrast, loading WM cognitive control with verbal rehearsal of a random letter set led to increased distractor effects. These findings confirm load theory predictions and provide a novel functional distinction between the roles of WM maintenance and cognitive control in selective attention.	\N	\N
25089573	One of the leading theories for dyslexia suggests that it is the result of a difficulty in auditory temporal processing (ATP). This theory, as well as others, is supported by studies showing group differences and correlation between phonological awareness and ATP. However, these studies do not provide causal relationship. In the current study the authors aimed to test causal relationship between ATP and phonological awareness by comparing the performance of dyslexic and normal reader students in phonological awareness tasks before and after a short-term (5-day) training in either temporal processing (dichotic temporal order judgment; TOJ), nontemporal processing (intensity discrimination), or no training. TOJ training resulted in significant reduction of TOJ threshold and increase in phonological awareness tasks' scores. Intensity discrimination training resulted in a decrease of intensity discrimination threshold, but with no change in phonological awareness tasks. Those who had no training, had no change in TOJ and intensity discrimination thresholds, as well as in the phonological awareness tasks. These results show that (a) a short-term training in temporal processing with no other perceptual cues for adult dyslexic and normal readers can be efficient in improving their phonological awareness; and (b) phonological awareness (dis) ability has causal relationship to ATP.	\N	\N
25096110	Three-month-olds discriminate resolved harmonic complexes on the basis of missing fundamental (MF) pitch. In view of reported difficulty in discriminating unresolved complexes at 7 months and striking changes in the organization of the auditory system during early infancy, infants' ability to discriminate unresolved complexes is of some interest. This study investigated the ability of 3-month-olds, 7-month-olds, and adults to discriminate the pitch of unresolved harmonic complexes using an observer-based method. Stimuli were MF complexes bandpass filtered with a -12 dB/octave slope, combined in random phase, presented at 70 dB sound pressure level (SPL) for 650 ms with a 50 ms rise/fall with a pink noise at 65 dB SPL. The conditions were (1) "LOW" unresolved harmonics (2500-4500 Hz) based on MFs of 160 and 200 Hz and (2) "HIGH" unresolved harmonics (4000-6000 Hz) based on MFs of 190 and 200 Hz. To demonstrate MF discrimination, participants had to ignore spectral changes in complexes with the same fundamental and respond only when the fundamental changed. Nearly all infants tested categorized complexes by MF pitch suggesting discrimination of pitch extracted from unresolved harmonics by 3 months. Adults also categorized the complexes by MF pitch, although musically trained adults were more successful than musically untrained adults.	\N	\N
25096125	This paper investigated how auditory and vibrotactile feedback information is integrated within the context of violin quality evaluation. Fifteen violinists evaluated three violins on four criteria-"Rich Sound," "Loud and Powerful," "Alive and Responsive," and "Pleasure"-during a perceptual experiment. Violinists first evaluated the violins one at a time under three experimental conditions: (1) playing, (2) listening to it (played by a professional player) in an active way by fingering the score on an isolated neck, (3) same as (2) with vibrotactile feedback provided at the isolated neck. Violinists were then asked to evaluate the violins through pairwise comparisons under condition (3): Each violin was paired with itself while the level of vibrations of the isolated neck was either the original one or divided by two. The first part of the experiment demonstrated that Loud and Powerful judgments were affected by the presence of vibrations given that violins were rated louder in condition (3) than in (2). In the second part, violins were rated more positively with original vibration level at the isolated neck than with half the level, for all criteria but Alive and Responsive. Consistently with sensory interaction, the magnitude of the enhancement remained relatively constant across violins.	\N	\N
25111522	Assess surgical complications, postoperative residual hearing, and speech perception outcomes of placement of a middle ear implant on the round window in conductive and mixed hearing loss cases. Single-subject, repeated-measures design where each subject served as his or her own control. Tertiary referral medical systems. Eighteen subjects with either conductive or mixed hearing loss who could not benefit from conventional amplification were enrolled in a clinical trial investigating vibratory stimulation of the round window. The floating mass transducer (FMT) was positioned in the round window niche. Unaided residual hearing, and aided sound field thresholds and speech perception abilities were evaluated preoperatively, and at 1, 3, 6, and 10 months post-activation of the external speech processor. Six subjects experienced complications that either required further medical management or resolved on their own. There was no difference in residual bone conduction thresholds or unaided word discrimination over time. All subjects experienced a significant improvement in aided speech perception abilities as compared to preoperative performance. Subjects with conductive and mixed hearing loss with placement of the FMT in the round window niche experienced improved sound field thresholds and speech perception, without compromising residual hearing thresholds. Vibratory stimulation of the round window via a middle ear implant may be an appropriate treatment option for patients with conductive and mixed hearing loss. Additional research is needed on the preferred placement of the FMT, improvement of functional gain, and methods to limit postoperative complications and need for revision surgery.	\N	\N
25118919	To correlate the findings of an open-field audiometry with the thresholds of steady-state auditory-evoked potentials (SSAEPs) found in infants of up to 6 months of age with sensorineural hearing loss. This study included 19 infants with sensorineural hearing loss (8 males and 11 females), with minimum age of 2 months and maximum age of 6 months. The SSAEPs were assessed at 500 and 2000 Hz, and the audiometry was performed in open field through observation of behavioral responses to sound stimuli, at the same frequencies. We observed a significant correlation between the findings of both tests conducted at 500 and 2000 Hz, with p-values of 0.002 and 0.013, respectively. There was no statistical difference between ears (p=0.532) and genders (p=0.615). We conclude that there was a significant correlation between the SSAEP thresholds and the findings of the open-field audiometry. Therefore, we can affirm that the SSAEPs are a viable examination, able to predict the degree and configuration of hearing loss in infants of up to 6 months of age, and that they can be included in the clinical routine of hearing assessments conducted in children.	\N	\N
25133472	Hearing preservation (HP) surgery was initiated more than 10 years ago for combined electric and acoustic stimulation (EAS). Preserved residual low-frequency hearing has been demonstrated to improve speech perception in noise as well as music appreciation in EAS users up to 2 years. Multiple study groups aimed to evaluate initial loss of residual hearing (RH) as a consequence of HP surgery. However, after 1 year and 2 years of follow-up, further decline was reported. This study aimed to determine RH, speech perception, and the subjective benefits of EAS 10 years after HP surgery. Nine postlingual EAS partially deaf patients who underwent HP surgery at Antwerp University Hospital were included in this study (11 implanted ears). Hearing preservation (0% = loss of hearing; >0%-25% = minimal HP; >25%-75% = partial HP; >75% = complete HP), speech perception and subjective benefits were evaluated preoperatively; at 3, 6, 12, 18, and 24 months postoperatively; and annually thereafter. Complete HP was obtained in three of 11 ears; partial HP in five of 11 ears; and minimal HP in two of 11 ears, measured during their most recent follow-up. One subject lost his RH completely across time. The mean rate of HP was 48% (ranging from 6 months up to 10 years postoperatively). Speech perception analysis up to 10 years showed a continuous statistically significant improvement. The maximum subjective benefit was reached 3 months after implantation and subsequently remained statistically significant unchanged for the next 10 years. Long-term HP in EAS users after HP surgery is feasible, although a small continuous decline of HP rate of 3% per year was observed (measured from first fitting up to 6 years postoperative). Nevertheless, a continuous improvement was found in the speech perception results of the EAS users across 10 years. Moreover, the positive subjective benefit, assessed 3 months postoperative, remained stable up to 10 years.	\N	\N
25143548	When a high harmonic is removed from a cosine-phase harmonic complex, we hear a sine tone pop out of the perception; the sine tone has the pitch of the high harmonic, while the tone complex has the pitch of its fundamental frequency, f0. This phenomenon is commonly referred to as Duifhuis Pitch (DP). This paper describes, for the first time, the cortical representation of DP observed with magnetoencephalography. In experiment 1, conditions that produce the perception of a DP were observed to elicit a classic onset response in auditory cortex (P1m, N1m, P2m), and an increment in the sustained field (SF) established in response to the tone complex. Experiment 2 examined the effect of the phase spectrum of the complex tone on the DP activity: Schroeder-phase negative waves elicited a transient DP complex with a similar shape to that observed with cosine-phase waves but with much longer latencies. Following the transient DP activity, the responses of the negative and positive Schroeder-phase waves converged, and the increment in the SF slowly died away. In the absence of DP, the two Schroeder-phase conditions with low peak factors both produced larger SFs than cosine-phase waves with large peak factors. A model of the auditory periphery that includes coupling between adjacent frequency channels is used to explain the early neuromagnetic activity observed in auditory cortex.	\N	\N
25153664	This study was designed to evaluate the binaural effects from bimodal hearing according to the aided hearing threshold in the nonimplanted ear. Subjects included 17 individuals who continued to use a hearing aid (HA) in the nonimplanted ear for more than 6 months postoperatively. Speech perception and sound localization were tested with unilateral cochlear implantation (CI) and bimodal hearing with and without background noise. Materials were presented at an average of 70 dB sound pressure level from a front loudspeaker in a quiet condition and then with background noise at a signal-to-noise ratio of +10 dB HL. Speech perception scores were based on percent-correct performance of repeating a spoken word under each condition. Sound localization scores were obtained by averaging the sum of angle differences between the active loudspeaker and the loudspeaker indicated by the subject. Speech perception scores (mean ± SD) of unilateral CI and bimodal hearing were 63.3% ± 17.7% and 73.1% ± 18.5% under the quiet condition (p = 0.029) and 65.5% ± 21.9% and 70.9% ± 23.6% under the noisy condition (p = 0.01), respectively. Angle differences (mean ± SD) of unilateral CI and bimodal hearing were 72.8 ± 27.4 degrees and 84.1 ± 29.9 degrees under the quiet condition (p = 0.052) and 79.3 ± 26.9 degrees and 77.3 ± 22.0 degrees under the noisy condition (p = 0.906), respectively. Patients were divided into two groups according to their aided hearing thresholds: Group 1 (aided hearing threshold ≤50 dB HL; n = 8) and Group 2 (aided hearing threshold >50 dB HL; n = 9). The speech perception scores of bimodal hearing in each group were 85.3% ± 13.3% and 60.8% ± 17.5% (p = 0.023) under the quiet condition and 82.7% ± 9.0% and 59.4% ± 26.8% under the noisy condition (p = 0.052), respectively. For sound localization, the angle differences of bimodal hearing in each group were 54 ± 28.6 degrees and 83.9 ± 11.9 degrees under the quiet condition (p = 0.042) and 63.0 ± 23.5 degrees and 89 ± 22.6 degrees under the noisy condition (p = 0.049), respectively. Based on the relationship between the aided hearing level and bimodal hearing performance, this current study suggests that bimodal benefits for sound localization and speech perception in noise are significant but only when sound detection is adequate for the hearing aids. Therefore, bimodal hearing could be applied to selective patients with favorable aided hearing levels.	\N	\N
25153739	Unconscious priming is sensitive to contextual factors. The present study examined this adaptive process using masked arrow primes (< or >). Some targets required specific "fixed" left/right responses (< or >) and others required "free" left/right responses (<>). Different groups (n = 30 each) received response-congruent primes (SOA = 75 msec.) on 0.2, 0.5, or 0.8 of the fixed-response trials. Fixed responses were facilitated by congruent primes and free responses were faster when congruent with the prime. Critically, these masked priming effects emerged only in the 0.8 group. The pattern of extant prime-proportion effects in this paradigm best supports an adaptive associative-strength account rather than memory-recruitment or response-bias-suppression accounts.	\N	\N
25155249	Computational modeling and eye-tracking were used to investigate how phonological and semantic information interact to influence the time course of spoken word recognition. We extended our recent models (Chen & Mirman, 2012; Mirman, Britt, & Chen, 2013) to account for new evidence that competition among phonological neighbors influences activation of semantically related concepts during spoken word recognition (Apfelbaum, Blumstein, & McMurray, 2011). The model made a novel prediction: Semantic input modulates the effect of phonological neighbors on target word processing, producing an approximately inverted-U-shaped pattern with a high phonological density advantage at an intermediate level of semantic input-in contrast to the typical disadvantage for high phonological density words in spoken word recognition. This prediction was confirmed with a new analysis of the Apfelbaum et al. data and in a visual world paradigm experiment with preview duration serving as a manipulation of strength of semantic input. These results are consistent with our previous claim that strongly active neighbors produce net inhibitory effects and weakly active neighbors produce net facilitative effects.	\N	\N
25156097	The primary objective of the study was to investigate the feasibility, reliability, and validity of the Dutch digits in noise (DIN) test for measuring speech recognition in hearing aid and cochlear implant users and compare results to the standard sentences-in-noise (SIN) test. The relation between speech reception thresholds for DIN test and SIN test was analysed to determine the validity of the DIN test. As linguistic skills were expected to make different contributions in these tests, their influence was analysed. Participants were 12 normal-hearing listeners, 24 hearing aid users, and 24 cochlear implant users. The DIN test was feasible for more participants than the SIN test. Intraclass correlation coefficients showed high reliability. The standard error of measurement was smaller for the DIN test than for the SIN test. DIN test and SIN test were highly correlated (r = 0.95 and r = 0.56 for NH+ HA and CI users respectively). In the regression analysis no significant contribution of basic linguistic skills or personal factors was found. In the assessment of speech recognition in noise of aided hearing-impaired listeners with hearing aids or cochlear implants, the DIN test is a feasible, reliable and valid test.	\N	\N
25156757	In four experiments in which participants searched for multiple target digits we hypothesized that search should be fastest when the targets are arranged closely together on the number line without any intervening distractor digits, i.e., the targets form a contiguous and coherent group. In Experiment 1 search performance was better for targets defined by numerical magnitude than parity (i.e., evenness); this result supports our hypothesis but could also be due to the linear separability of targets from distractors or the numerical distance between them. Experiment 2 controlled for target-distractor linear separability and numerical distance, yielding faster search when targets were surrounded by distractors on the number line than when they surrounded distractors. This result is consistent with target contiguity and coherence but also with grouping by similarity of target shapes. Experiment 3 controlled for all three alternative explanations (linear separability, numerical distance, and shape similarity) and search performance was better for contiguous targets than separated targets. In Experiment 4 search performance was better for a coherent target group than one with intervening distractors. Of the possibilities we considered, only the hypothesis based on the contiguity and coherence of the target group on the number line can account for the results from all four experiments.	\N	\N
25158373	To evaluate cochlear functioning in patients (18-45 years old) with varying stages of chronic kidney disease (CKD). Using purposive sampling, 50 participants, 10 in each of the 5 stages of CKD, were selected and underwent pure tone audiometric testing and distortion product otoacoustic emissions (DPOAEs). Significant differences (p < 0.05) were found between pure tone audiometry and DPOAEs in detecting early cochlear dysfunction in the high-frequency range in stages 3 (6,000/5,000 Hz; p = 0.00), 4 (6,000/5,000 Hz; p < 0.03) and 5 (4,000/3,333 Hz; p < 0.01, 8,000/6,667 Hz: p < 0.05) with DPOAEs being more sensitive in identifying early cochlear dysfunction. Patients in stages 1 and 2 presented with normal puretone thresholds and DPOAEs, suggesting that cochlear functioning in these patients was normal. Early cochlear dysfunction, thereby indicating a subclinical hearing loss, was identified in stages 3, 4 and 5 by DPOAE testing. In addition, blood test results, drug intake and concomitant conditions were recorded and analysed which suggested a relationship between reduced cochlear functioning and increased electrolyte levels, treatment regimens and concomitant conditions. Participants in the later stages of CKD presented with early cochlear dysfunction, presenting with subclinical hearing loss. It was postulated that this subclinical hearing loss resulted from a combination of electrolytic, urea and creatinine imbalances, together with concomitant medical conditions and ototoxic drug intake. It was concluded that audiological monitoring be included in the management of patients with CKD and that DPOAEs be introduced as part of the test battery to monitor cochlear function in patients with varying degrees of CKD.	\N	\N
25170790	Absolute pitch (AP) is the rare ability to identify or produce different pitches without using reference tones. At least two sequential processing stages are assumed to contribute to this phenomenon. The first recruits a pitch memory mechanism at an early stage of auditory processing, whereas the second is driven by a later cognitive mechanism (pitch labeling). Several investigations have used active tasks, but it is unclear how these two mechanisms contribute to AP during passive listening. The present work investigated the temporal dynamics of tone processing in AP and non-AP (NAP) participants by using EEG. We applied a passive oddball paradigm with between- and within-tone category manipulations and analyzed the MMN reflecting the early stage of auditory processing and the P3a response reflecting the later cognitive mechanism during the second processing stage. Results did not reveal between-group differences in MMN waveforms. By contrast, the P3a response was specifically associated with AP and sensitive to the processing of different pitch types. Specifically, AP participants exhibited smaller P3a amplitudes, especially in between-tone category conditions, and P3a responses correlated significantly with the age of commencement of musical training, suggesting an influence of early musical exposure on AP. Our results reinforce the current opinion that the representation of pitches at the processing level of the auditory-related cortex is comparable among AP and NAP participants, whereas the later processing stage is critical for AP. Results are interpreted as reflecting cognitive facilitation in AP participants, possibly driven by the availability of multiple codes for tones.	\N	\N
25173195	Speaker's voice occupies a central role as the cornerstone of auditory social interaction. Here, we review the evidence suggesting that speaker's voice constitutes an integral context cue in auditory memory. Investigation into the nature of voice representation as a memory cue is essential to understanding auditory memory and the neural correlates which underlie it. Evidence from behavioral and electrophysiological studies suggest that while specific voice reinstatement (i.e., same speaker) often appears to facilitate word memory even without attention to voice at study, the presence of a partial benefit of similar voices between study and test is less clear. In terms of explicit memory experiments utilizing unfamiliar voices, encoding methods appear to play a pivotal role. Voice congruency effects have been found when voice is specifically attended at study (i.e., when relatively shallow, perceptual encoding takes place). These behavioral findings coincide with neural indices of memory performance such as the parietal old/new recollection effect and the late right frontal effect. The former distinguishes between correctly identified old words and correctly identified new words, and reflects voice congruency only when voice is attended at study. Characterization of the latter likely depends upon voice memory, rather than word memory. There is also evidence to suggest that voice effects can be found in implicit memory paradigms. However, the presence of voice effects appears to depend greatly on the task employed. Using a word identification task, perceptual similarity between study and test conditions is, like for explicit memory tests, crucial. In addition, the type of noise employed appears to have a differential effect. While voice effects have been observed when white noise is used at both study and test, using multi-talker babble does not confer the same results. In terms of neuroimaging research modulations, characterization of an implicit memory effect reflective of voice congruency is currently lacking.	\N	\N
25175541	Development of a sense of self is a fundamental process needed for human social interaction. Although functional neuroimaging studies have revealed the importance of medial prefrontal cortex (mPFC) in self-referencing, how this function develops in infancy remains poorly understood. To determine the cerebral basis underlying processing of self-related stimuli, we used behavioral measures and functional multi-channel near-infrared spectroscopy (fNIRS) to measure prefrontal cortical responses in 6-month-old infants hearing their own names. We also investigated the influence of a mother's voice on name perception in infants - an ability that plays a crucial role in the recognition of social signals. Experiment 1 measured the behavioral preferences of infants for their own names and for other names, spoken either by their mothers or by strangers. Results showed that infants significantly preferred their own name to other names, regardless of speaker type. Experiment 2 examined hemodynamic responses to the same four conditions in the prefrontal cortex. Compared with other names, hearing their own names, especially when spoken by their mother, elicited greater activity in the infant's dorsal mPFC. Furthermore, the magnitude of the cerebral response correlated with the degree of behavioral preference only when involving their mother's voice. These findings suggest that, particularly in the context of their mothers' voice, the dorsal mPFC of infants is already sensitive to social signals related to self at 6 months. At the same time, familiarity and affection related processing are also discussed as possible factors modulating dorsal mPFC activation at this age.	\N	\N
25178986	Working memory (WM) is a latent cognitive structure that serves to store and manipulate a limited amount of information over a short time period. How information is maintained in WM remains a debated issue: it is unclear whether stimuli from different sensory domains are maintained under distinct mechanisms or maintained under the same mechanism. Previous neuroimaging research on this issue to date has focused on individual brain regions and has not provided a comprehensive view of the functional networks underlying multi-domain WM. To study the functional networks involved in visual and auditory WM, we applied constrained principal component analysis (CPCA) to a functional magnetic resonance imaging (fMRI) dataset acquired when participants performed a change-detection task requiring them to remember only visual, only auditory, or both visual and auditory stimuli. Analysis revealed evidence of both [1] domain-specific networks responsive to either visual or auditory WM (but not both), and [2] domain-general networks responsive to both visual and auditory WM. The domain-specific networks showed load-dependent activations during only encoding, whereas a domain-general network was sensitive to WM load across encoding, maintenance, and retrieval. The latter domain-general network likely reflected attentional processes involved in WM encoding, retrieval, and possibly maintenance as well. These results do not support the domain-specific account of WM maintenance but instead favor the domain-general theory that items from different sensory domains are maintained under the same mechanism.	\N	\N
25178987	Current views suggest that autism spectrum disorders (ASDs) are characterised by enhanced low-level auditory discrimination abilities. Little is known, however, about whether enhanced abilities are universal in ASD and how they relate to symptomatology. We tested auditory discrimination for intensity, frequency and duration in 21 adults with ASD and 21 IQ and age-matched controls. Contrary to predictions, there were significant deficits in ASD on all acoustic parameters. The findings suggest that low-level auditory discrimination ability varies widely within ASD and this variability relates to IQ level, and influences the severity of restricted and repetitive behaviours (RRBs). We suggest that it is essential to further our understanding of the potential contributing role of sensory perception ability on the emergence of RRBs.	\N	\N
25186122	Sensory over-responsivity (SOR) refers to an exaggerated, intense, or prolonged behavioral response to ordinary sensory stimuli. The relationship of SOR to psychiatric disorders remains poorly understood. The current study examined the SOR construct within typically developing children with clinically significant anxiety, including the prevalence and course of SOR symptoms and relationship between SOR symptoms, demographic factors, and psychopathology. Children presenting at an anxiety specialty clinic (n = 88) completed a psychiatric diagnostic assessment, which included parent-report measures of SOR, anxiety, obsessive-compulsive disorder (OCD), and global behavior and child-report measures of anxiety, depression, and OCD. Sensory over-responsivity symptoms were very common: 93.2% were bothered by at least 1 tactile or auditory sensation, and the mean number of bothersome sensations was 9.2 (SD = 7.4). SOR symptoms were reported to be "moderately bothersome" on average and to onset at an early age. Sensory Over-Responsivity Inventory (SensOR) scores did not differ by psychiatric disorder diagnosis, but SensOR scores significantly correlated with measures of OCD and depression. Higher SensOR scores were associated with greater global impairment. A high rate of SOR symptom occurrence was observed in this sample of children seeking anxiety treatment, suggesting that SOR may not be entirely independent of anxiety and may be closely associated with OCD. Future research on the validity and nosology of SOR using psychiatric samples is warranted.	\N	\N
25190408	This study examines how visual speech information affects native judgments of the intelligibility of speech sounds produced by non-native (L2) speakers. Native Canadian English perceivers as judges perceived three English phonemic contrasts (/b-v, θ-s, l-ɹ/) produced by native Japanese speakers as well as native Canadian English speakers as controls. These stimuli were presented under audio-visual (AV, with speaker voice and face), audio-only (AO), and visual-only (VO) conditions. The results showed that, across conditions, the overall intelligibility of Japanese productions of the native (Japanese)-like phonemes (/b, s, l/) was significantly higher than the non-Japanese phonemes (/v, θ, ɹ/). In terms of visual effects, the more visually salient non-Japanese phonemes /v, θ/ were perceived as significantly more intelligible when presented in the AV compared to the AO condition, indicating enhanced intelligibility when visual speech information is available. However, the non-Japanese phoneme /ɹ/ was perceived as less intelligible in the AV compared to the AO condition. Further analysis revealed that, unlike the native English productions, the Japanese speakers produced /ɹ/ without visible lip-rounding, indicating that non-native speakers' incorrect articulatory configurations may decrease the degree of intelligibility. These results suggest that visual speech information may either positively or negatively affect L2 speech intelligibility.	\N	\N
25190410	Hearing-aid noise reduction should reduce background noise, but not disturb the target speech. This objective is difficult because noise reduction suffers from a trade-off between the amount of noise removed and signal distortion. It is unknown if this important trade-off differs between normal-hearing (NH) and hearing-impaired (HI) listeners. This study separated the negative effect of noise reduction (distortion) from the positive effect (reduction of noise) to allow the measurement of the detection threshold for noise-reduction (NR) distortion. Twelve NH subjects and 12 subjects with mild to moderate sensorineural hearing loss participated in this study. The detection thresholds for distortion were determined using an adaptive procedure with a three-interval, two-alternative forced-choice paradigm. Different levels of distortion were obtained by changing the maximum amount of noise reduction. Participants were also asked to indicate their preferred NR strength. The detection threshold for overall distortion was higher for HI subjects than for NH subjects, suggesting that stronger noise reduction can be applied for HI listeners without affecting the perceived sound quality. However, the preferred NR strength of HI listeners was closer to their individual detection threshold for distortion than in NH listeners. This implies that HI listeners tolerate fewer audible distortions than NH listeners.	\N	\N
25190427	The purpose of this study was to evaluate the feasibility and efficiency of an observer-based, two-interval forced-choice infant psychophysical testing procedure. Ten of 11 infants (7-9 months of age) achieved a criterion of 80%-correct detection of a 50-dB sound pressure level noise band in a single testing session. Fewer trials were needed to reach criterion using the two-interval procedure than previously reported for the single-interval observer-based psychophysical procedure [Olsho, Koch, Halpin, and Carter (1987). Devel. Psychol. 23, 627-640]. These results provide preliminary evidence that the two-interval procedure is feasible and efficient while controlling for observer and listener response bias.	\N	\N
25191774	This study aims to establish whether mothers of children with specific language impairments (SLI) have reduced emotional competence and whether individual dimensions of maternal emotional competence are related to emotional and behavioral problems in children. The clinical sample comprised 97 preschool children (23 girls) with SLI from, while the peer sample comprised 60 (34 girls) developmentally normal preschool children. The emotional competence of mothers was evaluated using the Emotional Competence Questionnaire (ESCQ-45). Emotional and behavioral difficulties in children were assessed by mothers, speech therapists, and teachers, using Achenbach's CBCL and CTRF scales. A lower emotional competence was found in mothers of children with specific language impairments. Mothers in clinical and peer samples differed in their ability to express emotions, while there was no statistically significant difference in their ability to recognize and manage emotions. Poor emotional regulation in mothers was linked to increased emotional reactivity, anxiety, and depressive manifestations in children with SLI, as well as to their speech comprehension. Emotional expression in mothers seems to be important for psychopathology in children with SLI, and their expressive and receptive speech. Our findings suggest that, in addition to the rehabilitation of children with SLI, clinical practice should implement preventative work with parents to enhance their emotional competence.	\N	\N
25196948	Research on how lexical tone is neuroanatomically represented in the human brain is central to our understanding of cortical regions subserving language. Past studies have exclusively focused on tone perception of the spoken language, and little is known as to the lexical tone processing in reading visual words and its associated brain mechanisms. In this study, we performed two experiments to identify neural substrates in Chinese tone reading. First, we used a tone judgment paradigm to investigate tone processing of visually presented Chinese characters. We found that, relative to baseline, tone perception of printed Chinese characters were mediated by strong brain activation in bilateral frontal regions, left inferior parietal lobule, left posterior middle/medial temporal gyrus, left inferior temporal region, bilateral visual systems, and cerebellum. Surprisingly, no activation was found in superior temporal regions, brain sites well known for speech tone processing. In activation likelihood estimation (ALE) meta-analysis to combine results of relevant published studies, we attempted to elucidate whether the left temporal cortex activities identified in Experiment one is consistent with those found in previous studies of auditory lexical tone perception. ALE results showed that only the left superior temporal gyrus and putamen were critical in auditory lexical tone processing. These findings suggest that activation in the superior temporal cortex associated with lexical tone perception is modality-dependent.	\N	\N
25198514	A growing body of evidence suggests that conscious visual awareness is not a prerequisite for human fear learning. For instance, humans can learn to be fearful of subliminal fear relevant images--images depicting stimuli thought to have been fear relevant in our evolutionary context, such as snakes, spiders, and angry human faces. Such stimuli could have a privileged status in relation to manipulations used to suppress usually salient images from awareness, possibly due to the existence of a designated sub-cortical 'fear module'. Here we assess this proposition, and find it wanting. We use binocular masking to suppress awareness of images of snakes and wallabies (particularly cute, non-threatening marsupials). We find that subliminal presentations of both classes of image can induce differential fear conditioning. These data show that learning, as indexed by fear conditioning, is neither contingent on conscious visual awareness nor on subliminal conditional stimuli being fear relevant.	\N	\N
25200176	Following prolonged exposure to asynchronous multisensory signals, the brain adapts to reduce the perceived asynchrony. Here, in three separate experiments, participants performed a synchrony judgment task on audiovisual, audiotactile or visuotactile stimuli and we used inter-trial analyses to examine whether temporal recalibration occurs rapidly on the basis of a single asynchronous trial. Even though all combinations used the same subjects, task and design, temporal recalibration occurred for audiovisual stimuli (i.e., the point of subjective simultaneity depended on the preceding trial's modality order), but none occurred when the same auditory or visual event was combined with a tactile event. Contrary to findings from prolonged adaptation studies showing recalibration for all three combinations, we show that rapid, inter-trial recalibration is unique to audiovisual stimuli. We conclude that recalibration occurs at two different timescales for audiovisual stimuli (fast and slow), but only on a slow timescale for audiotactile and visuotactile stimuli.	\N	\N
25211190	Children with a history of amblyopia, even if resolved, exhibit impaired visual-auditory integration and perceive speech differently. To determine whether a history of amblyopia is associated with abnormal visual-auditory speech integration. Retrospective observational study at an academic pediatric ophthalmologic clinic with an average of 4 years of follow-up. Participants were at least 3 years of age and without any history of neurologic or hearing disorders. Of 39 children originally in our study, 6 refused to participate. The remaining 33 participants completed the study. Twenty-four participants (mean [SD] age, 7.0 [1.5] years) had a history of amblyopia in 1 eye, with a visual acuity of at least 20/20 in the nonamblyopic eye. Nine controls (mean [SD] age, 8.0 [3.4] years) were recruited from referrals for visually insignificant etiologies or through preschool-screening eye examinations; all had 20/20 in both eyes. Participants were presented with a video demonstrating the McGurk effect (ie, a stimulus presenting an audio track playing the sound /pa/ and a separate video track of a person articulating /ka/). Normal visual-auditory integration produces the perception of hearing a fusion sound /ta/. Participants were asked to report which sound was perceived, /ka/, /pa/, or /ta/. Prevalence of perception of the fusion /ta/ sound. Prior to the study, amblyopic children were hypothesized to less frequently perceive /ta/. The McGurk effect was perceived by 11 of the 24 participants with amblyopia (45.8%) and all 9 controls (100%) (adjusted odds ratio, 22.3 [95% CI, 1.2-426.0]; P = .005). The McGurk effect was perceived by 100% of participants with amblyopia that was resolved by 5 years of age and by 100% of participants whose onset at amblyopia developed at or after 5 years of age. However, only 18.8% of participants with amblyopia that was unresolved by 5 years of age (n = 16) perceived the McGurk effect (adjusted odds ratio, 27.0 [95% CI, 1.1-654.0]; P = .02). This pilot study suggests that children with a history of amblyopia have impaired visual-auditory speech perception. Early childhood appears to serve as an approximate time point for the development of successful visual-auditory fusion, by which time amblyopia must have either resolved or begun. Interventions to resolve amblyopia may not only influence visual acuity but may also influence the perception of sound.	\N	\N
25217343	Attentional control theory suggests that heightened anxiety, whether due to trait or state factors, causes an increased vulnerability to distraction even when the distracters are emotionally neutral. Recent passive oddball studies appear to support this theory in relation to the distraction caused by emotionally neutral sounds. However such studies have manipulated emotional state via the content of task stimuli, thus potentially confounding changes in emotion with differences in task demands. To identify the effect of anxiety on the distraction caused by emotionally neutral sounds, 50 participants completed a passive oddball task requiring emotionally neutral sounds to be ignored. Crucially, state anxiety was manipulated independent of the task stimuli (via unrelated audiovisual stimuli) thus removing confounds relating to task demands. Neither state or trait anxiety was found to influence the susceptibility to distraction by emotionally neutral sounds. These findings contribute to the ongoing debate concerning the impact of emotion on attention.	\N	\N
25219227	To enhance speech recognition, as well as Mandarin tone recognition in noice, we proposed a speech coding strategy called zero-crossing of fine structure in low frequency (LFFS) for cochlear implant based on low frequency non-uniform sampling (LFFS for short). In the range of frequency perceived boundary of human ear, we used zero-crossing time of the fine structure to generate the stimulus pulse sequences based on the frequency selection rule. Acoustic simulation results showed that although on quiet background the performance of LFFS was similar to continuous interleaved sampling (CIS), on the noise background the performance of LFFS in Chinese tones, words and sentences were significantly better than CIS. In addition to this, we also got better Mandarin recognition factors distribution by using the improved index distribution model. LFFS contains more tonal information which was able to effectively improve Mandarin recognition of the cochlear implant.	\N	\N
25231617	Whenever the visual stream is abruptly disturbed by eye movements, blinks, masks, or flashes of light, the visual system needs to retrieve the new locations of current targets and to reconstruct the timing of events to straddle the interruption. This process may introduce position and timing errors. We here report that very similar errors are seen in human subjects across three different paradigms when disturbances are caused by either eye movements, as is well known, or, as we now show, masking. We suggest that the characteristic effects of eye movements on position and time, spatial and temporal compression and saccadic suppression of displacement, are consequences of the interruption and the subsequent reconnection and are seen also when visual input is masked without any eye movements. Our data show that compression and suppression effects are not solely a product of ocular motor activity but instead can be properties of a correspondence process that links the targets of interest across interruptions in visual input, no matter what their source.	\N	\N
25234404	In this study, we investigated the role of interactive auditory feedback in modulating the inadvertent forward drift experienced while attempting to walk in place with closed eyes following a few minutes of treadmill walking. Simulations of footstep sounds upon surface materials such as concrete and snow were provided by means of a system composed of headphones and shoes augmented with sensors. In a control condition, participants could hear their actual footstep sounds. Results showed an overall enhancement of the forward drift after treadmill walking independent of the sound perceived, while the strength of the aftereffect, measured as the proportional increase (posttest/pretest) in forward drift, was higher under the influence of snow compared to both concrete and actual sound. In addition, a higher knee angle flexion was found during the snow sound condition both before and after treadmill walking. Behavioral results confirmed those of a perceptual questionnaire, which showed that the snow sound was effective in producing strong pseudo-haptic illusions. Our results provide evidence that the walking in place aftereffect results from a recalibration of haptic, visuo-motor but also sound-motor control systems. Self-motion perception is multimodal.	\N	\N
25234884	The medial olivocochlear reflex (MOCR) modulates cochlear amplifier gain and is thought to facilitate the detection of signals in noise. High-resolution distortion product otoacoustic emissions (DPOAEs) were recorded in teens, young, middle-aged, and elderly adults at moderate levels using primary tones swept from 0.5 to 4 kHz with and without a contralateral acoustic stimulus (CAS) to elicit medial efferent activation. Aging effects on magnitude and phase of the 2f1-f2 DPOAE and on its components were examined, as was the link between speech-in-noise performance and MOCR strength. Results revealed a mild aging effect on the MOCR through middle age for frequencies below 1.5 kHz. Additionally, positive correlations were observed between strength of the MOCR and performance on select measures of speech perception parsed into features. The elderly group showed unexpected results including relatively large effects of CAS on DPOAE, and CAS-induced increases in DPOAE fine structure as well as increases in the amplitude and phase accumulation of DPOAE reflection components. Contamination of MOCR estimates by middle ear muscle contractions cannot be ruled out in the oldest subjects. The findings reiterate that DPOAE components should be unmixed when measuring medial efferent effects to better consider and understand these potential confounds.	\N	\N
25234912	With a cochlear implant, when stimulation from multiple channels is interleaved, the perceived loudness is greater than the loudness associated with any of the individual channels presented in isolation. This phenomenon is known as loudness summation. This study examined if loudness summation with monopolar and tripolar stimulation were equivalent at two loudnesses and two spacing configurations. Results suggest that loudness summation is similar for monopolar and tripolar modes. However, larger summation differences were observed for softer sounds and louder sounds with a larger spatial separation. The results are consistent with the idea that loudness summation is dependent on channel interaction and have implications for implementing current-focused processing strategies.	\N	\N
25238461	Language comprehension is more than a process of decoding the literal meaning of a speaker's utterance. Instead, by making the assumption that speakers choose their words to be informative in context, listeners routinely make pragmatic inferences that go beyond the linguistic data. If language learners make these same assumptions, they should be able to infer word meanings in otherwise ambiguous situations. We use probabilistic tools to formalize these kinds of informativeness inferences-extending a model of pragmatic language comprehension to the acquisition setting-and present four experiments whose data suggest that preschool children can use informativeness to infer word meanings and that adult judgments track quantitatively with informativeness.	\N	\N
25243992	Less proficient basic auditory processing has been previously connected to dyslexia. However, it is unclear whether a low proficiency level is a correlate of having a familial risk for reading problems, or whether it causes dyslexia. In this study, children's processing of amplitude rise time (ART), intensity and frequency differences was measured with event-related potentials (ERPs). ERP components of interest are components reflective of auditory change detection; the mismatch negativity (MMN) and late discriminative negativity (LDN). All groups had an MMN to changes in ART and frequency, but not to intensity. Our results indicate that fluent readers at risk for dyslexia, poor readers at risk for dyslexia and fluent reading controls have an LDN to changes in ART and frequency, though the scalp activation of frequency processing was different for familial risk children. On intensity, only controls showed an LDN. Contrary to previous findings, our results suggest that neither ART nor frequency processing is related to reading fluency. Furthermore, our results imply that diminished sensitivity to changes in intensity and differential lateralization of frequency processing should be regarded as correlates of being at familial risk for dyslexia, that do not directly relate to reading fluency.	\N	\N
25246562	Temporal cues are important for discerning word boundaries and syllable segments in speech; their perception facilitates language acquisition and development. Beat synchronization and neural encoding of speech reflect precision in processing temporal cues and have been linked to reading skills. In poor readers, diminished neural precision may contribute to rhythmic and phonological deficits. Here we establish links between beat synchronization and speech processing in children who have not yet begun to read: preschoolers who can entrain to an external beat have more faithful neural encoding of temporal modulations in speech and score higher on tests of early language skills. In summary, we propose precise neural encoding of temporal modulations as a key mechanism underlying reading acquisition. Because beat synchronization abilities emerge at an early age, these findings may inform strategies for early detection of and intervention for language-based learning disabilities.	\N	\N
25248621	We used a haptic enumeration task to investigate whether enumeration can be facilitated by perceptual grouping in the haptic modality. Eight participants were asked to count tangible dots as quickly and accurately as possible, while moving their finger pad over a tactile display. In Experiment 1, we manipulated the number and organization of the dots, while keeping the total exploration area constant. The dots were either evenly distributed on a horizontal line (baseline condition) or organized into groups based on either proximity (dots placed in closer proximity to each other) or configural cues (dots placed in a geometric configuration). In Experiment 2, we varied the distance between the subsets of dots. We hypothesized that when subsets of dots can be grouped together, the enumeration time will be shorter and accuracy will be higher than in the baseline condition. The results of both experiments showed faster enumeration for the configural condition than for the baseline condition, indicating that configural grouping also facilitates haptic enumeration. In Experiment 2, faster enumeration was also observed for the proximity condition than for the baseline condition. Thus, perceptual grouping speeds up haptic enumeration by both configural and proximity cues, suggesting that similar mechanisms underlie perceptual grouping in both visual and haptic enumeration.	\N	\N
25251488	A continuing debate in language acquisition research is whether there are critical periods (CPs) in development during which the system is most responsive to environmental input. Recent advances in neurobiology provide a mechanistic explanation of CPs, with the balance between excitatory and inhibitory processes establishing the onset and molecular brakes establishing the offset of windows of plasticity. In this article, we review the literature on human speech perception development within the context of this CP model, highlighting research that reveals the interplay of maturational and experiential influences at key junctures in development and presenting paradigmatic examples testing CP models in human subjects. We conclude with a discussion of how a mechanistic understanding of CP processes changes the nature of the debate: The question no longer is, "Are there CPs?" but rather what processes open them, keep them open, close them, and allow them to be reopened.	\N	\N
25255646	The aim of this study was to investigate distinctive change in the hearing impaired elderly listeners, especially about speech recognition. Subjects were 525 patients (235 males, 290 females), from 60 to 98 years of age who had visited the Hearing Aid Clinic of Otorhinolaryngology, National Center for Geriatrics and Gerontology Hospital, between June 2001 and December 2012. Pure-tone air conduction threshold determination was administered to each subject. The speech audiometry materials used to define speech discrimination ability were Japanese monosyllabic word lists, 67S word lists. Sex- and age-specific trends in maximum discrimination score (MDS) and rollover index (RI) were shown in this study. RI was computed by the formula (PBmax-PBmin)/PBmax. PBmax has almost the same meaning as MDS in Japan. PBmin represented the lowest PB score above the test intensity level of PBmax. Mean MDSs were 80.8% in their sixties, 75.3% in their seventies, 60.7% in their eighties, and 45.5% in their nineties. The rate of decrease in mean MDS per decade accelerated in the older generation. Mean RIs were 0.18 in patients in their sixties, 0.24 in their seventies, 0.30 in their eighties, and 0.30 in their nineties. It increased until the age of eighties. In the model 1, multiple logistic analyses were performed to examine the effect of age (in 10-year increments), sex and mean hearing levels in pure tone average of values at 500, 1000, 2000, 4000 Hz (in 10 dB increments) on the MDS < 60%. Significant associations were observed between MDS < 60% and age (odds ratio, 3.03; 95% confidence interval, 2.38 to 3.85), and mean hearing levels in pure tone average of values at 500, 1000, 2000, 4000 Hz (2.33; 2.03 to 2.68). Sex was not associated with MDS < 60%. In the model 2, multiple logistic analyses adjusted for age and sex were performed to examine the effect of hearing level at test frequencies of 125, 250, 500, 1000, 2000, 4000, and 8000 Hz (in 10 dB increments)on the MDS < 60%. Significant associations were observed between MDS < 60% and hearing level at 250 Hz (2.04; 1.44 to 2.89), and 2000 Hz (1.46; 1.16 to 1.83), and 4000 Hz(1.24; 1.02 to 1.50). These outcomes suggest that the important point in qualifying the fitting of hearing aid is to present the list words at an adequate sound pressure level for evaluation of speech understanding especially in the hearing impaired elderly listeners.	\N	\N
25276437	The present study investigated 24 individuals suffering from chronic tinnitus (TI) and 24 nonaffected controls (CO). We recorded resting-state EEG and collected psychometric data to obtain information about how chronic tinnitus experience affects the cognitive and emotional state of TI. The study was meant to disentangle TI with high distress from those who suffer less from persistent tinnitus based on both neurophysiological and behavioral data. A principal component analysis of psychometric data uncovers two distinct independent dimensions characterizing the individual tinnitus experience. These independent states are distress and presence, the latter is described as the perceived intensity of sound experience that increases with tinnitus duration devoid of any considerable emotional burden. Neuroplastic changes correlate with the two independent components. TI with high distress display increased EEG activity in the oscillatory range around 25 Hz (upper β-band) that agglomerates over frontal recording sites. TI with high presence show enhanced EEG signal strength in the δ-, α-, and lower γ-bands (30-40 Hz) over bilateral temporal and left perisylvian electrodes. Based on these differential patterns we suggest that the two dimensions, namely, distress and presence, should be considered as independent dimensions of chronic subjective tinnitus.	\N	\N
25299833	The present study aimed to determine the extent of hearing preservation retrospectively after atraumatic cochlear implant (CI) surgery using a specialized surgical technique and specially designed flexible electrode to minimize cochlear trauma. Retrospective study. Academic tertiary care center. A consecutive series of 34 patients who had some preoperative residual hearing were included in this study. Patients underwent CI surgery with a flexible 28-mm electrode using a round window insertion technique. All patients had at least 6 months of postoperative follow-up including audiometric testing and speech perception determined using the Freiburg monosyllable word test and the Oldenburger Sentence Test in noise. Audiometric testing served as a proxy for the evaluation of cochlear trauma and hearing preservation. Hearing was preserved to within 20 dB of preoperative low-frequency pure-tone audiometry (PTA) in 40.7% of patients. Hearing was preserved to within 20 dB of preoperative high-frequency PTA in 35.7% of patients. Overall, a deterioration in hearing thresholds was observed between preoperative assessment and first fitting. Speech perception improved significantly over time after surgery. Using appropriate surgical techniques, and electrodes specially designed to minimize cochlear trauma, hearing preservation can be achieved.	\N	\N
25301014	To isolate the neural mechanisms associated with recognizing objects from those processing basic visual properties, control stimuli are required that contain the same perceptual properties as the objects but are unrecognizable. We demonstrate that conventional methods for generating control stimuli (phase scrambling, box scrambling, texture scrambling) yield poor controls because they dramatically distort the basic visual properties (e.g., spatial frequency, perceptual organization) to which even the earliest stages of visual processing are sensitive. We developed a new scrambling method, using a diffeomorphic transformation that preserves the basic perceptual properties of the image while removing meaning. We acquired perceptual ratings to determine the least amount of scrambling necessary to remove recognition. We hypothesized that our "diffeomorphic" images would produce neural activity at the earliest stages of the visual system that more closely matched activity in response to intact images relative to the other scrambling methods. To test this hypothesis, we used the HMAX computational model of object recognition and compared the simulated neural activity at the earliest stages of the visual system (layers S1, C1, and S2) between a set of 149 images scrambled using each distortion method to their intact version. We found that scrambled "diffeomorphed" images were indistinguishable to intact images in each layer of the model, but all of the other distortion methods yielded quite different patterns. Our results indicate that "diffeomorphed" images serve as more appropriate control stimuli in neuroimaging studies that aim to disentangle the representations of perceptual and semantic object properties.	\N	\N
25315376	Under normal conditions, human speech is remarkably robust to degradation by noise and other distortions. However, people with hearing loss, including those with cochlear implants, often experience great difficulty in understanding speech in noisy environments. Recent work with normal-hearing listeners has shown that the amplitude fluctuations inherent in noise contribute strongly to the masking of speech. In contrast, this study shows that speech perception via a cochlear implant is unaffected by the inherent temporal fluctuations of noise. This qualitative difference between acoustic and electric auditory perception does not seem to be due to differences in underlying temporal acuity but can instead be explained by the poorer spectral resolution of cochlear implants, relative to the normally functioning ear, which leads to an effective smoothing of the inherent temporal-envelope fluctuations of noise. The outcome suggests an unexpected trade-off between the detrimental effects of poorer spectral resolution and the beneficial effects of a smoother noise temporal envelope. This trade-off provides an explanation for the long-standing puzzle of why strong correlations between speech understanding and spectral resolution have remained elusive. The results also provide a potential explanation for why cochlear-implant users and hearing-impaired listeners exhibit reduced or absent masking release when large and relatively slow temporal fluctuations are introduced in noise maskers. The multitone maskers used here may provide an effective new diagnostic tool for assessing functional hearing loss and reduced spectral resolution.	\N	\N
25322936	Social learning in infancy is known to be facilitated by multimodal (e.g., visual, tactile, and verbal) cues provided by caregivers. In parallel with infants' development, recent research has revealed that maternal neural activity is altered through interaction with infants, for instance, to be sensitive to infant-directed speech (IDS). The present study investigated the effect of mother- infant multimodal interaction on maternal neural activity. Event-related potentials (ERPs) of mothers were compared to non-mothers during perception of tactile-related words primed by tactile cues. Only mothers showed ERP modulation when tactile cues were incongruent with the subsequent words, and only when the words were delivered with IDS prosody. Furthermore, the frequency of mothers' use of those words was correlated with the magnitude of ERP differentiation between congruent and incongruent stimuli presentations. These results suggest that mother-infant daily interactions enhance multimodal integration of the maternal brain in parenting contexts.	\N	\N
25324090	Brief exposure to time-compressed speech yields both learning and generalization. Whether such learning continues over the course of multi-session training and if so whether it is more or less specific than exposure-induced learning is not clear, because the outcomes of intensive practice with time-compressed speech have rarely been reported. The goal here was to determine whether prolonged training on time-compressed speech yields additional learning and generalization beyond that induced by brief exposure. Listeners practiced the semantic verification of time-compressed sentences for one or three training sessions. Identification of trained and untrained tokens was subsequently compared between listeners who trained for one or three sessions, listeners who were briefly exposed to 20 time-compressed sentences and naive listeners. Trained listeners outperformed the other groups of listeners on the trained condition, but only the group that was trained for three sessions outperformed the other groups when tested with untrained tokens. These findings suggest that although learning of distorted speech can occur rapidly, more stable learning and generalization might be achieved with longer, multi-session practice. It is suggested that the findings are consistent with the framework proposed by the Reverse Hierarchy Theory of perceptual learning.	\N	\N
25324114	This paper presents an efficient method to compute the numerical solutions of transmission-line (TL) cochlear models, and its application on the model of Verhulst et al. The stability region of the model is extended by adopting a variable step numerical method to solve the system of ordinary differential equations that describes it, and by adopting an adaptive scheme to take in account variations in the system status within each numerical step. The presented method leads to improve simulations numerical accuracy and large computational savings, leading to employ TL models for more extensive simulations than currently possible.	\N	\N
25325841	To determine factors related to high levels of speech recognition in patients with the auditory brainstem implant (ABI). Retrospective case review. International multicenter data from hospitals and tertiary referral facilities. Patients with neurofibromatosis type 2 (NF2) and bilateral vestibular schwannomas. ABIs were placed after the removal of vestibular schwannomas. Demographic and surgical data were collected from 26 patients with ABIs who achieved scores of better than 30% correct identification of sentences presented in quiet listening conditions and without lipreading cues. Scores better than 30% speech recognition of standard sentence test materials (HINT or equivalent) in quiet listening conditions were obtained in 26 of the 84 NF2 patients (31%). ABI speech recognition was correlated with surgical position, length of deafness, the number of distinct pitch electrodes, perceptual levels, and ABI stimulation rate, but not correlated with tumor size, tumor stage, the number of electrodes used, or electrophysiological recordings. This paper presents the consensus opinion from a meeting of surgeons to compare outcomes across ABI surgical centers. The consensus opinion was that brainstem trauma is a primary factor in the variability of outcomes in NF2 patients. The significant co-factors in outcomes implied that ABI surgery should be accomplished with great care to minimize physical and venous trauma to the brainstem. It is clear that high levels of speech recognition, including high levels of open-set speech recognition, are possible with the ABI even in patients with NF2 and large tumors.	\N	\N
25329080	How is semantic memory influenced by individual differences under conditions of distraction? This question was addressed by observing how participants recalled visual target words--drawn from a single category--while ignoring spoken distractor words that were members of either the same or a different (single) category. Working memory capacity (WMC) was related to disruption only with synchronous, not asynchronous, presentation, and distraction was greater when the words were presented synchronously. Subsequent experiments found greater negative priming of distractors among individuals with higher WMC, but this may be dependent on targets and distractors being comparable category exemplars. With less dominant category members as distractors, target recall was impaired--relative to control--only among individuals with low WMC. The results highlight the role of cognitive control resources in target-distractor selection and the individual-specific cost implications of such cognitive control.	\N	\N
25333740	Words are made up of speech sounds. Almost all accounts of child speech development assume that children learn the pronunciation of first language (L1) speech sounds by imitation, most claiming that the child performs some kind of auditory matching to the elements of ambient speech. However, there is evidence to support an alternative account and we investigate the non-imitative child behavior and well-attested caregiver behavior that this account posits using Elija, a computational model of an infant. Through unsupervised active learning, Elija began by discovering motor patterns, which produced sounds. In separate interaction experiments, native speakers of English, French and German then played the role of his caregiver. In their first interactions with Elija, they were allowed to respond to his sounds if they felt this was natural. We analyzed the interactions through phonemic transcriptions of the caregivers' utterances and found that they interpreted his output within the framework of their native languages. Their form of response was almost always a reformulation of Elija's utterance into well-formed sounds of L1. Elija retained those motor patterns to which a caregiver responded and formed associations between his motor pattern and the response it provoked. Thus in a second phase of interaction, he was able to parse input utterances in terms of the caregiver responses he had heard previously, and respond using his associated motor patterns. This capacity enabled the caregivers to teach Elija to pronounce some simple words in their native languages, by his serial imitation of the words' component speech sounds. Overall, our results demonstrate that the natural responses and behaviors of human subjects to infant-like vocalizations can take a computational model from a biologically plausible initial state through to word pronunciation. This provides support for an alternative to current auditory matching hypotheses for how children learn to pronounce.	\N	\N
25345762	Sudden sensorineural hearing loss (SSNHL) is strictly related to inner ear vascular injuries and recently to some atherosclerotic risk factors. The pathogenic role of inflammatory molecules in atherosclerosis is well established. However, there is little knowledge about the potential role of inflammatory cytokines and adhesion molecules on SSNHL etiology. The aim of this study was to evaluate the role of proinflammatory genetic polymorphisms of the MCP-1 (CCL2), E-selectin, and interleukin (IL)-6 gene in SSNHL patients. We evaluated the frequency and distribution of selected single nucleotide polymorphisms of the MCP-1 (CCL2), E-selectin, and IL-6 gene in 87 SSNHL patients and 107 healthy controls. Our results did not show significant difference between the compared groups for MCP-1 and E-selectin genes, whereas a significant difference was reported for the IL-6 gene (P < .0001). The main finding of our study is that the 174G/G polymorphism (with a wider distribution of wt/wt genotype in SSNHL patients than in the healthy controls) of the IL-6 gene is significantly associated with the risk of SSNHL, which is consistent with a previous finding on serum levels of IL-6 in SSNHL. It is possible that the variant acts as a triggering agent of different lipidemia-related phenotypes. Both the -174G/G polymorphism and elevated IL-6 levels in SSNHL patients could suggest that IL-6 plays a role in the inner ear involvement by atherosclerotic inflammatory events.	\N	\N
25349105	To assess spoken language comprehension in non-speaking children with severe cerebral palsy (CP) and to explore possible associations with motor type and disability. Eighty-seven non-speaking children (44 males, 43 females, mean age 6y 8mo, SD 2y 1mo) with spastic (54%) or dyskinetic (46%) CP (Gross Motor Function Classification System [GMFCS] levels IV [39%] and V [61%]) underwent spoken language comprehension assessment with the computer-based instrument for low motor language testing (C-BiLLT), a new and validated diagnostic instrument. A multiple linear regression model was used to investigate which variables explained the variation in C-BiLLT scores. Associations between spoken language comprehension abilities (expressed in z-score or age-equivalent score) and motor type of CP, GMFCS and Manual Ability Classification System (MACS) levels, gestational age, and epilepsy were analysed with Fisher's exact test. A p-value <0.05 was considered statistically significant. Chronological age, motor type, and GMFCS classification explained 33% (R=0.577, R(2) =0.33) of the variance in spoken language comprehension. Of the children aged younger than 6 years 6 months, 52.4% of the children with dyskinetic CP attained comprehension scores within the average range (z-score ≥-1.6) as opposed to none of the children with spastic CP. Of the children aged older than 6 years 6 months, 32% of the children with dyskinetic CP reached the highest achievable age-equivalent score compared to 4% of the children with spastic CP. No significant difference in disability was found between CP-related variables (MACS levels, gestational age, epilepsy), with the exception of GMFCS which showed a significant difference in children aged younger than 6 years 6 months (p=0.043). Despite communication disabilities in children with severe CP, particularly in dyskinetic CP, spoken language comprehension may show no or only moderate delay. These findings emphasize the importance of introducing alternative and/or augmentative communication devices from early childhood.	\N	\N
25350759	We examined neural indices of pre-attentive phonological and attentional auditory discrimination in children with developmental language disorder (DLD, n = 23) and typically developing (n = 16) peers from a geographically isolated Russian-speaking population with an elevated prevalence of DLD. Pre-attentive phonological MMN components were robust and did not differ in two groups. Children with DLD showed attenuated P3 and atypically distributed P2 components in the attentional auditory discrimination task; P2 and P3 amplitudes were linked to working memory capacity, development of complex syntax, and vocabulary. The results corroborate findings of reduced processing capacity in DLD and support a multifactorial view of the disorder.	\N	\N
25372405	A major cue to the location of a sound source is the interaural time difference (ITD)-the difference in sound arrival time at the two ears. The neural representation of this auditory cue is unresolved. The classic model of ITD coding, dominant for a half-century, posits that the distribution of best ITDs (the ITD evoking a neuron's maximal response) is unimodal and largely within the range of ITDs permitted by head-size. This is often interpreted as a place code for source location. An alternative model, based on neurophysiology in small mammals, posits a bimodal distribution of best ITDs with exquisite sensitivity to ITDs generated by means of relative firing rates between the distributions. Recently, an optimal-coding model was proposed, unifying the disparate features of these two models under the framework of efficient coding by neural populations. The optimal-coding model predicts that distributions of best ITDs depend on head size and sound frequency: for high frequencies and large heads it resembles the classic model, for low frequencies and small head sizes it resembles the bimodal model. The optimal-coding model makes key, yet unobserved, predictions: for many species, including humans, both forms of neural representation are employed, depending on sound frequency. Furthermore, novel representations are predicted for intermediate frequencies. Here, we examine these predictions in neurophysiological data from five mammalian species: macaque, guinea pig, cat, gerbil and kangaroo rat. We present the first evidence supporting these untested predictions, and demonstrate that different representations appear to be employed at different sound frequencies in the same species.	\N	\N
25375171	Gender dysphoria (also known as "transsexualism") is characterized as a discrepancy between anatomical sex and gender identity. Research points towards neurobiological influences. Due to the sexually dimorphic characteristics of the human voice, voice gender perception provides a biologically relevant function, e.g. in the context of mating selection. There is evidence for a better recognition of voices of the opposite sex and a differentiation of the sexes in its underlying functional cerebral correlates, namely the prefrontal and middle temporal areas. This fMRI study investigated the neural correlates of voice gender perception in 32 male-to-female gender dysphoric individuals (MtFs) compared to 20 non-gender dysphoric men and 19 non-gender dysphoric women. Participants indicated the sex of 240 voice stimuli modified in semitone steps in the direction to the other gender. Compared to men and women, MtFs showed differences in a neural network including the medial prefrontal gyrus, the insula, and the precuneus when responding to male vs. female voices. With increased voice morphing men recruited more prefrontal areas compared to women and MtFs, while MtFs revealed a pattern more similar to women. On a behavioral and neuronal level, our results support the feeling of MtFs reporting they cannot identify with their assigned sex.	\N	\N
25379450	Autism Spectrum Disorder (ASD) is characterized by impairments in language and social-emotional cognition. Yet, findings of emotion recognition from affective prosody in individuals with ASD are inconsistent. This study investigated emotion recognition and neural processing of affective prosody in high-functioning adults with ASD relative to neurotypical (NT) adults. Individuals with ASD showed mostly typical brain activation of the fronto-temporal and subcortical brain regions in response to affective prosody. Yet, the ASD group showed a trend towards increased activation of the right caudate during processing of affective prosody and rated the emotional intensity lower than NT individuals. This is likely associated with increased attentional task demands in this group, which might contribute to social-emotional impairments.	\N	\N
25382428	To verify the receiver in the ear and receiver in the aid adaptations by measuring in situ the speech perception and users' level of satisfaction. The study was approved by the research ethics committee (Process: 027/2011). Twenty subjects older than 18 years with audiological diagnosis of mild and moderate bilateral descending sensorineural hearing loss were evaluated. The subjects were divided into two groups, where G1 (group 1) was fitted with open-fit hearing aids with the built-in receiver unit (receiver in the ear) and G2 (group 2) was fitted with open-fit hearing aids with RITE. A probe microphone measurement was performed to check the gain and output provided by the amplification and for assessment of speech perception with Hearing in Noise Test with and without hearing aids. After a period of six weeks of use without interruption, the subjects returned for follow-up and answered the Satisfaction with Amplification in Daily Life questionnaire, and were again subjected to Hearing in Noise Test. Both groups presented better test results for speech recognition in the presence of noise. Groups 1 and 2 were satisfied with the use of hearing aids and improved speech recognition in silent and noisy situations with hearing aids.	\N	\N
25382429	There is still no consensus in the literature as to the best acoustic stimulus for capturing vestibular evoked myogenic potential (VEMP). Low-frequency tone bursts are generally more effective than high-frequency, but recent studies still use clicks. Reproducibility is an important analytical parameter to observe the reliability of responses. To determine the reproducibility of p13 and n23 latency and amplitude of the VEMP for stimuli with different tone-burst frequencies, and to define the best test frequency. Cross-sectional cohort study. VEMP was captured in 156 ears, on the sternocleidomastoid muscle, using 100 tone-burst stimuli at frequencies of 250, 500, 1000, and 2000Hz, and sound intensity of 95dB nHL. Responses were replicated, that is, recorded three times on each side. No significant difference was observed for p13 and n23 latencies of the VEMP, captured at three moments with tone-burst stimuli at 250, 500, and 1000Hz. Only the frequency of 2000Hz showed a difference between captures of this potential (p<0.001). p13 and n23 amplitude analysis was also similar in the test-retest for all frequencies analyzed. p13 and n23 latencies and amplitudes of VEMP for tone-burst stimuli at frequencies of 250, 500, and 1000Hz are reproducible.	\N	\N
25424987	The closure positive shift (CPS) event related potential (ERP) is commonly used as a neural measure of phrase boundary perception in speech. The present study investigated whether the CPS was elicited by acoustic cues at phrase boundaries in English. ERPs were recorded when participants listened passively to sentences with either early or late phrase boundaries. The closure positive shift (CPS) ERP was elicited at both early and late phrase boundaries. However, the latency, amplitude, and scalp distribution of these passive CPS ERPs in English sentences differed to active CPS ERPs measured in non-English sentences in previous studies. These results show that acoustic cues at the phrase boundaries in English are sufficient to elicit the CPS, and suggest that different processes might be involved in the generation of the CPS in active and passive conditions.	\N	\N
25438583	The present study assessed brain activity changes related to perception of consonant and dissonant chords by musicians and non-musicians. Perception of dissonant chords in non-musicians was accompanied by increase of lower theta activity over right anterior regions, while consonant chords induced greater theta activity over left anterior regions; this pattern of asymmetrical activation was not observed in musicians. ERP analysis revealed that musicians had greater amplitude of early components (P100, N200) than non-musicians irrespective of chord type. The obtained results reflect more efficient musical harmony processing and, possibly, less emotional perception of chords in musicians.	\N	\N
25445998	The localization of neuronal generators during an ERP study, using a high-density electroencephalogram (HD-EEG) equipment was made on three Evoked Related Potential (ERP) components, i.e., the Mismatch Negativity (MMN), the P300 and the N400. Furthermore, the ERP characteristics, their field distribution and the area of their maximum field intensity were extracted and compared between young and elderly, as well as between females and males. A two tone oddball experiment was conducted, involving 27 young adults and 18 elderly, healthy and right handed, and HD-EEG data were acquired. These data were then subjected to auditory ERPs extraction and thorough statistical analysis. The derived experimental results revealed significant age-related differences to both the latencies and the amplitudes of the MMN and the P300 and the topographic distribution of the HD-EEG amplitudes. Additionally, a shift in the maximum intensities from frontal to temporal lobe with aging appeared in the case of the P300, whereas no effect was observed for the MMN component. No statistical significant differences (p>0.05) due to age was found in N400 characteristics. Finally, gender-related differences were significant in the response time of the subjects, finding males response faster. The level and the location of the maximum intensity of sources also differed between genders, especially in young subjects. These findings justify the enhanced potential of HD-EEG data to accurately reflect the age and gender dependencies at the three components of simple auditory ERPs and pave the way for the investigation of neurodegenerative pathologies, such as the Alzheimer's disease.	\N	\N
25446245	Perceptual grouping is the process of organizing sounds into perceptually meaningful elements. Psychological studies have found that tones presented as a regular frequency or temporal pattern are grouped according to gestalt principles, such as similarity, proximity, and good continuity. Predictive coding theory suggests that this process helps create an internal model for the prediction of sounds in a tone sequence and that an omission-related brain response reflects the violation of this prediction. However, it remains unclear which brain areas are related to this process, especially in paying attention to the stimuli. To clarify this uncertainty, the present study investigated the neural correlates of perceptual grouping effects. Using magnetoencephalography (MEG), we recorded the evoked response fields (ERFs) of amateur musicians and nonmusicians to sound omissions in tone sequences with a regular or random pattern of three different frequencies during an omission detection task. Omissions in the regular sequences were detected faster and evoked greater activity in the left Heschl's gyrus (HG), right postcentral gyrus, and bilateral superior temporal gyrus (STG) than did omissions in the irregular sequences. Additionally, an interaction between musical experience and regularity was found in the left HG/STG. Tone-evoked responses did not show this difference, indicating that the expertise effect did not reflect the superior tone processing acquired by amateur musicians due to musical training. These results suggest that perceptual grouping based on repetition of a pattern of frequencies affects the processing of omissions in tone sequences and induces more activation of the bilateral auditory cortex by violating internal models. The interaction in the left HG/STG may suggest different styles of processing for musicians and nonmusicians, although this difference was not reflected at the behavioral level.	\N	\N
25447067	The effects of ear of presentation and competing speech on N400s to spoken words in context were examined in a dichotic sentence priming paradigm. Auditory sentence contexts with a strong or weak semantic bias were presented in isolation to the right or left ear, or with a competing signal presented in the other ear at a SNR of -12 dB. Target words were congruent or incongruent with the sentence meaning. Competing speech attenuated N400s to both congruent and incongruent targets, suggesting that the demand imposed by a competing signal disrupts the engagement of semantic comprehension processes. Bias strength affected N400 amplitudes differentially depending upon ear of presentation: weak contexts presented to the le/RH produced a more negative N400 response to targets than strong contexts, whereas no significant effect of bias strength was observed for sentences presented to the re/LH. The results are consistent with a model of semantic processing in which the RH relies on integrative processing strategies in the interpretation of sentence-level meaning.	\N	\N
25448166	In this article, we review the PET neuroimaging literature, which indicates peculiarities of brain networks involved in speech restoration after cochlear implantation. We consider data on implanted patients during stimulation as well as during resting state, which indicates basic long-term reorganisation of brain functional architecture. On the basis of our analysis of neuroimaging literature and considering our own studies, we indicate that auditory recovery in deaf patients after cochlear implantation partly relies on visual cues. The brain develops mechanisms of audio-visual integration as a strategy to achieve high levels of speech recognition. It turns out that this neuroimaging evidence is in line with behavioural findings of better audiovisual integration in these patients. Thus, strong visually and audio-visually based rehabilitation during the first months after cochlear implantation would significantly improve and fasten the functional recovery of speech intelligibility and other auditory functions in these patients. We provide perspectives for further neuroimaging studies in cochlear implanted patients, which would help understand brain organisation to restore auditory cognitive processing in the implanted patients and would potentially suggest novel approaches for their rehabilitation. This article is part of a Special Issue entitled <Lasker Award>.	\N	\N
25459663	In his pioneering research on the neural mechanisms of filial imprinting, Gabriel Horn has gone a long way to fulfilling Karl Lashley's dream of finding the 'engram' or memory trace in the brain. Here we review recent research into the engram(s) of song learning in songbirds, particularly zebra finches. When juvenile songbirds learn their songs from a tutor, they form and alter a central representation of the tutor song, known as the 'template'. Secondary auditory regions in the caudal medial pallium are likely to contain the neural substrate for the representation of tutor song, but the roles of the different regions remain to be elucidated. Female zebra finches do not sing, but nevertheless form an auditory memory of their father's song, for which the neural substrate is located in the caudomedial pallium. In males that are learning their songs, there is continual interaction between the secondary auditory regions and sensorimotor regions, similar to the interaction between Broca's and Wernicke's areas in human infants acquiring speech and language.	\N	\N
25460240	Visual attention and perceptual grouping both help us from being overloaded by the vast amount of information, and attentional search is delayed when a target overlaps with a snake-like collinear distractor (Jingling & Tseng, 2013). We assessed whether awareness of the collinear distractor is required for this modulation. We first identified that visible long (=9 elements), but not short (=3 elements) collinear distractor slowed observers' detection of an overlapping target. Then we masked part of a long distractor (=9 elements) with continuous flashing color patches (=6 elements) so that the combined dichoptic percept to observers' awareness was a short collinear distractor (=3 elements). We found that the invisible collinear parts, like visible ones, can form a continuous contour to impair search, suggesting that conscious awareness is not a pre-requisite for contour integration and its interaction with selective attention.	\N	\N
25461917	Recent studies have demonstrated the positive effects of musical training on the perception of vocally expressed emotion. This study investigated the effects of musical training on event-related potential (ERP) correlates of emotional prosody processing. Fourteen musicians and fourteen control subjects listened to 228 sentences with neutral semantic content, differing in prosody (one third with neutral, one third with happy and one third with angry intonation), with intelligible semantic content (semantic content condition--SCC) and unintelligible semantic content (pure prosody condition--PPC). Reduced P50 amplitude was found in musicians. A difference between SCC and PPC conditions was found in P50 and N100 amplitude in non-musicians only, and in P200 amplitude in musicians only. Furthermore, musicians were more accurate in recognizing angry prosody in PPC sentences. These findings suggest that auditory expertise characterizing extensive musical training may impact different stages of vocal emotional processing.	\N	\N
25463460	Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central auditory system. Altered GABAergic neurotransmission has been found in both the inferior colliculus and the auditory cortex in animal models of presbycusis. Edited magnetic resonance spectroscopy (MRS), using the MEGA-PRESS sequence, is the most widely used technique for detecting GABA in the human brain. However, to date there has been a paucity of studies exploring changes to the GABA concentrations in the auditory region of patients with presbycusis. In this study, sixteen patients with presbycusis (5 males/11 females, mean age 63.1 ± 2.6 years) and twenty healthy controls (6 males/14 females, mean age 62.5 ± 2.3 years) underwent audiological and MRS examinations. Pure tone audiometry from 0.125 to 8 kHz and tympanometry were used to assess the hearing abilities of all subjects. The pure tone average (PTA; the average of hearing thresholds at 0.5, 1, 2 and 4 kHz) was calculated. The MEGA-PRESS sequence was used to measure GABA+ concentrations in 4 × 3 × 3 cm(3) volumes centered on the left and right Heschl's gyri. GABA+ concentrations were significantly lower in the presbycusis group compared to the control group (left auditory regions: p = 0.002, right auditory regions: p = 0.008). Significant negative correlations were observed between PTA and GABA+ concentrations in the presbycusis group (r = -0.57, p = 0.02), while a similar trend was found in the control group (r = -0.40, p = 0.08). These results are consistent with a hypothesis of dysfunctional GABAergic neurotransmission in the central auditory system in presbycusis and suggest a potential treatment target for presbycusis.	\N	\N
25463556	Previous research has revealed that the inhibition of return (IOR) effect emerges when individuals respond to a target at the same location as their own previous response or the previous response of a co-actor. The latter social IOR effect is thought to occur because the observation of co-actor's response evokes a representation of that action in the observer and that the observation-evoked response code subsequently activates the inhibitory mechanisms underlying IOR. The present study was conducted to determine if knowledge of the co-actor's response alone is sufficient to evoke social IOR. Pairs of participants completed responses to targets that appeared at different button locations. Button contact generated location-contingent auditory stimuli (high and low tones in Experiment 1 and colour words in Experiment 2). In the Full condition, the observer saw the response and heard the auditory stimuli. In the Auditory Only condition, the observer did not see the co-actor's response, but heard the auditory stimuli generated via button contact to indicate response endpoint. It was found that, although significant individual and social IOR effects emerged in the Full conditions, there were no social IOR effects in the Auditory Only conditions. These findings suggest that knowledge of the co-actor's response alone via auditory information is not sufficient to activate the inhibitory processes leading to IOR. The activation of the mechanisms that lead to social IOR seems to be dependent on processing channels that code the spatial characteristics of action.	\N	\N
25468188	Schizophrenia and bipolar disorder share common etiological factors and pathophysiological pathways and have overlapping clinical features. Only few studies have directly compared early auditory information processing in the two disorders. The objective of this study was to investigate the M100 and M200 auditory responses in patients with schizophrenia and bipolar disorder and compare them with healthy controls using magnetoencephalography (MEG). Whole-head MEG data were acquired during an auditory oddball paradigm in 24 schizophrenia patients, 26 bipolar I disorder patients, and 31 healthy controls. The strengths and latencies of M100 and M200 in both hemispheres and the dipole source localizations were investigated from the standard stimuli. The M100 and M200 dipolar sources were localized to the left and right posterior portion of the superior temporal gyrus (STG) in all the subjects. An asymmetric pattern of M100 and M200 auditory response with more anterior sources in the right STG was observed in the healthy controls. However, both the schizophrenia and bipolar disorder patients showed a symmetric M100 and M200 source pattern. When compared with the healthy control group, both patient groups showed significantly reduced M100 and M200 source strength in both hemispheres. Our study suggests that early auditory information processing deficits may be similar in schizophrenia and bipolar disorder and may be related to abnormalities of the STG.	\N	\N
25470620	The aim was to investigate whether frequency compression (FC) hearing aids provide additional benefit to that conferred by conventional amplification. Participants wore the same hearing aid with FC enabled and disabled for six weeks (ABA design) in each condition. Speech recognition tests (in both quiet and in noise) were administered alongside two questionnaires. Performance was compared across the two signal processing conditions and at different time points. Twelve experienced hearing-aid users (aged 65-84 years old) with moderate-to-severe high-frequency hearing loss participated in the study. FC resulted in statistically significantly higher mean scores in all of the administered speech tests. Improvements over time were limited to high frequency phoneme perception. No effect of FC on self-report outcomes was observed. FC may lead to significant improvements in speech perception outcomes in both quiet and noise for many individuals. No participant was significantly disadvantaged by the use of FC.	\N	\N
25480080	Although there is an emerging consensus that both musical and linguistic pitch processing can be problematic for individuals with a developmental disorder termed congenital amusia, the nature of such a pitch-processing deficit, especially that demonstrated in a speech setting, remains unclear. Therefore, this study tested the performance of native Mandarin speakers, both with and without amusia, on discrimination and imitation tasks for Cantonese level tones, aiming to shed light on this issue. Results suggest that the impact of the phonological deficit, coupled with that of the domain-general pitch deficit, could provide a more comprehensive interpretation of Mandarin amusics' speech impairment. Specifically, when there was a high demand for pitch sensitivity, as in fine-grained pitch discriminations, the operation of the pitch-processing deficit played the more predominant role in modulating amusics' speech performance. But when the demand was low, as in discriminating naturally produced Cantonese level tones, the impact of the phonological deficit was more pronounced compared to that of the pitch-processing deficit. However, despite their perceptual deficits, Mandarin amusics' imitation abilities were comparable to controls'. Such selective impairment in tonal perception suggests that the phonological deficit more severely implicates amusics' input pathways.	\N	\N
25481793	Auditory categorization is a vital skill for perceiving the acoustic environment. Categorization depends on the discriminability of the sensory input as well as on the ability of the listener to adaptively make use of the relevant features of the sound. Previous studies on categorization have focused either on speech sounds when studying discriminability or on visual stimuli when assessing optimal cue utilization. Here, by contrast, we examined neural sensitivity to stimulus discriminability and optimal cue utilization when categorizing novel, non-speech auditory stimuli not affected by long-term familiarity. In a functional magnetic resonance imaging (fMRI) experiment, listeners categorized sounds from two category distributions, differing along two acoustic dimensions: spectral shape and duration. By introducing spectral degradation after the first half of the experiment, we manipulated both stimulus discriminability and the relative informativeness of acoustic cues. Degradation caused an overall decrease in discriminability based on spectral shape, and therefore enhanced the informativeness of duration. A relative increase in duration-cue utilization was accompanied by increased activity in left parietal cortex. Further, discriminability modulated right planum temporale activity to a higher degree when stimuli were spectrally degraded than when they were not. These findings provide support for separable contributions of parietal and posterior temporal areas to perceptual categorization. The parietal cortex seems to support the selective utilization of informative stimulus cues, while the posterior superior temporal cortex as a primarily auditory brain area supports discriminability particularly under acoustic degradation.	\N	\N
25485662	In recent years, a number of models of orthographic coding have been proposed in which the orthographic code consists of a set of units representing bigrams (open-bigram models). Three masked priming experiments were undertaken in an attempt to evaluate this idea: a conventional masked priming experiment, a sandwich priming experiment (Lupker & Davis, 2009) and an experiment involving a masked prime same-different task (Norris & Kinoshita, 2008). Three prime types were used, first-letter superset primes (e.g., wjudge-JUDGE), last-letter superset primes (e.g., judgew-JUDGE) and standard substitution-letter primes (e.g., juwge-JUDGE). In none of the experiments was there any evidence that the superset primes were more effective primes, the prediction made by open-bigram models. In fact, in the second and third experiments, first-letter superset primes were significantly worse primes than the other two prime types. These results provide no evidence for the existence of open-bigram units. They also suggest that prime-target mismatches at the first position produce orthographic codes that are less similar than mismatches at other positions. Implications for models of orthographic coding are discussed.	\N	\N
25486807	The spatial specificity of auditory aftereffect was studied after a short-time adaptation (5 s) to the broadband noise (20-20000 Hz). Adapting stimuli were sequences of noise impulses with the constant amplitude, test stimuli--with the constant and changing amplitude: an increase of amplitude of impulses in sequence was perceived by listeners as approach of the sound source, while a decrease of amplitude--as its withdrawal. The experiments were performed in an anechoic chamber. The auditory aftereffect was estimated under the following conditions: the adapting and test stimuli were presented from the loudspeaker located at a distance of 1.1 m from the listeners (the subjectively near spatial domain) or 4.5 m from the listeners (the subjectively near spatial domain) or 4.5 m from the listeners (the subjectively far spatial domain); the adapting and test stimuli were presented from different distances. The obtained data showed that perception of the imitated movement of the sound source in both spatial domains had the common characteristic peculiarities that manifested themselves both under control conditions without adaptation and after adaptation to noise. In the absence of adaptation for both distances, an asymmetry of psychophysical curves was observed: the listeners estimated the test stimuli more often as approaching. The overestimation by listeners of test stimuli as the approaching ones was more pronounced at their presentation from the distance of 1.1 m, i. e., from the subjectively near spatial domain. After adaptation to noise the aftereffects showed spatial specificity in both spatial domains: they were observed only at the spatial coincidence of adapting and test stimuli and were absent at their separation. The aftereffects observed in two spatial domains were similar in direction and value: the listeners estimated the test stimuli more often as withdrawing as compared to control. The result of such aftereffect was restoration of the symmetry of psychometric curves and of the equiprobable estimation of direction of movement of test signals.	\N	\N
25487588	A pilot study found the masking level difference (MLD) normal value of Chinese aged from 10 to 40, served to clinical practice. Seventy-three normal persons with hearing threshold < 20 dB and no disorder of otology were divided into three groups: classified 10-20 age as A group, 21-30 age as B group, 31-40 age as C group. MLD of age, gender and race were determined by the audiometer with dual channel by playing audio test disc. Same tests were compared with English language. The mean value of MLD in Chinese was (11.1 ± 3.4) dB and the 95% normal reference values were between 4.4 to 17.8 dB . There was no difference in term of gender. The value of MLD increased with age. In the term of language, foreign showed high value of MLD than that of Chinese. The measuring of MLD depends on age and language but not depends on gender. The normal threshold of MLD depends on age and language should be measured when normal values were applied to assess MLD in clinical practice.	\N	\N
25495831	Individuals with autism spectrum disorders (ASD) show enhanced perceptual and memory abilities in the domain of pitch, but also perceptual deficits in other auditory domains. The present study investigated their skills with respect to "echoic memory," a form of short-term sensory memory intimately tied to auditory perception, using a developmental perspective. We tested 23 high-functioning participants with ASD and 26 typically developing (TD) participants, distributed in two age groups (children vs. young adults; mean ages: ∼11 and ∼21 years). By means of an adaptive psychophysical procedure, we measured the longest period for which periodic (i.e., repeated) noise could be reliably discriminated from nonperiodic (i.e., plain random) noise. On each experimental trial, a single noise sample was presented to the participant, who had to classify this sound as periodic or nonperiodic. The TD adults performed, on average, much better than the other three groups, who performed similarly overall. As a function of practice, the measured thresholds improved for the TD participants, but did not change for the ASD participants. Thresholds were not correlated to performance in a test assessing verbal memory. The variance of the participants' response biases was larger among the ASD participants than among the TD participants. The results mainly suggest that echoic memory takes a long time to fully develop in TD humans, and that this development stops prematurely in persons with ASD.	\N	\N
25497692	Listeners vary substantially in their ability to recognize speech in noisy environments. Here we examined the role of genetic variation on individual differences in speech recognition in various noise backgrounds. Background noise typically varies in the levels of energetic masking (EM) and informational masking (IM) imposed on target speech. Relative to EM, release from IM is hypothesized to place greater demand on executive function to selectively attend to target speech while ignoring competing noises. Recent evidence suggests that the long allele variant in exon III of the DRD4 gene, primarily expressed in the prefrontal cortex, may be associated with enhanced selective attention to goal-relevant high-priority information even in the face of interference. We investigated the extent to which this polymorphism is associated with speech recognition in IM and EM conditions. In an unscreened adult sample (Experiment 1) and a larger screened replication sample (Experiment 2), we demonstrate that individuals with the DRD4 long variant show better recognition performance in noise conditions involving significant IM, but not in EM conditions. In Experiment 2, we also obtained neuropsychological measures to assess the underlying mechanisms. Mediation analysis revealed that this listening condition-specific advantage was mediated by enhanced executive attention/working memory capacity in individuals with the long allele variant. These findings suggest that DRD4 may contribute specifically to individual differences in speech recognition ability in noise conditions that place demands on executive function.	\N	\N
25500178	The challenge in getting a decent signal to the brain for users of cochlear implants (CIs) is described. A breakthrough occurred in 1989 that later enabled most users to understand conversational speech with their restored hearing alone. Subsequent developments included stimulation in addition to that provided with a unilateral CI, either with electrical stimulation on both sides or with acoustic stimulation in combination with a unilateral CI, the latter for persons with residual hearing at low frequencies in either or both ears. Both types of adjunctive stimulation produced further improvements in performance for substantial fractions of patients. Today, the CI and related hearing prostheses are the standard of care for profoundly deaf persons and ever-increasing indications are now allowing persons with less severe losses to benefit from these marvelous technologies. The steps in achieving the present levels of performance are traced, and some possibilities for further improvements are mentioned. This article is part of a Special Issue entitled <Lasker Award>.	\N	\N
25502451	A systematic review of the literature to evaluate the clinical outcome of cochlear implantation for patients with single-sided deafness (SSD) or asymmetrical hearing loss (AHL). We searched the PubMed, Embase, Cochrane Library, and CINAHL databases from their inception up to December 10, 2013 for SSD or AHL and cochlear implantation or their synonyms. In total, 781 articles were retrieved, of which 15 satisfied the eligibility criteria. Our outcomes of interest were speech perception in noise, sound localization, quality of life (QoL), and tinnitus. Critical appraisal showed that six studies reported on less than five patients or that they carried a low directness of evidence or a high risk of bias. Therefore, we extracted the data of nine studies (n = 112). Patient numbers, age, duration of deafness, classification of deafness, pure tone audiometry, follow-up duration, and outcome measurements were extracted from all nine articles. Because of large heterogeneity between studies, we were not able to pool data in a meta-analysis. We therefore summarized the results of the studies specified per outcome. There are no high-level-of-evidence studies concerning cochlear implantation in patients with SSD or AHL. Current literature suggests important benefits of cochlear implantation regarding sound localization, QoL, and tinnitus. Varying results were reported for speech perception in noise, possibly caused by the large clinical heterogeneity between studies. Larger and high-quality studies are certainly warranted.	\N	\N
25512041	The issue of whether human perception of speech and song recruits integrated or dissociated neural systems is contentious. This issue is difficult to address directly since these stimulus classes differ in their physical attributes. We therefore used a compelling illusion (Deutsch et al. 2011) in which acoustically identical auditory stimuli are perceived as either speech or song. Deutsch's illusion was used in a functional MRI experiment to provide a direct, within-subject investigation of the brain regions involved in the perceptual transformation from speech into song, independent of the physical characteristics of the presented stimuli. An overall differential effect resulting from the perception of song compared with that of speech was revealed in right midposterior superior temporal sulcus/right middle temporal gyrus. A left frontotemporal network, previously implicated in higher-level cognitive analyses of music and speech, was found to co-vary with a behavioural measure of the subjective vividness of the illusion, and this effect was driven by the illusory transformation. These findings provide evidence that illusory song perception is instantiated by a network of brain regions that are predominantly shared with the speech perception network.	\N	\N
25536235	A large number of neuroimaging studies have investigated imagined sensory processing and motor behaviours. These studies have reported neural activation patterns for imagined processes that resemble those of real sensory and motor events. The widespread use of such methods has raised questions about the extent to which imagined sensorimotor events mimic their overt counterparts, including their ability to elicit sensorimotor interactions. Direct behavioural evidence of imagery-induced multisensory interactions has been found recently in tasks involving auditory and visual processing. An influence of sensory imagery on the control of motor action, however, has not been investigated previously. Here, we show that both real and imagined moving sounds induce involuntary ocular movement in a nonvisual tracking task. The present data build on the results of previous studies of sensory imagery by showing that such conditions activate sensory neural areas. Moreover, we show an engagement of functional sensorimotor networks for imagined stimuli in a manner similar to the processing of real auditory stimuli.	\N	\N
25536844	A central problem in recent research on speech production concerns the question to what extent speakers adapt their linguistic expressions to the needs of their addressees. It is claimed that speakers sometimes leak information about objects that are only visible for them and not for their listeners. Previous research only takes the occurrence of adjectives as evidence for the leakage of privileged information. The present study hypothesizes that leaked information is also encoded in the prosody of those adjectives. A production experiment elicited adjectives that leak information and adjectives that do not leak information. An acoustic analysis and prominence rating task showed that adjectives that leak information were uttered with a higher pitch and perceived as more prominent compared to adjectives that do not leak information. Furthermore, a guessing task suggested that the adjectives' prosody relates to how listeners infer possible privileged information.	\N	\N
25545633	Past experience of everyday life activities, which forms the basis of our knowledge about the world, greatly affects how we understand stories. Yet, little is known about how this influence is instantiated in the human brain. Here, we used functional magnetic resonance imaging to investigate how past experience facilitates functional connectivity during the comprehension of stories rich in perceptual and motor details. We found that comprehenders' past experience with the scenes and actions described in the narratives selectively modulated functional connectivity between lower- and higher-level areas within the neural systems for visual and motor processing, respectively. These intramodal interactions may play an important role in integrating personal knowledge about a narrated situation with an evolving discourse representation. This study provides empirical evidence consistent with the idea that regions related to visual and motor processing are involved in the reenactment of experience as proposed by theories of embodied cognition.	\N	\N
25549509	The motor system is engaged when we perceive movement in the environment, even when we have no sensorimotor experience of that movement. It has been suggested that this ability relies on internal models that comprise specific exteroceptive representations, such as audition and vision. It has been shown that, for human movements, the quality of perception depends on the closeness between the perceived movement and the perceiver's own capability of reproducing it. Thus, if we are able to reproduce a movement, we also have the interoceptive motor memories that enable us to run internal models and perceive the same movements more accurately when merely observed. In a behavioral study we investigated if participants would be able to distinguish between self-produced and other-produced movement sounds from a previously recorded hurdling performance. We also analyzed if participants' discriminative ability would vary as a function of specific sound features, examining rhythmic step structure and amplitude range. The results reveal that participants were able to distinguish between their own and others' movement sounds. However, changing either rhythmic step structure or amplitude range of the sounds did not influence this self-other discrimination. We suggest that identification of one's own movement sounds is holistically achieved as an auditory gestalt.	\N	\N
25567437	To investigate the functional evaluation of auditory cortex by functional magnetic resonance imaging (fMRI) before cochlear implantation (CI). Twenty-one children with severe to profound sensorineural hearing loss (SNHL) (7 cases with normal inner ear structure, 3 cases with large vestibular aqueduct syndrome, 1 case with cochlear nerve hypoplasia) and 7 children with normal hearing were examined by fMRI under sedation. The subjects received acoustic stimuli at four random frequencies (500, 1 000, 2 000, 4 000 Hz) during fMRI examination. Tones were interleaved with silence in a block-periodic fMRI design with 16-second on-off intervals.Each stimulus repeated twice and the total acquisition time was 4 minutes and 28 seconds. Activation was identified in the auditory cortex of the 28 subjects in response to monaural and binaural acoustic stimulation, which was shown in the transverse temporal gyrus (Heschl gyrus), the thalamus and both.Of the 21 patients with SNHL, contralateral dominance was shown in six cases, ipsilateral dominance in five cases and bilateral equilibrium in 10 cases when one ear was exposed to the stimuli. Of the seven children with normal hearing, contralateral dominance was shown in three cases, ipsilateral dominance in two cases and bilateral equilibrium in two cases.No significant difference of the activation intensity in auditory cortex was shown between children with SNHL and normal hearing (P > 0.05). Good hearing recovery was obtained in the 21 patients after CI. No significant difference in the level of hearing and speech rehabilitation was shown between children with LVAS and with normal inner ear structure.Listening behavior response threshold was 55 dBHL in the case with cochlear nerve hypoplasia 10 months after CI. fMRI would be a feasible means of evaluating the function of the auditory cortex, which can be used for assessing the function of the entire auditory system prior to CI combined with ABR and imaging.	\N	\N
25575604	Cochlear implant users show a profile of residual, yet poorly understood, musical abilities. An ability that has received little to no attention in this population is entrainment to a musical beat. We show for the first time that a heterogeneous group of cochlear implant users is able to find the beat and move their bodies in time to Latin Merengue music, especially when the music is presented in unpitched drum tones. These findings not only reveal a hidden capacity for feeling musical rhythm through the body in the deaf and hearing impaired population, but illuminate promising avenues for designing early childhood musical training that can engage implanted children in social musical activities with benefits potentially extending to non-musical domains.	\N	\N
25596462	Emotional verbal messages are typically encountered in meaningful contexts, for instance, during face-to-face communication in social situations. Yet, they are often investigated by confronting single participants with isolated words on a computer screen, thus potentially lacking ecological validity. In the present study we recorded event-related brain potentials (ERPs) during emotional word processing in communicative situations provided by videos of a speaker, assuming that emotion effects should be augmented by the presence of a speaker addressing the listener. Indeed, compared to non-communicative situations or isolated word processing, emotion effects were more pronounced, started earlier and lasted longer in communicative situations. Furthermore, while the brain responded most strongly to negative words when presented in isolation, a positivity bias with more pronounced emotion effects for positive words was observed in communicative situations. These findings demonstrate that communicative situations--in which verbal emotions are typically encountered--strongly enhance emotion effects, underlining the importance of social and meaningful contexts in processing emotional and verbal messages.	\N	\N
25603582	Learning and transfer were investigated for a categorical structure that could be mapped without loss of information from 1 sensory modality to another. The category space was composed of 3 nonoverlapping, linearly separable categories whose members were structured, temporal events. Each stimulus was composed of a sequence of on-off events that varied in duration and number of subevents (complexity). Categories were learned visually, haptically, or auditorily and transferred to the same or another modality. Despite the.isomorphism across modalities, significant differences appeared in both learning and transfer. The visual modality showed an early learning advantage, with information on the transfer test preserved best when encoded visually during learning, worst when encoded haptically, with auditory encoding intermediate. False recognition rates were elevated when categories were learned haptically and transferred to another modality. In general, classification accuracy was highest for the category prototype, with false recognition of the category prototype higher in the cross-modality conditions. The results are discussed in terms of current theories in modality transfer including the difficulties inherent when calculation of similarity must be considered in a cross-modal situation.	\N	\N
25611595	Most general theories on serial order working memory (WM) assume the existence of position markers that are bound to the to-be-remembered items to keep track of the serial order. So far, the exact cognitive/neural characteristics of these markers have remained largely underspecified, while direct empirical evidence for their existence is mostly lacking. In the current study we demonstrate that retrieval from verbal serial order WM can be facilitated or hindered by spatial cuing: begin elements of a verbal WM sequence are retrieved faster after cuing the left side of space, while end elements are retrieved faster after cuing the right side of space. In direct complement to our previous work--where we showed the reversed impact of WM retrieval on spatial processing--we argue that the current findings provide us with a crucial piece of evidence suggesting a direct and functional involvement of space in verbal serial order WM. We outline the idea that serial order in verbal WM is coded within a spatial coordinate system with spatial attention being involved when searching through WM, and we discuss how this account can explain several hallmark observations related to serial order WM.	\N	\N
25620313	Despite a robust hearing conservation program, military personnel continue to be at high risk for noise induced hearing loss (NIHL). For more than a decade, a number of laboratories have investigated the use of antioxidants as a safe and effective adjunct to hearing conservation programs. Of the antioxidants that have been investigated, N-acetylcysteine (NAC) has consistently reduced permanent NIHL in the laboratory, but its clinical efficacy is still controversial. This study provides a prospective, randomized, double-blinded, placebo-controlled clinical trial investigating the safety profile and the efficacy of NAC to prevent hearing loss in a military population after weapons training. Of the 566 total study subjects, 277 received NAC while 289 were given placebo. The null hypothesis for the rate of STS was not rejected based on the measured results. While no significant differences were found for the primary outcome, rate of threshold shifts, the right ear threshold shift rate difference did approach significance (p = 0.0562). No significant difference was found in the second primary outcome, percentage of subjects experiencing an adverse event between placebo and NAC groups (26.7% and 27.4%, respectively, p = 0.4465). Results for the secondary outcome, STS rate in the trigger hand ear, did show a significant difference (34.98% for placebo-treated, 27.14% for NAC-treated, p-value = 0.0288). Additionally, post-hoc analysis showed significant differences in threshold shift rates when handedness was taken into account. While the secondary outcomes and post-hoc analysis suggest that NAC treatment is superior to the placebo, the present study design failed to confirm this. The lack of significant differences in overall hearing loss between the treatment and placebo groups may be due to a number of factors, including suboptimal dosing, premature post-exposure audiograms, or differences in risk between ears or subjects. Based on secondary outcomes and post hoc analyses however, further studies seem warranted and are needed to clarify dose response and the factors that may have played a role in the observed results.	\N	\N
25620314	This study explored the role of formant transitions and F0-contour continuity in binding together speech sounds into a coherent stream. Listening to a repeating recorded word produces verbal transformations to different forms; stream segregation contributes to this effect and so it can be used to measure changes in perceptual coherence. In experiment 1, monosyllables with strong formant transitions between the initial consonant and following vowel were monotonized; each monosyllable was paired with a weak-transitions counterpart. Further stimuli were derived by replacing the consonant-vowel transitions with samples from adjacent steady portions. Each stimulus was concatenated into a 3-min-long sequence. Listeners only reported more forms in the transitions-removed condition for strong-transitions words, for which formant-frequency discontinuities were substantial. In experiment 2, the F0 contour of all-voiced monosyllables was shaped to follow a rising or falling pattern, spanning one octave. Consecutive tokens either had the same contour, giving an abrupt F0 change between each token, or alternated, giving a continuous contour. Discontinuous sequences caused more transformations and forms, and shorter times to the first transformation. Overall, these findings support the notion that continuity cues provided by formant transitions and the F0 contour play an important role in maintaining the perceptual coherence of speech.	\N	\N
25631452	Schizophrenia patients with auditory verbal hallucinations (AVH) have reduced structural integrity in the left arcuate fasciculus (AFL) compared to healthy controls. However, it is neither known whether these changes are specific to AVH, as opposed to hallucinations or schizophrenia per se, nor how radial and/or axial diffusivity are altered. This study aimed to test the hypothesis that reductions to the structural integrity of the AFL are specifically associated with AVH in schizophrenia. Diffusion tensor imaging scans and clinical data were obtained from the Australian Schizophrenia Research Bank for 39 schizophrenia patients with lifetime AVH (18 current, 21 remitted), 74 schizophrenia patients with no lifetime AVH (40 with lifetime hallucinations in other modalities, 34 no lifetime hallucinations) and 40 healthy controls. Fractional anisotropy was significantly reduced in the AFL of patients with lifetime AVH compared to both healthy controls (Cohen's d=1.24) and patients without lifetime AVH (d=.72), including compared to the specific subsets of patients without AVH who either had hallucinations in other modalities (d=.69) or no history of any hallucinations (d=.73). Radial, but not axial, diffusivity was significantly increased in patients with lifetime AVH compared to both healthy controls (d=.89) and patients without lifetime AVH (d=.39). Evidence was found for a non-linear relation between fractional anisotropy in the AFL and state AVH. Reduced integrity of the AFL is specifically associated with AVH, as opposed to schizophrenia in general or hallucinations in other modalities. Increased radial diffusivity suggests dysmyelination or demyelination of the AFL may play a role in AVH.	\N	\N
25632078	Despite recent progress in our understanding of sensorimotor integration in speech learning, a comprehensive framework to investigate its neural basis is lacking at behaviorally relevant timescales. Structural and functional imaging studies in humans have helped us identify brain networks that support speech but fail to capture the precise spatiotemporal coordination within the networks that takes place during speech learning. Here we use neuronal oscillations to investigate interactions within speech motor networks in a paradigm of speech motor adaptation under altered feedback with continuous recording of EEG in which subjects adapted to the real-time auditory perturbation of a target vowel sound. As subjects adapted to the task, concurrent changes were observed in the theta-gamma phase coherence during speech planning at several distinct scalp regions that is consistent with the establishment of a feedforward map. In particular, there was an increase in coherence over the central region and a decrease over the fronto-temporal regions, revealing a redistribution of coherence over an interacting network of brain regions that could be a general feature of error-based motor learning in general. Our findings have implications for understanding the neural basis of speech motor learning and could elucidate how transient breakdown of neuronal communication within speech networks relates to speech disorders.	\N	\N
25644083	French-learning infants have language-specific difficulties in processing lexical stress due to the lack of lexical stress in French. These difficulties in discriminating between words with stress-initial (trochaic) and stress-final (iambic) patterns emerge by 10months of age in the easier context of low variability (using a single item pronounced with a trochaic pattern vs. an iambic pattern) as well as in the more challenging context of high segmental variability (using lists of segmentally different trochaic and iambic items). These findings raise the question of stress pattern perception in simultaneous bilinguals learning French and a second language using stress at the lexical level. Bijeljac-Babic, Serres, Höhle, and Nazzi (2012) established that at 10 months of age, in the simpler context of low variability, such bilinguals have better stress discrimination abilities than French-learning monolinguals. The current study explored whether this advantage extends to the more challenging context of high segmental variability. Results first establish stress pattern discrimination in a group of bilingual 10-month-olds learning French and one language with (variable) lexical stress, but not in French-learning 10-month-old monolinguals. Second, discrimination in bilinguals appeared not to be affected by the language balance of the infants, suggesting that sensitivity to stress patterns might be maintained in these bilingual infants provided that they hear at least 30% of a language with lexical stress.	\N	\N
25653380	In the diverse mechanosensory systems that animals evolved, the waveform of stimuli can be encoded by phase locking in spike trains of primary afferents. Coding of the fine structure of sounds via phase locking is thought to be critical for hearing. The upper frequency limit of phase locking varies across species and is unknown in humans. We applied a method developed previously, which is based on neural adaptation evoked by forward masking, to analyze mass potentials recorded on the cochlea and auditory nerve in the cat. The method allows us to separate neural phase locking from receptor potentials. We find that the frequency limit of neural phase locking obtained from mass potentials was very similar to that reported for individual auditory nerve fibers. The results suggest that this is a promising approach to examine neural phase locking in humans with normal or impaired hearing or in other species for which direct recordings from primary afferents are not feasible.	\N	\N
25656319	Models of speech production explain event-related suppression of the auditory cortical response as reflecting a comparison between auditory predictions and feedback. The present MEG study was designed to test two predictions from this framework: (1) whether the reduced auditory response varies as a function of the mismatch between prediction and feedback; (2) whether individual variation in this response is predictive of speech-motor adaptation. Participants alternated between online imitation and listening tasks. In the imitation task, participants began each trial producing the same vowel (/e/) and subsequently listened to and imitated auditorily-presented vowels varying in acoustic distance from /e/. Results replicated suppression, with a smaller M100 during speaking than listening. Although we did not find unequivocal support for the first prediction, participants with less M100 suppression were better at the imitation task. These results are consistent with the enhancement of M100 serving as an error signal to drive subsequent speech-motor adaptation.	\N	\N
25660196	Under certain conditions, sighted and blind humans can use echoes to discern characteristics of otherwise silent objects. Previous research concluded that robust horizontal-plane object localisation ability, without using head movement, depends on information above 2 kHz. While a strong interaural level difference (ILD) cue is available, it was not clear if listeners were using that or the monaural level cue that necessarily accompanies ILD. In this experiment, 13 sighted and normal-hearing listeners were asked to identify the right-vs.-left position of an object in virtual auditory space. Sounds were manipulated to remove binaural cues (binaural vs. diotic presentation) and prevent the use of monaural level cues (using level roving). With low- (<2 kHz) and high- (>2 kHz) frequency bands of noise, performance with binaural presentation and level rove exceeded that expected from use of monaural level cues and that with diotic presentation. It is argued that a high-frequency binaural cue (most likely ILD), and not a monaural level cue, is crucial for robust object localisation without head movement.	\N	\N
25660759	Impairments in neural function are common when oxygen supply to the brain is reduced. This study examined neurocognitive processes that are vulnerable to oxygen deprivation. We induced moderate-to-severe hypoxia in healthy adults, thereby inducing impairments caused by low brain oxygen availability. 22 healthy adults participated in this matched-pairs study with a single-blind, randomised design. Baseline neurocognitive function was examined during a familiarisation trial and participants were assigned to hypoxia (10% O2) or sham (21% O2) groups. Neurocognitive performance was assessed via computerised test battery after 50 min of breathing a gas mixture that reduced arterial oxygen saturation by 20% (p<0.01). Hypoxia severely reduced performance across all neurocognitive domain scores; with significant drops in neurocognitive index (-20%), composite memory (-30%), verbal memory (-34%), visual memory (-23%), processing speed (-36%), executive function (-20%), psychomotor speed (-24%), reaction time (-10%), complex attention (-19%) and cognitive flexibility (-18%; all p<0.05). Practice effects were blocked by hypoxia but occurred in sham for information processing speed (+30%), executive function (+14%), psychomotor speed (+18%), reaction time (+5%), cognitive flexibility (+14%), and overall cognitive functioning (+9%; all p<0.05). Neuropsychological performance decrements caused by acute experimental hypoxia are comparable to cognitive domains impaired with high altitude exposure and mild traumatic brain injury.	\N	\N
25676810	Neurologically healthy individuals use sensory feedback to alter future movements by updating internal models of the effector system and environment. For example, when visual feedback about limb movements or auditory feedback about speech movements is experimentally perturbed, the planning of subsequent movements is adjusted - i.e., sensorimotor adaptation occurs. A separate line of studies has demonstrated that experimentally delaying the sensory consequences of limb movements causes the sensory input to be attributed to external sources rather than to one's own actions. Yet similar feedback delays have remarkably little effect on visuo-motor adaptation (although the rate of learning varies, the amount of adaptation is only moderately affected with delays of 100-200ms, and adaptation still occurs even with a delay as long as 5000ms). Thus, limb motor learning remains largely intact even in conditions where error assignment favors external factors. Here, we show a fundamentally different result for sensorimotor control of speech articulation: auditory-motor adaptation to formant-shifted feedback is completely eliminated with delays of 100ms or more. Thus, for speech motor learning, real-time auditory feedback is critical. This novel finding informs theoretical models of human motor control in general and speech motor control in particular, and it has direct implications for the application of motor learning principles in the habilitation and rehabilitation of individuals with various sensorimotor speech disorders.	\N	\N
25678274	While there is growing understanding of visual selective attention in children, some aspects such as selection in the presence of distractors are not well understood. Adult studies suggest that when presented with a visual search task, an enhanced negativity is seen beginning around 200 ms (the N2pc) that reflects selection of a target item among distractors. However, it is not known if similar selective attention-related activity is seen in children during visual search. This study was designed to investigate the presence of the N2pc in children. Nineteen children (ages 9-12 years) and 21 adults (ages 18-22 years) completed a visual search task in which they were asked to attend to a fixation surrounded by both a target and a distractor stimulus. Three types of displays were analyzed at parietal electrodes P7 and P8; lateral target/lateral distractor, lateral target/midline distractor, and midline target/lateral distractor. Both adults and children showed a significant increased negativity contralateral compared to ipsilateral to the target (reflected in the N2pc) in both displays with a lateral target while no such effect was seen in displays with a midline target. This suggests that children also utilized additional resources to select a target item when distractors are present. These findings demonstrate that the N2pc can be used as a marker of attentional object selection in children.	\N	\N
25681737	Aging usually decreases the ability to understand language under difficult listening conditions. However, aging is also associated with increased between-subject variability. Here, we studied potential sources of inter-individual differences and investigated spoken language understanding of younger and older adults (age ranges 21-35 and 57-74 years, respectively) in a simulated "cocktail-party" scenario. A naturalistic "stock-price monitoring" task was employed in which prices of listed companies were simultaneously recited by four speakers at different locations in space. The participants responded when prices of a target company exceeded specific values, while ignoring all other companies. According to their individual performance levels three subgroups of participants were composed, consisting of 12 high-performing and 12 low-performing older adults, and 12 young adults matching the high-performing older group. The analysis of the event-related brain potentials indicated that all older adults showed delayed attentional control (indicated by a later P2) and reduced speech processing (indicated by a reduced N400), relative to the younger adults. High-performing older adults differed in increased allocation of attention and inhibitory control (indicated by a stronger P2-N2 complex) from their low-performing counterparts. The results are consistent with the idea of an adjustment of mental resources that could help compensating potential deficiencies in peripheral and central auditory processing.	\N	\N
25704552	Grapheme-color synesthetes perceive achromatic graphemes to be inherently colored. In this study grapheme-color synesthetes and non-synesthetes discriminated (1) the color of visual targets presented along with aurally presented digit primes, and (2) the identity of aurally presented digit targets presented with visual color primes. Reaction times to visual color targets were longer when the color of the target was incongruent with the synesthetic percept reported for the prime. Likewise, discriminating aurally presented digit targets took longer when the color of the prime was incongruent with the synesthetic percept for the target. These priming effects were absent in non-synesthetes. We conclude that binding between digits and colors in grapheme-color synesthetes can occur bidirectionally across senses. The results are in line with the idea that synesthesia is the result of linking inducing stimuli (e.g. digits) to synesthetic percepts (colors) at an abstract - supra-modal - conceptual level of processing.	\N	\N
25705651	Noise is a major cause of health disorders in workers and has unique importance in the auditory analysis of people exposed to it. The purpose of this study is to evaluate the arithmetic mean of the auditory thresholds at frequencies of 3, 4, and 6 kHz of workers from five professional categories exposed to occupational noise. We propose a retrospective cross-sectional cohort study to analyze 2.140 audiograms from seven companies having five sectors of activity: one footwear company, one beverage company, two ceramics companies, two metallurgical companies, and two transport companies. When we compared two categories, we noticed a significant difference only for cargo carriers in comparison to the remaining categories. In all activity sectors, the left ear presented the worst values, except for the footwear professionals (P > 0.05). We observed an association between the noise exposure time and the reduction of audiometric values for both ears. Significant differences existed for cargo carriers in relation to other groups. This evidence may be attributed to different forms of exposure. A slow and progressive deterioration appeared as the exposure time increased.	\N	\N
25705995	To investigate audiological and quality of life outcomes for a new active transcutaneous device, called the bone conduction implant (BCI), where the transducer is implanted under intact skin. A clinical study with sound field audiometry and questionnaires at six-month follow-up was conducted with a bone-anchored hearing aid on a softband as reference device. Six patients (age 18-67 years) with mild-to-moderate conductive or mixed hearing loss. The surgical procedure was found uneventful with no adverse events. The first hypothesis that BCI had a statistically significant improvement over the unaided condition was proven by a pure-tone-average improvement of 31.0 dB, a speech recognition threshold improvement in quiet (27.0 dB), and a speech recognition score improvement in noise (51.2 %). At speech levels, the signal-to-noise ratio threshold for BCI was - 5.5 dB. All BCI results were better than, or similar to the reference device results, and the APHAB and GBI questionnaires scores showed statistically significant improvements versus the unaided situation, supporting the second and third hypotheses. The BCI provides significant hearing rehabilitation for patients with mild-to-moderate conductive or mixed hearing impairments, and can be easily and safely implanted under intact skin.	\N	\N
25707867	The magnitude of spatial distance between sound stimuli is critically important for their preattentive discrimination, yet the effect of stimulus context on auditory motion processing is not clear. This study investigated the effects of acoustical change and stimulus context on preattentive spatial change detection. Auditory event-related potentials (ERPs) were recorded for stationary midline noises and two patterns of sound motion produced by linear or abrupt changes of interaural time differences. Each of the three types of stimuli was used as standard or deviant in different blocks. Context effects on mismatch negativity (MMN) elicited by stationary and moving sound stimuli were investigated by reversing the role of standard and deviant stimuli, while the acoustical stimulus parameters were kept the same. That is, MMN amplitudes were calculated by subtracting ERPs to identical stimuli presented as standard in one block and deviant in another block. In contrast, effects of acoustical change on MMN amplitudes were calculated by subtracting ERPs of standards and deviants presented within the same block. Preattentive discrimination of moving and stationary sounds indexed by MMN was strongly dependent on the stimulus context. Higher MMNs were produced in oddball configurations where deviance represented increments of the sound velocity, as compared to configurations with velocity decrements. The effect of standard-deviant reversal was more pronounced with the abrupt sound displacement than with gradual sound motion.	\N	\N
25722025	Most high-level auditory functions require one to detect the onset and offset of sound sequences as well as registering the rate at which sounds are presented within the sound trains. By recording event-related brain potentials to onsets and offsets of tone trains as well as to changes in the presentation rate, we tested whether these fundamental auditory capabilities are functional at birth. Each of these events elicited significant event-related potential components in sleeping healthy neonates. The data thus demonstrate that the newborn brain is sensitive to these acoustic features suggesting that infants are geared towards the temporal aspects of segregating sound sources, speech and music perception already at birth.	\N	\N
25726273	Auditory processing is remarkably fast and sensitive to the precise temporal structure of acoustic signals over a range of scales, from submillisecond phenomena such as localization to the construction of elementary auditory attributes at tens of milliseconds to basic properties of speech and music at hundreds of milliseconds. In light of the rapid (and often transitory) nature of auditory phenomena, in order to investigate the neurocomputational basis of auditory perception and cognition, a technique with high temporal resolution is appropriate. Here we briefly outline the utility of magnetoencephalography (MEG) for the study of the neural basis of audition. The basics of MEG are outlined in brief, and some of the most-used neural responses are described. We discuss the classic transient evoked fields (e.g., M100), responses elicited by change in a stimulus (e.g., pitch-onset response), the auditory steady-state response, and neural oscillations (e.g., theta-phase tracking). Because of the high temporal resolution and the good spatial resolution of MEG, paired with the convenient location of human auditory cortex for MEG-based recording, electromagnetic recording of this type is well suited to investigate various aspects from audition, from crafted laboratory experiments on pitch perception or scene analysis to naturalistic speech and music tasks.	\N	\N
25730639	In serial recall tasks, presenting items in alternating female and male voices impairs performance relative to the single-voice presentation. This phenomenon, termed the talker-variability effect (TVE), was recently reexamined by Hughes, Marsh, and Jones (2009, 2011), who used the effect as confirmatory evidence for their perceptual-gestural account of serial recall performance. Despite the authors' claim of generalisability, the serial recall paradigm employed did not reflect the standard parameters more generally adopted in verbal short-term memory research. Specifically, the presentation rate of the stimuli was almost 3 times that typically used. We sought to determine if the TVE, as observed by Hughes et al., was generalisable to the standard serial recall task by directly comparing recall performance in talker-variable conditions at fast and slow stimulus presentation rates. Experiment 1 employed a systematic replication of the foundational study undertaken by Hughes et al. (2009). Utilising a novel stimulus set, Experiment 2 provided a subsequent test of the generalisability of the TVE, examining the influence of item properties. Both experiments showed a robust TVE at the atypical fast presentation rate; however, for the slower item presentation, the TVE was unreliable. Furthermore, error analysis suggests that item recall also contributes to the TVE, contrary to the current explanation proposed by Hughes et al. (2009, 2011). The challenge of the present data to the perceptual-gestural account of the TVE is explored. Alternative accounts that focus on the resource cost of categorical speech perception in the context of talker variability are posited.	\N	\N
25732931	Pacific bluefin tuna (Thunnus orientalis) is a highly migratory, commercially valuable species potentially vulnerable to acoustic noise generated from human activities which could impact behavior and fitness. Although significant efforts have been made to understand hearing abilities of fishes, the large size and need to continuously swim for respiration have hindered investigations with tuna and other large pelagic species. In this study, Pacific bluefin tuna were trained to respond to a pure tone sound stimulus ranging 325-800 Hz and their hearing abilities quantified using a staircase psychophysical technique. Hearing was most sensitive from 400 to 500 Hz in terms of particle motion (radial acceleration -88 dB re 1 m s(-2); vertical acceleration -86 dB re 1 m s(-2)) and sound pressure (83 dB re 1 μPa). Compared to yellowfin tuna (Thunnus albacares) and kawakawa (Euthynnus affinis), Pacific bluefin tuna has a similar bandwidth of hearing and best frequency, but greater sensitivity overall. Careful calibration of the sound stimulus and experimental tank environment, as well as the adoption of behavioral methodology, demonstrates an experimental approach highly effective for the study of large fish species in the laboratory.	\N	\N
25740512	In normal listeners, the tonal rules of music guide musical expectancy. In a minority of individuals, known as amusics, the processing of tonality is disordered, which results in severe musical deficits. It has been shown that the tonal rules of music are neurally encoded, but not consciously available in amusics. Previous neurophysiological studies have not explicitly controlled the level of attention in tasks where participants ignored the tonal structure of the stimuli. Here, we test whether access to tonal knowledge can be demonstrated in congenital amusia when attention is controlled. Electric brain responses were recorded while asking participants to detect an individually adjusted near-threshold click in a melody. In half the melodies, a note was inserted that violated the tonal rules of music. In a second task, participants were presented with the same melodies but were required to detect the tonal deviation. Both tasks required sustained attention, thus conscious access to the rules of tonality was manipulated. In the click-detection task, the pitch deviants evoked an early right anterior negativity (ERAN) in both groups. In the pitch-detection task, the pitch deviants evoked an ERAN and P600 in controls but not in amusics. These results indicate that pitch regularities are represented in the cortex of amusics, but are not consciously available. Moreover, performing a pitch-judgment task eliminated the ERAN in amusics, suggesting that attending to pitch information interferes with perception of pitch. We propose that an impaired top-down frontotemporal projection is responsible for this disorder.	\N	\N
25740534	When two musical notes with simple frequency ratios are played simultaneously, the resulting musical chord is pleasing and evokes a sense of resolution or "consonance". Complex frequency ratios, on the other hand, evoke feelings of tension or "dissonance". Consonance and dissonance form the basis of harmony, a central component of Western music. In earlier work, we provided evidence that consonance perception is based on neural temporal coding in the brainstem (Bones et al., 2014). Here, we show that for listeners with clinically normal hearing, aging is associated with a decline in both the perceptual distinction and the distinctiveness of the neural representations of different categories of two-note chords. Compared with younger listeners, older listeners rated consonant chords as less pleasant and dissonant chords as more pleasant. Older listeners also had less distinct neural representations of consonant and dissonant chords as measured using a Neural Consonance Index derived from the electrophysiological "frequency-following response." The results withstood a control for the effect of age on general affect, suggesting that different mechanisms are responsible for the perceived pleasantness of musical chords and affective voices and that, for listeners with clinically normal hearing, age-related differences in consonance perception are likely to be related to differences in neural temporal coding.	\N	\N
25744662	Hearing loss is one of the most common symptoms of mitochondrial disorders. However, audiological phenotypes associated with different molecular defects in mtDNA are not yet well characterized. A large cohort of 1499 nonconsanguineous patients aged 5-40 years with hearing loss of unknown etiology was screened for mutations in mtDNA. For further analysis, patients harboring m.1555A>G and m.3243A>G were selected. Hearing status of the patients was assessed by pure tone audiometry. Patterns of audiograms (hearing threshold levels at each examined frequency) were statistically compared among the carriers of the m.1555A>G and the m.3243A>G mutations. We identified 20 patients positive for m.1555A>G mutation and 16 patients positive for m.3243A>G change. The frequency of the above transitions was calculated in our cohort as 1.33% and 1.06%, respectively. Seventeen affected family members carrying the mutations were included into the study. Typical shape of the audiograms in patients with m.1555A>G mutation presented a ski-slope pattern, whereas the audiometric curves among the m.3243A>G individuals had a pantonal shape (a flat curve) with slight downward sloping at the higher frequencies. The differences were statistically significant. The onset of hearing loss was noted earlier among m.1555A>G than m.3243A>G patients (12.5 and 26 years, respectively). Aminoglycoside administration was declared in both groups in 11 and 4 cases respectively, and caused abrupt hearing deterioration in all cases. A pattern of audiogram in patients with mitochondrial deafness may suggest a localization of mtDNA mutation. The pathogenesis of the audiometric differences needs further study.	\N	\N
25768088	Cartilage conduction (CC) is a new form of sound transmission which is induced by a transducer being placed on the aural cartilage. Although the conventional forms of sound transmission to the cochlea are classified into air or bone conduction (AC or BC), previous study demonstrates that CC is not classified into AC or BC (Laryngoscope 124: 1214-1219). Next interesting issue is whether CC is a hybrid of AC and BC. Seven volunteers with normal hearing participated in this experiment. The threshold-shifts by water injection in the ear canal were measured. AC, BC, and CC thresholds at 0.5-4 kHz were measured in the 0%-, 40%-, and 80%-water injection conditions. In addition, CC thresholds were also measured for the 20%-, 60%-, 100%-, and overflowing-water injection conditions. The contributions of the vibrations of the cartilaginous portion were evaluated by the threshold-shifts. For AC and BC, the threshold-shifts by the water injection were 22.6-53.3 dB and within 14.9 dB at the frequency of 0.5-4 kHz, respectively. For CC, when the water was filled within the bony portion, the thresholds were elevated to the same degree as AC. When the water was additionally injected to reach the cartilaginous portion, the thresholds at 0.5 and 1 kHz dramatically decreased by 27.4 and 27.5 dB, respectively. In addition, despite blocking AC by the injected water, the CC thresholds in force level were remarkably lower than those for BC. The vibration of the cartilaginous portion contributes to the sound transmission, particularly in the low frequency range. Although the airborne sound is radiated into the ear canal in both BC and CC, the mechanism underlying its generation is different between them. CC generates airborne sound in the canal more efficiently than BC. The current findings suggest that CC is not a hybrid of AC and BC.	\N	\N
25784489	Electrical stimulation of upper limb nerves evokes a train of high-frequency wavelets (high-frequency oscillations, HFOs) on the human scalp. These HFOs are related to the influence of arousal-promoting structures on somatosensory input processing, and are generated in the primary somatosensory cortex (post-synaptic HFOs) and the terminal tracts of thalamocortical radiations (pre-synaptic HFOs). We previously reported that HFOs do not undergo habituation to repeated stimulations; here, we verified whether HFOs could be modulated by external sensitizing stimuli. We recorded somatosensory evoked potentials (SSEPs) in 15 healthy volunteers before and after sensitization training with an auditory stimulus. Pre-synaptic HFO amplitudes, reflecting somatosensory thalamic/thalamocortical activity, significantly increased after the sensitizing acoustic stimulation, whereas both the low-frequency N20 SSEP component and post-synaptic HFOs were unaffected. Cross-talk between subcortical arousal-related structures is a probable mechanism for the pre-synaptic HFO effect observed in this study. We propose that part of the ascending somatosensory input encoded in HFOs is specifically able to convey sensitized inputs. This preferential involvement in sensitization mechanisms suggests that HFOs play a critical role in the detection of potentially relevant stimuli, and act at very early stages of somatosensory input processing.	\N	\N
25813739	Perception of simultaneity and temporal order is studied with simultaneity judgment (SJ) and temporal-order judgment (TOJ) tasks. In the former, observers report whether presentation of two stimuli was subjectively simultaneous; in the latter, they report which stimulus was subjectively presented first. SJ and TOJ tasks typically give discrepant results, which has prompted the view that performance is mediated by different processes in each task. We looked at these discrepancies from a model that yields psychometric functions whose parameters characterize the timing, decisional, and response processes involved in SJ and TOJ tasks. We analyzed 12 data sets from published studies in which both tasks had been used in within-subjects designs, all of which had reported differences in performance across tasks. Fitting the model jointly to data from both tasks, we tested the hypothesis that common timing processes sustain simultaneity and temporal-order judgments, with differences in performance arising from task-dependent decisional and response processes. The results supported this hypothesis, also showing that model psychometric functions account for aspects of SJ and TOJ data that classical analyses overlook. Implications for research on perception of simultaneity and temporal order are discussed.	\N	\N
25813742	Previous studies have shown that humans are sensitive to statistical patterns indicating the likely locations, identities, and timings of visual targets. Here we tested whether participants can also use this kind of information to ameliorate the attentional blink (AB)—a reduction in accuracy for the second of two targets (T1, T2) presented at brief intertarget intervals (lags). In particular, we asked whether participants can use patterns arising from differential distributions of intertarget lags across trials to predict the arrival of T2. We tested this by comparing the ABs in an aging versus a nonaging distribution of trials, where aging refers to the increased likelihood of T2, given that it has not yet occurred, when lags occur with equal frequencies. Experiments 1 and 2 showed that the aging condition yielded greater T2 accuracy at longer lags than did the nonaging condition. In Experiment 3, we used a more sensitive response time measure to show faster T2 discrimination at shorter lags in the nonaging condition. These results demonstrate that participants can predict the likely onset of T2 by using statistical patterns present in the AB task, and that they can use this ability to more effectively direct limited processing resources.	\N	\N
25827259	Infants' attention is captured by the redundancy of amodal stimulation in multimodal objects and events. Evidence from this study demonstrates that intersensory redundancy can facilitate discrimination of rhythm changes presented in the visual modality alone in visually impaired infants, suggesting that multisensory rehabilitation strategies could prove helpful in this population.	\N	\N
25862624	Animal models of tinnitus complement human findings and potentially deepen our insight into the neural substrates of tinnitus. The fact that animal data are largely based on recordings from the auditory system, in particular from subcortical structures, makes comparison with human electrophysiological data from predominantly cortical areas difficult. Electro/magnetoencephalography and imaging data extend beyond the auditory cortex. The most challenging link to be made is the one between the macroscopic data in humans and the microscopic (single neuron action potentials) and mesoscopic (local field potentials) results obtained in animal models. Since invasive recordings in humans are rare, a bridge needs to be built on the basis of changes in brain rhythms in animals with putative tinnitus.	\N	\N
25878278	There is substantial evidence that sensory deprivation leads to important cross-modal brain reorganization that is paralleled by enhanced perceptual abilities. However, it remains unclear how widespread these enhancements are, and whether they are intercorrelated or arise at the expense of other perceptual abilities. One specific area where such a trade-off might arise is that of spatial hearing, where blind individuals have been shown to possess superior monaural localization abilities in the horizontal plane, but inferior localization abilities in the vertical plane. While both of these tasks likely involve the use of monaural cues due to the absence of any relevant binaural signal, there is currently no proper explanation for this discrepancy, nor has any study investigated both sets of abilities in the same sample of blind individuals. Here, we assess whether the enhancements observed in the horizontal plane are related to the deficits observed in the vertical plane by testing sound localization in both planes in groups of blind and sighted persons. Our results show that the blind individuals who displayed the highest accuracy at localizing sounds monaurally in the horizontal plane are also the ones who exhibited the greater deficit when localizing in the vertical plane. These findings appear to argue against the idea of generalized perceptual enhancements in the early blind, and instead suggest the possibility of a trade-off in the localization proficiency between the two auditory spatial planes, such that learning to use monaural cues for the horizontal plane comes at the expense of using those cues to localize in the vertical plane.	\N	\N
25880903	Stuttering is a neurodevelopmental disorder that affects the timing and rhythmic flow of speech production. When speech is synchronized with an external rhythmic pacing signal (e.g., a metronome), even severe stuttering can be markedly alleviated, suggesting that people who stutter may have difficulty generating an internal rhythm to pace their speech. To investigate this possibility, children who stutter and typically-developing children (n=17 per group, aged 6-11 years) were compared in terms of their auditory rhythm discrimination abilities of simple and complex rhythms. Children who stutter showed worse rhythm discrimination than typically-developing children. These findings provide the first evidence of impaired rhythm perception in children who stutter, supporting the conclusion that developmental stuttering may be associated with a deficit in rhythm processing.	\N	\N
25896774	In this report, we used filtered noise bands to constrain listeners' access to interaural level differences (ILDs) and interaural time differences (ITDs) in a sound source localization task. The samples of interest were listeners with single-sided deafness (SSD) who had been fit with a cochlear implant in the deafened ear (SSD-CI). The comparison samples included listeners with normal hearing and bimodal hearing, i.e., with a cochlear implant in 1 ear and low-frequency acoustic hearing in the other ear. The results indicated that (i) sound source localization was better in the SSD-CI condition than in the SSD condition, (ii) SSD-CI patients rely on ILD cues for sound source localization, (iii) SSD-CI patients show functional localization abilities within 1-3 months after device activation and (iv) SSD-CI patients show better sound source localization than bimodal CI patients but, on average, poorer localization than normal-hearing listeners. One SSD-CI patient showed a level of localization within normal limits. We provide an account for the relative localization abilities of the groups by reference to the differences in access to ILD cues.	\N	\N
25912703	In this review we analyse cochlear implantation in terms of the fundamental aspects of the functioning of the auditory system. Concepts concerning neuronal plasticity applied to electrical stimulation in perinatal and adult deep hypoacusis are reviewed, and the latest scientific bases that justify early implantation following screening for congenital deafness are discussed. Finally, this review aims to serve as an example of the importance of fostering the sub-specialty of neurotology in our milieu, with the aim of bridging some of the gaps between specialties and thus improving both the knowledge in the field of research on auditory pathologies and in the screening of patients. The objectives of this review, targeted above all towards specialists in the field of otorhinolaryngology, are to analyse some significant neurological foundations in order to reach a better understanding of the clinical events that condition the indications and the rehabilitation of patients with cochlear implants, as well as to use this means to foster the growth of the sub-specialty of neurotology.	\N	\N
25914938	The study examined the effect of structural composition, position of occlusion, and education background on response time and accuracy rate of adult participants in recognition of occluded Chinese characters used in graphic design. Based on 18 Chinese characters selected from the top 4,000 most commonly used characters, a recognition experiment was conducted. Results indicated that, for the characters with two different composition structures, the right position was the best position of occlusion because the recognition of the radical or feature of a character would be least affected, leading to a shorter response time and more accurate reading comprehension. Educational background did not have a significant influence on response time and recognition accuracy.	\N	\N
25914939	This study examined the effects of audio-visual aids on anxiety, comprehension test scores, and retention in reading and listening to short stories in English as a Foreign Language (EFL) classrooms. Reading and listening tests, general and test anxiety, and retention were measured in English-major college students in an experimental group with audio-visual aids (n=83) and a control group without audio-visual aids (n=94) with similar general English proficiency. Lower reading test anxiety, unchanged reading comprehension scores, and better reading short-term and long-term retention after four weeks were evident in the audiovisual group relative to the control group. In addition, lower listening test anxiety, higher listening comprehension scores, and unchanged short-term and long-term retention were found in the audiovisual group relative to the control group after the intervention. Audio-visual aids may help to reduce EFL learners' listening test anxiety and enhance their listening comprehension scores without facilitating retention of such materials. Although audio-visual aids did not increase reading comprehension scores, they helped reduce EFL learners' reading test anxiety and facilitated retention of reading materials.	\N	\N
25948273	The human brain has evolved to operate effectively in highly complex acoustic environments, segregating multiple sound sources into perceptually distinct auditory objects. A recent theory seeks to explain this ability by arguing that stream segregation occurs primarily due to the temporal coherence of the neural populations that encode the various features of an individual acoustic source. This theory has received support from both psychoacoustic and functional magnetic resonance imaging (fMRI) studies that use stimuli which model complex acoustic environments. Termed stochastic figure-ground (SFG) stimuli, they are composed of a "figure" and background that overlap in spectrotemporal space, such that the only way to segregate the figure is by computing the coherence of its frequency components over time. Here, we extend these psychoacoustic and fMRI findings by using the greater temporal resolution of electroencephalography to investigate the neural computation of temporal coherence. We present subjects with modified SFG stimuli wherein the temporal coherence of the figure is modulated stochastically over time, which allows us to use linear regression methods to extract a signature of the neural processing of this temporal coherence. We do this under both active and passive listening conditions. Our findings show an early effect of coherence during passive listening, lasting from ∼115 to 185 ms post-stimulus. When subjects are actively listening to the stimuli, these responses are larger and last longer, up to ∼265 ms. These findings provide evidence for early and preattentive neural computations of temporal coherence that are enhanced by active analysis of an auditory scene.	\N	\N
25951749	The debate about the causal role of the motor system in speech perception has been reignited by demonstrations that motor processes are engaged during the processing of speech sounds. Here, we evaluate which aspects of auditory speech processing are affected, and which are not, in a stroke patient with dysfunction of the speech motor system. We found that the patient showed a normal phonemic categorical boundary when discriminating two non-words that differ by a minimal pair (e.g., ADA-AGA). However, using the same stimuli, the patient was unable to identify or label the non-word stimuli (using a button-press response). A control task showed that he could identify speech sounds by speaker gender, ruling out a general labelling impairment. These data suggest that while the motor system is not causally involved in perception of the speech signal, it may be used when other cues (e.g., meaning, context) are not available.	\N	\N
25970594	Previous studies investigating speech perception in noise have typically been conducted with static masker positions. The aim of this study was to investigate the effect of spatial separation of source and masker (spatial release from masking, SRM) in a moving masker setup and to evaluate the impact of adaptive beamforming in comparison with fixed directional microphones in cochlear implant (CI) users. Speech reception thresholds (SRT) were measured in S0N0 and in a moving masker setup (S0Nmove) in 12 normal hearing participants and 14 CI users (7 subjects bilateral, 7 bimodal with a hearing aid in the contralateral ear). Speech processor settings were a moderately directional microphone, a fixed beamformer, or an adaptive beamformer. The moving noise source was generated by means of wave field synthesis and was smoothly moved in a shape of a half-circle from one ear to the contralateral ear. Noise was presented in either of two conditions: continuous or modulated. SRTs in the S0Nmove setup were significantly improved compared to the S0N0 setup for both the normal hearing control group and the bilateral group in continuous noise, and for the control group in modulated noise. There was no effect of subject group. A significant effect of directional sensitivity was found in the S0Nmove setup. In the bilateral group, the adaptive beamformer achieved lower SRTs than the fixed beamformer setting. Adaptive beamforming improved SRT in both CI user groups substantially by about 3 dB (bimodal group) and 8 dB (bilateral group) depending on masker type. CI users showed SRM that was comparable to normal hearing subjects. In listening situations of everyday life with spatial separation of source and masker, directional microphones significantly improved speech perception with individual improvements of up to 15 dB SNR. Users of bilateral speech processors with both directional microphones obtained the highest benefit.	\N	\N
26027328	The parallel psychophysical and MMN study focused at the sensitivity of human hearing system to variations in velocity of sound image movement. The motion of sound stimuli with various velocities in the 450 deg/s to 732 deg/s range in increments of 6 deg/s to the left or to the right from the head midline was simulated by introducing linear changes of interaural delay into dichotic stimuli. The psychophysical experiments were designed according to the 2-alternative forced choice paradigm. The subjects were presented by pairs of moving stimuli and were asked to decide which moved faster. The stimuli created for the present study ensured that the subjects performed the discrimination task without relying on associated cues of sound displacement or duration. The psychophysical measures were compared with electrophysiological indexes of sound processing (auditory evoked responses (ERPs) and mismatch negativity (MMN)). Significant MMN was elicited by the difference of 170 deg/s between the reference and test velocity, which corresponded to the relative velocity increase of 38%. At the same time, the difference thresholds for velocity were much higher and exceeded 50%. The results suggest that MMN magnitude depended on the velocity difference between standard and deviant stimuli and was more sensitive to velocity difference than psychophysical measure.	\N	\N
26067532	In peripheral vision, objects that are easily discriminated on their own become less discriminable in the presence of surrounding clutter. This phenomenon is known as crowding.The neural mechanisms underlying crowding are not well understood. Better insight might come from single-neuron recording in nonhuman primates, provided they exhibit crowding; however, previous demonstrations of crowding have been confined to humans. In the present study, we set out to determine whether crowding occurs in rhesus macaque monkeys. We found that animals trained to identify a target letter among flankers displayed three hallmarks of crowding as established in humans. First, at a given eccentricity, increasing the spacing between the target and the flankers improved recognition accuracy. Second, the critical spacing, defined as the minimal spacing at which target discrimination was reliable, was proportional to eccentricity. Third, the critical spacing was largely unaffected by object size. We conclude that monkeys, like humans, experience crowding. These findings open the door to studies of crowding at the neuronal level in the monkey visual system.	\N	\N
26075675	Vibroplasty has offered a new modality of hearing rehabilitation in patients with mixed, conductive, and sensorineural hearing loss who cannot wear hearing aids. Potentially, the positioning of the floating mass transducer (FMT) in vibroplasty surgery has a critical effect on hearing outputs. In this study, the impact on hearing outputs and coupling efficiency are evaluated by comparing various vibroplasty applications in the middle ear. No other study to date has examined the coupling efficiency of round window (RW) versus an ossicular vibroplasty application. Prospective cohort study of patients with underlying ear pathologies who were not able to wear hearing aids. This is an ongoing prospective study of 16 patients. All patients had a standard audiological test battery. Direct drive transfer function analysis results were correlated with bone conduction thresholds to assess the efficiency of the FMT coupling. Speech perception in quiet and quality of life measure questionnaires were used to assess outcomes. Nine patients had round window vibroplasty, six patients had stapes vibroplasty, and one patient had traditional incus vibroplasty. Patients with a soft tissue coupler between the FMT and the RW had significantly reduced coupling efficiency. Patients who had direct RW contact had significantly improved coupling efficiency. Patients who underwent stapes or incus vibroplasty had the greatest coupling efficiency. This study demonstrates that attachment to the stapes or incus provides the best coupling when compared to round window vibroplasty. When applicable, stapes or incus coupling should be the first choice when implementing vibroplasty.	\N	\N
26184883	Communication by sounds requires that the communication channels (i.e. speech/speakers and other sound sources) had been established. This allows to separate concurrently active sound sources, to track their identity, to assess the type of message arriving from them, and to decide whether and when to react (e.g., reply to the message). We propose that these functions rely on a common generative model of the auditory environment. This model predicts upcoming sounds on the basis of representations describing temporal/sequential regularities. Predictions help to identify the continuation of the previously discovered sound sources to detect the emergence of new sources as well as changes in the behavior of the known ones. It produces auditory event representations which provide a full sensory description of the sounds, including their relation to the auditory context and the current goals of the organism. Event representations can be consciously perceived and serve as objects in various cognitive operations.	\N	\N
26222939	To compare children with typical language development (TLD) and evolutional phonological disorder (EPD) regarding the phonemic discrimination and the linguistic performance of language levels (morphological, syntactic, semantic, and perceptual and productive vocabulary). The sample comprised 36 children, aged between 5 years and 7 years and 11 months, with TLD and EPD. Children with EPD were awaiting care in the speech units of two higher education institutions and children with TLD were screened in public schools. For inclusion in the study, the criteria were the following: being authorized by the informed consent and being within the required age group. After the inclusion of children, all subjects underwent the phonemic discrimination test with figures, to the average phrase value test, which assesses the morphosyntactic and semantic/lexical aspects, and the expressive vocabulary test. For statistical evaluation of the influence of variables, Spearman's nonparametric correlation coefficient was used, and for comparison between the groups regarding evaluation performance, Mann-Whitney test was used. Only children with EPD showed influence of phonemic discrimination in other linguistic levels. In addition, a significant difference was observed between the performances of both groups in relation to the phonemic discrimination, vocabulary, and all levels assessed in the questions and description modality. The comparison between both groups showed a statistically significant difference in phonemic discrimination and morphosyntactic and lexical/semantic development, with better performance in the TLD group.	\N	\N
26222946	To analyze the intra- and inter-rater agreement for visual analog scale and numerical scale in task of sustained vowel and to determine numerical cutoff points to visual analog scale corresponding to the degrees of the numeric scale. We selected 205 samples of the usual task of the sustained vowel /a/. Six voice specialists rated the overall degree of vocal deviation, first by visual analog scale and, after two days, by the numeric scale. The results obtained by both scales were compared and the intra- and inter-rater agreement, the correlation between the scales, and the estimated cutoff points using the intraclass correlation and concordance Kappa coefficients, the Spearman coefficient, and analysis of variance, and the values of sensitivity and specificity were analyzed. A strong correlation was observed between the scales. The following numerical cutoff values were found for visual analog scale corresponding to the numerical scale: neutral (degree zero) - 0 to 34 mm; mild (degree one) - 34.1 to 51 mm; moderate (degree two) - 51.1 to 63.5 mm; intense (degree three) - 63.6 to 77.5 mm; and extreme (degree four) - above 77.5 mm. The visual analog scale and numerical scale showed a strong correlation, being observed the greater intra- and inter-rater agreement in visual analog scale. Numerical cutoff values for visual analog scale were found. This correlation enables the comparison between the results found in the evaluation of the overall degree of vocal deviation by both scales, which are widely used in research and in the clinical speech therapy routine.	\N	\N
26356376	During dental treatments, patients may experience negative emotions associated with the procedure. This study was conducted with the aim of using functional magnetic resonance imaging (fMRI) to visualize cerebral cortical stimulation among dental patients in response to auditory stimuli produced by ultrasonic scaling and power suction equipment. Subjects (n = 7) aged 23-35 years were recruited for this study. All were right-handed and underwent clinical pure-tone audiometry testing to reveal a normal hearing threshold below 20 dB hearing level (HL). As part of the study, subjects initially underwent a dental calculus removal treatment. During the treatment, subjects were exposed to ultrasonic auditory stimuli originating from the scaling handpiece and salivary suction instruments. After dental treatment, subjects were imaged with fMRI while being exposed to recordings of the noise from the same dental instrument so that cerebral cortical stimulation in response to aversive auditory stimulation could be observed. The independent sample confirmatory t-test was used. Subjects also showed stimulation in the amygdala and prefrontal cortex, indicating that the ultrasonic auditory stimuli elicited an unpleasant response in the subjects. Patients experienced unpleasant sensations caused by contact stimuli in the treatment procedure. In addition, this study has demonstrated that aversive auditory stimuli such as sounds from the ultrasonic scaling handpiece also cause aversive emotions. This study was indicated by observed stimulation of the auditory cortex as well as the amygdala, indicating that noise from the ultrasonic scaling handpiece was perceived as an aversive auditory stimulus by the subjects. Subjects can experience unpleasant sensations caused by the sounds from the ultrasonic scaling handpiece based on their auditory stimuli.	\N	\N
26380996	The purpose was to evaluate brain plasticity that contributes to speech performance after cochlear implantation (CI) in postlingual elderly (>60 years) patients. Fifteen elderly postlingual deaf patients who underwent preoperative brain fluorodeoxyglucose positron emission tomography (FDG-PET) and were followed-up for more than 1 year after CI were included. The mean age of these patients was 64.6 years (range, 60-80 years). Based on their sentence score at 1 year after CI surgery, the patients were classified into two groups: poor performers (CID score of <80) and good performers (CID score of ≥80). The duration of deafness, age at operation, preoperative residual hearing, and preoperative brain metabolism were analyzed. SPM5 software was used for FDG-PET image preprocessing and statistical analysis. Neither deafness duration nor preoperative residual hearing was associated with speech performance. The age at operation had little association with speech performance. Deaf patients whose brain metabolism was higher in frontotemporal regions became good CI users but those with higher metabolism in visual association areas became poor CI users. No significant cortical area of higher metabolism was associated with the duration of deafness. Overactivation in the visual processing pathway correlated with a poor CI outcome at 1 year. Deaf patients who are going to be poorer performers with CI devices maintain visual information processing during preoperative silent resting periods.	\N	\N
26381009	The occurrence of oval window atresia is a rare anomaly with conductive hearing loss. Traditional atresia surgeries involve challenging surgical techniques with risks of irreversible inner ear damage. Recent reports on Bonebridge (Medel, Innsbruck, Austria), a novel implantable bone conduction hearing aid system, assert that the device is safe and effective for conductive hearing loss. We present a case of Bonebridge implantation in an eight-year-old girl with bilateral oval window atresia.	\N	\N
26382004	Previewing distracters enhances the efficiency of visual search. Watson and Humphreys (1997) proposed that the preview benefit rests on visual marking, a mechanism which actively encodes distracter locations at preview and inhibits them afterwards at search. As Watson and Humphreys did, we used a letter-color search task to study constraints of visual marking in conjunction search and near-efficient single-feature search with single-colored and homogeneous distracter letters. Search performance was measured for fixed target and distracter features (block design) and for randomly changed features across trials (random design). In single-feature search there was a full preview benefit for both block and random designs. In conjunction search a full preview benefit was obtained only for the block design; randomly changing target and distracter features disrupted the preview benefit. However, the preview benefit was restored when the distracters were organized in spatially coherent blocks. These findings imply that the temporal segregation of old and new items is sufficient for visual marking in near-efficient single-feature search, while in conjunction search it is not. We propose a supplanting grouping principle for the preview benefit: When the new items add a new color, conjunction search is initialized and attentional resources are withdrawn from the marking mechanism. Visual marking can be restored by a second grouping principle that joins with temporal asynchrony. This principle can be either spatial or feature based. In the case of the latter, repetition priming is necessary to establish joint grouping by color and temporal asynchrony.	\N	\N
26463676	The effects of inner ear abnormality on audibility have been explored since the early 20th century when sound detection measures were first used to define and quantify 'hearing loss'. The development in the 1970s of objective measures of cochlear hair cell function (cochlear microphonics, otoacoustic emissions, summating potentials) and auditory nerve/brainstem activity (auditory brainstem responses) have made it possible to distinguish both synaptic and auditory nerve disorders from sensory receptor loss. This distinction is critically important when considering aetiology and management. In this review we address the clinical and pathophysiological features of auditory neuropathy that distinguish site(s) of dysfunction. We describe the diagnostic criteria for: (i) presynaptic disorders affecting inner hair cells and ribbon synapses; (ii) postsynaptic disorders affecting unmyelinated auditory nerve dendrites; (iii) postsynaptic disorders affecting auditory ganglion cells and their myelinated axons and dendrites; and (iv) central neural pathway disorders affecting the auditory brainstem. We review data and principles to identify treatment options for affected patients and explore their benefits as a function of site of lesion.	\N	\N
22284837	Best practices concerning the audiological management of the child diagnosed with auditory neuropathy spectrum disorder (ANSD) have not been definitively defined nor fully understood. One reason is that previous studies have demonstrated conflicting findings regarding the outcomes of cochlear implantation for children with ANSD. Thus, the question remains whether children with ANSD are able to achieve similar outcomes following cochlear implantation as those children with sensorineural hearing loss (SNHL). To assess speech perception outcomes for children with cochlear implants who have a diagnosis of ANSD as well as their age-matched peers who have sensorineural hearing loss. Retrospective study Thirty-five subject pairs (n = 70) ranging in age at implant activation from to 10 to 121 mo (mean 39.2 mo) were included in this retrospective study. Subjects were matched on variables including age at initial implant activation and months of implant use at postoperative test point. Speech recognition scores for monosyllabic and multisyllabic stimuli were compared across the subject groups. For those not developmentally and/or linguistically ready for completion of open-set speech recognition testing with recorded stimuli, GASP (Glendonald Auditory Screening Procedure) word recognition and/or questionnaire data using either the LittlEARS or Meaningful Auditory Integration Scale were compared across the groups. Statistical analysis using a repeated-measures analysis of variance (ANOVA) evaluated the effects of etiology (ANSD or SNHL) on postoperative outcomes. The results of this study demonstrate that children with ANSD can clearly benefit from cochlear implantation and that their long-term outcomes are similar to matched peers with SNHL on measures of speech recognition. There were no significant differences across the ANSD and SNHL groups on any of the tested measures. Cochlear implantation is a viable treatment option for children with a diagnosis of ANSD who are not making auditory progress with hearing aids that have been fit using the Desired Sensation Level method (DSL v5.0). Expected outcomes of cochlear implantation for children with ANSD, excluding children with cochlear nerve deficiency, are no different than for children with non-ANSD SNHL. These results are important for counseling families on the expected outcomes and realistic expectations following cochlear implantation for children with ANSD who demonstrate no evidence of cochlear nerve deficiency.	\N	\N
20044890	The present study aimed to examine the influence of musical expertise on the metric and semantic aspects of speech processing. In two attentional conditions (metric and semantic tasks), musicians listened to short sentences ending in trisyllabic words that were semantically and/or metrically congruous or incongruous. Both ERPs and behavioral data were analyzed and the results were compared to previous nonmusicians' data. Regarding the processing of meter, results showed that musical expertise influenced the automatic detection of the syllable temporal structure (P200 effect), the integration of metric structure and its influence on word comprehension (N400 effect), as well as the reanalysis of metric violations (P600 and late positivities effects). By contrast, results showed that musical expertise did not influence the semantic level of processing. These results are discussed in terms of transfer of training effects from music to speech processing.	\N	\N
20117764	We present new evidence based on fMRI for the existence and neural architecture of an abstract supramodal language system that can integrate linguistic inputs arising from different modalities such that speech and print each activate a common code. Working with sentence material, our aim was to find out where the putative supramodal system is located and how it responds to comprehension challenges. To probe these questions we examined BOLD activity in experienced readers while they performed a semantic categorization task with matched written or spoken sentences that were either well-formed or contained anomalies of syntactic form or pragmatic content. On whole-brain scans, both anomalies increased net activity over non-anomalous baseline sentences, chiefly at left frontal and temporal regions of heteromodal cortex. The anomaly-sensitive sites correspond approximately to those that previous studies (Michael et al., 2001; Constable et al., 2004) have found to be sensitive to other differences in sentence complexity (object relative minus subject relative). Regions of interest (ROIs) were defined by peak response to anomaly averaging over modality conditions. Each anomaly-sensitive ROI showed the same pattern of response across sentence types in each modality. Voxel-by-voxel exploration over the whole brain based on a cosine similarity measure of common function confirmed the specificity of supramodal zones.	\N	\N
20146608	The neural responses to sensory consequences of a self-produced motor act are suppressed compared with those in response to a similar but externally generated stimulus. Previous studies in the somatosensory and auditory systems have shown that the motor-induced suppression of the sensory mechanisms is sensitive to delays between the motor act and the onset of the stimulus. The present study investigated time-dependent neural processing of auditory feedback in response to self-produced vocalizations. ERPs were recorded in response to normal and pitch-shifted voice auditory feedback during active vocalization and passive listening to the playback of the same vocalizations. The pitch-shifted stimulus was delivered to the subjects' auditory feedback after a randomly chosen time delay between the vocal onset and the stimulus presentation. Results showed that the neural responses to delayed feedback perturbations were significantly larger than those in response to the pitch-shifted stimulus occurring at vocal onset. Active vocalization was shown to enhance neural responsiveness to feedback alterations only for nonzero delays compared with passive listening to the playback. These findings indicated that the neural mechanisms of auditory feedback processing are sensitive to timing between the vocal motor commands and the incoming auditory feedback. Time-dependent neural processing of auditory feedback may be an important feature of the audio-vocal integration system that helps to improve the feedback-based monitoring and control of voice structure through vocal error detection and correction.	\N	\N
20347261	In this study, the subjective and objective voice measures of seven female physical education student teachers during a semester of student teaching were investigated. The participants completed the voice measures at three data collection time points: baseline, middle, and end of the semester. The voice measures included acoustic and aerodynamic data, perceptual rating scales of vocal quality and vocal fatigue, an end-of-semester questionnaire, and the Voice Handicap Index. Results demonstrated that the subjective and objective voice measures changed at the middle and the end of the semester as compared with those at baseline. The change in the voice measures may suggest that the vocal mechanism was adapting to the increased vocal demands of teaching physical education.	\N	\N
20411315	Noisy recordings of dialogue often serve as evidence in criminal proceedings. The present article explores the ability of two types of contextual information, currently present in the legal system, to bias subjective interpretations of such evidence. The present experiments demonstrate that the general context of the legal system and the presence of transcripts of the recorded speech are both able to bias interpretations of degraded & benign recordings into interpretable & incriminating. Furthermore we demonstrate a curse of knowledge whereby people become miscalibrated to the true quality of degraded recordings when provided transcripts. Current methods of dealing with auditory evidence are insufficient to mollify the effects of biasing information within the criminal justice system.	\N	\N
20433240	On the basis of results from behavioral studies that spatial attention improves the exclusion of external noise in the target region, we predicted that attending to a spatial region would reduce the impact of external noise on the BOLD response in corresponding cortical areas, seen as reduced BOLD responses in conditions with large amounts of external noise but relatively low signal, and increased dynamic range of the BOLD response to variations in signal contrast. We found that, in the presence of external noise, covert attention reduced the trial-by-trial BOLD response by 15.5-18.9% in low signal contrast conditions in V1. It also increased the BOLD dynamic range in V1, V2, V3, V3A/B, and V4 by a factor of at least three. Overall, covert attention reduced the impact of external noise by about 73-85% in these early visual areas. It also increased the contrast gain by a factor of 2.6-3.8.	\N	\N
20576373	Patients with systemic lupus erythematosus (SLE) may develop hearing and balance disorders as a result of the immune-mediated inner ear damage due to vasculitis or ototoxicity of drugs used in SLE treatment. The aim of the study was evaluation of the hearing organ disorders in patients with SLE with particular regard to their prevalence and relationship to duration and severity of disease. The severity was assessed from involvement of organs that resulted in poorer SLE outcome, i.e. kidneys and central nervous system (CNS), and from the presence of antibodies associated with unfavourable SLE prognosis. Thirty-five unselected, consecutive patients (33 women, two men, mean age 47.8 years) with SLE diagnosed in compliance to the international diagnostic criteria of the American Rheumatism Association (1982) were enrolled into the study. The control group consisted of 30 otologically healthy persons matched to the SLE group for age and sex. Case history was recorded for all patients from questionnaire data and laryngological examinations were performed, followed by pure-tone, speech and impedance audiometry and auditory brainstem response audiometry (ABR). In the anamnesis 71.4% of patients reported vertigo, 62.9% headaches, 40% tinnitus, 25.7% hyperacusis, 17.1% hearing loss and 2.9% ear fullness. It was found that SLE patients had a significantly poorer mean hearing thresholds than the control group for all frequencies, except for 500; 2000 and 4000 Hz. Longer ABR latency averages were observed in the group of SLE patients compared to control. Ten patients (28.6%) developed high-frequency and symmetric sensorineural hearing loss (SNHL). Significant positive correlation between mean air-conduction hearing thresholds and SLE duration (r = 0.46, p < 0.001) was found. After taking age into consideration, hearing acuity in SLE was related to duration of disease in younger patients. Furthermore, no relation was seen between hearing level and severity of disease. Auditory system involvement ought to be considered as one of elements of the clinical picture of systemic lupus erythematosus while determination of its character, original or secondary, requires further research.	\N	\N
20599334	The children with difficulty in receiving sounds presented at rapid rates in speech sounds and language learning period, may have delay in speech sounds and language development due to hearing speech sounds not clearly. Auditory temporal processing (ATP) is the ability to perceive auditory signals of brief duration accurately when presented at rapid rates. ATP can be evaluated by the random gap detection test (RGDT), which detects a brief gap between two stimuli. In this study, we investigated performance of children with previous language delay (PLD), currently having disorders in more than one speech sounds, on random gap detection test (RGDT) and RGDT-expanded (RGDT-EXP) tests. 12 children (8 male, 4 female) with previous language delay (PLD) and complaint of expressing speech sounds distorted, were included into the study. They had applied language training for at least one-year period in the past and in the current time, their language development is normal. They expressed one or more speech sounds as distorted. The control group consisted of 10 normal hearing children with normal phonological development and language matched for age; and who had not PLD (5 male, 5 female). Children language levels were evaluated by Preschool Language Scale-4 test; or Clinical evaluation of language fundamentals, fourth edition (CELF-4) according to child's age. Speech sounds development was assessed by Speech Sound Development Test (SSDT). They were applied RGDT and/if necessary, RGDT-EXP. Each child responded whether he/she heard one or two tones. Their responses were taken as verbally and/or hold up one finger or two fingers. In the second test, they were applied speech discrimination test in quiet environment and in noise. Gap detection thresholds (GDTs) were detected at 500-4000 Hz; and Composite GDTs (CGDTs) were found for the study and control groups. GDT/CGDT > 20 ms was considered as abnormal for temporal processing disorder. In the study group with PLD, mean of the GDTs were all over the normal limits; and in control group, mean of GDTs were all in normal limits. The difference between the mean GDTs of the study group were significantly higher than the control groups at all frequencies of 500-4000 Hz. In PLD group, CGDT (103.53 ± 11.63 ms) was significantly higher than that of the control group, (10.35 ± 0.65 ms) (p=0.021). The children with PLD have difficulties in perception of speech sounds at a certain rate, even they have not language learning difficulties. Therefore, difficulty in distinguishing of speech sounds may cause especially receptive language development delay. We believe that perception of the speech sounds and language in a certain speed; and temporally degraded speech programmes should be incorporated into the training programme and may help to prevent delays.	\N	\N
20617885	The present study investigated the effects of auditory selective attention on the processing of syntactic information in music and speech using event-related potentials. Spoken sentences or musical chord sequences were either presented in isolation, or simultaneously. When presented simultaneously, participants had to focus their attention either on speech, or on music. Final words of sentences and final harmonies of chord sequences were syntactically either correct or incorrect. Irregular chords elicited an early right anterior negativity (ERAN), whose amplitude was decreased when music was simultaneously presented with speech, compared to when only music was presented. However, the amplitude of the ERAN-like waveform elicited when music was ignored did not differ from the conditions in which participants attended the chord sequences. Irregular sentences elicited an early left anterior negativity (ELAN), regardless of whether speech was presented in isolation, was attended, or was to be ignored. These findings suggest that the neural mechanisms underlying the processing of syntactic structure of music and speech operate partially automatically, and, in the case of music, are influenced by different attentional conditions. Moreover, the ERAN was slightly reduced when irregular sentences were presented, but only when music was ignored. Therefore, these findings provide no clear support for an interaction of neural resources for syntactic processing already at these early stages.	\N	\N
20642737	Acoustic and visual interceptive actions were tested in this research by comparing the performance of blind, blind-folded, and sighted individuals. An indirect interception method was employed in which the participant had to roll an intercepting ball towards a moving target on a perpendicular track. The interception task used conditions that varied the speed, rolling distance, and target size/intensity. While performance was highly consistent and accurate for visual participants in this research, the blind and blind-folded participants demonstrated much more performance variability in response to changes in speed and distance. Manipulation of target size and intensity did not affect judgments, however performance tended to be more accurate at shorter distances and with faster target speeds. Results from this research are discussed in terms of their implications for tau in acoustic interception, and the use of spatial and temporal cues for guiding interceptive actions.	\N	\N
20644955	Two experiments investigated the effects of interval duration ratio on perception of local timing perturbations, accuracy of rhythm production, and phase correction in musicians listening to or tapping in synchrony with cyclically repeated auditory two-interval rhythms. Ratios ranged from simple (1:2) to complex (7:11, 5:13), and from small (5:13 = 0.38) to large (6:7 = 0.86). Rhythm production and perception exhibited similar ratio-dependent biases: rhythms with small ratios were produced with increased ratios, and timing perturbations in these rhythms tended to be harder to detect when they locally increased the ratio than when they reduced it. The opposite held for rhythms with large ratios. This demonstrates a close relation between rhythm perception and production. Unexpectedly, however, the neutral "attractor" was not the simplest ratio (1:2 = 0.50) but a complex ratio near 4:7 (= 0.57). Phase correction in response to perturbations was generally rapid and did not show the ratio-dependent biases observed in rhythm perception and production. Thus, phase correction operates efficiently and autonomously even in synchronization with rhythms exhibiting complex interval ratios.	\N	\N
20663254	Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex. Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants' level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants' arcuate fasciculus was used to predict their level of cortical suppression in the three conditions. While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient's level of N1 suppression was linearly related to the FA of their arcuate fasciculus. These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination.	\N	\N
20665720	The effect of stimulus modulation rate on the underlying neural activity in human auditory cortex is not clear. Human studies (using both invasive and noninvasive techniques) have demonstrated that at the population level, auditory cortex follows stimulus envelope. Here we examined the effect of stimulus modulation rate by using a rare opportunity to record both spiking activity and local field potentials (LFP) in auditory cortex of patients during repeated presentations of an audio-visual movie clip presented at normal, double, and quadruple speeds. Mean firing rate during evoked activity remained the same across speeds and the temporal response profile of firing rate modulations at increased stimulus speeds was a linearly scaled version of the response during slower speeds. Additionally, stimulus induced power modulation of local field potentials in the high gamma band (64-128 Hz) exhibited similar temporal scaling as the neuronal firing rate modulations. Our data confirm and extend previous studies in humans and anesthetized animals, supporting a model in which both firing rate, and high-gamma LFP power modulations in auditory cortex follow the temporal envelope of the stimulus across different modulation rates.	\N	\N
20666594	Spoken word recognition is achieved via competition between activated lexical candidates that match the incoming speech input. The competition is modulated by prelexical cues that are important for segmenting the auditory speech stream into linguistic units. One such prelexical cue that listeners rely on in spoken word recognition is phonotactics. Phonotactics defines possible combinations of phonemes within syllables or words in a given language. The present study aimed at investigating both temporal and topographical aspects of the neuronal correlates of phonotactic processing by simultaneously applying ERPs and functional near-infrared spectroscopy (fNIRS). Pseudowords, either phonotactically legal or illegal with respect to the participants' native language, were acoustically presented to passively listening adult native German speakers. ERPs showed a larger N400 effect for phonotactically legal compared to illegal pseudowords, suggesting stronger lexical activation mechanisms in phonotactically legal material. fNIRS revealed a left hemispheric network including fronto-temporal regions with greater response to phonotactically legal pseudowords than to illegal pseudowords. This confirms earlier hypotheses on a left hemispheric dominance of phonotactic processing most likely due to the fact that phonotactics is related to phonological processing and represents a segmental feature of language comprehension. These segmental linguistic properties of a stimulus are predominantly processed in the left hemisphere. Thus, our study provides first insights into temporal and topographical characteristics of phonotactic processing mechanisms in a passive listening task. Differential brain responses between known and unknown phonotactic rules thus supply evidence for an implicit use of phonotactic cues to guide lexical activation mechanisms.	\N	\N
20801079	Tinnitus can be considered an auditory phantom percept, in which patients hear an internal sound in the absence of any external sound source, mimicking tonal memory. Tinnitus however can be perceived exclusively uni- or bilaterally. The neurophysiological differences were investigated between unilateral and bilateral tinnitus using LORETA source localized resting state EEG recordings. The difference between unilateral and bilateral tinnitus is reflected by high frequency activity (beta and gamma) in the superior prefrontal gurus, right parahippocampus, right angular gyrus and right auditory cortex. Unilateral tinnitus is characterized by contralateral beta2 in the superior prefrontal gyrus in comparison to bilateral tinnitus, but gamma in comparison to non-tinnitus subjects. Bilateral tinnitus has delta activity in the ventrolateral prefrontal cortex in comparison to unilateral tinnitus, and bilateral beta1 in comparison to non-tinnitus subjects. Bilateral tinnitus is also characterized by bilateral frontopolar beta1 activity. Unilateral and bilateral tinnitus can be differentiated based on their resting state oscillation patterns: beta3 and gamma-band activity in the superior premotor cortex, parahippocampal area and angular gyrus seem to form the core of a spatial localization network involved in tinnitus. These differences should be taken into account when evaluating functional neuroimaging data relating to tinnitus.	\N	\N
20808225	The purpose of this study was to examine speech recognition through hearing aids for seven telephone listening conditions. Speech recognition scores were measured for 20 participants in six wireless routing transmission conditions and one acoustic telephone condition. In the wireless conditions, the speech signal was delivered to both ears simultaneously (bilateral speech) or to one ear (unilateral speech). The effect of changing the noise level in the nontest ear during unilateral conditions was also examined. Participants were fitted with hearing aids using both nonoccluding and occluding dome ear tips. Participants were seated in a room with background noise present and speech was transmitted to the participants without additional noise. There was no effect of changing the noise level in the nontest ear and no difference between unilateral wireless routing and acoustic telephone listening. For wireless transmission, bilateral presentation resulted in significantly better speech recognition than unilateral presentation. Bilateral wireless conditions allowed for significantly better recognition than the acoustic telephone condition for participants fitted with occluding ear tips only. Routing the signal to both hearing aids resulted in significantly better speech recognition than unilateral signal routing. Wireless signal routing was shown to be beneficial compared with acoustic telephone listening and in some conditions resulted in the best performance of all of the listening conditions evaluated. However, this advantage was only evident when the signal was routed to both ears and when hearing aid wearers were fitted with occluding domes. Therefore, it is expected that the benefits of this new wireless streaming technology over existing telephone coupling methods will be most evident clinically in hearing aid wearers who require more limited venting than is typically used in open canal fittings.	\N	\N
20812786	In contrast to visual object processing, relatively little is known about how the human brain processes everyday real-world sounds, transforming highly complex acoustic signals into representations of meaningful events or auditory objects. We recently reported a fourfold cortical dissociation for representing action (nonvocalization) sounds correctly categorized as having been produced by human, animal, mechanical, or environmental sources. However, it was unclear how consistent those network representations were across individuals, given potential differences between each participant's degree of familiarity with the studied sounds. Moreover, it was unclear what, if any, auditory perceptual attributes might further distinguish the four conceptual sound-source categories, potentially revealing what might drive the cortical network organization for representing acoustic knowledge. Here, we used functional magnetic resonance imaging to test participants before and after extensive listening experience with action sounds, and tested for cortices that might be sensitive to each of three different high-level perceptual attributes relating to how a listener associates or interacts with the sound source. These included the sound's perceived concreteness, effectuality (ability to be affected by the listener), and spatial scale. Despite some variation of networks for environmental sounds, our results verified the stability of a fourfold dissociation of category-specific networks for real-world action sounds both before and after familiarity training. Additionally, we identified cortical regions parametrically modulated by each of the three high-level perceptual sound attributes. We propose that these attributes contribute to the network-level encoding of category-specific acoustic knowledge representations.	\N	\N
20844257	It is important to ensure that hearing aid fitting strategies for infants take into account the infant's developing speech perception system. As a way of exploring this issue, this study examined how 6- and 9-month-olds with normal hearing perceive native-language speech in which the natural spectral shape was altered to emphasize either high-frequency (positive spectral tilt) or low-frequency (negative spectral tilt) information. Discrimination was tested using a visual habituation procedure. Forty-eight 6-month-olds and forty-eight 9-month-olds were presented with a fricative contrast, /f/-/s/, in 1 of 3 conditions: (a) as unmodified speech; (b) with a -6 dB/octave tilt; or (c) with a +6 dB/octave tilt. Six-month-olds showed evidence of discriminating /f/-/s/ in all 3 conditions, but 9-month-olds showed such evidence only in the unmodified condition. The findings suggest that the perceptual reorganization that emerges for consonants at the end of the first year affects 9-month-olds' discrimination of native speech sounds. Perceptual reorganization is usually indexed by a decline in the ability to discriminate nonnative speech sounds. In this study, 6-month-olds demonstrated an acoustic-based sensitivity to both modified and unmodified native speech sounds, but 9-month-olds were most sensitive to the unmodified speech sounds that adhered to the native spectral profile.	\N	\N
20864070	Auditory and visual processes demonstrably enhance each other based on spatial and temporal coincidence. Our recent results on visual search have shown that auditory signals also enhance visual salience of specific objects based on multimodal experience. For example, we tend to see an object (e.g., a cat) and simultaneously hear its characteristic sound (e.g., "meow"), to name an object when we see it, and to vocalize a word when we read it, but we do not tend to see a word (e.g., cat) and simultaneously hear the characteristic sound (e.g., "meow") of the named object. If auditory-visual enhancements occur based on this pattern of experiential associations, playing a characteristic sound (e.g., "meow") should facilitate visual search for the corresponding object (e.g., an image of a cat), hearing a name should facilitate visual search for both the corresponding object and corresponding word, but playing a characteristic sound should not facilitate visual search for the name of the corresponding object. Our present and prior results together confirmed these experiential association predictions. We also recently showed that the underlying object-based auditory-visual interactions occur rapidly (within 220ms) and guide initial saccades towards target objects. If object-based auditory-visual enhancements are automatic and persistent, an interesting application would be to use characteristic sounds to facilitate visual search when targets are rare, such as during baggage screening. Our participants searched for a gun among other objects when a gun was presented on only 10% of the trials. The search time was speeded when a gun sound was played on every trial (primarily on gun-absent trials); importantly, playing gun sounds facilitated both gun-present and gun-absent responses, suggesting that object-based auditory-visual enhancements persistently increase the detectability of guns rather than simply biasing gun-present responses. Thus, object-based auditory-visual interactions that derive from experiential associations rapidly and persistently increase visual salience of corresponding objects.	\N	\N
20883507	The prior entry hypothesis of attention holds that attended stimuli are perceived earlier than unattended stimuli. Whereas this speeding of perceptual processing has been repeatedly demonstrated for spatial attention, it has not been reported within the temporal domain. To fill this gap, we tested whether temporal attention accelerates auditory perceptual processing by employing event-related potentials as on-line indicators of perceptual processing. In a modified oddball paradigm, we presented a single tone in each trial, either a frequent standard tone or an infrequent deviant or target tone. Temporal attention to tones was manipulated via constant foreperiods. We observed that the latency of the N2, an event-related potential reflecting perceptual processing, is shortened by temporal attention. This result provides first evidence for the idea that temporal attention accelerates perceptual processing as suggested by the prior entry hypothesis.	\N	\N
20890206	Perception-in-noise deficits have been demonstrated across many populations and listening conditions. Many factors contribute to successful perception of auditory stimuli in noise, including neural encoding in the central auditory system. Physiological measures such as cortical auditory-evoked potentials (CAEPs) can provide a view of neural encoding at the level of the cortex that may inform our understanding of listeners' abilities to perceive signals in the presence of background noise. To understand signal-in-noise neural encoding better, we set out to determine the effect of signal type, noise type, and evoking paradigm on the P1-N1-P2 complex. Tones and speech stimuli were presented to nine individuals in quiet and in three background noise types: continuous speech spectrum noise, interrupted speech spectrum noise, and four-talker babble at a signal-to-noise ratio of -3 dB. In separate sessions, CAEPs were evoked by a passive homogenous paradigm (single repeating stimulus) and an active oddball paradigm. The results for the N1 component indicated significant effects of signal type, noise type, and evoking paradigm. Although components P1 and P2 also had significant main effects of these variables, only P2 demonstrated significant interactions among these variables. Signal type, noise type, and evoking paradigm all must be carefully considered when interpreting signal-in-noise evoked potentials. Furthermore, these data confirm the possible usefulness of CAEPs as an aid to understand perception-in-noise deficits.	\N	\N
20932562	Functional neuroimaging studies of syntactic processing have been interpreted as identifying the neural locations of parsing and interpretive operations. However, current behavioral studies of sentence processing indicate that many operations occur simultaneously with parsing and interpretation. In this review, we point to issues that arise in discriminating the effects of these concurrent processes from those of the parser/interpreter in neural measures and to approaches that may help resolve them.	\N	\N
20934172	This paper presents the results of three studies of intelligibility and quality of speech recorded through a bone conduction microphone (BCM). All speech signals were captured and recorded using a Temco HG-17 BCM. Twelve locations on or close to the skull were selected for the BCM placement. In the first study, listeners evaluated the intelligibility and quality of the bone conducted speech signals presented through traditional earphones. Listeners in the second study evaluated the intelligibility and quality of signals presented through a loudspeaker. In the third study the signals were reproduced through a bone conduction headset; however, signal evaluation was limited to speech intelligibility only. In all three studies, the Forehead and Temple BCM locations yielded the highest intelligibility and quality rating scores. The Collarbone location produced the least intelligible and lowest quality signals across all tested BCM locations.	\N	\N
20950509	To assess the hearing changes associated with sacrificing an intact ossicular chain during cholesteatoma surgery. We reviewed the operation notes of surgical procedures performed by the senior author between October 2000 and April 2006. Thirty-three cases were identified in which cholesteatoma surgery had been performed in the presence of a mobile, intact ossicular chain. One set of case notes was missing; therefore, 32 cases were included in the analysis. The ossicular chain was preserved in 17 cases (14 males and three females) and sacrificed in 15 (eight males and seven females). At the first post-operative assessment, a median air-bone gap deterioration of 3.3 dB was seen in patients in whom the ossicular chain had been sacrificed, while a median air-bone gap improvement of 3.3 dB was seen in those in whom the chain had been preserved. However, multivariable logistic regression analysis suggested that this difference in hearing outcomes was due to pre-operative hearing status, and that preservation of the ossicular chain did not lead to a better outcome. In cholesteatoma surgery, there is at most a marginal benefit in preserving the ossicular chain. In the current study, the better hearing outcomes associated with preservation of the ossicular chain were accounted for by patients' better pre-operative hearing status. This study did not demonstrate a difference in residual disease rate, but was underpowered to do so.	\N	\N
20961518	Researchers often conduct visual world studies to investigate how listeners integrate linguistic information with prior context. Such studies are likely to generate anticipatory baseline effects (ABEs), differences in listeners' expectations about what a speaker might mention that exist before a critical speech stimulus is presented. ABEs show that listeners have attended to and accessed prior contextual information in time to influence the processing of the critical speech stimulus. However, further evidence is required to show that the information actually did influence subsequent processing. ABEs can compromise the validity of inferences about information integration if they are not appropriately controlled. We discuss four solutions: statistical estimation, experimental control, elimination of "on-target" trials, and neutral gaze. An experiment compares the performance of these solutions, and suggests that the elimination of on-target trials introduces bias in the direction of ABEs, due to the statistical phenomenon of regression toward the mean. We conclude that statistical estimation, possibly coupled with experimental control, offers the most valid and least biased solution.	\N	\N
21060141	To investigate the effects of increased syntactic complexity and utterance length demands on speech production and comprehension in individuals with Parkinson's disease (PD) using behavioral and physiological measures. Speech response latency, interarticulatory coordinative consistency, accuracy of speech production, and response latency and accuracy on a receptive language task were analyzed in 16 individuals with PD and 16 matched control participants. Individuals with PD had higher oral motor coordination variability, took a longer time to initiate speech, and made more errors on the speaking task compared with the control group. They also received lower scores on the 2 complex conditions of the receptive language task. Increased length and syntactic complexity negatively affected performance in both groups of speakers. These findings provide a novel window into the speech deficits associated with PD by examining performance on longer, sentence-level utterances in contrast to earlier investigations of single-word or nonword productions. Speech motor control processes and language comprehension were adversely affected in the majority of our participants with mild to moderate PD compared to the control group. Finally, increased syntactic complexity and sentence length affected both the healthy aging and PD groups' speech production performance at the behavioral and kinematic levels.	\N	\N
21067852	Integration of simultaneous auditory and visual information about an event can enhance our ability to detect that event. This is particularly evident in the perception of speech, where the articulatory gestures of the speaker's lips and face can significantly improve the listener's detection and identification of the message, especially when that message is presented in a noisy background. Speech is a particularly important example of multisensory integration because of its behavioural relevance to humans and also because brain regions have been identified that appear to be specifically tuned for auditory speech and lip gestures. Previous research has suggested that speech stimuli may have an advantage over other types of auditory stimuli in terms of audio-visual integration. Here, we used a modified adaptive psychophysical staircase approach to compare the influence of congruent visual stimuli (brief movie clips) on the detection of noise-masked auditory speech and non-speech stimuli. We found that congruent visual stimuli significantly improved detection of an auditory stimulus relative to incongruent visual stimuli. This effect, however, was equally apparent for speech and non-speech stimuli. The findings suggest that speech stimuli are not specifically advantaged by audio-visual integration for detection at threshold when compared with other naturalistic sounds.	\N	\N
21073461	Impaired cognitive control has been implicated as an important developmental pathway to attention deficit/hyperactivity disorder (ADHD). Cognitive control is crucial to suppress interference resulting from conflicting information and can be measured by Stroop-like tasks. This study was conducted to gain insight into conflict processing in children with ADHD. Event-related potentials (ERPs) were recorded in an auditory Stroop task. Twenty-four children with ADHD were compared with 24 control children (aged 8-12 years). No deficit in interference control was found on the auditory Stroop task in children with ADHD. Children with ADHD responded more slowly, less accurately and more variably compared to controls. No differences between the groups occurred in the early conflict-related ERPs. However, the difference between the congruent and the incongruent condition in the 450-550 ms time window was absent in the ADHD group compared to controls. In addition, the conflict sustained potential was found frontally in the ADHD group but parietally in the control group. These ERP findings suggest that children with ADHD evaluate conflict to a lesser extent and differ in the way their brains select appropriate responses during conflict compared with controls.	\N	\N
21144500	Phonetic variation has been considered a barrier that listeners must overcome in speech perception, but has been proved beneficial in category learning. In this paper, I show that listeners use within-speaker variation to accommodate gross categorical variation. Within the perceptual learning paradigm, listeners are exposed to p-initial words in English produced by a native speaker of French. Critically, listeners are trained on these words with either invariant or highly-variable VOTs. While a gross boundary shift is made for participants exposed to the variable VOTs, no such shift is observed after exposure to the invariant stimuli. These data suggest that increasing variation improves the mapping of perceptually mismatched stimuli.	\N	\N
21150681	To evaluate the results of late cochlear implantation in prelingually deaf patients with significant residual hearing loss and to evaluate patient factors relevant to postoperative auditory outcomes in this patient group. Analysis of results of cochlear implantation using postoperative speech perception test scores per each condition. Tertiary referral center. Thirty-two subjects with severe to profound hearing loss that developed before the age of 4. Subjects were implanted at a mean age of 24.8 years (range, 16-44) with Nucleus CI24 (n = 18, 56%), Clarion HiRes 90K (n = 11, 34%), and Medel PULSA (n = 3, 10%) device. Details of etiology, duration of deafness, hearing aid history, hearing thresholds before operation, communication mode, and educational environment were investigated. Speech perception tests were performed preoperatively and 12 months after the operation. Postoperative speech perception test scores between different options within patient group. : The results showed significant improvement in open set speech perception (sentence) scores after the implantation (mean scores from 7.0 to 46.7, p < 0.05). Preoperative hearing of better ear and preoperative speech perception scores correlated with postoperative performances (r = -0.70 and r = 0.46, respectively, p < 0.05). Education and communication mode were also closely related to postoperative performances. In the group with poorer performances, preoperative hearing thresholds were significantly worse than those with better performances, and a larger portion of those patients attended special schools and used sign language. We found that residual auditory capacity in the better ear is an important factor in predicting outcomes after cochlear implantation in patients with prelingual hearing loss.	\N	\N
21161816	The present study focuses on language laterality as measured with dichotic listening (DL) to consonant-vowel syllables (CV syllables) in refugees with post-traumatic stress disorder (PTSD). PTSD is associated with impaired callosal transfer and with increased right hemisphere activation and impaired executive skills that could influence the processing of dichotic stimuli. A total of 22 participants with PTSD were compared to 23 participants without a diagnosis of PTSD. All participants had similar experiences of acts of war and political violence. They were tested with dichotic listening to CV syllables with free recall and directed attention following the forced attention paradigm. The PTSD group showed increased right ear advantage due to impaired left ear reporting and also smaller attention modulation compared to the control group, and the performance shared variance with self-report measures of arousal and intrusive memories. The results are discussed towards a model of impaired functionality of the frontal lobe and right hemisphere versus impaired callosal transfer, both yielding predictions for the processing of the left ear input and the ability to attention modulation of the performance.	\N	\N
21167923	Psychoacoustic studies have shown that complex tones containing resolved harmonics evoke stronger pitches than complex tones with only unresolved harmonics. Also, unresolved harmonics presented in alternating sine and cosine (ALT) phase produce a doubling of pitch. We examine here whether the temporal pattern of phase-locked neural activity reflected in the scalp recorded human frequency following response (FFR) preserves information relevant to pitch strength, and to the doubling of pitch for ALT stimuli. Results revealed stronger neural periodicity strength for resolved stimuli, although the effect of resolvability was weak compared to the effect observed behaviorally; autocorrelation functions and FFR spectra suggest a different pattern of phase-locked neural activity for ALT stimuli with resolved and unresolved harmonics consistent with the doubling of pitch observed in our behavioral estimates; and the temporal pattern of neural activity underlying pitch encoding appears to be similar at the auditory nerve (auditory nerve model response) and the rostral brainstem level (FFR). These findings suggest that the phase-locked neural activity reflected in the scalp recorded FFR preserves neural information relevant to pitch that could serve as an electrophysiological correlate of the behavioral pitch measure. The scalp recorded FFR may provide for a non-invasive analytic tool to evaluate neural encoding of complex sounds in humans.	\N	\N
21178803	To determine the response to treatment of pediatric patients diagnosed with autoimmune inner ear disease. Seven children who presented with sensorineural hearing loss and were diagnosed with autoimmune inner ear disease. Diagnosis through blood testing. Treatment with steroids and/or cytotoxic medication. Improvement in pure-tone average and speech discrimination scores on audiometric testing. Six of the 7 children (85.7%) improved with treatment, and the remaining patient had no measurable progression of disease. Children with autoimmune inner ear disease seem to benefit from treatment with steroids and/or cytotoxic medication. Although such medications must be used with caution in the pediatric population, they should not be withheld simply because of young age.	\N	\N
21196054	Humans and other animals can attend to one of multiple sounds and follow it selectively over time. The neural underpinnings of this perceptual feat remain mysterious. Some studies have concluded that sounds are heard as separate streams when they activate well-separated populations of central auditory neurons, and that this process is largely pre-attentive. Here, we argue instead that stream formation depends primarily on temporal coherence between responses that encode various features of a sound source. Furthermore, we postulate that only when attention is directed towards a particular feature (e.g. pitch) do all other temporally coherent features of that source (e.g. timbre and location) become bound together as a stream that is segregated from the incoherent features of other sources.	\N	\N
21198980	Important to Western tonal music is the relationship between pitches both within and between musical chords; melody and harmony are generated by combining pitches selected from the fixed hierarchical scales of music. It is of critical importance that musicians have the ability to detect and discriminate minute deviations in pitch in order to remain in tune with other members of their ensemble. Event-related potentials indicate that cortical mechanisms responsible for detecting mistuning and violations in pitch are more sensitive and accurate in musicians as compared with non-musicians. The aim of the present study was to address whether this superiority is also present at a subcortical stage of pitch processing. Brainstem frequency-following responses were recorded from musicians and non-musicians in response to tuned (i.e. major and minor) and detuned (± 4% difference in frequency) chordal arpeggios differing only in the pitch of their third. Results showed that musicians had faster neural synchronization and stronger brainstem encoding for defining characteristics of musical sequences regardless of whether they were in or out of tune. In contrast, non-musicians had relatively strong representation for major/minor chords but showed diminished responses for detuned chords. The close correspondence between the magnitude of brainstem responses and performance on two behavioral pitch discrimination tasks supports the idea that musicians' enhanced detection of chordal mistuning may be rooted at pre-attentive, sensory stages of processing. Findings suggest that perceptually salient aspects of musical pitch are not only represented at subcortical levels but that these representations are also enhanced by musical experience.	\N	\N
21211833	Metaphonological tasks, such as rhyme judgment, have been the primary tool for the investigation of the effects of orthographic knowledge on spoken language. However, it has been recently argued that the orthography effect in rhyme judgment does not reflect the automatic activation of orthographic codes but rather stems from sophisticated response strategies. Such a claim stands in sharp contrast with recent findings using event-related brain potentials (ERPs) in lexical and semantic tasks, which were taken to suggest that orthographic information occurs early enough to affect the core process of lexical access. Here, we show that the electrophysiological signature of the orthography effect in rhyme judgment is indeed different from the one obtained in online lexical or semantic tasks. That is, we did not find the orthography effect in the 300-350 ms time window which has previously been shown to process lexical information in the lexico-semantic tasks, but the effect appeared within the 175-250 ms and the 375-750 ms time-windows which we interpreted to reflect segmentation and decisional process, respectively. We conclude that the interactions between phonology and orthography are task-specific. Metaphonological tasks appear of limited use for studying the core processes and interactions that underlie lexical access.	\N	\N
21216396	We show that comprehenders' expectations about upcoming discourse coherence relations influence the resolution of local structural ambiguity. We employ cases in which two clauses share both a syntactic relationship and a discourse relationship, and hence in which syntactic and discourse processing might be expected to interact. An off-line sentence-completion study and an on-line self-paced reading study examined readers' expectations for high/low relative-clause attachments following implicit-causality and non-implicit causality verbs (John detests/babysits the children of the musician who…). In the off-line study, the widely reported low-attachment preference for English is observed in the non-implicit causality condition, but this preference gives way to more high attachments in the implicit-causality condition in cases in which (i) the verb's causally implicated referent occupies the high-attachment position and (ii) the relative clause provides an explanation for the event described by the matrix clause (e.g., …who are arrogant and rude). In the on-line study, a similar preference for high attachment emerges in the implicit-causality context-crucially, before the occurrence of any linguistic evidence that the RC does in fact provide an explanation-whereas the low-attachment preference is consistent elsewhere. These findings constitute the first demonstration that expectations about ensuing discourse coherence relationships can elicit full reversals in syntactic attachment preferences, and that these discourse-level expectations can affect on-line disambiguation as rapidly as lexical and morphosyntactic cues.	\N	\N
21236276	Categorical perception (CP) is a mechanism whereby non-identical stimuli that have the same underlying meaning become invariantly represented in the brain. Through behavioral identification and discrimination tasks, CP has been demonstrated to occur broadly across the auditory modality, including in perception of speech (e.g. phonemes) and music (e.g. chords) stimuli. Several functional imaging studies have linked CP of speech with activity in multiple regions of the left superior temporal sulcus (STS). As language processing is generally left-hemisphere dominant and, conversely, fine-grained spectral processing shows a right hemispheric bias, we hypothesized that CP of musical stimuli would be associated with right STS activity. Here, we used functional magnetic resonance imaging (fMRI) to test healthy, musically-trained volunteers as they (a) underwent a musical chord adaptation/habituation paradigm and (b) performed an active discrimination task on within- and between-category chord pairs, as well as an acoustically-matched, more continuously-perceived orthogonal sound set. As predicted, greater right STS activity was linked to categorical processing in both experimental paradigms. The results suggest that the left and right STS are functionally specialized and that the right STS may take on a key role in CP of spectrally complex sounds.	\N	\N
21236499	To evaluate the audiological outcome of children with congenital cytomegalovirus infection. In a prospective study, the hearing of ninety seven congenitally cytomegalovirus-infected children, born between January 2003 and July 2009, was systematically evaluated until the age of six, applying the Flemish CMV protocol. Depending on the age of the child, the protocol provides hearing evaluation by objective-, play- or conventional audiometry. Symptomatic children with hearing loss at birth were treated with ganciclovir, if parents consented. Seventy children had a pass on initial screening, 27 had unilateral or bilateral hearing loss. Within the normal hearing group, one asymptomatic and two symptomatic children developed late-onset hearing loss. Within the group with hearing loss, 8 children received ganciclovir, while 8 symptomatic and 11 asymptomatic children did not receive ganciclovir. As for the treated group, 37.5% of the children had stable hearing loss, one child had progressive and one child had fluctuating hearing loss. Improvement of hearing threshold occurred in 37.5% of the children. Among the untreated symptomatic children, hearing loss remained stable in 50%, while progression occurred in 37.5%. In the group of asymptomatic children with hearing loss, hearing loss was most commonly stable (72.7%). Within the group of normal hearing ears at birth (n=156), there is a significant better progression in pure tone average for ears of asymptomatic subjects in comparison to ears of symptomatic subjects (p≤0.0001). As for the group of ears with hearing loss at birth (n=38), analysis shows no evidence for a difference in pure tone average progression between the different groups (p=0.38). Cytomegalovirus infection may cause hearing loss, in both symptomatic and asymptomatic children. Our data show a significant difference, between both groups, in the progression of pure tone average of normal hearing ears at birth, in favor of the asymptomatic children. This is not the case for ears with hearing loss at birth. However, this may be due to the small number of ears in this group. Our data show the tendency that treatment with ganciclovir increases the likelihood of improvement and reduces the likelihood of deterioration of the hearing.	\N	\N
21241284	Several studies have found that women tend to demonstrate stronger preferences for masculine men as short-term partners than as long-term partners, though there is considerable variation among women in the magnitude of this effect. One possible source of this variation is individual differences in the extent to which women perceive masculine men to possess antisocial traits that are less costly in short-term relationships than in long-term relationships. Consistent with this proposal, here we show that the extent to which women report stronger preferences for men with low (i.e., masculine) voice pitch as short-term partners than as long-term partners is associated with the extent to which they attribute physical dominance and low trustworthiness to these masculine voices. Thus, our findings suggest that variation in the extent to which women attribute negative personality characteristics to masculine men predicts individual differences in the magnitude of the effect of relationship context on women's masculinity preferences, highlighting the importance of perceived personality attributions for individual differences in women's judgments of men's vocal attractiveness and, potentially, their mate preferences.	\N	\N
21251921	Recent neuroimaging studies proposed the importance of the anterior auditory pathway for speech comprehension. Its clinical significance is implicated by semantic dementia or pure word deafness. Neurodegenerative or cerebrovascular nature, however, precluded precise localization of the cortex responsible for speech perception. Electrical cortical stimulation could delineate such localization by producing transient, functional impairment. We investigated engagement of the left anterior temporal cortex in speech perception by means of direct electrical cortical stimulation. Subjects were two partial epilepsy patients, who underwent direct cortical stimulation as a part of invasive presurgical evaluations. Stimulus sites were coregistered to presurgical 3D-MRI, and then to MNI standard space for anatomical localization. Separate from the posterior temporal language area, electrical cortical stimulation revealed a well-restricted language area in the anterior part of the superior temporal sulcus and gyrus (aSTS/STG) in both patients. Auditory sentence comprehension was impaired upon electrical stimulation of aSTS/STG. In one patient, additional investigation revealed that the functional impairment was restricted to auditory sentence comprehension with preserved visual sentence comprehension and perception of music and environmental sounds. Both patients reported that they could hear the voice but not understand the sentence well (e.g., heard as a series of meaningless utterance). The standard coordinates of this restricted area at left aSTS/STG well corresponded with the coordinates of speech perception reported in neuroimaging activation studies in healthy subjects. The present combined anatomo-functional case study, for the first time, demonstrated that aSTS/STG in the language dominant hemisphere actively engages in speech perception.	\N	\N
21255123	To advance our understanding of the biological basis of speech-in-noise perception, we investigated the effects of background noise on both subcortical- and cortical-evoked responses, and the relationships between them, in normal hearing young adults. The addition of background noise modulated subcortical and cortical response morphology. In noise, subcortical responses were later, smaller in amplitude and demonstrated decreased neural precision in encoding the speech sound. Cortical responses were also delayed by noise, yet the amplitudes of the major peaks (N1, P2) were affected differently, with N1 increasing and P2 decreasing. Relationships between neural measures and speech-in-noise ability were identified, with earlier subcortical responses, higher subcortical response fidelity and greater cortical N1 response magnitude all relating to better speech-in-noise perception. Furthermore, it was only with the addition of background noise that relationships between subcortical and cortical encoding of speech and the behavioral measures of speech in noise emerged. Results illustrate that human brainstem responses and N1 cortical response amplitude reflect coordinated processes with regards to the perception of speech in noise, thereby acting as a functional index of speech-in-noise perception.	\N	\N
21261450	Many models of spoken word recognition posit that the acoustic stream is parsed into phoneme level units, which in turn activate larger representations [McClelland, J. L., & Elman, J. L. The TRACE model of speech perception. Cognitive Psychology, 18, 1-86, 1986], whereas others suggest that larger units of analysis are activated without the need for segmental mediation [Greenberg, S. A multitier theoretical framework for understanding spoken language. In S. Greenberg & W. A. Ainsworth (Eds.), Listening to speech: An auditory perspective (pp. 411-433). Mahwah, NJ: Erlbaum, 2005; Klatt, D. H. Speech perception: A model of acoustic-phonetic analysis and lexical access. Journal of Phonetics, 7, 279-312, 1979; Massaro, D. W. Preperceptual images, processing time, and perceptual units in auditory perception. Psychological Review, 79, 124-145, 1972]. Identifying segmental effects in the brain's response to speech may speak to this question. For example, if such effects were localized to relatively early processing stages in auditory cortex, this would support a model of speech recognition in which segmental units are explicitly parsed out. In contrast, segmental processes that occur outside auditory cortex may indicate that alternative models should be considered. The current fMRI experiment manipulated the phonotactic frequency (PF) of words that were auditorily presented in short lists while participants performed a pseudoword detection task. PF is thought to modulate networks in which phoneme level units are represented. The present experiment identified activity in the left inferior frontal gyrus that was positively correlated with PF. No effects of PF were found in temporal lobe regions. We propose that the observed phonotactic effects during speech listening reflect the strength of the association between acoustic speech patterns and articulatory speech codes involving phoneme level units. On the basis of existing lesion evidence, we interpret the function of this auditory-motor association as playing a role primarily in production. These findings are consistent with the view that phoneme level units are not necessarily accessed during speech recognition.	\N	\N
21261634	Tones that are self-generated elicit a smaller N1 than externally triggered tones. Typically, however, self-generated tones are also more predictable in time than externally triggered ones. The present study investigated whether the attenuated N1 can be explained by predictability based on the temporal relationship between action and effect. Participants listened to tones that were self-generated by a key-press or preceded by a visual cue. The tones followed the key-presses or cues after a fixed (predictable context) or variable delay (unpredictable context). Tones triggered by a key-press elicited a smaller N1 than tones following a visual cue. This finding suggests that the reduced N1 to self-generated tones is not merely due to the fact that the tone's timing can be predicted based on its temporal relationship to the key-press. Whether a tone was presented in a predictable or an unpredictable context did not affect the N1.	\N	\N
21264707	When two targets are presented in rapid succession at the same spatial location, processing of the first is highly efficient, while processing of the second is often profoundly impaired at brief inter-target intervals (attentional blink; AB). While the AB has been shown to impact many processes, it is still unclear whether this includes the ability to shift spatial attention. The present study examined this question using a more sensitive dependent measure than past studies; namely, response times. It also evaluated whether masking of the cue stimulus modulated the effect of the AB on spatial shifts. The results showed significant cueing effects on T2 response times that were strongly modulated by the AB. This supports suggested links between mechanisms underlying object processing and spatial shifts of attention.	\N	\N
21264734	The fast and accurate enumeration of a small set of objects, called subitizing, is thought to involve a different mechanism from other numerosity judgments, such as those based on estimation. In this report, we examine the subitizing limit using a novel enumeration task that obtained the perceived locations of enumerated objects. Observers were shown brief masked displays (50, 200, and 350 ms) of 2-9 small black discs randomly placed on a gray screen and then asked to place a marker where each disc had been located. The number of these markers provided an estimate of the number of items processed. This "pointing" methodology enabled observers to accurately "enumerate" displays containing up to six items in contrast with the four-item limit typically found when using standard reporting methods (and replicated here in Experiment 2). These results suggest a different account of the limits found in most subitizing and enumeration studies.	\N	\N
21272630	The auditory system can encode interaural delays in highpass-filtered complex sounds by phase locking to their slowly modulating envelopes. Spectrotemporal analysis of interaurally time-delayed highpass waveforms reveals the presence of a concomitant interaural level cue. The current study systematically investigated the contribution of time and concomitant level cues carried by positive and negative envelope slopes of a modified sinusoidally amplitude-modulated (SAM) high-frequency carrier. The waveforms were generated from concatenation of individual modulation cycles whose envelope peaks were extended by the desired interaural delay, allowing independent control of delays in the positive and negative modulation slopes. In experiment 1, thresholds were measured using a 2-interval forced-choice adaptive task for interaural delays in either the positive or negative modulation slopes. In a control condition, thresholds were measured for a standard SAM tone. In experiment 2, decision weights were estimated using a multiple-observation correlational method in a single-interval forced-choice task for interaural delays carried simultaneously by the positive, and independently, negative slopes of the modulation envelope. In experiment 3, decision weights were measured for groups of 3 modulation cycles at the start, middle, and end of the waveform to determine the influence of onset dominance or recency effects. Results were consistent across experiments: thresholds were equal for the positive and negative modulation slopes. Decision weights were positive and equal for the time cue in the positive and negative envelope slopes. Weights were also larger for modulations cycles near the waveform onset. Weights estimated for the concomitant interaural level cue were positive for the positive envelope slope and negative for the negative slope, consistent with exclusive use of time cues.	\N	\N
21272930	Using event-related potentials (ERPs), we investigated the N400 (an ERP component that occurs in response to meaningful stimuli) in children aged 8-10 years old and examined relationships between the N400 and individual differences in listening comprehension, word recognition and non-word decoding. Moreover, we tested the claim that the N400 effect provides a valuable indicator of behavioural vocabulary knowledge. Eighteen children were presented with picture-word pairs that were either 'congruent' (the picture depicted the spoken word) or 'incongruent' (they were unrelated). Three peaks were observed in the ERP waveform triggered to the onset of the picture-word stimuli: an N100 in fronto-central channels, an N200 in central-parietal channels and an N400 in frontal, central and parietal channels. In contrast to the N100 peak, the N200 and N400 peaks were sensitive to semantic incongruency with greater peak amplitudes for incongruent than congruent conditions. The incongruency effects for each peak correlated positively with listening comprehension but when the peak amplitudes were averaged across congruent/incongruent conditions they correlated positively with non-word decoding. These findings provide neurophysiological support for the position that sensitivity to semantic context (reflected in the N400 effect) is crucial for comprehension whereas phonological decoding skill relates to more general processing differences reflected in the ERP waveform. There were no correlations between ERP and behavioural measures of expressive or receptive vocabulary knowledge for the same items, suggesting that the N400 effect may not be a reliable estimate of vocabulary knowledge in children aged 8-10 years.	\N	\N
21275499	Hearing-aid users' problems with their own voice caused by occlusion are well known. Conversely, it remains essentially undocumented whether hearing-aid users expected not to have occlusion-related problems experience own-voice issues. To investigate this topic, a dedicated Own Voice Qualities (OVQ) questionnaire was developed and used in two experiments with stratified samples. In the main experiment, the OVQ was administered to 169 hearing-aid users (most of whom were expected not to have occlusion-related problems) and to a control group of 56 normally-hearing people. In the follow-up experiment, the OVQ was used in a cross-over study where 43 hearing-aid users rated own voice for an open fitting and a small-vent earmould fitting. The results from the main experiment show that hearing-aid users (without occlusion) have more problems than the normal-hearing controls on several dimensions of own voice. The magnitude of these differences was found to be generally larger than the differences observed between the open fitting and the small-vent fitting in the follow-up experiment. This suggests that own voice is a potentially important concern, even for hearing-aid users who are not expected to have occlusion-related problems.	\N	\N
21295773	Does extensive practice reduce or eliminate central interference in dual-task processing? We explored the reorganization of task architecture with practice by combining interference analysis (delays in dual-task experiment) and random-walk models of decision making (measuring the decision and non-decision contributions to RT). The main delay observed in the Psychologically Refractory Period at short stimulus onset asynchronies (SOA) values was largely unaffected by training. However, the range of SOAs over which this interference regime held diminished with learning. This was consistent with an overall shift observed in single-task performance from a highly variable decision time to a reliable (non-decision time) contribution to response time. Executive components involved in coordinating dual-task performance decreased (and became more stable) after extensive practice. The results suggest that extensive practice reduces the duration of central decision stages, but that the qualitative property of central seriality remains a structural invariant.	\N	\N
21299376	To implement a fast method for measuring psychophysical tuning curves (PTCs) for use in clinical applications, such as assessment of frequency selectivity and detection of dead regions in the cochlea. The method is based on that described by Sek et al (2005) and has been implemented in software that can be run on a PC with a good-quality sound card. In addition to the main narrowband noise masker, a lowpass noise masker can be generated to prevent detection of a distortion band corresponding to the simple difference tone. The software includes a routine for measuring the absolute threshold at the signal frequency and includes methods for estimating the frequency at the tip of the PTC. A PTC can typically be determined in about three minutes. A small amount of practice (two to three runs) may be required to achieve stable results. The software implementation allows PTCs to be measured quickly without a requirement for specialised equipment.	\N	\N
21305548	To investigate the level of hearing loss and the configuration of the mean audiometric curve over the course of Menière's disease, correcting the data according to patient age. A retrospective study of 3,963 hearing tests. Descriptive, longitudinal study of pure-tone audiometries of 237 patients at a tertiary hospital who had been diagnosed with definitive Menière's disease according to the American Academy of Otorhinolaryngology criteria. All audiometric results were age-corrected, and patients were followed for 1 to 31 years. In patients who had undergone surgery, only the data collected before the operation were assessed. In patients with unilateral disease, the mean hearing loss was characteristically low frequency, even in very advanced stages of the disease. Hearing loss was accentuated at 5 and 15 years from onset. In bilateral cases, hearing loss was slightly more severe and the average loss produced a flatter audiometric curve than in unilateral cases. In Menière's disease, audiometry results corrected for patient age show an inherent upward-sloping configuration of the mean audiometric curve at all time points during the disease. The hearing pattern differs between unilateral and bilateral disease. The audiometric curve configuration may be an indicator of future bilateral disease.	\N	\N
21305666	Both sighted and blind individuals can readily interpret meaning behind everyday real-world sounds. In sighted listeners, we previously reported that regions along the bilateral posterior superior temporal sulci (pSTS) and middle temporal gyri (pMTG) are preferentially activated when presented with recognizable action sounds. These regions have generally been hypothesized to represent primary loci for complex motion processing, including visual biological motion processing and audio-visual integration. However, it remained unclear whether, or to what degree, life-long visual experience might impact functions related to hearing perception or memory of sound-source actions. Using functional magnetic resonance imaging (fMRI), we compared brain regions activated in congenitally blind versus sighted listeners in response to hearing a wide range of recognizable human-produced action sounds (excluding vocalizations) versus unrecognized, backward-played versions of those sounds. Here, we show that recognized human action sounds commonly evoked activity in both groups along most of the left pSTS/pMTG complex, though with relatively greater activity in the right pSTS/pMTG by the blind group. These results indicate that portions of the postero-lateral temporal cortices contain domain-specific hubs for biological and/or complex motion processing independent of sensory-modality experience. Contrasting the two groups, the sighted listeners preferentially activated bilateral parietal plus medial and lateral frontal networks, whereas the blind listeners preferentially activated left anterior insula plus bilateral anterior calcarine and medial occipital regions, including what would otherwise have been visual-related cortex. These global-level network differences suggest that blind and sighted listeners may preferentially use different memory retrieval strategies when hearing and attempting to recognize action sounds.	\N	\N
21309643	To measure the mental health status of deaf adolescents with cochlear implants (CI). STUDY SAMPLE AND DESIGN: We used the "Strengths and Difficulties Questionnaire" (SDQ) to assess the mental health problems of 32 adolescents with CI (mean age 15.0 years) and 212 normal hearing peers (mean age 15.0 years). Parent and teacher ratings for the CI subjects (ES emotional symptoms, HA inattention-hyperactivity, CP conduct-problems and PBS pro-social behavior) did not differ significantly from the results of normal hearing peers. However, teachers rated significantly more cases as having peer problems (PP) and more cases as having very high (clinical) total difficulty scores (TDS) in the CI group. The SDQ results of the CI users correlated significantly with poor results in auditory performance and special school education. The age at CI implantation was not found to be a correlated with emotional, behavioral and social problems. Our findings indicate that the mental health of deaf adolescents with CI is comparable to that of normal hearing peers.	\N	\N
21315158	Music perception generally involves processing the frequency relationships between successive pitches and extraction of the melodic contour. Previous evidence has suggested that the 'ups' and 'downs' of melodic contour are categorically and automatically processed, but knowledge of the brain regions that discriminate different types of contour is limited. Here, we examined melodic contour discrimination using multivariate pattern analysis (MVPA) of fMRI data. Twelve non-musicians were presented with various ascending and descending melodic sequences while being scanned. Whole-brain MVPA was used to identify regions in which the local pattern of activity accurately discriminated between contour categories. We identified three distinct cortical loci: the right superior temporal sulcus (rSTS), the left inferior parietal lobule (lIPL), and the anterior cingulate cortex (ACC). These results complement previous findings of melodic processing within the rSTS, and extend our understanding of the way in which abstract auditory sequences are categorized by the human brain.	\N	\N
21316354	This study examined the electrophysiological correlates of auditory and visual working memory in children with Specific Language Impairments (SLI). Children with SLI and age-matched controls (11;9-14;10) completed visual and auditory working memory tasks while event-related potentials (ERPs) were recorded. In the auditory condition, children with SLI performed similarly to controls when the memory load was kept low (1-back memory load). As expected, when demands for auditory working memory were higher, children with SLI showed decreases in accuracy and attenuated P3b responses. However, children with SLI also evinced difficulties in the visual working memory tasks. In both the low (1-back) and high (2-back) memory load conditions, P3b amplitude was significantly lower for the SLI as compared to CA groups. These data suggest a domain-general working memory deficit in SLI that is manifested across auditory and visual modalities.	\N	\N
21325685	Our auditory system separates and tracks temporally interleaved sound sources by organizing them into distinct auditory streams. This streaming phenomenon is partly determined by physical stimulus properties but additionally depends on the internal state of the listener. As a consequence, streaming perception is often bistable and reversals between one- and two-stream percepts may occur spontaneously or be induced by a change of the stimulus. Here, we used functional MRI to investigate perceptual reversals in streaming based on interaural time differences (ITD) that produce a lateralized stimulus perception. Listeners were continuously presented with two interleaved streams, which slowly moved apart and together again. This paradigm produced longer intervals between reversals than stationary bistable stimuli but preserved temporal independence between perceptual reversals and physical stimulus transitions. Results showed prominent transient activity synchronized with the perceptual reversals in and around the auditory cortex. Sustained activity in the auditory cortex was observed during intervals where the ΔITD could potentially produce streaming, similar to previous studies. A localizer-based analysis additionally revealed transient activity time locked to perceptual reversals in the inferior colliculus. These data suggest that neural activity associated with streaming reversals is not limited to the thalamo-cortical system but involves early binaural processing in the auditory midbrain, already.	\N	\N
21327367	Identification of the second of two targets (T1, T2, inserted in a stream of distractors) is impaired when presented within 500 ms after the first (attentional blink, AB). Barring a T1-T2 task-switch, it is thought that T2 must be backward-masked to obtain an AB (Giesbrecht & Di Lollo, Journal of Experimental Psychology: Human Perception and Performance, 24, 1454-1466, 1998). We tested the hypothesis that Giesbrecht & Di Lollo's findings were vitiated by ceiling constraints arising from either response scale (experiment 1) or data limitations (experiment 2). In experiment 1, digit-distractors were replaced with pseudoletters to increase task difficulty, bringing performance below ceiling. An AB occurred without backward masking of T2. In experiment 2, a ceiling-free procedure estimated the number of noise dots needed for 80% T2 identification. An AB was revealed: fewer noise dots were required during the AB period than outside it. Both outcomes confirm that an AB can be obtained without either masking of T2 or task switching.	\N	\N
21335029	Brain-computer interface (BCI) is a developing, novel mode of communication for individuals with severe motor impairments or those who have no other options for communication aside from their brain signals. However, the majority of current BCI systems are based on visual stimuli or visual feedback, which may not be applicable for severe locked-in patients that have lost their eyesight or the ability to control their eye movements. In the present study, we investigated the feasibility of using auditory steady-state responses (ASSRs), elicited by selective attention to a specific sound source, as an electroencephalography (EEG)-based BCI paradigm. In our experiment, two pure tone burst trains with different beat frequencies (37 and 43 Hz) were generated simultaneously from two speakers located at different positions (left and right). Six participants were instructed to close their eyes and concentrate their attention on either auditory stimulus according to the instructions provided randomly through the speakers during the inter-stimulus interval. EEG signals were recorded at multiple electrodes mounted over the temporal, occipital, and parietal cortices. We then extracted feature vectors by combining spectral power densities evaluated at the two beat frequencies. Our experimental results showed high classification accuracies (64.67%, 30 commands/min, information transfer rate (ITR) = 1.89 bits/min; 74.00%, 12 commands/min, ITR = 2.08 bits/min; 82.00%, 6 commands/min, ITR = 1.92 bits/min; 84.33%, 3 commands/min, ITR = 1.12 bits/min; without any artifact rejection, inter-trial interval = 6s), enough to be used for a binary decision. Based on the suggested paradigm, we implemented a first online ASSR-based BCI system that demonstrated the possibility of materializing a totally vision-free BCI system.	\N	\N
21342695	The purpose of this exploratory study was to assess perceptions of quality of life for individuals with hearing impairment who have not consulted for services and their significant others who are in same-sex relationships vs. those who are in different-sex relationships. Data were collected on a total of 20 older couples: 10 in same-sex relationships and 10 in different-sex relationships. In each of the couples, one member self-identified as having hearing impairment. The couples completed an audiologic evaluation, a disease-specific quality of life questionnaire, and a short, structured interview (which served as a general measure of quality of life). No differences between the groups were found on demographic or audiologic variables. Differences between the groups and within the couples were found on the disease-specific and overall quality of life measures. Participants with hearing impairment in different-sex relationships reported significantly more total consequences of hearing impairment than those in the same-sex relationships. Differences were found in the rate of reporting for various contributors to overall quality of life and consequences of hearing impairment on quality of life. There was more congruity between same-sex couples than different-sex couples. There appear to be important differences in perceptions of both disease-specific and overall quality of life based on sexual orientation for older couples who have not consulted for hearing services. These differences can help inform clinical practice with this under-researched population. Readers will be able to: (1) Describe quality of life variables for individuals with hearing problems in same- and different-sex relationships, (2) understand the differences in quality of life variables between same- and different-sex couples, (3) consider the clinical implications of these quality of life variables.	\N	\N
21358012	The aim of the current study is to investigate hearing function in patients with allergic rhinitis. Fifty-eight patients with positive skin prick test (Group 1) (116 ears) and 31 subjects with negative skin prick test (62 ears) as group 2 were included. Pure tone audiometry at 250, 500, 1000, 2000, 4000 and 8000 Hz and immittance measures, including tympanometry and acoustic reflex tests, were performed in both groups. There was statistically significant difference between pure-tone threshold of the group 1 and group 2 at 8000 Hz (p< 0.05). Based on our study, the patients with allergic rhinitis had better hearing than the control group at 8000 Hz.	\N	\N
21361412	Perturbation analysis was used to determine the relative contribution of target enhancement and noise cancellation in the identification of rudimentary sound source in noise. In a two-interval, forced-choice procedure, listeners identified the impact sound produced by the larger of two stretched membranes as target. The noise on each presentation was the impact sound of a variable-sized plate. For four of five listeners, the relative weights on the noise were positive indicating enhancement, and for the remaining listeners, they were negative indicating cancellation. The results underscore the difficulty with evaluating models of masking solely in terms of measures of performance accuracy.	\N	\N
21361445	Low-frequency masking by intense high-frequency noise bands, referred to as remote masking (RM), was the first evidence to challenge energy-detection models of signal detection. Its underlying mechanisms remain unknown. RM was measured in five normal-hearing young-adults at 250, 350, 500, and 700 Hz using equal-power, spectrally matched random-phase noise (RPN) and low-noise noise (LNN) narrowband maskers. RM was also measured using equal-power, two-tone complex (TC2) and eight-tone complex (TC8). Maskers were centered at 3000 Hz with one or two equivalent rectangular bandwidths (ERBs). Masker levels varied from 80 to 95 dB sound pressure level in 5 dB steps. LNN produced negligible masking for all conditions. An increase in bandwidth in RPN yielded greater masking over a wider frequency region. Masking for TC2 was limited to 350 and 700 Hz for one ERB but shifted to only 700 Hz for two ERBs. A spread of masking to 500 and 700 Hz was observed for TC8 when the bandwidth was increased from one to two ERBs. Results suggest that high-frequency noise bands at high levels could generate significant low-frequency masking. It is possible that listeners experience significant RM due to the amplification of various competing noises that might have significant implications for speech perception in noise.	\N	\N
21361446	The additivity of nonsimultaneous masking was studied using Gaussian-shaped tone pulses (referred to as Gaussians) as masker and target stimuli. Combinations of up to four temporally separated Gaussian maskers with an equivalent rectangular bandwidth of 600 Hz and an equivalent rectangular duration of 1.7 ms were tested. Each masker was level-adjusted to produce approximately 8 dB of masking. Excess masking (exceeding linear additivity) was generally stronger than reported in the literature for longer maskers and comparable target levels. A model incorporating a compressive input/output function, followed by a linear summation stage, underestimated excess masking when using an input/output function derived from literature data for longer maskers and comparable target levels. The data could be predicted with a more compressive input/output function. Stronger compression may be explained by assuming that the Gaussian stimuli were too short to evoke the medial olivocochlear reflex (MOCR), whereas for longer maskers tested previously the MOCR caused reduced compression. Overall, the interpretation of the data suggests strong basilar membrane compression for very short stimuli.	\N	\N
21368435	A human factors experiment employed a hemi-anechoic sound field in which listeners were required to localize a vehicular backup alarm warning signal (both a standard and a frequency-augmented alarm) in 360-degrees azimuth in pink noise of 60 dBA and 90 dBA. Measures of localization performance included: (1) percentage correct localization, (2) percentage of right--left localization errors, (3) percentage of front-rear localization errors, and (4) localization absolute deviation in degrees from the alarm's actual location. In summary, the data demonstrated that, with some exceptions, normal hearing listeners' ability to localize the backup alarm in 360-degrees azimuth did not improve when wearing augmented hearing protectors (including dichotic sound transmission earmuffs, flat attenuation earplugs, and level-dependent earplugs) as compared to when wearing conventional passive earmuffs or earplugs of the foam or flanged types. Exceptions were that in the 90 dBA pink noise, the flat attenuation earplug yielded significantly better accuracy than the polyurethane foam earplug and both the dichotic and the custom-made diotic electronic sound transmission earmuffs. However, the flat attenuation earplug showed no benefit over the standard pre-molded earplug, the arc earplug, and the passive earmuff. Confusions of front-rear alarm directions were most significant in the 90 dBA noise condition, wherein two types of triple-flanged earplugs exhibited significantly fewer front-rear confusions than either of the electronic muffs. On all measures, the diotic sound transmission earmuff resulted in the poorest localization of any of the protectors due to the fact that its single-microphone design did not enable interaural cues to be heard. Localization was consistently more degraded in the 90 dBA pink noise as compared with the relatively quiet condition of the 60 dBA pink noise. A frequency-augmented backup alarm, which incorporated 400 Hz and 4000 Hz components to exploit the benefits of interaural phase and intensity cues respectively, slightly but significantly improved localization compared with the standard, more narrow-bandwidth backup alarm, and these results have implications for the updating of backup alarm standards.	\N	\N
21368442	Numerous studies have shown that the reliability of using laboratory measurements to predict individual or even group hearing protector attenuation for occupationally exposed workers is quite poor. This makes it difficult to properly assign hearing protectors when one wishes to closely match attenuation to actual exposure. An alternative is the use of field-measurement methods, a number of which have been proposed and are beginning to be implemented. We examine one of those methods, namely the field microphone-in-real-ear (F-MIRE) approach in which a dual-element microphone probe is used to measure noise reduction by quickly sampling the difference in noise levels outside and under an earplug, with appropriate adjustments to predict real-ear attenuation at threshold (REAT). We report on experiments that validate the ability of one commercially available F-MIRE device to predict the REAT of an earplug fitted identically for two tests. Results are reported on a representative roll-down foam earplug, stemmed-style pod plug, and pre-molded earplug, demonstrating that the 95% confidence level of the Personal Attenuation Rating (PAR) as a function of the number of fits varies from ± 4.4 dB to ± 6.3 dB, depending on the plug type, which can be reduced to ± 3.1 dB to ± 4.5 dB with a single repeat measurement. The added measurement improves precision substantially. However, the largest portion of the error is due to the user's fitting variability and not the uncertainty of the measurement system. Further we evaluated the inherent uncertainty of F-MIRE vs. the putative "gold standard" REAT procedures finding, that F-MIRE measurement uncertainty is less than one-half that of REAT at most test frequencies. An American National Standards Institute (ANSI) working group (S12/WG11) is currently involved in developing methods similar to those in this paper so that procedures for evaluating and reporting uncertainty on all types of field attenuation measurement systems can be standardized. We conclude that the hearing conservationist now has available a portable, convenient, quick, and easy-to-use system that can improve training and motivation of employees, assign hearing protection devices based on noise exposures, and address other management and compliance issues.	\N	\N
21380585	With a new metric called phonological Levenshtein distance (PLD20), the present study explores the effects of phonological similarity and word frequency on spoken word recognition, using polysyllabic words that have neither phonological nor orthographic neighbors, as defined by neighborhood density (the N-metric). Inhibitory effects of PLD20 were observed for these lexical hermits: Close-PLD20 words were recognized more slowly than distant PLD20 words, indicating lexical competition. Importantly, these inhibitory effects were found only for low- (not high-) frequency words, in line with previous findings that phonetically related primes inhibit recognition of low-frequency words. These results indicate that the properties of PLD20--a continuous measure of word-form similarity--make it a promising new metric for quantifying phonological distinctiveness in spoken word recognition research.	\N	\N
21382386	Although developmental dyslexia is often referred to as a cross-modal disturbance, tests of different modalities using the same stimuli are lacking. We compared the performance of 23 children with dyslexia and 42 chronologically matched control readers on reading versus repetition tasks and visual versus auditory lexical decision using the same stimuli. With respect to control readers, children with dyslexia were impaired only on stimuli in the visual modality; they had no deficit on the repetition and auditory lexical decision tasks. By applying the rate-amount model (Faust et al., 1999), we showed that performance of children with dyslexia on visual (but not auditory) tasks was associated with that of control readers by a linear relationship (with a 1.78 slope), suggesting that a global factor accounts for visual (but not auditory) task performance. We conclude that the processing of linguistic stimuli in the visual and auditory modalities is carried out by independent processes and that dyslexic children have a selective deficit in the visual modality.	\N	\N
21388613	Perceptual implicit memory is typically most robust when the perceptual processing at encoding matches the perceptual processing required during retrieval. A consistent exception is the robust priming that semantic generation produces on the perceptual identification test (Masson & MacLeod, 2002), a finding which has been attributed to either (1) conceptual influences in this nominally perceptual task, or (2) covert orthographic processing during generative encoding. The present experiments assess these possibilities using both auditory and visual perceptual identification, tests in which participants identify auditory words in noise or rapidly-presented visual words. During the encoding phase of the experiments, participants generated some words and perceived others in an intermixed study list. The perceptual control condition was visual (reading) or auditory (hearing), and varied across participants. The reading and hearing conditions exhibited the expected modality-specificity, producing robust intra-modal priming and non-significant cross-modal priming. Priming in the generate condition depended on the perceptual control condition. With a read control condition, semantic generation produced robust visual priming but no auditory priming. With a hear control condition, the results were reversed: semantic generation produced robust auditory priming but not visual priming. This set of results is not consistent with a straightforward application of either the conceptual-influence or covert-orthography account, and implies that the nature of encoding in the generate condition is influenced by the broader list context.	\N	\N
21389700	Bone conduction (BC) is the way sound energy is transmitted by the skull bones to the cochlea causing a sound perception. Even if the BC sound transmission involves several pathways including sound pressure induced in the ear canal, inertial forces acting on the middle ear ossicles and cochlear fluids, alteration of the cochlear space, and pressure transmission through the 3rd window of the cochlea, the BC sound ultimately produces a wave motion on the basilar membrane similar to that of air-conducted sound. The efficiency of the BC stimulation is largely dependent on the skull bone where the skull acts as a rigid body at low frequencies and incorporates different types of wave transmission at higher frequencies. The interaural stimulation difference is determined by the difference between contralateral and ipsilateral BC sound transmission: the transcranial BC sound transmission. To benefit from binaural processing, the transcranial transmission should be low, while the same should be high when using BC hearing aids for unilateral deaf subjects. By appropriately positioning the stimulation, high or low transcranial transmission can be achieved.	\N	\N
21390207	Human languages evolve continuously, and a puzzling problem is how to reconcile the apparent robustness of most of the deep linguistic structures we use with the evidence that they undergo possibly slow, yet ceaseless, changes. Is the state in which we observe languages today closer to what would be a dynamical attractor with statistically stationary properties or rather closer to a non-steady state slowly evolving in time? Here we address this question in the framework of the emergence of shared linguistic categories in a population of individuals interacting through language games. The observed emerging asymptotic categorization, which has been previously tested--with success--against experimental data from human languages, corresponds to a metastable state where global shifts are always possible but progressively more unlikely and the response properties depend on the age of the system. This aging mechanism exhibits striking quantitative analogies to what is observed in the statistical mechanics of glassy systems. We argue that this can be a general scenario in language dynamics where shared linguistic conventions would not emerge as attractors, but rather as metastable states.	\N	\N
21398015	A meaningful interaction with our environment relies on the ability to focus on relevant sensory input and to ignore irrelevant information, i.e. top-down control and attention processes are employed to select from competing stimuli following internal goals. In this, the demands for the recruitment of top-down control processes depend on the relative perceptual salience of the competing stimuli. In the present functional magnetic resonance imaging (fMRI) study, we investigated the recruitment of top-down control processes in response to varying degrees of control demands in the auditory modality. For this purpose, we tested 20 male and 20 female subjects with a dichotic listening paradigm, in which the relative perceptual salience of two simultaneously presented stimuli was systematically manipulated by varying the inter-aural intensity difference (IID) and asking the subjects to selectively attend to either ear. The analysis showed that the interaction between IID and attentional direction involves two networks in the brain. A fronto-parietal network, including the pre-supplementary motor area, anterior cingulate cortex, inferior frontal junction, insula and inferior parietal lobe, was recruited during cognitively demanding conditions and can thus be seen as a top-down cognitive control network. In contrast, a second network including the superior temporal and the post-central gyri was engaged under conditions with low cognitive control demands. These findings demonstrate how cognitive control is achieved through the interplay of distinct brain networks, with their differential engagement determined as a function of the level of competition between the sensory stimuli.	\N	\N
21417674	This study was designed to evaluate an automated pure-tone audiometric procedure (AMTAS(®)) for 4-8 year-old children, and a quality assessment method (QUALIND(®)) that predicts the accuracy of the test. Children were tested with AMTAS and conventional manual air-conduction audiometry. A group of adults was tested for comparison. Eighty-one 4-8 year-old children and 15 adults. Most had normal hearing. For most subjects (93% of adults and 91% of children) differences between AMTAS and manual thresholds were similar to differences that occur when two experienced audiologists test the same subjects. QUALIND detected the inaccurate audiograms with a sensitivity of 71% and a specificity of 91%. When inaccurate audiograms identified by QUALIND are excluded, the accuracy of AMTAS is similar to the accuracy of manual audiometry. AMTAS produces accurate air-conduction audiograms in a high proportion of 4-8 year-old children and adults. QUALIND successfully identified most inaccurate AMTAS audiograms. The method can decrease the cost and increase efficiency and accessibility of hearing testing.	\N	\N
21420739	Perception of environmental sounds from impacted materials (Wood, Metal and Glass) was examined by conducting a categorization experiment. Stimuli consisted of sound continua evoking progressive transitions between material categories. Results highlighted shallower response curves in subjects with schizophrenia than healthy participants, and are discussed in the framework of Signal Detection Theory and in terms of impaired perception of specific timbre features in schizophrenia.	\N	\N
21420989	There is ongoing debate with respect to interpretation of the finding that, in contrast to perceptual size judgments, actions are relatively unaffected by the Müller-Lyer illusion. In normal unrestricted viewing situations observers cannot perform an action directed at an object without simultaneously perceiving the object - this makes it difficult to unequivocally establish whether observed effects are a function of vision for perception, vision for action, a combination of both, or of a single all-purpose visual system. However, there is evidence that observers are capable of performing actions towards objects of which they are not consciously aware, implying that two distinct visual thresholds may exist; one accompanying vision for action and one accompanying vision for perception. To investigate this possibility we created a situation in which visual information was presented below the perception threshold, but above the purported action threshold, allowing examination of action responses independent of contributions from vision for perception. Following a perceptual categorization task, participants performed delayed pointing movements towards briefly exposed masked Müller-Lyer targets of different sizes. When the targets were presented below the perception threshold, participants were unable to discriminate between them, yet their delayed pointing movements were affected by target size (but not the illusion). The results imply that vision for action is functional even after a delay and/or that the pickup of egocentric information is associated with a lower visual threshold than the pickup of allocentric information.	\N	\N
21422306	To evaluate the significance of the Carhart notch (a 2-kHz bone conduction threshold dip [2KBD]) in the diagnosis of stapes fixation by comparing its incidence among ears with various ossicular chain abnormalities. Retrospective study. University hospital. A total of 153 ears among 127 consecutive patients with a congenital ossicular anomaly or otosclerosis. The 2KBD depth was defined as the threshold at 2 kHz minus the mean of thresholds at 1 and 4 kHz. The presence of 2KBD (depth, ≥10 dB), 2KBD depth, relationship between 2KBD depth and air-bone gap, and 2-kHz bone conduction recovery after operation were evaluated in a stapes fixation group (which included cases of otosclerosis and congenital stapes fixation), an incudostapedial joint detachment group, and a malleus or incus fixation group. A 2KBD was present in 32 of 102 stapes fixation ears (31.4%), 5 of 19 incudostapedial joint detachment ears (26.3%), and 6 of 20 malleus or incus fixation ears (30.0%) (12 ears had other diagnoses). The mean (SD) 2KBD depths were 17.3 (5.2) dB in the stapes fixation group, 18.5 (2.2) dB in the incudostapedial joint detachment group, and 16.3 (2.1) dB in the malleus or incus fixation group. No statistically significant differences were noted among these 3 groups. No correlation was noted between 2KBD depth and air-bone gap extent. Recovery of 2-kHz bone conduction threshold in the stapes fixation group was less than that in the other 2 groups. Incidence of 2KBD was similar among the stapes fixation, incudostapedial joint detachment, and malleus or incus fixation groups, implying that 2KBD is not a useful predictor of stapes fixation.	\N	\N
21424256	Assessing intentions, direction, and velocity of others is necessary for most daily tasks, and such information is often made available by both visual and auditory motion cues. Therefore, it is not surprising our great ability to perceive human motion. Here, we explore the multisensory integration of cues of biological motion walking speed. After testing for audiovisual asynchronies (visual signals led auditory ones by 30 ms in simultaneity temporal windows of 76.4 ms), in the main experiment, visual, auditory, and bimodal stimuli were compared to a standard audiovisual walker in a velocity discrimination task. Results in variance reduction conformed to optimal integration of congruent bimodal stimuli across all subjects. Interestingly, the perceptual judgements were still close to optimal for stimuli at the smallest level of incongruence. Comparison of slopes allows us to estimate an integration window of about 60 ms, which is smaller than that reported in audiovisual speech.	\N	\N
21431434	Our objective is to determine whether the degree of endolymphatic hydrops as it is detected in vivo in patients with definite Meniere's disease correlates with audiovestibular function. In this prospective study, 37 patients with definite Meniere's disease according to AAO-HNS criteria were included. Intratympanic contrast enhanced temporal bone MRI was performed using a 3D FLAIR protocol. The degree of endolymphatic hydrops in the cochlea and the vestibulum was graded on a Likert scale (0-3). The degree of hydrops was then analyzed with respect to its correlation with audiometric hearing levels, electrocochleographic SP/AP ratios, interaural amplitude ratios of vestibular evoked myogenic potentials and degree of horizontal semicircular canal paresis on caloric irrigation. There was a significant correlation between the degree of hydrops on the one hand and the averaged hearing level at 0.25-1 and 0.5-3 kHz and the vestibular evoked myogenic potential interaural amplitude ratio on the other hand. A trend toward a correlation was noticed between the hydrops and the caloric response, no correlation was noticed between the hydrops and the SP/AP ratio. The degree of endolymphatic hydrops correlates with a progressive loss of auditory and sacculus function in patients with Meniere`s disease.	\N	\N
21432625	Emotional inferences from speech require the integration of verbal and vocal emotional expressions. We asked whether this integration is comparable when listeners are exposed to their native language and when they listen to a language learned later in life. To this end, we presented native and non-native listeners with positive, neutral and negative words that were spoken with a happy, neutral or sad tone of voice. In two separate tasks, participants judged word valence and ignored tone of voice or judged emotional tone of voice and ignored word valence. While native listeners outperformed non-native listeners in the word valence task, performance was comparable in the voice task. More importantly, both native and non-native listeners responded faster and more accurately when verbal and vocal emotional expressions were congruent as compared to when they were incongruent. Given that the size of the latter effect did not differ as a function of language proficiency, one can conclude that the integration of verbal and vocal emotional expressions occurs as readily in one's second language as it does in one's native language.	\N	\N
21440971	Congenital amusia manifests as a lifelong difficulty in making sense of musical sound. The extent to which this disorder is accompanied by deficits in visuo-spatial processing is an important question, bearing on the issue of whether pitch processing draws on supramodal spatial representations. The present study assessed different aspects of visuo-spatial processing with a range of tasks (Shepard-Metzler Mental Rotation, Corsi Blocks Task, Visual Patterns Test) in 14 amusics and matched controls. The absence of a group difference on any of these tasks fails to support a previous claim that the disorder is strongly related to deficits in spatial processing. However, a subgroup of amusics, with significantly elevated thresholds on a pitch direction discrimination task relative to the rest of the group, were slower, but equally accurate, at Mental Rotation. This finding is discussed in relation to the nature of supramodal representations of contour and strategies for dynamic mental transformation.	\N	\N
21458056	Speech production can be broadly separated into two distinct components: Phonation and Articulation. These two aspects require the efficient control of several phono-articulatory effectors. Speech is indeed generated by the vibration of the vocal-folds in the larynx (F0) followed by ''filtering" by articulators, to select certain resonant frequencies out of that wave (F1, F2, F3, etc.). Recently it has been demonstrated that the motor representation of articulators (lips and tongue) participates in the discrimination of articulatory sounds (lips- and tongue-related speech sounds). Here we investigate whether the results obtained on articulatory sounds discrimination could be extended to phonation by applying a dual-pulse TMS protocol while subjects had to discriminate F0-shifted vocal utterances [a]. Stimulation over the larynx motor representation, compared to the control site (tongue/lips motor cortex), induced a reduction in RT for stimuli including a subtle pitch shift. We demonstrate that vocal pitch discrimination, in analogy with the articulatory component, requires the contribution of the motor system and that this effect is somatotopically organized.	\N	\N
21463563	Bone-conduction thresholds have been used in audiologic assessments of both infants and adults to differentiate between conductive and sensorineural hearing losses. However, air- and bone-conduction thresholds estimated for infants with normal hearing using physiological measures have identified an "air-bone gap" in the low frequencies that does not result from conductive hearing impairment but, rather, from maturational differences in sensitivity. This maturational air-bone gap appears to be present up to at least 2 yr of age. Because most infants older than 6 mo of age are clinically assessed behaviorally, rather than physiologically, it is necessary to determine whether a similar maturational air-bone gap is present for behavioral air- and bone-conduction thresholds. The purpose of this study was to estimate behavioral bone-conduction thresholds for infants using a standard clinical visual reinforcement audiometry (VRA) protocol to determine whether frequency-dependent maturational patterns exist as previously reported for physiological bone-conduction thresholds. Behavioral bone-conduction minimum response levels were estimated at 500, 1000, 2000, and 4000 Hz using VRA for each participant. Young (7-15 mo; N = 17) and older (18-30 mo; N = 20) groups of infants were assessed. All infants were screened and considered to be at low risk for hearing loss. Preliminary "normal levels" were determined by calculating the 90th percentile for responses present as a cumulative percentage. Mean bone-conduction thresholds were compared and analyzed using a mixed-model analysis of variance across frequency and age group. Linear regression analysis was also performed to assess the effect of age on bone-conduction thresholds. Results of this study indicate that, when measured behaviorally, infants under 30 mo of age show frequency-dependent bone-conduction thresholds whereby their responses at 500 and 1000 Hz are significantly better than those at 2000 and 4000 Hz. However, thresholds obtained from the younger group of infants (mean age of 10.6 mo) were not significantly different from those obtained from the older group of infants (mean age of 23.0 mo) at any frequency. The findings of the present study are similar to the results obtained from previous physiological studies. Compared to previously documented air-conduction thresholds of infants using similar VRA techniques, a maturational air-bone gap is observed in the low frequencies. Therefore, differences between infant and adult bone-conduction thresholds persist until at least 30 mo of age. As a result, different "normal levels" should be used when assessing bone-conduction hearing sensitivity of infants using behavioral methods.	\N	\N
21476653	Different non-exponential decays such as the concave and the convex double sloped decays in the coupled rooms provide distinct sound qualities. These are commonly considered to occur in the less reverberant sub-room and the more reverberant sub-room, respectively. However, numerical simulations and experiments in this paper show that the demarcation line is not located along the physical boundaries (e.g., the partition and the coupling aperture), but in the more reverberant sub-room. The sound field with the concave double sloped decay penetrates into the auxiliary sub-room to an extent which is influenced by the difference between the two natural reverberations of the sub-rooms. Furthermore the sound energy flows in different regions are investigated, demonstrating how energy feedback leads to the concave double sloped decay.	\N	\N
21476654	Talkers adjust their vocal effort to communicate at different distances, aiming to compensate for the sound propagation losses. The present paper studies the influence of four acoustically different rooms on the speech produced by 13 male talkers addressing a listener at four distances. Talkers raised their vocal intensity by between 1.3 and 2.2 dB per double distance to the listener and lowered it as a linear function of the quantity "room gain" at a rate of -3.6 dB/dB. There were also significant variations in the mean fundamental frequency, both across distance (3.8 Hz per double distance) and among environments (4.3 Hz), and in the long-term standard deviation of the fundamental frequency among rooms (4 Hz). In the most uncomfortable rooms to speak in, talkers prolonged the voiced segments of the speech they produced, either as a side-effect of increased vocal intensity or in order to compensate for a decrease in speech intelligibility.	\N	\N
21476664	The enhancement effect is consistently shown when simultaneously masked stimuli are preceded by the masker alone, with a reduction in the amount of masking relative to when that precursor is absent. One explanation for this effect proposed by Viemeister and Bacon [(1982). J. Acoust. Soc. Am. 71, 1502-1507] is the adaptation of inhibition, which predicts that an enhanced component (the "target") will be effectively more intense within the auditory system than one that has not been enhanced. Forward masking studies have indicated this effect of increased gain; however, other explanations of the enhancement effect have also been suggested. In order to provide an alternative measure of the amount of effective gain for an enhanced target, a subjective binaural centering task was used in which listeners matched the intensities of enhanced and unenhanced 2-kHz tones presented to opposite ears to produce a centered stimulus. The results showed that the enhancement effect produces an effective 4-5 dB increase in the level of the enhanced target. The enhancement effect was also measured using other enhancement paradigms which yielded similar results over a range of levels for the target, supporting an account based on adaptation of inhibition.	\N	\N
21477909	Operatic music involves both singing and acting (as well as rich audiovisual background arising from the orchestra and elaborate scenery and costumes) that multiply the mechanisms by which emotions are induced in listeners. The present study investigated the effects of music, plot, and acting performance on emotions induced by opera. There were three experimental conditions: (1) participants listened to a musically complex and dramatically coherent excerpt from Tosca; (2) they read a summary of the plot and listened to the same musical excerpt again; and (3) they re-listened to music while they watched the subtitled film of this acting performance. In addition, a control condition was included, in which an independent sample of participants succesively listened three times to the same musical excerpt. We measured subjective changes using both dimensional, and specific music-induced emotion questionnaires. Cardiovascular, electrodermal, and respiratory responses were also recorded, and the participants kept track of their musical chills. Music listening alone elicited positive emotion and autonomic arousal, seen in faster heart rate, but slower respiration rate and reduced skin conductance. Knowing the (sad) plot while listening to the music a second time reduced positive emotions (peacefulness, joyful activation), and increased negative ones (sadness), while high autonomic arousal was maintained. Watching the acting performance increased emotional arousal and changed its valence again (from less positive/sad to transcendent), in the context of continued high autonomic arousal. The repeated exposure to music did not by itself induce this pattern of modifications. These results indicate that the multiple musical and dramatic means involved in operatic performance specifically contribute to the genesis of music-induced emotions and their physiological correlates.	\N	\N
21491357	Obesity may be associated with increased tissue bulk in the laryngeal airway, neck, and chest wall, and as such may affect vocal function. Eight obese and eight nonobese adults participated in this study; the obese participants underwent bariatric surgical procedures. This mixed-design study included cross-sectional analysis for group differences and longitudinal analysis for multidimensional changes in vocal function from four assessments collected over 6 months. No significant differences were detected between groups from the preoperative assessment. Further, no changes were detected over time for acoustic parameters, maximum phonation time, laryngeal airway resistance, and airflow during a sustained vowel for either group. Only minor differences were detected for strain, pitch, and loudness perceptions of voice over time, but not between groups. Phonation threshold pressure (PTP), at comfortable and high pitches (30% and 80% of the F0 range) changed significantly over time, but not between groups. Examination of individual data revealed a trend for PTP at 30% F0 to decrease as body mass index decreased. PTP may be informative for assessing vocal function in clients who present with obesity and voice symptoms.	\N	\N
21493300	The aim of this prospective study was to audiologically evaluate consecutive glaucoma patients with or without exfoliation. Prospective study. Glaucoma Unit and Audiology Department at a university hospital. Consecutive subjects with exfoliative glaucoma (XFG) or primary open-angle glaucoma (POAG) aged between 50 and 70 years were enrolled. Auditory thresholds at 0.5, 1.0, 2.0, 4.0, and 8.0 Hz were measured bilaterally. Cochlear activity was assessed by recording distortion product otoacoustic emissions (DPOEs). Functional changes in the retrocochlear auditory pathway were evaluated by auditory brainstem responses (ABRs). One hundred and ten patients with XFG and 85 patients with POAG who presented in a glaucoma clinic were investigated. The mean age of study patients was 66.2 ± 5.6 years; range, 50-70 years). The odds of pathologic ABR central transmission time (interpeak latencies I-III, III-V, and I-V and waves I, III, and V) were 4.34 times higher in patients with XFG than in patients with POAG (95% confidence interval [CI], 2.22-8.49; P < .001). This significant association remained after adjusting for sex and age (odds ratio [OR] 4.12; 95% CI, 2.07-8.22; P < .001). Furthermore, the odds of ABR remained significantly higher in patients with XFG than in patients with POAG (OR 4.36; 95% CI, 2.10-9.06; P < .001) after controlling for systemic diseases (arterial hypertension, coronary heart disease, high cholesterol, and stroke). In the first study to compare XFG and POAG monitoring of the peripheral and central auditory pathway, it has been documented that XFG patients show a greater prevalence of retrocochlear pathology.	\N	\N
21493334	To compare noise reduction of commercially available ear-level hearing protection (muffs/inserts) to that of firearm muzzle suppressors. Experimental sound measurements under consistent environmental conditions. None. Muzzle suppressors for 2 pistol and 2 rifle calibers were tested using the Bruel & Kjaer 2209 sound meter and Bruel & Kjaer 4136 microphone calibrated with the Bruel & Kjaer Pistonphone using Military-Standard 1474D placement protocol. Five shots were recorded unsuppressed and 10 shots suppressed under consistent environmental conditions. Sound reduction was then compared with the real-world noise reduction rate of the best available ear-level protectors. All suppressors offered significantly greater noise reduction than ear-level protection, usually greater than 50% better. Noise reduction of all ear-level protectors is unable to reduce the impulse pressure below 140 dB for certain common firearms, an international standard for prevention of sensorineural hearing loss. Modern muzzle-level suppression is vastly superior to ear-level protection and the only available form of suppression capable of making certain sporting arms safe for hearing. The inadequacy of standard hearing protectors with certain common firearms is not recognized by most hearing professionals or their patients and should affect the way hearing professionals counsel patients and the public.	\N	\N
21506894	To assess the effect of the static force of a bone vibrator on the results of bone conduction (BC) threshold measurements and comfort. BC thresholds were determined for 40 participants using the standardized P-3333 headband and a leather adjustable headstrap with variable static forces (2.4, 3.4, 4.4, 5.4 N). Comfort ratings were examined using a five-point Likert scale. Mean BC thresholds were within ± 2 dB across all conditions; differences may be considered small enough to be clinically insignificant. Participants experienced significantly greater discomfort with the P-3333 versus the adjustable headstrap. The mean static force of the P-3333 varied considerably and was higher in situ than the calibration standard of 5.4 N. The results suggest that future revisions of relevant international and national standards should address the use of an adjustable headstrap and a static force less than 5.4 N.	\N	\N
21512424	To evaluate the outcomes of younger (<60 yr) and older (≥60 yr) patients implanted with the Vibrant Soundbridge (VSB). The aim was to determine if there were differences between groups. A retrospective study was used to evaluate all patients who were implanted and fit with a VSB during 2008 and 2009 at the Department of Otorhinolaryngology-Head and Neck Surgery, Medical University Innsbruck. Differences in audiologic, medical, and surgical outcomes between younger and older patients were evaluated. No patients had major complications during or after the surgical procedure. All patients had a good hearing benefit as supported by improvements in hearing thresholds from the preoperative to the postoperative condition in the sound field. There were differences between groups in speech understanding postoperatively; however, the differences were not statistically significant. All patients had, independent of age, good audiologic benefit from VSB use. Based on the low risk of medical or surgical complications, the easy use of the hearing implant, audiologic improvements, and potential social benefits, we think that the VSB should be regularly offered to adults with hearing loss, whether they are young or old.	\N	\N
21517207	The purpose of this study was to examine the effects of expertise on motion anticipation. We conducted 2 experiments in which novices and expert pilots viewed simulated aircraft landing scenes. The scenes were interrupted by the display of a black screen and then started again after a forward or backward shift. The participant's task was to determine whether the moving scene had been shifted forward or backward. A forward misjudgment of the final position of the moving scene was interpreted as a representational momentum (RM) effect. Experiment 1 showed that an RM effect was detected only for experts. The lack of motion anticipation on the part of novices is a surprising result for the RM literature. It could be related to scene unfamiliarity, encoding time, or shift size. Experiment 2 was run with novices only. It was aimed at testing the potential impact of 2 factors on the RM effect: scene encoding time and shift size. As a whole, the results showed that encoding time and shift size are important factors in anticipation processes in realistic dynamic situations.	\N	\N
21524739	Word segmentation from continuous speech is a difficult task that is faced by human infants when they start to learn their native language. Several studies indicate that infants might use several different cues to solve this problem, including intonation, linguistic stress, and transitional probabilities between subsequent speech sounds. In this work, a computational model for word segmentation and learning of primitive lexical items from continuous speech is presented. The model does not utilize any a priori linguistic or phonemic knowledge such as phones, phonemes or articulatory gestures, but computes transitional probabilities between atomic acoustic events in order to detect recurring patterns in speech. Experiments with the model show that word segmentation is possible without any knowledge of linguistically relevant structures, and that the learned ungrounded word models show a relatively high selectivity towards specific words or frequently co-occurring combinations of short words.	\N	\N
21525779	The results reported in this paper indicate that native speakers of Mandarin Chinese rate the perceptual similarities among the lexical tones of Mandarin differently than do native speakers of American English. Mandarin listeners were sensitive to tone contour while English listeners attended to pitch levels. Chinese listeners also rated tones that are neutralized by phonological tone sandhi rules in Mandarin as more similar to each other than did English speakers--indicating a role of phonology in determining perceptual salience. In two further experiments, we found that some of these differences were eliminated when the listening task focused listeners' attention on the auditory properties of the stimuli, but, interestingly, a degree of language specificity remained even in the most purely psychophysical listening tasks with speech stimuli.	\N	\N
21540053	The auditory system faithfully represents sufficient details from sound sources such that downstream cognitive processes are capable of acting upon this information effectively even in the face of signal uncertainty, degradation or interference. This robust sound source representation leads to an invariance in perception vital for animals to interact effectively with their environment. Due to unique nonlinearities in the cochlea, sound representations early in the auditory system exhibit a large amount of variability as a function of stimulus intensity. In other words, changes in stimulus intensity, such as for sound sources at differing distances, create a unique challenge for the auditory system to encode sounds invariantly across the intensity dimension. This challenge and some strategies available to sensory systems to eliminate intensity as an encoding variable are discussed, with a special emphasis upon sound encoding.	\N	\N
21543605	The mammalian auditory system contains descending neural pathways, some of which project onto the cochlea via the medial olivocochlear (MOC) system. The function of this efferent auditory system is not entirely clear. Behavioral studies in animals with olivocochlear (OC) lesions suggest that the MOC serves to facilitate sound localization in noise. In the current work, noise-induced OC activity (the OC reflex) and sound-localization performance in noise were measured in normal-hearing humans. Consistent with earlier studies, both measures were found to vary substantially across individuals. Importantly, significant correlations were observed between OC-reflex strength and the effect of noise on sound-localization performance; the stronger the OC reflex, the less marked the effect of noise. These results suggest that MOC activation by noise helps to counteract the detrimental effects of background noise on neural representations of direction-dependent spectral features, which are especially important for accurate localization in the up/down and front/back dimensions.	\N	\N
21545768	Previous studies have demonstrated a relation between cognitive capacity, in particular working memory, and the ability to understand speech in noise with different types of hearing aid signal processing. The present study investigates the relation between working memory capacity and the speech recognition performance of persons with hearing impairment under both aided and unaided conditions, following a period of familiarization to both fast- and slow-acting compression settings in the participants' own hearing aids. Speech recognition was tested in modulated and steady state noise with fast and slow compression release settings (for aided conditions) with each of two materials. Working memory capacity was also measured. Thirty experienced hearing aid users with a mean age of 70 yr (SD = 7.8) and pure-tone average hearing threshold across the frequencies 0.25, 0.5, 1, 2, 3, 4, and 6 kHz (PTA7) and for both ears of 45.8 dB HL (SD = 6.6. 9 wk experience with each of fast-acting and slow-acting compression. Speech recognition data were analyzed using repeated measures analysis of variance with the within-subjects factors of material (high constraint, low constraint), noise type (steady state, modulated), and compression (fast, slow), and the between-subjects factor working memory capacity (high, low). With high constraint material, there were three-way interactions including noise type and working memory as well as compression, in aided conditions, and performance level, in unaided conditions, but no effects of either working memory or compression with low constraint material. Investigation of simple main effects showed a significant effect of working memory during speech recognition under conditions of both "high degradation" (modulated noise, fast-acting compression, low signal-to-noise ratio [SNR]) and "low degradation" (steady state noise, slow-acting compression, high SNR). The finding of superior performance of persons with high working memory capacity in modulated noise with fast-acting compression agrees with findings of previous studies including a familiarization period of at least 9 wk, in contrast to studies with familiarization of 4 wk or less that have shown that persons with lower cognitive capacity may benefit from slow-acting compression. Working memory is a crucial factor in speech understanding in noise for persons with hearing impairment, irrespective of whether hearing is aided or unaided. Working memory supports speech understanding in noise under conditions of both "high degradation" and "low degradation." A subcomponent view of working memory may contribute to our understanding of these phenomena. The effect of cognition on speech understanding in modulated noise with fast-acting compression may only pertain after a period of 4-9 wk of familiarization and that prior to such a period, persons with lower cognitive capacity may benefit more from slow-acting compression.	\N	\N
21547604	Listeners require context to understand the highly reduced words that occur in casual speech. The present study reports four auditory lexical decision experiments in which the role of semantic context in the comprehension of reduced versus unreduced speech was investigated. Experiments 1 and 2 showed semantic priming for combinations of unreduced, but not reduced, primes and low-frequency targets. In Experiment 3, we crossed the reduction of the prime with the reduction of the target. Results showed no semantic priming from reduced primes, regardless of the reduction of the targets. Finally, Experiment 4 showed that reduced and unreduced primes facilitate upcoming low-frequency related words equally if the interstimulus interval is extended. These results suggest that semantically related words need more time to be recognized after reduced primes, but once reduced primes have been fully (semantically) processed, these primes can facilitate the recognition of upcoming words as well as do unreduced primes.	\N	\N
21554838	Tinnitus is a disturbing symptom and is often the main reason for otology referral. It is usually associated with hearing loss of varying aetiology, and is thought to begin in the cochlea, with later abnormal central activity. We hypothesise that tinnitus without hearing loss may be caused by central and subcortical abnormalities and altered outer hair cell function. To compare the auditory brainstem responses, middle latency responses and otoacoustic emissions in normal-hearing individuals with and without tinnitus. The audiological test results of 25 normal hearing subjects with tinnitus (age 18-45 years) were determined, and compared with those of a control group. A statistically significant difference was found between study group tinnitus ears vs control group ears, as regards wave I latency prolongation, shortening of wave V and absolute I-III and I-V interpeak latency, enlargement of wave Na and Pa amplitude, and distortion product and transient evoked otoacoustic emission signal-to-noise ratios. There was no statistically significant difference between unilateral vs bilateral tinnitus ears. The pathogenesis and optimum management of tinnitus are still unclear. It often occurs with primary ear disease, usually associated with hearing loss, but may occur in patients with normal hearing. Observed changes in auditory brainstem and middle latency responses indicate central auditory alterations. Tinnitus involves both peripheral and central activity, and complete audiological and neurophysiological investigation is required. Management should be based on both audiological and neurophysiological findings.	\N	\N
21563460	To understand the usage of MP3 and effects on hearing of middle school students in Xi'an, and discuss controlling strategies. Stratified random cluster sampling method was used in the 1567 middle school students in Xi'an through questionnaire survey, ear examination and hearing examination, data were analysed by the SPSS13.0 statistical software. 1) The rate of holding MP3 in the middle school students was 85.2%. Average daily use time was (1.41 +/- 1.11) h. 2) The noise group of pure tone hearing threshold was significantly higher compared with the control group (P<0.01), and increased the detection rate of hearing loss with the increasing use of MP3. 3) The detection rate of symptoms increased with the increasing use of MP3. The usage of MP3 can harm hearing in middle school students, which can result in neurasthenic syndrome.	\N	\N
21568377	The ability of listeners with bilateral sensorineural hearing loss to localize a speech source in a multitalker mixture was measured. Five simultaneous words spoken by different talkers were presented over loudspeakers in a small room, and listeners localized one target word. Errors were significantly larger in this group compared to a control group with normal hearing. Localization of the target presented alone was not different between groups. The results suggest that hearing loss does not impair spatial hearing per se, but degrades the spatial representation of multiple simultaneous sounds.	\N	\N
21568378	A previous letter by Gee et al. [J. Acoust. Soc. Am. 121, EL1-EL7 (2007)] revealed likely shortcomings in using common, stationary (long-term) spectrum-based measures to quantify the perception of nonlinearly propagated noise. Here, the Glasberg and Moore [J. Audio Eng. Soc. 50, 331-342 (2002)] algorithm for time-varying loudness is investigated. Their short-term loudness, when applied to a shock-containing broadband signal and a phase-randomized signal with equivalent long-term spectrum, does not show a significant difference in loudness between the signals. Further analysis and discussion focus on the possible utility of the instantaneous loudness and the need for additional investigation in this area.	\N	\N
21569784	In recent years it has been shown that a disorder in recognizing familiar people can be observed in patients with lesions affecting the anterior parts of the temporal lobes and that these disorders can be multi-modal, simultaneously affecting the visual, auditory and linguistic channels that allow person identification. Several authors have also shown that patients with right anterior temporal atrophy are more impaired in assessing familiarity and in retrieving person-specific semantic information from faces than from names, whereas the opposite pattern of performance can be observed in patients with left temporal lobe atrophy. Voice recognition disorders have been studied much less even despite their clinical and theoretical importance. The aim of the present review, therefore, was to compare recognition of familiar faces and voices, taking into account not only results obtained in individual patients with right anterior temporal lesions, but also those of group studies of unselected right- and left brain-damaged patients and results of experimental investigations conducted on face and voice recognition in normal subjects. Results of the review showed that: (1) voice recognition disorders are mainly due to right temporal lesions, similarly to face recognition disorders; (2) famous voice recognition disorders can be dissociated from unfamiliar voice discrimination impairments; (3) although face and voice recognition disorders tend to co-occur, they can also dissociate and in these patients there is a prevalent involvement of the right fusiform gyrus when face recognition disorders are on the foreground, and of the right superior temporal gyrus when voice recognition disorders are prominent; (4) normal subjects have greater difficulty evaluating familiarity and drawing semantic information from the voices than from the faces of celebrities. These data are at variance with models which assume that familiarity feelings may be generated at the level of person identity nodes (PINs) and that the latter may be considered as modality-free gateways to single semantic systems in which information about people is stored in an amodal format.	\N	\N
21586256	In a number of European countries, a functional self-test to screen for hearing impairment is available via telephone and the Internet. The tests estimate speech-reception thresholds using an adaptive procedure in which digit triplets are presented at varying signal-to-noise ratios. In different languages, the stimuli were created either with or without coarticulation; and some implementations use fresh noise samples, while others do not. The present investigation concerns the influence of coarticulation, prosody, and noise freshness on measured thresholds. We performed a laboratory study using 12 normal-hearing listeners. In a blocked design we compared speech-reception thresholds for conditions with and without fresh noise tokens. In each block we used three types of triplets: with coarticulation and prosody, with neither, and without coarticulation but with prosody. Thirty-six thresholds were recorded per subject, and they were analyzed using analyses of variance. The results showed no significant differences among the three triplet conditions. The freshness of the noise did not affect thresholds when, at least, a fresh noise token was used per threshold estimate (23 presentations). Scores dropped significantly when a whole experimental block was performed with a single noise token.	\N	\N
21601842	Evolution and the brain have done a marvelous job solving many tricky problems in action control, including problems of learning, hierarchical control over serial behavior, continuous recalibration, and fluency in the face of slow feedback. Given that evolution tends to be conservative, it should not be surprising that these solutions are exploited to solve other tricky problems, such as the design of a communication system. We propose that a mechanism of motor control, paired controller/predictor models, has been exploited for language learning, comprehension, and production. Our account addresses the development of grammatical regularities and perspective, as well as how linguistic symbols become meaningful through grounding in perception, action, and emotional systems.	\N	\N
21603614	Recent studies suggest that human auditory perception follows a prolonged developmental trajectory, sometimes continuing well into adolescence. Whereas both sensory and cognitive accounts have been proposed, the development of the ability to base current perceptual decisions on prior information, an ability that strongly benefits adult perception, has not been directly explored. Here we ask whether the auditory frequency discrimination of preschool children also improves when given the opportunity to use previously presented standard stimuli as perceptual anchors, and whether the magnitude of this anchoring effect undergoes developmental changes. Frequency discrimination was tested using two adaptive same/different protocols. In one protocol (with-reference), a repeated 1-kHz standard tone was presented repeatedly across trials. In the other (no-reference), no such repetitions occurred. Verbal memory and early reading skills were also evaluated to determine if the pattern of correlations between frequency discrimination, memory and literacy is similar to that previously reported in older children and adults. Preschool children were significantly more sensitive in the with-reference than in the no-reference condition, but the magnitude of this anchoring effect was smaller than that observed in adults. The pattern of correlations among discrimination thresholds, memory and literacy replicated previous reports in older children. The processes allowing the use of context to form perceptual anchors are already functional among preschool children, albeit to a lesser extent than in adults. Nevertheless, immature anchoring cannot fully account for the poorer frequency discrimination abilities of young children. That anchoring is present among the majority of typically developing preschool children suggests that the anchoring deficits observed among individuals with dyslexia represent a true deficit rather than a developmental delay.	\N	\N
21604886	Inhibitory control functions in old age were investigated with the "masked prime" paradigm in which participants executed speeded manual choice responses to simple visual targets. These were preceded--either immediately or at some earlier time--by a backward-masked prime. Young adults produced positive compatibility effects (PCEs)--faster and more accurate responses for matching than for nonmatching prime-target pairs--when prime and target immediately followed each other, and the reverse effect (negative compatibility effect, NCE) for targets that followed the prime after a short interval. Older adults produced similar PCEs to young adults, indicating intact low-level motor activation, but failed to produce normal NCEs even with longer delays (Experiment 1), increased opportunity for prime processing (Experiment 2), and prolonged learning (Experiment 3). However, a fine-grained analysis of each individual's time course of masked priming effects revealed NCEs in the majority of older adults, of the same magnitude as those of young adults. These were significantly delayed (even more than expected on the basis of general slowing), indicating a disproportionate impairment of low-level inhibitory motor control in old age.	\N	\N
21616987	This project examined receptive vocabulary treatment outcomes in the two languages of a bilingual preschooler with moderate to severe language impairment. A series of single-subject experimental designs was used to compare English-only (EO) and bilingual (BI) approaches to receptive vocabulary treatment. The participant, Nam, was a boy age 3;11 (years;months) who was learning Vietnamese as a first language at home and English in his early childhood education program. Treatment was implemented by an EO interventionist using a computer interface and prerecorded audio files in Vietnamese and English. The dependent measure was the percentage of items that were correctly identified in each language. Combined studies revealed that the BI approach increased Nam's attention to task and was as effective as the EO approach for increasing his receptive vocabulary in English. Nam made vocabulary gains in both treatment conditions; receptive vocabulary gains were evident in both Vietnamese and English. This project showed that it is feasible for an EO clinician to promote gains in both the home and school languages of a BI child through creative collaborations with BI colleagues and the use of technology. Replication with additional participants and treatment activities is needed to make further generalizations.	\N	\N
21623776	Isotretinoin is widely used in the treatment of extensive and nodulocystic acne. The objective of this prospective study was to investigate whether oral isotretinoin could affect the hearing system. Thirty-eight patients with acne vulgaris (76 ears) who were diagnosed and treated at the Department of Dermatology were included in the current study. Study evaluation visits were performed at baseline and at Weeks 1, 2 and 3. Pure-tone averages (PTAs) of air conduction thresholds at 250 Hz (PTA1); 500, 1000, and 2000 Hz (PTA2); 4000, 8000, and 10,000 Hz (PTA3); and 12,500, 16,000, 18,000 and 20,000 Hz (PTA4) for each ear were calculated separately. Assessment of the efficacy was based on the audiometric findings. Compared with pre-treatment evaluation, the PTAs of patients were found to be significantly different at the first week for PTA2 (P = 0.033) and PTA3 (P = 0.001), at the second week for PTA1 (P = 0.036), and at the third week for PTA4 (P = 0.002). Our results suggest that the oral isotretinoin (13-cis retinoic acid), which is a derivative of retinol (vitamin A), improved the hearing level of the patients in all audiometric frequencies in a short-period follow-up.	\N	\N
21624926	Cognitive impairment is a core element shared by a large number of different neurological and neuropsychiatric diseases. Irrespective of their different aetiologies and symptomatologies, most appear to converge at the functional deficiency of the auditory-frontal cortex network of auditory discrimination, which indexes cognitive impairment shared by these abnormalities. This auditory-frontal cortical deficiency, and hence cognitive decline, can now be objectively measured with the mismatch negativity and its magnetic equivalent. The auditory-frontal cortical network involved seems, therefore, to play a pivotal, unifying role in the different abnormalities. It is, however, more likely that the dysfunction that can be detected with the mismatch negativity and its magnetoencephalographic equivalent manifests a more widespread brain disorder, namely, a deficient N-methyl-D-aspartate receptor function, shared by these abnormalities and accounting for most of the cognitive decline.	\N	\N
21625011	The McGurk effect demonstrates the influence of visual cues on auditory perception. Mismatching information from both sensory modalities can fuse to a novel percept that matches neither the auditory nor the visual stimulus. This illusion is reported in 60-80% of trials. We were interested in the impact of ongoing brain oscillations-indexed by fluctuating local excitability and interareal synchronization-on upcoming perception of identical stimuli. The perception of the McGurk effect is preceded by high beta activity in parietal, frontal, and temporal areas. Beta activity is pronounced in the left superior temporal gyrus (lSTG), which is considered as a site of multimodal integration. This area is functionally (de)coupled to distributed frontal and temporal regions in illusion trials. The disposition to fuse multisensory information is enhanced as the lSTG is more strongly coupled to frontoparietal regions. Illusory perception is accompanied by a decrease in poststimulus theta-band activity in the cuneus, precuneus, and left superior frontal gyrus. Event-related activity in the left middle temporal gyrus is pronounced during illusory perception. Thus, the McGurk effect depends on fluctuating brain states suggesting that functional connectedness of left STS at a prestimulus stage is crucial for an audiovisual percept.	\N	\N
21639675	It is well established that in masked priming, a target word (e.g., JUDGE) is primed more effectively by a transposed letter (TL) prime (e.g., jugde) than by an orthographic control prime (e.g., junpe). This is inconsistent with the slot coding schemes used in many models of visual word recognition. Several alternative coding schemes have been proposed in which special bigram detectors for frequently occurring nonadjacent letter combinations are developed as a product of perceptual learning. In order to examine this perceptual learning hypothesis, we asked whether bigram detectors are defined in terms of visuospatial coordinates. Japanese-English bilinguals who were equally familiar with horizontal and vertical text in Japanese demonstrated strong TL priming in both orientations when reading Japanese words, but, when reading English words, the evidence for vertical TL priming was not as strong. However, native English speakers showed a clear TL priming effect with vertically presented English words despite minimal exposure to vertical text, which is not consistent with a perceptual learning account. It is proposed instead that the initial letter array is transformed into an abstract ordinal code (first to last) regardless of orientation and that the speed with which this transformation is carried out depends on the familiarity of the script.	\N	\N
21645986	The etiology of developmental dyslexia remains widely debated. An appealing theory postulates that the reading and spelling problems in individuals with dyslexia originate from reduced sensitivity to slow-rate dynamic auditory cues. This low-level auditory deficit is thought to provoke a cascade of effects, including inaccurate speech perception and eventually unspecified phoneme representations. The present study investigated sensitivity to frequency modulation and amplitude rise time, speech-in-noise perception and phonological awareness in 11-year-old children with dyslexia and a matched normal-reading control children. Group comparisons demonstrated that children with dyslexia were less sensitive than normal-reading children to slow-rate dynamic auditory processing, speech-in-noise perception, phonological awareness and literacy abilities. Correlations were found between slow-rate dynamic auditory processing and phonological awareness, and speech-in-noise perception and reading. Yet, no significant correlation between slow-rate dynamic auditory processing and speech-in-noise perception was obtained. Together, these results indicate that children with dyslexia have difficulties with slow-rate dynamic auditory processing and speech-in-noise perception and that these problems persist until sixth grade.	\N	\N
21647889	To study to what extent it is possible to achieve identical insertion depths and to maintain the same performance after cochlear reimplantation. Outcome research on a retrospective case series in a tertiary university referral center. Data were collected for 12 adults and three children who underwent reimplantation during the last 3 years with a new HiRes90K device with HiFocus 1J electrode owing to failure of the feed-through seal. Multislice computed tomography scans were used to compare positions of the original and newly placed electrode arrays. The speech-perception scores on a consonant-vowel-consonant word test before and after reimplantation were compared. All reimplantations were successfully performed by two experienced cochlear implantation surgeons, and no complications were observed. Postoperative imaging showed that the average displacement of the new implant was only 0.59 mm. Reactivation of the implant gave immediate open set speech understanding in all patients, and speech perception rapidly returned to the previous level obtained with the original implant within weeks; it was even significantly better at the 3-month follow-up. No relation was found between changes in performance and the amount of displacement of the electrode array. After cochlear reimplantation with the same device, electrode-array position can be accurately replicated and speech perception can be regained or even improved within weeks.	\N	\N
21649758	This event-related functional magnetic resonance imaging (fMRI) study was designed in such a manner so as to contribute to the present debate on behavioural and functional transfer effects associated with intensive language training. To address this novel issue, we measured professional simultaneous interpreters and control subjects while they performed a non-verbal auditory discrimination task that primarily relies on attention and categorization functions. The fMRI results revealed that the discrimination of the target stimuli was associated with differential blood oxygen level-dependent responses in fronto-parietal regions between the two groups, even though in-scanner behavioural results did not show significant group differences. These findings are in line with previous observations showing the contribution of fronto-parietal regions to auditory attention and categorization functions. Our results imply that language training modulates brain activity in regions involved in the top-down regulation of auditory functions.	\N	\N
21669859	It is generally agreed that considerable amounts of low-level sensory processing of visual stimuli can occur without conscious awareness. On the other hand, the degree of higher level visual processing that occurs in the absence of awareness is as yet unclear. Here, event-related potential (ERP) measures of brain activity were recorded during a sandwich-masking paradigm, a commonly used approach for attenuating conscious awareness of visual stimulus content. In particular, the present study used a combination of ERP activation contrasts to track both early sensory-processing ERP components and face-specific N170 ERP activations, in trials with versus without awareness. The electrophysiological measures revealed that the sandwich masking abolished the early face-specific N170 neural response (peaking at ~170 ms post-stimulus), an effect that paralleled the abolition of awareness of face versus non-face image content. Furthermore, however, the masking appeared to render a strong attenuation of earlier feedforward visual sensory-processing signals. This early attenuation presumably resulted in insufficient information being fed into the higher level visual system pathways specific to object category processing, thus leading to unawareness of the visual object content. These results support a coupling of visual awareness and neural indices of face processing, while also demonstrating an early low-level mechanism of interference in sandwich masking.	\N	\N
21675563	This study examined the effects of visual-verbalload (as measured by a visually presented reading-memory task with three levels) on a visual/auditory stimulus-response task. The three levels of load were defined as follows: "No Load" meant no other stimuli were presented concurrently; "Free Load" meant that a letter (A, B, C, or D) appeared at the same time as the visual or auditory stimulus; and "Force Load" was the same as "Free Load," but the participants were also instructed to count how many times the letter A appeared. The stimulus-response task also had three levels: "irrelevant," "compatible," and "incompatible" spatial conditions. These required different key-pressing responses. The visual stimulus was a red ball presented either to the left or to the right of the display screen, and the auditory stimulus was a tone delivered from a position similar to that of the visual stimulus. Participants also processed an irrelevant stimulus. The results indicated that participants perceived auditory stimuli earlier than visual stimuli and reacted faster under stimulus-response compatible conditions. These results held even under a high visual-verbal load. These findings suggest the following guidelines for systems used in driving: an auditory source, appropriately compatible signal and manual-response positions, and a visually simplified background.	\N	\N
21676085	The phonological deficit theory of dyslexia assumes that degraded speech sound representations might hamper the acquisition of stable letter-speech sound associations necessary for learning to read. However, there is only scarce and mainly indirect evidence for this assumed letter-speech sound association problem. The present study aimed at clarifying the nature and the role of letter-speech sound association problems in dyslexia by analysing event-related potentials (ERP) of 11-year-old dyslexic children to speech sounds in isolation or combined with letters, which were presented either simultaneously with or 200 ms before the speech sounds. Recent studies with normal readers revealed that letters systematically modulated speech sound processing in an early (mismatch negativity or MMN) and late (Late Discriminatory Negativity or LDN) time-window. The amplitude of the MMN and LDN to speech sounds was enhanced when speech sounds were presented with letters. The dyslexic readers in the present study, however, did not exhibit any early influences of letters on speech sounds even after 4 years of reading instruction, indicating no automatic integration of letters and speech sounds. Interestingly, they revealed a systematic late effect of letters on speech sound processing, probably reflecting the mere association of letters and speech sounds. This pattern is strongly divergent from that observed in age-matched normal readers, who showed both early and late effects, but reminiscent of that observed in beginner normal readers in a previous study (Froyen, Bonte, van Atteveldt & Blomert, 2009). The finding that the quality of letter-speech sound processing is directly related to reading fluency urges further research into the role of audiovisual integration in the development of reading failure in dyslexia.	\N	\N
21676091	Early post-natal nutrition influences later development, but there are no studies comparing brain function in healthy infants as a function of dietary intake even though the major infant diets differ significantly in nutrient composition. We studied brain responses (event-related potentials; ERPs) to speech sounds for infants who were fed either breast milk (BF), milk-based formula (MF), or soy formula (SF) during the first 6 months of life. Two syllables presented in an oddball paradigm elicited a late positive wave (P350) from temporal and frontal brain regions involved in language processes. All groups showed significantly greater response amplitudes to the infrequent syllable across sites at 3 months and frontally at 6 months, but significant discrimination at temporal sites was only observed at 6 months in BF infants. Decreases in response amplitudes from 3 to 6 months were greater for the frequently presented syllable, most prominent in BF infants, and greater in females than males. The results indicate greater syllable discrimination in BF than formula-fed infants, but whether this can be attributed to dietary influences alone remains unclear. Feeding method and background factor differences between breastfed and formula-fed infants may also contribute to the observed differences. The general absence of differences between formula-fed groups is notable and suggests that milk-based formula and soy formula equally support brain development and function during the first post-natal 6 months. Finally, the results indicate gender differences in the development of neural and temporal processes involved in sensory discrimination, and suggest that at 6 months these processes are better developed in females.	\N	\N
21676999	The conditions of sound fields used in research, especially testing and fitting of hearing aids, are usually simplified or reduced to fundamental physical fields, such as the free or the diffuse sound field. The concepts of such ideal conditions are easily introduced in theoretical and experimental investigations and in models for directional microphones, for example. When it comes to real-world application of hearing aids, however, the field conditions are more complex with regard to specific stationary and transient properties in room transfer functions and the corresponding impulse responses and binaural parameters. Sound fields can be categorized in outdoor rural and urban and indoor environments. Furthermore, sound fields in closed spaces of various sizes and shapes and in situations of transport in vehicles, trains, and aircrafts are compared with regard to the binaural signals. In laboratory tests, sources of uncertainties are individual differences in binaural cues and too less controlled sound field conditions. Furthermore, laboratory sound fields do not cover the variety of complex sound environments. Spatial audio formats such as higher-order ambisonics are candidates for sound field references not only in room acoustics and audio engineering but also in audiology.	\N	\N
21678230	Studies of change detection have increased our understanding of attention, perception, and memory. In two innovative experiments we showed that the change detection phenomenon can be used to examine other areas of cognition-specifically, the processing of linguistic and indexical information in spoken words. One hypothesis suggests that cognitive resources must be used to process indexical information, whereas an alternative suggests that it is processed more slowly than linguistic information. Participants performed a lexical decision task and were asked whether the voice presenting the stimuli changed. Nonwords varying in their likeness to real words were used in the lexical decision task to encourage participants to vary the amount of cognitive resources/processing time. More cognitive resources/processing time are required to make a lexical decision with word-like nonwords. Participants who heard word-like nonwords were more likely to detect the change when it occurred (Experiment 1) and were more confident that the voice was the same when it did not change (Experiment 2). These results suggest that indexical information is processed more slowly than linguistic information and demonstrate how change detection can provide insight to other areas of cognition.	\N	\N
21681660	Two experiments examined whether perceptual recovery from Korean consonant-cluster simplification is based on language-specific phonological knowledge. In tri-consonantal C1C2C3 sequences such as /lkt/ and /lpt/ in Seoul Korean, either C1 or C2 can be completely deleted. Seoul Koreans monitored for C2 targets (/p/ or / k/, deleted or preserved) in the second word of a two-word phrase with an underlying /l/-C2-/t/ sequence. In Experiment 1 the target-bearing words had contextual lexical-semantic support. Listeners recovered deleted targets as fast and as accurately as preserved targets with both Word and Intonational Phrase (IP) boundaries between the two words. In Experiment 2, contexts were low-pass filtered. Listeners were still able to recover deleted targets as well as preserved targets in IP-boundary contexts, but better with physically-present targets than with deleted targets in Word-boundary contexts. This suggests that the benefit of having target acoustic-phonetic information emerges only when higher-order (contextual and phrase-boundary) information is not available. The strikingly efficient recovery of deleted phonemes with neither acoustic-phonetic cues nor contextual support demonstrates that language-specific phonological knowledge, rather than language-universal perceptual processes which rely on fine-grained phonetic details, is employed when the listener perceives the results of a continuous-speech process in which reduction is phonetically complete.	\N	\N
21682395	The perceived negative influence of standard hearing protectors on communication is a common argument for not wearing them. Thus, "augmented" protectors have been developed to improve speech intelligibility. Nevertheless, their actual benefit remains a point of concern. In this paper, speech perception with active earplugs is compared to standard passive custom-made earplugs. The two types of active protectors included amplify the incoming sound with a fixed level or to a user selected fraction of the maximum safe level. For the latter type, minimal and maximal amplification are selected. To compare speech intelligibility, 20 different speech-in-noise fragments are presented to 60 normal-hearing subjects and speech recognition is scored. The background noise is selected from realistic industrial noise samples with different intensity, frequency, and temporal characteristics. Statistical analyses suggest that the protectors' performance strongly depends on the noise condition. The active protectors with minimal amplification outclass the others for the most difficult and the easiest situations, but they also limit binaural listening. In other conditions, the passive protectors clearly surpass their active counterparts. Subsequently, test fragments are analyzed acoustically to clarify the results. This provides useful information for developing prototypes, but also indicates that tests with human subjects remain essential.	\N	\N
21682407	When a test sound consisting of pure tones with equal intensities is preceded by a precursor sound identical to the test sound except for a reduction in the intensity of one tone, an auditory "enhancement" phenomenon occurs: In the test sound, the tone which was previously softer stands out perceptually. Here, enhancement was investigated using inharmonic sounds made up of five pure tones well resolved in the auditory periphery. It was found that enhancement can be elicited not only by increases in intensity but also by shifts in frequency. In both cases, when the precursor and test sounds are separated by a 500-ms delay, inserting a burst of pink noise during the delay has little effect on enhancement. Presenting the precursor and test sounds to opposite ears rather than to the same ear significantly reduces the enhancement resulting from increases in intensity, but not the enhancement resulting from shifts in frequency. This difference suggests that the mechanisms of enhancement are not identical for the two types of change. For frequency shifts, enhancement may be partly based on the existence of automatic "frequency-shift detectors" [Demany and Ramos, J. Acoust. Soc. Am. 117, 833-841 (2005)].	\N	\N
21688937	Cross-modal temporal recalibration describes a shift in the point of subjective simultaneity (PSS) between 2 events following repeated exposure to asynchronous cross-modal inputs--the adaptors. Previous research suggested that audiovisual recalibration is insensitive to the spatial relationship between the adaptors. Here we show that audiovisual recalibration can be driven by cross-modal spatial grouping. Twelve participants adapted to alternating trains of lights and tones. Spatial position was manipulated, with alternating sequences of a light then a tone, or a tone then a light, presented on either side of fixation (e.g., left tone--left light--right tone--right light, etc.). As the events were evenly spaced in time, in the absence of spatial-based grouping it would be unclear if tones were leading or lagging lights. However, any grouping of spatially colocalized cross-modal events would result in an unambiguous sense of temporal order. We found that adapting to these stimuli caused the PSS between subsequent lights and tones to shift toward the temporal relationship implied by spatial-based grouping. These data therefore show that temporal recalibration is facilitated by spatial grouping.	\N	\N
21689988	Mozart's Sonata for Two Pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart Effect. Our previous work revealed that epileptiform discharges in children with epilepsy decrease during and right after listening to Mozart K.448. However, the duration of the effect was not studied. In the study described here, we evaluated the long-term effect of Mozart K.448 on epileptiform discharges in children with epilepsy. Eighteen children with epilepsy whose seizures were clinically well controlled with antiepileptic drugs were included. For each child, EEGs had revealed persistent epileptiform discharges for at least 6 months. These patients listened to Mozart K.448 for 8 minutes once a day before bedtime for 6 months. Epileptiform discharges were recorded and compared before and after 1, 2, and 6 months of listening to Mozart K.448. All of the children remained on the same antiepileptic drug over the 6 months. Relationships between number of epileptiform discharges and foci of discharges, intelligence, epilepsy etiology, age, and gender were analyzed. Epileptiform discharges significantly decreased by 53.2±47.4, 64.4±47.1, and 71.6±45.8%, respectively, after listening to Mozart K.448 for 1, 2, and 6 months. All patients except those with occipital discharges showed a significant decrease in epileptiform discharges. Patients with normal intelligence and idiopathic epilepsy had greater decreases than those with mental retardation and symptomatic epilepsy. Age and gender did not affect the results. We conclude that long-term listening to Mozart K.448 may be effective in decreasing epileptiform discharges in children with epilepsy in a chronologically progressive manner.	\N	\N
21700953	We previously reported that fast-moving dot arrays cause orientation-tuned masking of static gratings (D. Apthorp, J. Cass, & D. Alais, 2010), which we attribute to "motion streaks." Using similar "streaky" dot motion, we describe spatial frequency tuning of grating threshold elevations caused by masking (Experiment 1) and adaptation (Experiment 2) to motion. To compare the streaks with psychophysical tunings, we Fourier analyzed time-averaged translating dots, which were bandpass (peaking at ∼2.3 c/deg). Masking, however, was strongest at lower test frequencies (≤1 c/deg) and largely isotropic over orientation, although a small orientation-tuned effect occurred at ∼1.2 c/deg. Results were broadly similar across monoptic and dichoptic conditions. Adaptation to fast motion produced spatially bandpass threshold elevations for parallel test gratings, peaking slightly lower than the peak Fourier frequency, with little elevation below 1 c/deg (unlike the low-pass elevation resulting from masking). Slow adaptation produced little elevation for parallel gratings. For orthogonal test gratings, fast motion adaptation produced low-pass threshold elevations and slow motion produced bandpass elevations, suggesting that separable mechanisms process fast (streaky) and slow motion. The different threshold elevation patterns over spatial frequency for masking and adaptation suggest that the adaptation effects are mainly within-channel suppression, whereas the masking effects may be mainly due to between-channel suppression.	\N	\N
21717096	The ocular vestibular evoked myogenic potential (oVEMP) is a relatively new method used to assess otolith-ocular pathways in humans. When elicited using air-conducted (AC) sound stimulation, the oVEMP is thought to reflect mostly saccular activation. However, it has been recently suggested that utricular afferents may also contribute to the AC evoked oVEMP. While previous frequency tuning studies of the AC evoked oVEMP report predominately high frequency sensitivity (>400 Hz), few have included the lower frequencies (<200 Hz) at which it has been proposed the utricle is most sensitive. In this study, ten normal subjects were stimulated with AC sound delivered unilaterally using headphones over frequencies from 50 to 1,200 Hz at a near constant A-weighted intensity of 120 dB peak sound pressure level. For AC stimulation, the oVEMP demonstrated maximum amplitudes around 600 Hz, with a second, smaller peak occurring around 100 Hz. The AC evoked oVEMP tuning has two peaks, a dominant one consistent with excitation of the saccule and a smaller one consistent with excitation of the utricle.	\N	\N
21724369	In spite of voice being an important parameter of mate choice, none of the studies have described the acoustic characteristics of the sexually appealing voice. Two hundred adults (100 men and 100 women) in the age range of 18-24 years were asked to narrate a topic, which was recorded directly onto Computerized Speech Lab (CSL) 6103 hardware. Recorded stimuli were presented to the six judges, and they were asked to indicate if the voice is sexually appealing on a five-point rating scale. The voices, which are consistently identified as sexually very attractive and unattractive were subjected to cepstral analysis through CSL. The results of perceptual analysis revealed that 28 of the female voice samples and 39 of the male voice samples were rated as sexually attractive. These ratings were consistent within and across the judges. The cepstral analysis was then performed in all the voice samples and the results of independent t test revealed higher values of cepstral peak parameter (CPP) in the sexually attractive voices in comparison to the other voice samples in both the genders. The obtained results are discussed with respect to the harmonic organization in the voice samples. The results of cepstral analysis in sexually attractive voices revealed higher values of CPP in comparison to the voices rated as sexually not appealing. This could be because of the presence of well-defined harmonic structure evidenced in the sexually appealing voice in comparison to voices rated as very unappealing. Our findings suggest that cepstral analysis is a good indicator of sexually appealing voice.	\N	\N
21728456	Cognitive control resolves conflicts between appropriate and inappropriate response tendencies. Is this achieved by a unitary all-purpose conflict control system, or do independent subsystems deal with different aspects of conflicting information? In a fully factorial hybrid prime-Simon task, participants responded to the identity of targets displayed at different nominally irrelevant screen locations, preceded by nominally irrelevant, consciously or nonconsciously perceived primes. The response required by the target's identity could match or mismatch (a) the target's location, and (b) the prime's identity, resulting in potential conflict (a) across and (b) within stimulus domains. Conflict effects were investigated within and across trials. Results suggest that (i) nonconsciously perceived information elicits within-trial control, but--unlike consciously perceived information--no across-trial behavioral modulation; (ii) separate subsystems deal with conflicts arising from different stimulus domains; and (iii) occasional apparent interactions between domains reflect a particular difficulty in reactivating a just-discarded response (reactivation aversion effect, RAE).	\N	\N
21728464	Increasing perceptual load reduces the processing of visual stimuli outside the focus of attention, but the mechanism underlying these effects remains unclear. Here we tested an account attributing the effects of perceptual load to modulations of visual cortex excitability. In contrast to stimulus competition accounts, which propose that load should affect simultaneous, but not sequential, stimulus presentations, the visual excitability account makes the novel prediction that load should affect detection sensitivity for both simultaneous and sequential presentations. Participants fixated a stimulus stream, responding to targets defined by either a color (low load) or color and orientation conjunctions (high load). Additionally, detection sensitivity was measured for a peripheral critical stimulus (CS) presented occasionally. Increasing load at fixation reduced sensitivity to the peripheral CSs; this effect was similar regardless of whether CSs were presented simultaneously with central stimuli or during the (otherwise empty) interval between them. Controls ruled out explanations of the results in terms of strategic task prioritization. These findings support a cortical excitability account for perceptual load, challenging stimulus competition accounts.	\N	\N
21729437	To describe the effect of age and noise on high frequency hearing thresholds in an Italian population aged 70 years and older, in order to investigate the interaction between presbycusis and noise exposure. We compared 460 subjects: 367 affected by presbycusis alone (204 women and 163 men) and 93 affected by presbycusis and noise exposure (eight women and 85 men). Pure tone average hearing thresholds, for each ear, were compared between groups, and between sexes and ages within groups. A slight threshold difference was found between the two groups at 4 kHz. After adjusting for age and gender, this difference was found to be related only to differing patient age. Men's and women's thresholds differed significantly in both groups, especially at high frequencies, at which threshold deterioration was worse in men than women. The threshold differences between patients with presbycusis with and without noise exposure were limited. Larger studies are needed to assess the relative effects of ageing and noise exposure on hearing thresholds.	\N	\N
21750713	In the present study we investigated the capacity of the memory store underlying the mismatch negativity (MMN) response in musicians and nonmusicians for complex tone patterns. While previous studies have focused either on the kind of information that can be encoded or on the decay of the memory trace over time, we studied capacity in terms of the length of tone sequences, i.e., the number of individual tones that can be fully encoded and maintained. By means of magnetoencephalography (MEG) we recorded MMN responses to deviant tones that could occur at any position of standard tone patterns composed of four, six or eight tones during passive, distracted listening. Whereas there was a reliable MMN response to deviant tones in the four-tone pattern in both musicians and nonmusicians, only some individuals showed MMN responses to the longer patterns. This finding of a reliable capacity of the short-term auditory store underlying the MMN response is in line with estimates of a three to five item capacity of the short-term memory trace from behavioural studies, although pitch and contour complexity covaried with sequence length, which might have led to an understatement of the reported capacity. Whereas there was a tendency for an enhancement of the pattern MMN in musicians compared to nonmusicians, a strong advantage for musicians could be shown in an accompanying behavioural task of detecting the deviants while attending to the stimuli for all pattern lengths, indicating that long-term musical training differentially affects the memory capacity of auditory short-term memory for complex tone patterns with and without attention. Also, a left-hemispheric lateralization of MMN responses in the six-tone pattern suggests that additional networks that help structuring the patterns in the temporal domain might be recruited for demanding auditory processing in the pitch domain.	\N	\N
21755126	To assess the difficulty of paced auditory serial addition test (PASAT) in a population of high intellectual level, under ideal cognitive testing circumstances. One hundred medical students underwent PASAT testing. They had slept well the night before, they had eaten before the assessment, they were not using any drugs that could affect the central nervous system and they did not have depression, anxiety or any chronic disease. The average result from the three-second version of PASAT was 57.5% and, from the two-second version, it was 44.3%. Even under ideal circumstances, PASAT is a very difficult test for the general population. It may not be ideal for neurologists to screen, assess and follow up patients with cognitive function in multiple sclerosis.	\N	\N
21762032	Reaction times for categorization of a probe face according to its sex or fame were contrasted as a function of whether the category of a preceding, sandwich-masked prime face was congruent or incongruent. Prime awareness was measured by the ability to later categorize the primes, and this was close to chance and typically uncorrelated with priming. When prime faces were never presented as visible probes within a test, priming was not reliable; when prime faces were also seen as probes, priming was only reliable if visible and masked presentation of faces were interleaved (not simply if primes had been visible in a previous session). In the latter case, priming was independent of experimentally induced face-response or face-category contingencies, ruling out any simple form of stimulus-response learning. We conclude that the reliable masked congruency priming reflects bindings between stimuli and multiple, abstract classifications that can be generated both overtly and covertly.	\N	\N
21762876	Schizophrenia patients have vocal affect (prosody) deficits that are treatment resistant and associated with negative symptoms and poor outcome. The neural correlates of this dysfunction are unclear. Prior study has suggested that schizophrenia vocal affect perception deficits stem from an inability to use acoustic cues, notably pitch, in decoding emotion. Functional magnetic resonance imaging was performed in 24 schizophrenia patients and 28 healthy control subjects, during the performance of a four-choice (happiness, fear, anger, neutral) vocal affect identification task in which items for each emotion varied parametrically in affective salient acoustic cue levels. We observed that parametric increases in cue levels in schizophrenia failed to produce the same identification rate increases as in control subjects. These deficits correlated with diminished reciprocal activation changes in superior temporal and inferior frontal gyri and reduced temporo-frontal connectivity. Task activation also correlated with independent measures of pitch perception and negative symptom severity. These findings illustrate the interplay between sensory and higher-order cognitive dysfunction in schizophrenia. Sensory contributions to vocal affect deficits also suggest that this neurobehavioral marker could be targeted by pharmacological or behavioral remediation of acoustic feature discrimination.	\N	\N
21765387	To compare hearing results in patients undergoing ossiculoplasty using either partial ossicular replacement prosthesis (PORP) or total ossicular replacement prosthesis (TORP) with Silastic banding and malleus relocation techniques in cases with malleus and stapes both present and mobile. Prospective nonrandomized clinical study. Tertiary referral center. Five hundred eighty-five patients undergoing ossiculoplasty were enrolled in this study from April 1991 to May 2010. Comparative analyses were made between a group of 304 patients who underwent ossiculoplasty with partial prosthesis positioned from the malleus to the stapes head and 281 patients who underwent ossiculoplasty with total prosthesis positioned from the malleus to the stapes footplate. Preoperative and postoperative audiometric evaluation using conventional audiometry, that is, air-bone gap (ABG), bone-conduction thresholds, and air-conduction thresholds were assessed. In the PORP group, the mean postoperative ABG was 13.1 dB compared with 8.9 dB in the TORP group, (95% confidence interval [CI], 2.2-6.2 dB; p ≤ 0.001). Fifty-four percent of patients from the PORP group had a postoperative ABG of 10 dB or less, compared with 68.9% in the TORP group (mean difference, 14.6%; 95% CI, 6%-23%; p < 0.001). The postoperative ABG was closed to within 20 dB in 70.4% of cases in the PORP group compared with 86.9% in the TORP group (mean difference, 14.5%; 95% CI, 10%-23%; p < 0.001). In patients with an absent incus and intact stapes and malleus, ossicular reconstruction with TORP combined with our malleus relocation and Silastic banding technique results in significantly better hearing outcomes compared with reconstructions with PORP.	\N	\N
21767048	The urge to move in response to music, combined with the positive affect associated with the coupling of sensory and motor processes while engaging with music (referred to as sensorimotor coupling) in a seemingly effortless way, is commonly described as the feeling of being in the groove. Here, we systematically explore this compelling phenomenon in a population of young adults. We utilize multiple levels of analysis, comprising phenomenological, behavioral, and computational techniques. Specifically, we show (a) that the concept of the groove is widely appreciated and understood in terms of a pleasurable drive toward action, (b) that a broad range of musical excerpts can be appraised reliably for the degree of perceived groove, (c) that the degree of experienced groove is inversely related to experienced difficulty of bimanual sensorimotor coupling under tapping regimes with varying levels of expressive constraint, (d) that high-groove stimuli elicit spontaneous rhythmic movements, and (e) that quantifiable measures of the quality of sensorimotor coupling predict the degree of experienced groove. Our results complement traditional discourse regarding the groove, which has tended to take the psychological phenomenon for granted and has focused instead on the musical and especially the rhythmic qualities of particular genres of music that lead to the perception of groove. We conclude that groove can be treated as a psychological construct and model system that allows for experimental exploration of the relationship between sensorimotor coupling with music and emotion.	\N	\N
21786896	The form of the psychometric function (PF) for auditory frequency discrimination is of theoretical interest and practical importance. In this study, PFs for pure-tone frequency discrimination were measured for several standard frequencies (200-8000 Hz) and levels [35-85 dB sound pressure level (SPL)] in normal-hearing listeners. The proportion-correct data were fitted using a cumulative-Gaussian function of the sensitivity index, d', computed as a power transformation of the frequency difference, Δf. The exponent of the power function corresponded to the slope of the PF on log(d')-log(Δf) coordinates. The influence of attentional lapses on PF-slope estimates was investigated. When attentional lapses were not taken into account, the estimated PF slopes on log(d')-log(Δf) coordinates were found to be significantly lower than 1, suggesting a nonlinear relationship between d' and Δf. However, when lapse rate was included as a free parameter in the fits, PF slopes were found not to differ significantly from 1, consistent with a linear relationship between d' and Δf. This was the case across the wide ranges of frequencies and levels tested in this study. Therefore, spectral and temporal models of frequency discrimination must account for a linear relationship between d' and Δf across a wide range of frequencies and levels.	\N	\N
21787870	Repetition has been shown to activate the so-called 'dorsal stream', a network of temporo-parieto-frontal areas subserving the mapping of acoustic speech input onto articulatory-motor representations. Among these areas, a region in the posterior Sylvian fissure at the temporo-parietal boundary (also called 'area Spt') has been suggested to play a central role particularly with increasing computational demands on phonological processing. Most of the relevant evidence stems from tasks requiring metalinguistic processing. To date, the relevance of area Spt in natural phonological operations based on implicit linguistic knowledge has not yet been investigated. We examined two types of phonological processes assumed to be lateralized differently, i.e., the processing of syllabic stress versus subsyllabic segmental processing. In two ways, subjects modified an auditorily presented pseudoword before reproducing it overtly: (a) by a prosodic manipulation involving a stress shift across syllable boundaries, (b) by a segmental manipulation involving a vowel substitution. Manipulation per se was expected to engage area Spt. Segmental compared to prosodic processing was expected to reveal predominantly left lateralized activation, while prosodic compared to segmental processing was expected to result in bilateral or right-lateralized activation. Contrary to expectation, activation in area Spt did not vary with increased phonological processing demand. Instead, area Spt was engaged regardless of whether subjects simply repeated a pseudoword or performed a phonological manipulation before reproduction. However, for both segmental and prosodic stimuli, reproduction after manipulation (compared to repetition) activated the left intraparietal sulcus and left inferior frontal cortex. We propose that these parieto-frontal regions are recruited when the task requires phonological manipulation over and above the more automated transfer of auditory into articulatory verbal codes, which appears to involve area Spt. When directly contrasted with prosodic manipulation, segmental manipulation resulted in increased activation predominantly in left inferior frontal areas. This may be due to an increased demand on phonological sequencing operations at the subsyllabic phoneme level. Contrasted with segmental manipulations, prosodic manipulation did not result in increased activation, which may be due to a lower degree of morphosyntactic and to syllable-level processing.	\N	\N
21792976	To evaluate vestibular function in patients with the mitochondrial A3243G mutation. Data from patients with the A3243G mutation attending an academic tertiary referral center were prospectively recorded. The clinical histories of 13 unrelated patients with the mitochondrial A3243G mutation (six mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; and seven maternally inherited diabetes and deafness) were recorded, in particular their history of vestibular symptoms. Vestibular examinations including caloric testing and vestibular evoked myogenic potentials in response to air-conducted sound (ACS-VEMPs) were performed. In seven patients who showed abnormal ACS-VEMP, VEMP in response to galvanic stimuli (galvanic-VEMP) were also recorded. Eleven of the 13 patients had vestibular symptoms. The age of onset of vestibular symptoms was significantly later than the ages of onset of hearing loss and diabetes mellitus (P < .05). Ten of the 13 patients showed abnormal caloric responses, whereas 12 patients showed abnormal ACS-VEMPs on one or both sides. All of the seven patients who underwent galvanic-VEMP testing showed normal responses. The A3243G mutation is associated with vestibular dysfunction involving both the superior and inferior vestibular nerve systems. Furthermore, our results from galvanic-VEMP testing suggests that a labyrinthine lesion is primarily responsible for the symptoms of vestibular dysfunction.	\N	\N
21812557	Several perspectives on speech perception posit a central role for the representation of articulations in speech comprehension, supported by evidence for premotor activation when participants listen to speech. However, no experiments have directly tested whether motor responses mirror the profile of selective auditory cortical responses to native speech sounds or whether motor and auditory areas respond in different ways to sounds. We used fMRI to investigate cortical responses to speech and nonspeech mouth (ingressive click) sounds. Speech sounds activated bilateral superior temporal gyri more than other sounds, a profile not seen in motor and premotor cortices. These results suggest that there are qualitative differences in the ways that temporal and motor areas are activated by speech and click sounds: Anterior temporal lobe areas are sensitive to the acoustic or phonetic properties, whereas motor responses may show more generalized responses to the acoustic stimuli.	\N	\N
21812560	Complex auditory exposures in ambient environments include systems of not only linguistic but also musical sounds. Because musical exposure is often passive, consisting of listening rather than performing, examining listeners without formal musical training allows for the investigation of the effects of passive exposure on our nervous system without active use. Additionally, studying listeners who have exposure to more than one musical system allows for an evaluation of how the brain acquires multiple symbolic and communicative systems. In the present fMRI study, listeners who had been exposed to Western-only (monomusicals) and both Indian and Western musical systems (bimusicals) since childhood and did not have significant formal musical training made tension judgments on Western and Indian music. Significant group by music interactions in temporal and limbic regions were found, with effects predominantly driven by between-music differences in temporal regions in the monomusicals and by between-music differences in limbic regions in the bimusicals. Effective connectivity analysis of this network via structural equation modeling (SEM) showed significant path differences across groups and music conditions, most notably a higher degree of connectivity and larger differentiation between the music conditions within the bimusicals. SEM was also used to examine the relationships among the degree of music exposure, affective responses, and activation in various brain regions. Results revealed a more complex behavioral-neural relationship in the bimusicals, suggesting that affective responses in this group are shaped by multiple behavioral and neural factors. These three lines of evidence suggest a clear differentiation of the effects of the exposure of one versus multiple musical systems.	\N	\N
21812631	To determine administration times for word recognition presented via monitored live voice (MLV) and compact disc (CD) recordings. A quasi-experimental design was used. Fifty-word NU-6 lists were presented in three conditions: (1) MLV, (2) short ISI CD recording, and (3) long ISI CD recording. Listeners with normal hearing (NH) and hearing impairment (HI) participated in this study. Average administration time using MLV was significantly shorter than using recorded word lists for both groups of listeners. MLV presentation to the NH listeners was significantly faster than the MLV presentation to the HI listeners. There were no significant differences between groups in the administration times for any of the recorded lists (long or short ISI). Considerably more variability in administration time was observed for MLV presentation compared to recorded presentations. MLV presentation was about one minute faster than the shortest CD recording of the NU-6 fifty-item word lists, but it was only 49 seconds quicker when administering tests to individuals with hearing loss. Because the majority of our patients are hearing impaired, the difference of 49 seconds is not clinically significant. This difference is even less when 25-item word lists are used.	\N	\N
21812635	The objective of this study was to evaluate hearing loss among workers exposed to styrene, alone or with noise. This cross-sectional study was conducted as part of NoiseChem, a European Commission 5th Framework Programme research project, by occupational health institutes in Finland, Sweden, and Poland. Participants' ages ranged from 18-72 years (n = 1620 workers). Participants exposed to styrene, alone or with noise, were from reinforced fiberglass products manufacturing plants (n = 862). Comparison groups were comprised of workers noise-exposed (n = 400) or controls (n = 358). Current styrene exposures ranged from 0 to 309 mg/m(3), while mean current noise levels ranged from 70-84 dB(A). Hearing thresholds of styrene-exposed participants were compared with Annexes A and B from ANSI S3.44, 1996. The audiometric thresholds of styrene exposed workers were significantly poorer than those in published standards. Age, gender, and styrene exposure met the significance level criterion in the multiple logistic regression for the binary outcome 'hearing loss' (P = 0.0000). Exposure to noise (<85 dBA p = 0.0001; ≥85 dB(A) p = 0.0192) interacted significantly with styrene exposure. Occupational exposure to styrene is a risk factor for hearing loss, and styrene-exposed workers should be included in hearing loss prevention programs.	\N	\N
21817926	Recent studies have shown that audiovisual synchrony is recalibrated after exposure to asynchronous auditory and visual signals. This temporal recalibration has been shown only under a dual-task situation for speech signals. Here we examined whether the temporal recalibration occurs for audiovisual speech in a single-task situation using an offline adaptation method. In the experiment, participants were exposed to synchronous or asynchronous audiovisual syllables (either congruent or incongruent) for 3 min. The adaptation phase was followed by test trials, in which participants judged whether the auditory or visual stimulus was presented first. Results showed shifts in the point of subjective simultaneity and the sensitivity. Our results suggest that attention to adaptation stimuli is necessary to induce temporal recalibration for speech.	\N	\N
21824022	Attentional bias to threatening visual stimuli (words or pictures) is commonly present in anxious individuals, but not in non-anxious people. There is evidence to show that attentional bias to threat can be induced in all individuals when threat is imposed by threat not of symbolic nature, but by cues that predict aversive stimulation (loud noise or electric shock). However, it is not known whether attentional bias in such situations is still influenced by individual differences in anxiety. This question was addressed in two experiments using a spatial cuing task in which visual cues predicted the occurrence of an aversive event consisting of a loud human scream. Speeded attentional engagement to threat cues was positively correlated with trait anxiety in Experiment 1. Experiment 2 showed that speeded attentional engagement was present only in participants selected for high anxiety but not in low-anxious participants. In both experiments, slower disengagement from threat cues was found in all participants, irrespective of their trait anxiety levels.	\N	\N
21826005	Reduced hearing ability has been shown to influence various aspects of daily life, such as communication, psychosocial functioning, and working life. The aim of this study is to examine the association between hearing ability in noise and both sick leave and self-reported work productivity. In addition, the relationship between hearing ability and perceived health-caused limitations at work is examined. Data were collected at the baseline measurement of the Dutch "National Longitudinal Study on Hearing" and at each month during a subsequent period of 3 mo. Hearing ability was determined by means of the National Hearing Test, a speech-in-noise test over the Internet using digit triplets. The sample comprised 748 workers (385 with normal hearing ability and 363 with insufficient or poor hearing ability). Linear regression analyses revealed a significant adverse association between reduced hearing ability and self-reported absolute and differential productivity; for every dB signal-to-noise ratio (dB SNR) poorer hearing ability, self-rated absolute productivity for people experiencing little social support decreased by 0.054 points on a scale from 0 to 10 (b = -0.054; 95% confidence interval [CI] = -0.088 to -0.02). For people with less than three other chronic conditions, self-rated differential productivity also decreased significantly with decreasing hearing ability (no chronic conditions: b = -0.048 points/dB SNR on a scale from -10 to + 10, 95% CI = -0.094 to -0.001; one or two other chronic conditions: b = -0.035 points/dB SNR, 95% CI = -0.067 to -0.002). With adjustment for confounders, poorer hearing ability in noise furthermore significantly increased the odds for experiencing limitations (in the type or amount of work one could do) sometimes (odds ratio = 1.14; 95% CI = 1.07-1.21) and often to very often (odds ratio = 1.24; 95% CI = 1.05-1.45) in comparison with experiencing limitation seldom to never. A higher level of need for recovery among people with poorer hearing ability appeared to be one of the factors mediating the higher odds for sick leave of more than 5 days. Reduced hearing ability in noise was significantly associated with a lower self-reported absolute and differential productivity in specific cases. Also, poorer hearing increased the odds for experiencing health-caused limitations in the type or amount of work one can do. The significant relationship between hearing ability and sick leave, which was found when not adjusting for confounders, could partly be explained by a higher need for recovery among people with reduced hearing ability in noise.	\N	\N
21832862	To investigate interactions (if any) in the bone-conduction auditory steady-state response (BC ASSR) between multiple brief tones presented simultaneously. 500-, 1,000-, 2,000-, and 4,000-Hz brief tones, repeated at a rate of 77-101 Hz, were presented using a B-71 vibrator. BC ASSR thresholds and amplitudes at 50 dB nHL were measured in two conditions where the stimulus was either presented alone or together with other stimuli. Significantly larger amplitudes in the single-stimulus condition were found at 50 dB nHL. However, there was no significant threshold difference between single- and multiple-stimulus conditions. The BC ASSR thresholds (means ± SD) at 500, 1,000, 2,000, and 4,000 Hz were 96.7 ± 9.7, 75.3 ± 11.5, 65.6 ± 7.4, and 57.8 ± 7.2 dB re 1 μN ppe, respectively. Interactions occurred in the multiple-stimulus condition at high presentation levels, but not at threshold levels. The results of the present study imply that BC ASSR thresholds to multiple brief-tone stimuli can be assessed at the same time, at least in normal-hearing adults.	\N	\N
21832892	This report focuses on how speech perception, speech production, language, and literacy performance in adolescence are influenced by a common set of predictor variables obtained during elementary school in a large group of teenagers using cochlear implants (CIs). Time-lag analyses incorporating seven common predictor variables associated with the elementary school test period were evaluated. The elementary school-age variables included five contributors across the performance domains: gender, performance intelligence quotient, family size, socioeconomic status, and duration of deafness (operationally defined as the time period between the age of implantation and the onset of deafness). Regression analyses then examined how communication mode in early elementary grades influenced skills exhibited in high school and how this influence was mediated by information capacity of immediate memory. High correlations occurred between outcome measures collected at CI-E session and similar measures collected at CI-HS (values ranging from 0.75 to 0.83), indicating that the relative standing of individuals on these outcomes is highly stable over time. The best performers in elementary grades exhibit the best outcomes in high school, and early difficulties tend to persist throughout the elementary and high school years. The most highly related outcome areas were language and reading/literacy (values ranging from 0.74 to 0.88). These skills seem closely linked, and CI children who demonstrate the best vocabulary and syntax skills in elementary grades achieved the highest literacy performance in high school. Speech perception and speech production skills are also highly correlated with one another (r = 0.69 to 0.87), suggesting that the most direct result of improved auditory input from a CI is the child's ability to produce intelligible speech. The lowest correlations are observed between reading/literacy and speech perception (r = 0.30 to 0.54) or speech production (values ranging from 0.31 to 0.58). CI-E verbal rehearsal speed is an independent and powerful predictor of each early performance outcome, accounting for between 13% and 30% of the variance in early outcomes above and beyond that accounted for by gender, family size, socioeconomic status, performance intelligence quotient, duration of deafness, and the CI-E sign enhancement ratio. Group mean scores for language, reading, and social adjustment were generally within an SD of normative samples of typically developing age-mates with normal hearing. Use of sign to enhance spoken communication negatively influenced verbal rehearsal speed, which was a strong predictor of all early outcomes, which in turn strongly influenced later outcomes. These analyses suggest that early communication mode exerts a powerful influence on early outcomes that persist into later years. Speech perception, speech intelligibility, language, literacy, and psychosocial adjustment far exceeded that reported for similar groups before the advent of CI technology.	\N	\N
21835531	Behavioral and neurophysiological transfer effects from music experience to language processing are well-established but it is currently unclear whether or not linguistic expertise (e.g., speaking a tone language) benefits music-related processing and its perception. Here, we compare brainstem responses of English-speaking musicians/non-musicians and native speakers of Mandarin Chinese elicited by tuned and detuned musical chords, to determine if enhancements in subcortical processing translate to improvements in the perceptual discrimination of musical pitch. Relative to non-musicians, both musicians and Chinese had stronger brainstem representation of the defining pitches of musical sequences. In contrast, two behavioral pitch discrimination tasks revealed that neither Chinese nor non-musicians were able to discriminate subtle changes in musical pitch with the same accuracy as musicians. Pooled across all listeners, brainstem magnitudes predicted behavioral pitch discrimination performance but considering each group individually, only musicians showed connections between neural and behavioral measures. No brain-behavior correlations were found for tone language speakers or non-musicians. These findings point to a dissociation between subcortical neurophysiological processing and behavioral measures of pitch perception in Chinese listeners. We infer that sensory-level enhancement of musical pitch information yields cognitive-level perceptual benefits only when that information is behaviorally relevant to the listener.	\N	\N
21840170	This study investigates the effect of consensus training of listeners on intrarater and interrater reliability and agreement of perceptual voice analysis. The use of such training, including a reference voice sample, could be assumed to make the internal standards held in memory common and more robust, which is of great importance to reduce the variability of auditory perceptual ratings. A prospective design with testing before and after training. Thirteen students of audiologopedics served as listening subjects. The ratings were made using a multidimensional protocol with four-point equal-appearing interval scales. The stimuli consisted of text reading by authentic dysphonic patients. The consensus training for each perceptual voice parameter included (1) definition, (2) underlying physiology, (3) presentation of carefully selected sound examples representing the parameter in three different grades followed by group discussions of perceived characteristics, and (4) practical exercises including imitation to make use of the listeners' proprioception. Intrarater reliability and agreement showed a marked improvement for intermittent aphonia but not for vocal fry. Interrater reliability was high for most parameters before training with a slight increase after training. Interrater agreement showed marked increases for most voice quality parameters as a result of the training. The results support the recommendation of specific consensus training, including use of a reference voice sample material, to calibrate, equalize, and stabilize the internal standards held in memory by the listeners.	\N	\N
21842332	The visible movement of a talker's face is an influential component of speech perception. However, the ability of this influence to function when large areas of the face (~50%) are covered by simple substantial occlusions, and so are not visible to the observer, has yet to be fully determined. In Experiment 1, both visual speech identification and the influence of visual speech on identifying congruent and incongruent auditory speech were investigated using displays of a whole (unoccluded) talking face and of the same face occluded vertically so that the entire left or right hemiface was covered. Both the identification of visual speech and its influence on auditory speech perception were identical across all three face displays. Experiment 2 replicated and extended these results, showing that visual and audiovisual speech perception also functioned well with other simple substantial occlusions (horizontal and diagonal). Indeed, displays in which entire upper facial areas were occluded produced performance levels equal to those obtained with unoccluded displays. Occluding entire lower facial areas elicited some impairments in performance, but visual speech perception and visual speech influences on auditory speech perception were still apparent. Finally, implications of these findings for understanding the processes supporting visual and audiovisual speech perception are discussed.	\N	\N
21846981	The Nucleus Straight Research Array (SRA) cochlear implant has a new 25-mm electrode carrier designed to minimize insertion trauma, in particular allowing easy insertion via the round window. The aims of this study were to measure preoperative to postoperative benefit in terms of speech recognition in quiet and in noise in three groups of patients (electrical complement, EC; electrical stimulation, ES; electro-acoustic stimulation, EAS) with varying levels of low-frequency hearing, and to evaluate the preservation of residual hearing after implantation with the SRA cochlear implant. The study design was prospective with sequential enrolment and within-subject comparisons: 23 adult cochlear implant candidates were divided into three groups according to their level of preoperative residual hearing at 500 Hz (EC ≤50 dB; 50 dB < EAS < 80 dB; ES ≥80 dB). Monosyllabic word recognition using the SRA cochlear implant in combination with residual low-frequency hearing was assessed at 4 and 13 months after implantation. Hearing threshold levels were also monitored over time. Subjects across all three groups had significant improvements in speech recognition scores (i.e. >20 percentage points) both for listening in quiet (71% of subjects) and in noise (100% of subjects). The average score at 4 months after operation for words presented in quiet was 61.7%, and in 10 dB SNR noise 46.5%, compared to 34.4 and 10.6% preoperatively (p < 0.001). All subjects retained measurable hearing at 500 Hz in the implanted ear at 4 months after the operation; mean increases were 19, 29 and 1 dB for the EC, EAS and ES groups (n = 21). Across frequencies of 125-1000 Hz, the median increase in thresholds was 15 dB up to 13 months postoperatively (n = 15). Speech recognition performance of subjects with various levels of residual low-frequency hearing was significantly improved with the SRA cochlear implant. A high level and rate of hearing preservation was achieved with the SRA implanted using a round window surgical technique. Subjects with preoperative low-frequency hearing levels between 50 and 80 dB HL (EAS group) tended to lose more hearing than those with either better or worse hearing.	\N	\N
21848924	Tinnitus is characterized by an ongoing conscious perception of a sound in the absence of any external sound source. Chronic tinnitus is notoriously characterized by its resistance to treatment. In the present study the objective was to verify whether the neural generators and/or the neural tinnitus network, evaluated through EEG recordings, change over time as previously suggested by MEG. We therefore analyzed the source-localized EEG recordings of a very homogenous group of left-sided narrow-band noise tinnitus patients. Results indicate that the generators involved in tinnitus of recent onset seem to change over time with increased activity in several brain areas [auditory cortex, supplementary motor area and dorsal anterior cingulate cortex (dACC) plus insula], associated with a decrease in connectivity between the different auditory and nonauditory brain structures. An exception to this general connectivity decrease is an increase in gamma-band connectivity between the left primary and secondary auditory cortex and the left insula, and also between the auditory cortices and the right dorsal lateral prefrontal cortex. These networks are both connected to the left parahippocampal area. Thus acute and chronic tinnitus are related to differential activity and connectivity in a network comprising the auditory cortices, insula, dACC and premotor cortex.	\N	\N
21849065	Segregating auditory scenes into distinct objects or streams is one of our brain's greatest perceptual challenges. Streaming has classically been studied with bistable sound stimuli, perceived alternately as a single group or two separate groups. Throughout the last decade different methodologies have yielded inconsistent evidence about the role of auditory cortex in the maintenance of streams. In particular, studies using functional magnetic resonance imaging (fMRI) have been unable to show persistent activity within auditory cortex (AC) that distinguishes between perceptual states. We use bistable stimuli, an explicit perceptual categorization task, and a focused region of interest (ROI) analysis to demonstrate an effect of perceptual state within AC. We find that AC has more activity when listeners perceive the split percept rather than the grouped percept. In addition, within this ROI the pattern of acoustic response across voxels is significantly correlated with the pattern of perceptual modulation. In a whole-brain exploratory test, we corroborate previous work showing an effect of perceptual state in the intraparietal sulcus. Our results show that the maintenance of auditory streams is reflected in AC activity, directly relating sound responses to perception, and that perceptual state is further represented in multiple, higher level cortical regions.	\N	\N
21861386	The listener-distinctive features of recognition of different emotional intonations (positive, negative and neutral) of male and female speakers in the presence or absence of background noise were studied in 49 adults aged 20-79 years. In all the listeners noise produced the most pronounced decrease in recognition accuracy for positive emotional intonation ("joy") as compared to other intonations, whereas it did not influence the recognition accuracy of "anger" in 65-79-year-old listeners. The higher emotion recognition rates of a noisy signal were observed for speech emotional intonations expressed by female speakers. Acoustic characteristics of noisy and clear speech signals underlying perception of speech emotional prosody were found for adult listeners of different age and gender.	\N	\N
21862447	The distractibility that older adults experience when listening to speech in challenging conditions has been attributed in part to reduced inhibition of irrelevant information within and across sensory systems. Whereas neuroimaging studies have shown that younger adults readily suppress visual cortex activation when listening to auditory stimuli, it is unclear the extent to which declining inhibition in older adults results in reduced suppression or compensatory engagement of other sensory cortices. The current functional magnetic resonance imaging study examined the effects of age and stimulus intelligibility in a word listening task. Across all participants, auditory cortex was engaged when listening to words. However, increasing age and declining word intelligibility had independent and spatially similar effects: both were associated with increasing engagement of visual cortex. Visual cortex activation was not explained by age-related differences in vascular reactivity but rather auditory and visual cortices were functionally connected across word listening conditions. The nature of this correlation changed with age: younger adults deactivated visual cortex when activating auditory cortex, middle-aged adults showed no relation, and older adults synchronously activated both cortices. These results suggest that age and stimulus integrity are additive modulators of crossmodal suppression and activation.	\N	\N
21875609	Event-related potential (ERP) evidence indicates that listeners selectively attend to word onsets in continuous speech, but the reason for this preferential processing is unknown. The current study measured ERPs elicited by syllable onsets in an artificial language to test the hypothesis that listeners direct attention to word onsets because their identity is unpredictable. Both before and after recognition training, participants listened to a continuous stream of six nonsense words arranged in pairs, such that the second word in each pair was completely predictable. After training, first words in pairs elicited a larger negativity beginning around 100 ms after onset. This effect was not evident for the completely predictable second words in pairs. These results suggest that listeners are most likely to attend to the segments in speech that they are least able to predict.	\N	\N
21877811	The conventional articulation index (AI) measure cannot be applied in situations where non-linear operations are involved and additive noise is present. This is because the definitions of the target and masker signals become vague following non-linear processing, as both the target and masker signals are affected. The aim of the present work is to modify the basic form of the AI measure to account for non-linear processing. This was done using a new definition of the output or effective SNR obtained following non-linear processing. The proposed output SNR definition for a specific band was designed to handle cases where the non-linear processing affects predominantly the target signal rather than the masker signal. The proposed measure also takes into consideration the fact that the input SNR in a specific band cannot be improved following any form of non-linear processing. Overall, the proposed measure quantifies the proportion of input band SNR preserved or transmitted in each band after non-linear processing. High correlation (r = 0.9) was obtained with the proposed measure when evaluated with intelligibility scores obtained by normal-hearing listeners in 72 noisy conditions involving noise-suppressed speech corrupted in four different real-world maskers.	\N	\N
21884311	Infants attune to their birth language during the second half of infancy. However, internationally adopted children are often uniquely required to attune to their birth language, and then reattune to their adoptive language. Children who were adopted from India into America at ages 6-60 months (N = 8) and had minimal further exposure to their birth languages were compared to age-matched American non-adopted controls. Without training, neither group could discriminate a phonemic contrast that occurs in their birth language but not in English. However, after training on the contrast, the adopted group (N = 8) improved significantly and discriminated the contrast more accurately than their non-adopted peers. While English had explicitly replaced the birth language of the adopted sample, traces of early exposure conferred privileges on subsequent learning. These findings are consistent with behavioral and neurophysiological data from animals that have identified some of the mechanisms underlying such a 'retention without further use' phenomenon.	\N	\N
21895386	An important step in developing a theory of calibration is establishing what it is that participants become calibrated to as a result of feedback. Three experiments used a transfer of calibration paradigm to investigate this issue. In particular, these experiments investigated whether recalibration of perception of length transferred from audition to dynamic (i.e., kinesthetic) touch when objects were grasped at one end (Experiment 1), when objects were grasped at one end and when they were grasped at a different location (i.e., the middle) (Experiment 2), and when false (i.e., inflated) feedback was provided about object length (Experiment 3). In all three experiments, there was a transfer of recalibration of perception of length from audition to dynamic touch when feedback was provided on perception by audition. Such results suggest that calibration is not specific to a particular perceptual modality and are also consistent with previous research that perception of object length by audition and dynamic touch are each constrained by the object's mechanical properties.	\N	\N
21898434	To determine the effect of cochlear implantation (CI) on health-related quality of life (HRQoL), tinnitus, and psychological comorbidity in patients with severe to profound postlingual hearing loss and to analyze the relationship between these parameters. Prospective study. Using six validated questionnaires, we evaluated the pre-CI and post-CI scores of HRQoL, tinnitus, perceived stress, symptoms of depression and anxiety, and coping strategies in 43 patients implanted unilaterally with a multichannel implant for at least 6 months. In addition to improvements in hearing, speech understanding, and disease-specific HRQoL, psychological comorbidity was reduced and coping strategies were improved following CI. In the 39 tinnitus patients, their tinnitus was reduced. We found negative correlations between HRQoL and stress, depression, and anxiety. Pre-CI, tinnitus severity did not correlate with HRQoL and psychological comorbidity. However, patients with a high-level tinnitus had lower HRQoL as well as a higher level of perceived stress and anxiety symptoms than patients with a low-level tinnitus and no/incidental tinnitus before CI. Moreover, patients with severe hearing loss had a higher level of perceived symptoms of stress and depression than patients with profound hearing loss before CI. The present study provides evidence that tinnitus and psychological comorbidity may play an important role in the rehabilitation of CI patients, and that there is a correlation between HRQoL and these parameters. In addition to hearing tests, tinnitus, stress, and psychological comorbidity should be assessed using validated questionnaires before and after CI. This will help to improve the rehabilitation process.	\N	\N
21902007	The purpose of the present study was to see if 7-10-year-old socially anxious children (n = 26) made systematic errors in identifying and sending emotions in facial expressions, paralanguage, and postures as compared with the more random errors of children who were inattentive-hyperactive (n = 21). It was found that socially anxious children made more errors in identifying anger and fear in children's facial expressions and anger in adults' postures and in expressing anger in their own facial expressions than did their inattentive-hyperactive peers. Results suggest that there may be systematic difficulties specifically in visual nonverbal emotion communication that contribute to the personal and social difficulties socially anxious children experience.	\N	\N
21902880	In visual competition, the perception of ambiguous visual patterns changes spontaneously. Although the process causing this perceptual alternation remains unclear, recent evidence suggests various types of non-visual influences in resolving visual ambiguity. In the present study, we investigated cross-modal modulation of a transient stimulus on visual perceptual stability (i.e., alternation frequency). Participants observed an ambiguous visual figure and reported their perceptual alternations. Concurrently, we presented visual and auditory transient events. The results revealed that the auditory as well as visual transient events destabilize the current perception (i.e., they increase alternation frequency) around 0.5-1.5 s after the event. In addition, the magnitudes of auditory and visual effects were comparable and positively correlated within participants. These results suggest that the visual perceptual stability can be under the influence of processes that are shared by different senses.	\N	\N
21903084	Rainstorms, insect swarms, and galloping horses produce "sound textures"--the collective result of many similar acoustic events. Sound textures are distinguished by temporal homogeneity, suggesting they could be recognized with time-averaged statistics. To test this hypothesis, we processed real-world textures with an auditory model containing filters tuned for sound frequencies and their modulations, and measured statistics of the resulting decomposition. We then assessed the realism and recognizability of novel sounds synthesized to have matching statistics. Statistics of individual frequency channels, capturing spectral power and sparsity, generally failed to produce compelling synthetic textures; however, combining them with correlations between channels produced identifiable and natural-sounding textures. Synthesis quality declined if statistics were computed from biologically implausible auditory models. The results suggest that sound texture perception is mediated by relatively simple statistics of early auditory representations, presumably computed by downstream neural populations. The synthesis methodology offers a powerful tool for their further investigation.	\N	\N
21904250	The diversion of attention from a primary goal by irrelevant events is known as attention capture, and is often followed by a directed action. The hypothesis that corticospinal excitability is modulated by attention capture was tested using transcranial magnetic stimulation. Participants watched a video while sounds were intermittently presented. Motor evoked potentials (MEPs) were elicited in each hand using transcranial magnetic stimulation 1 s after sound onset. MEP amplitudes were assessed as a function of hand (dominant, nondominant), sound location (ipsilateral or contralateral to hand location), and sound sample valence (negative, neutral, positive). Results showed that MEP amplitudes increased during sound presentation, but only for the dominant hand. There were no effects of location or emotional valence. The selective modulation of the dominant hand motor cortex may indicate that auditory events can prime the preferred hand for action.	\N	\N
21909974	A key requirement for encoding the auditory environment is the ability to dynamically alter cochlear sensitivity. However, merely attaining a steady state of maximal sensitivity is not a viable solution since the sensory cells and ganglion cells of the cochlea are prone to damage following exposure to loud sound. Most often, such damage is via initial metabolic insult that can lead to cellular death. Thus, establishing the highest sensitivity must be balanced with protection against cellular metabolic damage that can lead to loss of hair cells and ganglion cells, resulting in loss of frequency representation. While feedback mechanisms are known to exist in the cochlea that alter sensitivity, they respond only after stimulus encoding, allowing potentially damaging sounds to impact the inner ear at times coincident with increased sensitivity. Thus, questions remain concerning the endogenous signaling systems involved in dynamic modulation of cochlear sensitivity and protection against metabolic stress. Understanding endogenous signaling systems involved in cochlear protection may lead to new strategies and therapies for prevention of cochlear damage and consequent hearing loss. We have recently discovered a novel cochlear signaling system that is molecularly equivalent to the classic hypothalamic-pituitary-adrenal (HPA) axis. This cochlear HPA-equivalent system functions to balance auditory sensitivity and susceptibility to noise-induced hearing loss, and also protects against cellular metabolic insults resulting from exposures to ototoxic drugs. We review the anatomy, physiology, and cellular signaling of this system, and compare it to similar signaling in other organs/tissues of the body.	\N	\N
21914244	How do children develop the mapping between prosody and other levels of linguistic knowledge? This question has received considerable attention in child language research. In the present study two experiments were conducted to investigate four- to five-year-old Mandarin-speaking children's sensitivity to prosody in ambiguity resolution. Experiment 1 used eye-tracking to assess children's use of stress in resolving structural ambiguities. Experiment 2 took advantage of special properties of Mandarin to investigate whether children can use intonational cues to resolve ambiguities involving speech acts. The results of our experiments show that children's use of prosodic information in ambiguity resolution varies depending on the type of ambiguity involved. Children can use prosodic information more effectively to resolve speech act ambiguities than to resolve structural ambiguities. This finding suggests that the mapping between prosody and semantics/pragmatics in young children is better established than the mapping between prosody and syntax.	\N	\N
21916216	Processing of auditory information in central nervous system bases on the series of quickly occurring neural processes that cannot be separately monitored using only the fMRI registration. Simultaneous recording of the auditory evoked potentials, characterized by good temporal resolution, and the functional magnetic resonance imaging with excellent spatial resolution allows studying higher auditory functions with precision both in time and space. was to implement the simultaneous AEP-fMRI recordings method for the investigation of information processing at different levels of central auditory system. Five healthy volunteers, aged 22-35 years, participated in the experiment. The study was performed using high-field (3T) MR scanner from Siemens and 64-channel electrophysiological system Neuroscan from Compumedics. Auditory evoked potentials generated by acoustic stimuli (standard and deviant tones) were registered using modified odd-ball procedure. Functional magnetic resonance recordings were performed using sparse acquisition paradigm. The results of electrophysiological registrations have been worked out by determining voltage distributions of AEP on skull and modeling their bioelectrical intracerebral generators (dipoles). FMRI activations were determined on the basis of deviant to standard and standard to deviant functional contrasts. Results obtained from electrophysiological studies have been integrated with functional outcomes. Morphology, amplitude, latency and voltage distribution of auditory evoked potentials (P1, N1, P2) to standard stimuli presented during simultaneous AEP-fMRI registrations were very similar to the responses obtained outside scanner room. Significant fMRI activations to standard stimuli were found mainly in the auditory cortex. Activations in these regions corresponded with N1 wave dipoles modeled based on auditory potentials generated by standard tones. Auditory evoked potentials to deviant stimuli were recorded only outside the MRI scanner. However, deviant stimuli induced significant fMRI activations. They were observed mainly in the anterior cingulate gyrus, insula and parietal lobes. These regions of the brain are related to attention and decision-making processes. The results showed that applied paradigm is suitable for investigation of acoustic processing on the level of auditory cortex. Technique of the simultaneous AEP-fMRI registrations seems to be promising for investigation of more complex nervous processes in central auditory system with good temporo-spatial resolution.	\N	\N
21917204	Modern health services need efficient tools for measuring outcomes from interventions, that is, tools of proven efficacy which make minimal demands on the time of clinicians in learning to administer tests and in interpreting results. This paper describes an apparatus designed to meet those requirements. The apparatus administers performance tests of spatial listening for children and adults with unilateral and bilateral cochlear implants. The apparatus was designed with guidance from clinicians. It possesses three key attributes: it is simple to use; the results of tests are scored automatically and are compared with reference data; the apparatus generates comprehensive personalized reports for individual participants that can be included in clinical notes. This paper describes the apparatus and reports results of a test measuring spatial release from masking of speech which illustrates the compatibility between the new apparatus and an older apparatus with which the reference data were gathered.	\N	\N
21917210	Bilateral cochlear implants (CIs) have been provided to children who are deaf in both ears with intent to promote binaural hearing. If it is possible to establish binaural hearing with two CIs, these children would be able to make use of interaural level and timing differences to localize sound and to distinguish between sounds separated in space. These skills are central to the ability to attend to one particular sound amidst a number of sound sources. This may be particularly important for children because they are typically learning and interacting in groups. However, the development of binaural processing could be disrupted by effects of bilateral deafness, effects of unilateral CI use, or issues related to the child's age at onset of deafness and age at the time of the first and second cochlear implantation. This research aims to determine whether binaural auditory processing is affected by these variables in an effort to determine the optimal timing for bilateral cochlear implantation in children. It is now clear that the duration of bilateral deafness should be limited in children to restrict reorganization in the auditory thalamo-cortical pathways. It has also been shown that unilateral CI use can halt such reorganization to some extent and promote auditory development. At the same time, however, unilateral input might compromise the development of binaural processing if CIs are provided sequentially. Mismatches in responses from the auditory brainstem and cortex evoked by the first and second CI after a long period of unilateral CI use suggest asymmetry in the bilateral auditory pathways which is significantly more pronounced than in children receiving bilateral implants simultaneously. Moreover, behavioural responses to level and timing differences between implants suggest that these important binaural cues are not being processed normally by children who received a second CI after a long period of unilateral CI use and at older ages. In sum, there may be multiple sensitive periods in the developing auditory system, which must be considered when determining the optimal timing for bilateral cochlear implantation.	\N	\N
21918451	To determine whether common approaches to setting stimulus parameters influence the depth of fine structure present in the distortion product otoacoustic emission (DPOAE) response. Because the presence of fine structure has been suggested as a possible source of errors, if one of the common parametric approaches results in reduced fine-structure depth, it may be preferred over other approaches. DPOAE responses were recorded in a group of 21 subjects with normal hearing for 1/3-octave intervals surrounding 3 f2s (1, 2, and 4 kHz) at three L2s (30, 45, and 55 dB SPL). For each f2 and L2 combination, L1 and f2/f1 were set according to three commonly used parametric approaches. These included a simple approach, the approach recommended by Kummer et al., and the approach described by Johnson et al. These three approaches primarily differ in the recommended relationship between L1 and L2. For each parametric approach, DPOAE fine structure was evaluated by varying f2 in small steps. Differences in DPOAE level and DPOAE fine-structure depth across f2, L2, and the various stimulus parameters were evaluated using repeated-measures analysis of variance. As expected, significant variations in DPOAE level were observed across the three parametric approaches. For stimulus levels #45 dB SPL, the simple stimuli resulted in lower DPOAE levels than were observed for other approaches. An unexpected finding was that stimulus parameters developed by Johnson et al., which were believed to produce higher DPOAE levels than other approaches, produced the lowest DPOAE levels of the three approaches when f2 = 4 kHz. Significant differences in fine-structure depth were also observed. Greater fine-structure depth was observed with the simple parameters, although this effect was restricted to L2 # 45 dB SPL. When L2 = 55 dB SPL, all three parametric approaches resulted in equivalent fine-structure depth. A significant difference in fine-structure depth across the 3 f2s was also observed. The interval surrounding 2 kHz was associated with greater fine-structure depth than the intervals surrounding 1 and 4 kHz. The simple stimulus parameters resulted in more fine structure than the other parametric approaches; however, this effect was restricted to L2 # 45 dB SPL. At the moderate stimulus levels used in most clinical applications of DPOAEs (L2 = 55 dB SPL), all three approaches resulted in similar fine-structure depths. These findings suggest that manipulating stimulus parameters, particularly the L1, L2 relationship, is not an effective technique for reducing fine structure, except at the lowest stimulus levels, and that all the common parameters result in equivalent fine structure for moderate stimulus levels. These results also suggest that the stimulus parameters used in future studies of the clinical implications of fine structure may be relatively unimportant, unless stimulus levels #45 dB SPL will be evaluated.	\N	\N
21921852	Bilateral stimulation through cochlear implants induces a brain activity pattern closer to the normal one than unilateral stimulation. Although it has been shown that speech comprehension through bilateral cochlear implants leads to better performances than after unilateral implantation, the existence of neural underpinnings of this improvement remains to be studied. We performed an H2O positron emission tomographic study of word recognition in 5 patients with bilateral cochlear implants and 5 normal-hearing controls. Subjects had to distinguish words from nonwords in binaural and monaural conditions. There was no overactivation in patients for binaural stimulation, with a hypoactivation in the right temporal cortex. For monaural stimulation, patients demonstrated more activation contralaterally to the stimulation side in the posterior temporal cortex and in the cerebellum. Binaural stimulation through cochlear implants is advantageous compared with the monaural at the neurofunctional level because the pattern of brain activity is closer to the normal one.	\N	\N
21924100	To explore the factors that influence the stability of evaluation results judged by a jury through a standard research on perceptual evaluation measurements of voice quality. Voice samples from 300 patients with dysphonia and 100 control subjects with normal voice were recorded and assessed by a jury composed of 6 experienced listeners from different hospitals. The voice samples were discourse voices and ordered randomly 3 times, and the mean of 3 evaluations using visual analogue scale were the final results. The jury was instructed to classify voice samples according to the G (grade), R (rough) and B (breathy) components of the GRBAS scale on a 4-point scale ranging from 0 for normal to 3 for severe dysphonia. Κ value was used to analyze the concordance of evaluation results and regression analysis was used to research the effects of the extent of voice disorder to the stability of perceptual evaluation. The discordance of evaluation existed both between the jury and in listeners themselves. The concordance of listeners themselves of each evaluation parameter was not bad, good, or even very good, and the concordance of evaluation of G was the best (κ value: 0.46 - 0.85), then R (κ value: 0.41 - 0.84) and B (κ value: 0.41 - 0.81). The concordance between the jury was worse than that in themselves. And except a listener whose concordance of evaluation was under the requirement, the concordance of evaluation of G was the best (κ value: 0.43 - 0.96), then R (κ value: 0.33 - 0.78) and B (κ value: 0.002 - 0.45). The stability of evaluation of normal voice and severe voice disorder was better than mild and moderate voice disorder. The discordance between the jury was the main factor that influence the stability of perceptual evaluation. The evaluation parameters and extent of voice disorder will influence the stability of perceptual evaluation of the jury.	\N	\N
21925521	The left inferior frontal gyrus (LIFG) exhibits increased responsiveness when people listen to words composed of speech sounds that frequently co-occur in the English language (Vaden, Piquado, & Hickok, 2011), termed high phonotactic frequency (Vitevitch & Luce, 1998). The current experiment aimed to further characterize the relation of phonotactic frequency to LIFG activity by manipulating word intelligibility in participants of varying age. Thirty six native English speakers, 19-79 years old (mean=50.5, sd=21.0) indicated with a button press whether they recognized 120 binaurally presented consonant-vowel-consonant words during a sparse sampling fMRI experiment (TR=8 s). Word intelligibility was manipulated by low-pass filtering (cutoff frequencies of 400 Hz, 1000 Hz, 1600 Hz, and 3150 Hz). Group analyses revealed a significant positive correlation between phonotactic frequency and LIFG activity, which was unaffected by age and hearing thresholds. A region of interest analysis revealed that the relation between phonotactic frequency and LIFG activity was significantly strengthened for the most intelligible words (low-pass cutoff at 3150 Hz). These results suggest that the responsiveness of the left inferior frontal cortex to phonotactic frequency reflects the downstream impact of word recognition rather than support of word recognition, at least when there are no speech production demands.	\N	\N
21932260	Cross-modal processing enables the utilization of information received via different sensory organs to facilitate more complicated human actions. We used functional MRI on early-blind individuals to study the neural processes associated with cross auditory-spatial learning. The auditory signals, converted from echoes of ultrasonic signals emitted from a navigation device, were novel to the participants. The subjects were trained repeatedly for 4 weeks in associating the auditory signals with different distances. Subjects' blood-oxygenation-level-dependent responses were captured at baseline and after training using a sound-to-distance judgment task. Whole-brain analyses indicated that the task used in the study involved auditory discrimination as well as spatial localization. The learning process was shown to be mediated by the inferior parietal cortex and the hippocampus, suggesting the integration and binding of auditory features to distances. The right cuneus was found to possibly serve a general rather than a specific role, forming an occipital-enhanced network for cross auditory-spatial learning. This functional network is likely to be unique to those with early blindness, since the normal-vision counterparts shared activities only in the parietal cortex.	\N	\N
21936759	The present study investigated the relationship between non-verbal behaviours and perceptions of the communication abilities of an individual with anomia secondary to traumatic brain injury (TBI). Thirty-four university students studying Communication Sciences and Disorders were randomly assigned to watch or listen to six short clips of an individual with TBI engaged in conversation. Participants rated the individual on communication parameters from a modified version of the Pragmatic Protocol and four other dependent measures of communicative competence. A significant positive correlation was identified between perceptions of gestures and ratings of overall communicative competence, and between perceptions of hand and arm movements and ratings of overall communicative competence. Participant raters who viewed the individual's movements as inappropriate also rated her overall communication abilities less favourably. This finding highlights individuality in perception of communication competence and the importance of assessing communication partners' perceptions in a client's environment to determine socially relevant treatment goals.	\N	\N
21939965	Listeners rapidly adjust to talkers' pronunciations, accommodating those pronunciations into the relevant phonemic category to improve subsequent perception. Previous work has suggested that such learning is restricted to pronunciations that are representative of how the speaker talks (Kraljic, Samuel, & Brennan, 2008). If an ambiguous pronunciation, for example, can be attributed to an external source (such as a pen in the speaker's mouth), or if it is preceded by normal pronunciations of the same sound, learning is blocked. In three experiments, we explore this blocking effect in more detail. Our aim is to better understand the nature of the representations underlying the perceptual learning process. Experiment 1 replicates the blocking effect. Experiments 2 and 3 demonstrate that it can be eliminated when certain visual information occurs simultaneously with the auditory signal. The pattern of learning and non-learning is best accounted for by the view that speech perception is mediated by episodic representations that include potentially relevant visual information.	\N	\N
21940463	Several studies report that adults and adolescents with reading disabilities also experience difficulties with selective attention. In the present study, event-related brain potentials (ERPs) were used to examine the neural mechanisms of selective attention in kindergarten children at risk for reading disabilities (AR group, n = 8) or on track in early literacy skills (OT group, n = 6) across the first semester of kindergarten. The AR group also received supplemental instruction with the Early Reading Intervention (ERI). Following ERI, the AR group demonstrated improved skills on standardized early literacy measures such that there were no significant differences between the AR and OT groups at posttest or winter follow-up. Analysis of the ERP data revealed that at the start of kindergarten, the AR group displayed reduced effects of attention on sensorineural processing compared to the OT group. Following intervention, this difference between groups disappeared, with the AR group only showing improvements in the effect of attention on sensorineural processing. These data indicate that the neural mechanisms of selective attention are atypical in kindergarten children at risk for reading failure but can be improved by effective reading interventions.	\N	\N
21942418	We report a series of experiments designed to demonstrate that the presentation of a sound can facilitate the identification of a concomitantly presented visual target letter in the backward masking paradigm. Two visual letters, serving as the target and its mask, were presented successively at various interstimulus intervals (ISIs). The results demonstrate that the crossmodal facilitation of participants' visual identification performance elicited by the presentation of a simultaneous sound occurs over a very narrow range of ISIs. This critical time-window lies just beyond the interval needed for participants to differentiate the target and mask as constituting two distinct perceptual events (Experiment 1) and can be dissociated from any facilitation elicited by making the visual target physically brighter (Experiment 2). When the sound is presented at the same time as the mask, a facilitatory, rather than an inhibitory effect on visual target identification performance is still observed (Experiment 3). We further demonstrate that the crossmodal facilitation of the visual target by the sound depends on the establishment of a reliable temporally coincident relationship between the two stimuli (Experiment 4); however, by contrast, spatial coincidence is not necessary (Experiment 5). We suggest that when visual and auditory stimuli are always presented synchronously, a better-consolidated object representation is likely to be constructed (than that resulting from unimodal visual stimulation).	\N	\N
21945200	The human auditory brainstem is known to be exquisitely sensitive to fine-grained spectro-temporal differences between speech sound contrasts, and the ability of the brainstem to discriminate between these contrasts is important for speech perception. Recent work has described a novel method for translating brainstem timing differences in response to speech contrasts into frequency-specific phase differentials. Results from this method have shown that the human brainstem response is surprisingly sensitive to phase differences inherent to the stimuli across a wide extent of the spectrum. Here we use an animal model of the auditory brainstem to examine whether the stimulus-specific phase signatures measured in human brainstem responses represent an epiphenomenon associated with far-field (i.e., scalp-recorded) measurement of neural activity, or alternatively whether these specific activity patterns are also evident in auditory nuclei that contribute to the scalp-recorded response, thereby representing a more fundamental temporal processing phenomenon. Responses in anaesthetized guinea pigs to three minimally-contrasting consonant-vowel stimuli were collected simultaneously from the cortical surface vertex and directly from central nucleus of the inferior colliculus (ICc), measuring volume conducted neural activity and multiunit, near-field activity, respectively. Guinea pig surface responses were similar to human scalp-recorded responses to identical stimuli in gross morphology as well as phase characteristics. Moreover, surface-recorded potentials shared many phase characteristics with near-field ICc activity. Response phase differences were prominent during formant transition periods, reflecting spectro-temporal differences between syllables, and showed more subtle differences during the identical steady state periods. ICc encoded stimulus distinctions over a broader frequency range, with differences apparent in the highest frequency ranges analyzed, up to 3000 Hz. Based on the similarity of phase encoding across sites, and the consistency and sensitivity of response phase measured within ICc, results suggest that a general property of the auditory system is a high degree of sensitivity to fine-grained phase information inherent to complex acoustical stimuli. Furthermore, results suggest that temporal encoding in ICc contributes to temporal features measured in speech-evoked scalp-recorded responses.	\N	\N
21949873	The modulation of brain activity as a function of auditory location was investigated using electro-encephalography in combination with standardized low-resolution brain electromagnetic tomography. Auditory stimuli were presented at various positions under anechoic conditions in free-field space, thus providing the complete set of natural spatial cues. Variation of electrical activity in cortical areas depending on sound location was analyzed by contrasts between sound locations at the time of the N1 and P2 responses of the auditory evoked potential. A clear-cut double dissociation with respect to the cortical locations and the points in time was found, indicating spatial processing (1) in the primary auditory cortex and posterodorsal auditory cortical pathway at the time of the N1, and (2) in the anteroventral pathway regions about 100 ms later at the time of the P2. Thus, it seems as if both auditory pathways are involved in spatial analysis but at different points in time. It is possible that the late processing in the anteroventral auditory network reflected the sharing of this region by analysis of object-feature information and spectral localization cues or even the integration of spatial and non-spatial sound features.	\N	\N
21957257	Children use information from both the auditory and visual modalities to aid in understanding speech. A dramatic illustration of this multisensory integration is the McGurk effect, an illusion in which an auditory syllable is perceived differently when it is paired with an incongruent mouth movement. However, there are significant interindividual differences in McGurk perception: some children never perceive the illusion, while others always do. Because converging evidence suggests that the posterior superior temporal sulcus (STS) is a critical site for multisensory integration, we hypothesized that activity within the STS would predict susceptibility to the McGurk effect. To test this idea, we used BOLD fMRI in 17 children aged 6-12 years to measure brain responses to the following three audiovisual stimulus categories: McGurk incongruent, non-McGurk incongruent, and congruent syllables. Two separate analysis approaches, one using independent functional localizers and another using whole-brain voxel-based regression, showed differences in the left STS between perceivers and nonperceivers. The STS of McGurk perceivers responded significantly more than that of nonperceivers to McGurk syllables, but not to other stimuli, and perceivers' hemodynamic responses in the STS were significantly prolonged. In addition to the STS, weaker differences between perceivers and nonperceivers were observed in the fusiform face area and extrastriate visual cortex. These results suggest that the STS is an important source of interindividual variability in children's audiovisual speech perception.	\N	\N
21959609	The literature suggests that contralateral acoustic stimulation (CAS) alters the amplitude of the distortion product otoacoustic emissions (DPOAEs), but it is still unknown whether the DPOAE Input/Output (I/O) functions are also affected. To elucidate this aspect of the DPOAEs, the present study assessed the effects of CAS on DPOAE I/O functions at the frequencies of 2 kHz and 4 kHz, in a sample of term neonatal subjects. Sixty randomly selected neonates were included in the study. The DPOAE I/O functions were obtained at 2 kHz and 4 kHz, in the presence of a 60 dB SPL broad band-contralateral white noise, using the TDH39 headphones contralaterally. DPOAEs were recorded up to a stimulus level of L2 = 35 dB peSPL. Significant DPOAE amplitude suppression effects were observed at various L2 stimulus levels for both tested frequencies at 2 and 4 kHz. In contrast, the corresponding DPOAE slopes showed various alterations that were not statistically significant. The data from the present study show that contralateral acoustic stimulation significantly affects only the amplitude of the DPOAE I/O functions; the slope is affected, but not significantly. This observation can shed light on the nature of CAS, suggesting that the latter is primarily a linear phenomenon without the cochlear compression and non-linear components seen in the healthy cochlea. From the available data it is not possible to infer whether the sample size has influenced the obtained results and the study should be repeated with a larger sample size and assessing more frequencies.	\N	\N
21964385	Temporal summation of C-fiber evoked responses generates an increase in action potential discharge in second-order neurons and in perceived pain intensity (wind-up). This may be related to the central serotonergic system which modulates and partly inhibits sensory input. Aim of the study was to investigate the relationship between wind-up and serotonergic activity using loudness dependence of auditory evoked potentials (LDAEP). 18 healthy subjects were compared to 18 patients with major depression, a disease with a putative serotonin deficit. They were examined with quantitative sensory testing (QST) using the protocol of the German Research Network on Neuropathic Pain (DFNS), including the wind-up ratio (WUR), LDAEP, and psychometric measurements. We found a slight positive correlation between WUR and LDAEP both in healthy controls and depressed patients combined (r=0.340, p=0.043), indicating that WUR may be modulated by serotonergic activity. It can be concluded that inhibitory control to noxious stimuli is partly associated with the central serotonergic function as indicated by LDAEP.	\N	\N
21972849	Filmmakers use continuity editing to engender a sense of situational continuity or discontinuity at editing boundaries. The goal of this study was to assess the impact of continuity editing on how people perceive the structure of events in a narrative film and to identify brain networks that are associated with the processing of different types of continuity editing boundaries. Participants viewed a commercially produced film and segmented it into meaningful events, while brain activity was recorded with functional magnetic resonance imaging (MRI). We identified three degrees of continuity that can occur at editing locations: edits that are continuous in space, time, and action; edits that are discontinuous in space or time but continuous in action; and edits that are discontinuous in action as well as space or time. Discontinuities in action had the biggest impact on behavioral event segmentation, and discontinuities in space and time had minor effects. Edits were associated with large transient increases in early visual areas. Spatial-temporal changes and action changes produced strikingly different patterns of transient change, and they provided evidence that specialized mechanisms in higher order perceptual processing regions are engaged to maintain continuity of action in the face of spatiotemporal discontinuities. These results suggest that commercial film editing is shaped to support the comprehension of meaningful events that bridge breaks in low-level visual continuity, and even breaks in continuity of spatial and temporal location.	\N	\N
21973370	Within an auditory channel, the speech waveform contains both temporal envelope (E(O)) and temporal fine structure (TFS) information. Vocoder processing extracts a modified version of the temporal envelope (E') within each channel and uses it to modulate a channel carrier. The resulting signal, E'(Carr), has reduced information content compared to the original "E(O) + TFS" signal. The dynamic range over which listeners make additional use of E(O) + TFS over E'(Carr) cues was investigated in a competing-speech task. The target-and-background mixture was processed using a 30-channel vocoder. In each channel, E(O) + TFS replaced E'(Carr) at either the peaks or the valleys of the signal. The replacement decision was based on comparing the short-term channel level to a parametrically varied "switching threshold," expressed relative to the long-term channel level. Intelligibility was measured as a function of switching threshold, carrier type, target-to-background ratio, and replacement method. Scores showed a dependence on all four parameters. Derived intensity-importance functions (IIFs) showed that E(O) + TFS information from 8-13 dB below to 10 dB above the channel long-term level was important. When E(O) + TFS information was added at the peaks, IIFs peaked around -2 dB, but when E(O) + TFS information was added at the valleys, the peaks lay around +1 dB.	\N	\N
21973372	Deutsch's octave illusion occurs when two tones that are spaced an octave apart are repeatedly presented in alternation; the sequence is presented to both ears simultaneously but offset by one tone, so that two dichotic chords are repeatedly presented in alternation. The most common illusory percept consists of an intermittent high tone in one ear alternating with an intermittent low tone in the other ear. The aim of this study was to investigate whether, once the illusory percept has emerged, the illusion will persist when the original sequence is followed by another sequence consisting of the repeated presentation of one of the two dichotic chords. Forty naïve subjects were tested with stimuli consisting first of a priming sequence containing dichotic octaves alternating between ears followed immediately by a test sequence consisting of a single dichotic octave presented repeatedly. The durations of the priming and test sequences were manipulated. The findings showed that the illusory percept is maintained after the switch from alternation to repetition and that the relative length of the priming and test sequences has a negligible influence on the persistence of the illusory percept.	\N	\N
21974490	Naive listeners' perceptual assimilations of non-native vowels to first-language (L1) categories can predict difficulties in the acquisition of second-language vowel systems. This study demonstrates that listeners having two slightly different dialects as their L1s can differ in the perception of foreign vowels. Specifically, the study shows that Bohemian Czech and Moravian Czech listeners assimilate Dutch high front vowels differently to L1 categories. Consequently, the listeners are predicted to follow different paths in acquiring these Dutch vowels. These findings underscore the importance of carefully considering the specific dialect background of participants in foreign- and second-language speech perception studies.	\N	\N
21981669	The neural representation of segmental and tonal phonological distinctions has been shown by means of the MMN ERP, yet this is not the case for intonational discourse contrasts. In Catalan, a rising-falling intonational sequence can be perceived as a statement or as a counterexpectational question, depending exclusively on the size of the pitch range interval of the rising movement. We tested here, using the MMN, whether such categorical distinctions elicited distinct neurophysiological patterns of activity, supporting their specific neural representation. From a behavioral identification experiment, we set the boundary between the two categories and defined four stimuli across the continuum. Although the physical distance between each pair of stimuli was kept constant, the central pair represented an across-category contrast, whereas the other pairs represented within-category contrasts. These four auditory stimuli were contrasted by pairs in three different oddball blocks. The mean amplitude of the MMN was larger for the across-category contrast, suggesting that intonational contrasts in the target language can be encoded automatically in the auditory cortex. These results are in line with recent findings in other fields of linguistics, showing that, when a boundary between categories is crossed, the MMN response is not just larger but rather includes a separate subcomponent.	\N	\N
21985220	The high energy demand of the auditory and visual pathways render these sensory systems prone to diseases that impair mitochondrial function. Primary open-angle glaucoma, a neurodegenerative disease of the optic nerve, has recently been associated with a spectrum of mitochondrial abnormalities. This study sought to investigate auditory processing in individuals with open-angle glaucoma. DESIGN/STUDY SAMPLE: Twenty-seven subjects with open-angle glaucoma underwent electrophysiologic (auditory brainstem response), auditory temporal processing (amplitude modulation detection), and speech perception (monosyllabic words in quiet and background noise) assessment in each ear. A cohort of age, gender and hearing level matched control subjects was also tested. While the majority of glaucoma subjects in this study demonstrated normal auditory function, there were a significant number (6/27 subjects, 22%) who showed abnormal auditory brainstem responses and impaired auditory perception in one or both ears. The finding that a significant proportion of subjects with open-angle glaucoma presented with auditory dysfunction provides evidence of systemic neuronal susceptibility. Affected individuals may suffer significant communication difficulties in everyday listening situations.	\N	\N
21987910	When the fundamental frequency (f0) is removed from a complex stimulus, the pitch of the f0 is still perceived by the listener. Through the use of the scalp-recorded frequency-following response, this study examined the relative contributions of thef0 and its harmonics in pitch processing by systematically manipulating the speech stimulus to remove component frequencies. 12 American and 12 Chinese adults were recruited. There were statistically significant effects of pitch strength and frequency error for the experimental-condition factor. There were significantly larger responses to the harmonics-only conditions than those obtained in the f0-only and control conditions. No statistically significant difference was observed between the two groups of participants. These findings indicate that neural responses associated with individual harmonics dominate the pitch processing in the human brainstem, irrespective of whether the listener's native language is nontonal or tonal.	\N	\N
22000998	Recent years have seen a growing debate concerning the function of the cerebellum. Here we used a pitch discrimination task and PET to test for cerebellar involvement in the active control of sensory data acquisition. Specifically, we predicted greater cerebellar activity during active pitch discrimination compared to passive listening, with the greatest activity when pitch discrimination was most difficult. Ten healthy subjects were trained to discriminate deviant tones presented with a slightly higher pitch than a standard tone, using a Go/No Go paradigm. To ensure that discrimination performance was matched across subjects, individual psychometric curves were assessed beforehand using a two-step psychoacoustic procedure. Subjects were scanned while resting in the absence of any sounds, while passively listening to standard tones, and while detecting deviant tones slightly higher in pitch among these standard tones at four different performance levels. Consistent with our predictions, 1) passive listening alone elicited cerebellar activity (lobule IX), 2) cerebellar activity increased during pitch discrimination as compared to passive listening (crus I and II, lobules VI, VIIB, and VIIIB), and 3) this increase was correlated with the difficulty of the discrimination task (lobules V, VI, and IX). These results complement recent findings showing pitch discrimination deficits in cerebellar patients (Parsons et al., 2009) and further support a role for the cerebellum in sensory data acquisition. The data are discussed in the light of anatomical and physiological evidence functionally connecting auditory system and cerebellum.	\N	\N
22002633	Attentional blink (AB) refers to a phenomenon where the correct identification of a first target (i.e., target) impairs the processing of a second target (i.e., probe) nearby in time. In the present study, we investigate the influence of temporal attention on auditory AB by means of scalp-recorded event-related potentials. Participants were instructed to focus their attention on a particular time interval following the target (i.e., short, middle, or long temporal position) in order to detect the occurrence of the probe in a rapid series of distractor sounds. We found a large probe processing deficit when the probe occurred immediately after the target. This AB decreased as the time interval between the target and the probe increased and coincided with the generation of a positive wave at parietal sites (i.e., P3b). The P3b elicited by the probe peaked earlier when the probe occurred at the designated time than when it occurred at another position in time. The results indicate that temporal attention can be deployed to a particular time, which facilitates short-term consolidation of the probe.	\N	\N
22004192	Speech processing requires sensitivity to long-term regularities of the native language yet demands listeners to flexibly adapt to perturbations that arise from talker idiosyncrasies such as nonnative accent. The present experiments investigate whether listeners exhibit dimension-based statistical learning of correlations between acoustic dimensions defining perceptual space for a given speech segment. While engaged in a word recognition task guided by a perceptually unambiguous voice-onset time (VOT) acoustics to signal beer, pier, deer, or tear, listeners were exposed incidentally to an artificial "accent" deviating from English norms in its correlation of the pitch onset of the following vowel (F0) to VOT. Results across four experiments are indicative of rapid, dimension-based statistical learning; reliance on the F0 dimension in word recognition was rapidly down-weighted in response to the perturbation of the correlation between F0 and VOT dimensions. However, listeners did not simply mirror the short-term input statistics. Instead, response patterns were consistent with a lingering influence of sensitivity to the long-term regularities of English. This suggests that the very acoustic dimensions defining perceptual space are not fixed and, rather, are dynamically and rapidly adjusted to the idiosyncrasies of local experience, such as might arise from nonnative-accent, dialect, or dysarthria. The current findings extend demonstrations of "object-based" statistical learning across speech segments to include incidental, online statistical learning of regularities residing within a speech segment.	\N	\N
22005285	Feelings of deliciousness during having foods are mainly produced by perceptions of sensory information extracted from foods themselves, such as taste and olfaction. However, environmental factors might modify the feeling of deliciousness. In the present study, we investigated how the condition of audio-visual environments affects the feeling of deliciousness during having sweet foods. Electroencephalograms (EEGs) were recorded from the frontal region of the scalp of healthy participants under virtual scenes of tearoom and construction work, respectively. The participants were asked to rate deliciousness after the recordings. Frequency analyses were performed from the EEGs. During having the foods, occupancy rates of beta frequency band between tearoom scenes and construction work scenes were markedly different, but not in other frequency bands. During having no food, in contrast, there was no difference of occupancy rates in respective frequency bands between the two different scenes. With regard to deliciousness during having sweet foods, all participants rated high scores under the scenes of tearoom than those under the scenes of construction work. Interestingly, there is a positive correlation between occupancy rates of beta frequency band and scores of deliciousness. These findings suggest that comfortable audio-visual environments play an important role in increasing the feeling of deliciousness during having sweet foods, in which beta frequency rhythms may be concerned with producing comprehensive feelings of deliciousness.	\N	\N
22005291	Neural sensitivity to acoustic regularities supports fundamental human behaviors such as hearing in noise and reading. Although the failure to encode acoustic regularities in ongoing speech has been associated with language and literacy deficits, how auditory expertise, such as the expertise that is associated with musical skill, relates to the brainstem processing of speech regularities is unknown. An association between musical skill and neural sensitivity to acoustic regularities would not be surprising given the importance of repetition and regularity in music. Here, we aimed to define relationships between the subcortical processing of speech regularities, music aptitude, and reading abilities in children with and without reading impairment. We hypothesized that, in combination with auditory cognitive abilities, neural sensitivity to regularities in ongoing speech provides a common biological mechanism underlying the development of music and reading abilities. We assessed auditory working memory and attention, music aptitude, reading ability, and neural sensitivity to acoustic regularities in 42 school-aged children with a wide range of reading ability. Neural sensitivity to acoustic regularities was assessed by recording brainstem responses to the same speech sound presented in predictable and variable speech streams. Through correlation analyses and structural equation modeling, we reveal that music aptitude and literacy both relate to the extent of subcortical adaptation to regularities in ongoing speech as well as with auditory working memory and attention. Relationships between music and speech processing are specifically driven by performance on a musical rhythm task, underscoring the importance of rhythmic regularity for both language and music. These data indicate common brain mechanisms underlying reading and music abilities that relate to how the nervous system responds to regularities in auditory input. Definition of common biological underpinnings for music and reading supports the usefulness of music for promoting child literacy, with the potential to improve reading remediation.	\N	\N
22005389	Several studies demonstrated that active exploration as compared to passive observation of a variety of objects leads to improved performance concerning these actively studied objects later on. These results may be specifically due to an improvement in perceptual recognition but in principle they may also be due to a speeding up of responses to actively studied objects. Recently, however, it was suggested that the benefit of active exploration on perceptual recognition may be restricted to a specific class of (biologically relevant) stimuli. By employing measures derived from signal detection theory we were able to show in all our three experiments that active exploration of virtual 3D objects leads to improved perceptual sensitivity in a subsequent test phase. The improvement with these objects means that the benefit of active exploration is not restricted to a specific class of biologically relevant stimuli. The results of our second experiment further demonstrate that the benefit of active exploration is even strong enough to fully compensate for the effect of perceptual degradation, thereby emphasizing the major impact of active exploration. In our third experiment, we explored the possibility that effects of active exploration might be due to major changes in attentional strategies rather than to the action-related aspect. Results revealed that an attentional requirement left the active-passive difference by and large intact supporting the view that the advantage of active object exploration lies in the action itself.	\N	\N
22006524	This article provides a demonstration of an analytical technique that can be used to investigate the causes of perceptual phenomena. The technique is based on the concept of the ideal observer, an optimal signal classifier that makes decisions that maximize the probability of a correct response. To demonstrate the technique, an analysis was conducted to investigate the role of the auditory periphery in the production of temporal masking effects. The ideal observer classified output from four models of the periphery. Since the ideal observer is the best of all possible observers, if it demonstrates masking effects, then all other observers must as well. If it does not demonstrate masking effects, then nothing about the periphery requires masking to occur, and therefore masking would occur somewhere else. The ideal observer exhibited several forward masking effects but did not exhibit backward masking, implying that the periphery has a causal role in forward but not backward masking. A general discussion of the strengths of the technique and supplementary equations are also included.	\N	\N
22010902	Language acquisition involves both acquiring a set of words (i.e. the lexicon) and learning the rules that combine them to form sentences (i.e. syntax). Here, we show that consonants are mainly involved in word processing, whereas vowels are favored for extracting and generalizing structural relations. We demonstrate that such a division of labor between consonants and vowels plays a role in language acquisition. In two very similar experimental paradigms, we show that 12-month-old infants rely more on the consonantal tier when identifying words (Experiment 1), but are better at extracting and generalizing repetition-based srtuctures over the vocalic tier (Experiment 2). These results indicate that infants are able to exploit the functional differences between consonants and vowels at an age when they start acquiring the lexicon, and suggest that basic speech categories are assigned to different learning mechanisms that sustain early language acquisition.	\N	\N
22015572	Sparse and clustered-sparse temporal sampling fMRI protocols have been devised to reduce the influence of auditory scanner noise in the context of auditory fMRI studies. Here, we report an improvement of the previously established clustered-sparse acquisition scheme. The standard procedure currently used by many researchers in the field is a scanning protocol that includes relatively long silent pauses between image acquisitions (and therefore, a relatively long repetition time or cluster-onset asynchrony); it is during these pauses that stimuli are presented. This approach makes it unlikely that stimulus-induced BOLD response is obscured by scanner-noise-induced BOLD response. It also allows the BOLD response to drop near baseline; thus, avoiding saturation of BOLD signal and theoretically increasing effect size. A possible drawback of this approach is the limited number of stimulus presentations and image acquisitions that are possible in a given period of time, which could result in an inaccurate estimation of effect size (higher standard error). Since this line of reasoning has not yet been empirically tested, we decided to vary the cluster-onset asynchrony (7.5, 10, 12.5, and 15 s) in the context of a clustered-sparse protocol. In this study sixteen healthy participants listened to spoken sentences. We performed whole-brain fMRI group statistics and region of interest analysis with anatomically defined regions of interest (auditory core and association areas). We discovered that the protocol, which included a short cluster-onset asynchrony (7.5 s), yielded more advantageous results than the other protocols, which involved longer cluster-onset asynchrony. The short cluster-onset asynchrony protocol exhibited a larger number of activated voxels and larger mean effect sizes with lower standard errors. Our findings suggest that, contrary to prior experience, a short cluster-onset asynchrony is advantageous because more stimuli can be delivered within any given period of time. Alternatively, a given number of stimuli can be presented in less time, and this broadens the spectrum of possible fMRI applications.	\N	\N
22046436	The present study investigated the minimum amount of auditory stimulation that allows differentiation of spoken voices, instrumental music, and environmental sounds. Three new findings were reported. 1) All stimuli were categorized above chance level with 50 ms-segments. 2) When a peak-level normalization was applied, music and voices started to be accurately categorized with 20 ms-segments. When the root-mean-square (RMS) energy of the stimuli was equalized, voice stimuli were better recognized than music and environmental sounds. 3) Further psychoacoustical analyses suggest that the categorization of extremely brief auditory stimuli depends on the variability of their spectral envelope in the used set. These last two findings challenge the interpretation of the voice superiority effect reported in previously published studies and propose a more parsimonious interpretation in terms of an emerging property of auditory categorization processes.	\N	\N
22047947	Predictive coding theories posit that the perceptual system is structured as a hierarchically organized set of generative models with increasingly general models at higher levels. The difference between model predictions and the actual input (prediction error) drives model selection and adaptation processes minimizing the prediction error. Event-related brain potentials elicited by sensory deviance are thought to reflect the processing of prediction error at an intermediate level in the hierarchy. We review evidence from auditory and visual studies of deviance detection suggesting that the memory representations inferred from these studies meet the criteria set for perceptual object representations. Based on this evidence we then argue that these perceptual object representations are closely related to the generative models assumed by predictive coding theories.	\N	\N
22051554	Relative blindsight is said to occur when different levels of subjective awareness are obtained at equality of objective performance. Using metacontrast masking, Lau and Passingham (2006) reported relative blindsight in normal observers at the shorter of two stimulus-onset asynchronies (SOAs) between target and mask. Experiment 1 replicated the critical asymmetry in subjective awareness at equality of objective performance. We argue that this asymmetry cannot be regarded as evidence for relative blindsight because the observers' responses were based on different attributes of the stimuli (criterion contents) at the two SOAs. With an invariant criterion content (Experiment 2), there was no asymmetry in subjective awareness across the two SOAs even though objective performance was the same. Experiment 3 examined the effect of criterion level on estimates of relative blindsight. Collectively, the present results question whether metacontrast masking is a suitable paradigm for establishing relative blindsight. Implications for theories of consciousness are discussed.	\N	\N
22056506	Behavioral and neurophysiological studies have shown an enhancement of visual perception in crossmodal audiovisual stimulation conditions, both for sensitivity and reaction times, when the stimulation in the two sensory modalities occurs in condition of space and time congruency. The purpose of the present work is to verify whether congruent visual and acoustic stimulations can improve the detection of visual stimuli in people affected by low vision. Participants were asked to detect the presence of a visual stimulus (yes/no task) either presented in isolation (i.e., unimodal visual stimulation) or simultaneously with auditory stimuli, which could be placed in the same spatial position (i.e., crossmodal congruent conditions) or in different spatial positions (i.e., crossmodal incongruent conditions). The results show for the first time audiovisual integration effects in low vision individuals. In particular, it has been observed a significant visual detection benefit in the crossmodal congruent as compared to the unimodal visual condition. This effect is selective for visual stimulation that occurs in the portion of visual field that is impaired, and disappears in the region of space in which vision is spared. Surprisingly, there is a marginal crossmodal benefit when the sound is presented at 16 degrees far from the visual stimulus. The observed crossmodal effect seems to be determined by the contribution of both senses to a model of optimal combination, in which the most reliable provides the highest contribution. These results, indicating a significant beneficial effect of synchronous and spatially congruent sounds in a visual detection task, seem very promising for the development of a rehabilitation approach of low vision diseases based on the principles of multisensory integration.	\N	\N
22070077	To analyze the hearing loss profiles in patients with tinnitus, and then provide clinical foundation for further studying the etiology and examination methods of tinnitus. Ear specialist examination, acoustic impedance test,normal frequency pure tone audiometry and extended high frequency audiometry were applied to 200 patients with chief complaint of subjective tinnitus. Among the 200 tinnitus cases, 123 (61.5%) patients were diagnosed with unilateral tinnitus, 77 (38.5%) patients with bilateral tinnitus and 46 (23.0%) cases with normal hearing. In those patients with unilateral tinnitus, by comparing the hearing threshold of affected side and contralateral side (0.125-8 kHz), the difference was statistically significant (P < 0.05), but in extended high frequency (> 10 kHz), the difference between two groups was not statistically significant (P > 0.05). There was significant difference in hearing threshold between tinnitus patients with normal and abnormal hearing in normal frequency (P < 0.05), meantime the detection rate in abnormal hearing group was lower than the normal group. Tinnitus can occur in people with normal hearing. Early in tinnitus,further study need be undertaken on whether the audiometry extended high frequency can offer the early evidence of hearing loss for tinnitus patients or not.	\N	\N
22072599	Difficulty understanding speech in background noise, even with amplification to restore audibility, is a common problem for hearing-impaired individuals and is especially frequent in older adults. Despite the debilitating nature of the problem the cause is not yet completely clear. This review considers the role of spatial processing ability in understanding speech in noise, highlights the potential impact of disordered spatial processing, and attempts to establish if aging leads to reduced spatial processing ability. Evidence supporting and opposing the hypothesis that spatial processing is disordered among the aging population is presented. With a few notable exceptions, spatial processing ability was shown to be reduced in an older population in comparison to young adults, leading to poorer speech understanding in noise. However, it is argued that to conclude aging negatively effects spatial processing ability may be oversimplified or even premature given potentially confounding factors such as cognitive ability and hearing impairment. Further research is required to determine the effect of aging and hearing impairment on spatial processing and to investigate possible remediation options for spatial processing disorder.	\N	\N
22073602	The effectiveness of bone anchored hearing aid (BAHA) for the patients with congenital aural atresia was evaluated by multicenter clinical study in Japan. Twenty patients (17 bilateral and 3 hemilateral) of congenital auricular atresia were registered for this study and finally, 18 of them (15 bilateral and 3 unilateral) were subjected to further evaluation. Primary endpoint of this study was free sound-field pure-tone audiometory and speech threshold hearing test in quiet and noisy circumstances. Secondary endpoint of this study was patient's satisfaction based upon APHAB (Abbreviated Profile of Hearing Aid Benefit) questionnaire survey. These results were compared between before and 12 weeks after BAHA surgery. Both hearing level of pure tone and speech threshold significantly improved after BAHA surgery. APHAB scores also suggested the improvement of the QOL after BAHA usage, except for the scores that concerned with unpleasantness of noisy sound. BAHA is one of the useful options for the treatment of congenital auricular atresia.	\N	\N
22080221	Gender is salient, socially critical information obtained from faces and voices, yet the brain processes underlying gender discrimination have not been well studied. We investigated neural correlates of gender processing of voices in two ERP studies. In the first, ERP differences were seen between female and male voices starting at 87 ms, in both spatial-temporal and peak analyses, particularly the fronto-central N1 and P2. As pitch differences may drive gender differences, the second study used normal, high- and low-pitch voices. The results of these studies suggested that differences in pitch produced early effects (27-63 ms). Gender effects were seen on N1 (120 ms) with implicit pitch processing (study 1), but were not seen with manipulations of pitch (study 2), demonstrating that N1 was modulated by attention. P2 (between 170 and 230 ms) discriminated male from female voices, independent of pitch. Thus, these data show that there are two stages in voice gender processing; a very early pitch or frequency discrimination and a later more accurate determination of gender at the P2 latency.	\N	\N
22087889	The effect of temporal asymmetry on amplitude modulation detection was studied using sawtooth modulators with rising (ramped) or falling (damped) temporal envelopes within each period of modulation. For pure-tone carriers, damped modulation was more detectable than ramped modulation for a 5-kHz carrier (by a threshold difference of 3.2 dB on average) but not for a 1-kHz carrier. The threshold difference obtained at 5 kHz between the ramped and damped modulators was consistent across modulation rates (8-128 Hz). This carrier frequency dependence suggests that the effect of temporally asymmetry on modulation detection originates from envelope-based, within-channel mechanisms.	\N	\N
22087927	Speech-in-noise-measurements are important in clinical practice and have been the subject of research for a long time. The results of these measurements are often described in terms of the speech reception threshold (SRT) and SNR loss. Using the basic concepts that underlie several models of speech recognition in steady-state noise, the present study shows that these measures are ill-defined, most importantly because the slope of the speech recognition functions for hearing-impaired listeners always decreases with hearing loss. This slope can be determined from the slope of the normal-hearing speech recognition function when the SRT for the hearing-impaired listener is known. The SII-function (i.e., the speech intelligibility index (SII) against SNR) is important and provides insights into many potential pitfalls when interpreting SRT data. Standardized SNR loss, sSNR loss, is introduced as a universal measure of hearing loss for speech in steady-state noise. Experimental data demonstrates that, unlike the SRT or SNR loss, sSNR loss is invariant to the target point chosen, the scoring method or the type of speech material.	\N	\N
22088028	Monolingual Peruvian Spanish listeners identified natural tokens of the Canadian French (CF) and Canadian English (CE) /ɛ/ and /æ/, produced in five consonantal contexts. The results demonstrate that while the CF vowels were mapped to two different native vowels, /e/ and /a/, in all consonantal contexts, the CE contrast was mapped to the single native vowel /a/ in four out of five contexts. Linear discriminant analysis revealed that acoustic similarity between native and target language vowels was a very good predictor of context-specific perceptual mappings. Predictions are made for Spanish learners of the /ɛ/-/æ/ contrast in CF and CE.	\N	\N
22090001	The primary purpose of this study was to evaluate a group of postlingually deafened adults, whose aided speech recognition exceeded commonly accepted candidacy criteria for implantation. The study aimed to define performance and qualitative outcomes of cochlear implants in these individuals compared with their optimally fitted hearing aid(s). Retrospective case series. Tertiary referral center. All postlingually deafened subjects (N = 27), who were unsuccessful hearing aid users implanted between 2000 and 2010 with a preimplantation Hearing in Noise Test (HINT) score of 60% or more were included. We compared patients' preoperative performance (HINT score) with hearing aids to postoperative performance with the cochlear implant after 12 months of device use. In addition, the Hearing Handicap Inventory questionnaire was used to quantify the hearing-related handicap change perceived after the implantation. The study group demonstrated significant postoperative improvement on all outcome measures; most notably, the mean HINT score improved from 68.4% (standard deviation, 8.3) to 91.9% (standard deviation, 9.7). Additionally, there was a significant improvement in hearing-related handicap perceived by all patients. The envelope of implantation candidacy criteria continues to expand as shown by this study's cohort. Patient satisfaction and speech recognition results are very encouraging in support of treating those who currently perform at a level above the conventional candidacy threshold but struggle with optimally fitted hearing aids.	\N	\N
22099165	Behavioral and electrophysiological measures of target and distractor processing were examined in an auditory selective attention task before and after three weeks of distractor suppression training. Behaviorally, training improved target recognition and led to less conservative and more rapid responding. Training also effectively shortened the temporal distance between distractors and targets needed to achieve a fixed level of target sensitivity. The effects of training on event-related potentials were restricted to the distracting stimulus: earlier N1 latency, enhanced P2 amplitude, and weakened P3 amplitude. Nevertheless, as distractor P2 amplitude increased, so too did target P3 amplitude, connecting experience-dependent changes in distractor processing with greater distinctiveness of targets in working memory. We consider the effects of attention training on the processing priorities, representational noise, and inhibitory processes operating in working memory.	\N	\N
22100742	Tinnitus occurs with or without prior noise exposure (noise-induced tinnitus (NIT) and spontaneous tinnitus (ST)), and is considered a symptom related to permanent hearing impairment (HI) or temporary hearing threshold shift (TTS). To carry out a cross-sectional interview study on TTS, ST and NIT during a standard audiometric screening of 756 7-year-old children in Gothenburg. 41% out of 756 children reported either NIT or ST on several occasions, 17% reported recurrent TTS and 7% failed the audiometry screening. The probability of ST was 27% for children with no HI or TTS (OR=1.23 (95% CI 1.12 to 1.34)) but 63% (OR=1.16 (95% CI 1.02 to 1.33)) if exhibiting both HI and TTS. This study confirms an increased occurrence of spontaneous tinnitus in children with TTS or HI and in children with both TTS and HI, in particular, but also in children with normal hearing. Possibly, tinnitus in young children correlates with stress as in adolescents and adults.	\N	\N
22107443	The objective of this study was to compare two recently proposed methods for fast measurements of psychophysical tuning curves (fast-PTCs) in terms of resulting tuning curve features and training effects. Fast-PTCs with swept-noise (SN) and gated-noise (GN) maskers were measured at signal frequencies of 500, 1000, 2000, and 4000 Hz. The effect of amplitude modulating the signal in the GN condition was evaluated. Two PTC runs were obtained for each condition to assess training effects. Eight normally-hearing young adults participated in the study. The SN and GN methods resulted in similar estimates of frequency selectivity when training effects were considered. Amplitude modulating the tone in the GN method reduced the effect of training. On average, SN-PTCs were most repeatable compared to the two other methods and they were not affected by training. Estimation of the shift in the PTC tip frequency was not affected by the measurement method or training effects. Fast-PTC methods resulted in similar estimates of tuning as compared to published notched-noise data. The SN method and the GN procedure with amplitude modulated signals allowed for time-efficient estimation of frequency selectivity that was unaffected by training.	\N	\N
22115727	We used a qualitative dissociation procedure to assess semantic priming from spatially attended and unattended masked words. Participants categorized target words that were preceded by parafoveal prime words belonging to either the same (20%) or the opposite (80%) category as the target. Using this paradigm, only non-strategic use of the prime would result in facilitation of the target responses in related trials. Primes were immediately masked or masked with a delay, while spatial attention was allocated to the primes' location or away from the primes' location. Immediate masked, strongly related primes facilitated target responses irrespective of the spatial attention. Delayed masked, related primes led to reversed (strategic) or facilitatory priming depending on whether they were cued or uncued. These findings demonstrate that perceiving a stimulus with or without awareness depends on both stimulus quality and attention orienting and that non-strategic priming can be observed from clear visible but spatially unattended words.	\N	\N
22119398	Impairment in long-term memory is one of the most salient alterations in cognitive aging. Findings of age-related deficits in source monitoring and recollection have revealed a selective decline in memory for detailed information. The underlying mechanism of this phenomenon is not well understood. We hypothesized that the influence of task-irrelevant visual stimuli present in our environment interferes with retrieval of detailed memories more for older than younger adults. We compared memory performance on a recall test for visual details when older adult participants' eyes were closed versus performance when their eyes were open and irrelevant visual stimuli were presented. The results showed that the presence of irrelevant visual information diminished long-term memory performance based on an objective measure of recollection for visual details. Comparison of the current results to findings from our earlier study using the same experimental paradigm with younger adults revealed that visual distraction disrupted recollection of relevant details to a greater degree in older than younger adults. This result suggests that visual distraction overwhelms older adults' declining cognitive control resources that are instrumental in the retrieval and selection of mnemonic details. More generally, these findings explicate a mechanistic basis for selective impairment of recollection in normal aging.	\N	\N
22124890	Interaural time differences (ITDs) can be used to localize sounds in the horizontal plane. ITDs can be extracted from either the fine structure of low-frequency sounds or from the envelopes of high-frequency sounds. Studies of the latter have included stimuli with periodic envelopes like amplitude-modulated tones or transposed stimuli, and high-pass filtered Gaussian noises. Here, four experiments are presented investigating the perceptual relevance of ITD cues in synthetic and recorded "rustling" sounds. Both share the broad long-term power spectrum with Gaussian noise but provide more pronounced envelope fluctuations than Gaussian noise, quantified by an increased waveform fourth moment, W. The current data show that the JNDs in ITD for band-pass rustling sounds tended to improve with increasing W and with increasing bandwidth when the sounds were band limited. In contrast, no influence of W on JND was observed for broadband sounds, apparently because of listeners' sensitivity to ITD in low-frequency fine structure, present in the broadband sounds. Second, it is shown that for high-frequency rustling sounds ITD JNDs can be as low as 30 μs. The third result was that the amount of dominance for ITD extraction of low frequencies decreases systematically with increasing amount of envelope fluctuations. Finally, it is shown that despite the exceptionally good envelope ITD sensitivity evident with high-frequency rustling sounds, minimum audible angles of both synthetic and recorded high-frequency rustling sounds in virtual acoustic space are still best when the angular information is mediated by interaural level differences.	\N	\N
22127548	The present acoustic-phonetic study explores whether voicing and devoicing assimilations of French fricatives are equivalent in magnitude and whether they operate similarly (i.e., complete vs. gradient, obligatory vs. optional, regressive vs. progressive). It concurrently assesses the contribution of speakers' articulation rate to the proportion of voicing (i.e., voicing ratios) in /s/ and /z/ embedded in fricative#stop sequences. Data analyses show that voicing and devoicing assimilation are similar in many regards: the absolute amounts of voicing change are equivalent in magnitude (0.77, 0.78) for the two processes: changes in voicing ratios are accompanied by changes in fricative and preceding vowel durations. These concomitant alterations result in the increased acoustic-phonetic similarity between the assimilated and the non-assimilated forms, suggesting that the two processes might be complete. In addition, the two processes operate regressively and across word-boundary. However, data show that the voicing assimilation of /s/ is not rate dependent, which suggest that it might be obligatory, while the devoicing assimilation of /z/ is rate dependent, which suggest that it might be optional.	\N	\N
22133279	To investigate the relationship between plasma reactive oxygen species (ROS) levels and severity of age-related hearing impairment in humans. We recruited 302 adult subjects aged 40-77 years with normal or symmetrical sensorineural hearing loss. The association of plasma ROS levels on pure tone average of low frequencies (PTA-low) and pure tone average of high frequencies (PTA-high) were analyzed. Luminol-dependent chemiluminescence signals, which reflect hydrogen peroxide (H(2)O(2)), hypochlorite (HOCl/OCl(-)) and hydroxyl radicals (•OH) levels, showed significant positive association with PTA-low and PTA-high after adjusting for age, gender, central obesity, systemic diseases, and health-related habits (smoking, drinking, antioxidant intake). Lucigenin-dependent chemiluminescence signals, which mainly reflect superoxide anion (O(2)•(-)) levels, showed significant positive association with PTA-low, but not with PTA-high after adjusting for other variables. We concluded that plasma ROS levels were associated with severity of age-related hearing impairment in humans. Various ROS may differently affect auditory dysfunctions.	\N	\N
22162387	In typically developing (TD) individuals, behavioral and event-related potential (ERP) studies suggest that audiovisual (AV) integration enables faster and more efficient processing of speech. However, little is known about AV speech processing in individuals with autism spectrum disorders (ASD). This study examined ERP responses to spoken words to elucidate the effects of visual speech (the lip movements accompanying a spoken word) on the range of auditory speech processing stages from sound onset detection to semantic integration. The study also included an AV condition, which paired spoken words with a dynamic scrambled face in order to highlight AV effects specific to visual speech. Fourteen adolescent boys with ASD (15-17 years old) and 14 age- and verbal IQ-matched TD boys participated. The ERP of the TD group showed a pattern and topography of AV interaction effects consistent with activity within the superior temporal plane, with two dissociable effects over frontocentral and centroparietal regions. The posterior effect (200-300 ms interval) was specifically sensitive to lip movements in TD boys, and no AV modulation was observed in this region for the ASD group. Moreover, the magnitude of the posterior AV effect to visual speech correlated inversely with ASD symptomatology. In addition, the ASD boys showed an unexpected effect (P2 time window) over the frontocentral region (pooled electrodes F3, Fz, F4, FC1, FC2, FC3, FC4), which was sensitive to scrambled face stimuli. These results suggest that the neural networks facilitating processing of spoken words by visual speech are altered in individuals with ASD.	\N	\N
22171057	Neural activity in the auditory system decreases with repeated stimulation, matching stimulus probability in multiple timescales. This phenomenon, known as stimulus-specific adaptation, is interpreted as a neural mechanism of regularity encoding aiding auditory object formation. However, despite the overwhelming literature covering recordings from single-cell to scalp auditory-evoked potential (AEP), stimulation timing has received little interest. Here we investigated whether timing predictability enhances the experience-dependent modulation of neural activity associated with stimulus probability encoding. We used human electrophysiological recordings in healthy participants who were exposed to passive listening of sound sequences. Pure tones of different frequencies were delivered in successive trains of a variable number of repetitions, enabling the study of sequential repetition effects in the AEP. In the predictable timing condition, tones were delivered with isochronous interstimulus intervals; in the unpredictable timing condition, interstimulus intervals varied randomly. Our results show that unpredictable stimulus timing abolishes the early part of the repetition positivity, an AEP indexing auditory sensory memory trace formation, while leaving the later part (≈ >200 ms) unaffected. This suggests that timing predictability aids the propagation of repetition effects upstream the auditory pathway, most likely from association auditory cortex (including the planum temporale) toward primary auditory cortex (Heschl's gyrus) and beyond, as judged by the timing of AEP latencies. This outcome calls for attention to stimulation timing in future experiments regarding sensory memory trace formation in AEP measures and stimulus probability encoding in animal models.	\N	\N
22172209	Using online measures of familiar word recognition in the looking-while-listening procedure, this prospective longitudinal study revealed robust links between processing efficiency and vocabulary growth from 18 to 30 months in children classified as typically developing (n = 46) and as "late talkers" (n = 36) at 18 months. Those late talkers who were more efficient in word recognition at 18 months were also more likely to "bloom," showing more accelerated vocabulary growth over the following year, compared with late talkers less efficient in early speech processing. Such findings support the emerging view that early differences in processing efficiency evident in infancy have cascading consequences for later learning and may be continuous with individual differences in language proficiency observed in older children and adults.	\N	\N
22174701	In this review paper aimed at the non-specialist, we explore the use that neuroscientists and musicians have made of perceptual illusions based on ambiguity. The pivotal issue is auditory scene analysis (ASA), or what enables us to make sense of complex acoustic mixtures in order to follow, for instance, a single melody in the midst of an orchestra. In general, ASA uncovers the most likely physical causes that account for the waveform collected at the ears. However, the acoustical problem is ill-posed and it must be solved from noisy sensory input. Recently, the neural mechanisms implicated in the transformation of ambiguous sensory information into coherent auditory scenes have been investigated using so-called bistability illusions (where an unchanging ambiguous stimulus evokes a succession of distinct percepts in the mind of the listener). After reviewing some of those studies, we turn to music, which arguably provides some of the most complex acoustic scenes that a human listener will ever encounter. Interestingly, musicians will not always aim at making each physical source intelligible, but rather express one or more melodic lines with a small or large number of instruments. By means of a few musical illustrations and by using a computational model inspired by neuro-physiological principles, we suggest that this relies on a detailed (if perhaps implicit) knowledge of the rules of ASA and of its inherent ambiguity. We then put forward the opinion that some degree perceptual ambiguity may participate in our appreciation of music.	\N	\N
22177410	The study of the neural basis of syntactic processing has greatly benefited from neuroimaging techniques. Research on syntactic processing in bilinguals has used a variety of techniques, including mainly functional magnetic resonance imaging (fMRI) and event-related potentials (ERP). This paper reports on a functional near-infrared spectroscopy (fNIRS) study on syntactic processing in highly proficient young adult speakers of Portuguese (mother tongue) (L1) and French (second language) (L2). They made a syntactic judgment of visually presented sentences, which either did or did not contain noun-verb agreement violations. The results showed that syntactic processing in both languages resulted in significant activation in anterior frontal regions of the left hemisphere and in the temporal superior posterior areas of the right hemisphere, with a more prominent activation for L2 in some areas. These findings corroborate previously reported neuroimaging evidence, showing the suitability of fNIRS for the study of syntactic processing in the bilingual brain.	\N	\N
22178743	Rhythm is a phenomenon that fundamentally affects the perception of events unfolding in time. In language, we define 'rhythm' as the temporal structure that underlies the perception and production of utterances, whereas 'meter' is defined as the regular occurrence of beats (i.e. stressed syllables). In stress-timed languages such as German, this regularity functions as a powerful temporal and structural cue in speech comprehension. Recent evidence shows that it also interacts with higher level linguistic faculties such as syntax (Schmidt-Kassow & Kotz, 2009a). The current ERP experiment investigated the impact of metric structure on lexico-semantic processing, comparing the effects of semantic and metric expectancy in regular and irregular metric sentence contexts. We predicted that (1) semantically unexpected words would result in an increased N400 amplitude and (2) metric context modulates the N400 amplitude. Our results confirm these predictions: semantically unexpected words elicit an N400 that is significantly smaller in a metrically regular than a metrically irregular sentence context. The current findings support the idea that metric regularity enhances the prediction of stress locations in a sentence context, which in turn facilitates lexico-semantic integration.	\N	\N
22183282	Different studies have been carried out in order to correlate audiometric thresholds and distortion product otoacoustic emissions measurements (DPOAE). However, high variability and external interferences make hearing thresholds estimates by means of the DPOAE very little sensitive. The aim of this study was to check the correspondence between the pure tone thresholds and the cochlear response thresholds by DPOAE Input/output functions, considering the influence of the following variables: gender, past of acute otitis media, and ear side. Prospective study comprehending 69 normal hearing individuals. Multiple mix regression models were applied to evaluate the correspondence between the two measurements studied. Statistically significant positive correlation was observed among all the frequencies compared (2000, 3000, 4000 e 6000 Hz). The 1 dB HL resolution pure tone thresholds and the above-mentioned variables had a direct impact on the high correlation between the measures studied, and it also reduced response variability. Nevertheless, response variability was still high, limiting the use of DPOAE I/O functions for hearing threshold estimates. We suggest that these variables should be considered for future studies with pure tone thresholds estimations by DPOAE I/O functions.	\N	\N
22197571	This study aimed to assess the effect of musical training in statistical learning of tone sequences using Magnetoencephalography (MEG). Specifically, MEG recordings were used to investigate the neural and functional correlates of the pre-attentive ability for detection of deviance, from a statistically learned tone sequence. The effect of long-term musical training in this ability is investigated by means of comparison of MMN in musicians to non-musicians. Both groups (musicians and non-musicians) showed a mismatch negativity (MMN) response to the deviants and this response did not differ amongst them neither in amplitude nor in latency. Another interesting finding of this study is that both groups revealed a significant difference between the standards and the deviants in the response of P50 and this difference was significantly larger in the group of musicians. The increase of this difference in the group of musicians underlies that intensive, specialized and long term exercise can enhance the ability of the auditory cortex to discriminate new auditory events from previously learned ones according to transitional probabilities. A behavioral discrimination task between the standard and the deviant sequences followed the MEG measurement. The behavioral results indicated that the detection of deviance was not explicitly learned by either group, probably due to the lack of attentional resources. These findings provide valuable insights on the functional architecture of statistical learning.	\N	\N
22199192	The effects of type of stimuli (i.e., nonspeech vs. speech), speech (i.e., natural vs. synthetic), gender of speaker and listener, speaker (i.e., self vs. other), and frequency alteration in self-produced speech on the late auditory cortical evoked potential were examined. Young adult men (n = 15) and women (n = 15), all with normal hearing, participated. P1-N1-P2 components were evoked with the following stimuli: 723-Hz tone bursts; naturally produced male and female /a/ tokens; synthetic male and female /a/ tokens; an /a/ token self-produced by each participant; and the same /a/ token produced by the participant but with a shift in frequency. In general, P1-N1-P2 component latencies were significantly shorter when evoked with the tonal stimulus versus speech stimuli and natural versus synthetic speech (p < .05). Women had significantly shorter latencies for only the P2 component (p < .05). For the tonal versus speech stimuli, P1 amplitudes were significantly smaller, and N1 and P2 amplitudes were significantly larger (p < .05). There was no significant effect of gender on the P1, N1, or P2 amplitude (p > .05). These findings are consistent with the notion that spectrotemporal characteristics of nonspeech and speech stimuli affect P1-N1-P2 latency and amplitude components.	\N	\N
22201556	Congenital amusia is a neurodevelopmental disorder that is characterized primarily by difficulties in the pitch domain. The aim of the present study was to investigate the perception of musical timbre in a group of individuals with congenital amusia by probing discrimination and short-term memory for real-world timbral stimuli as well as examining the ability of these individuals to sort instrumental tones according to their timbral similarity. Thirteen amusic individuals were matched with thirteen non-amusic controls on a range of background variables. The discrimination task included stimuli of two different durations and pairings of instrumental tones that reflected varying distances in a perceptual timbre space. Performance in the discrimination task was at ceiling for both groups. In contrast, amusic individuals scored lower than controls on the short-term timbral memory task. Amusic individuals also performed worse than controls on the sorting task, suggesting differences in the higher-order representation of musical timbre. These findings add to the emerging picture of amusia as a disorder that has consequences for the perception and memory of musical timbre, as well as pitch.	\N	\N
22209062	To investigate the relationships between objective measures and the results of subjective assessment of voice quality and speech intelligibility in patients submitted to total laryngectomy and tracheoesophageal (TE) puncture. Retrospective. Twenty patients implanted with voice prosthesis were studied. After surgery, the entire sample performed speech rehabilitation. The assessment protocol included maximum phonation time (MPT), number of syllables per deep breath, acoustic analysis of the sustained vowel /a/ and of a bisyllabic word, perceptual evaluation (pleasantness and intelligibility%), and self-assessment. The correlation between pleasantness and intelligibility% was statistically significant. Both the latter were significantly correlated with the acoustic signal type, the number of formant peaks, and the F2-F1 difference. The intelligibility% and number of formant peaks were significantly correlated with the MPT and number of syllables per deep breath. Moreover, significant correlations were found between the number of formant peaks and both intelligibility% and pleasantness. The higher the number of syllables per deep breath and the longer the MPT, significantly higher was the number of formant peaks and the intelligibility%. The study failed to show significant correlation between patient's self-assessment of voice quality and both pleasantness and communication effectiveness. The multidimensional assessment seems to be a reliable tool to evaluate the TE functional outcome. Particularly, the results showed that both pleasantness and intelligibility of TE speech are correlated to the availability of expired air and the function of the vocal tract.	\N	\N
22213748	To determine the efficacy of cochlear implantation (CI) in prelingually deafened adolescent children and to evaluate predictive variables for successful outcomes. Retrospective medical record review. Children aged 10 to 17 years with prelingual hearing loss (mean length of deafness, 11.5 years) who received a unilateral CI (mean age at CI, 12.9 years). Unilateral CI. Standard speech perception testing (Consonant-Nucleus-Consonant [CNC] monosyllabic word test and Hearing in Noise [HINT] sentence test) was performed preoperatively, 1 year postoperatively (year 1), and at the last follow-up/end of the study (EOS). There was a highly significant improvement in speech perception scores for both HINT sentence and CNC word testing from the preoperative testing to year 1 (mean change score, 51.10% and 32.23%, respectively; P < .001) and from the preoperative testing to EOS (mean change score, 60.02% and 38.73%, respectively; P < .001), with a significantly greater increase during the first year (P < .001). In addition, there was a highly significant correlation between improvements in performance scores on the CNC word and HINT sentence speech perception tests and both age at CI and length of deafness at the year 1 testing (P ≤.009) but not from the year 1 testing to EOS testing. Adolescents with progressive deafness and those using oral communication before CI performed significantly better than age-matched peers. Adolescents with prelingual deafness undergoing unilateral CI show significant improvement in objective hearing outcome measures. Patients with shorter lengths of deafness and earlier age at CI tend to outperform their peers. In addition, patients with progressive deafness and those using oral communication have significantly better objective outcomes than their peers.	\N	\N
22218296	Visual attention has temporal limitations. In the attentional blink (AB) a stream of stimuli such as letters or digits are presented to a participant on a computer monitor at a rapid rate. Embedded in the stream are two targets that the participant must try to identify. Identification of the second target is severely impaired if it is presented within approximately 500ms of the first target. This is the 'blink' in visual attention. In this study we examined the role of the magnocellular visual pathway in the AB. This fast conducting pathway has high temporal resolution and contrast sensitivity. It is also insensitive to the direction of chromatic contrast, and this attribute was exploited in order to isolate its contributions to temporal attention. Colour defined, luminance noise masked AB streams were compared to AB streams of varying achromatic contrast. The four observers, (2F and 2M) aged between 21 and 35years, had normal visual acuity and colour vision. The colour stimuli produced a similar blink to the moderate contrast achromatic stimuli. This indicates that the magnocellular pathway does not have a privileged role in the attentional blink. We provide an explanation of previous apparently contradictory findings in terms of the role of different types of visual masking in the attentional blink.	\N	\N
22232388	The goal of this study was to compare clinical and research-based cochlear implant (CI) measures using telehealth versus traditional methods. This prospective study used an ABA design (A = laboratory, B = remote site). All measures were made twice per visit for the purpose of assessing within-session variability. Twenty-nine adult and pediatric CI recipients participated. Measures included electrode impedance, electrically evoked compound action potential thresholds, psychophysical thresholds using an adaptive procedure, map thresholds and upper comfort levels, and speech perception. Subjects completed a questionnaire at the end of the study. Results for all electrode-specific measures revealed no statistically significant differences between traditional and remote conditions. Speech perception was significantly poorer in the remote condition, which was likely due to the lack of a sound booth. In general, subjects indicated that they would take advantage of telehealth options at least some of the time, if such options were available. Results from this study demonstrate that telehealth is a viable option for research and clinical measures. Additional studies are needed to investigate ways to improve speech perception at remote locations that lack sound booths and to validate the use of telehealth for pediatric services (e.g., play audiometry), sound-field threshold testing, and troubleshooting equipment.	\N	\N
22232404	Older adults exhibit difficulty understanding speech that has been experimentally degraded. Age-related changes to the speech mechanism lead to natural degradations in signal quality. We tested the hypothesis that older adults with hearing loss would exhibit declines in speech recognition when listening to the speech of older adults, compared with the speech of younger adults, and would report greater amounts of listening effort in this task. Nineteen individuals with age-related hearing loss completed speech recognition and listening effort scaling tasks. Both were conducted in quiet, when listening to high- and low-predictability phrases produced by younger and older speakers, respectively. No significant difference in speech recognition existed when stimuli were derived from younger or older speakers. However, perceived effort was significantly higher when listening to speech from older adults, as compared with younger adults. For older individuals with hearing loss, natural degradations in signal quality may require greater listening effort. However, they do not interfere with speech recognition-at least in quiet. Follow-up investigation of the effect of speaker age on speech recognition and listening effort under more challenging noise conditions appears warranted.	\N	\N
22232413	The ability to detect a tone added to a random masker improves when a preview of the masker is provided. In 2 experiments, the authors explored the role that perceptual organization plays in this release from masking. Detection thresholds were measured in informational masking studies. The maskers were drawn at random prior to each trial. Masker or signal-plus-masker precursors preceded the detection interval, and the time between the precursor and the detection interval was systematically altered. In Experiment 1, the signal frequency was either fixed or random. In Experiment 2, the random masker was composed of harmonics of a common fundamental frequency (F (0)), and the randomly chosen signal frequency was either harmonically related to, or mistuned from, the masker's F (0). For a masker precursor, the release from informational masking withstood longer precursor-detection interval delays (a) when the signal frequency was fixed versus random and (b) when the signal was mistuned relative to a harmonic of the masker's F (0). These results suggest that listeners' ability to attend to the signal may contribute to the long-lived release from masking with a masker precursor.	\N	\N
22237163	The aim of this study was to investigate potential effects of age on the ability of normal-hearing (NH) adult listeners to utilize spectral and temporal cues when performing a voice gender identification task. Ten younger and 10 older NH adult listeners were measured on their ability to correctly identify the speaker gender of six different vowel tokens (H-/vowel/-D) when spoken by eight speakers (four male and four female). Spectral (number of channels) and temporal cues (low-pass cut-off frequency for temporal envelope extraction) were systematically manipulated using noiseband vocoding techniques; stimuli contained 1, 4, 8, 16, or 32 spectral channels, while the low-pass cut-off frequency of the temporal envelope filter was 20, 50, 100, 200, or 400 Hz. Furthermore, the fundamental frequencies (F0s) of the vowel tokens were manipulated to create two conditions: "Expanded" (large range of F0 values) and "Compressed" (small range of F0 values). In general, younger listeners performed better than the older listeners but only when stimuli were spectrally degraded. For both the Expanded and Compressed conditions, the overall performance of the younger listeners was better than that of the older listeners, suggesting age-related deficits in both spectral and temporal processing. Furthermore, a significant interaction between age group and temporal envelope cues revealed that older listeners received less benefit from increasing temporal envelope information compared with the benefit observed among younger listeners. In particular, the performance of the younger NH group (collapsed across number of channels), but not the older NH group, improved as the temporal envelope cut-off frequency was increased from 50 to 400 Hz. The results reported here support previous findings of senescent declines in perceiving spectrally reduced speech and temporal amplitude modulation processing. These results suggest that when F0 values are similar to one another, younger listeners can use temporal cues alone to glean voice-pitch information but older listeners exhibit a lessened ability to use such cues. Previous studies have demonstrated the importance of temporal envelope cues in periodicity perception (e.g., gender recognition) by cochlear implant listeners. The results of this study suggest that aging affects the use of such cues, and consequently gender recognition might be poorer among older cochlear implant recipients.	\N	\N
22245012	An event-related potential, the Phonological Mapping Negativity (PMN), has been reported to reflect recognition of phonological mismatches in speech stimuli. The purpose of the present study was to explore how the PMN response to the auditory nonsense syllable reflects phonological processing in isolation without the letter prime or lexical/semantic context. Sixty-four nonsense syllable stimuli were composed for each of three stimulus conditions: phonological match (PM), phonological mismatch with similar sound (PMMS), and phonological mismatch with different sound (PMMD), making a total of 192 stimuli. The PMN was measured from fourteen normal-hearing listeners. Electroencephalogram (EEG) activity was recorded while subjects were listening to the stimuli and responding behaviorally. Subjects were asked to determine what vowel-consonant-vowel (VCV) (e.g. /apa/) would be formed from the combination of the preceding vowel (V) (e.g. /a/) and consonant-vowel (CV) (e.g. /pa/), and press a 'correct' or 'incorrect' response button as soon as they decided whether the target VCV stimulus matched their expectation. In this way, along with the PMN, behavioral response accuracy and reaction times were obtained. The results were as follows: (1) PMN amplitude was not different by stimulus condition, (2) PMN amplitude was larger over frontal and central than posterior regions, but not different between the left versus right hemisphere, (3) PMN was detected in the absence of N400, and (4) behavioral responses were more accurate and faster in PMMD than PM and PMMS. Results indicate that the PMN can reflect phonological processing of auditory nonsense syllables in isolation. The scalp distribution of PMN is most dominant in the fronto-central regions without lateralization. Lastly, behavioral response accuracy and reaction times appear to be influenced by the extent of the task difficulty or processing demand rather than by the extent of phonological violation.	\N	\N
22247221	We employed a variant of the mask-onset delay paradigm in order to limit the availability of visual information in central and peripheral vision within individual fixations during scene viewing. Subjects viewed full-color scene photos with instructions to search for a target object (Experiment 1) or to study them for a later memory test (Experiment 2). After a fixed interval following the onset of each eye fixation (50-100 ms), the scene was scrambled either in the central visual field or over the entire display. The intact scene was presented when the subject made an eye movement. Our results reconcile different sets of findings from prior research regarding the masking of central and peripheral visual information at different intervals following fixation onset. In particular, we found that when the entire display was scrambled, both search and memory performance were impaired even at relatively long mask-onset intervals. In contrast, when central vision was scrambled, there were subtle impairments that depended on the viewing task. In the 50-ms mask-onset interval, subjects were selectively impaired at identifying, but not in locating, the search target (Experiment 1), while memory performance (Experiment 2) was unaffected in this condition, and hence, the reliance on central and peripheral visual information depends partly on the viewing task.	\N	\N
22251050	Given that semantic processes mediate early processes in the elicitation of emotions, we expect that already activated emotion-specific information can influence the elicitation of an emotion. In Experiment 1, participants were exposed to masked International Affective Picture System (IAPS) pictures that elicited either disgust or fear. Following the presentation of the primes, other IAPS pictures were presented as targets that elicited either disgust or fear. The participants' task was to classify the target picture as either disgust or fear evoking. In Experiment 2, we substituted the IAPS primes with facial expressions of either disgust or fear. In Experiment 3, we substituted the IAPS primes with the words disgust or fear. In all three experiments, we found that prime-target combinations of the same emotion were responded to faster than prime-target combinations of different emotions. Our findings suggest that the influence of primes on the elicitation of emotion is mediated by activated schemata or appraisal processes.	\N	\N
22253008	Auditory brainstem implants (ABIs) can provide highly beneficial hearing sensations to individuals deafened by bilateral vestibular schwannomas (neurofibromatosis type 2). Relatively little is known about the status of stimulated neurons after long-term ABI use. Direct examination of the cochlear nuclear complex (CN) of one 5-year ABI user indicated no deleterious effect. Recently, we examined the brainstem of a patient who used his ABI daily for 15 years with excellent performance. There was good preservation of CN cell size, morphology, and packing density, a very favorable sign considering that a number of infants are now receiving ABIs.	\N	\N
22264101	Our findings show that all cochlear implanted temporal bones had a varied degree of trauma and inflammatory reaction from cochlear implantation. No definitive relationship was observed from our limited number of specimens between residual spiral ganglion cells (SGCs) in implanted temporal bones and clinical speech performance. We hypothesize that there is a relationship between residual SGCs in cochlear implanted temporal bones and clinical speech performance. Our aim was to examine the histopathology of multi-channel cochlear implant temporal bones and to evaluate the relationship of residual SGC counts to clinical hearing performance. Temporal bones from four cochlear implant patients were examined histologically. Comparisons were made between implanted and nonimplanted temporal bones. Clinical performance data were obtained from patient charts. There were varying amounts of inflammation in the basal turn of the cochleae in all four implanted temporal bones. Trauma to the facial nerve at the facial recess was noticed in one case. Surviving dendrites varied from 5% to 30% among four cases, with no relationship to clinical performance. The speech recognition scores, measured with Central Institute of the Deaf (CID) sentence score, varied among patients from 4% to 89%, while the patient with the highest SGCs had the best clinical outcome.	\N	\N
22280721	A psychophysical pitch function, describing the relation of perceived magnitude of pitch to the frequency of a pure tone, was determined by absolute magnitude estimation. Pitch estimates were made by listeners with relative pitch and by absolute pitch possessors for 27 tones spanning a frequency range of 31.5-12,500 Hz in 1/3 octave steps. Results show that the pitch function, plotted in log-log coordinates, is steeper below 200 Hz than at higher frequencies. It is hypothesized that the pitch function's bend may reflect the diversity of neurophysiological mechanisms of pitch encoding in frequency ranges below and above 200 Hz. The variation of the function's slope implies that pitch distances between tones with the same frequency ratios are perceived as larger below 200 Hz than at higher frequencies. It is argued that this implication may apply only to a purely sensory concept of pitch distance and cannot be extended to the perception of musical intervals, a phenomenon governed by musical cognitive principles. The results also show that pitch functions obtained for listeners with relative and absolute pitch have a similar shape, which means that quantitative pitch relations determined for both groups of listeners do not differ appreciably along the frequency scale.	\N	\N
22289507	In this event-related potential (ERP) study a masking technique that prevents conscious perception of words and non-words through attentional distraction was used to reveal the temporal dynamics of word processing under non-conscious and conscious conditions. In the non-conscious condition, ERP responses differed between masked words and non-words from 112 to 160 ms after stimulus-onset over posterior brain areas. The early onset of the word-non-word differences was compatible with previous studies that reported non-conscious access to orthographic information within this time period. Moreover, source localisations provided evidence for automatic activation of prelexical phonological information, whereas no evidence for non-conscious semantic processing was found. When subjects were informed about the masking technique, lexical differences occurred at later time intervals, suggesting conscious access to additional word related information. These results indicate that early visual word processing does not depend entirely on attentional resources, but that non-conscious processing probably is restricted to rather lower-level linguistic information.	\N	\N
22290344	Synesthesia is a sensory disorder where the stimulation of one sensory modality can lead to a reaction in another which would not usually be expected to respond; for instance, someone might see a color on hearing a word such as a day of the week. Disordered perception of sensory information also appears to contribute to the pathophysiology of irritable bowel syndrome (IBS). The purpose of this exploratory study was to ascertain whether these two conditions might be linked in any way. Two hundred consecutive IBS outpatients were screened for synesthesia and compared with 200 matched healthy volunteers (controls). Positive responders were tested for two types of synesthesia (grapheme-color and music-color/shape) using a questionnaire which was repeated after 3 months to test for reproducibility. Of the 200 IBS outpatients screened, 26 (13%) patients and six (3%) controls claimed to be synesthetic (P < 0.001). Reproducibility was more variable in IBS patients than controls but despite this variability, 15 (7.5%) patients compared with 5 (2.5%) controls had greater than 75% consistency (P = 0.036), and 19 (9.5%) patients and 6 (3%) controls had greater than 50% consistency (P = 0.012). A reproducibility of less than 50% was observed in seven (3.5%) patients and no controls (0%) (P = 0.015), and these individuals were classified as having pseudo-synesthesia. IBS patients clearly differ from controls in terms of claiming to have synesthetic experiences. These results justify additional studies on the relationship between IBS and synesthesia to further understand the neural mechanisms underpinning these two conditions and to establish whether they may be linked.	\N	\N
22292985	The effects of the use of cochlear implant (CI) on speech intelligibility, speaking rate, and vowel formant characteristics and the relationships between speech intelligibility, speaking rate, and vowel formant characteristics for children are clinically important. The purposes of this study were to report on the comparisons for speaking rate and vowel space area, and their relationship with speech intelligibility, between 24 Mandarin-speaking children with CI and 24 age-sex-education level matched normal hearing (NH) controls. Participants were audio recorded as they read a designed Mandarin intelligibility test, repeated prolongation of each of the three point vowels /i/, /a/, and /u/ five times, and repeated each of three sentences carrying one point vowel five times. Compared to the NH group, the CI group exhibited: (1) mild-to-moderate speech intelligibility impairment; (2) significantly reduced speaking rate mainly due to significantly longer inter-word pauses and larger pause proportion; and (3) significantly less vowel reduction in the horizontal dimension in sustained vowel phonation. The limitations of speech intelligibility development in children after cochlear implantation were related to atypical patterns and to a smaller degree in vowel reduction and slower speaking rate resulting from less efficient articulatory movement transition.	\N	\N
22302814	Understanding speech in noisy environments is often taken for granted; however, this task is particularly challenging for people with cochlear hearing loss, even with hearing aids or cochlear implants. A significant limitation to improving auditory prostheses is our lack of understanding of the neural basis for robust speech perception in noise. Perceptual studies suggest the slowly varying component of the acoustic waveform (envelope, ENV) is sufficient for understanding speech in quiet, but the rapidly varying temporal fine structure (TFS) is important in noise. These perceptual findings have important implications for cochlear implants, which currently only provide ENV; however, neural correlates have been difficult to evaluate due to cochlear transformations between acoustic TFS and recovered neural ENV. Here, we demonstrate the relative contributions of neural ENV and TFS by quantitatively linking neural coding, predicted from a computational auditory nerve model, with perception of vocoded speech in noise measured from normal hearing human listeners. Regression models with ENV and TFS coding as independent variables predicted speech identification and phonetic feature reception at both positive and negative signal-to-noise ratios. We found that: (1) neural ENV coding was a primary contributor to speech perception, even in noise; and (2) neural TFS contributed in noise mainly in the presence of neural ENV, but rarely as the primary cue itself. These results suggest that neural TFS has less perceptual salience than previously thought due to cochlear signal processing transformations between TFS and ENV. Because these transformations differ between normal and impaired ears, these findings have important translational implications for auditory prostheses.	\N	\N
22304406	Children ask questions and learn from the responses they receive; however, little is known about how children learn from listening to others ask questions. Five experiments examined preschoolers' (N = 179) ability to solve simple problems using information gathered from listening to question-and-answer exchanges between 2 parties present in the same room. Overall, the ability to efficiently use information gathered from overheard exchanges improved between ages 3 and 5. Critically, however, across ages children solved the majority of problems correctly, suggesting preschoolers are capable of learning from others' questions. Moreover, children learned from others' questions without explicit instruction and when engaged in another activity. Implications for the development of problem-solving skills are discussed.	\N	\N
22317269	The purpose of this study was to assess normal hearing listeners' performance in detecting a stationary backup alarm signal and to quantify the linear distance at detection point. Detection distances for 12 participants with normal hearing were measured while they were fitted with 7 hearing protectors and while they were unoccluded (open ear). A standard (narrowband) backup alarm signal and a broadband (pulsed white noise) backup alarm signal from Brigade[1] were used. The method of limits, with distance as the physical measurement variable and threshold detection as the task, was employed to find at which distance the participant could first detect the backup alarms. A within-subject Analysis of Variance (ANOVA) revealed a significant main effect of the listening conditions on the detection distance in feet. Post hoc analyses indicated that the Bilsom L3HV conventional passive earmuff (at 1132.2 ft detection distance) was significantly poorer compared to all other HPDs and the open ear in detection distance achieved, and that there were no statistically-significant differences between the unoccluded ear (1652.3 ft), EB-15-Lo BlastPLGTM (1546.2 ft), EB-15-Hi BlastPLGTM (1543.4 ft), E-A-R/3M Combat ArmsTM earplug-nonlinear, level-dependent state (1507.8 ft), E-A-R/3M HiFiTM earplug (1497.7 ft), and Bilsom ImpactTM dichotic electronic earmuff (1567.2 ft). In addition, the E-A-R/3M Combat ArmsTM earplug-passive steady state resulted in significantly longer detection distances than only the open ear condition, at 1474.1 ft versus 1652.3 ft for the open ear. ANOVA also revealed a significant main effect of the backup alarm type on detection distance. The means were 1600.9 ft for the standard (narrowband) backup alarm signal, and a significantly closer 1379.4 ft was required for the Brigade broadband backup alarm signal. For on-ground workers, it is crucial to detect backup alarm signals as far away as possible rather than at close distances since this will provide them more time to react to approaching vehicles. The results of this study suggest that as the attenuation of the hearing protectors increases, precautions should be considered by safety professionals. This is because, as it was the case with the Bilsom passive earmuff and E-A-R/3M Combat ArmsTM earplug-passive steady state, high attenuation minimizes the detection distance and as a result on-foot workers will have less time to react to any approaching vehicle. The main effects of the type of backup alarm signal demonstrated a statistically-significant advantage of the standard backup alarm over the broadband backup alarm on detection distance in feet. The magnitude of the improvement produced by the standard backup alarm was 221.5 feet, a very large margin. For example, with a vehicle backing at 10 mph, the 221.5 ft decrease in detection distance with the Brigade alarm equates to the vehicle arriving 15 seconds sooner at the worker from the point at which its alarm was first heard.	\N	\N
22321294	This study was designed to separately test the effect of the cued/cueless nature of deviant stimuli and that of temporal distance between sound and deviance onsets on the mismatch negativity (MMN) as well as to look for discrepancies between behavioural discrimination performances and MMN amplitude when deviants are cueless. Ten healthy adults passively listened to stimuli that were contrasted by the presence or absence of a frequency sweep starting early or late within the sound. Discrimination performances were collected after the electrophysiological sessions. MMNs were much larger for cued than for cueless deviants. The temporal distance between sound and deviance onsets affected MMNs evoked by both cued and cueless deviants, even to the point of abolishing the MMN when cueless deviance occurred late in the stimulus. Behavioural data were at ceiling levels for all conditions, contrasting with the absence of MMN evoked by cueless deviants with late onset. Two mechanisms contribute to the MMN evoked by cued deviants: the memory comparison process and the adaptation/fresh-afferent one. Within the temporal window of integration, the delay at which each component disappears is different. Comparing waveforms evoked by cued versus cueless deviants provides a fairly simple way of isolating the MMN memory-based component.	\N	\N
22323627	The ability to detect and track relevant acoustic signals embedded in a background of other sounds is crucial for hearing in complex acoustic environments. This ability is exemplified by a perceptual phenomenon known as "rhythmic masking release" (RMR). To demonstrate RMR, a sequence of tones forming a target rhythm is intermingled with physically identical "Distracter" sounds that perceptually mask the rhythm. The rhythm can be "released from masking" by adding "Flanker" tones in adjacent frequency channels that are synchronous with the Distracters. RMR represents a special case of auditory stream segregation, whereby the target rhythm is perceptually segregated from the background of Distracters when they are accompanied by the synchronous Flankers. The neural basis of RMR is unknown. Previous studies suggest the involvement of primary auditory cortex (A1) in the perceptual organization of sound patterns. Here, we recorded neural responses to RMR sequences in A1 of awake monkeys in order to identify neural correlates and potential mechanisms of RMR. We also tested whether two current models of stream segregation, when applied to these responses, could account for the perceptual organization of RMR sequences. Results suggest a key role for suppression of Distracter-evoked responses by the simultaneous Flankers in the perceptual restoration of the target rhythm in RMR. Furthermore, predictions of stream segregation models paralleled the psychoacoustics of RMR in humans. These findings reinforce the view that preattentive or "primitive" aspects of auditory scene analysis may be explained by relatively basic neural mechanisms at the cortical level.	\N	\N
22337498	In this study, the authors (a) investigated whether a group of people with severe aphasia could learn a vocabulary of pantomime gestures through therapy and (b) compared their learning of gestures with their learning of words. The authors also examined whether gesture therapy cued word production and whether naming therapy cued gestures. Fourteen people with severe aphasia received 15 hr of gesture and naming treatments. Evaluations comprised repeated measures of gesture and word production, comparing treated and untreated items. Baseline measures were stable but improved significantly following therapy. Across the group, improvements in naming were greater than improvements in gesture. This trend was evident in most individuals' results, although 3 participants made better progress in gesture. Gains were item specific, and there was no evidence of cross-modality cueing. Items that received gesture therapy did not improve in naming, and items that received naming therapy did not improve in gesture. Results show that people with severe aphasia can respond to gesture and naming therapies. Given the unequal gains, naming may be a more productive therapy target than gesture for many (although not all) individuals with severe aphasia. The communicative benefits of therapy were not examined but are addressed in a follow-up article.	\N	\N
22352496	The standard method for the calibration of audiometric bone vibrators requires the use of an artificial mastoid, a device that converts vibratory energy to an electrical analog. The mechanical input impedance of the device is designed to represent the average mechanical impedance of the human head. For calibration purposes, it is not necessary that the coupling device represent the impedance of the head. It is only necessary that it provides a repeatable measurement of the output of the vibrator that can be related to the normal threshold of hearing at each test frequency. In addition to the mechanical output that serves as the stimulus for the hearing test, bone vibrators produce an acoustic signal that is proportional to the mechanical force delivered to the head. By determining the transfer function relating the acoustic sound pressure to the mechanical force, the acoustic signal can serve as a proxy for the vibratory stimulus. This article describes the design and validation of an acoustic coupler for the calibration of audiometric bone vibrators.	\N	\N
22352502	The reliability of distortion-product otoacoustic emission (DPOAE) measurements and their relation to loudness measurements was examined in 16 normal-hearing subjects and 58 subjects with hearing loss. The level of the distortion product (L(d)) was compared across two sessions and resulted in correlations that exceeded 0.90. The reliability of DPOAEs was less when parameters from nonlinear fits to the input/output (I/O) functions were compared across visits. Next, the relationship between DPOAE I/O parameters and the slope of the low-level portion of the categorical loudness scaling (CLS) function (soft slope) was assessed. Correlations of 0.65, 0.74, and 0.81 at 1, 2, and 4 kHz were observed between CLS soft slope and combined DPOAE parameters. Behavioral threshold had correlations of 0.82, 0.83, and 0.88 at 1, 2, and 4 kHz with CLS soft slope. Combining DPOAEs and behavioral threshold provided little additional information. Lastly, a multivariate approach utilizing the entire DPOAE I/O function was used to predict the CLS rating for each input level (dB SPL). Standard error of the estimate when using this method ranged from 2.4 to 3.0 categorical units (CU), suggesting that DPOAE I/O functions can predict CLS measures within the CU step size used in this study (5).	\N	\N
22352514	Cross-generational and cross-dialectal variation in vowels among speakers of American English was examined in terms of vowel identification by listeners and vowel classification using pattern recognition. Listeners from Western North Carolina and Southeastern Wisconsin identified 12 vowel categories produced by 120 speakers stratified by age (old adults, young adults, and children), gender, and dialect. The vowels /ɝ, o, ʊ, u/ were well identified by both groups of listeners. The majority of confusions were for the front /i, ɪ, e, ɛ, æ/, the low back /ɑ, ɔ/ and the monophthongal North Carolina /aɪ/. For selected vowels, generational differences in acoustic vowel characteristics were perceptually salient, suggesting listeners' responsiveness to sound change. Female exemplars and native-dialect variants produced higher identification rates. Linear discriminant analyses which examined dialect and generational classification accuracy showed that sampling the formant pattern at vowel midpoint only is insufficient to separate the vowels. Two sample points near onset and offset provided enough information for successful classification. The models trained on one dialect classified the vowels from the other dialect with much lower accuracy. The results strongly support the importance of dynamic information in accurate classification of cross-generational and cross-dialectal variations.	\N	\N
22352516	This study examined whether speech-on-speech masking is sensitive to variation in the degree of similarity between the target and the masker speech. Three experiments investigated whether speech-in-speech recognition varies across different background speech languages (English vs Dutch) for both English and Dutch targets, as well as across variation in the semantic content of the background speech (meaningful vs semantically anomalous sentences), and across variation in listener status vis-à-vis the target and masker languages (native, non-native, or unfamiliar). The results showed that the more similar the target speech is to the masker speech (e.g., same vs different language, same vs different levels of semantic content), the greater the interference on speech recognition accuracy. Moreover, the listener's knowledge of the target and the background language modulate the size of the release from masking. These factors had an especially strong effect on masking effectiveness in highly unfavorable listening conditions. Overall this research provided evidence that that the degree of target-masker similarity plays a significant role in speech-in-speech recognition. The results also give insight into how listeners assign their resources differently depending on whether they are listening to their first or second language.	\N	\N
22352522	Automatic speech recognition (ASR) refers to the task of extracting a transcription of the linguistic content of an acoustical speech signal automatically. Despite several decades of research in this important area of acoustic signal processing, the accuracy of ASR systems is still far behind human performance, especially in adverse acoustic scenarios. In this context, one of the most challenging situations is the one concerning simultaneous speech in cocktail-party environments. Although source separation methods have already been investigated to deal with this problem, the separation process is not perfect and the resulting artifacts pose an additional problem to ASR performance. In this paper, a specific training to improve the percentage of recognized words in real simultaneous speech cases is proposed. The combination of source separation and this specific training is explored and evaluated under different acoustical conditions, leading to improvements of up to a 35% in ASR performance.	\N	\N
22352609	There is substantial performance variability among listeners who transcribe degraded speech. Error patterns from 88 listeners who transcribed dysarthric speech were examined to identify differential use of syllabic strength cues for lexical segmentation. Transcripts from listeners were divided into four groups (ranging from Better- to Poorer- performing). Phrases classified as Higher- and Lower-intelligibility were analyzed separately for each performance group to assess the independent variable of severity. Results revealed that all four listener groups used syllabic strength cues for lexical segmentation of Higher-intelligibility speech, but only the Poorer listeners persisted with this strategy for the Lower-intelligibility phrases. This finding and additional analyses suggest testable hypotheses to address the role of cue-use and performance patterns.	\N	\N
22353676	Age-related declines in auditory and cognitive processing may contribute to the difficulties with listening in noise that are often reported by older adults. Such difficulties are reported even by those who have relatively good audiograms that could be considered "normal" for their age (ISO 7029-2000 [ISO, 2000]). The Speech, Spatial, and Qualities of Hearing Scale (SSQ; Gatehouse and Noble, 2004) is a questionnaire developed to measure a listener's self-reported ability to hear in a variety of everyday situations, such as those that are challenging for older adults, and it can provide insights into the possible contributions of auditory and cognitive factors to their listening difficulties. The SSQ has been shown to be a sensitive and reliable questionnaire to detect benefits associated with the use of different hearing technologies and potentially other forms of intervention. Establishing how age-matched listeners with audiograms "normal" for their age rate the items on the SSQ could enable an extension of its use in audiological assessment and in setting rehabilitative goals. The main purpose of this study was to investigate how younger and older adults who passed audiometric screening and who had thresholds considered to be "normal" for their age responded on the SSQ. It was also of interest to compare these results to those reported previously for older listeners with hearing loss in an attempt to tease out the relative effects of age and hearing loss. The SSQ was administered to 48 younger (mean age = 19 yr; SD = 1.0) and 48 older (mean age = 70 yr, SD = 4.1) adults with clinically normal audiometric thresholds below 4 kHz. The younger adults were recruited through an introductory psychology course, and the older adults were volunteers from the local community. Both age groups completed the SSQ. The differences between the groups were analyzed. Correlations were used to compare the pattern of results across items for the two age groups in the present study and to assess the relationship between SSQ scores and objective measures of hearing. Comparisons were also made to published results for older adults with hearing loss. The pattern of reported difficulty across items was similar for both age groups, but younger adults had significantly higher scores than older adults on 42 of the 46 items. On average, younger adults scored 8.8 (SD = 0.6) out of 10 and older adults scored 7.7 (SD = 1.2) out of 10. By comparison, scores of 5.5 (SD = 1.9) have been reported for older adults (mean age = 71 yr, SD = 8.1) with moderate hearing loss (Gatehouse and Noble, 2004). By establishing the best scores that could reasonably be expected from younger and older adults with "normal" hearing thresholds, these results provide clinicians with information that should assist them in setting realistic targets for interventions for adults of different ages.	\N	\N
22355005	To determine (a) the effect of fundamental frequency (f₀) on speech intelligibility, acceptability, and perceived gender in electrolaryngeal (EL) speakers, and (b) the effect of known gender on speech acceptability in EL speakers. A 2-part study was conducted. In Part 1, 34 healthy adults provided speech recordings using electrolarynges set at 75 Hz, 130 Hz, and 175 Hz, and 36 listeners transcribed the recordings. In Part 2, 22 speech samples were presented to 16 listeners. First, listeners identified the gender of each speaker and judged his or her speech acceptability using rating scales. Second, listeners judged the same samples for speech acceptability when gender information was provided. In Part 1, speakers were significantly more intelligible when using 75-Hz devices. In Part 2, the f₀ of the speech signal significantly impacted listeners' accuracy in perceiving the speaker's gender: In gender-incongruent conditions (males using 175-Hz devices, females using 75-Hz devices), listeners were unable to identify female speakers. Speech acceptability judgments were directly related to intelligibility. Finally, listeners differentially penalized female speakers who used 75-Hz devices when gender information was known. Low f₀ facilitated speech intelligibility. However, at low f₀, listeners were unable to identify females as female, and females were differentially penalized for speech acceptability. Results may have implications for rehabilitation.	\N	\N
22355541	The potentiality to find precursors of human language in nonhuman primates is questioned because of differences related to the genetic determinism of human and nonhuman primate acoustic structures. Limiting the debate to production and acoustic plasticity might have led to underestimating parallels between human and nonhuman primates. Adult-young differences concerning vocal usage have been reported in various primate species. A key feature of language is the ability to converse, respecting turn-taking rules. Turn-taking structures some nonhuman primates' adult vocal exchanges, but the development and the cognitive relevancy of this rule have never been investigated in monkeys. Our observations of Campbell's monkeys' spontaneous vocal utterances revealed that juveniles broke the turn-taking rule more often than did experienced adults. Only adults displayed different levels of interest when hearing playbacks of vocal exchanges respecting or not the turn-taking rule. This study strengthens parallels between human conversations and nonhuman primate vocal exchanges.	\N	\N
22361165	Sensory-motor interactions between auditory and articulatory representations in the dorsal auditory processing stream are suggested to contribute to speech perception, especially when bottom-up information alone is insufficient for purely auditory perceptual mechanisms to succeed. Here, we hypothesized that the dorsal stream responds more vigorously to auditory syllables when one is engaged in a phonetic identification/repetition task subsequent to perception compared to passive listening, and that this effect is further augmented when the syllables are embedded in noise. To this end, we recorded magnetoencephalography while twenty subjects listened to speech syllables, with and without noise masking, in four conditions: passive perception; overt repetition; covert repetition; and overt imitation. Compared to passive listening, left-hemispheric N100m equivalent current dipole responses were amplified and shifted posteriorly when perception was followed by covert repetition task. Cortically constrained minimum-norm estimates showed amplified left supramarginal and angylar gyri responses in the covert repetition condition at ~100ms from stimulus onset. Longer-latency responses at ~200ms were amplified in the covert repetition condition in the left angular gyrus and in all three active conditions in the left premotor cortex, with further enhancements when the syllables were embedded in noise. Phonetic categorization accuracy and magnitude of voice pitch change between overt repetition and imitation conditions correlated with left premotor cortex responses at ~100 and ~200ms, respectively. Together, these results suggest that the dorsal stream involvement in speech perception is dependent on perceptual task demands and that phonetic categorization performance is influenced by the left premotor cortex.	\N	\N
22364395	Young infants perceive an object's trajectory as continuous across occlusion provided the temporal or spatial gap in perception is small. In 3 experiments involving 72 participants the authors investigated the effects of different forms of auditory information on 4-month-olds' perception of trajectory continuity. Provision of dynamic auditory information about the object's trajectory enhanced perception of trajectory continuity. However, a smaller positive effect was also obtained when the sound was continuous but provided no information about the object's location. Finally, providing discontinuous auditory information or auditory information that was dislocated relative to vision had negative effects on trajectory perception. These results are discussed relative to the intersensory redundancy hypothesis and emphasize the need to take an intersensory approach to infant perception.	\N	\N
22364434	Vowels with extreme articulatory-acoustic properties act as natural referents. Infant perceptual asymmetries point to an underlying bias favoring these referent vowels. However, as language experience is gathered, distributional frequency of speech sounds could modify this initial bias. The perception of the /i/-/e/ contrast was explored in 144 Catalan- and Spanish-learning infants (2 languages with a different distribution of vowel frequency of occurrence) at 4, 6, and 12 months. The results confirmed an acoustic bias at 4 and 6 months in all infants. However, at 12 months, discrimination was not affected by the acoustic bias but by the frequency of occurrence of the vowel.	\N	\N
22366801	Many studies have shown that the visual cortex of blind humans is activated in non-visual tasks. However, the electrophysiological signals underlying this cross-modal plasticity are largely unknown. Here, we characterize the neuronal population activity in the visual and auditory cortex of congenitally blind humans and sighted controls in a complex cognitive task. We recorded magnetoencephalographic responses from participants performing semantic categorization of meaningful sounds that followed the presentation of a semantically related or unrelated haptic object. Source analysis of the spectrally resolved magnetoencephalography data revealed that: (i) neuronal responses to sounds were stronger and longer lasting in the auditory cortex of blind subjects; (ii) auditory stimulation elicited strong oscillatory responses in the visual cortex of blind subjects that closely resembled responses to visual stimulation in sighted humans; (iii) the signal in the gamma frequency range was modulated by semantic congruency between the sounds and the preceding haptic objects; and (iv) signal power in the gamma range was correlated on a trial-by-trial basis between auditory and visual cortex in blind subjects, and the strength of this correlation was modulated by semantic congruency. Our results suggest that specifically oscillatory activity in the gamma range reflects non-visual processing in the visual cortex of blind individuals. Moreover, our results provide evidence that the deprived visual cortex is functionally integrated into a larger network that serves non-visual functions.	\N	\N
22367585	In recent years, it has become evident that neural responses previously considered to be unisensory can be modulated by sensory input from other modalities. In this regard, visual neural activity elicited to viewing a face is strongly influenced by concurrent incoming auditory information, particularly speech. Here, we applied an additive-factors paradigm aimed at quantifying the impact that auditory speech has on visual event-related potentials (ERPs) elicited to visual speech. These multisensory interactions were measured across parametrically varied stimulus salience, quantified in terms of signal to noise, to provide novel insights into the neural mechanisms of audiovisual speech perception. First, we measured a monotonic increase of the amplitude of the visual P1-N1-P2 ERP complex during a spoken-word recognition task with increases in stimulus salience. ERP component amplitudes varied directly with stimulus salience for visual, audiovisual, and summed unisensory recordings. Second, we measured changes in multisensory gain across salience levels. During audiovisual speech, the P1 and P1-N1 components exhibited less multisensory gain relative to the summed unisensory components with reduced salience, while N1-P2 amplitude exhibited greater multisensory gain as salience was reduced, consistent with the principle of inverse effectiveness. The amplitude interactions were correlated with behavioral measures of multisensory gain across salience levels as measured by response times, suggesting that change in multisensory gain associated with unisensory salience modulations reflects an increased efficiency of visual speech processing.	\N	\N
22371164	The finding that serial recall performance for visually presented items is impaired by concurrently presented task-irrelevant speech or sounds is referred to as the irrelevant-speech/-sound effect (ISE). Substantial evidence has indicated that the impairment of serial rehearsal can result in an ISE, and this may be explained by several models. The present series of experiments has demonstrated an ISE in surprise nonserial recognition tasks in which participants were unaware of the need to maintain a large number of visual items for a later memory test, suggesting that neither the rehearsal nor maintenance of order information is necessary for observing the ISE. This effect was observed for both steady-state and changing-state irrelevant sounds, suggesting that the present results do not derive from a confusion of order information, but instead provide evidence that identity representations can also be impaired by irrelevant sound.	\N	\N
22371616	Auditory streaming and visual plaids have been used extensively to study perceptual organization in each modality. Both stimuli can produce bistable alternations between grouped (one object) and split (two objects) interpretations. They also share two peculiar features: (i) at the onset of stimulus presentation, organization starts with a systematic bias towards the grouped interpretation; (ii) this first percept has 'inertia'; it lasts longer than the subsequent ones. As a result, the probability of forming different objects builds up over time, a landmark of both behavioural and neurophysiological data on auditory streaming. Here we show that first percept bias and inertia are independent. In plaid perception, inertia is due to a depth ordering ambiguity in the transparent (split) interpretation that makes plaid perception tristable rather than bistable: experimental manipulations removing the depth ambiguity suppressed inertia. However, the first percept bias persisted. We attempted a similar manipulation for auditory streaming by introducing level differences between streams, to bias which stream would appear in the perceptual foreground. Here both inertia and first percept bias persisted. We thus argue that the critical common feature of the onset of perceptual organization is the grouping bias, which may be related to the transition from temporally/spatially local to temporally/spatially global computation.	\N	\N
22371621	Auditory stream segregation involves linking temporally separate acoustic events into one or more coherent sequences. For any non-trivial sequence of sounds, many alternative descriptions can be formed, only one or very few of which emerge in awareness at any time. Evidence from studies showing bi-/multistability in auditory streaming suggest that some, perhaps many of the alternative descriptions are represented in the brain in parallel and that they continuously vie for conscious perception. Here, based on a predictive coding view, we consider the nature of these sound representations and how they compete with each other. Predictive processing helps to maintain perceptual stability by signalling the continuation of previously established patterns as well as the emergence of new sound sources. It also provides a measure of how well each of the competing representations describes the current acoustic scene. This account of auditory stream segregation has been tested on perceptual data obtained in the auditory streaming paradigm.	\N	\N
22379692	The attentional blink (AB) is a well-established paradigm in which identification of a target T2 is reduced shortly after presentation of an earlier target T1. An important question concerns the importance of backward masking during the AB. While task switching has been found to be a strong modulator mediating the AB without any masking of T2, the present study investigated whether spatial switching could similarly produce an AB without masking. Using a spatial AB paradigm in which items appeared at different locations; we found (a) a significant AB without backward masking of T2 but no AB when no distractors followed T2, (b) no evidence for Lag 1 sparing. These findings show that when there is a spatial switch between the targets, presenting the distractor following T2 at the same location than T2 (backward masking) is not a necessary condition for the AB to occur, but T2 has to be followed by surrounding distractors (appearing at different locations than T2). This pattern of data confirms that spatial switching is a robust modulator of the AB, but to a less extent than task switching.	\N	\N
22384765	Hemodynamic changes can be noninvasively real-time monitored in stroke patients by means of transcranial Doppler sonography (TCD). The aim of this pilot study was to assess hemodynamic changes in both middle cerebral arteries (MCA) in aphasic stroke patients by means of TCD during verbal stimulation. Eight aphasic patients with stroke in the territory of the left MCA were tested by modified Boston Diagnostic Aphasia Examination (BDAE) within 3 days of stroke onset. Both MCA were monitored simultaneously by means of TCD with 2 MHz probes. Basic MCA mean blood flow velocity (MBFV) values were assessed and monitored during verbal stimulation. Verbal stimulation was performed with 30 photos of objects for daily usage, arranged by function. The same test was performed in 16 right-handed healthy controls. In stroke patients, the mean MBFV were 56 cm/s in the left MCA and 56 cm/s in the right MCA. A mean 30% increase was observed in the left MCA and 22% in the right MCA. In healthy controls, a mean 21.7% increase was observed in the left MCA and 18% in the right MCA. A trend toward higher percentage of MBFV increase was observed in the left MCA during verbal stimulations in aphasic patients as compared to control subjects.	\N	\N
22390292	Human multisensory systems are known to bind inputs from the different sensory modalities into a unified percept, a process that leads to measurable behavioral benefits. This integrative process can be observed through multisensory illusions, including the McGurk effect and the sound-induced flash illusion, both of which demonstrate the ability of one sensory modality to modulate perception in a second modality. Such multisensory integration is highly dependent upon the temporal relationship of the different sensory inputs, with perceptual binding occurring within a limited range of asynchronies known as the temporal binding window (TBW). Previous studies have shown that this window is highly variable across individuals, but it is unclear how these variations in the TBW relate to an individual's ability to integrate multisensory cues. Here we provide evidence linking individual differences in multisensory temporal processes to differences in the individual's audiovisual integration of illusory stimuli. Our data provide strong evidence that the temporal processing of multiple sensory signals and the merging of multiple signals into a single, unified perception, are highly related. Specifically, the width of right side of an individuals' TBW, where the auditory stimulus follows the visual, is significantly correlated with the strength of illusory percepts, as indexed via both an increase in the strength of binding synchronous sensory signals and in an improvement in correctly dissociating asynchronous signals. These findings are discussed in terms of their possible neurobiological basis, relevance to the development of sensory integration, and possible importance for clinical conditions in which there is growing evidence that multisensory integration is compromised.	\N	\N
22390745	The purpose of this study was to investigate the effect of the Global Voice Therapy Model (GVTM) on acoustic, aerodynamic, and perceptual voice measures of four adults seeking voice therapy for a voice disorder. A speech-language pathologist facilitated speaking voice therapy with the four participants using the GVTM. Participants completed acoustic, aerodynamic, and perceptual voice measures at pre- and post-therapy time points. Differences were seen in the voice measures from pre- to post-therapy. The GVTM was successful in facilitating an improvement in the acoustic, aerodynamic, and perceptual measures of the participants.	\N	\N
22395654	Tactile sensation, which is one of the earliest developing sensory systems, is very important in the perception of an individual's body and the surrounding physical environment, especially in newborns. However, currently, only little is known about the response of a newborn's brain to tactile sensation. The objective of the present study was to determine the response of a newborn's brain to tactile sensation and to compare the brain responses to various sensory stimuli. Ten healthy newborns, 2-9 days after birth, were enrolled. A multichannel near-infrared spectroscopy system was used to measure brain responses. The probe array covered broad cortical areas, including the parietal, temporal, and occipital areas. We measured cortical hemodynamic changes in response to three different types of stimuli: tactile, auditory, and visual. Activated areas were analyzed by t-tests, and the number of activated channels among the three different stimuli was compared by χ²-tests. The results showed that when the brain responded to each type of stimulation, the corresponding primary sensory area was activated, and tactile stimuli induced broader areas of brain activation than the other two types of stimuli (auditory or visual). Thus, broad brain areas, including the temporal and parietal areas, were activated by tactile stimuli in early newborn periods. These results suggest that there are differences in newborns' reactions to various types of sensory stimuli, which may reflect the importance of tactile sensation in the early newborn period.	\N	\N
22403933	Often it is difficult to find a natural explanation as to why a surprising coincidence occurs. In attempting to find one, people may be inclined to accept paranormal explanations. The objective of this study was to investigate whether people with a lower threshold for being surprised by coincidences have a greater propensity to become believers compared to those with a higher threshold. Participants were exposed to artificial coincidences, which were formally defined as less or more probable, and were asked to provide remarkability ratings. Paranormal belief was measured by the Australian Sheep-Goat Scale. An analysis of the remarkability ratings revealed a significant interaction effect between Sheep-Goat score and type of coincidence, suggesting that people with lower thresholds of surprise, when experiencing coincidences, harbor higher paranormal belief than those with a higher threshold. The theoretical aspects of these findings were discussed.	\N	\N
22405960	Transcranial magnetic stimulation (TMS) and neuroimaging studies suggest a functional link between the emotion-related brain areas and the motor system. It is not well understood, however, whether the motor cortex activity is modulated by specific emotions experienced during music listening. In 23 healthy volunteers, we recorded the motor evoked potentials (MEP) following TMS to investigate the corticospinal excitability while subjects listened to music pieces evoking different emotions (happiness, sadness, fear, and displeasure), an emotionally neutral piece, and a control stimulus (musical scale). Quality and intensity of emotions were previously rated in an additional group of 30 healthy subjects. Fear-related music significantly increased the MEP size compared to the neutral piece and the control stimulus. This effect was not seen with music inducing other emotional experiences and was not related to changes in autonomic variables (respiration rate, heart rate). Current data indicate that also in a musical context, the excitability of the corticomotoneuronal system is related to the emotion expressed by the listened piece.	\N	\N
22405961	Conceptual knowledge is classically supposed to be abstract and represented in an amodal unitary system, distinct from the sensory and motor brain systems. A more recent embodiment view of conceptual knowledge, however, proposes that concepts are grounded in distributed modality-specific brain areas which typically process sensory or action-related object information. Recent neuroimaging evidence suggested the significance of left auditory association cortex encompassing posterior superior and middle temporal gyrus in coding conceptual sound features of everyday objects. However, a causal role of this region in processing conceptual sound information has yet to be established. Here we had the unique chance to investigate a patient, JR, with a focal lesion in left posterior superior and middle temporal gyrus. To test the necessity of this region in conceptual and perceptual processing of sound information we administered four different experimental tasks to JR: Visual word recognition, category fluency, sound recognition and voice classification. Compared with a matched control group, patient JR was consistently impaired in conceptual processing of sound-related everyday objects (e.g., "bell"), while performance for non-sound-related everyday objects (e.g., "armchair"), animals, whether they typically produce sounds (e.g., "frog") or not (e.g., "tortoise"), and musical instruments (e.g., "guitar") was intact. An analogous deficit pattern in JR was also obtained for perceptual recognition of the corresponding sounds. Hence, damage to left auditory association cortex specifically impairs perceptual and conceptual processing of sounds from everyday objects. In support of modality-specific theories, these findings strongly evidence the necessity of auditory association cortex in coding sound-related conceptual information.	\N	\N
22410432	This article reports on an investigation of graphophonological processes in deaf readers of French over a 1-year period. Deaf readers are known to have a phonological deficit compared to hearing peers, and conclusions from studies on this question are often conflicting. Among the different types of phonological processing, we can identify graphophonological processes based on correspondences between the oral and the written language. In this investigation, we evaluated graphophonemic and graphosyllabic processes using, in each case, two different tasks varying in their degree of cognitive constraints (CC- vs. CC+). Nineteen 11 year-old deaf students were compared to younger normal readers of the same reading level (RA, n = 17) and to normal readers of the same age (CA, n = 20). Two variables were considered in the analyses: accuracy and response latency. Results show that deaf readers do process written items at the graphophonological level and that graphophonological processes are related to reading ability. Also, results indicate main effects of task (CC- vs. CC+), time (T1 vs. T2), and group. In general, deaf participants' performances are comparable to those of RA and differ from those of CA. Results are discussed within the framework of the study of phonology in deaf readers and its relation to reading acquisition.	\N	\N
22411494	To determine the effects of noise and speech style on word learning in typically developing school-age children. Thirty-one participants ages 9;0 (years;months) to 10;11 attempted to learn 2 sets of 8 novel words and their referents. They heard all of the words 13 times each within meaningful narrative discourse. Signal-to-noise ratio (noise vs. quiet) and speech style (plain vs. clear) were manipulated such that half of the children heard the new words in broadband white noise and half heard them in quiet; within those conditions, each child heard one set of words produced in a plain speech style and another set in a clear speech style. Children who were trained in quiet learned to produce the word forms more accurately than those who were trained in noise. Clear speech resulted in more accurate word form productions than plain speech, whether the children had learned in noise or quiet. Learning from clear speech in noise and plain speech in quiet produced comparable results. Noise limits expressive vocabulary growth in children, reducing the quality of word form representation in the lexicon. Clear speech input can aid expressive vocabulary growth in children, even in noisy environments.	\N	\N
22411713	This article describes the development and evaluation of The University of Western Ontario (UWO) Plurals Test, which is an English language measure of detection of the word-final fricative cue for plurality. Normative data are provided for 26 listeners with normal hearing and 24 listeners with hearing impairment (children and adults), as are evaluations of the acoustical properties of the stimuli, the test's test-retest reliability, and the test's sensitivity to changes in hearing aid signal processing (e.g., nonlinear frequency compression). Results indicate reliable, repeated outcome measurement at the level of the individual. When compared to a global measure of real-world listening preference, the UWO Plurals Test was found to be somewhat sensitive to the effects of changes in hearing aid signal processing. Findings suggest potential use of the UWO Plurals Test to evaluate aided and unaided ability of listeners between the ages of 6 and 81 years to detect the word-final fricatives /s/ and /z/ as they occur in English plural nouns.	\N	\N
22414595	Musicians' skills in auditory processing depend highly on instrument, performance practice, and on level of expertise. Yet, it is not known though whether the style/genre of music might shape auditory processing in the brains of musicians. Here, we aimed at tackling the role of musical style/genre on modulating neural and behavioral responses to changes in musical features. Using a novel, fast and musical sounding multi-feature paradigm, we measured the mismatch negativity (MMN), a pre-attentive brain response, to six types of musical feature change in musicians playing three distinct styles of music (classical, jazz, rock/pop) and in non-musicians. Jazz and classical musicians scored higher in the musical aptitude test than band musicians and non-musicians, especially with regards to tonal abilities. These results were extended by the MMN findings: jazz musicians had larger MMN-amplitude than all other experimental groups across the six different sound features, indicating a greater overall sensitivity to auditory outliers. In particular, we found enhanced processing of pith and sliding up to pitches in jazz musicians only. Furthermore, we observed a more frontal MMN to pitch and location compared to the other deviants in jazz musicians and left lateralization of the MMN to timbre in classical musicians. These findings indicate that the characteristics of the style/genre of music played by musicians influence their perceptual skills and the brain processing of sound features embedded in a musical context. Musicians' brain is hence shaped by the type of training, musical style/genre, and listening experiences.	\N	\N
22415447	Although it has been well documented that the spatial inhibitory effect induced by repetition of location (i.e., spatial inhibition of return, or IOR) occurs cross-modally, we do not yet know whether nonspatial (e.g., color-based) repetition-induced inhibition occurs in a cross-modal fashion as well. In the present study, a novel cross-modal paradigm with regard to color-based repetition was adopted. An intervening neutral cue, whose semantic identity was different from those of both the prime and the target, was introduced between the prime and the target in a repetition-priming task. The modalities of the prime, the neutral cue, and the target could be either visual or auditory, and the prime and the target could refer either to the same or to different semantic identities. By adopting this paradigm, we aimed to answer two questions: (1) What are the specific conditions under which cross-modal semantic-based repetition inhibition occurs? (2) Are the representations inhibited in the semantic-based repetition inhibition effect supramodal or modality-specific? Our results suggested that semantic-based repetition inhibition occurs only when the prime and the neutral cue are from the same sensory modality, and it occurs irrespective of whether the modality of the target is cued and irrespective of whether the modality of the target is auditory or visual. Taken together, our results suggest that the occurrence of cross-modal nonspatial repetition inhibition is conditional and that the nonspatial representations inhibited by the repetition inhibition are supramodal.	\N	\N
22419678	Infants must learn to make sense of real-world auditory environments containing simultaneous and overlapping sounds. In adults, event-related potential studies have demonstrated the existence of separate preattentive memory traces for concurrent note sequences and revealed perceptual dominance for encoding of the voice with higher fundamental frequency of 2 simultaneous tones or melodies. Here, we presented 2 simultaneous streams of notes (15 semitones apart) to 7-month-old infants. On 50% of trials, either the higher or the lower note was modified by one semitone, up or down, leaving 50% standard trials. Infants showed mismatch negativity (MMN) to changes in both voices, indicating separate memory traces for each voice. Furthermore, MMN was earlier and larger for the higher voice as in adults. When in the context of a second voice, representation of the lower voice was decreased and that of the higher voice increased compared with when each voice was presented alone. Additionally, correlations between MMN amplitude and amount of weekly music listening suggest that experience affects the development of auditory memory. In sum, the ability to process simultaneous pitches and the dominance of the highest voice emerge early during infancy and are likely important for the perceptual organization of sound in realistic environments.	\N	\N
22423819	Hearing-aid wearers have reported sound source locations as being perceptually internalized (i.e., inside their head). The contribution of hearing-aid design to internalization has, however, received little attention. This experiment compared the sensitivity of hearing-impaired (HI) and normal-hearing listeners to externalization cues when listening with their own ears and simulated behind-the-ear hearing-aids in increasingly complex listening situations and reduced pinna cues. Participants rated the degree of externalization using a multiple-stimulus listening test for mixes of internalized and externalized speech stimuli presented over headphones. The results showed that HI listeners had a contracted perception of externalization correlated with high-frequency hearing loss.	\N	\N
22427328	Imaging studies in blind subjects have consistently shown that sensory and cognitive tasks evoke activity in the occipital cortex, which is normally visual. The precise areas involved and degree of activation are dependent upon the cause and age of onset of blindness. Here, we investigated the cortical language network at rest and during an auditory covert naming task in five bilaterally anophthalmic subjects, who have never received visual input. When listening to auditory definitions and covertly retrieving words, these subjects activated lateral occipital cortex bilaterally in addition to the language areas activated in sighted controls. This activity was significantly greater than that present in a control condition of listening to reversed speech. The lateral occipital cortex was also recruited into a left-lateralized resting-state network that usually comprises anterior and posterior language areas. Levels of activation to the auditory naming and reversed speech conditions did not differ in the calcarine (striate) cortex. This primary 'visual' cortex was not recruited to the left-lateralized resting-state network and showed high interhemispheric correlation of activity at rest, as is typically seen in unimodal cortical areas. In contrast, the interhemispheric correlation of resting activity in extrastriate areas was reduced in anophthalmia to the level of cortical areas that are heteromodal, such as the inferior frontal gyrus. Previous imaging studies in the congenitally blind show that primary visual cortex is activated in higher-order tasks, such as language and memory to a greater extent than during more basic sensory processing, resulting in a reversal of the normal hierarchy of functional organization across 'visual' areas. Our data do not support such a pattern of organization in anophthalmia. Instead, the patterns of activity during task and the functional connectivity at rest are consistent with the known hierarchy of processing in these areas normally seen for vision. The differences in cortical organization between bilateral anophthalmia and other forms of congenital blindness are considered to be due to the total absence of stimulation in 'visual' cortex by light or retinal activity in the former condition, and suggests development of subcortical auditory input to the geniculo-striate pathway.	\N	\N
22431327	Previous neuroimaging studies have shown that the patterns of brain activity during the processing of personally relevant names (e.g., own name, friend's name, partner's name, etc.) and the names of famous people (e.g., celebrities) are different. However, it is not known how the activity in this network is influenced by the modality of the presented stimuli. In this fMRI study, we investigated the pattern of brain activations during the recognition of aurally and visually presented full names of the subject, a significant other, a famous person and unknown individuals. In both modalities, we found that the processing of self-name and the significant other's name was associated with increased activation in the medial prefrontal cortex (MPFC). Acoustic presentations of these names also activated bilateral inferior frontal gyri (IFG). This pattern of results supports the role of MPFC in the processing of personally relevant information, irrespective of their modality.	\N	\N
22432606	Contact quotient (CQ), measured by electroglottogram (EGG), is a ratio which illustrates the duration of vocal fold contact during one vocal fold period. In the present study CQ(EGG) was calculated from a sustained vowel phonation in three different phonation types (breathy, normal, pressed) at three amplitude threshold levels (25%, 35%, 50%). CQ(EGG) values were compared with experts' perceptual evaluation of the firmness of phonation. The contact time of the vocal folds differed significantly between the different phonation types at all threshold levels (P < 0.01). Perceptual evaluation correlated best with CQ(EGG) at threshold levels 25% and 35%. The results of the linear regression model suggested that by using threshold level 25% the effect of F0 and SPL on CQ(EGG) were not significant.	\N	\N
22434397	Female as opposed to male listeners were better able to use a delayed informative cue at the end of a long sentence to report an earlier word which was disrupted by noise. Informative (semantically related) or uninformative (semantically unrelated) word cues were presented 2, 6, or 10 words after a target word whose initial phoneme had been replaced with noise. A total of 84 young adults (45 males) listened to each sentence and then repeated it after its offset. The semantic benefit effect (SBE) was the difference in the accuracy of report of the disrupted target word during informative vs. uninformative sentences. Women had significantly higher SBEs than men even though there were no significant sex differences in terms of number of non-target words reported, the effect of distance between the disrupted target word and the informative cue, or kinds of errors generated. We suggest that the superior ability of women to use delayed semantic information to decode an earlier ambiguous speech signal may be linked to women's tendency to engage the hemispheres more bilaterally than men during word processing. Since the maintenance of semantic context under ambiguous conditions demands more right than left hemispheric resources, this may give women an advantage.	\N	\N
22454230	Vibrant Soundbridge (VSB) has been recommended for both adults and children with all types of hearing loss. The aim of this study was to evaluate the objective and subjective benefits with VSB and the difference in benefits for patients with different types of hearing loss. A retrospective case review was conducted on seven consecutive patients who had received VSB implantations at the National University Hospital of Singapore from March 2006 to November 2009. Patients were divided into the Sensorineural Hearing Loss (SNHL) Group and Conductive Hearing Loss (CHL)/Mixed Hearing Loss (MHL) Group. Surgical complications were evaluated, and objective and subjective results were compared between the two groups. No major complications were observed during the follow-up of up to 4 years. Greater objective and subjective benefits were observed in the CHL/MHL Group. Subjective benefits were consistent with objective improvements. Pre-operative counseling for realistic expectations is important, especially for patients with SNHL.	\N	\N
22459559	This study examined the role of modality in correct recognition and misinformation acceptance in a naturalistic event cognition task that reflected an everyday life sequence of events. Participants heard, observed or acted out a sequence of events and were tested on memory for these events after being presented with an accurate description of the events or a description containing misinformation. The results indicated that recognition of unaltered information was higher in the enactment condition than the auditory or visual conditions and that this effect persisted over time. Misinformation acceptance for the immediate recognition test was lowest in the auditory condition but this advantage disappeared over time. Modality congruence of the auditory condition with the modality in which misinformation was presented and different retrieval processes underlying recognition of altered and unaltered information may explain these findings.	\N	\N
22463939	This case study describes a 45-yr-old female with bilateral, profound sensorineural hearing loss due to Ménière's disease. She received her first cochlear implant in the right ear in 2008 and the second cochlear implant in the left ear in 2010. The case study examines the enhancement to speech recognition, particularly in noise, provided by bilateral cochlear implants. Speech recognition tests were administered prior to obtaining the second implant and at a number of test intervals following activation of the second device. Speech recognition in quiet and noise as well as localization abilities were assessed in several conditions to determine bilateral benefit and performance differences between ears. The results of the speech recognition testing indicated a substantial improvement in the patient's ability to understand speech in noise and her ability to localize sound when using bilateral cochlear implants compared to using a unilateral implant or an implant and a hearing aid. In addition, the patient reported considerable improvement in her ability to communicate in daily life when using bilateral implants versus a unilateral implant. This case suggests that cochlear implantation is a viable option for patients who have lost their hearing to Ménière's disease even when a number of medical treatments and surgical interventions have been performed to control vertigo. In the case presented, bilateral cochlear implantation was necessary for this patient to communicate successfully at home and at work.	\N	\N
22465324	Nonverbal emotional vocalizations are one of the most elementary ways of communicating in humans. We examined the impact of sex differences on neural responses to laughter and crying produced by the same and opposite sex. Thirty subjects (15 women) underwent functional magnetic resonance imaging during a sex identification task for laughter, crying, and neutral voices. The parahippocampal gyrus was involved in both men and women while hearing laughter of the same sex, suggesting greater positive emotional processing and greater attention toward emotional context in response to laughter of the same sex than of the opposite sex. The posterior cingulate was involved in both men and women while hearing crying of the opposite sex, suggesting that empathic processing may occur more in response to crying of the opposite sex than of the same sex. Furthermore, brain responses to crying of the opposite sex seem to reflect upon men's efforts to perform emotional regulation and women's empathic concerns.	\N	\N
22465475	Neglect is a neurological syndrome characterised by a lack of conscious perception of events localised in the contralesional side of space. Here, we consider the possible multisensory nature of this disorder, critically reviewing the literature devoted to multisensory manifestations and processing in neglect. Although its most striking manifestations have been observed in the visual domain, a number of studies demonstrate that neglect can affect virtually any sensory modality, in particular touch and audition. Furthermore, a few recent studies have reported a correlation in severity between visual and non-visual neglect-related deficits evaluated in the same patients, providing some preliminary support for a multisensory conception of neglect. Sensory stimulation and sensorimotor adaptation techniques, aimed at alleviating neglect, have also been shown to affect several sensory modalities, including some that were not directly affected by the intervention. Finally, in some cases neglect can bias multisensory interactions known to occur in healthy individuals, leading to abnormal behaviour or uncovering multisensory compensation mechanisms. This evidence, together with neurophysiological and neuroimaging data revealing the multisensory role played by the areas that are most commonly damaged in neglect patients, seems to speak in favour of neglect as a multisensory disorder. However, since most previous studies were not conducted with the specific purpose of systematically investigating the multisensory nature of neglect, we conclude that more research is needed to appropriately assess this question, and suggest some methodological guidelines that we hope will help clarify this issue. At present, the conception of neglect as a multisensory disorder remains a promising working hypothesis that may help define the pathophysiology of this syndrome.	\N	\N
22476724	That auditory perceptual training may alleviate tinnitus draws on two observations: (1) tinnitus probably arises from altered activity within the central auditory system following hearing loss and (2) sound-based training can change central auditory activity. Training that provides sound enrichment across hearing loss frequencies has therefore been hypothesised to alleviate tinnitus. We tested this prediction with two randomised trials of frequency discrimination training involving a total of 70 participants with chronic subjective tinnitus. Participants trained on either (1) a pure-tone standard at a frequency within their region of normal hearing, (2) a pure-tone standard within the region of hearing loss or (3) a high-pass harmonic complex tone spanning a region of hearing loss. Analysis of the primary outcome measure revealed an overall reduction in self-reported tinnitus handicap after training that was maintained at a 1-month follow-up assessment, but there were no significant differences between groups. Secondary analyses also report the effects of different domains of tinnitus handicap on the psychoacoustical characteristics of the tinnitus percept (sensation level, bandwidth and pitch) and on duration of training. Our overall findings and conclusions cast doubt on the superiority of a purely acoustic mechanism to underpin tinnitus remediation. Rather, the nonspecific patterns of improvement are more suggestive that auditory perceptual training affects impact on a contributory mechanism such as selective attention or emotional state.	\N	\N
22480025	In grammar books, the various functions of and as phrasal coordinator and clausal conjunction are treated as standard knowledge. In addition, studies on the uses of and in everyday talk-in-interaction have described its discourse-organizational functions on a more global level. In the phonetic literature, in turn, a range of phonetic forms of and have been listed. Yet, so far few studies have related the phonetic features of and to its function. This contribution surveys a range of phonetic forms of and in a corpus of private American English telephone conversations. It shows that the use of forms such as [ænd], [εn], or [en], among others, is not random but, in essence, correlates with the syntactic-pragmatic scope of and and the cognitive closeness of the items the and connects. This, in turn, allows the phonetic design of and to contribute to the organization of turn-taking. The findings presented are based on conversation-analytic and interactional-linguistic methodology, which includes quantitative analyses.	\N	\N
22480027	This paper investigates hearers' use of response tokens (back-channels), in maintaining and differentiating their actions. Initial observations suggest that hearers produce a sequence of phonetically similar responses to disengage from the current topic, and dissimilar responses to engage with the current topic. This is studied systematically by combining detailed interactional and phonetic analysis in a collection of naturally-occurring talk in Norwegian. The interactional analysis forms the basis for labeling actions as maintained ('doing the same') and differentiated ('NOT doing the same'), which is then used as a basis for phonetic analysis. The phonetic analysis shows that certain phonetic characteristics, including pitch, loudness, voice quality and articulatory characteristics, are associated with 'doing the same', as different from 'NOT doing the same'. Interactional analysis gives further evidence of how this differentiation is of systematic relevance in the negotiations of a next turn. This paper addresses phonetic variation and variability by focusing on the relationship between sequence and phonetics in the turn-by-turn development of meaning. This has important implications for linguistic/phonetic research, and for the study of back-channels.	\N	\N
22492193	The auditory system codes spatial locations in a way that deviates from the spatial representations found in other modalities. This difference is especially striking in the cortex, where neurons form topographical maps of visual and tactile space but where auditory space is represented through a population rate code. In this hemifield code, sound source location is represented in the activity of two widely tuned opponent populations, one tuned to the right and the other to the left side of auditory space. Scientists are only beginning to uncover how this coding strategy adapts to various spatial processing demands. This review presents the current understanding of auditory spatial processing in the cortex. To this end, the authors consider how various implementations of the hemifield code may exist within the auditory cortex and how these may be modulated by the stimulation and task context. As a result, a coherent set of neural strategies for auditory spatial processing emerges.	\N	\N
22500627	Behavior varies from trial to trial even when the stimulus is maintained as constant as possible. In many models, this variability is attributed to noise in the brain. Here, we propose that there is another major source of variability: suboptimal inference. Importantly, we argue that in most tasks of interest, and particularly complex ones, suboptimal inference is likely to be the dominant component of behavioral variability. This perspective explains a variety of intriguing observations, including why variability appears to be larger on the sensory than on the motor side, and why our sensors are sometimes surprisingly unreliable.	\N	\N
22501070	Judgments of whether a sinusoidal probe is higher or lower in frequency than the closest partial ("target") in a multi-partial complex are improved when the target is pulsed on and off. These experiments explored the contribution of reduction in perceptual confusion and recovery from adaptation to this effect. In experiment 1, all partials except the target were replaced by noise to reduce perceptual confusion. Performance was much better than when the background was composed of multiple partials. When the level of the target was reduced to avoid ceiling effects, no effect of pulsing the target occurred. In experiment 2, the target and background partials were irregularly and independently amplitude modulated. This gave a large effect of pulsing the target, suggesting that if recovery from adaptation contributes to the effect, amplitude fluctuations do not prevent this. In experiment 3, the background was composed of multiple steady partials, but the target was irregularly amplitude modulated. This gave better performance than when the target was unmodulated and a moderate effect of pulsing the target. It is argued that when the target and background are steady tones, pulsing the target may result both in reduction of perceptual confusion and recovery from adaptation.	\N	\N
22501078	Research on children's speech perception and production suggests that consonant voicing and place contrasts may be acquired early in life, at least in word-onset position. However, little is known about the development of the acoustic correlates of later-acquired, word-final coda contrasts. This is of particular interest in languages like English where many grammatical morphemes are realized as codas. This study therefore examined how various non-spectral acoustic cues vary as a function of stop coda voicing (voiced vs. voiceless) and place (alveolar vs. velar) in the spontaneous speech of 6 American-English-speaking mother-child dyads. The results indicate that children as young as 1;6 exhibited many adult-like acoustic cues to voicing and place contrasts, including longer vowels and more frequent use of voice bar with voiced codas, and a greater number of bursts and longer post-release noise for velar codas. However, 1;6-year-olds overall exhibited longer durations and more frequent occurrence of these cues compared to mothers, with decreasing values by 2;6. Thus, English-speaking 1;6-year-olds already exhibit adult-like use of some of the cues to coda voicing and place, though implementation is not yet fully adult-like. Physiological and contextual correlates of these findings are discussed.	\N	\N
22501083	This study tested the hypothesis that the reduction in spatial release from masking (SRM) resulting from sensorineural hearing loss in competing speech mixtures is influenced by the characteristics of the interfering speech. A frontal speech target was presented simultaneously with two intelligible or two time-reversed (unintelligible) speech maskers that were either colocated with the target or were symmetrically separated from the target in the horizontal plane. The difference in SRM between listeners with hearing impairment and listeners with normal hearing was substantially larger for the forward maskers (deficit of 5.8 dB) than for the reversed maskers (deficit of 1.6 dB). This was driven by the fact that all listeners, regardless of hearing abilities, performed similarly (and poorly) in the colocated condition with intelligible maskers. The same conditions were then tested in listeners with normal hearing using headphone stimuli that were degraded by noise vocoding. Reducing the number of available spectral channels systematically reduced the measured SRM, and again, more so for forward (reduction of 3.8 dB) than for reversed speech maskers (reduction of 1.8 dB). The results suggest that non-spatial factors can strongly influence both the magnitude of SRM and the apparent deficit in SRM for listeners with impaired hearing.	\N	\N
22511719	Monkeys can easily form lasting central representations of visual and tactile stimuli, yet they seem unable to do the same with sounds. Humans, by contrast, are highly proficient in auditory long-term memory (LTM). These mnemonic differences within and between species raise the question of whether the human ability is supported in some way by speech and language, e.g., through subvocal reproduction of speech sounds and by covert verbal labeling of environmental stimuli. If so, the explanation could be that storing rapidly fluctuating acoustic signals requires assistance from the motor system, which is uniquely organized to chain-link rapid sequences. To test this hypothesis, we compared the ability of normal participants to recognize lists of stimuli that can be easily reproduced, labeled, or both (pseudowords, nonverbal sounds, and words, respectively) versus their ability to recognize a list of stimuli that can be reproduced or labeled only with great difficulty (reversed words, i.e., words played backward). Recognition scores after 5-min delays filled with articulatory-suppression tasks were relatively high (75-80% correct) for all sound types except reversed words; the latter yielded scores that were not far above chance (58% correct), even though these stimuli were discriminated nearly perfectly when presented as reversed-word pairs at short intrapair intervals. The combined results provide preliminary support for the hypothesis that participation of the oromotor system may be essential for laying down the memory of speech sounds and, indeed, that speech and auditory memory may be so critically dependent on each other that they had to coevolve.	\N	\N
22516238	Over the years, a large body of work on the brain basis of language comprehension has accumulated, paving the way for the formulation of a comprehensive model. The model proposed here describes the functional neuroanatomy of the different processing steps from auditory perception to comprehension as located in different gray matter brain regions. It also specifies the information flow between these regions, taking into account white matter fiber tract connections. Bottom-up, input-driven processes proceeding from the auditory cortex to the anterior superior temporal cortex and from there to the prefrontal cortex, as well as top-down, controlled and predictive processes from the prefrontal cortex back to the temporal cortex are proposed to constitute the cortical language circuit.	\N	\N
22516315	The primary goal of this study was to evaluate a nonlinear dynamic approach to the acoustic analysis of dysphonia associated with vocal fold scar and sulcus vocalis. Case-control study. Acoustic voice samples from scar/sulcus patients and age-/sex-matched controls were analyzed using correlation dimension (D2) and phase plots, time-domain based perturbation indices (jitter, shimmer, signal-to-noise ratio [SNR]), and an auditory-perceptual rating scheme. Signal typing was performed to identify samples with bifurcations and aperiodicity. Type 2 and 3 acoustic signals were highly represented in the scar/sulcus patient group. When data were analyzed irrespective of signal type, all perceptual and acoustic indices successfully distinguished scar/sulcus patients from controls. Removal of type 2 and 3 signals eliminated the previously identified differences between experimental groups for all acoustic indices except D2. The strongest perceptual-acoustic correlation in our data set was observed for SNR and the weakest correlation was observed for D2. These findings suggest that D2 is inferior to time-domain based perturbation measures for the analysis of dysphonia associated with scar/sulcus; however, time-domain based algorithms are inherently susceptible to inflation under highly aperiodic (ie, type 2 and 3) signal conditions. Auditory-perceptual analysis, unhindered by signal aperiodicity, is therefore a robust strategy for distinguishing scar/sulcus patient voices from normal voices. Future acoustic analysis research in this area should consider alternative (e.g., frequency- and quefrency-domain based) measures alongside additional nonlinear approaches.	\N	\N
22522205	There is ample evidence that individuals with dyslexia have a phonological deficit. A growing body of research also suggests that individuals with dyslexia have problems with categorical perception, as evidenced by weaker discrimination of between-category differences and better discrimination of within-category differences compared to average readers. Whether the categorical perception problems of individuals with dyslexia are a result of their reading problems or a cause has yet to be determined. Whether the observed perception deficit relates to a more general auditory deficit or is specific to speech also has yet to be determined. To shed more light on these issues, the categorical perception abilities of children at risk for dyslexia and chronological age controls were investigated before and after the onset of formal reading instruction in a longitudinal study. Both identification and discrimination data were collected using identical paradigms for speech and non-speech stimuli. Results showed the children at risk for dyslexia to shift from an allophonic mode of perception in kindergarten to a phonemic mode of perception in first grade, while the control group showed a phonemic mode already in kindergarten. The children at risk for dyslexia thus showed an allophonic perception deficit in kindergarten, which was later suppressed by phonemic perception as a result of formal reading instruction in first grade; allophonic perception in kindergarten can thus be treated as a clinical marker for the possibility of later reading problems.	\N	\N
22524348	The present manuscript summarizes and discusses the implications of recent neuroimaging studies, which have investigated the relationship between musical expertise and structural, as well as functional, changes in an auditory-related association cortex, namely, the planum temporale (PT). Since the bilateral PT is known to serve as a spectrotemporal processor that supports perception of acoustic modulations in both speech and music, it comes as no surprise that musical expertise corresponds to functional sensitivity and neuroanatomical changes in cortical architecture. In this context, we focus on the following question: To what extent does musical expertise affect the functioning of the left and right plana temporalia? We discuss the relationship between behavioral, hemodynamic, and neuroanatomical data obtained from musicians in light of maturational and developmental issues. In particular, we introduce two studies of our group that show to what extent brains of musicians are more proficient in phonetic task performance.	\N	\N
22524375	Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by atypical social and communication skills, repetitive behaviors, and atypical visual and auditory perception. Studies in vision have reported enhanced detailed ("local") processing but diminished holistic ("global") processing of visual features in ASD. Individuals with ASD also show enhanced processing of simple visual stimuli but diminished processing of complex visual stimuli. Relative to the visual domain, auditory global-local distinctions, and the effects of stimulus complexity on auditory processing in ASD, are less clear. However, one remarkable finding is that many individuals with ASD have enhanced musical abilities, such as superior pitch processing. This review provides a critical evaluation of behavioral and brain imaging studies of auditory processing with respect to current theories in ASD. We have focused on auditory-musical processing in terms of global versus local processing and simple versus complex sound processing. This review contributes to a better understanding of auditory processing differences in ASD. A deeper comprehension of sensory perception in ASD is key to better defining ASD phenotypes and, in turn, may lead to better interventions.	\N	\N
22529921	Overall success of current tinnitus therapies is low, which may be due to the heterogeneity of tinnitus patients. Therefore, subclassification of tinnitus patients is expected to improve therapeutic allocation, which, in turn, is hoped to improve therapeutic success for the individual patient. The present study aims to define factors that differentially influence subjectively perceived tinnitus loudness and tinnitus-related distress. In a questionnaire-based cross-sectional survey, the data of 4705 individuals with tinnitus were analyzed. The self-report questionnaire contained items about subjective tinnitus loudness, type of onset, awareness and localization of the tinnitus, hearing impairment, chronic comorbidities, sleep quality, and psychometrically validated questionnaires addressing tinnitus-related distress, depressivity, anxiety, and somatic symptom severity. In a binary step-wise logistic regression model, we tested the predictive power of these variables on subjective tinnitus loudness and tinnitus-related distress. The present data contribute to the distinction between subjective tinnitus loudness and tinnitus-related distress. Whereas subjective loudness was associated with permanent awareness and binaural localization of the tinnitus, tinnitus-related distress was associated with depressivity, anxiety, and somatic symptom severity. Subjective tinnitus loudness and the potential presence of severe depressivity, anxiety, and somatic symptom severity should be assessed separately from tinnitus-related distress. If loud tinnitus is the major complaint together with mild or moderate tinnitus-related distress, therapies should focus on auditory perception. If levels of depressivity, anxiety or somatic symptom severity are severe, therapies and further diagnosis should focus on these symptoms at first.	\N	\N
22530620	The effortfulness hypothesis implies that difficulty in decoding the surface form, as in the case of age-related sensory limitations or background noise, consumes the attentional resources that are then unavailable for semantic integration in language comprehension. Because ageing is associated with sensory declines, degrading of the surface form by a noisy background can pose an extra challenge for older adults. In two experiments, this hypothesis was tested in a self-paced moving window paradigm in which younger and older readers' online allocation of attentional resources to surface decoding and semantic integration was measured as they read sentences embedded in varying levels of visual noise. When visual noise was moderate (Experiment 1), resource allocation among young adults was unaffected but older adults allocated more resources to decode the surface form at the cost of resources that would otherwise be available for semantic processing; when visual noise was relatively intense (Experiment 2), both younger and older participants allocated more attention to the surface form and less attention to semantic processing. The decrease in attentional allocation to semantic integration resulted in reduced recall of core ideas in both experiments, suggesting that a less organized semantic representation was constructed in noise. The greater vulnerability of older adults at relatively low levels of noise is consistent with the effortfulness hypothesis.	\N	\N
22533977	For pediatric cochlear implant (CI) users, CI processor technology, map characteristics, and fitting strategies are known to have a substantial impact on speech perception scores at young ages. It is unknown whether these benefits continue over time as these children reach adolescence. To document changes in CI technology, map characteristics, and speech perception scores in children between elementary grades and high school, and to describe relations between map characteristics and speech perception scores over time. A longitudinal design with participants 8-9-yr-old at session 1 and 15-18-yr-old at session 2. Participants were 82 adolescents with unilateral CIs, who are a subset of a larger longitudinal study. Mean age at implantation was 3.4 yr (range: 1.7-5.4), and mean duration of device use was 5.5 yr (range: 3.8-7.5) at session 1 and 13.3 yr (range: 10.9-15) at session 2. Speech perception tests at sessions 1 and 2 were the Lexical Neighborhood Test (LNT) presented at 70 dB SPL (LNT-70) and Bamford-Kowal-Bench sentences in quiet (BKB-Q) presented at 70 dB SPL. At session 2, the LNT was also administered at 50 dB SPL (LNT-50), and BKB sentences were administered in noise with a +10 dB SNR (BKB-N). CI processor technology type and CI map characteristics (coding strategy, number of electrodes, threshold levels, and comfort levels) were obtained at both sessions. Electrical dynamic range was computed, and descriptive statistics, correlations, and repeated-measures ANOVAs were employed. Participants achieved significantly higher LNT and BKB scores, at 70 dB SPL, at ages 15-18 than at ages 8-9 yr. Forty-two participants had 1-3 electrodes either activated or deactivated in their map between test sessions, and 40 had no change in number of active electrodes (mean change: -0.5; range: -3 to +2). After conversion from arbitrary clinical map units to charge-per-phase in nanocoulombs (nC), no significant difference was found for T levels across time. Average comfort levels (C levels) decreased by 19 nC. Seventy-three participants (89%) upgraded their CI processor technology type. At both sessions, significant correlations were found between electrical dynamic range (EDR) and all speech perception measures except LNT-50 (r range: .31 to .47; p < 0.01). Similarly, significant correlations were also found between C levels and all speech perception measures (r range: .29 to .49; p < 0.01). At session 2, a significant correlation was found between processor technology type and the LNT-50 scores (r = .38; p < 0.01). Significant improvement in speech scores was observed between elementary grades and high school for children who had used a CI since preschool. On average, T levels (nC) and electrode function remained stable for these long-term pediatric users. Analyses of maps did not allow for the determination of the exact cause of C level reductions, though power limitations in new processor systems and changes in perceived loudness over time are possible. Larger EDRs and higher C levels were associated with better speech scores. Newer speech processor technology was associated with better speech scores at a softer level.	\N	\N
22542616	Individuals with schizophrenia (SZ) have deviations in auditory perception perhaps attributable to altered neural oscillatory response properties in thalamo-cortical and/or local cortico-cortical circuits. Previous EEG studies of auditory steady-state responses (aSSRs; a measure of sustained neuronal entrainment to repetitive stimulation) in SZ have indicated attenuated gamma range (≈40 Hz) neural entrainment. Stimuli in most such studies have been relatively brief (500-1000 ms) trains of 1 ms clicks or amplitude modulated pure tones (1000 Hz) with short, fixed interstimulus intervals (200-1000 ms). The current study used extended (1500 ms), more aurally dense broadband stimuli (500-4000 Hz noise; previously demonstrated to elicit larger aSSRs) with longer, variable interstimulus intervals (2700-3300 ms). Dense array EEG (256 sensor) was collected while 17 SZ and 16 healthy subjects passively listed to stimuli modulated at 15 different frequencies spanning beta and gamma ranges (16-44 Hz in 2 Hz steps). Results indicate that SZ have augmented aSSRs that were most extreme in the gamma range. Results also constructively replicate previous findings of attenuated low frequency auditory evoked responses (2-8 Hz) in SZ. These findings (i) highlight differential characteristics of low versus high frequency and induced versus entrained oscillatory auditory responses in both SZ and healthy stimulus processing, (ii) provide support for an NMDA-receptor hypofunction-based pharmacological model of SZ, and (iii) report a novel pattern of aSSR abnormalities suggesting that gamma band neural entrainment deviations among SZ may be more complex than previously supposed, including possibly being substantially influenced by physical stimulus properties.	\N	\N
22546730	Pseudoneglect is a normal left sided spatial bias observed with attempted bisections of horizontal lines and a normal upward bias observed with attempted bisections of vertical lines. Horizontal pseudoneglect has been attributed to right hemispheric dominance for the allocation of attention. The goal of this study was to test the hypothesis that the upward bias in vertical line bisection may also relate to right hemispheric dominance for the allocation of attention and/or action-intention. Twenty right handed healthy adults were asked to bisect vertical lines presented in the midsagittal plane (center space) and in sagittal planes to the left and right of the midsagittal plane (left and right hemispace) when using a pen held in either the right or left hand. Vertical line bisections were biased upward in all three sagittal planes and higher in left than right hemispace. However, bisections made with the left hand were lower than those made with the right hand. Whereas these results suggest a left hemispace-right hemispheric visuospatial attentional upward bias and a relative left hemispheric-right hand upward action-intentional bias, further studies are needed to document this intentional versus attentional bias and to understand the brain mechanisms that produce these biases.	\N	\N
22553024	The temporal context of an acoustic signal can greatly influence its perception. The present study investigated the neural correlates underlying perceptual facilitation by regular temporal contexts in humans. Participants listened to temporally regular (periodic) or temporally irregular (nonperiodic) sequences of tones while performing an intensity discrimination task. Participants performed significantly better on intensity discrimination during periodic than nonperiodic tone sequences. There was greater activation in the putamen for periodic than nonperiodic sequences. Conversely, there was greater activation in bilateral primary and secondary auditory cortices (planum polare and planum temporale) for nonperiodic than periodic sequences. Across individuals, greater putamen activation correlated with lesser auditory cortical activation in both right and left hemispheres. These findings suggest that temporal regularity is detected in the putamen, and that such detection facilitates temporal-lobe cortical processing associated with superior auditory perception. Thus, this study reveals a corticostriatal system associated with contextual facilitation for auditory perception through temporal regularity processing.	\N	\N
22553042	Signal duration is important for identifying sound sources and determining signal meaning. Duration-tuned neurons (DTNs) respond preferentially to a range of stimulus durations and maximally to a best duration (BD). Duration-tuned neurons are found in the auditory midbrain of many vertebrates, although studied most extensively in bats. Studies of DTNs across vertebrates have identified cells with BDs and temporal response bandwidths that mirror the range of species-specific vocalizations. Neural tuning to stimulus duration appears to be universal among hearing vertebrates. Herein, we test the hypothesis that neural mechanisms underlying duration selectivity may be similar across vertebrates. We instantiated theoretical mechanisms of duration tuning in computational models to systematically explore the roles of excitatory and inhibitory receptor strengths, input latencies, and membrane time constant on duration tuning response profiles. We demonstrate that models of duration tuning with similar neural circuitry can be tuned with species-specific parameters to reproduce the responses of in vivo DTNs from the auditory midbrain. To relate and validate model output to in vivo responses, we collected electrophysiological data from the inferior colliculus of the awake big brown bat, Eptesicus fuscus, and present similar in vivo data from the published literature on DTNs in rats, mice, and frogs. Our results support the hypothesis that neural mechanisms of duration tuning may be shared across vertebrates despite species-specific differences in duration selectivity. Finally, we discuss how the underlying mechanisms of duration selectivity relate to other auditory feature detectors arising from the interaction of neural excitation and inhibition.	\N	\N
22555987	Although it is well known that cisplatin is associated with ototoxicity, there is still a lack of knowledge concerning the ototoxicity of cisplatin, especially in Japanese head and neck cancer patients. The objectives of this study were to determine the incidence rate of cisplatin ototoxicity and to determine the threshold dose causing ototoxicity in the Japanese population. Before-and-after study in a tertiary referral hospital. The distortion product otoacoustic emission (DPOAE) was measured 1 week after each administration of cisplatin in 44 Japanese head and neck cancer patients treated at Kyoto University Hospital. We determined the incidence and threshold dose of cisplatin ototoxicity according to DPOAE data. The incidence of ototoxicity detected by DPOAE was 77.3%. The average DPOAE value was significantly lower in patients who received more than 200 mg/m(2) cisplatin than the baseline DPOAE value. The threshold dose for cisplatin ototoxicity was lower in Japanese patients than in European patients. Our data suggest that Japanese patients are more susceptible to cisplatin-induced ototoxicity. This is presumably caused by a genetic difference.	\N	\N
22559374	Previous studies investigating sensitivity to step changes in tempo and prediction of tone onset time have generally utilized isochronous sequences. This study investigates subjects' ability to detect deviations from a gradual change in the tempo of a tone sequence (experiment 1) and their judgment of the perceptually optimal timing of this tone (experiment 2). In experiment 1, inter-onset-intervals within pairs of eight-tone sequences followed a geometric progression to create a gradual tempo change. In one sequence, the final tone was presented either earlier or later than specified by the progression. Subjects performed well at detecting deviations that exaggerated the tempo progression but poorly when it was counteracted. Experiment 2 used similar pairs except that the final tone was always presented earlier in one sequence than the other. Final interval length was adaptively adjusted to subjects' judgments; it was adjudged in best agreement with the progression when its length was roughly half way between the mathematically correct value and the length of the penultimate interval. The data support "multiple-look" and entrainment models of tempo sensitivity and suggest that temporal prediction is based less on the tempo contour of a whole sequence than on the duration of the preceding interval.	\N	\N
22559382	Recent evidence suggests that spectral change, as measured by cochlea-scaled entropy (CSE), predicts speech intelligibility better than the information carried by vowels or consonants in sentences. Motivated by this finding, the present study investigates whether intelligibility indices implemented to include segments marked with significant spectral change better predict speech intelligibility in noise than measures that include all phonetic segments paying no attention to vowels/consonants or spectral change. The prediction of two intelligibility measures [normalized covariance measure (NCM), coherence-based speech intelligibility index (CSII)] is investigated using three sentence-segmentation methods: relative root-mean-square (RMS) levels, CSE, and traditional phonetic segmentation of obstruents and sonorants. While the CSE method makes no distinction between spectral changes occurring within vowels/consonants, the RMS-level segmentation method places more emphasis on the vowel-consonant boundaries wherein the spectral change is often most prominent, and perhaps most robust, in the presence of noise. Higher correlation with intelligibility scores was obtained when including sentence segments containing a large number of consonant-vowel boundaries than when including segments with highest entropy or segments based on obstruent/sonorant classification. These data suggest that in the context of intelligibility measures the type of spectral change captured by the measure is important.	\N	\N
22561890	The basic deficits underlying the severe and persistent reading difficulties in dyslexia are still highly debated. One of the major topics of debate is whether these deficits are language specific, or affect both verbal and non-verbal stimuli. Recently, Ahissar and colleagues proposed the "anchoring-deficit hypothesis" (Ahissar, Lubin, Putter-Katz, & Banai, 2006), which suggests that dyslexics have a general difficulty in automatic extraction of stimulus regularities from auditory inputs. This hypothesis explained a broad range of dyslexics' verbal and non-verbal difficulties. However, it was not directly tested in the context of reading and verbal memory, which poses the main stumbling blocks to dyslexics. Here we assessed the abilities of adult dyslexics to efficiently benefit from ("anchor to") regularities embedded in repeated tones, orally presented syllables, and written words. We also compared dyslexics' performance to that of individuals with attention disorder (ADHD), but no reading disability. We found an anchoring effect in all groups: all gained from stimulus repetition. However, in line with the anchoring-deficit hypothesis, controls and ADHD participants showed a significantly larger anchoring effect in all tasks. This study is the first that directly shows that the same domain-general deficit, poor anchoring, characterizes dyslexics' performance in perceptual, working memory and reading tasks.	\N	\N
22562828	The evidence of a deficit in working memory in specific language impairment (SLI) is of sufficient magnitude to suggest a primary role in developmental language disorder. However, little research has investigated memory in late talkers who recover from their early delay. Drawing on a longitudinal, community sample, this study compared the memory profiles of 3 groups of 5-year-olds: children with SLI who had been identified as late talkers, resolved late talkers (RLTs), and children with typical language development (TLD). Participants were 25 children with SLI, 45 RLTs, and 32 children with TLD. Subtests from the Working Memory Test Battery for Children and the Children's Memory Scale plus recalling sentences and nonword repetition tasks were administered to test the components of Baddeley's working memory model. The SLI group showed significantly poorer performance than the RLT and TLD groups on measures of the phonological loop and episodic buffer. The RLT and TLD groups scored similarly on all memory measures. The results support previous findings that sentence recall and nonword repetition are markers of SLI. Although residual effects of late-talking status may emerge over time, RLTs do not necessarily show memory deficits at 5 years of age despite delayed early vocabulary development.	\N	\N
22564904	This investigation examined the effect of repeated exposure to novel and repeated spoken words in typical environments on the intelligibility of 2 synthesized voices and human recorded speech in preschools. Eighteen preschoolers listened to and repeated single words presented in human-recorded speech, DECtalk Paul, and AT&T Voice Michael during 5 experimental sessions. Stimuli consisted of repeated and novel words presented in each speech output condition during each session. Sessions took place in the presence of typically occurring noise in classroom or home settings. There was a significant main effect for voice as participants accurately identified significantly more words in the human-recorded speech and AT&T Voice than in the DECtalk speech output condition. When averaged across speech output conditions, children increased their accuracy as they participated in additional sessions. There was a statistically significant interaction between session and voice. DECtalk had a slightly larger effect of session than did AT&T Voice and human-recorded speech.	\N	\N
22568633	Elevated levels of hypoxia-inducible factor 1α (HIF-1α) in middle ear effusion may play an important role in the pathogenesis of bone conduction impairment associated with otitis media with effusion (OME). The mechanism may be related to the up-regulation of nitric oxide (NO) expression. This study was undertaken to investigate the role of HIF-1α in the pathogenesis of sensorineural hearing loss associated with OME. One hundred and eight OME patients were divided into two groups: OME without bone conduction impairment (group 1) and OME with bone conduction impairment (group 2). The levels of HIF-1α, NO, and quinolinic acid (QUIN) in the middle ear effusion and serum of these patients were investigated. The relationship between these factors and the bone conduction threshold (BCT) differences were analyzed. The levels of HIF-1α and NO concentrations in the middle ear effusion were found to be signiﬁcantly higher in group 2 than in group 1 (both p < 0.05). The OME patients' BCT differences at 4000 Hz were correlated with the levels of HIF-1α and the NO concentrations in the middle ear effusion. Furthermore, the HIF-1α levels were correlated with the levels of NO but not with the levels of QUIN in the effusion.	\N	\N
22568993	Both 80 Hz auditory steady state responses (ASSRs) and tone burst auditory brainstem responses (ABRs) have been shown to provide reasonable estimates of the behavioral thresholds. Although ASSRs provide statistically objective estimates that can be easily automated by computers, they present no information for the neurophysiological interpretation of the results. ABRs, on the other hand, do not provide easily automated information and usually need expert interpretation of the recorded waveforms. A recently developed continuous loop averaging deconvolution algorithm offers an alternative solution by acquiring slightly jittered 80 Hz quasi auditory steady state responses (QASSRs), thus enabling the acquisition of both recordings simultaneously. The purpose of this study is to investigate a specially developed 80 Hz QASSR paradigm for simultaneous acquisition for both responses for threshold detection purposes. Sixteen ears from eight adults with normal hearing were tested. Amplitude modulated QASSRs were obtained using slightly jittered temporal sequences of tone bursts presented at a mean rate of 78.125 Hz. Four carrier frequencies (500, 1000, 2000, and 4000 Hz) at several stimulus intensity levels were monaurally presented and QASSRs to 128 sweeps blocks were recorded. The ABRs were extracted using the CLAD algorithm. Wave V was visually identified and analyzed in the time domain as in everyday clinical practice. In addition, statistically objective ƒMP computation method was used to automatically detect ABR threshold as well. The QASSRs were analyzed in the frequency domain and magnitudes, phase delays, and thresholds were obtained. Phasor (polar plot) diagrams were constructed. QASSR and ABR hearing thresholds were obtained and compared with behavioral thresholds. Study reveals that the QASSR method provides accurate objective estimation of the audiometric thresholds from extracted ASSRs and latency/amplitude information from extracted ABRs. The largest mean threshold difference for QASSR was within 5 dB for all carrier frequencies including 500 Hz. For auditory threshold estimation in adults with normal hearing, the Hotelling's T-Square test in four dimensions in the frequency domain was more accurate than the ƒMP or visual ABR threshold detection in the time domain. Simultaneously recorded ASSR and ABR from QASSRs provide accurate and effective method for frequency-specific hearing threshold estimation with neurophysiological information in adults with normal hearing. Further research is required for hearing-impaired adults, newborns, and infants.	\N	\N
22570723	Multisensory learning and resulting neural brain plasticity have recently become a topic of renewed interest in human cognitive neuroscience. Music notation reading is an ideal stimulus to study multisensory learning, as it allows studying the integration of visual, auditory and sensorimotor information processing. The present study aimed at answering whether multisensory learning alters uni-sensory structures, interconnections of uni-sensory structures or specific multisensory areas. In a short-term piano training procedure musically naive subjects were trained to play tone sequences from visually presented patterns in a music notation-like system [Auditory-Visual-Somatosensory group (AVS)], while another group received audio-visual training only that involved viewing the patterns and attentively listening to the recordings of the AVS training sessions [Auditory-Visual group (AV)]. Training-related changes in cortical networks were assessed by pre- and post-training magnetoencephalographic (MEG) recordings of an auditory, a visual and an integrated audio-visual mismatch negativity (MMN). The two groups (AVS and AV) were differently affected by the training. The results suggest that multisensory training alters the function of multisensory structures, and not the uni-sensory ones along with their interconnections, and thus provide an answer to an important question presented by cognitive models of multisensory training.	\N	\N
22571383	Previous studies of source monitoring and auditory hallucinations (AH) have often conflated spatial source (internal-external) with source agency (self-other). Other studies have used suboptimal manipulations of auditory space (e.g., imagine saying vs. saying aloud). We avoided these problems by presenting experimenter-generated stimuli over headphones in the voice of another person so that the location of the voice sounded either internal or external to the participant's head. Participants (N=121) studied 96 words and indicated for each whether it was presented internally or externally (online spatial source monitoring). At test, studied words were presented visually, intermixed randomly with 96 unstudied words. Participants indicated whether each item was old or new (item memory) and whether it was presented internally or externally during study (spatial source memory). Independent measures of memory accuracy and response bias were derived for online source monitoring, item memory and source memory using signal detection theory. Performance on these measures was compared between two groups of 30 participants who scored low or high on a measure of AH proneness. ANOVAs revealed no differences between the high- and low-AH groups in online spatial source monitoring, item memory, or spatial source memory. We found no evidence that proneness to AH in a sample of healthy volunteers was related to any of the measures of spatial source monitoring performance. We recommend that the methods introduced be applied to future investigations of spatial source monitoring with patient groups and with individuals at-risk for psychosis.	\N	\N
22584229	Children's language skills develop rapidly with increasing age, and several studies indicate that they use language- and age-specific strategies to understand complex sentences. In the present experiment, functional magnetic resonance imaging (fMRI) and behavioral measures were used to investigate the acquisition of case-marking cues for sentence interpretation in the developing brain of German preschool children with a mean age of 6 years. Short sentences were presented auditorily, consisting of a transitive verb and two case-marked arguments with canonical subject-initial or non canonical object-initial word order. Overall group results revealed mainly left hemispheric activation in the perisylvian cortex with increased activation in the inferior parietal cortex (IPC), and the anterior cingulate cortex (ACC) for object-initial compared to subject-initial sentences. However, single-subject analysis suggested two distinct activation patterns within the group which allowed a classification into two subgroups. One subgroup showed the predicted activation increase in the left inferior frontal gyrus (IFG) for the more difficult object-initial compared to subject-initial sentences, while the other group showed the reverse effect. This activation in the left IFG can be taken to reflect the degree to which adult-like sentence processing strategies, necessary to integrate case-marking information, are applied. Additional behavioral data on language development tests show that these two subgroups differ in their grammatical knowledge. Together with these behavioral findings, the results indicate that the use of a particular processing strategy is not dependent on age as such, but rather on the child's individual grammatical knowledge and the ability to use specific language cues for successful sentence comprehension.	\N	\N
22595658	The aim of this experiment was to examine the preattentive processing of syllables in 9-11-year-old children with dyslexia and matched controls using the Mismatch Negativity (MMN), an auditory Event-Related brain potential (ERP) related to preattentive discrimination. Children were presented with a sequence of syllables that included standards (the syllable "Ba") and deviants in vowel frequency, vowel duration and Voice Onset Time (VOT) that were either close to or far from the standard (Small and Large deviants). No between-group differences were found for frequency deviants. However, whilst normal-reading children showed larger MMNs to Large than to Small deviants in vowel duration and VOT, no such deviance size effect was found in children with dyslexia. These results are taken to indicate that the preattentive processing of vowel duration and VOT is impaired in children with dyslexia, with no impairment in the processing of vowel frequency deviants. By revealing processing deficits of both duration and VOT deviants, these results suggest a strong link between acoustical and phonological processing.	\N	\N
22609772	Older adults often find it more difficult than younger adults to attend to a target talker when there are other people talking. One possible reason for this difficulty is that it may take them longer to perceptually segregate the target speech from competing speech. This study investigated age-related differences in the time it takes to segregate target speech from either a speech spectrum noise masker or a babble masker (many people talking simultaneously). Specifically, we employed five different delays (0.1 s-1.1 s) between masker onset and target speech onset. Four signal-to-masker ratios were employed at each delay to determine the 50% thresholds for word recognition accuracy when target words were masked by either speech spectrum noise or multi-talker babble. Thresholds for word recognition decreased exponentially as a function of the masker-word-onset delay, at the same rate for younger and older adults, when the masker was speech spectrum noise. When the masker was babble, thresholds for younger adults decreased exponentially with delay at the same rate as they did when the masker was speech spectrum noise. The word recognition thresholds for older adults, however, did not appear to change over the range of delays explored in this study. In addition, the average difference between word recognition thresholds for younger and older adults (younger adult thresholds < older adult thresholds) was significantly larger when the masker was babble than when it was noise. These results indicate that older adults are as fast as younger adults at separating speech from a steady-state noise masker, but are not as capable as younger adults of taking advantage of the delayed onset of the speech target when the masker is babble. The potential contributions of age-related sensory and cognitive declines to these stream segregation effects are discussed. Finally, we conclude that age-related differences in the timeline for stream segregation contribute to the difficulties older adults experience in listening to speech in a background of babble.	\N	\N
22633004	While perceiving speech, people see mouth shapes that are systematically associated with sounds. In particular, a vertically stretched mouth produces a /woo/ sound, whereas a horizontally stretched mouth produces a /wee/ sound. We demonstrate that hearing these speech sounds alters how we see aspect ratio, a basic visual feature that contributes to perception of 3D space, objects and faces. Hearing a /woo/ sound increases the apparent vertical elongation of a shape, whereas hearing a /wee/ sound increases the apparent horizontal elongation. We further demonstrate that these sounds influence aspect ratio coding. Viewing and adapting to a tall (or flat) shape makes a subsequently presented symmetric shape appear flat (or tall). These aspect ratio aftereffects are enhanced when associated speech sounds are presented during the adaptation period, suggesting that the sounds influence visual population coding of aspect ratio. Taken together, these results extend previous demonstrations that visual information constrains auditory perception by showing the converse - speech sounds influence visual perception of a basic geometric feature.	\N	\N
22641191	The present study uses a systems engineering approach to delineate the relationship between tinnitus and hyperacusis as a result of either hearing loss in the ear or an imbalanced state in the brain. Specifically examined is the input-output function, or loudness growth as a function of intensity in both normal and pathological conditions. Tinnitus reduces the output dynamic range by raising the floor, while hyperacusis reduces the input dynamic range by lowering the ceiling or sound tolerance level. Tinnitus does not necessarily steepen the loudness growth function but hyperacusis always does. An active loudness model that consists of an expansion stage following a compression stage can account for these key properties in tinnitus and hyperacusis loudness functions. The active loudness model suggests that tinnitus is a result of increased central noise, while hyperacusis is due to increased nonlinear gain. The active loudness model also generates specific predictions on loudness growth in tinnitus, hyperacusis, hearing loss or any combinations of the three conditions. These predictions need to be verified by experimental data and have explicit implications for treatment of tinnitus and hyperacusis.	\N	\N
22646514	Sensory consequences of our own actions are perceived differently from the sensory stimuli that are generated externally. The present event-related potential (ERP) study examined the neural responses to self-triggered stimulation relative to externally-triggered stimulation as a function of delays between the motor act and the stimulus onset. While sustaining a vowel phonation, subjects clicked a mouse and heard pitch-shift stimuli (PSS) in voice auditory feedback at delays of either 0 ms (predictable) or 500-1000 ms (unpredictable). The motor effect resulting from the mouse click was corrected in the data analyses. For the externally-triggered condition, PSS were delivered by a computer with a delay of 500-1000 ms after the vocal onset. As compared to unpredictable externally-triggered PSS, P2 responses to predictable self-triggered PSS were significantly suppressed, whereas an enhancement effect for P2 responses was observed when the timing of self-triggered PSS was unpredictable. These findings demonstrate the effect of the temporal predictability of stimulus delivery with respect to the motor act on the neural responses to self-triggered stimulation. Responses to self-triggered stimulation were suppressed or enhanced compared with the externally-triggered stimulation when the timing of stimulus delivery was predictable or unpredictable. Enhancement effect of unpredictable self-triggered stimulation in the present study supports the idea that sensory suppression of self-produced action may be primarily caused by an accurate prediction of stimulus timing, rather than a movement-related non-specific suppression.	\N	\N
22648606	According to many theories of decision making, of which signal detection theory is the most prominent, randomness is the main factor responsible for imperfect performance. These theories imply that correcting for attenuation due to randomness should result in perfect scores as long as the participants use nonextreme decision criteria. On the basis of a recent advance termed potential performance theory (Trafimow & Rice, Psychological Review 115:447-462, 2008), we performed auditory and visual detection experiments and corrected the scores for attenuation. Most participants in both experiments tended to perform at a less-than-perfect level, even after their scores were corrected. The findings demonstrate that at least one systematic factor influences detection that is not included in signal detection theory.	\N	\N
22653919	The authors investigated lengthening effects in child-directed speech (CDS) across the sentence, testing the additive effects on duration of Word Position, Register, Focus, and Sentence Mode (statement/question). Five theater students produced 6 sentences containing 5 monosyllabic words in a simulated dialogue, varying in Register, Focus, and Sentence Mode. The authors segmented a total of 1,800 sentences using forced-alignment tools, and they analyzed the duration of each word. The results show significant effects of Register, Word Position, and their interactions. The simple effect of Register was significant in all 5 word positions, indicating a global elongation effect in CDS. Interestingly, there was no proportional increase of the final word in CDS. In addition, the 3-way interactions Register × Word Position × Focus and Register × Word Position × Sentence Mode were significant, which converge to the conclusion that the utterance-final word in CDS is additively elongated when it is focused and in a statement. Elongation in CDS is a global effect, but the additive effects of duration demonstrated in the authors' data suggest that the effect of enhanced utterance-final lengthening in CDS in naturalistic samples may be a by-product of discourse characteristics of CDS.	\N	\N
22664896	To examine the association between dehiscence length in patients with superior semicircular canal dehiscence syndrome and their clinical findings, including objective audiometric and vestibular testing results. Retrospective study. Tertiary referral center. Patients included in this study were diagnosed with superior semicircular canal dehiscence syndrome and underwent surgical repair of the dehiscence through middle fossa craniotomy. The dehiscence length was measured intraoperatively in all cases. Correlation between dehiscence length with pure-tone average (PTA), average bone-conduction threshold, maximal air-bone gap, cervical vestibular evoked myogenic potential thresholds, and presenting signs and symptoms. The correlation between dehiscence length and maximal air-bone gap was statistically significant on both univariate and multivariate regression analyses. The correlations between dehiscence length and PTA, average bone-conduction threshold, cervical vestibular evoked myogenic potential threshold, and presenting signs and symptoms were not statistically significant. The dehiscence length correlated positively with the maximal air-bone gap in patients with superior semicircular canal dehiscence. The correlation was statistically significant. The dehiscence length did not correlate with the other variables examined in this study.	\N	\N
22666781	The purpose of the study was to acoustically compare the performance of children who do and do not stutter on diadochokinesis tasks in terms of syllable duration, syllable periods, and peak intensity. In this case-control study, acoustical analyses were performed on 26 children who stutter and 20 aged-matched normally fluent children (both groups stratified into preschoolers and school-aged children) during a diadochokinesis task: the repetition of articulatory segments through a task testing the ability to alternate movements. Speech fluency was assessed using the Fluency Profile and the Stuttering Severity Instrument. The children who stutter and those who do not did not significantly differ in terms of the acoustic patterns they produced in the diadochokinesis tasks. Significant differences were demonstrated between age groups independent of speech fluency. Overall, the preschoolers performed poorer. These results indicate that the observed differences are related to speech-motor age development and not to stuttering itself. Acoustic studies demonstrate that speech segment durations are most variable, both within and between subjects, during childhood and then gradually decrease to adult levels by the age of eleven to thirteen years. One possible explanation for the results of the present study is that children who stutter presented higher coefficients of variation to exploit the motor equivalence to achieve accurate sound production (i.e., the absence of speech disruptions).	\N	\N
22672110	Auditory spatial deficits occur frequently after hemispheric damage; a previous case report suggested that the explicit awareness of sound positions, as in sound localisation, can be impaired while the implicit use of auditory cues for the segregation of sound objects in noisy environments remains preserved. By assessing systematically patients with a first hemispheric lesion, we have shown that (1) explicit and/or implicit use can be disturbed; (2) impaired explicit vs. preserved implicit use dissociations occur rather frequently; and (3) different types of sound localisation deficits can be associated with preserved implicit use. Conceptually, the dissociation between the explicit and implicit use may reflect the dual-stream dichotomy of auditory processing. Our results speak in favour of systematic assessments of auditory spatial functions in clinical settings, especially when adaptation to auditory environment is at stake. Further, systematic studies are needed to link deficits of explicit vs. implicit use to disability in everyday activities, to design appropriate rehabilitation strategies, and to ascertain how far the explicit and implicit use of spatial cues can be retrained following brain damage.	\N	\N
22686693	The goal of an action can consist of generating a change in the environment (to produce an effect) or changing one's own situation in the environment (to move to a physical target). To investigate whether the mechanisms of effect-directed and target-directed action control are similar, participants performed continuous reversal movements. They either synchronized movement reversals with regularly presented tones (temporal targets) or produced tones at reversals isochronously (temporal effects). In both goal conditions an irrelevant goal characteristic was integrated into the goal representation (loudness, Experiment 1). When targets and effects were presented within the same reversal movement, similarities were enhanced (Experiment 2). When the task posed spatial demands in addition to temporal demands, target- and effect-directed movement kinematics changed equally with tempo (Experiment 3). Correlations between target-directed and effect-directed movements in temporal variability indicated similar timing mechanisms (Experiments 1 and 2). Only gradual differences between target- and effect-directed movements were observed. We conclude that the same mechanisms of action control, including the anticipation of upcoming events, underlie effect-directed and target-directed movements. Ideomotor theories of action control should incorporate action targets as goals similar to action effects.	\N	\N
22696248	We examined the effects of hedges and the discourse marker like on how people recalled specific details about precise quantities in spontaneous speech. We found that listeners treated hedged information differently from like-marked information, although both are thought to be indicators of uncertainty or vagueness. In addition, hedges had different effects depending on whether speakers were (1) retelling conversations to another person or (2) answering questions about material they had heard. When retelling to another person, listeners were more likely to report information that was either unmarked or marked with a like than hedged information (Experiment 1). Yet when answering questions by themselves, hedges enhanced memory for details, in comparison with likes (Experiment 2). Hedges appear to provide pragmatic cues about what information is reliable enough to repeat in a conversational context. But although hedged information may be left out, it is not forgotten.	\N	\N
22696304	This study determined the effects of phonology and semantics on the distribution of cortical activity to the second of a pair of words in first and second language (mixed pairs). The effects of relative proficiency in the two languages and linguistic setting (monolinguistic or mixed) are reported in a companion paper. Ten early bilinguals and 14 late bilinguals listened to mixed pairs of words in Arabic (L1) and Hebrew (L2) and indicated whether both words in the pair had the same or different meanings. The spatio-temporal distribution of current densities of event-related potentials were estimated for each language and according to semantic and phonologic relationship (same or different) compared with the first word in the pair. During early processing (<300 ms), brain activity in temporal and temporoparietal auditory areas was enhanced by phonologic incongruence between words in the pair and in Wernicke's area by both phonologic and semantic priming. In contrast, brain activities during late processing (>300 ms) were enhanced by semantic incongruence between the two words, particularly in temporal areas and in left hemisphere Broca's and Wernicke's areas. The latter differences were greater when words were in L2. Surprisingly, no significant effects of relative proficiency on processing the second word in the pair were found. These results indicate that the distribution of brain activity to the second of two words presented bilingually is affected differently during early and late processing by both semantic and phonologic priming by- and incongruence with the immediately preceding word.	\N	\N
22698777	Functional near-infrared spectroscopy (fNIRS), a non-invasive neuroimaging optical technique which measures the cortical concentration changes in oxygenated and deoxygenated hemoglobin (O(2)Hb and HHb, respectively), has been extensively utilized in language studies. Most of these studies investigated the ventrolateral/dorsolateral cortex responses, while few language studies on the frontopolar cortex are reported. The aim of this study was to investigate by fNIRS the frontopolar cortex response to a letter verbal fluency task (VFT) in single healthy subjects to better understand the symmetry/asymmetry of language processing. The O(2)Hb and HHb changes were measured on 33 University students by a 8-channel fNIRS system. A significant increase in O(2)Hb (p<0.001), accompanied by a smaller significant decrease in HHb (p<0.001), was observed in each measurement point. However, the laterality index of 21 out of the 33 subjects evidenced a hemispheric dominance (right 9, left 12). Although these results have confirmed a bilateral activation over the frontopolar cortex upon VFT, no clear pattern of lateralization was found. Considering the importance of establishing a response pattern related to cognitive functions in clinical populations, the fNIRS investigation of the frontopolar cortex (and other areas involved in language) in single subject and the use of the laterality index are recommended.	\N	\N
22699985	To report and review the clinical experiences of patients who required reimplantation from an ongoing trial of patients with partial deafness who were treated with electroacoustic stimulation (EAS) cochlear implantation. Retrospective case series review. Tertiary referral center. Two patients with partial deafness, 1 child and 1 adult, who required reimplantation because of device failure occurring 12 to 18 months after hearing preservation cochlear implantation with a Med-El Sonata Flex-EAS electrode array. Reimplantation (with full insertion) of a Med-El Sonata Flex-EAS array (child) and the new complete cochlear coverage Med-El Sonata Flex-28 electrode array (adult). Surgical techniques used include round window insertion with slow insertion speed and the use of preoperative systemic steroids and preoperative, perioperative, and postimplantation intratympanic steroids. Preservation of residual hearing. Both patients had complete preservation of residual hearing after reimplantation. The adult patient had stable improvement in hearing from 750 to 2,000 Hz of 5 to 10 dB. Both patients reported increased benefit after reimplantation. We report a case series of successful pediatric and adult EAS reimplantation, in the adult hearing improvement after reimplantation with a deep insertion electrode was observed. Reimplantation with preservation of residual hearing in patients with EAS is possible with current surgical hearing preserving techniques and atraumatic electrode arrays of variable length.	\N	\N
22709398	Infants begin to segment novel words from speech by 7.5 months, demonstrating an ability to track, encode and retrieve words in the context of larger units. Although it is presumed that word recognition at this stage is a prerequisite to constructing a vocabulary, the continuity between these stages of development has not yet been empirically demonstrated. The goal of the present study is to investigate whether infant word segmentation skills are indeed related to later lexical development. Two word segmentation tasks, varying in complexity, were administered in infancy and related to childhood outcome measures. Outcome measures consisted of age-normed productive vocabulary percentiles and a measure of cognitive development. Results demonstrated a strong degree of association between infant word segmentation abilities at 7 months and productive vocabulary size at 24 months. In addition, outcome groups, as defined by median vocabulary size and growth trajectories at 24 months, showed distinct word segmentation abilities as infants. These findings provide the first prospective evidence supporting the predictive validity of infant word segmentation tasks and suggest that they are indeed associated with mature word knowledge. A video abstract of this article can be viewed at http://www.youtube.com/watch?v=jxzLi5oLZQ8.	\N	\N
22717191	Patients with schizophrenia consistently demonstrate information processing abnormalities assessed with visual masking (VM) tasks, and these deficits have been linked to clinical and functional severity. It has been suggested that VM impairments may be a vulnerability marker in individuals at risk for developing psychosis. Forward and backward VM performance was assessed in 72 first-episode (FE) psychosis patients, 98 subjects at risk (AR) for psychosis and 98 healthy controls (HC) using two identification tasks (with either a high- or low-energy mask) and a location task. VM was examined for stability in a subgroup (FE, n=15; AR, n=35; HC, n=21) and assessed relative to clinical and functional measures. In the identification tasks, backward VM deficits were observed in both FE and AR relative to HC whereas forward VM deficits were only present in FE patients compared to HC. In the location task, AR subjects demonstrated superior performance in forward VM relative to HC. VM performance was stable over time, and VM deficits were associated with baseline functional measures and predicted future negative symptom severity in AR subjects. Visual information processing deficits, as indexed by backward VM, are present before and after the onset of frank psychosis, and probably represent a stable vulnerability marker that is associated with negative symptoms and functional decline. Additionally, the paradoxically better performance of AR subjects in select forward tasks suggests that early compensatory changes may characterize an emerging psychotic state.	\N	\N
22721630	Vocal expressions commonly elicit activity in superior temporal and inferior frontal cortices, indicating a distributed network to decode vocally expressed emotions. We examined the involvement of this fronto-temporal network for the decoding of angry voices during attention towards (explicit attention) or away from emotional cues in voices (implicit attention) based on a reanalysis of previous data (Frühholz, S., Ceravolo, L., Grandjean, D., 2012. Cerebral Cortex 22, 1107-1117). The general network revealed high interconnectivity of bilateral inferior frontal gyrus (IFG) to different bilateral voice-sensitive regions in mid and posterior superior temporal gyri. Right superior temporal gyrus (STG) regions showed connectivity to the left primary auditory cortex and secondary auditory cortex (AC) as well as to high-level auditory regions. This general network revealed differences in connectivity depending on the attentional focus. Explicit attention to angry voices revealed a specific right-left STG network connecting higher-level AC. During attention to a nonemotional vocal feature we also found a left-right STG network implicitly elicited by angry voices that also included low-level left AC. Furthermore, only during this implicit processing there was widespread interconnectivity between bilateral IFG and bilateral STG. This indicates that while implicit attention to angry voices recruits extended bilateral STG and IFG networks for the sensory and evaluative decoding of voices, explicit attention to angry voices solely involves a network of bilateral STG regions probably for the integrative recognition of emotional cues from voices.	\N	\N
22723356	The integration of facial gestures and vocal signals is an essential process in human communication and relies on an interconnected circuit of brain regions, including language regions in the inferior frontal gyrus (IFG). Studies have determined that ventral prefrontal cortical regions in macaques [e.g., the ventrolateral prefrontal cortex (VLPFC)] share similar cytoarchitectonic features as cortical areas in the human IFG, suggesting structural homology. Anterograde and retrograde tracing studies show that macaque VLPFC receives afferents from the superior and inferior temporal gyrus, which provide complex auditory and visual information, respectively. Moreover, physiological studies have shown that single neurons in VLPFC integrate species-specific face and vocal stimuli. Although bimodal responses may be found across a wide region of prefrontal cortex, vocalization responsive cells, which also respond to faces, are mainly found in anterior VLPFC. This suggests that VLPFC may be specialized to process and integrate social communication information, just as the IFG is specialized to process and integrate speech and gestures in the human brain.	\N	\N
22724279	The main goal of this study was to investigate the effects of acoustic characteristics, including timbre and fundamental frequency (F0), on the musical pitch discrimination of cochlear implant users. Eight postlingually deafened cochlear implant users were recruited, along with 8 control subjects with normal hearing. Pitch discrimination tests were carried out using test stimuli from 4 musical instruments plus synthetic complex stimuli. Three reference tones with different F0s were used. The mean difference limens were 1.8 to 10.7 semitones in the just-noticeable difference task and 2.1 to 13.6 semitones in the pitch-direction discrimination task for different timbre and F0 combinations. Three-way analysis of variance showed that the acoustic characteristics of the musical stimuli, such as timbre and F0, significantly influenced pitch discrimination performance. Acoustic characteristics determine the complexity of the electrical stimulation pattern, which directly affects performance in pitch discrimination. A place pattern with a clear and regular low-order harmonic structure is most important for good pitch discrimination. A clear F0-related temporal pattern is also useful when the F0 is low. Pitch perception performance will worsen when there is interference in the high-frequency channels.	\N	\N
22727355	The objective of this study was to evaluate the relationship between developmental delays and speech perception in pre-lingually deafened cochlear implant recipients. This study was a retrospective review of patient charts conducted at a tertiary referral center. Thirty-five pre-lingually deafened children underwent multichannel cochlear implantation and habilitation at the Kyoto University Hospital Department of Otolaryngology-Head and Neck Surgery. A pre-operative cognitive-adaptive developmental quotient was evaluated using the Kyoto scale of psychological development. Post-operative speech performance was evaluated with speech perception tests two years after cochlear implantation. We computed partial correlation coefficients (controlled for age at the time of implantation and the average pre-operative aided hearing level) between the cognitive-adaptive developmental quotient and speech performance. A developmental delay in the cognitive-adaptive area was weakly correlated with speech perception (partial correlation coefficients for consonant-vowel syllables and phrases were 0.38 and 0.36, respectively). A pre-operative developmental delay was only weakly associated with poor post-operative speech perception in pre-lingually deafened cochlear implant recipients.	\N	\N
22728130	The neural processing of auditory information engages pathways that begin initially at the cochlea and that eventually reach forebrain structures. At these higher levels, the computations necessary for extracting auditory source and identity information rely on the neuroanatomical connections between the thalamus and cortex. Here, the general organization of these connections in the medial geniculate body (thalamus) and the auditory cortex is reviewed. In addition, we consider two models organizing the thalamocortical pathways of the non-tonotopic and multimodal auditory nuclei. Overall, the transfer of information to the cortex via the thalamocortical pathways is complemented by the numerous intracortical and corticocortical pathways. Although interrelated, the convergent interactions among thalamocortical, corticocortical, and commissural pathways enable the computations necessary for the emergence of higher auditory perception.	\N	\N
22731996	The influence of top-down cognitive control on 2 putatively distinct forms of distraction was investigated. Attentional capture by a task-irrelevant auditory deviation (e.g., a female-spoken token following a sequence of male-spoken tokens)-as indexed by its disruption of a visually presented recall task-was abolished when focal-task engagement was promoted either by increasing the difficulty of encoding the visual to-be-remembered stimuli (by reducing their perceptual discriminability; Experiments 1 and 2) or by providing foreknowledge of an imminent deviation (Experiment 2). In contrast, distraction from continuously changing auditory stimuli ("changing-state effect") was not modulated by task-difficulty or foreknowledge (Experiment 3). We also confirmed that individual differences in working memory capacity--typically associated with maintaining task-engagement in the face of distraction--predict the magnitude of the deviation effect, but not the changing-state effect. This convergence of experimental and psychometric data strongly supports a duplex-mechanism account of auditory distraction: Auditory attentional capture (deviation effect) is open to top-down cognitive control, whereas auditory distraction caused by direct conflict between the sound and focal-task processing (changing-state effect) is relatively immune to such control.	\N	\N
22753470	A visual scene is perceived in terms of visual objects. Similar ideas have been proposed for the analogous case of auditory scene analysis, although their hypothesized neural underpinnings have not yet been established. Here, we address this question by recording from subjects selectively listening to one of two competing speakers, either of different or the same sex, using magnetoencephalography. Individual neural representations are seen for the speech of the two speakers, with each being selectively phase locked to the rhythm of the corresponding speech stream and from which can be exclusively reconstructed the temporal envelope of that speech stream. The neural representation of the attended speech dominates responses (with latency near 100 ms) in posterior auditory cortex. Furthermore, when the intensity of the attended and background speakers is separately varied over an 8-dB range, the neural representation of the attended speech adapts only to the intensity of that speaker but not to the intensity of the background speaker, suggesting an object-level intensity gain control. In summary, these results indicate that concurrent auditory objects, even if spectrotemporally overlapping and not resolvable at the auditory periphery, are neurally encoded individually in auditory cortex and emerge as fundamental representational units for top-down attentional modulation and bottom-up neural adaptation.	\N	\N
22764349	Presenting synchronous auditory and visual stimuli in separate locations creates the illusion that the sound originates from the direction of the visual stimulus. Participants' auditory localization bias, called the ventriloquism effect, has revealed factors affecting the perceptual integration of audio-visual stimuli. However, many studies on audio-visual processes have focused on performance in simplified experimental situations, with a single stimulus in each sensory modality. These results cannot necessarily explain our perceptual behavior in natural scenes, where various signals exist within a single sensory modality. In the present study we report the contributions of a cognitive factor, that is, the audio-visual congruency of speech, although this factor has often been underestimated in previous ventriloquism research. Thus, we investigated the contribution of speech congruency on the ventriloquism effect using a spoken utterance and two videos of a talking face. The salience of facial movements was also manipulated. As a result, when bilateral visual stimuli are presented in synchrony with a single voice, cross-modal speech congruency was found to have a significant impact on the ventriloquism effect. This result also indicated that more salient visual utterances attracted participants' auditory localization. The congruent pairing of audio-visual utterances elicited greater localization bias than did incongruent pairing, whereas previous studies have reported little dependency on the reality of stimuli in ventriloquism. Moreover, audio-visual illusory congruency, owing to the McGurk effect, caused substantial visual interference to auditory localization. This suggests that a greater flexibility in responding to multi-sensory environments exists than has been previously considered.	\N	\N
22768163	Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD.	\N	\N
22773778	Because acoustic landscapes are complex and rapidly changing, auditory systems have evolved mechanisms that permit rapid detection of novel sounds, sound source segregation, and perceptual restoration of sounds obscured by noise. Perceptual restoration is particularly important in noisy environments because it allows organisms to track sounds over time even when they are masked. The continuity illusion is a striking example of perceptual restoration with sounds perceived as intact even when parts of them have been replaced by gaps and rendered inaudible by being masked by an extraneous sound. The mechanisms of auditory filling-in are complex and are currently not well-understood. The present study used the high temporal resolution of EEG to examine brain activity related to continuity illusion perception. Masking noise loudness was adjusted individually for each subject so that physically identical sounds on some trials elicited a continuity illusion (failure to detect a gap in a sound) and on other trials resulted in correct gap detection. This design ensured that any measurable differences in brain activity would be due to perceptual differences rather than physical differences among stimuli. We found that baseline activity recorded immediately before presentation of the stimulus significantly predicted the occurrence of the continuity illusion in 10 out of 14 participants based on power differences in γ-band EEG (34-80 Hz). Across all participants, power in the β and γ (12- to 80-Hz range) was informative about the subsequent perceptual decision. These data suggest that a subject's baseline brain state influences the strength of continuity illusions.	\N	\N
22774804	The issue investigated in the present research is the nature of the information that is responsible for producing masked priming effects (e.g., semantic information or stimulus-response [S-R] associations) when responding to number stimuli. This issue was addressed by assessing both the magnitude of the category congruence (priming) effect and the nature of the priming distance effect across trials using single-digit primes and targets. Participants made either magnitude (i.e., whether the number presented was larger or smaller than 5) or identification (i.e., press the left button if the number was either a 1, 2, 3, or 4 or the right button if the number was either a 6, 7, 8, or 9) judgments. The results indicated that, regardless of task instruction, there was a clear priming distance effect and a significantly increasing category congruence effect. These results indicated that both semantic activation and S-R associations play important roles in producing masked priming effects.	\N	\N
22776903	Stuttering is generally considered to be a speech disorder that affects ∼1% of the global population. Various forms of speech feedback have been shown to reduce overt stuttered speaking, and in particular, second speech signal through speech feedback has drastically reduced utterances of stuttered speech in adults with persistent stuttering. This study reports data for increased overt fluency of speech in an adult stuttering population, whereby the vocalization of the speaker is captured by a microphone or an accelerometer, signal processed, and returned as mechanical tactile speech feedback to the speaker's skin. A repeated measures analysis of variance was used to show that both the microphone and the accelerometer speaking conditions were significantly more fluent than a control (no feedback) condition, with the microphone-driven tactile feedback reducing instances of stuttering by 71% and the accelerometer-driven tactile feedback reducing instances of stuttering by 80%. It is apparent that self-generated tactile feedback can be used to enhance fluency significantly in those who stutter.	\N	\N
22777734	A growing literature has suggested that processing of visual information presented near the hands is facilitated. In this study, we investigated whether the near-hands superiority effect also occurs with the hands moving. In two experiments, participants performed a cyclical bimanual movement task requiring concurrent visual identification of briefly presented letters. For both the static and dynamic hand conditions, the results showed improved letter recognition performance with the hands closer to the stimuli. The finding that the encoding advantage for near-hand stimuli also occurred with the hands moving suggests that the effect is regulated in real time, in accordance with the concept of a bimodal neural system that dynamically updates hand position in external space.	\N	\N
22788230	Altered auditory feedback can facilitate speech fluency in adults who stutter. However, other findings suggest that adults who stutter show anomalies in 'audiovocal integration', such as longer phonation reaction times to auditory stimuli and less effective pitch tracking. To study audiovocal integration in adults who stutter using the pitch-shift paradigm. Fourteen adult stuttering participants and 16 normally fluent adults produced the vowel /a/while monitoring their own voice through earphones. Unanticipated pitch-shifts were applied in the upward or downward direction for 500 ms. Short latency pitch-shift responses (or pitch-shift responses) were elicited in all participants. In stuttering participants, vocal response onset latency was significantly delayed and amplitude tended to be reduced. Atypical audiovocal responses could be associated with stuttering. It is not clear how audiovocal integration influences stuttering, but could signal inadequate activation of internal models.	\N	\N
22796516	In the present study we examined the effect of positional noise on spatial resolution in younger and older observers. We used a yes/no discrimination task in which observers indicated whether the size of two gaps in a Landolt-C-like contour was the same or not. The proportion of trials observers perceived one gap larger was measured when gaps-position was fixed (low positional noise) and random (high positional noise). Specifically, we compared, across conditions and groups, the values of threshold, lower and upper asymptote of the psychometric function. In the younger group, noise does not prevent detection of gap-size difference although sensitivity is lower, as revealed by higher threshold and lower upper asymptote, i.e., the proportion of responses "I see a larger gap" at the largest gap-size difference (asymptotic performance). In the older group detection is prevented, as revealed by threshold, lower and upper asymptote data. This may be because, at stimulus onset, high positional noise has associated coarse filter analysers averaging across the two gaps, which cannot be switched off.	\N	\N
22799761	Little is known about how sex influences functional brain maturation. The current study investigated sex differences in the maturation of event-related potential (ERP) amplitudes during an auditory oddball task (N = 170; age = 6-17 years). Performance improved with age. N200 amplitude declined with age: parietal sites showed earlier development than temporal and frontal locations. Girls showed greater bilateral frontal P300 amplitude development, approaching the higher values observed in boys during childhood. After controlling for age, right frontal P300 amplitude was associated with reaction time in girls. The findings demonstrate sex differences in ERP maturation in line with behavioral and neuroimaging studies.	\N	\N
22802637	Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca's area in the frontal lobe and Wernicke's area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke's area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms.	\N	\N
22805019	To establish the method of conducting electrical evoked middle latency response (EMLR) monitoring in cochlear implantation operation and further to assess the neural response of auditory pathway under electrical stimulation. Twenty cases of cochlear implantation subjects were investigated in this study. Fourteen cases were pre-lingual deaf and 6 were post-lingual deaf. The surface recording electrodes were placed on the patients under general anesthesia, with language processor connected to the triggering port of the auditory evoked potential device. After the electrode was implanted, the electrode No.3 was selected to conduct. The electrically evoked auditory nerve compound active potentials (ECAP) were firstly tested in all patients, thereafter the EABR mode was selected, and the stimulation parameters were changed to EMLR mode with monopole biphasic, alternation stimulation, pulse width from 50 to 100 µs, the stimulation intensity decreased or increased from 20 CL above the strength of the ECAP threshold to the reaction threshold with a step of 5CL. To evaluate the correlation between the ECAP thresholds and EMLR, another 6 cases of normal hearing healthy subjects were recruited to record their short-sound evoked auditory middle-latency response (AMLR), as the control of morphology and latency of MLR by electrical stimulation. The typical AMLR waveforms could be recorded by the composition of five waves in the 6 cases of normal hearing healthy subjects, with an average response threshold of (12.5±8.6) dBnHL, close to the behavioral audiometric threshold (10.8±7.3) dBHL. The EMLR waveforms could be recorded in 20 patients, which was similar to the AMLR waveforms. However, the wave latency and wave interval shortened. There were lower volatility and longer latency in pre-lingual deaf than post-lingual deaf. The EMLR threshold (140.55±9.92) CL was significantly lower than the ECAP threshold (160.75±13.34) CL (t=10.467, P<0.01), a positive correlation between the thresholds was detected (r=0.763, P<0.01). We successfully established the method of EMLR monitoring in cochlear implantation surgery. The EMLR threshold is lower than the ECAP threshold but it is close to the behavioral audiometric threshold; EMLR can provide neural response information closer to the auditory center, and can serve as an effective objective method to evaluate the effect of hearing rehabilitation.	\N	\N
22829158	The aim of this study was to describe the outcome and possible complications of subtotal petrosectomy (SP) for Vibrant Soundbridge (VSB) device surgery in a tertiary referral center. A secondary objective was the evaluation of hearing results in a subgroup of subjects who received the VSB device. Between 2009 and early 2011, 22 adult subjects with chronic otitis media (COM) underwent a SP, blind sac closure of the external auditory canal and abdominal fat obliteration to facilitate the application of an active middle ear implant (AMEI) in a staged procedure. Indications consisted of mixed hearing loss after previous tympanomastoplasty and failure of hearing rehabilitation with a hearing aid or bone conduction device in COM. Pre- and postoperative pure-tone audiograms were analyzed in respect to deterioration of inner ear function, unaided and aided (hearing aid, bone-anchored hearing aid and VSB) speech audiograms were compared to verify improvements in communications skills and functional gains. Incidence and type of complications were reviewed. No significant change was observed regarding mean bone conduction thresholds after the first stage procedure. Some minor wound healing problems were noted. Speech perception using the VSB (n = 16) showed a mean aided speech discrimination at 65-dB SPL of 75 % [standard deviation (SD) 28.7], at 80-dB SPL of 90 % (SD 25.1). Our results suggest that for selected patients with open mastoid cavities and chronic middle ear disease, SP with abdominal fat obliteration is an effective and safe technique to facilitate safe AMEI placement.	\N	\N
22832675	Auditory-perceptual evaluation of dysphonia may be influenced by the type of speech/voice task used to render judgements during the clinical evaluation, i.e., sustained vowels versus continuous speech. This study explored (a) differences in listener dysphonia severity ratings on the basis of speech/voice tasks, (b) the influence of speech/voice task on dysphonia severity ratings of stimuli that combined sustained vowels and continuous speech, and (c) the differences in inter-rater reliability of dysphonia severity ratings between both speech tasks. Five experienced listeners rated overall dysphonia severity in sustained vowels, continuous speech and concatenated speech samples elicited by 39 subjects with various voice disorders and degrees of hoarseness. Data confirmed that sustained vowels are rated significantly more dysphonic than continuous speech. Furthermore, dysphonia severity in concatenated speech samples is least determined by the sustained vowel. Finally, no significant difference was found in inter-rater reliability between dysphonia severity ratings of sustained vowels versus continuous speech. Based upon the results, both types of speech/voice tasks (i.e., sustained vowel and continuous speech) should be elicited and judged by clinicians in the auditory-perceptual rating of dysphonia severity.	\N	\N
22844984	A fundamental issue in the design and the interpretation of experimental studies of perception relates to the question of whether the participants in these experiments could perform the perceptual task assigned to them using another feature, or cue, than that intended by the experimenter. An approach frequently used by auditory- and visual-perception researchers to guard against this possibility involves applying random variations to the stimuli across presentations or trials so as to make the "unwanted" cue unreliable for the participants. However, the theoretical basis of this widespread practice is not well developed. In this article, we describe a 2-channel model based on general principles of psychophysical signal detection theory, which can be used to assess the respective contributions of the unwanted cue and of the primary cue to performance or thresholds measured in perceptual discrimination experiments involving stimulus randomization. Example applications of the model to the analysis of results obtained in representative studies from the auditory- and visual-perception literature are provided. In several cases, the results of the model-based analyses indicate that the effectiveness of the randomization procedure was less than originally assumed by the authors of these studies. These findings underscore the importance of quantifying the potential influence of unwanted cues on the results of psychophysical experiments, even when stimulus randomization is used.	\N	\N
22846767	Previous studies have demonstrated that human evaluation of subjective loudness and acoustic comfort depends on a series of factors in a particular situation rather than only on sound pressure levels. In the present study, a large-scale subjective survey has been undertaken on underground shopping streets in Harbin, China, to determine how individual sound sources influence subjective loudness and acoustic comfort evaluation. Based on the analysis of case study results, it has been shown that all individual sound sources can increase subjective loudness to a certain degree. However, their levels of influence on acoustic comfort are different. Background music and the public address system can increase acoustic comfort, with a mean difference of 0.18 to 0.32 and 0.21 to 0.27, respectively, where a five-point bipolar category scale is used. Music from shops and vendor shouts can decrease acoustic comfort, with a mean difference of -0.11 to -0.38 and -0.39 to -0.62, respectively. The feasibility of improving acoustic comfort by changing certain sound sources is thus demonstrated.	\N	\N
22866682	Two experiments tested the effects of preview sentences and headings on the quality of college students' outlines of informational texts. Experiment 1 found that performance was much better in the preview sentences condition than in a no-signals condition for both printed text and text-to-speech (TTS) audio rendering of the printed text. In contrast, performance in the headings condition was good for the printed text but poor for the auditory presentation because the TTS software failed to communicate nonverbal information carried by the visual headings. Experiment 2 compared outlining performance for five headings conditions during TTS presentation. Using a theoretical framework, "signaling available, relevant, accessible" (SARA) information, to provide an analysis of the information content of headings in the printed text, the manipulation of the headings systematically restored information that was omitted by the TTS application in Experiment 1. The result was that outlining performance improved to levels similar to the visual headings condition of Experiment 1. It is argued that SARA is a useful framework for guiding future development of TTS software for a wide variety of text signaling devices, not just headings.	\N	\N
22891070	Perceptual training with spectrally degraded environmental sounds results in improved environmental sound identification, with benefits shown to extend to untrained speech perception as well. The present study extended those findings to examine longer-term training effects as well as effects of mere repeated exposure to sounds over time. Participants received two pretests (1 week apart) prior to a week-long environmental sound training regimen, which was followed by two posttest sessions, separated by another week without training. Spectrally degraded stimuli, processed with a four-channel vocoder, consisted of a 160-item environmental sound test, word and sentence tests, and a battery of basic auditory abilities and cognitive tests. Results indicated significant improvements in all speech and environmental sound scores between the initial pretest and the last posttest with performance increments following both exposure and training. For environmental sounds (the stimulus class that was trained), the magnitude of positive change that accompanied training was much greater than that due to exposure alone, with improvement for untrained sounds roughly comparable to the speech benefit from exposure. Additional tests of auditory and cognitive abilities showed that speech and environmental sound performance were differentially correlated with tests of spectral and temporal-fine-structure processing, whereas working memory and executive function were correlated with speech, but not environmental sound perception. These findings indicate generalizability of environmental sound training and provide a basis for implementing environmental sound training programs for cochlear implant (CI) patients.	\N	\N
22892280	Three studies investigated developmental changes in facial expression processing, between 3 years-of-age and adulthood. For adults and older children, the addition of sunglasses to upright faces caused an equivalent decrement in performance to face inversion. However, younger children showed better classification of expressions of faces wearing sunglasses than children who saw the same faces un-occluded. When the mouth area was occluded with a mask, children under nine years showed no impairment in expression classification, relative to un-occluded faces. An early selective focus of attention on the eyes may be optimal for socialization, but mediate against accurate expression classification. The data support a model in which a threshold level of attentional control must be reached before children can develop adult-like configural processing skills and be flexible in their use of face- processing strategies.	\N	\N
22892586	We introduce a new version of the perceptual retouch model. This model was used for explaining properties of temporal interaction of successive objects in reaching conscious representation. The new model incorporates two interactive binding operations - binding features for objects and binding the bound feature-objects with a large scale oscillatory system that corresponds to perceptual consciousness. Here, the typical result of masking experiments - second object advantage in conscious perception - is achieved by applying the effects of a common synchronizing oscillator with a delay. This delayed modulation of each of the feature-binding first-order oscillators that represent emerging and decaying neural activities of each of the objects guarantees that the oscillating synchrony of the feature-neurons of the following object is higher than the synchrony of the feature-neurons of the first presented object. Thus we model the fact that the following object dominates the preceding object in conscious perception. We also show the capacity of the model to simulate illusory misbinding of features from different objects. The third qualitative effect, the relative release of the first object from backward masking is achieved by priming the non-specific oscillatory modulation ahead in time.	\N	\N
22894217	Green [J. Acoust. Soc. Am. 87, 2662-2674 (1990)] suggested an efficient, maximum-likelihood-based approach for adaptively estimating thresholds. Such procedures determine the signal strength on each trial by first identifying the most likely psychometric functions among the pre-proposed alternatives based on responses from previous trials, and then finding the signal strength at the "sweet point" on that most likely function. The sweet point is the point on the psychometric function that is associated with the minimum expected variance. Here, that procedure is extended to reduce poor estimates that result from lapses in attention. The sweet points for the threshold, slope, and lapse parameters of a transformed logistic psychometric function are derived. In addition, alternative stimulus placement algorithms are considered. The result is a relatively fast and robust estimation of a three-parameter psychometric function.	\N	\N
22894232	Speaker variability and noise are two common sources of acoustic variability. The goal of this study was to examine whether these two sources of acoustic variability affected native and non-native perception of Mandarin fricatives to different degrees. Multispeaker Mandarin fricative stimuli were presented to 40 native and 52 non-native listeners in two presentation formats (blocked by speaker and mixed across speakers). The stimuli were also mixed with speech-shaped noise to create five levels of signal-to- noise ratios. The results showed that noise affected non-native identification disproportionately. By contrast, the effect of speaker variability was comparable between the native and non-native listeners. Confusion patterns were interpreted with reference to the results of acoustic analysis, suggesting native and non-native listeners used distinct acoustic cues for fricative identification. It was concluded that not all sources of acoustic variability are treated equally by native and non-native listeners. Whereas noise compromised non-native fricative perception disproportionately, speaker variability did not pose a special challenge to the non-native listeners.	\N	\N
22895701	Critical periods in language acquisition have been discussed primarily with reference to studies of people who are deaf or bilingual. Here, we provide evidence on the opening of sensitivity to the linguistic environment by studying the response to a change of phoneme at a native and nonnative phonetic boundary in full-term and preterm human infants using event-related potentials. Full-term infants show a decline in their discrimination of nonnative phonetic contrasts between 9 and 12 months of age. Because the womb is a high-frequency filter, many phonemes are strongly degraded in utero. Preterm infants thus benefit from earlier and richer exposure to broadcast speech. We find that preterms do not take advantage of this enriched linguistic environment: the decrease in amplitude of the mismatch response to a nonnative change of phoneme at the end of the first year of life was dependent on maturational age and not on the duration of exposure to broadcast speech. The shaping of phonological representations by the environment is thus strongly constrained by brain maturation factors.	\N	\N
22897876	Neurophysiological studies of infant speech suggest that mismatch responses (MMRs) have predictive value for later language. Their value, however, is diminished because unexplained differences in the MMR patterns are seen across studies. The current study aimed to identify the functional nature of infant MMRs by recording event-related-potentials (ERPs) to an infrequent English vowel change in internal or final positions of a sequence of ten vowels in six-month-old monolingually and bilingually exposed infants. Increased negativity of the MMR (infrequent minus frequent) was found in final compared to internal positions and correlated with an index of increased attention to the final position. This pattern helps explain the overall greater negativity to the speech sounds in the bilingually exposed female infants. These findings substantially advance our understanding of neural indices of speech perception development and show promise for furthering our understanding of bilingual language development.	\N	\N
22907183	Although central nervous system abnormalities are incidentally detected in preoperative brain magnetic resonance imaging (MRI) studies in pediatric cochlear implant (CI) candidates, the clinical significance of the abnormalities remains unclear. We aimed to assess post-implantation auditory and speech performance in patients with brain lesions seen on MRI. Pediatric CI recipients (n = 177) who underwent preoperative MRI scans of the brain between January 2002 and June 2009 were included in this study. Patients with brain lesions on MRI were reviewed and categorized into the following groups: brain parenchymal lesions (focal vs. diffuse), ventriculomegaly, and extra-axial lesion. The main communication mode as well as progress in auditory perception and speech production were evaluated preoperatively and at 3, 6, 12, and 24 months postoperatively. Performance in patients with brain lesions was compared with the age- and sex-matched control group. Various brain lesions were found in 27 out of 177 patients. Children with brain lesions who received CIs showed gradual progress in auditory and speech outcomes for 2 years, though performance was reduced compared with the control group. In addition, there was a significant difference in the main communication mode between the two groups at 2 years following cochlear implantation. This difference was especially significant in patients with diffuse brain parenchymal lesions after further stratification of the brain lesion group. Preoperative brain MRI may have a role in improving the prediction of adverse outcomes in pediatric CI recipients. In particular, children with diffuse brain parenchymal lesions should be counseled regarding the poor prognosis preoperatively, and followed up with special attention.	\N	\N
22922236	Cognitive models propose that auditory verbal hallucinations arise through inner speech misidentification. However, such models cannot explain why the voices in hallucinations often have identities different from the hearer. This study investigated whether a general voice identity recognition difficulty might be present in schizophrenia and related to auditory verbal hallucinations. Twenty-five schizophrenia patients and 13 healthy controls were tested on recognition of famous voices. Signal detection theory was used to calculate perceptual sensitivity and response criterion measures. Schizophrenia patients obtained fewer hits and had lower perceptual sensitivity to detect famous voices than healthy controls did. There were no differences between groups in false alarm rate or response criterion. A symptom-based analysis demonstrated that especially those patients with auditory verbal hallucinations performed poorly in the task. The results indicate that patients with hallucinations are impaired at voice identity recognition because of decreased sensitivity, which may result in inner speech misidentification.	\N	\N
22922606	To evaluate, with a long-term follow-up, the speech perception and language development in children with cytomegalovirus (CMV)-related deafness after cochlear implantation. A retrospective study on CMV-related profound deafness and cochlear implantation was performed from 1995 to 2010. Six children with an average follow-up of 10 years were included in this research. Medical history, imaging, cognitive delay, speech perception and production data were reviewed. Two of the 6 patients developed a functional language with the use of phrases and word sequences based on morphological and syntactic rules; the others demonstrated the development of a preverbal or transitional language with the use of single words only. Patients with CMV-related deafness benefit from cochlear implantation; however, the expectations of the parents must be evaluated in a series of counseling efforts prior to the surgery.	\N	\N
22923209	Autism spectrum disorder is typically associated with social deficits and is often specifically linked to difficulty with processing faces and other socially relevant stimuli. Emerging research has suggested that children with autism might also have deficits in basic perceptual abilities including multisensory processing (e.g., simultaneously processing visual and auditory inputs). The current study examined the relationship between multisensory temporal processing (assessed via a simultaneity judgment task wherein participants were to report whether a visual stimulus and an auditory stimulus occurred at the same time or at different times) and self-reported symptoms of autism (assessed via the Autism Spectrum Quotient questionnaire). Data from over 100 healthy adults revealed a relationship between these two factors as multisensory timing perception correlated with symptoms of autism. Specifically, a stronger bias to perceive auditory stimuli occurring before visual stimuli as simultaneous was associated with greater levels of autistic symptoms. Additional data and analyses confirm that this relationship is specific to multisensory processing and symptoms of autism. These results provide insight into the nature of multisensory processing while also revealing a continuum over which perceptual abilities correlate with symptoms of autism and that this continuum is not just specific to clinical populations but is present within the general population.	\N	\N
22925516	We live in a world rich in sensory information, and consequently the brain is challenged with deciphering which cues from the various sensory modalities belong together. Determinations regarding the relatedness of sensory information appear to be based, at least in part, on the spatial and temporal relationships between the stimuli. Stimuli that are presented in close spatial and temporal correspondence are more likely to be associated with one another and thus 'bound' into a single perceptual entity. While there is a robust literature delineating behavioral changes in perception induced by multisensory stimuli, maturational changes in multisensory processing, particularly in the temporal realm, are poorly understood. The current study examines the developmental progression of multisensory temporal function by analyzing responses on an audiovisual simultaneity judgment task in 6- to 23-year-old participants. The overarching hypothesis for the study was that multisensory temporal function will mature with increasing age, with the developmental trajectory for this change being the primary point of inquiry. Results indeed reveal an age-dependent decrease in the size of the 'multisensory temporal binding window', the temporal interval within which multisensory stimuli are likely to be perceptually bound, with changes occurring over a surprisingly protracted time course that extends into adolescence.	\N	\N
22926436	The results of two experiments are presented which explore the effect of distractor items on face and voice recognition. Following from the suggestion that voice processing is relatively weak compared to face processing, it was anticipated that voice recognition would be more affected by the presentation of distractor items between study and test compared to face recognition. Using a sequential matching task with a fixed interval between study and test that either incorporated distractor items or did not, the results supported our prediction. Face recognition remained strong irrespective of the number of distractor items between study and test. In contrast, voice recognition was significantly impaired by the presence of distractor items regardless of their number (Experiment 1). This pattern remained whether distractor items were highly similar to the targets or not (Experiment 2). These results offer support for the proposal that voice processing is a relatively vulnerable method of identification.	\N	\N
22946856	Motivational interviewing (MI) is a directive, client-centered therapeutic method employed in the treatment of substance abuse, with strong evidence of effectiveness. To date, the sole mechanism of action in MI with any consistent empirical support is "change talk" (CT), which is generally defined as client within-session speech in support of a behavior change. "Sustain talk" (ST) incorporates speech in support of the status quo. MI maintains that during treatment, clients essentially talk themselves into change. Multiple studies have now supported this theory, linking within-session speech to substance use outcomes. Although a causal chain has been established linking therapist behavior, client CT, and substance use outcome, the neural substrate of CT has been largely uncharted. We addressed this gap by measuring neural responses to clients' own CT using magnetoencephalography (MEG), a noninvasive neuroimaging technique with excellent spatial and temporal resolution. Following a recorded MI session, MEG was used to measure brain activity while participants heard multiple repetitions of their CT and ST utterances from that session, intermingled and presented in a random order. Results suggest that CT processing occurs in a right-hemisphere network that includes the inferior frontal gyrus, insula, and superior temporal cortex. These results support a representation of CT at the neural level, consistent with the role of these structures in self-perception. This suggests that during treatment sessions, clinicians who are able to evoke this special kind of language are tapping into neural circuitry that may be essential to behavior change.	\N	\N
22951258	Comprehension of spoken narratives requires coordination of multiple language skills. As such, for normal children narrative skills develop well into the school years and, during this period, are particularly vulnerable in the face of brain injury or developmental disorder. For these reasons, we sought to determine the developmental trajectory of narrative processing using longitudinal fMRI scanning. 30 healthy children between the ages of 5 and 18 enrolled at ages 5, 6, or 7, were examined annually for up to 10 years. At each fMRI session, children were presented with a set of five, 30s-long, stories containing 9, 10, or 11 sentences designed to be understood by a 5 year old child. fMRI data analysis was conducted based on a hierarchical linear model (HLM) that was modified to investigate developmental changes while accounting for missing data and controlling for factors such as age, linguistic performance and IQ. Performance testing conducted after each scan indicated well above the chance (p<0.002) comprehension performance. There was a linear increase with increasing age in bilateral superior temporal cortical activation (BAs 21 and 22) linked to narrative processing. Conversely, age-related decreases in cortical activation were observed in bilateral occipital regions, cingulate and cuneus, possibly reflecting changes in the default mode networks. The dynamic changes observed in this longitudinal fMRI study support the increasing role of bilateral BAs 21 and 22 in narrative comprehension, involving non-domain-specific integration in order to achieve final story interpretation. The presence of a continued linear development of this area throughout childhood and teenage years with no apparent plateau, indicates that full maturation of narrative processing skills has not yet occurred and that it may be delayed to early adulthood.	\N	\N
22957659	The Adaptive Tests of Temporal Resolution (ATTR©) software provides within-channel (WC) and across-channel (AC) adaptive measures of temporal resolution that are feasible for clinical applications. The purpose of the present study was to obtain normative values for young adults on two of the ATTR tests: the narrow-band noise within-channel (NBN-WC) test and the narrow-band noise across-channel (NBN-AC) test, at different stimulus intensities. Gap detection thresholds were measured at five sensation levels. A Latin square design was used to control for practice effects. The NBN-WC group and the NBN-AC group each consisted of 25 young adults with normal hearing. Gap detection thresholds for both conditions decreased with increasing stimulus intensity, and stimulus intensities above 20 dB SL were not associated with large improvements in performance. Variability was larger in the NBN-AC condition. Values obtained for the NBC-WC condition were very similar to previously reported ATTR results despite equipment and design differences. Results provide normative values for NBN-WC and NBN-AC performance on the ATTR and suggest that the ATTR is a robust test for clinical use.	\N	\N
22963230	Properties of auditory working memory for sounds that lack strong semantic associations and are not readily verbalized or sung are poorly understood. We investigated auditory working memory capacity for lists containing 2-6 easily discriminable abstract sounds synthesized within a constrained timbral space, at delays of 1-6 s (Experiment 1), and the effect of greater perceptual variability among list items on capacity estimates at delays of 1-6 s (Experiment 2). Working memory capacity estimates of 1-2 items were found in all conditions and increased significantly as the perceptual variability among the list items increased. Nonetheless, the capacity estimates were smaller than the commonly observed average working memory capacity limit of 3-5 items. Decay profiles in both experiments were comparable with those previously reported in the verbal and auditory working memory literature. The results help define boundary conditions on capacity estimates for nonverbalizable timbres that lack strong long-term memory associations.	\N	\N
22978899	A common complaint of the hearing impaired is the inability to understand speech in noisy environments even with their hearing assistive devices. Only a few single-channel algorithms have significantly improved speech intelligibility in noise for hearing-impaired listeners. The current study introduces a cochlear noise reduction algorithm. It is based on a cochlear representation of acoustic signals and real-time derivation of a binary speech mask. The contribution of the algorithm for enhancing word recognition in noise was evaluated on a group of 42 normal-hearing subjects, 35 hearing-aid users, 8 cochlear implant recipients, and 14 participants with bimodal devices. Recognition scores of Hebrew monosyllabic words embedded in Gaussian noise at several signal-to-noise ratios (SNRs) were obtained with processed and unprocessed signals. The algorithm was not effective among the normal-hearing participants. However, it yielded a significant improvement in some of the hearing-impaired subjects under different listening conditions. Its most impressive benefit appeared among cochlear implant recipients. More than 20% improvement in recognition score of noisy words was obtained by 12, 16, and 26 hearing-impaired at SNR of 30, 24, and 18 dB, respectively. The algorithm has a potential to improve speech intelligibility in background noise, yet further research is required to improve its performances.	\N	\N
22978901	The auditory octave illusion arises when dichotically presented tones, one octave apart, alternate rapidly between the ears. Most subjects perceive an illusory sequence of monaural tones: A high tone in the right ear (RE) alternates with a low tone, incorrectly localized to the left ear (LE). Behavioral studies suggest that the perceived pitch follows the RE input, and the perceived location the higher-frequency sound. To explore the link between the perceived pitches and brain-level interactions of dichotic tones, magnetoencephalographic responses were recorded to 4 binaural combinations of 2-min long continuous 400- and 800-Hz tones and to 4 monaural tones. Responses to LE and RE inputs were distinguished by frequency-tagging the ear-specific stimuli at different modulation frequencies. During dichotic presentation, ipsilateral LE tones elicited weaker and ipsilateral RE tones stronger responses than when both ears received the same tone. During the most paradoxical stimulus-high tone to LE and low tone to RE perceived as a low tone in LE during the illusion-also the contralateral responses to LE tones were diminished. The results demonstrate modified binaural interaction of dichotic tones one octave apart, suggesting that this interaction contributes to pitch perception during the octave illusion.	\N	\N
22981882	Dyslexia is heritable and associated with auditory processing deficits. We investigate whether temporal auditory processing is compromised in young children at-risk for dyslexia and whether it is associated with later language and reading skills. We recorded EEG from 17 months-old children with or without familial risk for dyslexia to investigate whether their auditory system was able to detect a temporal change in a tone pattern. The children were followed longitudinally and performed an intelligence- and language development test at ages 4 and 4.5 years. Literacy related skills were measured at the beginning of second grade, and word- and pseudo-word reading fluency were measured at the end of second grade. The EEG responses showed that control children could detect the temporal change as indicated by a mismatch response (MMR). The MMR was not observed in at-risk children. Furthermore, the fronto-central MMR amplitude correlated with preliterate language comprehension and with later word reading fluency, but not with phonological awareness. We conclude that temporal auditory processing differentiates young children at risk for dyslexia from controls and is a precursor of preliterate language comprehension and reading fluency.	\N	\N
22982103	Production of actions is highly dependent on concurrent sensory information. In speech production, for example, movement of the articulators is guided by both auditory and somatosensory input. It has been demonstrated in non-human primates that self-produced vocalizations and those of others are differentially processed in the temporal cortex. The aim of the current study was to investigate how auditory and motor responses differ for self-produced and externally produced speech. Using functional neuroimaging, subjects were asked to produce sentences aloud, to silently mouth while listening to a different speaker producing the same sentence, to passively listen to sentences being read aloud, or to read sentences silently. We show that that separate regions of the superior temporal cortex display distinct response profiles to speaking aloud, mouthing while listening, and passive listening. Responses in anterior superior temporal cortices in both hemispheres are greater for passive listening compared with both mouthing while listening, and speaking aloud. This is the first demonstration that articulation, whether or not it has auditory consequences, modulates responses of the dorsolateral temporal cortex. In contrast posterior regions of the superior temporal cortex are recruited during both articulation conditions. In dorsal regions of the posterior superior temporal gyrus, responses to mouthing and reading aloud were equivalent, and in more ventral posterior superior temporal sulcus, responses were greater for reading aloud compared with mouthing while listening. These data demonstrate an anterior-posterior division of superior temporal regions where anterior fields are suppressed during motor output, potentially for the purpose of enhanced detection of the speech of others. We suggest posterior fields are engaged in auditory processing for the guidance of articulation by auditory information.	\N	\N
22984436	Amplitude modulation can serve as a cue for segregating streams of sounds from different sources. Here we evaluate stream segregation in humans using ABA- sequences of sinusoidally amplitude modulated (SAM) tones. A and B represent SAM tones with the same carrier frequency (1000, 4000 Hz) and modulation depth (30, 100%). The modulation frequency of the A signals (f(modA)) was 30, 100 or 300 Hz, respectively. The modulation frequency of the B signals was up to four octaves higher (Δf(mod)). Three different ABA- tone patterns varying in tone duration and stimulus onset asynchrony were presented to evaluate the effect of forward suppression. Subjects indicated their 1- or 2-stream percept on a touch screen at the end of each ABA- sequence (presentation time 5 or 15 s). Tone pattern, f(modA), Δf(mod), carrier frequency, modulation depth and presentation time significantly affected the percentage of a 2-stream percept. The human psychophysical results are compared to responses of avian forebrain neurons evoked by different ABA- SAM tone conditions [1] that were broadly overlapping those of the present study. The neurons also showed significant effects of tone pattern and Δf(mod) that were comparable to effects observed in the present psychophysical study. Depending on the carrier frequency, modulation frequency, modulation depth and the width of the auditory filters, SAM tones may provide mainly temporal cues (sidebands fall within the range of the filter), spectral cues (sidebands fall outside the range of the filter) or possibly both. A computational model based on excitation pattern differences was used to predict the 50% threshold of 2-stream responses. In conditions for which the model predicts a considerably larger 50% threshold of 2-stream responses (i.e., larger Δf(mod) at threshold) than was observed, it is unlikely that spectral cues can provide an explanation of stream segregation by SAM.	\N	\N
22992710	Auditory perception of vowels in background noise is enhanced when combined with visually perceived speech features. The objective of this study was to investigate whether the influence of visual cues on vowel perception extends to incongruent vowels, in a manner similar to the McGurk effect observed with consonants. Identification of Dutch front vowels /i, y, e, Y/ that share all features other than height and lip-rounding was measured for congruent and incongruent audiovisual conditions. The audio channel was systematically degraded by adding noise, increasing the reliance on visual cues. The height feature was more robustly carried over through the auditory channel and the lip-rounding feature through the visual channel. Hence, congruent audiovisual presentation enhanced identification, while incongruent presentation led to perceptual fusions and thus decreased identification. Visual cues influence the identification of congruent as well as incongruent audiovisual vowels. Incongruent visual information results in perceptual fusions, demonstrating that the McGurk effect can be instigated by long phonemes such as vowels. This result extends to the incongruent presentation of the visually less reliably perceived height. The findings stress the importance of audiovisual congruency in communication devices, such as cochlear implants and videoconferencing tools, where the auditory signal could be degraded.	\N	\N
22993261	Temporal selection poses unique challenges to the perceptual system. Selection is needed to protect goal-relevant stimuli from interference from new sensory input. In addition, contextual information that occurs at the same time as goal-relevant stimuli may be critical for learning. Using fMRI, we characterized how visual cortical regions respond to the temporal selection of auditory and visual stimuli. Critically, we focused on brain regions that are not involved in processing the target itself. Participants pressed a button when they heard a prespecified target tone and did not respond to other tones. Although more attention was directed to auditory input when the target tone was selected, activity in primary visual cortex increased more after target tones than after distractor tones. In contrast to spatial attention, this effect was larger in V1 than in V2 and V3. It was present in regions not typically involved in representing the target stimulus. Additional experiments demonstrated that these effects were not due to multimodal processing, rare targets, or motor responses to the targets. Thus temporal selection of behaviorally relevant stimuli enhances, rather than reduces, activity in perceptual regions involved in processing other information.	\N	\N
22995182	Auditory feedback plays an important role in monitoring vocal output and determining when adjustments are necessary. In this study a group of untrained singers participated in a frequency altered feedback experiment to examine if accuracy at matching a note could predict the degree of compensation to auditory feedback that was shifted in frequency. Participants were presented with a target note and instructed to match the note in pitch and duration. Following the onset of the participants' vocalizations their vocal pitch was shifted down one semi-tone at a random time during their utterance. This altered auditory feedback was instantaneously presented back to them through headphones. Results indicated that note matching accuracy did not correlate with compensation magnitude, however, a significant correlation was found between baseline variability and compensation magnitude. These results suggest that individuals with a more stable baseline fundamental frequency rely more on feedforward control mechanisms than individuals with more variable vocal production. This increased weighting of feedforward control means they are less sensitive to mismatches between their intended vocal production and auditory feedback.	\N	\N
23000118	Users of a cochlear implant together with a hearing aid in the non-implanted ear currently use devices that were developed separately and are often fitted separately. This results in very different growth of loudness with level in the two ears, potentially leading to decreased wearing comfort and suboptimal perception of interaural level differences. A loudness equalisation strategy, named 'SCORE bimodal', is proposed. It equalises loudness growth for the two modalities using existing models of loudness for acoustic and electric stimulation, and is suitable for implementation in wearable devices. Loudness balancing experiments were performed with six bimodal listeners to validate the strategy. In a first set of experiments, the function of each loudness model used was validated by balancing the loudness of four harmonic complexes of different bandwidths, ranging from 200 Hz to 1000 Hz, separately for each ear. Both the electric and acoustic loudness models predicted the data well. In a second set of experiments, binaural balancing was done for the same stimuli. It was found that SCORE significantly improved binaural balance.	\N	\N
23000801	Cochlear implants (CIs) help many deaf children achieve near-normal speech and language (S/L) milestones. Nevertheless, high levels of unexplained variability in S/L outcomes are limiting factors in improving the effectiveness of CIs in deaf children. The objective of this study was to longitudinally assess the role of verbal short-term memory (STM) and working memory (WM) capacity as a progress-limiting source of variability in S/L outcomes after CI in children. Longitudinal study of 66 children with CIs for prelingual severe-to-profound hearing loss. Outcome measures included performance on digit span forward (DSF), digit span backward (DSB), and four conventional S/L measures that examined spoken-word recognition (Phonetically Balanced Kindergarten word test), receptive vocabulary (Peabody Picture Vocabulary Test ), sentence-recognition skills (Hearing in Noise Test), and receptive and expressive language functioning (Clinical Evaluation of Language Fundamentals Fourth Edition Core Language Score; CELF). Growth curves for DSF and DSB in the CI sample over time were comparable in slope, but consistently lagged in magnitude relative to norms for normal-hearing peers of the same age. For DSF and DSB, 50.5% and 44.0%, respectively, of the CI sample scored more than 1 SD below the normative mean for raw scores across all ages. The first (baseline) DSF score significantly predicted all endpoint scores for the four S/L measures, and DSF slope (growth) over time predicted CELF scores. DSF baseline and slope accounted for an additional 13 to 31% of variance in S/L scores after controlling for conventional predictor variables such as: chronological age at time of testing, age at time of implantation, communication mode (auditory-oral communication versus total communication), and maternal education. Only DSB baseline scores predicted endpoint language scores on Peabody Picture Vocabulary Test and CELF. DSB slopes were not significantly related to any endpoint S/L measures. DSB baseline scores and slopes taken together accounted for an additional 4 to 19% of variance in S/L endpoint measures after controlling for the conventional predictor variables. Verbal STM/WM scores, process measures of information capacity, develop at an average rate in the years after cochlear implantation, but were found to consistently lag in absolute magnitude behind those reported for normal-hearing peers. Baseline verbal STM/WM predicted long-term endpoint S/L outcomes, but verbal STM slopes predicted only endpoint language outcomes. Verbal STM/WM processing skills reflect important underlying core elementary neurocognitive functions and represent potential intervention targets for improving endpoint S/L outcomes in pediatric CI users.	\N	\N
23014760	In this paper, we present a Bayesian framework for the active multimodal perception of 3-D structure and motion. The design of this framework finds its inspiration in the role of the dorsal perceptual pathway of the human brain. Its composing models build upon a common egocentric spatial configuration that is naturally fitting for the integration of readings from multiple sensors using a Bayesian approach. In the process, we will contribute with efficient and robust probabilistic solutions for cyclopean geometry-based stereovision and auditory perception based only on binaural cues, modeled using a consistent formalization that allows their hierarchical use as building blocks for the multimodal sensor fusion framework. We will explicitly or implicitly address the most important challenges of sensor fusion using this framework, for vision, audition, and vestibular sensing. Moreover, interaction and navigation require maximal awareness of spatial surroundings, which, in turn, is obtained through active attentional and behavioral exploration of the environment. The computational models described in this paper will support the construction of a simultaneously flexible and powerful robotic implementation of multimodal active perception to be used in real-world applications, such as human-machine interaction or mobile robot navigation.	\N	\N
23015425	Depth-electrode recordings from the auditory cortex of humans undergoing presurgical evaluation for epilepsy allow the recording of ensemble responses to pitch in the form of local field potentials. These recordings allow another test of the hypothesis that there is a specialized neural ensemble for pitch within auditory cortex. Moreover, the technique allows recordings from multiple sites with millisecond temporal resolution to allow modeling of the effective connectivity between these sites. Here we argue that this takes the form of a hierarchical network of pitch-sensitive regions. Activity can be understood as reflecting predictive coding, in which perceptual predictions and error messages are continuously exchanged between a higher pitch center and lower-level auditory cortex.	\N	\N
23025156	Change blindness is the failure of observers to notice otherwise obvious changes to a visual scene when those changes are masked in some way (eg by blotches or a blanking ofthe screen). Typically, change blindness is taken as evidence that our representation of the visual world is capacity limited. The locus of this capacity limit is thought to be visual short-term memory (vSTM). The capacity of vSTM is usually estimated with a high-threshold model which assumes that each element in the stimulus array is either fully encoded or not encoded at all, and, furthermore, that false alarms can arise only by guessing, not by noise. Low-threshold models, by contrast, suggest that false alarms can arise by noise at the level of detection/discrimination and/or decision. In this study, we use a well-controlled stimulus display in which a single element changes over a blanking of the screen and contrast predictions from a popular high-threshold model of vSTM with the predictions of a low-threshold model (specifically, the sample-size model) of visual search and vSTM. The data were better predicted by the low-threshold model.	\N	\N
23025164	Cross-sensory correspondences automatically intrude on performance in elaborate laboratory tasks (see Spence 2011 Attention, Perception, & Psychophysics 73 971-995, for a review). Outside such tasks, might they be responsible for some popular misconceptions about natural phenomena? Four simple demonstrations reveal how the correspondences between surface-lightness and weight, and between surface-lightness and auditory pitch, generate misconceptions about the weight and movement of objects and the vocalisations of animals. Specifically, people expect darker objects to be heavier than lighter-coloured objects, to free-fall more quickly, to roll across a table more slowly, and to make lower-pitched vocalisations when they come to life.	\N	\N
23028516	We physically interact with external stimuli when they occur within a limited space immediately surrounding the body, i.e., Peripersonal Space (PPS). In the primate brain, specific fronto-parietal areas are responsible for the multisensory representation of PPS, by integrating tactile, visual and auditory information occurring on and near the body. Dynamic stimuli are particularly relevant for PPS representation, as they might refer to potential harms approaching the body. However, behavioural tasks for studying PPS representation with moving stimuli are lacking. Here we propose a new dynamic audio-tactile interaction task in order to assess the extension of PPS in a more functionally and ecologically valid condition. Participants vocally responded to a tactile stimulus administered at the hand at different delays from the onset of task-irrelevant dynamic sounds which gave the impression of a sound source either approaching or receding from the subject's hand. Results showed that a moving auditory stimulus speeded up the processing of a tactile stimulus at the hand as long as it was perceived at a limited distance from the hand, that is within the boundaries of PPS representation. The audio-tactile interaction effect was stronger when sounds were approaching compared to when sounds were receding. This study provides a new method to dynamically assess pps representation: The function describing the relationship between tactile processing and the position of sounds in space can be used to estimate the location of PPS boundaries, along a spatial continuum between far and near space, in a valuable and ecologically significant way.	\N	\N
23029113	An auditory neuron can preserve the temporal fine structure of a low-frequency tone by phase-locking its response to the stimulus. Apart from sound localization, however, much about the role of this temporal information for signal processing in the brain remains unknown. Through psychoacoustic studies we provide direct evidence that humans employ temporal fine structure to discriminate between frequencies. To this end we construct tones that are based on a single frequency but in which, through the concatenation of wavelets, the phase changes randomly every few cycles. We then test the frequency discrimination of these phase-changing tones, of control tones without phase changes, and of short tones that consist of a single wavelet. For carrier frequencies below a few kilohertz we find that phase changes systematically worsen frequency discrimination. No such effect appears for higher carrier frequencies at which temporal information is not available in the central auditory system.	\N	\N
23029492	Findings on song perception and song production have increasingly suggested that common but partially distinct neural networks exist for processing lyrics and melody. However, the neural substrates of song recognition remain to be investigated. The purpose of this study was to examine the neural substrates involved in the accessing "song lexicon" as corresponding to a representational system that might provide links between the musical and phonological lexicons using positron emission tomography (PET). We exposed participants to auditory stimuli consisting of familiar and unfamiliar songs presented in three ways: sung lyrics (song), sung lyrics on a single pitch (lyrics), and the sung syllable 'la' on original pitches (melody). The auditory stimuli were designed to have equivalent familiarity to participants, and they were recorded at exactly the same tempo. Eleven right-handed nonmusicians participated in four conditions: three familiarity decision tasks using song, lyrics, and melody and a sound type decision task (control) that was designed to engage perceptual and prelexical processing but not lexical processing. The contrasts (familiarity decision tasks versus control) showed no common areas of activation between lyrics and melody. This result indicates that essentially separate neural networks exist in semantic memory for the verbal and melodic processing of familiar songs. Verbal lexical processing recruited the left fusiform gyrus and the left inferior occipital gyrus, whereas melodic lexical processing engaged the right middle temporal sulcus and the bilateral temporo-occipital cortices. Moreover, we found that song specifically activated the left posterior inferior temporal cortex, which may serve as an interface between verbal and musical representations in order to facilitate song recognition.	\N	\N
23033450	This study aimed to compare sound production errors arising due to phonological processing impairment with errors arising due to motor speech impairment. Two speakers with similar clinical profiles who produced similar consonant cluster simplification errors were examined using a repetition task. We compared both overall accuracy and acoustic details of hundreds of productions with target consonant clusters to tokens with singletons. Changes in accuracy over the course of the study were also compared. In target words with consonant cluster simplification, the individual whose errors reflected phonological impairment produced articulatory timing consistent with singleton onsets. These productions improved when resyllabification was possible, but error rates were not affected by exposure. In contrast, the individual with motoric-based errors produced simplifications that contained the articulatory timing associated with clusters. Accuracy was not affected by the ability to resyllabify, but it did significantly improve following repeated production. Our findings reveal clear differences between errors arising in phonological processing and in motor planning that reflect the underlying systems. The changes over the course of the study suggest that error types with different sources are responsive to different intervention strategies.	\N	\N
23036182	The present event-related potential (ERP) study examined the developmental mechanisms of auditory-vocal integration in normally developing children. Neurophysiological responses to altered auditory feedback were recorded to determine whether they are affected by age and sex. Forty-two children were pairwise matched for sex and were divided into a group of younger (10-12years) and a group of older (13-15years) children. Twenty healthy young adults (20-25years) also participated in the experiment. ERPs were recorded from the participants who heard their voice pitch feedback unexpectedly shifted -50, -100, or -200 cents during sustained vocalization. P1 amplitudes became smaller as subjects increased in age from childhood to adulthood, and males produced larger N1 amplitudes than females. An age-related decrease in the P1-N1 latencies was also found: latencies were shorter in young adults than in school children. A complex age-by-sex interaction was found for the P2 component, where an age-related increase in P2 amplitudes existed only in girls, and boys produced longer P2 latencies than girls but only in the older children. These findings demonstrate that neurophysiological responses to pitch errors in voice auditory feedback depend on age and sex in normally developing children. The present study provides evidence that there is a sex-specific development of the neural mechanisms involved in auditory-vocal integration.	\N	\N
23047260	To determine the effect of oral steroid treatment on hearing in unilateral Ménière's disease and endolymphatic hydrops patients. Retrospective chart review. Tertiary referral center. All patients presenting during the 2010 calendar year with confirmed unilateral Ménière's disease or endolymphatic hydrops. Those with a first visit and second visit audiogram (n = 58) were included in the analysis of oral steroid treatment effect. Steroid treatment for hearing loss. Change in hearing, as defined by change in affected ear threshold values or speech discrimination score from pretreatment visit to posttreatment visit. Hearing (threshold, speech discrimination score) in patients' affected ear did not significantly change from first visit to second visit after treatment with steroids relative to patients who did not receive steroid treatment. The results of this and other studies would indicate that a Ménière's disease or endolymphatic hydrops patient is unlikely to experience an improvement in hearing from a short course of oral steroid. Clinically observed temporary improvement did not sustain over several months. Further work to elucidate the mechanisms underlying hearing loss in hydrops, perhaps focusing on the dendrite damage noted in animal models of hydrops, is warranted.	\N	\N
23056592	Time-compressed speech, a form of rapidly presented speech, is harder to comprehend than natural speech, especially for non-native speakers. Although it is possible to adapt to time-compressed speech after a brief exposure, it is not known whether additional perceptual learning occurs with further practice. Here, we ask whether multiday training on time-compressed speech yields more learning than that observed during the initial adaptation phase and whether the pattern of generalization following successful learning is different than that observed with initial adaptation only. Two groups of non-native Hebrew speakers were tested on five different conditions of time-compressed speech identification in two assessments conducted 10-14 days apart. Between those assessments, one group of listeners received five practice sessions on one of the time-compressed conditions. Between the two assessments, trained listeners improved significantly more than untrained listeners on the trained condition. Furthermore, the trained group generalized its learning to two untrained conditions in which different talkers presented the trained speech materials. In addition, when the performance of the non-native speakers was compared to that of a group of naïve native Hebrew speakers, performance of the trained group was equivalent to that of the native speakers on all conditions on which learning occurred, whereas performance of the untrained non-native listeners was substantially poorer. Multiday training on time-compressed speech results in significantly more perceptual learning than brief adaptation. Compared to previous studies of adaptation, the training induced learning is more stimulus specific. Taken together, the perceptual learning of time-compressed speech appears to progress from an initial, rapid adaptation phase to a subsequent prolonged and more stimulus specific phase. These findings are consistent with the predictions of the Reverse Hierarchy Theory of perceptual learning and suggest constraints on the use of perceptual-learning regimens during second language acquisition.	\N	\N
23059750	The ability to identify stop consonants from brief onset spectra was compared between a group of Chinese children with phonological dyslexia (the PD group, with a mean age of 10 years 4 months) and a group of chronological age-matched control children. The linguistic context, which included vowels and speakers, and durations of stop onset spectra were varied. Children with PD showed lower identification accuracy and exhibited a smaller vowel context effect for some stop-vowel combinations compared with the chronological age-matched control group. Further analyses revealed that the PD group had more variable response patterns, and their responses were less consistent with the acoustic characteristics of stop onset spectra. The results suggest that Chinese children with PD do not show greater sensitivity to allophonic acoustic variability compared with control children and exhibit a generally less robust response pattern to phonetic categories.	\N	\N
23085111	Recent electrophysiological studies have reported short latency modulations in cortical regions for multisensory stimuli, thereby suggesting a subcortical, possibly thalamic origin of these modulations. Concurrently, there is an ongoing debate, whether multisensory interplay reflects automatic, bottom-up driven processes or relies on top-down influences. Here, we dissociated the effects of task set and stimulus configurations on BOLD-signals in the human thalamus with event-related functional magnetic resonance imaging (fMRI). We orthogonally manipulated temporal and spatial congruency of audio-visual stimulus configurations, while subjects judged either their temporal or spatial congruency. Voxel-based fMRI results revealed increased fMRI-signals for the temporal versus spatial task in posterior and central thalamus, respectively. A more sensitive region of interest (ROI)-analysis confirmed that the posterior thalamic nuclei showed a preference for the temporal task and central thalamic nuclei for the spatial task. Moreover, the ROI-analysis also revealed enhanced fMRI-signals for spatially incongruent stimuli in the central thalamus. Together, our results demonstrate that both audio-visual stimulus configurations and task-related processing of spatial or temporal stimulus features selectively modulate thalamic processing and thus are in a position to influence cortical processing at an early stage.	\N	\N
23088507	Sensitivity to frequency ratios is essential for the perceptual processing of complex sounds and the appreciation of music. This study assessed the effect of ratio simplicity on ratio discrimination for pure tones presented either simultaneously or sequentially. Each stimulus consisted of four 100-ms pure tones, equally spaced in terms of frequency ratio and presented at a low intensity to limit interactions in the auditory periphery. Listeners had to discriminate between a reference frequency ratio of 0.97 octave (about 1.96:1) and target frequency ratios, which were larger than the reference. In the simultaneous condition, the obtained psychometric functions were nonmonotonic: as the target frequency ratio increased from 0.98 octave to 1.04 octaves, discrimination performance initially increased, then decreased, and then increased again; performance was better when the target was exactly one octave (2:1) than when the target was slightly larger. In the sequential condition, by contrast, the psychometric functions were monotonic and there was no effect of frequency ratio simplicity. A control experiment verified that the non-monotonicity observed in the simultaneous condition did not originate from peripheral interactions between the tones. Our results indicate that simultaneous octaves are recognized as "special" frequency intervals by a mechanism that is insensitive to the sign (positive or negative) of deviations from the octave, whereas this is apparently not the case for sequential octaves.	\N	\N
23094319	The paper reports on a perception experiment in German that investigated the neuro-cognitive processing of information structural concepts and their prosodic marking using event-related brain potentials (ERPs). Experimental conditions controlled the information status (given vs. new) of referring and non-referring target expressions (nouns vs. adjectives) and were elicited via context sentences, which did not - unlike most previous ERP studies in the field--trigger an explicit focus expectation. Target utterances displayed prosodic realizations of the critical words which differed in accent position and accent type. Electrophysiological results showed an effect of information status, maximally distributed over posterior sites, displaying a biphasic N400--Late Positivity pattern for new information. We claim that this pattern reflects increased processing demands associated with new information, with the N400 indicating enhanced costs from linking information with the previous discourse and the Late Positivity indicating the listener's effort to update his/her discourse model. The prosodic manipulation registered more pronounced effects over anterior regions and revealed an enhanced negativity followed by a Late Positivity for deaccentuation, probably also reflecting costs from discourse linking and updating respectively. The data further lend indirect support for the idea that givenness applies not only to referents but also to non-referential expressions ('lexical givenness').	\N	\N
23095266	A retrospective review was performed of patients treated for middle ear cholesteatoma with bone defects of the skull base via a combined transmastoid/middle fossa approach at the University of Tsukuba Hospital from 2006 through 2011 to determine the safety and effectiveness of a combined transmastoid/middle fossa approach for the treatment of cholesteatoma involving the middle cranial fossa. The bone defects of the skull base were reconstructed with a galeal flap pedicled with a parietal branch of the superficial temporal artery and an autologous bone flap. The clinical and radiological data were analyzed. This series included 8 patients (6 men and 2 women) with a mean age of 46.3 years (range 10-67 years). One of the patients preoperatively exhibited meningoencephalocele of the middle fossa skull base, and in the remaining 7 patients, petrous bone involvement such as involvement of the supralabyrinthine cells was observed. The cholesteatoma lesion was totally removed and inner ear function preserved in all the patients. Cerebrospinal fluid leakage was observed in 1 patient during and after the surgery. Neither meningitis nor recurrence was observed in any patient during the follow-up periods (mean 29.4 months, range 6-64 months). The combined transmastoid/middle fossa approach allowed complete removal of cholesteatoma with middle cranial fossa involvement while preserving hearing and preventing postoperative cerebrospinal fluid leakage and meningitis.	\N	\N
23102977	For children, learning often occurs in the presence of background noise. As such, there is growing desire to improve a child's access to a target signal in noise. Given adult musicians' perceptual and neural speech-in-noise enhancements, we asked whether similar effects are present in musically-trained children. We assessed the perception and subcortical processing of speech in noise and related cognitive abilities in musician and nonmusician children that were matched for a variety of overarching factors. Outcomes reveal that musicians' advantages for processing speech in noise are present during pivotal developmental years. Supported by correlations between auditory working memory and attention and auditory brainstem response properties, we propose that musicians' perceptual and neural enhancements are driven in a top-down manner by strengthened cognitive abilities with training. Our results may be considered by professionals involved in the remediation of language-based learning deficits, which are often characterized by poor speech perception in noise.	\N	\N
23103362	Adolescence is a time of great change in the brain in terms of structure and function. It is possible to track the development of neural function across adolescence using auditory event-related potentials (ERPs). We measured passive auditory ERPs to pure tones and consonant-vowel (CV) syllables in 90 children and adolescents aged 10-18 years, as well as 10 adults. With one exception, the pattern of results were the same for tones and speech: Across adolescence, the P1 ERP peak decreased in size and latency, the N1 increased in size and decreased in latency, the P2 remained constant in size, and the N2 decreased in size but remained stable across adolescence. The exception was P2 latency, which increased for speech but remained stable for tones. Interesting step-like changes were observed for N1 latency for both tones and speech stimuli in 15- to 16-year-olds. These may stem from rapid hormonal changes that affect neurotransmitter activity of the ERP-generating neurons.	\N	\N
23103517	The present study builds on our previous study within the framework of Wyer and Collin's comprehension-elaboration theory of humor processing. In this study, an attempt is made to segregate the neural substrates of incongruity detection and incongruity resolution during the comprehension of verbal jokes. Although a number of fMRI studies have investigated the incongruity-resolution process, the differential neurological substrates of comprehension are still not fully understood. The present study utilized an event-related fMRI design incorporating three conditions (unfunny, nonsensical and funny) to examine distinct brain regions associated with the detection and resolution of incongruities. Stimuli in the unfunny condition contained no incongruities; stimuli in the nonsensical condition contained irresolvable incongruities; and stimuli in the funny condition contained resolvable incongruities. The results showed that the detection of incongruities was associated with greater activation in the right middle temporal gyrus and right medial frontal gyrus, and the resolution of incongruities with greater activation in the left superior frontal gyrus and left inferior parietal lobule. Further analysis based on participants' rating scores provided converging results. Our findings suggest a three-stage neural circuit model of verbal humor processing: incongruity detection and incongruity resolution during humor comprehension and inducement of the feeling of amusement during humor elaboration.	\N	\N
23106730	The acquisition of the function of case-marking is a key step in the development of sentence processing for German-speaking children since case-marking reveals the relations between sentential arguments. In this study, we investigated the development of the processing of case-marking and argument structures in children at 3, 4;6 and 6 years of age, as well as its processing in adults. Using EEG, we measured event-related potentials (ERPs) in response to object-initial compared to subject-initial German sentences including transitive verbs and case-marked noun phrases referring to animate arguments. We also tested children's behavioral competence in a sentence-picture matching task. Word order and case-marking were manipulated in German main clauses. Adults' behavioral performance was close to perfect and their ERPs revealed a negativity for the processing of the topicalized accusative marked noun phrase (NP1) and no effect for the second NP (NP2) in the object-initial structure. Children's behavioral data showed a significant above-chance outcome in the subject-initial condition for all age groups, but not for the object-initial condition. In contrast to adults, the ERPs of 3-year-olds showed a positivity at NP1, indicating difficulties in processing the non-canonical object-initial structures. Children at the age of 4;6 did not differ in the processing patterns of object-initial vs. subject-initial sentences at NP1 but showed a slight positivity at NP2. This positivity at NP2, which implies syntactic integration difficulties, is more pronounced in 6-year-olds but is absent in adults. At NP1, however, 6-year-olds show the same negativity as adults. In sum, the behavioral and electrophysiological findings demonstrate that children in each age group use different strategies, which are indicative of their developmental stage. While 3-year-olds merely detect differences in the two sentence structures without being able to use this information for sentence comprehension, 4;6-year-olds proceed to use mainly a word-order strategy, processing NP1 in both conditions in the same manner, which leads to processing difficulties upon detecting case-marking cues at NP2. At the age of 6, children are able to use case-marking cues for comprehension but still show enhanced effort for correct thematic-role assignment.	\N	\N
23106737	Integrating the multisensory features of talking faces is critical to learning and extracting coherent meaning from social signals. While we know much about the development of these capacities at the behavioral level, we know very little about the underlying neural processes. One prominent behavioral milestone of these capacities is the perceptual narrowing of face-voice matching, whereby young infants match faces and voices across species, but older infants do not. In the present study, we provide neurophysiological evidence for developmental decline in cross-species face-voice matching. We measured event-related brain potentials (ERPs) while 4- and 8-month-old infants watched and listened to congruent and incongruent audio-visual presentations of monkey vocalizations and humans mimicking monkey vocalizations. The ERP results indicated that younger infants distinguished between the congruent and the incongruent faces and voices regardless of species, whereas in older infants, the sensitivity to multisensory congruency was limited to the human face and voice. Furthermore, with development, visual and frontal brain processes and their functional connectivity became more sensitive to the congruence of human faces and voices relative to monkey faces and voices. Our data show the neural correlates of perceptual narrowing in face-voice matching and support the notion that postnatal experience with species identity is associated with neural changes in multisensory processing (Lewkowicz & Ghazanfar, 2009).	\N	\N
23110123	The common marmoset (Callithrix jacchus) is a small New World primate that has increasingly been used as a non-human model in the fields of sensory, motor, and cognitive neuroscience. However, little knowledge exists regarding behavioral methods in this species. Developing an understanding of the neural basis of perception and cognition in an animal model requires measurement of both brain activity and behavior. Here we describe an operant conditioning behavioral training method developed to allow controlled psychoacoustic measurements in marmosets. We demonstrate that marmosets can be trained to consistently perform a Go/No-Go auditory task in which a subject licks at a feeding tube when it detects a sound. Correct responses result in delivery of a food reward. Crucially, this operant conditioning task generates little body movement and is well suited for pairing behavior with single-unit electrophysiology. Successful implementation of an operant conditioning behavior opens the door to a wide range of new studies in the field of auditory neuroscience using the marmoset as a model system.	\N	\N
23110674	Evaluation of pure-tone audiometry (PTA) in hearing screening of a population with mild to profound intellectual disability (ID). PTA was performed at six frequencies at the screening level 20 dB HL. Referral criteria were threshold levels ≥ 25 dB HL at two or more frequencies for one ear or both. 1478 participants aged 7-91 years were included. 1470 (99.5%) people cooperated in screening of which 1325 (90%) could be tested on both ears at all six frequencies. A majority, 987 (66.8%), performed ordinary PTA, 234 (15.8%) conditioned play audiometry, and 249 (16.9%) behavioural observation audiometry. Six hundred and sixty-nine (45%) passed and 809 (55%) failed according to referral criteria. Of those failing, 441 (54.5%) accepted referral to clinical evaluation. PTA with slight modifications is applicable for screening of a population with mild to profound intellectual disability. The most challenging and time-consuming activity is to introduce the test procedure in a way that reduces anxiety and establishes trust.	\N	\N
23116815	The supratemporal plane contains several functionally heterogeneous subregions that respond strongly to speech. Much of the prior work on the issue of speech processing in the supratemporal plane has focused on neural responses to single speech vs. non-speech sounds rather than focusing on higher-level computations that are required to process more complex auditory sequences. Here we examined how information is integrated over time for speech and non-speech sounds by quantifying the BOLD fMRI response to stochastic (non-deterministic) sequences of speech and non-speech naturalistic sounds that varied in their statistical structure (from random to highly structured sequences) during passive listening. Behaviorally, the participants were accurate in segmenting speech and non-speech sequences, though they were more accurate for speech. Several supratemporal regions showed increased activation magnitude for speech sequences (preference), but, importantly, this did not predict sensitivity to statistical structure: (i) several areas showing a speech preference were sensitive to statistical structure in both speech and non-speech sequences, and (ii) several regions that responded to both speech and non-speech sounds showed distinct responses to statistical structure in speech and non-speech sequences. While the behavioral findings highlight the tight relation between statistical structure and segmentation processes, the neuroimaging results suggest that the supratemporal plane mediates complex statistical processing for both speech and non-speech sequences and emphasize the importance of studying the neurocomputations associated with auditory sequence processing. These findings identify new partitions of functionally distinct areas in the supratemporal plane that cannot be evoked by single stimuli. The findings demonstrate the importance of going beyond input preference to examine the neural computations implemented in the superior temporal plane.	\N	\N
23117057	Introducing coherent masker envelope modulation to frequency regions neighboring the signal frequency can reduce detection thresholds for a pure-tone signal. Verhey and Ernst (2009) reported that irregular masker modulation conferred greater benefit than regular modulation when the masker was broadband, but that there was no difference when the masker was narrowband. The present study evaluated two possible explanations for this result: one based on modulation adaptation and the other based on the introduction of relatively long-duration modulation minima in the irregular masker modulation condition. The first experiment replicated the results of Verhey and Ernst (2009), but also included conditions in which a 12.5-ms signal was presented in a 12.5-ms modulation minimum, which was exempted from envelope jitter. The second experiment used a continuous masker and suspended jitter during epochs associated with either a 12.5- or 87.5-ms signal. No benefit of masker envelope irregularity before or after the signal was observed in either experiment. These findings are inconsistent with an explanation based on modulation adaptation, implicating instead the introduction of relatively long-duration modulation minima in the large masking release obtained for a long-duration signal in an irregularly modulated masker.	\N	\N
23123219	The current study was undertaken to investigate changes in forward masking patterns using on-frequency and off-frequency maskers of 7 and 10 kHz probes in the Sprague-Dawley rat. Off-frequency forward masking growth functions have been shown in humans to be non-linear, while on-frequency functions behave linearly. The non-linear nature of the off-frequency functions is attributable to active processing from the outer hair cells, and was therefore expected to be sensitive to noise-induced cochlear damage. For the study, nine Sprague-Dawley rats' auditory brainstem responses (ABRs) were recorded with and without forward maskers. Forward masker-induced changes in latency and amplitude of the initial positive peak of the rats' auditory brainstem responses were assessed with both off-frequency and on-frequency maskers. The rats were then exposed to a noise designed to induce 20-40 dB of permanent threshold shift. Twenty-one days after the noise exposure, the forward masking growth functions were measured to assess noise-induced changes in the off-frequency and on-frequency forward masking patterns. Pre-exposure results showed compressive non-linear masking effects of the off-frequency conditions on both latency and amplitude of the auditory brainstem response. The noise rendered the off-frequency forward masking patterns more linear, consistent with human behavioral findings. On- and off-frequency forward masking growth functions were calculated, and they displayed patterns consistent with human behavioral functions, both prior to noise and after the noise exposure.	\N	\N
23132604	Common-coding theory posits that (1) perceiving an action activates the same representations of motor plans that are activated by actually performing that action, and (2) because of individual differences in the ways that actions are performed, observing recordings of one's own previous behavior activates motor plans to an even greater degree than does observing someone else's behavior. We hypothesized that if observing oneself activates motor plans to a greater degree than does observing others, and if these activated plans contribute to perception, then people should be able to lipread silent video clips of their own previous utterances more accurately than they can lipread video clips of other talkers. As predicted, two groups of participants were able to lipread video clips of themselves, recorded more than two weeks earlier, significantly more accurately than video clips of others. These results suggest that visual input activates speech motor activity that links to word representations in the mental lexicon.	\N	\N
23135616	The objective was to develop and evaluate a new sentence test, the Sentence Test with Adaptive Randomized Roving levels, intended to emulate everyday listening experience, using both normal-hearing (NH) and cochlear implant (CI) groups, examining practicality, learning, test-retest variability, and interlist variability. In experiment 1, each of 25 NH adults was tested using five lists, each comprising 30 sentences. One male and one female speaker each spoke 15 sentences. Ten sentences were presented at each of three presentation levels: 50, 65, and 80 dB SPL. The relative level of a speech-shaped noise was varied adaptively to estimate the speech reception threshold (SRT). Counterbalance for list order was achieved by staggering the allocation of lists to participants. To allow assessment of learning effects, no practice was given. The variability of mean SRTs across lists was small, but correction factors were derived for each list so that, after correction, all lists gave the same mean SRT. Test-retest variability was estimated by examining the corrected SRTs for each subject's five lists. In experiment 2, 25 CI users each received one test list after a small amount of practice. Experiment 3 examined the effect of speech rate using time-compressed speech, for age-matched NH and CI users. The mean SRT for the NH participants was approximately -6 dB and was similar for the male and female speakers. There was a small but significant improvement in SRTs between the first and later lists administered, but no further improvement for subsequent lists. On the basis of the variability of the corrected SRTs within each participant, a 2.2 dB difference in SRT is meaningful for comparisons using one test list per condition, for a single participant. The percentage of key words correct varied with presentation level over a 13% range, being best at 65 dB SPL. Only 40% of the CI group achieved an SRT lower than 20 dB for both speakers. There was large individual variability in the SRTs, and SRTs were higher for the female than for the male speaker. For the CI participants, the percentage of key words correct varied markedly with level, from 19% at the lowest level to 57% at the medium level. Time compression had a small effect for NH participants but a very large effect for CI participants. The Sentence Test with Adaptive Randomized Roving levels seems practical to administer and is reasonably sensitive. For NH participants, a 2.2 dB difference in SRT is meaningful for a single list per condition and a single participant. Although learning effects were small for NH participants, it seems prudent to provide some practice sentences when testing hearing-impaired or CI participants. The very large effect of time compression for the CI group has implications for live voice testing of children, because speech rate is only poorly controlled in such testing.	\N	\N
23144191	This is the first study on adults' physiological reactivity to infant cry sounds and the association with intended harsh parenting using salivary α-amylase (sAA) as a novel and noninvasive marker of autonomic nervous system activity. The sample consisted of 184 adult twin pairs. In an experimental design, cry sounds were presented and adults' perception and their intended caregiving responses were measured. Saliva samples were collected after each cry sound. For the majority of the sample, a decrease in sAA across the cry paradigm was observed. However, adults who indicated that they would respond in a harsh way to the crying infant were significantly less likely to show a decrease in sAA. Consistent with previous studies on physiological hyperreactivity in abusive parents, these findings suggest that failure to habituate to repeated infant crying may be one of the mediating mechanisms through which excessive, inconsolable, and high-pitched infant crying triggers less optimal caregiving.	\N	\N
23145600	Subjective evaluation of acoustics was studied by recording nine concert halls with a simulated symphony orchestra on a seat 12 m from the orchestra. The recorded music was spatially reproduced for subjective listening tests and individual vocabulary profiling. In addition, the preferences of the assessors and objective parameters were gathered. The results show that concert halls were discriminated using perceptual characteristics, such as Envelopment/Loudness, Reverberance, Bassiness, Proximity, Definition, and Clarity. With these perceptual dimensions the preference ratings can be explained. Seventeen assessors were divided into two groups based on their preferences. The first group preferred concert halls with relatively intimate sound, in which it is quite easy to hear individual instruments and melody lines. In contrast, the second group preferred a louder and more reverberant sound with good envelopment and strong bass. Even though all halls were recorded exactly at the same distance, the preference is best explained with subjective Proximity and with Bassiness, Envelopment, and Loudness to some extent. Neither the preferences nor the subjective ratings could be fully explained by objective parameters (ISO3382-1:2009), although some correlations were found.	\N	\N
23151776	To examine and compare the family environment of preschool- and school-age children with cochlear implants and assess its influence on children's executive function and spoken language skills. Retrospective between-subjects design. Outpatient research laboratory. Prelingually deaf children with cochlear implants and no additional disabilities and their families. Cochlear implantation and speech-language therapy. Parents completed the Family Environment Scale and the Behavior Rating Inventory of Executive Function (or the preschool version). Children were tested using the Peabody Picture Vocabulary Test-4 and either the Preschool Language Scales-4 or the Clinical Evaluation of Language Fundamentals-4. The family environments of children with cochlear implants differed from normative data obtained from hearing children, but average scores were within 1 standard deviation of norms on all subscales. Families of school-age children reported higher levels of control than those of preschool-age children. Preschool-age children had fewer problems with emotional control when families reported higher levels of support and lower levels of conflict. School-age children had fewer problems with inhibition but more problems with shifting of attention when families reported lower levels of conflict. School-age children's receptive vocabularies were enhanced by families with lower levels of control and higher levels of organization. Family environment and its relation to language skills and executive function development differed across the age groups in this sample of children with cochlear implants. Because family dynamics is one developmental/environmental factor that can be altered with therapy and education, the present results have important clinical implications for family-based interventions for deaf children with cochlear implants.	\N	\N
23151778	To present the preliminary results of new malleus replacement prosthesis combined with a total ossicular prosthesis in middle ear reconstruction in patients missing the malleus and stapes. Prospective experimental and nonrandomized clinical study. Tertiary referral center. An original titanium malleus replacement prosthesis (MRP) was designed to be inserted into the external auditory canal and to replace a missing malleus for various middle ear pathologies. The MRP was tested experimentally and clinically. The vibratory properties of the new prosthesis were measured using laser Doppler vibrometry. Ninety patients with missing malleus and stapes, undergoing 92 ossicular reconstructions were enrolled in this study from September 1994 to March 2012. Comparative analyses were made between a group of 34 cases of ossicular reconstructions with total prosthesis (TORP) positioned from the tympanic membrane to the stapes footplate (TM-to-footplate assembly) and a group of 58 cases of ossicular reconstructions with TORP positioned from a newly designed malleus replacement prosthesis (MRP) to the stapes footplate (MRP-to-footplate assembly). Preoperative and postoperative audiometric evaluation using conventional audiometry, that is, air-bone gap (ABG), bone-conduction thresholds (BC), and air-conduction thresholds (AC) were assessed. Experimentally, the vibratory properties of the MRP are promising and remain very good even when the MRP is cemented into the bony canal wall mimicking its complete osseous-integration, if this were to occur. This finding supports the short-term clinical results as in the TM-to-footplate group; the 3-month postoperative mean ABG was 23.3 dB compared with 12.5 dB in the MRP-to-footplate group (difference, 10.8; 95% confidence interval, 4.0-17.6); 37.0% of patients from the TM-to-footplate group had a postoperative ABG of 10 dB or less, and 48.1% of patients had a postoperative ABG of 20 dB or less, as compared with 58.1% and 79.1%, respectively, in the MRP-to-footplate group. The average gain in AC was 11.0 dB in the TM-to-footplate group as compared with 21.3 dB in the MRP-to-footplate group (difference, -10.3; 95% confidence interval, -18.2 to -2.4). The results of this study indicate that superior postoperative hearing thresholds could be achieved using a MRP-to-footplate assembly, compared with a TM-to-footplate assembly in patients with an absent malleus undergoing ossiculoplasty. The postoperative AC thresholds, after 3 months and 1 year, are significantly lower in patients treated with the MRP-to-footplate assembly.	\N	\N
23156899	The study presented in this paper aimed to investigate the pattern of semantic priming effects, under masked and unmasked conditions, in the lexical decision task, manipulating type of semantic relation and associative strength. Three different kinds of word relations were examined in two experiments: only-semantically related words [e.g., codo (elbow)-rodilla (knee)] and semantic/associative related words with strong [e.g., mesa (table)-silla (chair) and weak association strength [e.g., sapo (toad)-rana (frog)]. In Experiment 1 a masked priming procedure was used with a prime duration of 56 ms, and in Experiment 2, the prime was presented unmasked for 150 ms. The results showed that there were masked priming effects with strong associates, but no evidence of these effects was found with weak associates or only-semantic related word pairs. When the prime was presented unmasked, the three types of relations produced significant priming effects and they were not influenced by association strength.	\N	\N
23165224	This study describes a vocoder-based frequency-lowering system that enhances spectral cues for nonsonorant consonants differing in place of articulation. The goal of this study was to evaluate the efficacy of this system for speech recognition by hearing-impaired listeners. Experiment 1 evaluated fricative consonant recognition in quiet. Eight fricatives in /VCV/ context were used. Experiment 2 evaluated consonant recognition in quiet with 22 consonants. Six listeners with steeply sloping high-frequency sensorineural hearing loss participated in experiment 1. The same six listeners and three additional listeners with flat/mid-frequency sensorineural hearing loss participated in experiment 2. Two processing conditions-frequency lowering and conventional amplification-were tested in each experiment. Insertion gains based on the NAL-RP formula were provided up to 8000 Hz for each processing condition. In addition, speech stimuli were low-pass (LP) filtered at 1000, 1500, and 2000 Hz to evaluate the effect of lack of high-frequency speech information on consonant perception with and without frequency lowering. For these LP speech conditions, amplification was provided up to the cutoff frequencies. Overall percent correct and percent information transmission were calculated for each processing and speech condition. The frequency-lowering system provided significant benefit for the perception of fricative consonants and perception of the place-of-articulation feature for hearing-impaired listeners without affecting their perception of sonorant consonants and other consonant features (i.e., voicing and nasality). The improvement of fricative consonant perception was observed for both wideband and LP speech conditions for the steeply sloping hearing-loss listeners. The results indicate that individuals with unaidable hearing loss above 1000 to 2000 Hz would receive significant benefit with the system compared with conventional amplification for the perception of fricative consonants, and more importantly, significant benefit for the perception of place of articulation.	\N	\N
23165382	To objectively determine changes in sensorineural hearing in children with mucopolysaccharidosis (MPS) by comparing audiological data before and after hematopoietic stem cell transplantation (HSCT). Retrospective medical chart analysis. Tertiary referral hospital. Thirty pediatric patients with the diagnosis of MPS who underwent HSCT and had audiological data before and after HSCT. Data were extracted from medical charts for patients seen at our institution from January 1, 1999, to December 1, 2009. Hearing was assessed using behavioral audiometry testing and auditory brainstem responses (ABR) before and after HSCT. Patient demographics, diagnosis, and age at HSCT were also evaluated. Thirty patients with MPS were included. Four (13%) had MPS type 3a, 2 (7%) had MPS type 2, and 24 (80%) had MPS type 1. The average age at HSCT was 19 months (range, 5-44 months). Hearing improvement was evaluated by audiogram (20 patients), ABR (8 patients), and qualitative measures (30 patients). On average, patients did not show improvement on audiogram (P = .28; paired t test). The ABR click threshold improved 19 dB on average (P < .001). Qualitatively, 3 patients had normal hearing before and after HSCT. Of the remaining 27 patients, 20 (67%) showed improvement in sensorineural hearing (P < .001). Five (17%) had hearing loss and did not improve. Two (7%) had worsening hearing. Hematopoietic stem cell transplantation at the age of 25 months or younger was significantly correlated with hearing improvement (P = .03). Hematopoietic stem cell transplantation may provide improvement in MPS-associated sensorineural hearing loss. Hearing improvement is more likely to occur in patients who undergo transplantation at 25 months or younger.	\N	\N
23166292	Functional magnetic resonance imaging (fMRI) was employed to identify neural regions engaged during the encoding of contextual features belonging to different modalities. Subjects studied objects that were presented to the left or right of fixation. Each object was paired with its name, spoken in either a male or a female voice. The test requirement was to discriminate studied from unstudied pictures and, for each picture judged old, to retrieve its study location and the gender of the voice that spoke its name. Study trials associated with accurate rather than inaccurate location memory demonstrated enhanced activity in the fusiform and parahippocampal cortex and the hippocampus and reduced activity (a negative subsequent memory effect) in the medial occipital cortex. Successful encoding of voice information was associated with enhanced study activity in the right middle superior temporal sulcus and activity reduction in the right superior frontal cortex. These findings support the proposal that encoding of a contextual feature is associated with enhanced activity in regions engaged during its online processing. In addition, they indicate that negative subsequent memory effects can also demonstrate feature-selectivity. Relative to other classes of study trials, trials for which both contextual features were later retrieved demonstrated enhanced activity in the lateral occipital complex and reduced activity in the temporo-parietal junction. These findings suggest that multifeatural encoding was facilitated when the study item was processed efficiently and study processing was not interrupted by redirection of attention toward extraneous events.	\N	\N
23167712	Despite its fundamental relevance for representing the emotional world surrounding us, human affective neuroscience research has widely neglected the auditory system, at least in comparison to the visual domain. Here, we have investigated the spatiotemporal dynamics of human affective auditory processing using time-sensitive whole-head magnetoencephalography. A novel and highly challenging affective associative learning procedure, 'MultiCS conditioning', involving multiple conditioned stimuli (CS) per affective category, was adopted to test whether previous findings from intramodal conditioning of multiple click-tones with an equal number of auditory emotional scenes (Bröckelmann et al., 2011 J. Neurosci., 31, 7801) would generalise to crossmodal conditioning of multiple click-tones with an electric shock as single aversive somatosensory unconditioned stimulus (UCS). Event-related magnetic fields were recorded in response to 40 click-tones before and after four contingent pairings of 20 CS with a shock and the other half remaining unpaired. In line with previous findings from intramodal MultiCS conditioning we found an affect-specific modulation of the auditory N1m component 100-150 ms post-stimulus within a distributed frontal-temporal-parietal neural network. Increased activation for shock-associated tones was lateralised to right-hemispheric regions, whereas unpaired safety-signalling tones were preferentially processed in the left hemisphere. Participants did not show explicit awareness of the contingent CS-UCS relationship, yet behavioural conditioning effects were indicated on an indirect measure of stimulus valence. Our findings imply converging evidence for a rapid and highly differentiating affect-specific modulation of the auditory N1m after intramodal as well crossmodal MultiCS conditioning and a correspondence of the modulating impact of emotional attention on early affective processing in vision and audition.	\N	\N
23168357	We investigated gender differences in the identification of personally familiar voices in a gender-balanced sample of 40 listeners. From various types of utterances, listeners had to identify by name 20 speakers (10 female) among a set of 70 possible classmates who were all 12th grade pupils from the same local secondary school. Mean identification rates were 67% from sentences, and around 35% for an isolated /Hello/ or a VCV syllable. Even from non-verbal harrumphs, speakers were identified with an accuracy of 18%, i.e. highly above chance levels. Substantial individual differences were observed between listeners. Importantly, superior overall performance of female listeners was qualified by an interaction between voice gender and listener gender. Male listeners exhibited an own-gender bias (i.e. better identification for male than female voices), whereas female listeners identified voices of both genders at similar levels. Individual own-gender identification biases were correlated with differences in reported contact to a speaker's voice and voice distinctiveness. Overall, the present study establishes a number of factors that account for substantial individual differences in personal voice identification.	\N	\N
23169196	Patients with single-sided deafness (SSD), where one ear has an unaidable hearing loss and the other ear has normal or aidable hearing, often complain of difficulties understanding speech and localizing sound sources, and report a higher self-perceived hearing disability. Patients with SSD may benefit from using contralateral routing of signal (CROS) or bilateral contralateral routing of the signal (BiCROS) amplification. Dissatisfaction of previously available (Bi)CROS devices has been reported, such as, interfering transmissions, low-fidelity sound quality, poor "user-friendly" set-up, and a bulky and cosmetically cumbersome appearance. Recent advances in hearing aid technology have improved (Bi)CROS hearing aids; however, these devices have not been experimentally evaluated. We hypothesized that newer technology with reports of improved digital signal processing, wireless transmission, and physical design would be as good, or better than, our participants' previous-generation BiCROS systems. A within-subjects, pretest-posttest design was executed. Thirty-nine veterans (one female, 38 males; mean age = 74 yr, range = 49-85 yr) from the Audiology Section of the Bay Pines Veterans Affair Healthcare System participated. All participants were previously experienced BiCROS hearing aid users with varying degrees of sensorinerual hearing impairment in their better ear. Participants were provided at least 4 wk of consistent use with the new BiCROS. DATA COLLECTION AND ANALYSES: Participants completed three research visits. At Visit 1, with their previous BiCROS, and at Visit 3, with their new BiCROS, the following objective and subjective measures were obtained: (1) soundfield speech-in-noise testing using the Words-In-Noise (WIN) test; (2) speech, spatial, and qualities of the hearing scale (SSQ) questionnaire; (3) selected questions from the MarkeTrak questionnaire; and, (4) three open-ended questions. Data were analyzed using parametric and nonparametric statistics. Overall, the objective (WIN) and subjective (SSQ, MarkeTrak, and open-ended questions) measures indicated that the new BiCROS provided better outcomes than the previous BiCROS system. In addition, an overlap of favorable results was seen across measures. Of the 39 participants, 95% reported improvements with the new BiCROS and chose to utilize the device regularly. The favorable objective and subjective outcomes indicate that the new BiCROS system is as good, or better than, what was previously utilized by our sample of veterans.	\N	\N
23174416	Speech contains a variety of acoustic cues to auditory and phonetic contrasts that are exploited by the listener in decoding the acoustic signal. In three experiments, we tried to elucidate whether listeners rely on formant peak frequencies or whole spectrum attributes in vowel discrimination. We created two vowel continua in which the acoustic distance in formant frequencies was constant but the continua differed in spectral moments (i.e., the whole spectrum modeled as a probability density function). In Experiment 1, we measured reaction times and response accuracy while listeners performed a go/no-go discrimination task. The results indicated that the performance of the listeners was based on the spectral moments (especially the first and second moments), and not on formant peaks. Behavioral results in Experiment 2 showed that, when the stimuli were presented in noise eliminating differences in spectral moments between the two continua, listeners employed formant peak frequencies. In Experiment 3, using the same listeners and stimuli as in Experiment 1, we measured an automatic brain potential, the mismatch negativity (MMN), when listeners did not attend to the auditory stimuli. Results showed that the MMN reflects sensitivity only to the formant structure of the vowels. We suggest that the auditory cortex automatically and pre-attentively encodes formant peak frequencies, whereas attention can be deployed for processing additional spectral information, such as spectral moments, to enhance vowel discrimination.	\N	\N
23178211	Blind people may compensate for their visual loss by the increased use of auditory spatial information, thus showing normal or even supra-normal ability to localize sources of sound. However, the problem of how blind persons develop and maintain an internal concept of the topography of the auditory space in the absence of calibration by visual information is still unsolved. The present study demonstrated a substantial superiority of blind subjects in perception of auditory motion: The minimum audible movement angle of blind subjects (mean 3°) was about half the value found in matched sighted controls, whereas no such advantage was demonstrable for localization of stationary sound. There were no significant differences between early or congenitally blind subjects and late blind subjects, suggesting that long-term visual deprivation per se, independently of the point in time of its onset, was relevant for the superiority in auditory motion perception. The results were compatible with the hypothesis that in the absence of visual input the calibration of the auditory space is performed by audiomotor feedback, that is, by the evaluation of systematic changes of auditory spatial cues resulting from head and body movements. It is reasonable to assume that with blindness the neuronal circuits specifically concerned with the analysis of auditory motion are more intensely trained than in sighted people. It seems possible that the higher demand of motion analysis associated with blindness is related to processes of reorganization in the brain, as have been previously reported to occur also in areas known to be involved in auditory and/or visual motion analysis in sighted persons.	\N	\N
23231122	Measures of spectral ripple resolution have become widely used psychophysical tools for assessing spectral resolution in cochlear-implant (CI) listeners. The objective of this study was to compare spectral ripple discrimination and detection in the same group of CI listeners. Ripple detection thresholds were measured over a range of ripple frequencies and were compared to spectral ripple discrimination thresholds previously obtained from the same CI listeners. The data showed that performance on the two measures was correlated, but that individual subjects' thresholds (at a constant spectral modulation depth) for the two tasks were not equivalent. In addition, spectral ripple detection was often found to be possible at higher rates than expected based on the available spectral cues, making it likely that temporal-envelope cues played a role at higher ripple rates. Finally, spectral ripple detection thresholds were compared to previously obtained speech-perception measures. Results confirmed earlier reports of a robust relationship between detection of widely spaced ripples and measures of speech recognition. In contrast, intensity difference limens for broadband noise did not correlate with spectral ripple detection measures, suggesting a dissociation between the ability to detect small changes in intensity across frequency and across time.	\N	\N
23231815	Normal temporal processing is important for the perception of speech in quiet and in difficult listening situations. Temporal resolution is commonly measured using a behavioral gap detection task, where the patient or subject must participate in the evaluation process. This is difficult to achieve with subjects who cannot reliably complete a behavioral test. However, recent research has investigated the use of evoked potential measures to evaluate gap detection. The purpose of the current study was to record N1-P2 responses to gaps in broadband noise in normal hearing young adults. Comparisons were made of the N1 and P2 latencies, amplitudes, and morphology to different length gaps in noise in an effort to quantify the changing responses of the brain to these stimuli. It was the goal of this study to show that electrophysiological recordings can be used to evaluate temporal resolution and measure the influence of short and long gaps on the N1-P2 waveform. This study used a repeated-measures design. All subjects completed a behavioral gap detection procedure to establish their behavioral gap detection threshold (BGDT). N1-P2 waveforms were recorded to the gap in a broadband noise. Gap durations were 20 msec, 2 msec above their BGDT, and 2 msec. These durations were chosen to represent a suprathreshold gap, a near-threshold gap, and a subthreshold gap. Fifteen normal-hearing young adult females were evaluated. Subjects were recruited from the local university community. Latencies and amplitudes for N1 and P2 were compared across gap durations for all subjects using a repeated-measures analysis of variance. A qualitative description of responses was also included. Most subjects did not display an N1-P2 response to a 2 msec gap, but all subjects had present clear evoked potential responses to 20 msec and 2+ msec gaps. Decreasing gap duration toward threshold resulted in decreasing waveform amplitude. However, N1 and P2 latencies remained stable as gap duration changed. N1-P2 waveforms can be elicited by gaps in noise in young normal-hearing adults. The responses are present as low as 2 msec above behavioral gap detection thresholds (BGDT). Gaps that are below BGDT do not generally evoke an electrophysiological response. These findings indicate that when a waveform is present, the gap duration is likely above their BGDT. Waveform amplitude is also a good index of gap detection, since amplitude decreases with decreasing gap duration. Future studies in this area will focus on various age groups and individuals with auditory disorders.	\N	\N
23231816	Most cochlear implant (CI) users describe music as a noise-like and unpleasant sound. Using behavioral tests, most prior studies have shown that perception of pitch-based melody and timbre is poor in CI users. This article will focus on cortical encoding of timbre changes in CI users, which may allow us to find solutions to further improve CI benefits. Furthermore, the value of using objective measures to reveal neural encoding of timbre changes may be reflected in this study. A case-control study of the mismatch negativity (MMN) using electrophysiological technique was conducted. To derive MMNs, three randomly arranged oddball paradigms consisting of standard/deviant instrumental pairs: saxophone/piano, cello/trombone, and flute/French horn, respectively, were presented. Ten CI users and ten normal-hearing (NH) listeners participated in this study. After filtering, epoching, and baseline correction, independent component analysis (ICA) was performed to remove artifacts. The averaged waveforms in response to the standard stimuli (STANDARD waveform) and the deviant stimuli (DEVIANT waveform) in each condition were separately derived. The responses from nine electrodes in the fronto-central area were averaged to form one waveform. The STANDARD waveform was subtracted from the DEVIANT waveform to derive the difference waveform, for which the MMN was judged to be present or absent. The measures used to evaluate the MMN included the MMN peak latency and amplitude as well as MMN duration. The MMN, which reflects the ability to automatically detect acoustic changes, was present in all NH listeners but only approximately half of CI users. In CI users with present MMNs, the MMN peak amplitude and duration were significantly smaller and shorter compared to those in NH listeners. Our electrophysiological results were consistent with prior behavioral results that CI users' performance in timbre perception was significantly poorer than that in NH listeners. Our results may suggest that timbre information is poorly registered in the auditory cortex of CI users and the capability of automatic detection of timbre changes is degraded in CI users. Although there are some limitations of the MMN in CI users, along with other objective auditory evoked potential tools, the MMN may be a useful objective tool to indicate the extent of sound registration in auditory cortex in the future efforts of improving CI design and speech strategy.	\N	\N
23237416	Children with phonological impairment (PI) often have difficulties perceiving insufficiencies in their own speech. The use of recordings has been suggested as a way of directing the child's attention toward his/her own speech, despite a lack of evidence that children actually recognize their recorded voice as their own. We present two studies of children's self-voice identification, one exploring developmental aspects, and one exploring potential effects of having a PI. The results indicate that children from 4 to 8 years recognize their recorded voice well (around 80% accuracy), regardless of whether they have a PI or not. A subtle change in this ability from 4 to 8 years is observed that could be linked to a development in short-term memory. Clinically, one can indeed expect an advantage of using recordings in therapy; this could constitute an intermediate step toward the more challenging task of online self-monitoring.	\N	\N
23238175	To investigate the relationship between the threshold and the interaural amplitude difference ratio (IADR) in cervical vestibular evoked myogenic potential (cVEMP) testing and pursuit the clinical significance of the parameters. cVEMP responses were recorded while the SCM contraction was controlled using a pressure cuff. The intensities of the sound stimulation decreased from 95 dB n HL by 5 dB, until no responses were evoked. Thresholds, interaural threshold difference (ITD), amplitudes, and interaural amplitude difference ratio at the stimulation of 95 dB n HL were calculated and the relationship between them was examined. All subjects showed cVEMP responses bilaterally. Thresholds measured were overall 76 dB n HL and most (92%) ears showed the ITD of 0 or 5 dB. The amplitudes of cVEMP responses showed a positive correlation with the sound intensities, and more specifically with the sound intensity above each threshold value. There was no significant difference in IADR values by the ITD. Based on our study, the ITD is less than 10 dB in most normal subjects and estimation of threshold should be added to cVEMP testing for probing vestibular asymmetry. Getting a threshold might be helpful in determining whether the abnormal interaural amplitude difference ratio is related to the abnormal ITD.	\N	\N
23241212	Coloured-hearing (CH) synesthesia is a perceptual phenomenon in which an acoustic stimulus (the inducer) initiates a concurrent colour perception (the concurrent). Individuals with CH synesthesia "see" colours when hearing tones, words, or music; this specific phenomenon suggesting a close relationship between auditory and visual representations. To date, it is still unknown whether the perception of colours is associated with a modulation of brain functions in the inducing brain area, namely in the auditory-related cortex and associated brain areas. In addition, there is an on-going debate as to whether attention to the inducer is necessarily required for eliciting a visual concurrent, or whether the latter can emerge in a pre-attentive fashion. By using the EEG technique in the context of a pre-attentive mismatch negativity (MMN) paradigm, we show that the binding of tones and colours in CH synesthetes is associated with increased MMN amplitudes in response to deviant tones supposed to induce novel concurrent colour perceptions. Most notably, the increased MMN amplitudes we revealed in the CH synesthetes were associated with stronger intracerebral current densities originating from the auditory cortex, parietal cortex, and ventral visual areas. The automatic binding of tones and colours in CH synesthetes is accompanied by an early pre-attentive process recruiting the auditory cortex, inferior and superior parietal lobules, as well as ventral occipital areas.	\N	\N
23249352	Psychophysical experiments show that auditory change detection can be disturbed in situations in which listeners have to monitor complex auditory input. We made use of this change deafness effect to segregate the neural correlates of physical change in auditory input from brain responses related to conscious change perception in an fMRI experiment. Participants listened to two successively presented complex auditory scenes, which consisted of six auditory streams, and had to decide whether scenes were identical or whether the frequency of one stream was changed between presentations. Our results show that physical changes in auditory input, independent of successful change detection, are represented at the level of auditory cortex. Activations related to conscious change perception, independent of physical change, were found in the insula and the ACC. Moreover, our data provide evidence for significant effective connectivity between auditory cortex and the insula in the case of correctly detected auditory changes, but not for missed changes. This underlines the importance of the insula/anterior cingulate network for conscious change detection.	\N	\N
23258317	Steady state responses (SSRs), between 75 and 110 Hz, evoked by auditory amplitude modulated single or multiple tone stimuli, may be used to estimate objective hearing threshold. The aim of this study was to compare SSRs and click-evoked auditory brainstem responses (ABRs) in both ears of 20 adults (10 males and 10 females, aged between 24 and 36 years) with normal hearing threshold. Mean ABR threshold was found at 21.25 (± 5.9) dB nHL. Mean SSR threshold was found at 15.6 (± 9.6) dB nHL after a single frequency stimulus (1 kHz); at 10.5 (± 18.2) dB nHL and at 7.1 (± 12.4) dB nHL after bifrequency stimulation (0.5 and 2 kHz). SSR thresholds after multifrequency stimulation (0.5, 1, 2 and 4 kHz) were found, respectively, at 12.1 (± 12.9) dB nHL, 12.2 (± 12.8) dB nHL, 12.3 (± 8.3) dB nHL and 18.9 (± 17.2) dB nHL. Mean duration of the recording session was 6 min in the case of ABRs, while it was 25 min in the single frequency condition and 29 min in the multifrequency condition in the case of SSRs. SSRs can be used for frequency-specific objective audiometry. The multifrequency stimulation greatly reduces the whole testing time.	\N	\N
23258616	Modern digital hearing aids have provided improved fidelity over those of earlier decades for speech. The same however cannot be said for music. Most modern hearing aids have a limitation of their "front end," which comprises the analog-to-digital (A/D) converter. For a number of reasons, the spectral nature of music as an input to a hearing aid is beyond the optimal operating conditions of the "front end" components. Amplified music tends to be of rather poor fidelity. Once the music signal is distorted, no amount of software manipulation that occurs later in the circuitry can improve things. The solution is not a software issue. Some characteristics of music that make it difficult to be transduced without significant distortion include an increased sound level relative to that of speech, and the crest factor- the difference in dB between the instantaneous peak of a signal and its RMS value. Clinical strategies and technical innovations have helped to improve the fidelity of amplified music and these include a reduction of the level of the input that is presented to the A/D converter.	\N	\N
23263015	Anesthesiology requires performing visually oriented procedures while monitoring auditory information about a patient's vital signs. A concern in operating room environments is the amount of competing information and the effects that divided attention has on patient monitoring, such as detecting auditory changes in arterial oxygen saturation via pulse oximetry. The authors measured the impact of visual attentional load and auditory background noise on the ability of anesthesia residents to monitor the pulse oximeter auditory display in a laboratory setting. Accuracies and response times were recorded reflecting anesthesiologists' abilities to detect changes in oxygen saturation across three levels of visual attention in quiet and with noise. Results show that visual attentional load substantially affects the ability to detect changes in oxygen saturation concentrations conveyed by auditory cues signaling 99 and 98% saturation. These effects are compounded by auditory noise, up to a 17% decline in performance. These deficits are seen in the ability to accurately detect a change in oxygen saturation and in speed of response. Most anesthesia accidents are initiated by small errors that cascade into serious events. Lack of monitor vigilance and inattention are two of the more commonly cited factors. Reducing such errors is thus a priority for improving patient safety. Specifically, efforts to reduce distractors and decrease background noise should be considered during induction and emergence, periods of especially high risk, when anesthesiologists has to attend to many tasks and are thus susceptible to error.	\N	\N
23268357	Fine structure in the frequency response of distortion product otoacoustic emissions (DPOAEs) can severely limit the usefulness of DPOAEs in estimating auditory thresholds. Here, fine structure is removed by extracting the primary-source DPOAE component using the onset-decomposition technique (Vetešník et al., 2009) and auditory threshold estimates are compared to those obtained from DPOAEs in response to conventional, continuous two-tone stimulation. Auditory thresholds are predicted using the estimated distortion product thresholds (EDPTs), obtained from linear regression of input-output (I/O) functions of DPOAE pressure amplitude versus second-tone stimulus level (Boege and Janssen, 2002). The accuracy of the auditory-threshold predictions is derived by comparison with measured auditory thresholds. The parameters of the two primary stimulus tones of frequency f(1) and f(2) and levels of L(1) and L(2) are chosen as: f(2)/f(1) = 1.2 with 1.5 ≤ f(2) ≤ 2.5 kHz, and L(1) = 0.4L(2) + 39 dB SPL, with 25 ≤ L(2) ≤ 65 dB SPL. Data are from 12 normal-hearing subjects with profound DPOAE fine structure. 255 DPOAE I/O functions were measured for each of the two DPOAE paradigms. An EDPT value was accepted as reliable if: 1) the squared correlation coefficient, r(2) ≥ 0.8, 2) the regression slope, s(I/O) ≥ 0.2 μPa/dB, and 3) the standard deviation of the EDPT, σ(EDPT) ≤ 10 dB. The proportion of rejected I/O functions was 8% for onset-decomposition DPOAEs, and 25% for continuous-tone DPOAEs. Removal of data points from the saturation region of the DPOAE I/O function by an automated algorithm reduced the rejection rate, to zero for onset-decomposition DPOAEs, but to only 13% for continuous-tone DPOAEs. In the absence of saturated DPOAE responses, auditory thresholds were predicted with standard deviation of only 4 dB for onset-decomposition DPOAEs, but 12 dB for continuous-tone DPOAEs. In summary, by extracting the primary-source component of the DPOAE by the method of onset-decomposition it is possible to predict human auditory threshold with hitherto unattainable accuracy.	\N	\N
23268783	According to predictive coding models of sensory processing, stimulus expectations have a profound effect on sensory cortical responses. This was supported by experimental results, showing that fMRI repetition suppression (fMRI RS) for face stimuli is strongly modulated by the probability of stimulus repetitions throughout the visual cortical processing hierarchy. To test whether processing of voices is also affected by stimulus expectations, here we investigated the effect of repetition probability on fMRI RS in voice-selective cortical areas. Changing ('alt') and identical ('rep') voice stimulus pairs were presented to the listeners in blocks, with a varying probability of alt and rep trials across blocks. We found auditory fMRI RS in the nonprimary voice-selective cortical regions, including the bilateral posterior STS, the right anterior STG and the right IFC, as well as in the IPL. Importantly, fMRI RS effects in all of these areas were strongly modulated by the probability of stimulus repetition: auditory fMRI RS was reduced or not present in blocks with low repetition probability. Our results revealed that auditory fMRI RS in higher-level voice-selective cortical regions is modulated by repetition probabilities and thus suggest that in audition, similarly to the visual modality, processing of sensory information is shaped by stimulus expectation processes.	\N	\N
23274182	Speech recognition is improved when complementary visual information is available, especially under noisy acoustic conditions. Functional neuroimaging studies have suggested that the superior temporal sulcus (STS) plays an important role for this improvement. The spectrotemporal dynamics underlying audiovisual speech processing in the STS, and how these dynamics are affected by auditory noise, are not well understood. Using electroencephalography, we investigated how auditory noise affects audiovisual speech processing in event-related potentials (ERPs) and oscillatory activity. Spoken syllables were presented in audiovisual (AV) and auditory only (A) trials at three different auditory noise levels (no, low, and high). Responses to A stimuli were subtracted from responses to AV stimuli, separately for each noise level, and these responses were subjected to the statistical analysis. Central ERPs differed between the no noise and the two noise conditions from 130 to 150 ms and 170 to 210 ms after auditory stimulus onset. Source localization using the local autoregressive average procedure revealed an involvement of the lateral temporal lobe, encompassing the superior and middle temporal gyrus. Neuronal activity in the beta-band (16 to 32 Hz) was suppressed at central channels around 100 to 400 ms after auditory stimulus onset in the averaged AV minus A signal over the three noise levels. This suppression was smaller in the high noise compared to the no noise and low noise condition, possibly reflecting disturbed recognition or altered processing of multisensory speech stimuli. Source analysis of the beta-band effect using linear beamforming demonstrated an involvement of the STS. Our study shows that auditory noise alters audiovisual speech processing in ERPs localized to lateral temporal lobe and provides evidence that beta-band activity in the STS plays a role for audiovisual speech processing under regular and noisy acoustic conditions.	\N	\N
23275424	Fitting a cochlear implant (CI) for optimal speech perception does not necessarily optimize listening effort. This study aimed to show that listening effort may change between CI processing conditions for which speech intelligibility remains constant. Nineteen normal-hearing participants listened to CI simulations with varying numbers of spectral channels. A dual-task paradigm combining an intelligibility task with either a linguistic or nonlinguistic visual response-time (RT) task measured intelligibility and listening effort. The simultaneously performed tasks compete for limited cognitive resources; changes in effort associated with the intelligibility task are reflected in changes in RT on the visual task. A separate self-report scale provided a subjective measure of listening effort. All measures showed significant improvements with increasing spectral resolution up to 6 channels. However, only the RT measure of listening effort continued improving up to 8 channels. The effects were stronger for RTs recorded during listening than for RTs recorded between listening. The results suggest that listening effort decreases with increased spectral resolution. Moreover, these improvements are best reflected in objective measures of listening effort, such as RTs on a secondary task, rather than intelligibility scores or subjective effort measures.	\N	\N
23290461	The white matter bundles that underlie comprehension and production of language have been investigated for a number of years. Several studies have examined which fiber bundles (or tracts) are involved in auditory language processing, and which kind of language information is transmitted by which fiber tract. However, there is much debate about exactly which fiber tracts are involved, their precise course in the brain, how they should be named, and which functions they fulfill. Therefore, the present article reviews the available language-related literature, and educes a neurocognitive model of the pathways for auditory language processing. Besides providing an overview of the current methods used for relating fiber anatomy to function, this article details the precise anatomy of the fiber tracts and their roles in phonological, semantic and syntactic processing, articulation, and repetition.	\N	\N
23297922	Previous studies have suggested that cochlear implant users may have particular difficulties exploiting opportunities to glimpse clear segments of a target speech signal in the presence of a fluctuating masker. Although it has been proposed that this difficulty is associated with a deficit in linking the glimpsed segments across time, the details of this mechanism are yet to be explained. The present study introduces a method called Zebra-speech developed to investigate the relative contribution of simultaneous and sequential segregation mechanisms in concurrent speech perception, using a noise-band vocoder to simulate cochlear implants. One experiment showed that the saliency of the difference between the target and the masker is a key factor for Zebra-speech perception, as it is for sequential segregation. Furthermore, forward masking played little or no role, confirming that intelligibility was not limited by energetic masking but by across-time linkage abilities. In another experiment, a binaural cue was used to distinguish the target and the masker. It showed that the relative contribution of simultaneous and sequential segregation depended on the spectral resolution, with listeners relying more on sequential segregation when the spectral resolution was reduced. The potential of Zebra-speech as a segregation enhancement strategy for cochlear implants is discussed.	\N	\N
23298012	The present study explored the acoustic characteristics of prosodic cues that indicate a speaker's reluctance when giving permission or agreement using a single word ("okay"). Eight speakers (four male, four female) produced the recorded materials that were subsequently validated through a listening experiment using 12 normal-hearing listeners. Acoustic analyses revealed that significantly longer word duration was the cue used most consistently across speakers to communicate reluctance. Voice quality, fundamental voice frequency, and intensity cues also differed significantly between the two prosodic conditions, but the manner in which these cues were applied varied greatly across speakers.	\N	\N
23301004	For humans and animals, the ability to discriminate speech and conspecific vocalizations is an important physiological assignment of the auditory system. To reveal the underlying neural mechanism, many electrophysiological studies have investigated the neural responses of the auditory cortex to conspecific vocalizations in monkeys. The data suggest that vocalizations may be hierarchically processed along an anterior/ventral stream from the primary auditory cortex (A1) to the ventral prefrontal cortex. To date, the organization of vocalization processing has not been well investigated in the auditory cortex of other mammals. In this study, we examined the spike activities of single neurons in two early auditory cortical regions with different anteroposterior locations: anterior auditory field (AAF) and posterior auditory field (PAF) in awake cats, as the animals were passively listening to forward and backward conspecific calls (meows) and human vowels. We found that the neural response patterns in PAF were more complex and had longer latency than those in AAF. The selectivity for different vocalizations based on the mean firing rate was low in both AAF and PAF, and not significantly different between them; however, more vocalization information was transmitted when the temporal response profiles were considered, and the maximum transmitted information by PAF neurons was higher than that by AAF neurons. Discrimination accuracy based on the activities of an ensemble of PAF neurons was also better than that of AAF neurons. Our results suggest that AAF and PAF are similar with regard to which vocalizations they represent but differ in the way they represent these vocalizations, and there may be a complex processing stream between them.	\N	\N
23306571	The phenomenon of Late-Onset Unilateral Auditory Deprivation was first reported in 1984. However, a high number of unilateral hearing aid fittings are still carried out in cases of bilateral hearing loss, justified by non-auditory factors such as cost, vanity, misinformation and public health policies. To carry out behavioral and electrophysiological assessment of the auditory performance of adults using unilateral amplification compared with individuals exposed to bilateral symmetric auditory stimulation. Thirty five adults, all with symmetric bilateral sensorineural hearing loss, regular users of unilateral hearing aid, bilateral hearing aids and not users of hearing aids, were assessed on behavioral and electrophysiological tests. Variance analysis revealed that in the unilaterally fitted group, P300 latency was significantly greater in ears with auditory deprivation compared with those fitted with the hearing aid (p < 0.05). This same group also had poorer performance on the Sentence Recognition Test in Noise held in free field. These results corroborate findings in the literature showing that unilateral auditory deprivation can lead to physiological and perceptual changes.	\N	\N
23307427	Using a tactile variant of the negative-priming paradigm, we analyzed the influence of Gestalt grouping on the ability of participants to ignore distracting tactile information. The distance between participants' hands, to which the target and distractor stimuli were simultaneously delivered, was varied (near/touching hands vs. hands far apart). In addition, the influence of touching hands was controlled, as participants wore gloves and their hands were blocked from vision by a cover. The magnitude of the tactile negative-priming effect was modulated by the interaction between hand separation and whether or not gloves were worn. When the hands were touching, negative priming emerged only while wearing gloves that prevented direct skin-to-skin contact. In contrast, when the separation between the participants' hands was larger, negative priming emerged only when gloves were not worn. This pattern of results is interpreted in terms of the competing influences of two interacting Gestalt principles--namely, connectedness and proximity--on the processing of tactile distractors.	\N	\N
23316925	The event-related potential (ERP) correlates of sound detection are attenuated when eliciting sounds coincide with our own actions. The role of attention in this effect was investigated in two experiments by presenting tones separated by random intervals. In the homogeneous condition of Experiments 1 and 2, the same tone was repeated, whereas in the mixed condition of Experiment 1, tones with five different frequencies were presented. Participants performed a time-interval production task by marking intervals with keypresses in Experiment 1, and tried to produce keypress-tone coincidences in Experiment 2. Although the auditory ERPs were attenuated for coincidences, no modulation by the multiplicity of tone frequencies in Experiment 1, or by the task-relevancy of tones and coincidences in Experiment 2, was found. This suggests that coincidence-related ERP attenuation cannot be fully explained by voluntary attentional mechanisms.	\N	\N
23321588	To assess the auditory performance of Digisonic(®) cochlear implant users with electric stimulation (ES) and electro-acoustic stimulation (EAS) with special attention to the processing of low-frequency temporal fine structure. Six patients implanted with a Digisonic(®) SP implant and showing low-frequency residual hearing were fitted with the Zebra(®) speech processor providing both electric and acoustic stimulation. Assessment consisted of monosyllabic speech identification tests in quiet and in noise at different presentation levels, and a pitch discrimination task using harmonic and disharmonic intonating complex sounds ( Vaerenberg et al., 2011 ). These tests investigate place and time coding through pitch discrimination. All tasks were performed with ES only and with EAS. Speech results in noise showed significant improvement with EAS when compared to ES. Whereas EAS did not yield better results in the harmonic intonation test, the improvements in the disharmonic intonation test were remarkable, suggesting better coding of pitch cues requiring phase locking. These results suggest that patients with residual hearing in the low-frequency range still have good phase-locking capacities, allowing them to process fine temporal information. ES relies mainly on place coding but provides poor low-frequency temporal coding, whereas EAS also provides temporal coding in the low-frequency range. Patients with residual phase-locking capacities can make use of these cues.	\N	\N
23327452	In order to provide effective intervention for children with specific language impairment (SLI), it is crucial that there is an understanding of the underlying deficit in SLI. This study utilized a battery of phonological processing tasks to compare the phonological processing skills of children with SLI to typically-developing peers matched for age or language. The children with SLI had significantly poorer performance than age-matched peers on measures of phonological representations, phonological awareness, rapid automatized naming, phonological short-term memory, and one measure of working memory. Of particular significance, the SLI group also demonstrated significantly weaker performance than language-matched peers on one measure of phonological representations, and one measure of working memory. The findings provide some support for a phonological processing account of SLI and highlight the utility of using tasks that draw on a comprehensive model of speech processing to profile and consider children's phonological processing skills in detail.	\N	\N
23331545	The auditory N1 event-related potential has previously been observed to be attenuated for tones that are triggered by human actions. This attenuation is thought to be generated by motor prediction mechanisms and is considered to be important for agency attribution. The present study was designed to rigorously test the notion of action prediction-based sensory attenuation. Participants performed one of four voluntary actions on each trial, with each button associated with either predictable or unpredictable action effects. In addition, actions with each hand could result in action effects that were either congruent or incongruent with hand-specific prediction. We observed no significant differences in N1 amplitude between predictable and unpredictable tones. When contrasting action effects that were congruent or incongruent with hand-specific prediction, we observed significant attenuation for prediction-congruent compared to prediction-incongruent action-effects. These novel findings suggest that accurate action-effect prediction drives sensory attenuation of auditory stimuli. These findings have important implications for understanding the mechanisms of action-effect prediction and sensory attenuation, and may have clinical implications for studies investigating action awareness and agency in schizophrenia.	\N	\N
23334356	Several studies have shown that the ability to identify the timbre of musical instruments is reduced in cochlear implant (CI) users compared with normal-hearing (NH) listeners. However, most of these studies have focused on tasks that require specific musical knowledge. In contrast, the present study investigates the perception of timbre by CI subjects using a multidimensional scaling (MDS) paradigm. The main objective was to investigate whether CI subjects use the same cues as NH listeners do to differentiate the timbre of musical instruments. Three groups of 10 NH subjects and one group of 10 CI subjects were asked to make dissimilarity judgments between pairs of instrumental sounds. The stimuli were 16 synthetic instrument tones spanning a wide range of instrument families. All sounds had the same fundamental frequency (261 Hz) and were balanced in loudness and in perceived duration before the experiment. One group of NH subjects listened to unprocessed stimuli. The other two groups of NH subjects listened to the same stimuli passed through a four-channel or an eight-channel noise vocoder, designed to simulate the signal processing performed by a real CI. Subjects were presented with all possible combinations of pairs of instruments and had to estimate, for each pair, the amount of dissimilarity between the two sounds. These estimates were used to construct dissimilarity matrices, which were further analyzed using an MDS model. The model output gave, for each subject group, an optimal graphical representation of the perceptual distances between stimuli (the so-called "timbre space"). For all groups, the first two dimensions of the timbre space were strikingly similar and correlated strongly with the logarithm of the attack time and with the center of gravity of the spectral envelope, respectively. The acoustic correlate of the third dimension differed across groups but only accounted for a small proportion of the variance explained by the MDS solution. Surprisingly, CI subjects and NH subjects listening to noise-vocoded simulations gave relatively more weight to the spectral envelope dimension and less weight to the attack-time dimension when making their judgments than NH subjects listening to unprocessed stimuli. One possible reason for the relatively higher salience of spectral envelope cues in real and simulated CIs may be that the degradation of local fine spectral details produced a more stable spectral envelope across the stimulus duration. The internal representation of musical timbre for isolated musical instrument sounds was found to be similar in NH and in CI listeners. This suggests that training procedures designed to improve timbre recognition in CIs will indeed train CI subjects to use the same cues as NH listeners. Furthermore, NH subjects listening to noise-vocoded sounds appear to be a good model of CI timbre perception as they show the same first two perceptual dimensions as CI subjects do and also exhibit a similar change in perceptual weights applied to these two dimensions. This last finding validates the use of simulations to evaluate and compare training procedures to improve timbre perception in CIs.	\N	\N
23336003	A large-scale subjective survey was conducted in six shopping malls in Harbin City, China, to determine the influence of social and behavioural characteristics of users on their evaluation of subjective loudness and acoustic comfort. The analysis of social characteristics shows that evaluation of subjective loudness is influenced by income and occupation, with correlation coefficients or contingency coefficients of 0.10 to 0.40 (p<0.05 or p<0.01). Meanwhile, evaluation of acoustic comfort evaluation is influenced by income, education level, and occupation, with correlation coefficients or contingency coefficients of 0.10 to 0.60 (p<0.05 or p<0.01). The effect of gender and age on evaluation of subjective loudness and acoustic comfort is statistically insignificant. The effects of occupation are mainly caused by the differences in income and education level, in which the effects of income are greater than that of education level. In terms of behavioural characteristics, evaluation of subjective loudness is influenced by the reason for visit, frequency of visit, and length of stay, with correlation coefficients or contingency coefficients of 0.10 to 0.40 (p<0.05 or p<0.01). Evaluation of acoustic comfort is influenced by the reason for visit to the site, the frequency of visit, length of stay, and also season of visit, with correlation coefficients of 0.10 to 0.30 (p<0.05 or p<0.01). In particular, users who are waiting for someone show lower evaluation of acoustic comfort, whereas users who go to shopping malls more than once a month show higher evaluation of acoustic comfort. On the contrary, the influence of the period of visit and the accompanying persons are found insignificant.	\N	\N
23339556	This study explored the developmental trends and phonetic category formation in bilingual children and adults. Participants included 30 fluent Spanish-English bilingual children, aged 8-11, and bilingual adults, aged 18-40. All completed gating tasks that incorporated code-mixed Spanish-English stimuli. There were significant differences in performance according to phonotactic construction of the stimuli, with fastest word recognition on words with voiceless initial consonants. Analysis of developmental trends revealed significant differences in children's performance by grade level and fastest recognition on English voiceless initial consonants than Spanish voiceless initial consonants. Differences in voice onset time between English and Spanish may have contributed to quicker recognition of English voiceless consonants than Spanish voiceless consonants. It is also possible that increased exposure to both spoken and written English may account for faster recognition of English voiceless words than Spanish voiceless words. In conclusion, multiple factors may influence perception of a second language.	\N	\N
23340379	Since deafness is the most common sensorineural disorder in humans, better understanding of the underlying causes is necessary to improve counseling and rehabilitation. A Dutch family with autosomal dominantly inherited sensorineural hearing loss was clinically and genetically assessed. The MYO6 gene was selected to be sequenced because of similarities with other, previously described DFNA22 phenotypes and a pathogenic c.3610C > T (p.R1204W) mutation was found to co-segregate with the disease. This missense mutation results in a flat configured audiogram with a mild hearing loss, which becomes severe to profound and gently to steeply downsloping later in life. The age-related typical audiograms (ARTA) constructed for this family resemble presbyacusis. Speech audiometry and results of loudness scaling support the hypothesis that the phenotype of this specific MYO6 mutation mimics presbyacusis.	\N	\N
23341954	Two experiments investigated deaf individuals' ability to discriminate between same-sex talkers based on vibrotactile stimulation alone. Nineteen participants made same/different judgments on pairs of utterances presented to the lower back through voice coils embedded in a conforming chair. Discrimination of stimuli matched for F0, duration, and perceived magnitude was successful for pairs of spoken sentences in Experiment 1 (median percent correct = 83%) and pairs of vowel utterances in Experiment 2 (median percent correct = 75%). Greater difference in spectral tilt between "different" pairs strongly predicted their discriminability in both experiments. The current findings support the hypothesis that discrimination of complex vibrotactile stimuli involves the cortical integration of spectral information filtered through frequency-tuned skin receptors.	\N	\N
23351131	The suppression of the auditory N1 event-related potential (ERP) to self-initiated sounds became a popular tool to tap into sensory-specific forward modeling. It is assumed that processing in the auditory cortex is attenuated due to a match between sensory stimulation and a specific sensory prediction afforded by a forward model of the motor command. The present study shows that N1 suppression was dramatically increased with long (≈ 3 s) stimulus onset asynchronies (SOA), whereas P2 suppression was equal in all SOA conditions (0.8, 1.6, 3.2 s). Thus, the P2 was found to be more sensitive to self-initiation effects than the N1 with short SOAs. Moreover, only the unspecific but not the sensory-specific N1 components were suppressed for self-initiated sounds suggesting that N1-suppression effects mainly reflect an attenuated orienting response. We argue that the N1-suppression effect is a rather indirect measure of sensory-specific forward models.	\N	\N
23351849	This work investigates the nature of the comprehension impairment in Wernicke's aphasia (WA), by examining the relationship between deficits in auditory processing of fundamental, non-verbal acoustic stimuli and auditory comprehension. WA, a condition resulting in severely disrupted auditory comprehension, primarily occurs following a cerebrovascular accident (CVA) to the left temporo-parietal cortex. Whilst damage to posterior superior temporal areas is associated with auditory linguistic comprehension impairments, functional-imaging indicates that these areas may not be specific to speech processing but part of a network for generic auditory analysis. We examined analysis of basic acoustic stimuli in WA participants (n = 10) using auditory stimuli reflective of theories of cortical auditory processing and of speech cues. Auditory spectral, temporal and spectro-temporal analysis was assessed using pure-tone frequency discrimination, frequency modulation (FM) detection and the detection of dynamic modulation (DM) in "moving ripple" stimuli. All tasks used criterion-free, adaptive measures of threshold to ensure reliable results at the individual level. Participants with WA showed normal frequency discrimination but significant impairments in FM and DM detection, relative to age- and hearing-matched controls at the group level (n = 10). At the individual level, there was considerable variation in performance, and thresholds for both FM and DM detection correlated significantly with auditory comprehension abilities in the WA participants. These results demonstrate the co-occurrence of a deficit in fundamental auditory processing of temporal and spectro-temporal non-verbal stimuli in WA, which may have a causal contribution to the auditory language comprehension impairment. Results are discussed in the context of traditional neuropsychology and current models of cortical auditory processing.	\N	\N
23354172	Visual speech inputs can enhance auditory speech information, particularly in noisy or degraded conditions. The natural statistics of audiovisual speech highlight the temporal correspondence between visual and auditory prosody, with lip, jaw, cheek and head movements conveying information about the speech envelope. Low-frequency spatial and temporal modulations in the 2-7 Hz range are of particular importance. Dyslexic individuals have specific problems in perceiving speech envelope cues. In the current study, we used an audiovisual noise-vocoded speech task to investigate the contribution of low-frequency visual information to intelligibility of 4-channel and 16-channel noise vocoded speech in participants with and without dyslexia. For the 4-channel speech, noise vocoding preserves amplitude information that is entirely congruent with dynamic visual information. All participants were significantly more accurate with 4-channel speech when visual information was present, even when this information was purely spatio-temporal (pixelated stimuli changing in luminance). Possible underlying mechanisms are discussed.	\N	\N
23357092	Here we present two experiments investigating the implicit orienting of attention over time by entrainment to an auditory rhythmic stimulus. In the first experiment, participants carried out a detection and discrimination tasks with auditory and visual targets while listening to an isochronous, auditory sequence, which acted as the entraining stimulus. For the second experiment, we used musical extracts as entraining stimulus, and tested the resulting strength of entrainment with a visual discrimination task. Both experiments used reaction times as a dependent variable. By manipulating the appearance of targets across four selected metrical positions of the auditory entraining stimulus we were able to observe how entraining to a rhythm modulates behavioural responses. That our results were independent of modality gives a new insight into cross-modal interactions between auditory and visual modalities in the context of dynamic attending to auditory temporal structure.	\N	\N
23362674	It has been shown that humans are able to recognise their own movement. While visual cues have been amply studied, the contribution of auditory cues is not clear. Our aim was to investigate the role of temporal auditory cues in the identification of one's own or others' performance in a complex movement--a golf swing. We investigated whether golfers are able to discriminate between the sounds associated with their own swings and other golfers' swings, by using the relative timing and the overall duration of the movement. The sounds produced by the participants performing 65 m shots have been recorded and used to create the stimuli. The experimental conditions were: participants' swing sounds and the sounds of other golfers having equal both relative timing and overall duration, equal relative timing but different overall duration, different relative timing but equal overall duration, and both different relative timing and overall duration. The task of the participants was to say whether each sound corresponded or did not correspond to their own swing. Results show that golfers are able to recognise their own movements, but they also recognise as their own the sound produced by other athletes having equal both relative timing and overall duration.	\N	\N
23363116	Detection thresholds for 100 ms of either 5- or 20-Hz frequency modulation (FM) were measured at various temporal positions within a 600-ms, 4-kHz pure-tone carrier. The results indicated that the temporal position of the signal relative to the fringe influences detection thresholds, including an effect that is reminiscent of auditory backward recognition masking. A task involving frequency increments, rather than sinusoidal FM, yielded similar results. Additional manipulation of total carrier duration indicated that FM detection thresholds improve as the duration of the forward fringe increases, while a backward fringe only degrades performance in the absence of any forward fringe. The results suggest that listeners are insensitive to subtle frequency changes that occur at the onset of a longer stimulus and that the interaction between the opposing effects of the forward and backward fringes is not additive.	\N	\N
23363122	The vocal tract length of a speaker is the primary determinant of the range of formant frequencies (FFs) produced by that speaker. Listeners have demonstrated sensitivity to the average FFs produced by voices, for example, in estimating the relative heights of two speakers based on their speech. However, it is not known whether they can learn to identify voices based on the acoustic characteristic associated with the average FFs produced by a voice (this characteristic will be referred to as FF-scaling). To investigate this, a series of vowels corresponding to voices that differed in their average f0 and/or FF-scaling were synthesized. Listeners (n = 71) were trained to identify these voices using a training procedure where, for each trial, they heard the vowels representing a voice and then had to identify the stimulus voice from among a series of candidate voices that differed in terms of their FF-scaling and/or their f0. Results indicate that listeners can identify voices on the basis of FF-scaling quite accurately and consistently after only a short training session and that, although f0 weakly influences these estimates, they are most strongly determined by the stimulus FFs.	\N	\N
23363188	Good localization accuracy depends on an auditory spatial map that provides consistent binaural information across frequency and level. This study investigated whether mapping bilateral cochlear implants (CIs) independently contributes to distorted perceptual spatial maps. In a meta-analysis, interaural level differences necessary to perceptually center sound images were calculated for 127 pitch-matched pairs of electrodes; many needed large current adjustments to be perceptually centered. In a separate experiment, lateralization was also found to be inconsistent across levels. These findings suggest that auditory spatial maps are distorted in the mapping process, which likely reduces localization accuracy and target-noise separation in bilateral CIs.	\N	\N
23363191	Listeners presented with noise were asked to press a key whenever they heard the vowels [a] or [i:]. The noise had a random spectrum, with levels in 60 frequency bins changing every 0.5 s. Reverse correlation was used to average the spectrum of the noise prior to each key press, thus estimating the features of the vowels for which the participants were listening. The formant frequencies of these reverse-correlated vowels were similar to those of their respective whispered vowels. The success of this response-triggered technique suggests that it may prove useful for estimating other internal representations, including perceptual phenomena like tinnitus.	\N	\N
23363193	Speech understanding difficulties for older adults (OAs) are well documented. Very little is known about whether age-related changes affect their speech production as well. Intelligibility of conversational and clear speech sentences produced by five OA talkers was examined. The results of the sentence-in-noise listening tests revealed that OAs enhanced their intelligibility for young adult (YA) listeners through clear speech modifications. Importantly, though, OAs were less effective at improving their speech to benefit listeners compared to YA talkers [reported in Smiljanic and Bradlow, J. Acoust. Soc. Am. 118(3), 1677-1688 (2005)]. The results suggest that auditory and cognitive changes across lifespan can affect OA's speech patterns and intelligibility.	\N	\N
23363194	Stilp and Kluender [(2010). Proc. Natl. Acad. Sci. U.S.A. 107(27), 12387-12392] reported measures of sensory change over time (cochlea-scaled spectral entropy, CSE) reliably predicted sentence intelligibility for normal-hearing listeners. Here, implications for listeners with atypical hearing were explored using noise-vocoded speech. CSE was parameterized as Euclidean distances between biologically scaled spectra [measured before sentences were noise vocoded (CSE)] or between channel amplitude profiles in simulated cochlear-implant processing [measured after vocoding (CSE(CI))]. Sentence intelligibility worsened with greater amounts of information replaced by noise; patterns of performance did not differ between CSE and CSE(CI). Results demonstrate the importance of information-bearing change for speech perception in simulated electric hearing.	\N	\N
23366748	Emotional arousal, or affective patterns, can be probed using observable bioelectric signals, in particular using the fluctuations of electroencephalographic potentials from the human scalp. Hearing impairment related to increased threshold of audio tone detection may cause the loss of intelligibility of speech resulting in an innate automatic emotional response. An adaptive support vector machine can be trained to identify a subject's unique affective response based upon an audiogram hearing test. This paper presents the efficacy of our model, initial SVM classification data, and discusses potential application.	\N	\N
23398728	Superior semi-circular canal dehiscence (SSCD) is a known cause of hearing loss. This study quantifies hearing loss in SSCD ears in a frequency-specific fashion. A meta-analysis of English language literature pertaining to SSCD was performed, with extraction and evaluation of available human audiometric data. Our own institution's case series of SSCD patients was also similarly analysed. Hearing loss in SSCD ears was compared to same patient control ears and to age-matched normative audiometric data. Ears with SSCD had statistically significant worse hearing as compared to both normative data and to own normal ear controls at 2000 Hz and below. The effect appears to diminish with increasing frequency. The presence of statistically significant conductive hearing loss in the low frequencies was confirmed for SSCD ears. SSCD may also predispose ears to high frequency sensorineural hearing loss.	\N	\N
23404529	The purpose of the study was to investigate the potential clinical advantages of incorporating a contralateral routing of signals (CROS) microphone in unilateral cochlear implant (CI) users. A prospective study was undertaken on a group of 21 postlingually deafened adults who were all implanted with the same multichannel CI system. Performance with a unilateral CI was compared with performance using both a unilateral implant and a CROS microphone system worn on the opposite site (CI-CROS). Speech understanding using the AzBio sentence was evaluated in quiet, with speech presented at 0° and 270° azimuth in the horizontal plane. Speech understanding in noise was performed with speech at 0°, and noise at 0°, 90°, and 270°. A significant gain in speech understanding using CI-CROS compared to the unilateral CI alone was found in quiet when speech was presented at 270° (average improvement of 8.8%, P < .01). Participants also demonstrated statistically significant improvement using CI-CROS compared with the unilateral CI alone when noise was presented at 90° and speech at 0° (average improvement of 6.7%, P < .01). Adding a contralateral microphone to a unilateral CI resulted in a significant improvement in speech understanding in different conditions. This method could provide a greater cost/benefit ratio than bilateral CIs and be a potential improvement for those who are not candidates for bilateral CIs.	\N	\N
23418635	Cochlear implantation (CI) has proven in long term prospective trials to reduce significantly incapacitating tinnitus in single sided deafness (SSD). Discussion arises whether electrical stimulation near the round window (RW) is also able to reduce tinnitus. to assess whether electrical stimulation of the basal first 4 intracochlear electrodes of a CI could sufficiently reduce tinnitus and to compare these results with stimulation with all CI electrodes. 7 patients who met the criteria of severe tinnitus due to SSD were implanted with a Med-El Sonata Ti100 with a FlexSoftTM or Flex24TM electrode. After 4 weeks only the basal electrode pair (E12) nearest to the RW was activated. Each week the following pair was activated until the 4th pair.Thereafter all electrodes were activated. Tinnitus was assessed before CI surgery and before each electrode pair was activated. When all electrodes were fitted, evaluation was done after 1, 3 and 6 months.Tinnitus was assessed with Visual Analogue Scale (VAS) for loudness, psychoacoustic tinnitus loudness comparison at 1 kHz and Tinnitus Questionnaire (TQ) for the effect on quality of life. To evaluate the natural evolution, a tightly matched control group with severe tinnitus due to SSD was followed prospectively. All the tinnitus outcome measures remained unchanged with 1, 2, 3 or 4 activated electrode pairs. With complete CI activation, the tinnitus decreased significantly comparable with earlier reports.Pre-implantation the tinnitus loudness was 8.2/10 on the VAS and was reduced to 4.1/10 6 months postimplantation.Psychometrically the loudness level went from 21.7 dB SL (SD: 16.02) to 7.5 dB SL (SD: 5.24)and the TQ from 60/84 to 39/84. The non-implanted group had no decrease of the tinnitus, the average VAS remained stable at 8.9/10 throughout the follow-up period of 6 months. with the current stimulation parameters electrical stimulation in the first 8e10 mm of the basal part of the scala tympani is insufficient to reduce tinnitus. However, stimulation over the complete CI length yields immediate tinnitus reduction confirming earlier results.	\N	\N
23421638	BACKGROUND/STUDY CONTEXT: The perception of naturalistic events depends on the ability to integrate perceptual information from multiple sensory systems. Currently, little is known about how multisensory integration is affected by normal aging. The authors conducted two experiments to investigate audiovisual temporal processing in younger (18-29 years) and older (70+ years) adults. In both experiments, participants were presented with a brief visual stimulus and a brief auditory stimulus separated by various temporal offsets, and participants judged which stimulus was presented first. In Experiment 1, the auditory and visual stimuli were presented from the same perceived location, whereas in Experiment 2 they were presented from different locations. The authors found no effect of stimulus location, and no evidence of age-related declines in performance in either experiment. Older adults appear to retain the ability to discriminate the temporal order of audiovisual stimuli and can perform similarly to younger adults.	\N	\N
23422927	Prosody includes suprasegmental components of speech, such as intonation and rate, which add meaning beyond the words being spoken. Sensitivity to pragmatic prosody could improve communication within conversations. These studies investigated adults' and preschoolers' sensitivity to pragmatic prosody. Experiment 1 demonstrated that adults and children comprehend pragmatic prosody; they selected fast actions when descriptions were spoken fast versus when descriptions were spoken slowly. Experiment 2 demonstrated that adults and children spontaneously produce pragmatic prosody-their descriptions of fast actions were faster than their descriptions of slow actions-even when it was not necessary for the task. These studies conclude that children, like adults, are capable of using and producing pragmatic prosody; however, children are less sensitive than adults to subtle prosodic distinctions.	\N	\N
23426091	To maintain optimal understanding, persons with sensorineural hearing loss (SNHL) often report a need for increased attention, concentration, and "listening effort" compared with persons without hearing loss. It is generally assumed that this increased effort is related to subjective reports of mental fatigue in persons with hearing loss. Although the benefits of hearing aids for improving intelligibility are well documented, their impact on listening effort and mental fatigue are less clear. This study used subjective and objective measures to examine the effects of hearing aid use and advanced hearing aid features on listening effort and mental fatigue in adults with SNHL. Sixteen adults (aged 47-69 years) with mild to severe sloping SNHL participated. A dual-task paradigm assessed word recognition, word recall, and visual reaction times (RTs) to objectively quantify listening effort and fatigue. Mental fatigue was operationally defined as a decrement in performance over the duration of the experiment (approximately 1 hr). Participants were fitted with study hearing aids and tested unaided and in two aided conditions (omnidirectional and with directional processing and digital noise reduction active). Subjective ratings of listening effort experienced during the day and ratings of fatigue and attentiveness immediately before and after the dual-task were also obtained. Word recall was better and dual-task RTs were significantly faster in the aided compared with unaided conditions, suggesting a decrease in listening effort when listening aided. Word recognition and recall in unaided and aided conditions remained relatively stable over the duration of the dual-task, suggesting these processes were resistant to mental fatigue. In contrast, dual-task RTs systematically increased over the duration of the speech task when listening unaided, consistent with development of mental fatigue. However, dual-task RTs remained stable over time in both aided conditions suggesting that hearing aid use reduced susceptibility to mental fatigue. Subjective ratings of fatigue and attentiveness also increased significantly after completion of the dual-task; however, no differences between unaided and aided subjective ratings were observed. Correlation analyses between subjective and objective measures of listening effort and mental fatigue showed no strong or consistent relationship. Likewise, subject variables such as age and degree of hearing loss showed no strong or consistent relationship to either subjective or objective measures of listening effort or mental fatigue. Results from subjective and select objective measures suggest sustained speech-processing demands can lead to mental fatigue in persons with hearing loss. It is important to note that the use of clinically fit hearing aids may reduce listening effort and susceptibility to mental fatigue associated with sustained speech-processing demands. The present study design did not reveal additional benefits, in terms of reduced listening effort or fatigue, from use of directional processing and digital noise-reduction algorithms. However, experimental design limitations suggest further work in this area is needed. Finally, subjective and objective measures of listening effort and mental fatigue due to sustained speech-processing demands, were not strongly associated, suggesting that these measures may assess different aspects of listening effort and mental fatigue.	\N	\N
23438484	Two experiments tested the effect of exposure to masked phobic stimuli at a very brief stimulus onset asynchrony on reducing the subjective experience of fear caused by in vivo exposure to a feared object. In the main experiment, 35 spider-fearful and 35 non-fearful participants were identified with a questionnaire and a behavioural avoidance test (BAT) with a live tarantula. One week later, they were individually administered one of two continuous series of masked images: spiders or flowers. They engaged in the BAT again immediately thereafter. They provided ratings of subjective fear at the end of each BAT (pre- and post-manipulation). Very brief exposure to images of spiders reduced the fearful group's and not the non-fearful group's experience of fear at the end of the BAT. This effect was replicated with another sample of 26 spider-fearful participants from the same population. Theoretical implications are discussed.	\N	\N
23442566	Performance in tone perception and production are correlated in prelingually deafened pediatric cochlear implant (CI) users across individuals. Demographic variables, such as age at implantation, contribute to the performance variability. Poor representation of pitch information in CI devices hinders pitch perception and affects perception of lexical tones in cochlear implant users who speak tonal languages. One hundred ten Mandarin-speaking, prelingually deafened CI subjects and 125 typically developing, normal-hearing subjects were recruited from Beijing, China. Lexical tone perception was measured using a computerized tone contrast test. Tone production was judged by native Mandarin-speaking adult listeners as well as analyzed acoustically and with an artificial neural network. A general linear model analysis was performed to determine factors that accounted for performance variability. CI subjects scored ≈ 67% correct on the lexical tone perception task. The degree of differentiation of tones produced by the CI group was significantly lower than the control group as revealed by acoustic analysis. Tone production performance assessed by the neural network was highly correlated with that evaluated by human listeners. There was a moderate correlation between the overall tone perception and production performance across CI subjects. Duration of implant use and age at implantation jointly explained ≈ 29% of the variance in the tone perception performance. Age at implantation was the only significant predictor for tone production performance in the CI subjects. Tone production performance in pediatric CI users is dependent on accurate perception. Early implantation predicts a better outcome in lexical tone perception and production.	\N	\N
23446715	It is generally agreed that the auditory perception skills of children with developmental language disorders are more limited than those of typically developing children. It is not easy to determine exactly how the capacity to discriminate and the capacity to pronounce phonemes influence each other in children with language disorders. For most authors, the inability to discriminate certain phonemes accurately causes a developmental delay in pronunciation, whereas others claim the influence is mutual. The aim of this study is to determine in which consonants perceptive difficulty is more likely to occur and in which cases there is a greater probability of difficulty when it comes to articulating them. The sample used in the study consisted of 86 children with a mean age of 4 years and 7 months. The phonological processes involved in simplifying speech were identified. Their errors were used as the basis on which to construct and apply a specific speech perception test. The relationship between the articulatory and perceptive skills of children with substitutive processes were analysed by means of two comparisons: first, in all the processes detected taken as a whole and, second, in the three most frequent substitutive processes. These analyses were carried out to determine whether the nature of the consonant implied a greater probability of perceptive difficulty. The findings provide information about a relation between the articulatory and perceptive skills, and about whether the nature of the consonant determines a higher probability of perceptive or articulatory difficulties. These results can be of value in the assessment, design and effectiveness of speech therapy programmes.	\N	\N
23448103	To evaluate the auditory brainstem response (ABR) amplitudes evoked by tone pip and narrowband chirp (NB CE-Chirp) stimuli when testing post-screening newborns and to determine the difference in estimated hearing level correction values. Tests were performed with tone pips and NB CE-Chirps at 4 kHz or 1 kHz. The response amplitude, response quality (Fmp), and residual noise were compared for both stimuli. Thirty babies (42 ears) who passed our ABR discharge criterion at 4 kHz following referral from their newborn hearing screen. Overall, NB CE-Chirp responses were 64% larger than the tone pip responses, closer to those evoked by clicks. Fmp was significantly higher for NB CE-Chirps. It is anticipated that there could be significant reductions in test time for the same signal to noise ratio by using NB CE-Chirps when testing newborns. This effect may vary in practice and is likely to be most beneficial for babies with low amplitude ABR responses. We propose that the ABR nHL threshold to eHL correction for NB CE-Chirps should be approximately 5 dB less than the corrections for tone pips at 4 and 1 kHz.	\N	\N
23453221	This study examined the ability of prelingually deaf children with bilateral implants to identify emotion (i.e. happiness or sadness) in speech and music. Participants in Experiment 1 were 14 prelingually deaf children from 5-7 years of age who had bilateral implants and 18 normally hearing children from 4-6 years of age. They judged whether linguistically neutral utterances produced by a man and woman sounded happy or sad. Participants in Experiment 2 were 14 bilateral implant users from 4-6 years of age and the same normally hearing children as in Experiment 1. They judged whether synthesized piano excerpts sounded happy or sad. Child implant users' accuracy of identifying happiness and sadness in speech was well above chance levels but significantly below the accuracy achieved by children with normal hearing. Similarly, their accuracy of identifying happiness and sadness in music was well above chance levels but significantly below that of children with normal hearing, who performed at ceiling. For the 12 implant users who participated in both experiments, performance on the speech task correlated significantly with performance on the music task and implant experience was correlated with performance on both tasks. Child implant users' accurate identification of emotion in speech exceeded performance in previous studies, which may be attributable to fewer response alternatives and the use of child-directed speech. Moreover, child implant users' successful identification of emotion in music indicates that the relevant cues are accessible at a relatively young age.	\N	\N
23458475	The purpose of this study was to measure real-ear aided and saturated responses of SpeechEasy™ devices and compare responses while devices delivered altered auditory feedback (AAF) and non-altered feedback (NAF). A repeated measures quasi-experimental design was employed. Ten people fitted with completely-in-the-canal or open fit behind-the-ear devices participated. Probe microphone measures were obtained with speech, and 17 chirp stimuli presented at 75 dB and 85 dB SPL, respectively. Measurements were compared with devices delivering AAF (i.e. delayed and frequency shifted) versus NAF. Maximum outputs were approximately 100-105 dB SPL in the 2000-4000 Hz range. Statistically significant differences in device SPL output as a function of device setting (AAF vs. NAF) were found for seven chirp stimuli (p <.05) when levels were sampled at points that were not temporally aligned with the output chirps but not for speech stimulus (p = .17). Device output varied across individuals and with open fit devices dominated by ear canal resonance effects. Real-ear aided responses were equivalent with speech input when devices delivered AAF and NAF. Real-ear saturated responses were not, however, comparable between AAF and NAF settings and may be underestimated if AAF delay is not accounted for.	\N	\N
23461765	Advantages associated with the left ear (right brain hemisphere) have been reported in some studies. Of these, some have specifically suggested that the left ear has a more heightened ability to detect emotional tones. Meanwhile others have pointed to factors such as age and gender as potentially leading to manifestations of human laterality. This study investigates which brain hemisphere is more involved in emotional processing of auditory information in Arab participants. We aimed to replicate the previous studies because no single study has been done in the Arabic region previously. Additionally, people in this region prefer to use the right side of their body, e.g., hand, ear, foot, etc., for most daily tasks. To acquire data a dichotic listening task (DLT) was administered to 28 male and 23 female (Edinburgh, UK) university students aged 19 to 38; 13 were left-handed and 38 were right-handed. The results showed a significant left ear advantage in the auditory processing of emotional information. There was a significant negative correlation between ear preference and handedness. Left ear advantage related only to handedness. Thus right-handed participants were more likely than left-handers to have a left ear advantage. The relationship between ear preference and gender was non-significant. The conclusion that might be drawn from this study is that the left ear (right hemisphere) is more involved in emotional processing than the right ear (left hemisphere), especially for right-handed people.	\N	\N
23462430	We set out to determine whether extra-striate ventral stream function was compromised in amblyopia and to compare any observed deficit with previous data on comparable dorsal stream function. We devised a multi-element orientation task where orientation coherence sensitivity could be measured in a comparable way to motion coherence. The use of spatial frequency narrowband elements allowed for accurate correction of any upstream contrast sensitivity influence and ensured that the orientation bandwidth of our elements did not covary with the measured coherence. Using a standard equivalent noise analysis, we varied both the local orientation bandwidth of individual elements as well as the global orientation bandwidth of the element array to obtain estimates of both local and global internal noise and efficiency. The results show that for this ventral stream task there is only a subtle amblyopic deficit in processing global orientation relative to control observers. This deficit is present for both amblyopic and fixing eyes, and appears to reflect poorer efficiency in processing local orientation, suggesting a subtle deficit at the input stage to extra-striate cortex where orientation coherence is processed.	\N	\N
23463992	A decision weight analysis is used to investigate transition bandwidths [Berg (2007). J. Acoust. Soc. Am. 121, 3639-2645]. The psychophysical task is similar to a standard profile analysis experiment except that the spacing of the tones comprising the stimuli is linear and very narrow (e.g., 20 Hz). An increment in the level of the central tone constitutes the signal. Pitch cues and single channel energy cues are degraded with randomization procedures. Thresholds increase as the number of tones comprising the stimulus (n) increases up to a transition bandwidth and then decrease or stay constant with further increases in n. It is proposed that the transition bandwidth reflects a discrete change in the underlying process, with a temporal process (e.g., envelope processor) dominating for stimulus bandwidths less than the transition bandwidth and a process of spectral profile analysis at wider bandwidths. Estimates of decision weights support the proposal.	\N	\N
23464020	Just noticeable differences in interaural correlation (ρ-jnds) from diffuse sound field reference correlations are obtained. In a three-interval, three-alternative forced-choice procedure, ρ-jnds are measured for positive and negative deviations from nine narrowband reference conditions. Stimuli are 1 equivalent rectangular bandwidth wide noise bursts with center frequencies between 165 and 1500 Hz. The frequency dependent reference correlation (ρref) is determined by the simulated interaural correlation under ideal diffuse sound field conditions. Results show that the interaural correlation at threshold for deviation toward the positive correlation range follows the reference curve in a nonlinear fashion. For deviation toward the negative correlation range the interaural correlation at threshold is further afar the reference curve and does not markedly resemble its trend. The results indicate that the previously found asymmetry for correlation discrimination from uncorrelated broadband stimuli to the positive and negative correlation range becomes less pronounced for narrowband stimuli. For positive deviation, the highest jnds are found for the region where the reference curve occupies the global minimum in ρref; despite that, the interaural correlation at threshold for positive deviation exhibits its lowest value at that point.	\N	\N
23464027	Acousticians generally assess the acoustic qualities of a concert hall or any other room using impulse response-based measures such as the reverberation time, clarity index, and others. These parameters are used to predict perceptual attributes related to the acoustic qualities of the room. Various studies show that these physical measures are not able to predict the related perceptual attributes sufficiently well under all circumstances. In particular, it has been shown that physical measures are dependent on the state of occupation, are prone to exaggerated spatial fluctuation, and suffer from lacking discrimination regarding the kind of acoustic stimulus being presented. Accordingly, this paper proposes a method for the derivation of signal-based measures aiming at predicting aspects of room acoustic perception from content specific signal representations produced by a binaural, nonlinear model of the human auditory system. Listening tests were performed to test the proposed auditory parameters for both speech and music. The results look promising; the parameters correlate with their corresponding perceptual attributes in most cases.	\N	\N
23464028	Several lines of evidence indicate that auditory temporal resolution improves over childhood, whereas other data implicate the development of processing efficiency. The present study used the masking period pattern paradigm to examine the maturation of temporal processing in normal-hearing children (4.8 to 10.7 yrs) compared to adults. Thresholds for a brief tone were measured at 6 temporal positions relative to the period of a 5-Hz quasi-square-wave masker envelope, with a 20-dB modulation depth, as well as in 2 steady maskers. The signal was a pure tone at either 1000 or 6500 Hz, and the masker was a band of noise, either spectrally wide or narrow (21.3 and 1.4 equivalent rectangular bandwidths, respectively). Masker modulation improved thresholds more for wide than narrow bandwidths, and adults tended to receive more benefit from modulation than young children. Fits to data for the wide maskers indicated a change in window symmetry with development, reflecting relatively greater backward masking for the youngest listeners. Data for children >6.5 yrs of age appeared more adult-like for the 6500- than the 1000-Hz signal. Differences in temporal window asymmetry with listener age cannot be entirely explained as a consequence of a higher criterion for detection in children, a form of inefficiency.	\N	\N
23464037	In spoken word identification and memory tasks, stimulus variability from numerous sources impairs performance. In the current study, the influence of foreign-accent variability on spoken word identification was evaluated in two experiments. Experiment 1 used a between-subjects design to test word identification in noise in single-talker and two multiple-talker conditions: multiple talkers with the same accent and multiple talkers with different accents. Identification performance was highest in the single-talker condition, but there was no difference between the single-accent and multiple-accent conditions. Experiment 2 further explored word recognition for multiple talkers in single-accent versus multiple-accent conditions using a mixed design. A detriment to word recognition was observed in the multiple-accent condition compared to the single-accent condition, but the effect differed across the language backgrounds tested. These results demonstrate that the processing of foreign-accent variation may influence word recognition in ways similar to other sources of variability (e.g., speaking rate or style) in that the inclusion of multiple foreign accents can result in a small but significant performance decrement beyond the multiple-talker effect.	\N	\N
23466938	Change deafness describes the failure to perceive even intense changes within complex auditory input, if the listener does not attend to the changing sound. Remarkably, previous psychophysical data provide evidence that this effect occurs independently of successful stimulus encoding, indicating that undetected changes are processed to some extent in auditory cortex. Here we investigated cortical representations of detected and undetected auditory changes using electroencephalographic (EEG) recordings and a change deafness paradigm. We applied a one-shot change detection task, in which participants listened successively to three complex auditory scenes, each of them consisting of six simultaneously presented auditory streams. Listeners had to decide whether all scenes were identical or whether the pitch of one stream was changed between the last two presentations. Our data show significantly increased middle-latency Nb responses for both detected and undetected changes as compared to no-change trials. In contrast, only successfully detected changes were associated with a later mismatch response in auditory cortex, followed by increased N2, P3a and P3b responses, originating from hierarchically higher non-sensory brain regions. These results strengthen the view that undetected changes are successfully encoded at sensory level in auditory cortex, but fail to trigger later change-related cortical responses that lead to conscious perception of change.	\N	\N
23467170	Cochlear implant (CI) users typically have excellent speech recognition in quiet but struggle with understanding speech in noise. It is thought that broad current spread from stimulating electrodes causes adjacent electrodes to activate overlapping populations of neurons which results in interactions across adjacent channels. Current focusing has been studied as a way to reduce spread of excitation, and therefore, reduce channel interactions. In particular, partial tripolar stimulation has been shown to reduce spread of excitation relative to monopolar stimulation. However, the crucial question is whether this benefit translates to improvements in speech perception. In this study, we compared speech perception in noise with experimental monopolar and partial tripolar speech processing strategies. The two strategies were matched in terms of number of active electrodes, microphone, filterbanks, stimulation rate and loudness (although both strategies used a lower stimulation rate than typical clinical strategies). The results of this study showed a significant improvement in speech perception in noise with partial tripolar stimulation. All subjects benefited from the current focused speech processing strategy. There was a mean improvement in speech recognition threshold of 2.7 dB in a digits in noise task and a mean improvement of 3 dB in a sentences in noise task with partial tripolar stimulation relative to monopolar stimulation. Although the experimental monopolar strategy was worse than the clinical, presumably due to different microphones, frequency allocations and stimulation rates, the experimental partial-tripolar strategy, which had the same changes, showed no acute deficit relative to the clinical.	\N	\N
23489145	Under adverse listening conditions, speech comprehension profits from the expectancies that listeners derive from the semantic context. However, the neurocognitive mechanisms of this semantic benefit are unclear: How are expectancies formed from context and adjusted as a sentence unfolds over time under various degrees of acoustic degradation? In an EEG study, we modified auditory signal degradation by applying noise-vocoding (severely degraded: four-band, moderately degraded: eight-band, and clear speech). Orthogonal to that, we manipulated the extent of expectancy: strong or weak semantic context (±con) and context-based typicality of the sentence-last word (high or low: ±typ). This allowed calculation of two distinct effects of expectancy on the N400 component of the evoked potential. The sentence-final N400 effect was taken as an index of the neural effort of automatic word-into-context integration; it varied in peak amplitude and latency with signal degradation and was not reliably observed in response to severely degraded speech. Under clear speech conditions in a strong context, typical and untypical sentence completions seemed to fulfill the neural prediction, as indicated by N400 reductions. In response to moderately degraded signal quality, however, the formed expectancies appeared more specific: Only typical (+con +typ), but not the less typical (+con -typ) context-word combinations led to a decrease in the N400 amplitude. The results show that adverse listening "narrows," rather than broadens, the expectancies about the perceived speech signal: limiting the perceptual evidence forces the neural system to rely on signal-driven expectancies, rather than more abstract expectancies, while a sentence unfolds over time.	\N	\N
23495123	We assessed the automaticity of spatial-numerical and spatial-musical associations by testing their intentionality and load sensitivity in a dual-task paradigm. In separate sessions, 16 healthy adults performed magnitude and pitch comparisons on sung numbers with variable pitch. Stimuli and response alternatives were identical, but the relevant stimulus attribute (pitch or number) differed between tasks. Concomitant tasks required retention of either color or location information. Results show that spatial associations of both magnitude and pitch are load sensitive and that the spatial association for pitch is more powerful than that for magnitude. These findings argue against the automaticity of spatial mappings in either stimulus dimension.	\N	\N
23503620	Abnormal auditory adaptation is a standard clinical tool for diagnosing auditory nerve disorders due to acoustic neuromas. In the present study we investigated auditory adaptation in auditory neuropathy owing to disordered function of inner hair cell ribbon synapses (temperature-sensitive auditory neuropathy) or auditory nerve fibres. Subjects were tested when afebrile for (i) psychophysical loudness adaptation to comfortably-loud sustained tones; and (ii) physiological adaptation of auditory brainstem responses to clicks as a function of their position in brief 20-click stimulus trains (#1, 2, 3 … 20). Results were compared with normal hearing listeners and other forms of hearing impairment. Subjects with ribbon synapse disorder had abnormally increased magnitude of loudness adaptation to both low (250 Hz) and high (8000 Hz) frequency tones. Subjects with auditory nerve disorders had normal loudness adaptation to low frequency tones; all but one had abnormal adaptation to high frequency tones. Adaptation was both more rapid and of greater magnitude in ribbon synapse than in auditory nerve disorders. Auditory brainstem response measures of adaptation in ribbon synapse disorder showed Wave V to the first click in the train to be abnormal both in latency and amplitude, and these abnormalities increased in magnitude or Wave V was absent to subsequent clicks. In contrast, auditory brainstem responses in four of the five subjects with neural disorders were absent to every click in the train. The fifth subject had normal latency and abnormally reduced amplitude of Wave V to the first click and abnormal or absent responses to subsequent clicks. Thus, dysfunction of both synaptic transmission and auditory neural function can be associated with abnormal loudness adaptation and the magnitude of the adaptation is significantly greater with ribbon synapse than neural disorders.	\N	\N
23506662	Various dimensions of auditory processing, especially the perception of speech in the presence of background competition, have been shown to deteriorate with age. A persistent problem in the assessment of these age-related changes has been the high prevalence of age-related high-frequency hearing loss in elderly persons. Some investigators have suggested that a more fruitful approach to the study of age-related decline might be to study middle-aged, rather than elderly, persons, where confounding high-frequency hearing loss is less prevalent. To determine whether an increase in the left-ear disadvantage (LED) in dichotic listening could be demonstrated in a group of middle-aged persons. The N400 component of the auditory event-related potential (AERP) was utilized to evaluate interaural asymmetry in a quasi-dichotic competing speech task. Electrophysiological responses were obtained on a word-pair semantic categorization task presented through a front loudspeaker while the listener ignored competing speech presented through either left (competition left [CL]) or right (competition right [CR]) loudspeakers. Study Samples: Twenty young (18-24 yr) and 20 middle-aged (44-57 yr) females with normal hearing sensitivity. Individual, as well as grand-averaged, AERP waveforms and scalp topographies were analyzed for the word pairs. Peak amplitude and latency measures of the N400 component were subjected to a mixed design analysis of variance (ANOVA). No significant interaural asymmetry was found in the AERP waveform for the reference word condition in either age group. In response to the second word of the pair, however, middle-aged females showed significantly greater N400 negativity in the CR condition than in the CL condition. No significant laterality effect was found in the young females. The study of young versus middle-aged participants may be an effective way of avoiding the confound of high-frequency hearing loss in elderly persons when studying age effects on auditory processing.	\N	\N
23507387	It was the aim of this study to delineate the areas along the right superior temporal sulcus (STS) for processing of faces, voices, and face-voice integration using established functional magnetic resonance imaging (fMRI) localizers and to assess their structural connectivity profile with diffusion tensor imaging (DTI). We combined this approach with an fMRI adaptation design during which the participants judged emotions in facial expressions and prosody and demonstrated response habituation in the orbitofrontal cortex (OFC) which occurred irrespective of the sensory modality. These functional data were in line with DTI findings showing separable fiber projections of the three different STS modules converging in the OFC which run through the external capsule for the voice area, through the dorsal superior longitudinal fasciculus (SLF) for the face area and through the ventral SLF for the audiovisual integration area. The OFC was structurally connected with the supplementary motor area (SMA) and activation in these two areas was correlated with faster stimulus evaluation during repetition priming. Based on these structural and functional properties, we propose that the OFC is part of the extended system for perception of emotional information in faces and voices and constitutes a neural interface linking sensory areas with brain regions implicated in generation of behavioral responses.	\N	\N
23518401	This study investigated the development of children's skills in identifying ecologically relevant sound objects within naturalistic listening environments, using a non-linguistic analog of the classic 'cocktail-party' situation. Children aged 7-12.5 years completed a closed-set identification task in which brief, commonly encountered environmental sounds were presented at varying signal-to-noise ratios. To simulate the complexity of real-world acoustic environments, target sounds were embedded in either a single, stereophonically presented scene, or in one of two different scenes, with each scene presented to a single ear. Each target sound was either congruent or incongruent with the auditory context. Identification accuracy improved with increasing age, particularly in trials with low signal-to-noise ratios. Performance was most accurate when target sounds were incongruent with the background scene, and when sounds were presented in a single background scene. The presence of two backgrounds disproportionately disrupted children's performance relative to that of previously tested adults, and reduced children's sensitivity to contextual cues. Successful identification of familiar sounds in complex auditory contexts is the outcome of a protracted learning process, with children reaching adult levels of performance after a decade or more of experience.	\N	\N
23523270	The ability to perceive and produce speech undergoes important changes in late adulthood. The goal of the present study was to characterize functional and structural age-related differences in the cortical network that support speech perception and production, using magnetic resonance imaging, as well as the relationship between functional and structural age-related changes occurring in this network. We asked young and older adults to observe videos of a speaker producing single words (perception), and to observe and repeat the words produced (production). Results show a widespread bilateral network of brain activation for Perception and Production that was not correlated with age. In addition, several regions did show age-related change (auditory cortex, planum temporale, superior temporal sulcus, premotor cortices, SMA-proper). Examination of the relationship between brain signal and regional and global gray matter volume and cortical thickness revealed a complex set of relationships between structure and function, with some regions showing a relationship between structure and function and some not. The present results provide novel findings about the neurobiology of aging and verbal communication.	\N	\N
23534128	The aim of this study was to establish the expression rate of autoimmunity in patients with sudden sensorineural hearing loss and to determine whether a positive marker is associated with a higher rate of hearing recovery after steroid treatment. A prospective study was performed on 137 patients who experienced sudden sensorineural hearing loss and underwent immunoserologic investigations. Autoantibodies evaluated on the day of admission included anti-double-stranded DNA, rheumatoid factor, antiphospholipid immunoglobulins G and M, antinuclear antibody, and complements C3 and C4. Of 137 patients, 75 were male and 62 were female (mean age, 45.1 years). Hearing loss was found on the left side in 61 patients and on the right side in 76 patients. Elevation of at least 1 autoantibody or abnormal complement levels were found in 80 patients (58%), and abnormalities of 2 or more antibodies were found in 28 (20%). There were no statistically significant correlations between autoantibody abnormalities and age, initial hearing level, or positive treatment response. There is no clear evidence of a correlation between autoimmunity and hearing improvement in patients with autoantibody abnormalities. A high (but not significant) expression rate of autoantibody abnormality and complement level was seen in patients with sudden sensorineural hearing loss.	\N	\N
23539259	Cochlear implant systems that combine electric and acoustic stimulation in the same ear are now commercially available and the number of patients using these devices is steadily increasing. In particular, electric-acoustic stimulation is an option for patients with severe, high frequency sensorineural hearing impairment. There have been a range of approaches to combining electric stimulation and acoustic hearing in the same ear. To develop a better understanding of fitting practices for devices that combine electric and acoustic stimulation, we conducted a systematic review addressing three clinical questions: what is the range of acoustic hearing in the implanted ear that can be effectively preserved for an electric-acoustic fitting?; what benefits are provided by combining acoustic stimulation with electric stimulation?; and what clinical fitting practices have been developed for devices that combine electric and acoustic stimulation? A search of the literature was conducted and 27 articles that met the strict evaluation criteria adopted for the review were identified for detailed analysis. The range of auditory thresholds in the implanted ear that can be successfully used for an electric-acoustic application is quite broad. The effectiveness of combined electric and acoustic stimulation as compared with electric stimulation alone was consistently demonstrated, highlighting the potential value of preservation and utilization of low frequency hearing in the implanted ear. However, clinical procedures for best fitting of electric-acoustic devices were varied. This clearly identified a need for further investigation of fitting procedures aimed at maximizing outcomes for recipients of electric-acoustic devices.	\N	\N
23540912	The present study investigated phonological encoding skills in children who stutter (CWS) and those who do not (CNS). Participants were 9 CWS (M=11.8 years, SD=1.5) and 9 age and sex matched CNS (M=11.8 years, SD=1.5). Participants monitored target phonemes located at syllable onsets and offsets of bisyllabic words. Performance in the phoneme monitoring task was compared to an auditory tone monitoring task. Repeated measures analysis of the response time data revealed significant Group×Task×Position interaction with the CWS becoming progressively slower than the CNS in monitoring subsequent phonemes located within the bisyllabic words; differences were not observed in the auditory tone monitoring task. Repeated measures analysis of the error data indicated that the groups were comparable in the percent errors in phoneme vs. tone monitoring. The CWS group was also significantly slower in a picture naming task compared to the CNS. Present findings suggest that CWS experience temporal asynchronies in one or more processes leading up to phoneme monitoring. The findings are interpreted within the scope of contemporary theories of stuttering. At the end of this activity the reader will be able to: (a) discuss the literature on phonological encoding skills in children who stutter, (b) identify theories of phonological encoding in stuttering, (c) define the process of phonological encoding and its implications for fluent speech, (d) suggest future areas of research in the investigation of phonological encoding abilities in children who stutter.	\N	\N
23544047	Because classical music has greatly affected our life and culture in its long history, it has attracted extensive attention from researchers to understand laws behind it. Based on statistical physics, here we use a different method to investigate classical music, namely, by analyzing cumulative distribution functions (CDFs) and autocorrelation functions of pitch fluctuations in compositions. We analyze 1,876 compositions of five representative classical music composers across 164 years from Bach, to Mozart, to Beethoven, to Mendelsohn, and to Chopin. We report that the biggest pitch fluctuations of a composer gradually increase as time evolves from Bach time to Mendelsohn/Chopin time. In particular, for the compositions of a composer, the positive and negative tails of a CDF of pitch fluctuations are distributed not only in power laws (with the scale-free property), but also in symmetry (namely, the probability of a treble following a bass and that of a bass following a treble are basically the same for each composer). The power-law exponent decreases as time elapses. Further, we also calculate the autocorrelation function of the pitch fluctuation. The autocorrelation function shows a power-law distribution for each composer. Especially, the power-law exponents vary with the composers, indicating their different levels of long-range correlation of notes. This work not only suggests a way to understand and develop music from a viewpoint of statistical physics, but also enriches the realm of traditional statistical physics by analyzing music.	\N	\N
23544676	Sound sequences, such as music, are usually organized perceptually into concurrent "streams." The mechanisms underlying this "auditory streaming" phenomenon are not completely known. The present study sought to test the hypothesis that synchrony limits listeners' ability to separate sound streams. To test this hypothesis, both perceptual-organization judgments and performance measures were used. In Experiment 1, listeners indicated whether they perceived sequences of alternating or synchronous tones as a single stream or as two streams. In Experiments 2 and 3, listeners detected rare changes in the intensity of "target" tones at one frequency in the presence of synchronous or asynchronous random-intensity "distractor" tones at another frequency. The results of these experiments showed that, for large frequency separations between the tones, the probability of perceiving two streams was lower on average for synchronous than for alternating tones, and that sensitivity to intensity changes in the target sequence was greater for asynchronous than for synchronous distractors. Overall, these results are consistent with the hypothesis that synchrony limits listeners' ability to form separate streams and/or to attend selectively to certain sounds in the presence of other sounds, even when the target and distractor sounds are well separated from each other in frequency.	\N	\N
23547103	Intertrial repetition priming plays a striking role in visual search. For instance, when searching for a target with a unique color, performance is substantially better when the specific color of the target repeats on successive trials (Maljkovic & Nakayama, 1994). Recent research has relied on objective measures of performance to show that priming improves the perceptual quality of the repeated target. Here, we examined the relation between priming and conscious perception of the target by adding a subjective measure of perception. We used backward masking to create liminal perception, that is, different levels of subjectively conscious perception of the target using exactly the same stimulus conditions. The displays in either probe trials (in which priming benefits are measured, experiment 1) or in prime trials (in which memory traces are laid down, experiment 2) were masked. The results showed that intertrial priming improves full access to awareness of the repeated target but only for targets that already achieved partial access to awareness. In addition, they show that full awareness of the target is necessary in both the prime and probe trials for intertrial priming effects to emerge. Implications for the role of implicit short-term memory in visual search are discussed.	\N	\N
23547105	When two objects are flashed at one location in close temporal proximity in the visual periphery, an intriguing illusion occurs whereby a single flash presented concurrently at another location appears to flash twice (the visual double-flash illusion: Chatterjee et al., 2011, Wilson & Singer, 1981). Here, for the first time, we investigate the time course of the effect, and directly compare it to the time course of the auditory (sound-induced flash illusion) effect, for both fission (single test flash, double inducer) and fusion (double test flash, single inducer) conditions, across stimulus onset asynchronies (SOAs) of 30 to 250 ms. In addition, using a novel audiovisual stimulus, we directly compare the cue strength of the two modalities, and whether they are additive in effect. The results show that the time course of fission and fusion is different for visual inducers, but not for auditory inducers. In audiovisual conditions, in situations of uncertainty, observers tended to follow the more reliable (auditory) cue. There was little evidence for a superadditive effect of auditory and visual cues; rather, observers tended to follow one or the other modality. The results suggest that the visually induced flash illusion and the auditory-induced effect may both stem from perceptual uncertainty, with the difference in time courses attributable to the lower temporal resolution of vision compared to audition.	\N	\N
23555217	The processing characteristics of neurons in the central auditory system are directly shaped by and reflect the statistics of natural acoustic environments, but the principles that govern the relationship between natural sound ensembles and observed responses in neurophysiological studies remain unclear. In particular, accumulating evidence suggests the presence of a code based on sustained neural firing rates, where central auditory neurons exhibit strong, persistent responses to their preferred stimuli. Such a strategy can indicate the presence of ongoing sounds, is involved in parsing complex auditory scenes, and may play a role in matching neural dynamics to varying time scales in acoustic signals. In this paper, we describe a computational framework for exploring the influence of a code based on sustained firing rates on the shape of the spectro-temporal receptive field (STRF), a linear kernel that maps a spectro-temporal acoustic stimulus to the instantaneous firing rate of a central auditory neuron. We demonstrate the emergence of richly structured STRFs that capture the structure of natural sounds over a wide range of timescales, and show how the emergent ensembles resemble those commonly reported in physiological studies. Furthermore, we compare ensembles that optimize a sustained firing code with one that optimizes a sparse code, another widely considered coding strategy, and suggest how the resulting population responses are not mutually exclusive. Finally, we demonstrate how the emergent ensembles contour the high-energy spectro-temporal modulations of natural sounds, forming a discriminative representation that captures the full range of modulation statistics that characterize natural sound ensembles. These findings have direct implications for our understanding of how sensory systems encode the informative components of natural stimuli and potentially facilitate multi-sensory integration.	\N	\N
23556554	Auditory and visual digit span tests were administered to a group of absolute pitch (AP) possessors, and a group of AP nonpossessors matched for age, and for age of onset and duration of musical training. All subjects were speakers of English. The AP possessors substantially and significantly outperformed the nonpossessors on the auditory test, while the two groups did not differ significantly on the visual test. It is conjectured that a large auditory memory span, including memory for speech sounds, facilitates the development of associations between pitches and their verbal labels early in life, so promoting the acquisition of AP.	\N	\N
23556594	Thresholds for sinusoids interaurally in phase (S0) and antiphase (Sπ) were measured in the presence of a diotic notched-noise masker (N0) as a function of notch width. The signal frequency was 250, 500, 1000, or 2000 Hz. For all signal frequencies, the difference between N0S0 and N0Sπ thresholds (binaural masking-level difference, BMLD) decreased continuously as the notch width increased. Model simulations showed that this result cannot be accounted for by a model that only processes the output of the auditory filter centered at the signal frequency, even if the nonlinear behavior of the monaural frequency selectivity or interaural differences in the filter shape are considered. The data were predicted well if a detrimental across-channel process was included, either by an addition of portions of the output of adjacent filters to the output of the on-frequency filter or by a notch-width dependent adverse shift in interaural phase in the binaural stage. The strength of this detrimental across-channel process tends to decrease with increasing signal frequencies.	\N	\N
23573184	Stress is prevalent in human life and threatens both physical and mental health; stress coping is thus of adaptive value for individual's survival and well-being. Although there has been extensive research on how the neural and physiological systems respond to stressful stimulation, relatively little is known about how the brain dynamically copes with stress evoked by this stimulation. Here we investigated how stress is relieved by a popular coping behavior, namely, gum chewing. In an fMRI study, we used loud noise as an acute stressor and asked participants to rate their feeling of stress in gum-chewing and no-chewing conditions. The participants generally felt more stressful when hearing noise, but less so when they were simultaneously chewing gum. The bilateral superior temporal sulcus (STS) and the left anterior insula (AI) were activated by noise, and their activations showed a positive correlation with the self-reported feeling of stress. Critically, gum chewing significantly reduced the noise-induced activation in these areas. Psychophysiological interaction (PPI) analysis showed that the functional connectivity between the left AI and the dorsal anterior cingulate cortex (dACC) was increased by noise to a lesser extent when the participants were chewing gum than when not chewing gum. Dynamic causality modeling (DCM) demonstrated that gum chewing inhibited the connectivity from the STS to the left AI. These findings demonstrate that gum chewing relieves stress by attenuating the sensory processing of external stressor and by inhibiting the propagation of stress-related information in the brain stress network.	\N	\N
23575462	It would be clinically valuable if an electrophysiological validation of hearing aid effectiveness in conveying speech information could be performed when a device is first provided to the individual after electroacoustic verification. This study evaluated envelope following responses (EFRs) elicited by English vowels in a steady state context and in natural sentences. It was the purpose of this study to determine whether EFRs could be detected rapidly enough to be clinically useful. EFRs were elicited using 5 vowels spanning the English vowel space, /i/, /ε/, /æ/, /(Equation is included in full-text article.)/, and /u/. These were presented either as concatenated steady state vowels (total duration 10.04 seconds) or in three 5-word sentences (total duration 11.77 seconds), where each vowel appeared once per sentence. Single-channel electroencephalogram was recorded from vertex (Cz) to the nape of the neck for 190 and 160 repetitions of the steady state vowels and sentences, respectively. The stimuli were presented at 70 dBA SPL. The fundamental frequency (f0) track from the stimuli was used with a Fourier analyzer to estimate the EFRs to each vowel. Noise amplitudes were also calculated at neighboring frequencies. Fifteen normal-hearing subjects who were 20 to 34 years of age participated in the experiment. In the analysis of steady state vowels, the mean response amplitude of /i/ was statistically the largest at 173 nV. The other 4 steady state vowels did not differ in mean response amplitude, which varied between 73 and 106 nV. In the analysis of vowels from the 3 sentences, the largest response amplitudes tended to be for /u/. Mean amplitudes for /u/ were 164, 111, and 140 nV for the words "booed," "food," and "Sue," respectively. The vowel /u/ produced statistically larger responses than /i/, /ε/, and /(Equation is included in full-text article.)/ when grouped across words, whereas other vowels did not differ. Mean response amplitudes for the other vowel categories in the sentences varied between 82 and 105 nV. All subjects showed significant EFRs in response to the words "Bee's" and "booed," but only 9 subjects showed significant EFRs for "pet," "bed," and "Bob." The authors were readily able to detect significant EFRs elicited by vowels in a steady state context and from 3 natural sentences. These results are promising as an early step in developing a clinical tool for validating that vowel stimuli are at least partially encoded at the level of the auditory brainstem. Future research will require evaluation of the technique with aided listeners, where the natural sentences are expected to be treated as typical speech by hearing aid signal-processing algorithms.	\N	\N
23576809	Major depression goes along with affective and social-cognitive deficits. Most research on affective deficits in depression has, however, only focused on unimodal emotion processing, whereas in daily life, emotional perception is often highly dependent on the evaluation of multimodal inputs. We thus investigated emotional audiovisual integration in patients with depression and healthy subjects. Subjects rated the expression of happy, neutral and fearful faces while concurrently being exposed to emotional or neutral sounds. Results demonstrated group differences in left inferior frontal gyrus and inferior parietal cortex when comparing incongruent to congruent happy facial conditions, mainly due to a failure of patients to deactivate these regions in response to congruent stimulus pairs. Moreover, healthy subjects decreased activation in right posterior superior temporal gyrus/sulcus and midcingulate cortex when an emotional stimulus was paired with a neutral rather than another emotional one. In contrast, patients did not show such deactivation when neutral stimuli were integrated. These results demonstrate aberrant neural response in audiovisual processing in depression, indicated by failure to deactivate regions involved in inhibition and salience processing when congruent and neutral audiovisual stimuli pairs are integrated, providing a possible mechanism of constant arousal and readiness to act in this patient group.	\N	\N
23591684	Migraine attacks consist of head pain and hypersensitivities to somatosensory, visual, auditory, and olfactory stimuli. Investigating how the migraine brain simultaneously processes and responds to multiple incoming stimuli may yield insights into migraine pathophysiology and migraine symptoms. The presence and intensity of hypersensitivity to one stimulus type are positively associated with the presence and intensity of hypersensitivities to other stimuli and to headache intensity. Furthermore, exposure to visual, auditory, and olfactory stimuli can trigger migraine attacks. These relationships suggest a role for multisensory integration in migraine. Multisensory integration of somatosensory, visual, auditory, and olfactory stimuli by the migraine brain may be an important concept for understanding migraine.	\N	\N
23593198	It has been proposed that the loudness dependence of auditory evoked potentials (LDAEP) would be a reliable indicator of central serotonin system activity in humans. Serotonin levels and turnover are also increased by brain-derived neurotrophic factor (BDNF). The aim of the present study was to determine whether there is an association between genetic polymorphisms of BDNF and the LDAEP in healthy Korean young adults. The cohort comprised 211 mentally and physically healthy subjects, all of whom were nonsmokers (111 males, 100 females; age: 20∼32 years). To avoid hormonal effects, the LDAEP was measured during days 2-5 after the beginning of menstruation for female subjects. In addition, BDNF polymorphisms (rs6265, rs2030324, and rs1491850) were genotyped. The strength of the LDAEP differed significantly among the BDNF genotype groups. Furthermore, the distribution of genotypic frequencies differed significantly between subjects with high and low LDAEPs. In particular, subjects with the Val/Met (A/G) genotype for rs6265, the T/T genotype for rs2030324, or the C/C genotype for rs1491850 had a higher LDAEP, indicating lower central serotonergic activity. A low LDAEP was more prevalent than a high LDAEP among those with the C-T haplotype (C genotype for rs2030424 and T genotype for rs1491850). Our results concur with previous findings on BDNF polymorphisms and serotonergic drug responses in psychiatric disorder patients. The present results suggest the possibility that BDNF polymorphisms and LDAEP patterns can predict altered serotonergic activity.	\N	\N
23603423	Language is more than a source of information for accessing higher-order conceptual knowledge. Indeed, language may determine how people perceive and interpret visual stimuli. Visual processing in linguistic contexts, for instance, mirrors language processing and happens incrementally, rather than through variously-oriented fixations over a particular scene. The consequences of this atypical visual processing are yet to be determined. Here, we investigated the integration of visual and linguistic input during a reasoning task. Participants listened to sentences containing conjunctions or disjunctions (Nancy examined an ant and/or a cloud) and looked at visual scenes containing two pictures that either matched or mismatched the nouns. Degree of match between nouns and pictures (referential anchoring) and between their expected and actual spatial positions (spatial anchoring) affected fixations as well as judgments. We conclude that language induces incremental processing of visual scenes, which in turn becomes susceptible to reasoning errors during the language-meaning verification process.	\N	\N
23613083	The lack of fine structure information in conventional cochlear implant (CI) encoding strategies presumably contributes to the generally poor music perception with CIs. To improve CI users' music perception, a harmonic-single-sideband-encoder (HSSE) strategy was developed , which explicitly tracks the harmonics of a single musical source and transforms them into modulators conveying both amplitude and temporal fine structure cues to electrodes. To investigate its effectiveness, vocoder simulations of HSSE and the conventional continuous-interleaved-sampling (CIS) strategy were implemented. Using these vocoders, five normal-hearing subjects' melody and timbre recognition performance were evaluated: a significant benefit of HSSE to both melody (p < 0.002) and timbre (p < 0.026) recognition was found. Additionally, HSSE was acutely tested in eight CI subjects. On timbre recognition, a significant advantage of HSSE over the subjects' clinical strategy was demonstrated: the largest improvement was 35% and the mean 17% (p < 0.013). On melody recognition, two subjects showed 20% improvement with HSSE; however, the mean improvement of 7% across subjects was not significant (p > 0.090). To quantify the temporal cues delivered to the auditory nerve, the neural spike patterns evoked by HSSE and CIS for one melody stimulus were simulated using an auditory nerve model. Quantitative analysis demonstrated that HSSE can convey temporal pitch cues better than CIS. The results suggest that HSSE is a promising strategy to enhance music perception with CIs.	\N	\N
23615803	Although the ferret has become an important model species for studying both fundamental and clinical aspects of spatial hearing, previous behavioral work has focused on studies of sound localization and spatial release from masking in the free field. This makes it difficult to tease apart the role played by different spatial cues. In humans and other species, interaural time differences (ITDs) and interaural level differences (ILDs) play a critical role in sound localization in the azimuthal plane and also facilitate sound source separation in noisy environments. In this study, we used a range of broadband noise stimuli presented via customized earphones to measure ITD and ILD sensitivity in the ferret. Our behavioral data show that ferrets are extremely sensitive to changes in either binaural cue, with levels of performance approximating that found in humans. The measured thresholds were relatively stable despite extensive and prolonged (>16 weeks) testing on ITD and ILD tasks with broadband stimuli. For both cues, sensitivity was reduced at shorter durations. In addition, subtle effects of changing the stimulus envelope were observed on ITD, but not ILD, thresholds. Sensitivity to these cues also differed in other ways. Whereas ILD sensitivity was unaffected by changes in average binaural level or interaural correlation, the same manipulations produced much larger effects on ITD sensitivity, with thresholds declining when either of these parameters was reduced. The binaural sensitivity measured in this study can largely account for the ability of ferrets to localize broadband stimuli in the azimuthal plane. Our results are also broadly consistent with data from humans and confirm the ferret as an excellent experimental model for studying spatial hearing.	\N	\N
23616552	The combined use of multisensory signals is often beneficial. Based on neuronal recordings in the superior colliculus of cats, three basic rules were formulated to describe the effectiveness of multisensory signals: the enhancement of neuronal responses to multisensory compared with unisensory signals is largest when signals occur at the same location ("spatial rule"), when signals are presented at the same time ("temporal rule"), and when signals are rather weak ("principle of inverse effectiveness"). These rules are also considered with respect to multisensory benefits as observed with behavioral measures, but do they capture these benefits best? To uncover the principles that rule benefits in multisensory behavior, we here investigated the classical redundant signal effect (RSE; i.e., the speedup of response times in multisensory compared with unisensory conditions) in humans. Based on theoretical considerations using probability summation, we derived two alternative principles to explain the effect. First, the "principle of congruent effectiveness" states that the benefit in multisensory behavior (here the speedup of response times) is largest when behavioral performance in corresponding unisensory conditions is similar. Second, the "variability rule" states that the benefit is largest when performance in corresponding unisensory conditions is unreliable. We then tested these predictions in two experiments, in which we manipulated the relative onset and the physical strength of distinct audiovisual signals. Our results, which are based on a systematic analysis of response time distributions, show that the RSE follows these principles very well, thereby providing compelling evidence in favor of probability summation as the underlying combination rule.	\N	\N
23627836	Theories of auditory attention suggest that humans decompose complex auditory input into individual auditory objects, which then compete for attention to dominate auditory perception. Since emotional significance of external stimuli has been argued to provide cues for sensory prioritization and allocation of attention, emotionally salient auditory objects can receive attention to dominate auditory perception. On the basis of the function of audition as an alarm system that informs the organism about its immediate surroundings, and on empirical evidence that emotion can modulate auditory perception, we argue that auditory stimuli with greater emotional saliency would dominate perception in multisource environments. To test our hypothesis, we employed a change detection task in which participants were asked to indicate whether multisource auditory scenes were identical or different. Participants were better at detecting changes at the presence of an emotionally negative environment compared to neutral environment. Further, we found that participants were better at detecting changes of emotionally negative targets compared to neutral targets. Our results demonstrate that detecting changes in auditory scenes is influenced by emotion. The findings are discussed in the light of the theories of auditory attention, emotional modulation of attention, and the adaptive function of emotion for perception.	\N	\N
23632885	It has been suggested that an auditory phantom percept is the result of multiple, parallel but overlapping networks. One of those networks encodes tinnitus loudness and is electrophysiologically separable from a nonspecific distress network. The present study investigates how these networks anatomically overlap, what networks are involved, and how and when these networks interact. Electroencephalography data of 317 tinnitus patients and 256 healthy subjects were analyzed, using independent component analysis. Results demonstrate that tinnitus is characterized by at least 2 major brain networks, each consisting of multiple independent components. One network reflects tinnitus distress, while another network reflects the loudness of the tinnitus. The component coherence analysis shows that the independent components that make up the distress and loudness networks communicate within their respective network at several discrete frequencies in parallel. The distress and loudness networks do not intercommunicate for patients without distress, but do when patients are distressed by their tinnitus. The obtained data demonstrate that the components that build up these 2 separable networks communicate at discrete frequencies within the network, and only between the distress and loudness networks in those patients in whom the symptoms are also clinically linked.	\N	\N
23632973	The purpose of this study was to determine how the bandwidth of the hearing aid (HA) fitting affects bimodal speech recognition of listeners with a cochlear implant (CI) in one ear and severe-to-profound hearing loss in the unimplanted ear (but with residual hearing sufficient for wideband amplification using National Acoustic Laboratories Revised, Profound [NAL-RP] prescriptive guidelines; unaided thresholds no poorer than 95 dB HL through 2000 Hz). Recognition of sentence material in quiet and in noise was measured with the CI alone and with CI plus HA as the amplification provided by the HA in the high and mid-frequency regions was systematically reduced from the wideband condition (NAL-RP prescription). Modified bandwidths included upper frequency cutoffs of 2000, 1000, or 500 Hz. On average, significant bimodal benefit was obtained when the HA provided amplification at all frequencies with aidable residual hearing. Limiting the HA bandwidth to only low-frequency amplification (below 1000 Hz) did not yield significant improvements in performance over listening with the CI alone. These data suggest the importance of providing amplification across as wide a frequency region as permitted by audiometric thresholds in the HA used by bimodal users.	\N	\N
23639338	To investigate auditory perception, speech production, and language ability of prelingually deaf toddlers with cerebral palsy (CP) who were implanted within a sensitive period and who received proper speech therapy. Comparison of their outcomes with age- and sex-matched CI recipients without additional disabilities was also performed. We retrospectively reviewed a cohort of pediatric CI in Samsung Medical Center. Eight CP subjects who received CI before 3 years of age and age-sex matched control recipients who had no additional disabilities except idiopathic sensorineural hearing loss (SNHL) were included for the analysis. Preoperative evaluation included the Categories of Auditory Performance (CAP) score, Korean Version of the Ling's Stage (K-Ling), Sequenced Language Scale for Infants (SELSI), Bailey Scales of Infant Development II assessment, Social Maturity Scale test, and grading of CP severity using severity level and Gross Motor Function Classification System for CP (GMFCS). To measure the outcome, the CAP scores, K-Ling, and SELSI were performed at 3, 6, 12, and 24 months after implantation. Four CP children with outstanding performances showed comparable achievement with matched control recipients. These patients had less severe motor disabilities (mild-moderate severity, GMFCS level 1-3), better social quotient, and better cognitive abilities. Although the others showed poor language abilities and hardly produced meaningful speech, their CAP scores reached 1 or 2 in 24 months after implantation. Deaf children with CP could have various ranges of benefits up to the levels of normal peers whose only disability was hearing loss, when CI was performed within a critical period. Especially, children with mild or moderate CP had a favorable outcome after CI, equivalent to that of normal peers.	\N	\N
23653412	It has previously been shown that the perceived roughness of a surface touched by one digit is influenced by the roughness of a different surface touched simultaneously by another digit on the same hand. The present study was designed to examine whether this is the case when surfaces of varying roughness are touched using digits on separate hands. Participants touched pairs of sandpaper surfaces, in sequence, using the same digit, and identified which of the two was rougher. Roughness discrimination was measured in the presence of distractor surfaces touched simultaneously with the target surface, but using a different digit either on the same or on the other hand. The overall perception of roughness of the attended surfaces was better on the left than on the right hand. Perceived roughness also varied systematically with the roughness of the distractor surfaces. Attended surfaces were more likely to be perceived as smoother when they were paired with smooth rather than rough distractors. Likewise, attended surfaces tended to be perceived as rougher with rough distractors. This pattern of results occurred whether the attended and distractor digits were on the same hand or different hands. These data confirm that it is difficult to restrict tactile attention for roughness to a single digit and show that this difficulty extends to restricting attention to a single hand. Furthermore, the effect of a stimulus at an unattended body location was not simply to impair perception in general, but to bias it in the roughness direction of the distractor surface.	\N	\N
23654389	Auditory filter bandwidths are measured for a temporal process using an amplitude-modulation detection task. The signal is a 200 Hz wide, sinusoidally amplitude-modulated band of noise centered within an unmodulated notched-noise masker. A modulation rate of 10 Hz is used to avoid possible information loss at more central processing levels for high modulation rates. Threshold functions are obtained for 10-14 notch widths for each of four different center frequencies (0.6, 1, 2, and 4 kHz) to determine the maximum notch width at which the masker has an effect. The ratio of center frequency to maximum notch width is ~2 at all center frequencies. It is proposed that the bandwidths observed in temporal tasks, which are consistently greater than expected from the viewpoint of critical band theory, be characterized as "temporal critical bands." This proposal does not oppose, but provides a complement to the traditional critical band obtained in tasks involving spectral discrimination.	\N	\N
23654392	Measurement of sensitivity to differences in the rate of change of auditory signal parameters is complicated by confounds among duration, extent, and velocity of the changing signal. Dooley and Moore [(1988) J. Acoust. Soc. Am. 84(4), 1332-1337] proposed a method for measuring sensitivity to rate of change using a duration discrimination task. They reported improved duration discrimination when an additional intensity or frequency change cue was present. The current experiments were an attempt to use this method to measure sensitivity to the rate of change in intensity and spatial position. Experiment 1 investigated whether duration discrimination was enhanced when additional cues of rate of intensity change, rate of spatial position change, or both were provided. Experiment 2 determined whether participant listening experience or the testing environment influenced duration discrimination task performance. Experiment 3 assessed whether duration discrimination could be used to measure sensitivity to rates of changes in intensity and spatial position for stimuli with lower rates of change, as well as emphasizing the constancy of the velocity cue. Results of these experiments showed that duration discrimination was impaired rather than enhanced by the additional velocity cues. The findings are discussed in terms of the demands of listening to concurrent changes along multiple auditory dimensions.	\N	\N
23654413	Inharmonicity of piano tones is an essential property of their timbre that strongly influences the tuning, leading to the so-called octave stretching. It is proposed in this paper to jointly model the inharmonicity and tuning of pianos on the whole compass. While using a small number of parameters, these models are able to reflect both the specificities of instrument design and tuner's practice. An estimation algorithm is derived that can run either on a set of isolated note recordings, but also on chord recordings, assuming that the played notes are known. It is applied to extract parameters highlighting some tuner's choices on different piano types and to propose tuning curves for out-of-tune pianos or piano synthesizers.	\N	\N
23656101	In this study, two methods are proposed to modify the normalized covariance metric (NCM) measure to reduce the effects of gain-induced nonlinear distortions introduced by most noise-suppression algorithms. Considering that the gain-induced distortions behave differently dependent on the signal-to-noise ratio between the noise-reduced speech and the noise, the first approach introduces a penalty factor involving this ratio in the modified NCM measure. The second approach deemphasizes segments marked with amplification distortions that contribute less to intelligibility via adaptive thresholding. Significantly higher correlations with intelligibility scores were obtained from the modified NCM measures compared with the original NCM measures.	\N	\N
23656102	A reference-free speech quality measure is proposed and assessed for hearing aid applications. The proposed speech quality metric is validated with subjective ratings obtained from hearing impaired listeners under a number of noisy and reverberant conditions. In addition, a comparison is drawn between the proposed measure and a state-of-the-art electroacoustic measure that relies on a clean reference signal. The results showed that the reference-free measure had a lower correlation with the subjective ratings of hearing aid speech quality in comparison to the correlations achieved by the measure utilizing a reference signal. Nevertheless, advantages of the reference-free approach are discussed.	\N	\N
23658664	In reverberant rooms with multiple-people talking, spatial separation between speech sources improves recognition of attended speech, even though both the head-shadowing and interaural-interaction unmasking cues are limited by numerous reflections. It is the perceptual integration between the direct wave and its reflections that bridges the direct-reflection temporal gaps and results in the spatial unmasking under reverberant conditions. This study further investigated (1) the temporal dynamic of the direct-reflection-integration-based spatial unmasking as a function of the reflection delay, and (2) whether this temporal dynamic is correlated with the listeners' auditory ability to temporally retain raw acoustic signals (i.e., the fast decaying primitive auditory memory, PAM). The results showed that recognition of the target speech against the speech-masker background is a descending exponential function of the delay of the simulated target reflection. In addition, the temporal extent of PAM is frequency dependent and markedly longer than that for perceptual fusion. More importantly, the temporal dynamic of the speech-recognition function is significantly correlated with the temporal extent of the PAM of low-frequency raw signals. Thus, we propose that a chain process, which links the earlier-stage PAM with the later-stage correlation computation, perceptual integration, and attention facilitation, plays a role in spatially unmasking target speech under reverberant conditions.	\N	\N
23665378	The integration of auditory feedback with vocal motor output is important for the control of voice fundamental frequency (F0). We used a pitch-shift paradigm where subjects respond to an alteration, or shift, of voice pitch auditory feedback with a reflexive change in F0. We presented varying magnitudes of pitch shifted auditory feedback to subjects during vocalization and passive listening and measured event related potentials (ERPs) to the feedback shifts. Shifts were delivered at +100 and +400 cents (200 ms duration). The ERP data were modeled with dynamic causal modeling (DCM) techniques where the effective connectivity between the superior temporal gyrus (STG), inferior frontal gyrus and premotor areas were tested. We compared three main factors: the effect of intrinsic STG connectivity, STG modulation across hemispheres and the specific effect of hemisphere. A Bayesian model selection procedure was used to make inference about model families. Results suggest that both intrinsic STG and left to right STG connections are important in the identification of self-voice error and sensory motor integration. We identified differences in left-to-right STG connections between 100 cent and 400 cent shift conditions suggesting that self- and non-self-voice error are processed differently in the left and right hemisphere. These results also highlight the potential of DCM modeling of ERP responses to characterize specific network properties of forward models of voice control.	\N	\N
23667666	Audition--what listeners hear--is generally studied in terms of the physical properties of sound stimuli and physiological properties of the auditory system. Based on recent work in vision, we here consider an alternative perspective that sensory percepts are based on past experience. In this framework, basic auditory qualities (e.g., loudness and pitch) are based on the frequency of occurrence of stimulus patterns in natural acoustic stimuli. To explore this concept of audition, we examined five well-documented psychophysical functions. The frequency of occurrence of acoustic patterns in a database of natural sound stimuli (speech) predicts some qualitative aspects of these functions, but with substantial quantitative discrepancies. This approach may offer a rationale for auditory phenomena that are difficult to explain in terms of the physical attributes of the stimuli as such.	\N	\N
23678126	For effective interactions with our dynamic environment, it is critical for the brain to integrate motion information from the visual and auditory senses. Combining fMRI and psychophysics, this study investigated how the human brain integrates auditory and visual motion into benefits in motion discrimination. Subjects discriminated the motion direction of audiovisual stimuli that contained directional motion signal in the auditory, visual, audiovisual, or no modality at two levels of signal reliability. Therefore, this 2 × 2 × 2 factorial design manipulated: (1) auditory motion information (signal vs noise), (2) visual motion information (signal vs noise), and (3) reliability of motion signal (intact vs degraded). Behaviorally, subjects benefited significantly from audiovisual integration primarily for degraded auditory and visual motion signals while obtaining near ceiling performance for "unisensory" signals when these were reliable and intact. At the neural level, we show audiovisual motion integration bilaterally in the visual motion areas hMT+/V5+ and implicate the posterior superior temporal gyrus/planum temporale in auditory motion processing. Moreover, we show that the putamen integrates audiovisual signals into more accurate motion discrimination responses. Our results suggest audiovisual integration processes at both the sensory and response selection levels. In all of these regions, the operational profile of audiovisual integration followed the principle of inverse effectiveness, in which audiovisual response suppression for intact stimuli turns into response enhancements for degraded stimuli. This response profile parallels behavioral indices of audiovisual integration, in which subjects benefit significantly from audiovisual integration only for the degraded conditions.	\N	\N
23684863	In ordinary conversations, literal meanings of an utterance are often quite different from implicated meanings and the inference about implicated meanings is essentially required for successful comprehension of the speaker's utterances. Inference of finding implicated meanings is based on the listener's assumption that the conversational partner says only relevant matters according to the maxim of relevance in Grice's theory of conversational implicature. To investigate the neural correlates of comprehending implicated meanings under the maxim of relevance, a total of 23 participants underwent an fMRI task with a series of conversational pairs, each consisting of a question and an answer. The experimental paradigm was composed of three conditions: explicit answers, moderately implicit answers, and highly implicit answers. Participants were asked to decide whether the answer to the Yes/No question meant 'Yes' or 'No'. Longer reaction time was required for the highly implicit answers than for the moderately implicit answers without affecting the accuracy. The fMRI results show that the left anterior temporal lobe, left angular gyrus, and left posterior middle temporal gyrus had stronger activation in both moderately and highly implicit conditions than in the explicit condition. Comprehension of highly implicit answers had increased activations in additional regions including the left inferior frontal gyrus, left medial prefrontal cortex, left posterior cingulate cortex and right anterior temporal lobe. The activation results indicate involvement of these regions in the inference process to build coherence between literally irrelevant but pragmatically associated utterances under the maxim of relevance. Especially, the left anterior temporal lobe showed high sensitivity to the level of implicitness and showed increased activation for highly versus moderately implicit conditions, which imply its central role in inference such as semantic integration. The right hemisphere activation, uniquely found in the anterior temporal lobe for highly implicit utterances, suggests its competence for integrating distant concepts in implied utterances under the relevance principle.	\N	\N
23691185	Listening to and understanding people in a "cocktail-party situation" is a remarkable feature of the human auditory system. Here we investigated the neural correlates of the ability to localize a particular sound among others in an acoustically cluttered environment with healthy subjects. In a sound localization task, five different natural sounds were presented from five virtual spatial locations during functional magnetic resonance imaging (fMRI). Activity related to auditory stream segregation was revealed in posterior superior temporal gyrus bilaterally, anterior insula, supplementary motor area, and frontoparietal network. Moreover, the results indicated critical roles of left planum temporale in extracting the sound of interest among acoustical distracters and the precuneus in orienting spatial attention to the target sound. We hypothesized that the left-sided lateralization of the planum temporale activation is related to the higher specialization of the left hemisphere for analysis of spectrotemporal sound features. Furthermore, the precuneus - a brain area known to be involved in the computation of spatial coordinates across diverse frames of reference for reaching to objects - seems to be also a crucial area for accurately determining locations of auditory targets in an acoustically complex scene of multiple sound sources. The precuneus thus may not only be involved in visuo-motor processes, but may also subserve related functions in the auditory modality.	\N	\N
23694737	Multiple auditory steady-state responses (ASSRs) to air- and bone-conduction stimuli were recorded in young children with otitis media with effusion (OME). After treatment for OME, differences between pre-treatment bone-conduction ASSR levels and post-treatment conditioned orientation reflex (COR) or air-conduction ASSR levels were examined, and compared with ASSR-estimated air-bone gap (ABG) before treatment. Navigator Pro with Master was used to assess the threshold of air- and bone-conduction ASSR in both ears at 500Hz, 1000Hz, 2000Hz and 4000Hz. For bone-conduction ASSR, RadioEar B-71 bone-vibrator placed on the mastoid was used with white-noise masking on the contralateral ear. After ventilation tube placement, the thresholds of COR got closer to those of pre-treatment bone-conduction ASSR in young children with OME. Moreover, post-treatment air-conduction ASSR thresholds also got closer to those of pre-treatment bone-conduction ASSR. The differences between pre-treatment bone-conduction ASSR thresholds and post-treatment COR or air-conduction ASSR thresholds became much smaller than ASSR-estimated ABG before treatment. These findings suggest that bone-conduction ASSR can assess the normal or near normal cochlear sensitivity in young children with conductive hearing loss. It is also suggested that ASSR-estimated ABG can be used clinically to predict their accurate ABG.	\N	\N
23694738	The aim of our study is to investigate the relationship between the complaint of speech understanding in noisy environments and the findings of contralateral suppression of transient evoked otoacoustic emissions and speech recognition in noise test methods in individuals with normal hearing. Sixty-nine subjects between 18 and 53 years of age with normal hearing participated in the present study. The subjects were assigned to one of two groups, reported difficulty understanding speech in noise or no reported difficulty understanding speech in noise. After hearing and immitancemetric evaluation, contralateral suppression of transient evoked otoacoustic emissions and speech recognition in noise tests were administered to both groups. Suppression was calculated in half-octave frequency bands centered at 1.0, 1.5, 2.0, 3.0 and 4.0kHz. We found out that the speech recognition in noise scores and contralateral suppression values were lower in subjects with the complaint of speech understanding in noise than those who do not have such complaints. We concluded that the complaint of speech understanding in noise may be related to the medial efferent system dysfunction, so central auditory nervous system.	\N	\N
23700960	We investigated the effects of focusing attention towards auditory or somatosensory stimuli on perceptual sensitivity and response bias using a signal detection task. Participants (N = 44) performed an unspeeded detection task in which weak (individually calibrated) somatosensory or auditory stimuli were delivered. The focus of attention was manipulated by the presentation of a visual cue at the start of each trial. The visual cue consisted of the word "warmth" or the word "tone". This word cue was predictive of the corresponding target on two-thirds of the trials. As hypothesised, the results showed that cueing attention to a specific sensory modality resulted in a higher perceptual sensitivity for validly cued targets than for invalidly cued targets, as well as in a more liberal response criterion for reporting stimuli in the valid modality than in the invalid modality. The value of this experimental paradigm for investigating excessive attentional focus or hypervigilance in various non-clinical and clinical populations is discussed.	\N	\N
23705807	Cochlear implantation (CI) is a standard treatment for severe-profound sensorineural hearing loss (SNHL). However, consensus has yet to be reached on its effectiveness for hearing loss caused by auditory neuropathy spectrum disorder (ANSD). This review aims to summarize and synthesize current evidence of the effectiveness of CI in improving speech recognition in children with ANSD. Systematic review. A total of 27 studies from an initial selection of 237. All selected studies were observational in design, including case studies, cohort studies, and comparisons between children with ANSD and SNHL. Most children with ANSD achieved open-set speech recognition with their CI. Speech recognition ability was found to be equivalent in CI users (who previously performed poorly with hearing aids) and hearing-aid users. Outcomes following CI generally appeared similar in children with ANSD and SNHL. Assessment of study quality, however, suggested substantial methodological concerns, particularly in relation to issues of bias and confounding, limiting the robustness of any conclusions around effectiveness. Currently available evidence is compatible with favourable outcomes from CI in children with ANSD. However, this evidence is weak. Stronger evidence is needed to support cost-effective clinical policy and practice in this area.	\N	\N
23708733	Dyslexic and non-dyslexic readers engaged in a short training aimed at learning eight basic letter-speech sound correspondences within an artificial orthography. We examined whether a letter-speech sound binding deficit is behaviorally detectable within the initial steps of learning a novel script. Both letter knowledge and word reading ability within the artificial script were assessed. An additional goal was to investigate the influence of instructional approach on the initial learning of letter-speech sound correspondences. We assigned children from both groups to one of three different training conditions: (a) explicit instruction, (b) implicit associative learning within a computer game environment, or (c) a combination of (a) and (b) in which explicit instruction is followed by implicit learning. Our results indicated that dyslexics were outperformed by the controls on a time-pressured binding task and a word reading task within the artificial orthography, providing empirical support for the view that a letter-speech sound binding deficit is a key factor in dyslexia. A combination of explicit instruction and implicit techniques proved to be a more powerful tool in the initial teaching of letter-sound correspondences than implicit training alone.	\N	\N
23714710	To investigate safety and efficacy of a new transcutaneous bone conduction hearing implant, over a 3-month follow-up period. Prospective, single-subject repeated-measures design in which each subject serves as his/her own control. Departments of Otolaryngology at 4 hospitals in Germany and Austria. Subjects were 12 German-speaking adults who suffered from conductive or mixed hearing loss. The upper bone conduction threshold limit was set to 45 dB HL at frequencies between 500 Hz and 4 kHz. Implantation of a transcutaneous bone conduction hearing implant. Subjects' speech perception (word recognition scores and SRT 50%) and audiometric thresholds (air conduction, bone conduction and sound field at frequencies 500 Hz to 8 kHz) were assessed preoperatively, 1 month postoperatively and 3 months postoperatively. The subjects were monitored for adverse events and given a questionnaire to assess their satisfaction levels. Speech perception as measured by word recognition scores and SRT 50% improved on average about 78.8% and 25 dB HL, respectively, 3 months after implantation. Aided thresholds also improved postoperatively at all tested frequencies and continued to improve from 1 to 3 months postoperatively. Air conduction and bone conduction thresholds showed no significant changes, confirming that subjects' residual unaided hearing was not deteriorated by the treatment. Only minor adverse events were reported and resolved by the end of the study. The new transcutaneous bone conduction implant was demonstrated to be safe and effective in adults up to 3 months of device use.	\N	\N
23715097	In this study, we used magnetoencephalography and a mismatch paradigm to investigate speech processing in stroke patients with auditory comprehension deficits and age-matched control subjects. We probed connectivity within and between the two temporal lobes in response to phonemic (different word) and acoustic (same word) oddballs using dynamic causal modelling. We found stronger modulation of self-connections as a function of phonemic differences for control subjects versus aphasics in left primary auditory cortex and bilateral superior temporal gyrus. The patients showed stronger modulation of connections from right primary auditory cortex to right superior temporal gyrus (feed-forward) and from left primary auditory cortex to right primary auditory cortex (interhemispheric). This differential connectivity can be explained on the basis of a predictive coding theory which suggests increased prediction error and decreased sensitivity to phonemic boundaries in the aphasics' speech network in both hemispheres. Within the aphasics, we also found behavioural correlates with connection strengths: a negative correlation between phonemic perception and an inter-hemispheric connection (left superior temporal gyrus to right superior temporal gyrus), and positive correlation between semantic performance and a feedback connection (right superior temporal gyrus to right primary auditory cortex). Our results suggest that aphasics with impaired speech comprehension have less veridical speech representations in both temporal lobes, and rely more on the right hemisphere auditory regions, particularly right superior temporal gyrus, for processing speech. Despite this presumed compensatory shift in network connectivity, the patients remain significantly impaired.	\N	\N
23716019	Our environment is richly structured, with objects producing correlated information within and across sensory modalities. A prominent challenge faced by our perceptual system is to learn such regularities. Here, we examined statistical learning and addressed learners' ability to track transitional probabilities between elements in the auditory and visual modalities. Specifically, we investigated whether cross-modal information affects statistical learning within a single modality. Participants were familiarized with a statistically structured modality (e.g., either audition or vision) accompanied by different types of cues in a second modality (e.g., vision or audition). The results revealed that statistical learning within either modality is affected by cross-modal information, with learning being enhanced or reduced according to the type of cue provided in the second modality.	\N	\N
23716122	Cross-orientation masking (XOM) occurs when the detection of a test grating is masked by a superimposed grating at an orthogonal orientation, and is thought to reveal the suppressive effects mediating contrast normalization. Medina and Mullen (2009) reported that XOM was greater for chromatic than achromatic stimuli at equivalent spatial and temporal frequencies. Here we address whether the greater suppression found in binocular color vision originates from a monocular or interocular site, or both. We measure monocular and dichoptic masking functions for red-green color contrast and achromatic contrast at three different spatial frequencies (0.375, 0.75, and 1.5 cpd, 2 Hz). We fit these functions with a modified two-stage masking model (Meese & Baker, 2009) to extract the monocular and interocular weights of suppression. We find that the weight of monocular suppression is significantly higher for color than achromatic contrast, whereas dichoptic suppression is similar for both. These effects are invariant across spatial frequency. We then apply the model to the binocular masking data using the measured values of the monocular and interocular sources of suppression and show that these are sufficient to account for color binocular masking. We conclude that the greater strength of chromatic XOM has a monocular origin that transfers through to the binocular site.	\N	\N
23716218	High-frequency pure tones (>6 kHz), which alone do not produce salient melodic pitch information, provide melodic pitch information when they form part of a harmonic complex tone with a lower fundamental frequency (F0). We explored this phenomenon in normal-hearing listeners by measuring F0 difference limens (F0DLs) for harmonic complex tones and pure-tone frequency difference limens (FDLs) for each of the tones within the harmonic complexes. Two spectral regions were tested. The low- and high-frequency band-pass regions comprised harmonics 6-11 of a 280- or 1,400-Hz F0, respectively; thus, for the high-frequency region, audible frequencies present were all above 7 kHz. Frequency discrimination of inharmonic log-spaced tone complexes was also tested in control conditions. All tones were presented in a background of noise to limit the detection of distortion products. As found in previous studies, F0DLs in the low region were typically no better than the FDL for each of the constituent pure tones. In contrast, F0DLs for the high-region complex were considerably better than the FDLs found for most of the constituent (high-frequency) pure tones. The data were compared with models of optimal spectral integration of information, to assess the relative influence of peripheral and more central noise in limiting performance. The results demonstrate a dissociation in the way pitch information is integrated at low and high frequencies and provide new challenges and constraints in the search for the underlying neural mechanisms of pitch.	\N	\N
23716223	We report a series of psychophysics experiments that investigated listeners' sensitivity to changes in complex acoustic scenes. Specifically, we sought to test the hypothesis that change detection is supported by sensitivity to change-related transients (an abrupt change in stimulus power within a certain frequency band, associated with the appearance or disappearance of a scene element). This hypothesis, in the context of natural scenes, is commonly dismissed on account that the elements of the scene may themselves be characterized by on-going energy fluctuations that would mask any genuine change-related transients. We created artificial 'scenes' populated by multiple pure-tone components. Tones were modulated (by a square wave at a distinct rate) so as to mimic the fluctuation properties of complex sounds. "Change" was defined as the appearance or disappearance of one such element. Importantly, such scenes lack semantic attributes, which may have been a limiting factor in interpreting previous auditory change-detection studies, thus allowing us to probe the low-level, pre-semantic, processes involved in auditory change perception. In Experiment 1 we measured listeners' ability to detect item appearance and disappearance in conditions where change-related transients are masked by a silent gap. In Experiment 2, we investigated the effect of an acoustic distractor - a brief signal that occurs at the time of change, but does not mask any scene components. The data show that gaps adversely affected the processing of item appearance but not disappearance. However, distractors reduced both -appearance and disappearance detection. Together our results suggest a role for sensitivity to transients in the process of auditory change detection, similar to what has been demonstrated for visual change detection.	\N	\N
23716230	Advances in the design of cochlear implants (CIs), as well as improved CI surgical techniques, have led to an increase in the number of patients who retain some residual low-frequency acoustic hearing in the implanted ear. Many of these patients also possess some hearing in the unimplanted ear. Although their low-frequency audiometric configurations will likely be asymmetrical across ears, they may nevertheless be able to process interaural time differences (ITDs) which might aid them in localizing sound sources and achieving a spatial release from masking. We recently published research (Brown and Yost 2011) showing how sensitivity to ITD differences was affected when the stimulus bandwidths were varied between the ears, to simulate asymmetrical hearing loss in the low-frequency region. We showed that ITD discrimination thresholds decreased as the bandwidth of the noise presented to one ear increased beyond that presented to the other ear. In the current experiment, we expand upon those conditions to ­further explore ITD processing in the presence of interaural spectral differences. ITD sensitivity was measured when a fixed band of noise was presented to one ear and the center frequency of a spectral band of the same width was moved upward in frequency in the other ear. The data suggest that listeners have difficulty attending to ITD differences in one spectral region when there are other spectral regions that contain conflicting or inconsistent spatial information, which is likely to be the case for many CI patients who possess bilateral residual hearing.	\N	\N
23716240	Jørgensen and Dau (J Acoust Soc Am 130:1475-1487, 2011) proposed the speech-based envelope power spectrum model (sEPSM) in an attempt to overcome the limitations of the classical speech transmission index (STI) and speech intelligibility index (SII) in conditions with nonlinearly processed speech. Instead of considering the reduction of the temporal modulation energy as the intelligibility metric, as assumed in the STI, the sEPSM applies the signal-to-noise ratio in the envelope domain (SNRenv). This metric was shown to be the key for predicting the intelligibility of reverberant speech as well as noisy speech processed by spectral subtraction. The key role of the SNRenv metric is further supported here by the ability of a short-term version of the sEPSM to predict speech masking release for different speech materials and modulated interferers. However, the sEPSM cannot account for speech subjected to phase jitter, a condition in which the spectral structure of the intelligibility of speech signal is strongly affected, while the broadband temporal envelope is kept largely intact. In contrast, the effects of this distortion can be predicted -successfully by the spectro-temporal modulation index (STMI) (Elhilali et al., Speech Commun 41:331-348, 2003), which assumes an explicit analysis of the spectral "ripple" structure of the speech signal. However, since the STMI applies the same decision metric as the STI, it fails to account for spectral subtraction. The results from this study suggest that the SNRenv might reflect a powerful decision metric, while some explicit across-frequency analysis seems crucial in some conditions. How such across-frequency analysis is "realized" in the auditory system remains unresolved.	\N	\N
23716257	We recently showed that listeners with normal hearing thresholds vary in their ability to direct spatial attention and that ability is related to the fidelity of temporal coding in the brainstem. Here, we recruited additional middle-aged listeners and extended our analysis of the brainstem response, measured using the frequency-following response (FFR). We found that even though age does not predict overall selective attention ability, middle-aged listeners are more susceptible to the detrimental effects of reverberant energy than young adults. We separated the overall FFR into orthogonal envelope and carrier components and used an existing model to predict which auditory channels drive each component. We find that responses in mid- to high-frequency auditory channels dominate envelope FFR, while lower-frequency channels dominate the carrier FFR. Importantly, we find that which component of the FFR predicts selective attention performance changes with age. We suggest that early aging degrades peripheral temporal coding in mid-to-high frequencies, interfering with the coding of envelope interaural time differences. We argue that, compared to young adults, middle-aged listeners, who do not have strong temporal envelope coding, have more trouble following a conversation in a reverberant room because they are forced to rely on fragile carrier ITDs that are susceptible to the degrading effects of reverberation.	\N	\N
23716261	Humans and other animals can attend to one of multiple sounds, and -follow it selectively over time. The neural underpinnings of this perceptual feat remain mysterious. Some studies have concluded that sounds are heard as separate streams when they activate well-separated populations of central auditory neurons, and that this process is largely pre-attentive. Here, we propose instead that stream formation depends primarily on temporal coherence between responses that encode various features of a sound source. Furthermore, we postulate that only when attention is directed toward a particular feature (e.g., pitch or location) do all other temporally coherent features of that source (e.g., timbre and location) become bound together as a stream that is segregated from the incoherent features of other sources. Experimental -neurophysiological evidence in support of this hypothesis will be presented. The focus, however, will be on a computational realization of this idea and a discussion of the insights learned from simulations to disentangle complex sound sources such as speech and music. The model consists of a representational stage of early and cortical auditory processing that creates a multidimensional depiction of various sound attributes such as pitch, location, and spectral resolution. The following stage computes a coherence matrix that summarizes the pair-wise correlations between all channels making up the cortical representation. Finally, the perceived segregated streams are extracted by decomposing the coherence matrix into its uncorrelated components. Questions raised by the model are discussed, especially on the role of attention in streaming and the search for further neural correlates of streaming percepts.	\N	\N
23720086	The CHRNA4 gene is known to be associated with individual differences in attention. However, its associations with other cognitive functions remain to be elucidated. In the present study, we investigated the effects of genetic variations in CHRNA4 on rapid scene categorization by 100 healthy human participants. In Experiment 1, we also conducted the Attention Network Test (ANT) in order to examine whether the genetic effects could be accounted for by attention. CHRNA4 was genotyped as carrying the TT, CT, or CC allele. The scene categorization task required participants to judge whether the category of a scene image (natural or man-made) was consistent with a cue word displayed at the response phase. The target-mask stimulus onset asynchrony (SOA) ranged from 13 to 93 ms. In comparison with CC-allele carriers, CT- and TT-allele carriers responded more accurately at the long SOA (93 ms) only during natural-scene categorization. In contrast, we observed no consistent association between CHRNA4 and the ANT, and no intertask correlation between scene categorization and the ANT. To validate our natural-scene categorization results, Experiment 2, carried out with an independent sample of 100 participants and a different stimulus set, successfully replicated the association between CHRNA4 genotypes and natural-scene categorization accuracy at long SOAs (67 and 93 ms). Our findings demonstrate, for the first time, that genetic variations in CHRNA4 can moderately contribute to individual differences in natural-scene categorization performance.	\N	\N
23727710	Successful interactions between people are dependent on rapid recognition of social cues. We investigated whether head direction--a powerful social signal--is processed in the absence of conscious awareness. We used continuous flash interocular suppression to render stimuli invisible and compared the reaction time for face detection when faces were turned towards the viewer and turned slightly away. We found that faces turned towards the viewer break through suppression faster than faces that are turned away, regardless of eye direction. Our results suggest that detection of a face with attention directed at the viewer occurs even in the absence of awareness of that face. While previous work has demonstrated that stimuli that signal threat are processed without awareness, our data suggest that the social relevance of a face, defined more broadly, is evaluated in the absence of awareness.	\N	\N
23734220	To understand why human sensitivity for complex objects is so low, we study how word identification combines eye and ear or parts of a word (features, letters, syllables). Our observers identify printed and spoken words presented concurrently or separately. When researchers measure threshold (energy of the faintest visible or audible signal) they may report either sensitivity (one over the human threshold) or efficiency (ratio of the best possible threshold to the human threshold). When the best possible algorithm identifies an object (like a word) in noise, its threshold is independent of how many parts the object has. But, with human observers, efficiency depends on the task. In some tasks, human observers combine parts efficiently, needing hardly more energy to identify an object with more parts. In other tasks, they combine inefficiently, needing energy nearly proportional to the number of parts, over a 60∶1 range. Whether presented to eye or ear, efficiency for detecting a short sinusoid (tone or grating) with few features is a substantial 20%, while efficiency for identifying a word with many features is merely 1%. Why? We show that the low human sensitivity for words is a cost of combining their many parts. We report a dichotomy between inefficient combining of adjacent features and efficient combining across senses. Joining our results with a survey of the cue-combination literature reveals that cues combine efficiently only if they are perceived as aspects of the same object. Observers give different names to adjacent letters in a word, and combine them inefficiently. Observers give the same name to a word's image and sound, and combine them efficiently. The brain's machinery optimally combines only cues that are perceived as originating from the same object. Presumably such cues each find their own way through the brain to arrive at the same object representation.	\N	\N
23742322	This study tested the hypothesis that the reduced spatial release from speech-on-speech masking typically observed in listeners with sensorineural hearing loss results from increased energetic masking. Target sentences were presented simultaneously with a speech masker, and the spectral overlap between the pair (and hence the energetic masking) was systematically varied. The results are consistent with increased energetic masking in listeners with hearing loss that limits performance when listening in speech mixtures. However, listeners with hearing loss did not exhibit reduced spatial release from masking when stimuli were filtered into narrow bands.	\N	\N
23742375	This study investigates the effectiveness of three high variability training paradigms in training 42 speakers of American English to correctly perceive and produce Spanish intervocalic /d, r, r/. Since Spanish spirantization and English flapping both affect /d/ intervocalically, the acquisition of the /d/-/r/ contrast proves difficult for English learners of Spanish. The acquisition of the trill /r/ is also problematic because it is a new phoneme for English learners and is articulatorily difficult to produce. Past research reported that high-variability perceptual training improves both perception and production [Bradlow et al., J. Acoust. Soc. Am. 101, 2299-2310 (1997); Wang et al., J. Acoust. Soc. Am. 113, 1033-1043 (2003)] and that production training improves both as well [Hirata, Comp. Assisted Lang. Learning 17, 357-376 (2004)]. However, trainees were able to listen to stimuli during production training, making it unclear whether production training alone transfers to perception. This study systematically controls both training modalities so they can be directly compared and introduces a third training methodology that includes both perception and production. All three training paradigms proved effective. While perception and production trainees primarily made gains in perception, combination trainees made gains in production. The effectiveness of each training modality depended on the nature of the contrast being trained and the modality of the test.	\N	\N
23751862	We used magnetoencephalography (MEG) to localize brain activity related to the retention of tones differing in pitch. Participants retained one or two simultaneously presented tones. After a two second interval a test tone was presented and the task was to determine if that tone was in memory. We focused on brain activity during the retention interval that increased as the number of sounds retained in auditory short-term memory (ASTM) increased. Source analyses revealed that the superior temporal gyrus in both hemispheres is involved in ASTM. In the right hemisphere, the inferior temporal gyrus, the inferior frontal gyrus, and parietal structures also play a role. Our method provides good spatial and temporal resolution for investigating neuronal correlates of ASTM and, as it is the first MEG study using a memory load manipulation without using sequences of tones, it allowed us to isolate brain regions that most likely reflect the simple retention of tones.	\N	\N
23751864	Neurobiological correlates of adaptation to spectrally degraded speech were investigated with fMRI before and after exposure to a portable real-time speech processor that implements an acoustic simulation model of a cochlear implant (CI). The speech processor, in conjunction with isolating insert earphones and a microphone to capture environment sounds, was worn by participants over a two week chronic exposure period. fMRI and behavioral speech comprehension testing were conducted before and after this two week period. After using the simulator each day for 2h, participants significantly improved in word and sentence recognition scores. fMRI shows that these improvements came accompanied by changes in patterns of neuronal activation. In particular, we found additional recruitment of visual, motor, and working memory areas after the perceptual training period. These findings suggest that the human brain is able to adapt in a short period of time to a degraded auditory signal under a natural learning environment, and gives insight on how a CI might interact with the central nervous system. This paradigm can be furthered to investigate neural correlates of new rehabilitation, training, and signal processing strategies non-invasively in normal hearing listeners to improve CI patient outcomes.	\N	\N
23757047	Temporal orienting--that is, selective attention to instants in time--has been shown to modulate performance in terms of faster responses in a variety of paradigms. Electrophysiological recordings have shown that temporal orienting modulates neural processing at early, probably perceptual, and late, probably decision- or response-related, stages. Recently, it was shown that the effect of temporal orienting on early auditory brain potentials is independent of the effect of the physical sound feature intensity. This indicates that temporal orienting might not affect stimulus processing by increasing the sensory gain of attended stimuli. In the present study, we investigated whether the independence of temporal-orienting and sound-intensity effects could be replicated behaviorally. Sequences were presented that were either rhythmic, most likely creating temporal expectations, or arrhythmic, presumably not creating such expectations. As hypothesized, the main effects of temporal expectation and sound intensity on reaction times were independent (Experiment 1). The exact pattern of results was replicated with a slightly altered paradigm (Experiment 2) and with a different kind of task (Experiment 3). In sum, these results corroborate the notion that the effect of temporal orienting might not rely on the same processes as the effect of sound intensity does.	\N	\N
23760984	The neural mechanisms of pitch coding have been debated for more than a century. The two main mechanisms are coding based on the profiles of neural firing rates across auditory nerve fibers with different characteristic frequencies (place-rate coding), and coding based on the phase-locked temporal pattern of neural firing (temporal coding). Phase locking precision can be partly assessed by recording the frequency-following response (FFR), a scalp-recorded electrophysiological response that reflects synchronous activity in subcortical neurons. Although features of the FFR have been widely used as indices of pitch coding acuity, only a handful of studies have directly investigated the relation between the FFR and behavioral pitch judgments. Furthermore, the contribution of degraded neural synchrony (as indexed by the FFR) to the pitch perception impairments of older listeners and those with hearing loss is not well known. Here, the relation between the FFR and pure-tone frequency discrimination was investigated in listeners with a wide range of ages and absolute thresholds, to assess the respective contributions of subcortical neural synchrony and other age-related and hearing loss-related mechanisms to frequency discrimination performance. FFR measures of neural synchrony and absolute thresholds independently contributed to frequency discrimination performance. Age alone, i.e., once the effect of subcortical neural synchrony measures or absolute thresholds had been partialed out, did not contribute to frequency discrimination. Overall, the results suggest that frequency discrimination of pure tones may depend both on phase locking precision and on separate mechanisms affected in hearing loss.	\N	\N
23761928	In vision, humans use summary statistics (e.g., the average facial expression of a crowd) to efficiently perceive the gist of groups of features. Here, we present direct evidence that ensemble coding is also important for auditory processing. We found that listeners could accurately estimate the mean frequency of a set of logarithmically spaced pure tones presented in a temporal sequence (Experiment 1). Their performance was severely reduced when only a subset of tones from a given sequence was presented (Experiment 2), which demonstrates that ensemble coding is based on a substantial number of the tones in a sequence. This precise ensemble coding occurred despite very limited representation of individual tones from the sequence: Listeners were poor at identifying specific individual member tones (Experiment 3) and at determining their positions in the sequence (Experiment 4). Together, these results indicate that summary statistical coding is not limited to visual processing and is an important auditory mechanism for extracting ensemble frequency information from sequences of sounds.	\N	\N
23769004	A 3-year longitudinal study was conducted to investigate changes in vocal quality as a result of singing training at a tertiary level conservatorium in Australia. Singers performed a messa di voce (MDV) at intervals of 6 months over the 3-year period of training. The study investigated the evolving acoustic features of the singers' voices exhibited during the MDV, including sound pressure level (SPL), short-term energy ratio (STER), duration, and vibrato parameters of the fundamental frequency (F0), SPL, and STER. The maximum SPL exhibited a marginal systematic increase over the training period, but the maximum STER did not systematically change. F0 vibrato extent increased significantly, whereas the extent of SPL and STER vibrato did not change significantly.	\N	\N
23772828	Noise-induced hearing loss (NIHL) is the most reported occupational health disease in the Netherlands. The internet-based speech-in-noise test Earcheck (Albrecht et al, 2005; Leensen et al, 2011b) is designed to detect beginning NIHL and can be a valuable tool in occupational hearing health surveillance. The aim of this study is to investigate the validity of Earcheck compared to regular screening audiometry. Subjects performed online Earcheck tests at home. The results are compared to a pure-tone screening audiogram obtained during regular occupational health examination. A subgroup performed the measurements twice to assess test-retest reliability. Two hundred and forty-nine male construction employees who recently had a periodic occupational health examination participated. An average learning effect of -1.6 dB was found, that reduced with increasing test number. The test-retest variability was 1.6 dB. Sensitivity to detect beginning NIHL was 68%, with a specificity of 71%. Although sensitivity and specificity values are only moderate, the broad internet application still promises a valuable addition to current practice. The relatively high learning effect indicates that more reliable results can be obtained after a longer test session. When this is put into practice some improvement in sensitivity and specificity may be expected as well.	\N	\N
23774181	A linguistic construction is typically viewed as encoding the pairing of syntactic form and semantic information that is independent of the meaning of constituent words. Here with the event-related potentials (ERPs) we demonstrate that such a construction can also encode pragmatic constraints (event likelihood) that immediately influence online sentence comprehension and the associated neural activity. The lian…dou…construction in Chinese (similar to even in English) normally describes an event of low expectedness (a semantic constraint); it also introduces a pragmatic scale implying that any event with a higher likelihood than the event described must occur (pragmatic inference). By embedding a highly likely event (a rich man buying a house) or an underspecified event (a man buying a house) in the construction, we created an incongruent condition and an underspecified condition and compared both with a control condition in which an event of low expectedness (a poor man buying a house) was described. ERPs on the main verb phrases showed an N400 with a maximum in the right hemisphere followed by a late negativity with an anterior maximum for both the incongruent and underspecified conditions, with a larger N400 effect for the former than for the latter. ERPs on the sentence-final phrases showed a sustained negativity for the incongruent, but not for the underspecified condition. The N400 effect may reflect the increased difficulty in unifying the current event into the lian…dou… construction. The late negativity may reflect a second-pass revision according to the likelihood scale to satisfy the pragmatic constraints of the construction.	\N	\N
23786393	The purpose of this study was to test the ability to discriminate low-frequency pure-tone stimuli for ears with and without contralateral dead regions, in subjects with bilateral high-frequency hearing loss; we examined associations between hearing loss characteristics and frequency discrimination of low-frequency stimuli in subjects with high-frequency hearing loss. Cochlear dead regions were diagnosed using the TEN-HL test. A frequency discrimination test utilizing an adaptive three-alternative forced choice method provided difference limens for reference frequencies 0.25 kHz and 0.5 kHz. Among 105 subjects with bilateral high-frequency hearing loss, unilateral dead regions were found in 15 subjects. These, and an additional 15 matched control subjects without dead regions, were included in the study. Ears with dead regions performed best at the frequency discrimination test. Ears with a contralateral dead region performed significantly better than ears without a contralateral dead region at 0.5 kHz, the reference frequency closest to the mean audiogram cut-off, while the opposite result was obtained at 0.25 kHz. Results may be seen as sign of a contralateral effect of unilateral dead regions on the discrimination of stimuli with frequencies well below the audiogram cut-off in adult subjects with bilateral high-frequency hearing loss.	\N	\N
23786439	Most theories of human language production assume that generating a sentence involves several stages, including an initial stage where the prelinguistic message is determined and a subsequent stage of grammatical encoding. However, it is contentious whether grammatical encoding involves separate stages of grammatical-function assignment and linearization. To address this question, we examined the mapping between the message level and grammatical encoding in two structural priming experiments in which German speakers choose between three different structures expressing ditransitive events. Although speakers showed a tendency to repeat the order of constituents (noun phrase-prepositional phrase, NP-PP, vs. NP-NP), they were additionally primed to repeat the order of thematic roles when constituent structure was constant (NPRECIPIENT-NPTHEME vs. NPTHEME-NPRECIPIENT). Experiment 2 found that the latter effect could not be due to persistence of the order of phrases referring to animate and inanimate entities. These results suggest a direct mapping of thematic roles to word order, consistent with a model in which the message is mapped onto syntactic structure in a single stage.	\N	\N
23787044	Coordinating movements to music is often considered a uniquely human skill. A new study dispels this notion by showing that male Australian lyrebirds also perform 'dance' moves which are predictably matched with specific songs in their display routines.	\N	\N
23789391	Auditory evoked response and mismatch negativity potential have been studied using the reversed odd-ball paradigm of standard and deviant stimulus presentation. In the experiments, three types of spatial sound stimuli (stationary and moving either gradually or abruptly from the head midline) were presented in three configurations. Each configuration employed one stimulus type as standard and the other two types as deviants. It was demonstrated that the configuration reversals influenced significantly the evoked response and mismatch negativity. The results obtained are discussed as the possible evidence of the categorical perception of auditory motion revealed at the earlier stages of sound processing in the hearing system.	\N	\N
23789637	Pickering & Garrod (P&G) put forward the interesting idea that language production relies on forward modeling operating at multiple processing levels. The evidence currently available to substantiate this idea mostly concerns sensorimotor processes and not more abstract linguistic levels (e.g., syntax, semantics, phonology). The predictions that follow from the claim seem too general, in their current form, to guide specific empirical tests.	\N	\N
23789872	We welcome the proposal to use forward models to understand predictive processes in language processing. However, Pickering & Garrod (P&G) miss the opportunity to provide a strong framework for future work. Forward models need to be pursued in the context of learning. This naturally leads to questions about what prediction error these models aim to minimize.	\N	\N
23790043	Although the target article emphasizes the important role of prediction in language use, prediction may well also play a key role in the initial formation of linguistic representations, that is, in language development. We outline the role of prediction in three relevant language-learning domains: transitional probabilities, statistical preemption, and construction learning.	\N	\N
23792078	Abundant evidence from both field and lab studies has established that conspecific vocalizations (CVs) are of critical ecological significance for a wide variety of species, including humans, non-human primates, rodents, and other mammals and birds. Correspondingly, a number of experiments have demonstrated behavioral processing advantages for CVs, such as in discrimination and memory tasks. Further, a wide range of experiments have described brain regions in many species that appear to be specialized for processing CVs. For example, several neural regions have been described in both mammals and birds wherein greater neural responses are elicited by CVs than by comparison stimuli such as heterospecific vocalizations, nonvocal complex sounds, and artificial stimuli. These observations raise the question of whether these regions reflect domain-specific neural mechanisms dedicated to processing CVs, or alternatively, if these regions reflect domain-general neural mechanisms for representing complex sounds of learned significance. Inasmuch as CVs can be viewed as complex combinations of basic spectrotemporal features, the plausibility of the latter position is supported by a large body of literature describing modulated cortical and subcortical representation of a variety of acoustic features that have been experimentally associated with stimuli of natural behavioral significance (such as food rewards). Herein, we review a relatively small body of existing literature describing the roles of experience, learning, and memory in the emergence of species-typical neural representations of CVs and auditory system plasticity. In both songbirds and mammals, manipulations of auditory experience as well as specific learning paradigms are shown to modulate neural responses evoked by CVs, either in terms of overall firing rate or temporal firing patterns. In some cases, CV-sensitive neural regions gradually acquire representation of non-CV stimuli with which subjects have training and experience. These results parallel literature in humans describing modulation of responses in face-sensitive neural regions through learning and experience. Thus, although many questions remain, the available evidence is consistent with the notion that CVs may acquire distinct neural representation through domain-general mechanisms for representing complex auditory objects that are of learned importance to the animal. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives".	\N	\N
23792769	This event-related potential (ERP) study examines the time course of context-dependent talker normalization in spoken word identification. We found three ERP components, the N1 (100-220 ms), the N400 (250-500 ms) and the Late Positive Component (500-800 ms), which are conjectured to involve (a) auditory processing, (b) talker normalization and lexical retrieval, and (c) decisional process/lexical selection respectively. Talker normalization likely occurs in the time window of the N400 and overlaps with the lexical retrieval process. Compared with the nonspeech context, the speech contexts, no matter whether they have semantic content or not, enable listeners to tune to a talker's pitch range. In this way, speech contexts induce more efficient talker normalization during the activation of potential lexical candidates and lead to more accurate selection of the intended word in spoken word identification.	\N	\N
23809517	Cochlear implantation has significant effects on language abilities and reading skills. The current study compared the reading performance of children with cochlear implants with that of typically developing children in second and third grades. This descriptive-analytic study was performed including 24 children with cochlear implants and 24 typically developing peers. The grade range of the participants was second and third grades. All of students were selected from Tehran city elementary schools. The reading performance of children was assessed by the "Nama" reading test. The results showed that the means of reading scores of typically developed children were significantly greater than the children with cochlear implants (P < 0.01) and there was a significant relationship between reading skills and age of surgery (P < 0.05). Also, there was a significant relationship between reading skills and the period of cochlear implantation (P < 0.05). Children with cochlear implants showed a weak performance in reading skills in comparison to typically developing children due to lower accessibility to phonological information. However, this limitation can be compensated for partly by early surgery. Parents should refer their deaf children for cochlear implantation before the age of language learning.	\N	\N
23815480	The origin of the Western preference for consonance remains unresolved, with some suggesting that the preference is innate. In Experiments 1 and 2 of the present study, 6-month-old infants heard six different consonant/dissonant pairs of stimuli, including those tested in previous research. In contrast to the findings of others, infants in the present study failed to listen longer to consonant stimuli. After 3 minutes of exposure to consonant or dissonant stimuli in Experiment 3, 6-month-old infants listened longer to the familiar stimulus, whether consonant or dissonant. Our findings are inconsistent with innate preferences for consonant stimuli. Instead, the effect of short-term exposure is consistent with the view that familiarity underlies the origin of the Western preference for consonant intervals.	\N	\N
23819616	In an earlier study ( Beach et al, 2012 ), detailed noise exposure measurements were obtained through individual dosimetry. In this further analysis of the data we ask the question "Can the effort required to converse in noise be used to estimate the experienced A-weighted noise level?" The noise levels experienced during specific activities were obtained from the analysis of dosimetry results from personal noise exposure meters worn by study participants. The measured noise levels from particular events were compared to a subjectively judged 'loudness rating' reported by the person wearing the dosimeter during the measured event. Volunteers (females = 20, males = 22) between 18 and 35 years (average age = 26.8) willing to wear dosimeters and keep a simple activity log. The relation between the objectively measured and the subjectively judged levels was consistent for the group over a large number of events. The subjective loudness rating index was shown to be a convenient tool that can be utilized for the retrospective estimation of noise levels from individual activities.	\N	\N
23824440	In this study, the authors examined the effects of aging and residual hearing on the identification of acoustically similar and dissimilar vowels in adults with postlingual deafness who use hearing aids (HAs) and/or cochlear implants (CIs). The authors used two groups of acoustically similar and dissimilar vowels to assess vowel identification. Also, the Consonant-Nucleus-Consonant Word Recognition Test (Peterson & Lehiste, 1962) and sentences from the Hearing in Noise Test (Nilsson, Soli, & Sullivan, 1994) were administered. Forty CI recipients with postlingual deafness (ages 31-81 years) participated in the study. Acoustically similar vowels were more difficult to identify than acoustically dissimilar vowels. With increasing age, performance deteriorated when identifying acoustically similar vowels. Vowel identification was also affected by the use of a contralateral HA and the degree of residual hearing prior to implantation. Moderate correlations were found between speech perception and vowel identification performance. Identification performance was affected by the acoustic similarity of the vowels. Older adults experienced more difficulty identifying acoustically similar confusable vowels than did younger adults. The findings might lend support to the ease of language understanding model (Ronnberg, Rudner, Foo, & Lunner, 2008), which proposes that the quality and perceptual robustness of acoustic input affects speech perception.	\N	\N
23833281	The relations of phonological, orthographic, and morphological awareness and vocabulary to word reading and spelling were examined for 304 first-grade children who were receiving differentiated instruction in a Response to Intervention (RtI) model of instruction. First-grade children were assessed on their phonological, orthographic, and morphological awareness; expressive vocabulary; word reading; and spelling. Year-end word reading and spelling were outcome variables, and phonological, orthographic, and morphological awareness; expressive vocabulary; and RtI status (Tiers 1, 2, & 3) were predictor variables. The 3 linguistic awareness skills were unique predictors of word reading, and phonological and orthographic awareness were unique predictors of spelling. The contributions that these linguistic awareness skills and vocabulary made to word reading and spelling did not differ by children's RtI tier status. These results, in conjunction with previous studies, suggest that even beginning readers and spellers draw on multiple linguistic awareness skills for their word reading and spelling regardless of their level of literacy abilities. Educational implications are discussed.	\N	\N
23833989	To investigate hidden hearing loss in tinnitus patients with normal audiograms by means of auditory brainstem response (ABR) and explore the origin of tinnitus. Pure tone thresholds, ABR thresholds, amplitude of wave I and wave V of ABR were analyzed in 40 tinnitus patients and 15 controls. There was no significantly difference in pure tone thresholds and ABR thresholds between those tinnitus patients and controls while a reduced amplitude of wave I and normal amplitude of wave V of ABR in the tinnitus patients became evident. Tinnitus patients with normal audiograms have hidden hearing loss at the level of primary auditory nerve and the generation of tinnitus is likely attributed to a homeostatic response of neurons in brainstem.	\N	\N
23846434	CHENFIT-AMP is a novel nonlinear strategy that combines the fitting (gain prescription) and amplification (gain implementation) procedures for cochlear hearing loss. The fitting part of CHENFIT-AMP prescribes gain for outer hair cell (OHC) and inner hair cell (IHC) loss, respectively. The gain for OHC loss varies with the cochlear gain decided by the value of OHC loss and the input level. The gain for IHC loss varies with the value of IHC loss only and will be limited to a constant if there is a "dead region." The amplification part of CHENFIT-AMP is responsible for estimating the input level and cochlear gain based on Chen's loudness model. CHENFIT-AMP is evaluated with four typical audiograms and nine individual audiograms. A widely used nonlinear fitting procedure, NAL-NL2, is evaluated to compare prescription results with CHENFIT-AMP; a standard nonlinear amplification algorithm, multichannel compression (MCC), with the parameters provided by NAL-NL2, is also evaluated to compare amplification results with CHENFIT-AMP. For long-term average speech spectrum (LTASS) inputs, CHENFIT-AMP generally prescribes similar gain as NAL-NL2 for the typical audiograms; however, gain prescribed by CHENFIT-AMP is more individualized than NAL-NL2 for the individual audiograms, especially when the audiograms have big deviations in the slope. For LTASS-shaped noise input, the gain implemented by MCC with parameters provided by NAL-NL2 cannot completely realize the gain prescribed by NAL-NL2. For speech sentence inputs, average ratings by subjects indicated that amplification by CHENFIT-AMP was preferred and led to a louder perception than that by MCC with parameters from NAL-NL2.	\N	\N
23846719	Inner speech is one of the most common, but least investigated, mental activities humans perform. It is an internal copy of one's external voice and so is similar to a well-established component of motor control: corollary discharge. Corollary discharge is a prediction of the sound of one's voice generated by the motor system. This prediction is normally used to filter self-caused sounds from perception, which segregates them from externally caused sounds and prevents the sensory confusion that would otherwise result. The similarity between inner speech and corollary discharge motivates the theory, tested here, that corollary discharge provides the sensory content of inner speech. The results reported here show that inner speech attenuates the impact of external sounds. This attenuation was measured using a context effect (an influence of contextual speech sounds on the perception of subsequent speech sounds), which weakens in the presence of speech imagery that matches the context sound. Results from a control experiment demonstrated this weakening in external speech as well. Such sensory attenuation is a hallmark of corollary discharge.	\N	\N
23847464	Evaluating series of complex sounds like those in speech and music requires sequential comparisons to extract task-relevant relations between subsequent sounds. With the present functional magnetic resonance imaging (fMRI) study, we investigated whether sequential comparison of a specific acoustic feature within pairs of tones leads to a change in lateralized processing in the auditory cortex (AC) of humans. For this we used the active categorization of the direction (up vs. down) of slow frequency modulated (FM) tones. Several studies suggest that this task is mainly processed in the right AC. These studies, however, tested only the categorization of the FM direction of each individual tone. In the present study we ask the question whether the right lateralized processing changes when, in addition, the FM direction is compared within pairs of successive tones. For this we use an experimental approach involving contralateral noise presentation in order to explore the contributions made by the left and right AC in the completion of the auditory task. This method has already been applied to confirm the right-lateralized processing of the FM direction of individual tones. In the present study, the subjects were required to perform, in addition, a sequential comparison of the FM direction in pairs of tones. The results suggest a division of labor between the two hemispheres such that the FM direction of each individual tone is mainly processed in the right AC whereas the sequential comparison of this feature between tones in a pair is probably performed in the left AC.	\N	\N
23850664	Over the last four decades, a range of different neuroimaging tools have been used to study human auditory attention, spanning from classic event-related potential studies using electroencephalography to modern multimodal imaging approaches (e.g., combining anatomical information based on magnetic resonance imaging with magneto- and electroencephalography). This review begins by exploring the different strengths and limitations inherent to different neuroimaging methods, and then outlines some common behavioral paradigms that have been adopted to study auditory attention. We argue that in order to design a neuroimaging experiment that produces interpretable, unambiguous results, the experimenter must not only have a deep appreciation of the imaging technique employed, but also a sophisticated understanding of perception and behavior. Only with the proper caveats in mind can one begin to infer how the cortex supports a human in solving the "cocktail party" problem. This article is part of a Special Issue entitled Human Auditory Neuroimaging.	\N	\N
23855264	Accurate tuning is an important aspect of singing in harmony in the context of a choir or vocal ensemble. Tuning and 'pitch drift' are concerning factors in performance for even the most accomplished professional choirs when singing a cappella (unaccompanied). In less experienced choirs tuning often lacks precision, typically because individual singers have not developed appropriate listening skills. In order to investigate accuracy of tuning in ensemble singing situations, a chorally appropriate reference is required against which frequency measurements can be made. Since most basic choral singing involves chords in four parts, a four-part reference template is used in which the fundamental frequencies of the notes in each chord can be accurately set. This template can now be used in experiments where three of the reference parts are tuned in any musical temperament (tuning system), in this case equal and just temperaments, and played over headphones to a singer to allow her/his tuning strategy to be investigated. This paper describes a practical implementation of a four-part choral synthesis system in Pure Data (Pd) and its use in an investigation of tuning of notes by individual singers using an exercise originally written to explore pitch drift in a cappella choral singing.	\N	\N
23859060	To examine the relationship between portable digital audio player listening behaviours and (1) measured sound pressure levels, (2) audiometric measures, (3) self-reported hearing loss symptoms. A questionnaire to evaluate listening behaviours, including self-reported hearing loss symptoms and listening duration/volume settings. Multivariate regression analysis was used to determine the relationship between these variables, audiometric evaluation, calculated exposure levels, Lex(8hr), and measured sound pressure levels, Leq(32sec). This study included 103 males and 134 female subjects aged 10 to 17 years. Calculated Lex(8hr) and measured Leq(32sec) levels increased with age and self-reported usage time. Audiometric thresholds averaged over 4 and 8 kHz were higher when usage exceeded five years as compared to less than one year. Higher measured sound pressure levels were associated with worse audiometric thresholds at (0.5, 1, 2 kHz, averaged) and 4 kHz. Self-reported hearing loss symptoms were reported by 33% to 50% of subjects. In this cohort sample, our results support a statistical association between hearing acuity and (1) Self-reported weekly usage in hours; (2) Tightness of fit; (3) Years of usage; and (4) Measured sound pressure levels. Generalizing these results beyond the current sample would require additional research.	\N	\N
23862816	Tone-in-noise detection has been studied for decades; however, it is not completely understood what cue or cues are used by listeners for this task. Model predictions based on energy in the critical band are generally more successful than those based on temporal cues, except when the energy cue is not available. Nevertheless, neither energy nor temporal cues can explain the predictable variance for all listeners. In this study, it was hypothesized that better predictions of listeners' detection performance could be obtained using a nonlinear combination of energy and temporal cues, even when the energy cue was not available. The combination of different cues was achieved using the logarithmic likelihood-ratio test (LRT), an optimal detector in signal detection theory. A nonlinear LRT-based combination of cues was proposed, given that the cues have Gaussian distributions and the covariance matrices of cue values from noise-alone and tone-plus-noise conditions are different. Predictions of listeners' detection performance for three different sets of reproducible noises were computed with the proposed model. Results showed that predictions for hit rates approached the predictable variance for all three datasets, even when an energy cue was not available.	\N	\N
23862818	A number of precedence-effect models have been developed to simulate the robust localization performance of humans in reverberant conditions. Although they are able to reduce reverberant information for many conditions, they tend to fail for ongoing stimuli with truncated on/offsets, a condition human listeners master when localizing a sound source in the presence of a reflection, according to a study by Dizon and Colburn [J. Acoust. Soc. Am. 119, 2947-2964 (2006)]. This paper presents a solution for this condition by using an autocorrelation mechanism to estimate the delay and amplitude ratio between the leading and lagging signals. An inverse filter is then used to eliminate the lag signal, before it is localized with a standard localization algorithm. The current algorithm can operate on top of a basic model of the auditory periphery (gammatone filter bank, half-wave rectification) to simulate psychoacoustic data by Braasch et al. [Acoust. Sci. Tech. 24, 293-303 (2003)] and Dizon and Colburn. The model performs robustly with these on/offset truncated and interaural level difference based stimuli and is able to demonstrate the Haas effect.	\N	\N
23862821	In noise repetition-detection tasks, listeners have to distinguish trials of continuously running noise from trials in which noise tokens are repeated in a cyclic manner. Recently, it has been shown that using the exact same noise token across several trials ("reference noise") facilitates the detection of repetitions for this token [Agus et al. (2010). Neuron 66, 610-618]. This was attributed to perceptual learning. Here, the nature of the learning was investigated. In experiment 1, reference noise tokens were embedded in trials with or without cyclic presentation. Naïve listeners reported repetitions in both cases, thus responding to the reference noise even in the absence of an actual repetition. Experiment 2, with the same listeners, showed a similar pattern of results even after the design of the experiment was made explicit, ruling out a misunderstanding of the task. Finally, in experiment 3, listeners reported repetitions in trials containing the reference noise, even before ever hearing it presented cyclically. The results show that listeners were able to learn and recognize noise tokens in the absence of an immediate repetition. Moreover, the learning mandatorily interfered with listeners' ability to detect repetitions. It is concluded that salient perceptual changes accompany the learning of noise.	\N	\N
23862833	Effective communication between staff members is key to patient safety in hospitals. A variety of patient care activities including admittance, evaluation, and treatment rely on oral communication. Surprisingly, published information on speech intelligibility in hospitals is extremely limited. In this study, speech intelligibility measurements and occupant evaluations were conducted in 20 units of five different U.S. hospitals. A variety of unit types and locations were studied. Results show that overall, no unit had "good" intelligibility based on the speech intelligibility index (SII > 0.75) and several locations found to have "poor" intelligibility (SII < 0.45). Further, occupied spaces were found to have 10%-15% lower SII than unoccupied spaces on average. Additionally, staff perception of communication problems at nurse stations was significantly correlated with SII ratings. In a targeted second phase, a unit treated with sound absorption had higher SII ratings for a larger percentage of time as compared to an identical untreated unit. Taken as a whole, the study provides an extensive baseline evaluation of speech intelligibility across a variety of hospitals and unit types, offers some evidence of the positive impact of absorption on intelligibility, and identifies areas for future research.	\N	\N
23862901	Categorical perception experiments were performed on an English /b-p/ voice onset time (VOT) continuum with native (American English) and non-native (Korean) listeners to examine whether and how phonetic categorization is modulated by prosodic boundary and language experience. Results demonstrated perceptual shifting according to prosodic boundary strength: A longer VOT was required to identify a sound as /p/ after an intonational phrase than a word boundary, regardless of the listeners' language experience. This suggests that segmental perception is modulated by the listeners' computation of an abstract prosodic structure reflected in phonetic cues of phrase-final lengthening and domain-initial strengthening, which are common across languages.	\N	\N
23862903	A previous report [Margolis and Stiepan (2012). "Acoustic method for calibration of audiometric bone vibrators," J. Acoust. Soc. Am. 131, 1221-1225] described a reliable, inexpensive, acoustic method for calibration of audiometric bone vibrators. As a follow up to that report harmonic distortion measurements were made with the standard electromechanical method and the acoustic method using five Radioear B71 vibrators and one Radioear B81 prototype vibrator. Lower distortion was seen for measurements made with the acoustic method compared to the electromechanical method and for the Radioear B81 vibrator compared to the Radioear B71 vibrator.	\N	\N
23865332	Masking therapy can make patients accustom to tinnitus. This therapy is safe and easy to implement, so that it has become a widely used treatment of curing tinnitus. According to surveys of tinnitus sounds, cicada sound is one of the most usual tinnituses. Meanwhile, we have not hitherto found published papers concerning how to synthesize cicada sound and to use it to ameliorate tinnitus. Inspired by the human acoustics theory, we proposed a method to synthesize medical masking sound and to realize the diversity by illustrating the process of synthesizing various cicada sounds. In addition, energy attenuation problem in spectrum shifting process has been successfully solved. Simulation results indicated that the proposed method achieved decent results and would have practical value for the future applications.	\N	\N
23867553	We study the developmental trajectory of morphology and function of the superior temporal cortex (STC) in children (8-9 years), adolescents (14-15 years) and young adults. We analyze cortical surface landmarks and functional MRI (fMRI) responses to voices, other natural categories and tones and examine how hemispheric asymmetry and inter-subject variability change across age. Our results show stable morphological asymmetries across age groups, including a larger left planum temporale and a deeper right superior temporal sulcus. fMRI analyses show that a rightward lateralization for voice-selective responses is present in all groups but decreases with age. Furthermore, STC responses to voices change from being less selective and more spatially diffuse in children to highly selective and focal in adults. Interestingly, the analysis of morphological landmarks reveals that inter-subject variability increases during development in the right--but not in the left--STC. Similarly, inter-subject variability of cortically-realigned functional responses to voices, other categories and tones increases with age in the right STC. Our findings reveal asymmetric developmental changes in brain regions crucial for auditory and voice perception. The age-related increase of inter-subject variability in right STC suggests that anatomy and function of this region are shaped by unique individual developmental experiences.	\N	\N
23882002	To determine the relative importance of acoustic parameters (fundamental frequency [F0], formant frequencies [FFs], aperiodicity, and spectrum level [SL]) on voice gender perception, the authors used a novel parameter-morphing approach that, unlike spectral envelope shifting, allows the application of nonuniform scale factors to transform formants and more direct comparison of parameter impact. In each of 2 experiments, 16 listeners with normal hearing (8 female, 8 male) classified voice gender for morphs between female and male speakers, using syllable tokens from 2 male-female speaker pairs. Morphs varied single acoustic parameters (Experiment 1) or selected combinations (Experiment 2), keeping residual parameters androgynous, as determined in a baseline experiment. The strongest cue related to gender perception was F0, followed by FF and SL. Aperiodicity did not systematically influence gender perception. Morphing F0 and FF in conjunction produced convincing changes in perceived gender-changes that were equivalent to those for Full morphs interpolating all parameters. Despite the importance of F0, morphing FF and SL in combination produced effective changes in voice gender perception. The most important single parameters for gender perception are, in order, F0, FF, and SL. At the same time, F0 and vocal tract resonances have a comparable impact on voice gender perception.	\N	\N
23883861	The observation that near-threshold low-contrast visual distractors can equally influence perceptual state and goal-directed motor responses was recently taken as an argument against a sharp separation between a conscious vision for perception and an unconscious vision for action. However, data supporting the dual visual system theory have principally involved high-contrast stimuli. In the present study, we assessed the effect of varying the contrast of a near-threshold visual distractor while keeping its visibility constant with backward noise masks. Eight participants performed fast manual reaching movements toward a highly visible target while subsequently reporting the presence/absence of a near-threshold distractor appearing at the opposite location with respect to the body midline. For all distractor contrasts, hand trajectory deviations toward the distractor were observed when the distractor was present and detected. When the distractor remained undetected deviations also occurred, but for higher contrasts. The subliminal motor effect traditionally observed in visual masking studies may therefore primarily depend on the luminance contrast of the interfering stimuli. These results suggest that dissociations between perceptual and motor responses can be explained by a single-signal model involving differential thresholds for perception and action that are specifically modulated as a function of both the requirements of the task and the contrast level of the stimuli. Such modulation is compatible with neurophysiological accounts of visual masking in which feedforward activation to--and feedback activation from--higher visual areas are correlated with the actual presence of the stimulation and its conscious perception, respectively.	\N	\N
23902521	This study investigated the effect of electrode configuration, stimulus rate, and EEG rejection level on the efficiency of ABR testing in babies. ABR to click stimuli at 40 dB nHL were simultaneously recorded from two electrode configurations, ipsilateral mastoid to high forehead (Mi-Fh) and nape to high forehead (N-Fh), with two EEG rejection levels (± 5 μV and ± 10 μV). Stimulus rates were between 39.1 and 69.1 per second. Efficiency was measured by confidence in the ABR for a given test time. Thirty babies who had passed a targeted newborn hearing screen with ABR thresholds ≤ 40 dB nHL. The N-Fh configuration, as expected, gave on average a larger response amplitude compared to the Mi-Fh configuration but was only marginally significantly better in terms of test efficiency. There was no significant effect of stimulus rate on test efficiency between 39.1/s and 59.1/s. The lower ± 5 μV EEG rejection level was more test efficient. This study provides some evidence that, for ABR threshold testing in babies, alternatives of ipsilateral mastoid or nape electrode and a range of stimulus rates have little or no effect on test efficiency. The results support the use of low EEG rejection limits.	\N	\N
23915050	In everyday listening situations, we need to constantly switch between alternative sound sources and engage attention according to cues that match our goals and expectations. The exact neuronal bases of these processes are poorly understood. We investigated oscillatory brain networks controlling auditory attention using cortically constrained fMRI-weighted magnetoencephalography/EEG source estimates. During consecutive trials, participants were instructed to shift attention based on a cue, presented in the ear where a target was likely to follow. To promote audiospatial attention effects, the targets were embedded in streams of dichotically presented standard tones. Occasionally, an unexpected novel sound occurred opposite to the cued ear to trigger involuntary orienting. According to our cortical power correlation analyses, increased frontoparietal/temporal 30-100 Hz gamma activity at 200-1400 msec after cued orienting predicted fast and accurate discrimination of subsequent targets. This sustained correlation effect, possibly reflecting voluntary engagement of attention after the initial cue-driven orienting, spread from the TPJ, anterior insula, and inferior frontal cortices to the right FEFs. Engagement of attention to one ear resulted in a significantly stronger increase of 7.5-15 Hz alpha in the ipsilateral than contralateral parieto-occipital cortices 200-600 msec after the cue onset, possibly reflecting cross-modal modulation of the dorsal visual pathway during audiospatial attention. Comparisons of cortical power patterns also revealed significant increases of sustained right medial frontal cortex theta power, right dorsolateral pFC and anterior insula/inferior frontal cortex beta power, and medial parietal cortex and posterior cingulate cortex gamma activity after cued versus novelty-triggered orienting (600-1400 msec). Our results reveal sustained oscillatory patterns associated with voluntary engagement of auditory spatial attention, with the frontoparietal and temporal gamma increases being best predictors of subsequent behavioral performance.	\N	\N
23920156	The current study investigated the role of resumption in the interpretation of object relative clauses (RCs) in Persian-speaking children. Sixty-four (N=64) children aged 3;2-6;0 (M=4;8) completed a referent selection task that tested their comprehension of subject RCs, gapped object RCs, and object RCs containing either a resumptive pronoun or an object clitic. The results showed that the presence of a resumptive element (pronoun or clitic) had a facilitative effect on children's processing of object RCs. In both cases object RCs with resumptive elements were interpreted more accurately than gapped subject and object RCs, suggesting that resumptive elements ease processing burden in syntactically complex contexts because they provide local cues to thematic role assignment.	\N	\N
23926291	Previously, Gygi and Shafiro (2011) found that when environmental sounds are semantically incongruent with the background scene (e.g., horse galloping in a restaurant), they can be identified more accurately by young normal-hearing listeners (YNH) than sounds congruent with the scene (e.g., horse galloping at a racetrack). This study investigated how age and high-frequency audibility affect this Incongruency Advantage (IA) effect. In Experiments 1a and 1b, elderly listeners ( N = 18 for 1a; N = 10 for 1b) with age-appropriate hearing (EAH) were tested on target sounds and auditory scenes in 5 sound-to-scene ratios (So/Sc) between -3 and -18 dB. Experiment 2 tested 11 YNH on the same sound-scene pairings lowpass-filtered at 4 kHz (YNH-4k). The EAH and YNH-4k groups exhibited an almost identical pattern of significant IA effects, but both were at approximately 3.9 dB higher So/Sc than the previously tested YNH listeners. However, the psychometric functions revealed a shallower slope for EAH listeners compared with YNH listeners for the congruent stimuli only, suggesting a greater difficulty for the EAH listeners in attending to sounds expected to occur in a scene. These findings indicate that semantic relationships between environmental sounds in soundscapes are mediated by both audibility and cognitive factors and suggest a method for dissociating these factors.	\N	\N
23927115	Laback et al. [(2011). J. Acoust. Soc. Am. 129, 888-897] investigated the additivity of nonsimultaneous masking using short Gaussian-shaped tones as maskers and target. The present study involved Gaussian stimuli to measure the additivity of simultaneous masking for combinations of up to four spectrally separated maskers. According to most basilar membrane measurements, the maskers should be processed linearly at the characteristic frequency (CF) of the target. Assuming also compression of the target, all masker combinations should produce excess masking (exceeding linear additivity). The results for a pair of maskers flanking the target indeed showed excess masking. The amount of excess masking could be predicted by a model assuming summation of masker-evoked excitations in intensity units at the target CF and compression of the target, using compressive input/output functions derived from the nonsimultaneous masking study. However, the combinations of lower-frequency maskers showed much less excess masking than predicted by the model. This cannot easily be attributed to factors like off-frequency listening, combination tone perception, or between-masker suppression. It was better predicted, however, by assuming weighted intensity summation of masker excitations. The optimum weights for the lower-frequency maskers were smaller than one, consistent with partial masker compression as indicated by recent psychoacoustic data.	\N	\N
23927133	Much recent interest surrounds listeners' abilities to adapt to various transformations that distort speech. An extreme example is spectral rotation, in which the spectrum of low-pass filtered speech is inverted around a center frequency (2 kHz here). Spectral shape and its dynamics are completely altered, rendering speech virtually unintelligible initially. However, intonation, rhythm, and contrasts in periodicity and aperiodicity are largely unaffected. Four normal hearing adults underwent 6 h of training with spectrally-rotated speech using Continuous Discourse Tracking. They and an untrained control group completed pre- and post-training speech perception tests, for which talkers differed from the training talker. Significantly improved recognition of spectrally-rotated sentences was observed for trained, but not untrained, participants. However, there were no significant improvements in the identification of medial vowels in /bVd/ syllables or intervocalic consonants. Additional tests were performed with speech materials manipulated so as to isolate the contribution of various speech features. These showed that preserving intonational contrasts did not contribute to the comprehension of spectrally-rotated speech after training, and suggested that improvements involved adaptation to altered spectral shape and dynamics, rather than just learning to focus on speech features relatively unaffected by the transformation.	\N	\N
23933145	Prepulse inhibition (PPI) of startle is a measure of inhibitory function in which a weak leading stimulus suppresses the startle response to an intense stimulus. Usually, startle blink reflexes to an intense sound are used for measuring PPI. A recent magnetoencephalographic study showed that a similar phenomenon is observed for auditory change-related cortical response (Change-N1m) to an abrupt change in sound features. It has been well established that nicotine enhances PPI of startle. Therefore, in the present magnetoencephalographic study, the effects of acute nicotine on PPI of the Change-N1m were studied in 12 healthy subjects (two females and 10 males) under a repeated measures and placebo-controlled design. Nicotine (4 mg) was given as nicotine gum. The test Change-N1m response was elicited with an abrupt increase in sound pressure by 6 dB in a continuous background sound of 65 dB. PPI was produced by an insertion of a prepulse with a 3-dB-louder or 6-dB-weaker sound pressure than the background 75 ms before the test stimulus. Results show that nicotine tended to enhance the test Change-N1m response and significantly enhanced PPI for both prepulses. Therefore, nicotine's enhancing effect on PPI of the Change-N1m was similar to that on PPI of the startle. The present results suggest that the two measures share at least some mechanisms.	\N	\N
23973563	The physical intensity of a sound, usually expressed in dB on a logarithmic ratio scale, can easily be measured using technical equipment. Loudness is the perceptual correlate of sound intensity, and is usually determined by means of some sort of psychophysical scaling procedure. The interrelation of sound intensity and perceived loudness is still a matter of debate, and the physiological correlate of loudness perception in the human auditory pathway is not completely understood. Various studies indicate that the activation in human auditory cortex is more a representation of loudness sensation rather than of physical sound pressure level. This raises the questions (1), at what stage or stages in the ascending auditory pathway is the transformation of the physical stimulus into its perceptual correlate completed, and (2), to what extent other factors affecting individual loudness judgements might modulate the brain activation as registered by auditory neuroimaging. An overview is given about recent studies on the effects of sound intensity, duration, bandwidth and individual hearing status on the activation in the human auditory system, as measured by various approaches in auditory neuroimaging. This article is part of a Special Issue entitled Human Auditory Neuroimaging.	\N	\N
23974947	Tonal music is characterized by a continuous flow of tension and resolution. This flow of tension and resolution is closely related to processes of expectancy and prediction and is a key mediator of music-evoked emotions. However, the neural correlates of subjectively experienced tension and resolution have not yet been investigated. We acquired continuous ratings of musical tension for four piano pieces. In a subsequent functional magnetic resonance imaging experiment, we identified blood oxygen level-dependent signal increases related to musical tension in the left lateral orbitofrontal cortex (pars orbitalis of the inferior frontal gyrus). In addition, a region of interest analysis in bilateral amygdala showed activation in the right superficial amygdala during periods of increasing tension (compared with decreasing tension). This is the first neuroimaging study investigating the time-varying changes of the emotional experience of musical tension, revealing brain activity in key areas of affective processing.	\N	\N
23990061	We aim to evaluate the incidence and clinical manifestations of sensorineural hearing loss (SNHL) in adult patients with acute otitis media (AOM). Seventy-five patients (age > 18 years; 83 ears) diagnosed with AOM between January 2008 and March 2011 at our clinic were enroled and retrospectively reviewed. We detected audiometrically confirmed SNHL during the course of AOM in eight patients. The clinical course, treatment, and audiometric final outcome of each case were reviewed. SNHL was associated with AOM in 8 out of 83 ears (9.3%). The mean age of patients was 57.5 years, and the mean follow-up period was 21.1 months (range 0.6-46.3 months). The most common symptom was tinnitus. Mean bone conduction hearing threshold was 39.5 dB in pure tone audiometry. All patients showed high-frequency HL, and three showed pan-frequency HL. All patients were treated with oral antibiotics at the initial visit. Seven ears were treated with a combination of oral steroids. Myringotomy was also performed. Seven of eight patients showed improvement; however, 8 kHz thresholds were not improved. This suggested that the inflammation spread through the round window. The mean duration of recovery was 18.6 days. SNHL associated with AOM in adult patients occurs during the early phases of the disease course. High-frequency hearing was commonly affected and was well treated with oral antibiotics, myringotomy, and steroid therapy. Audiometry can be helpful for treating adult patients with AOM. Active treatment, including myringotomy, should be performed during the early phase, if SNHL is suspected.	\N	\N
23992133	The development of presbycusis, or age-related hearing loss, is determined by a combination of genetic and environmental factors. The auditory periphery exhibits a progressive bilateral, symmetrical reduction of auditory sensitivity to sound from high to low frequencies. The central auditory nervous system shows symptoms of decline in age-related cognitive abilities, including difficulties in speech discrimination and reduced central auditory processing, ultimately resulting in auditory perceptual abnormalities. The pathophysiological mechanisms of presbycusis include excitotoxicity, oxidative stress, inflammation, aging and oxidative stress-induced DNA damage that results in apoptosis in the auditory pathway. However, the originating signals that trigger these mechanisms remain unclear. For instance, it is still unknown whether insulin is involved in auditory aging. Auditory aging has preclinical lesions, which manifest as asymptomatic loss of periphery auditory nerves and changes in the plasticity of the central auditory nervous system. Currently, the diagnosis of preclinical, reversible lesions depends on the detection of auditory impairment by functional imaging, and the identification of physiological and molecular biological markers. However, despite recent improvements in the application of these markers, they remain under-utilized in clinical practice. The application of antisenescent approaches to the prevention of auditory aging has produced inconsistent results. Future research will focus on the identification of markers for the diagnosis of preclinical auditory aging and the development of effective interventions.	\N	\N
23992488	The state of hearing in 75-year old persons was measured in a population based epidemiological study with the aim of studying if hearing had changed during a time span of 29 years. An epidemiological study of generational effects in three age cohorts. Three age cohorts were included: cohort 1 (n: 267) born in 1976-77, cohort 4 (n: 197) in 1990-91, and cohort 6 (n: 570) in 2005. The same test procedures using pure-tone audiometry and a short questionnaire were applied to the three cohorts of 75-year old residents in the same city. The hearing was essentially unchanged during the span of the investigation-almost three decades. Low-frequency hearing was up to about 10 dB poorer in the most recently studied cohort compared to the previously studied cohorts. The reason for this difference is considered to depend on methodological factors. Self-assessed hearing and tinnitus was mainly unchanged, or had minor changes both to the better and to the worse. The hearing, both measured with pure-tone audiometry and with a short questionnaire, of 75-year old persons has not changed at all, or only marginally, over three decades.	\N	\N
23994183	Speech comprehension relies on auditory as well as visual information, and is enhanced in healthy subjects, when audiovisual (AV) information is present. Patients with schizophrenia have been reported to have problems regarding this AV integration process, but little is known about which underlying neural processes are altered. Functional magnetic resonance imaging was performed in 15 schizophrenia patients (SP) and 15 healthy controls (HC) to study functional connectivity of Broca's area by means of a beta series correlation method during perception of audiovisually presented bisyllabic German nouns, in which audio and video either matched or did not match. Broca's area of SP showed stronger connectivity with supplementary motor cortex for incongruent trials whereas HC connectivity was stronger for congruent trials. The right posterior superior temporal sulcus (RpSTS) area showed differences in connectivity for congruent and incongruent trials in HC in contrast to SP where the connectivity was similar for both conditions. These smaller differences in connectivity in SP suggest a less adaptive processing of audiovisually congruent and incongruent speech. The findings imply that AV integration problems in schizophrenia are associated with maladaptive connectivity of Broca's and RpSTS area in particular when confronted with incongruent stimuli. Results are discussed in light of recent AV speech perception models.	\N	\N
23998484	Electrode impedance increases following implantation and undergoes transitory reduction with onset of electrical stimulation. The studies in this paper measured the changes in access resistance and polarization impedance in vivo before and following electrical stimulation, and recorded the time course of these changes. Impedance measures recorded in (a) four cats following 6 months of cochlear implant use, and (b) three cochlear implant recipients with 1.5-5 years cochlear implant experience. Both the experimental and clinical data exhibited a reduction in electrode impedance, 20 and 5% respectively, within 15-30 minutes of stimulation onset. The majority of these changes occurred through reduction in polarization impedance. Cessation of stimulation was followed by an equivalent rise in impedance measures within 6-12 hours. Stimulus-induced reductions in impedance exhibit a rapid onset and are evident in both chronic in vivo models tested, even several years after implantation. Given the impedance changes were dominated by the polarization component, these findings suggest that the electrical stimulation altered the electrode surface rather than the bulk tissue and fluid in the cochlea.	\N	\N
24001008	Classical theories of semantic memory assume that concepts are represented in a unitary amodal memory system. In challenging this classical view, pure or hybrid modality-specific theories propose that conceptual representations are grounded in the sensory-motor brain areas, which typically process sensory and action-related information. Although neuroimaging studies provided evidence for a functional-anatomical link between conceptual processing of sensory or action-related features and the sensory-motor brain systems, it has been argued that aspects of such sensory-motor activation may not directly reflect conceptual processing but rather strategic imagery or postconceptual elaboration. In the present ERP study, we investigated masked effects of acoustic and action-related conceptual features to probe unconscious automatic conceptual processing in isolation. Subliminal feature-specific ERP effects at frontocentral electrodes were observed, which differed with regard to polarity, topography, and underlying brain electrical sources in congruency with earlier findings under conscious viewing conditions. These findings suggest that conceptual acoustic and action representations can also be unconsciously accessed, thereby excluding any postconceptual strategic processes. This study therefore further substantiates a grounding of conceptual and semantic processing in action and perception.	\N	\N
24002965	Dual-system models of visual category learning posit the existence of an explicit, hypothesis-testing reflective system, as well as an implicit, procedural-based reflexive system. The reflective and reflexive learning systems are competitive and neurally dissociable. Relatively little is known about the role of these domain-general learning systems in speech category learning. Given the multidimensional, redundant, and variable nature of acoustic cues in speech categories, our working hypothesis is that speech categories are learned reflexively. To this end, we examined the relative contribution of these learning systems to speech learning in adults. Native English speakers learned to categorize Mandarin tone categories over 480 trials. The training protocol involved trial-by-trial feedback and multiple talkers. Experiments 1 and 2 examined the effect of manipulating the timing (immediate vs. delayed) and information content (full vs. minimal) of feedback. Dual-system models of visual category learning predict that delayed feedback and providing rich, informational feedback enhance reflective learning, while immediate and minimally informative feedback enhance reflexive learning. Across the two experiments, our results show that feedback manipulations that targeted reflexive learning enhanced category learning success. In Experiment 3, we examined the role of trial-to-trial talker information (mixed vs. blocked presentation) on speech category learning success. We hypothesized that the mixed condition would enhance reflexive learning by not allowing an association between talker-related acoustic cues and speech categories. Our results show that the mixed talker condition led to relatively greater accuracies. Our experiments demonstrate that speech categories are optimally learned by training methods that target the reflexive learning system.	\N	\N
24003904	In a system where tens of thousands of words are made up of a limited number of phonemes, many words are bound to sound alike. This similarity of the words in the lexicon as characterized by phonological neighbourhood density (PhND) has been shown to affect speed and accuracy of word comprehension and production. Whereas there is a consensus about the interfering nature of neighbourhood effects in comprehension, the language production literature offers a more contradictory picture with mainly facilitatory but also interfering effects reported on word production. Here we report both of these two types of effects in the same study. Multiple regression mixed models analyses were conducted on PhND effects on errors produced in a naming task by a group of 21 participants with aphasia. These participants produced more formal errors (interfering effect) for words in dense phonological neighbourhoods, but produced fewer nonwords and semantic errors (a facilitatory effect) with increasing density. In order to investigate the nature of these opposite effects of PhND, we further analysed a subset of formal errors and nonword errors by distinguishing errors differing on a single phoneme from the target (corresponding to the definition of phonological neighbours) from those differing on two or more phonemes. This analysis confirmed that only formal errors that were phonological neighbours of the target increased in dense neighbourhoods, while all other errors decreased. Based on additional observations favouring a lexical origin of these formal errors (they exceeded the probability of producing a real-word error by chance, were of a higher frequency, and preserved the grammatical category of the targets), we suggest that the interfering effect of PhND is due to competition between lexical neighbours and target words in dense neighbourhoods.	\N	\N
24003982	This study employed Boothroyd and Nittrouer's k (1988) to directly quantify effectiveness in native versus non-native listeners' use of semantic cues. Listeners were presented speech-perception-in-noise sentences processed at three levels of concurrent multi-talker babble and reverberation. For each condition, 50 sentences with multiple semantic cues and 50 with minimum semantic cues were randomly presented. Listeners verbally reported and wrote down the target words. The metric, k, was derived from percent-correct scores for sentences with and without semantics. Ten native and 33 non-native listeners participated. The presence of semantics increased recognition benefit by over 250% for natives, but access to semantics remained limited for non-native listeners (90-135%). The k was comparable across conditions for native listeners, but level-dependent for non-natives. The k for non-natives was significantly different from 1 in all conditions, suggesting semantic cues, though reduced in importance in difficult conditions, were helpful for non-natives. Non-natives as a group were not as effective in using semantics to facilitate English sentence recognition as natives. Poor listening conditions were particularly adverse to the use of semantics in non-natives, who may rely on clear acoustic-phonetic cues before benefitting from semantic cues when recognizing connected speech.	\N	\N
24005532	It has been hypothesized that selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction can occur more frequently in patients with higher central serotonergic activity, and that this higher serotonergic activity can induce inhibition of sexual desire, ejaculation, and orgasm. Thus, the aim of this study was to determine the relationship between SSRI-induced sexual dysfunction and increased serotonin. Event-related potentials for the loudness dependence of auditory evoked potentials (LDAEP) were measured in 46 patients at a single time point. The subjects' scores on the Hamilton Depression Rating Scale and Antidepressant Side-Effect Checklist were also determined by the investigators at the same time point. All patients had received SSRI monotherapy. Overall, 37 % (17/46) of the patients experienced some form of SSRI-induced sexual dysfunction: lack of sexual desire, impotence, orgasm, and menstrual abnormality or mastalgia were experienced by 21.7, 8.3, 15.2, and 20.6 % of the patients, respectively. The subjects were thus divided into two groups-those with and without sexual dysfunction-and their data were compared. There was a tendency for the LDAEP to be lower in the group with sexual dysfunction (1.04 ± 0.77 μV) than the group without sexual dysfunction (1.45 ± 0.86 μV), although the difference was not statistically significant (p = 0.086). Furthermore, the distribution of the frequency of SSRI-induced sexual dysfunction differed marginally significantly between patients with low and high LDAEP, dichotomized according to the median LDAEP on the Cz electrode (χ (2) = 3.664, p = 0.056). There was a relatively high frequency of SSRI-induced sexual dysfunction in patients with low LDAEP.	\N	\N
24009759	Recent studies employing speech stimuli to investigate 'cocktail-party' listening have focused on entrainment of cortical activity to modulations at syllabic (5 Hz) and phonemic (20 Hz) rates. The data suggest that cortical modulation filters (CMFs) are dependent on the sound-frequency channel in which modulations are conveyed, potentially underpinning a strategy for separating speech from background noise. Here, we characterize modulation filters in human listeners using a novel behavioral method. Within an 'inverted' adaptive forced-choice increment detection task, listening level was varied whilst contrast was held constant for ramped increments with effective modulation rates between 0.5 and 33 Hz. Our data suggest that modulation filters are tonotopically organized (i.e., vary along the primary, frequency-organized, dimension). This suggests that the human auditory system is optimized to track rapid (phonemic) modulations at high sound-frequencies and slow (prosodic/syllabic) modulations at low frequencies.	\N	\N
24022792	Processing multiple complex features to create cohesive representations of objects is an essential aspect of both the visual and auditory systems. It is currently unclear whether these processes are entirely modality specific or whether there are amodal processes that contribute to complex object processing in both vision and audition. We investigated this using a dual-stream target detection task in which two concurrent streams of novel visual or auditory stimuli were presented. We manipulated the degree to which each stream taxed processing conjunctions of complex features. In two experiments, we found that concurrent visual tasks that both taxed conjunctive processing strongly interfered with each other but that concurrent auditory and visual tasks that both taxed conjunctive processing did not. These results suggest that resources for processing conjunctions of complex features within vision and audition are modality specific.	\N	\N
24023379	Effects of clicks and tonebursts on early and late auditory middle latency response (AMLR) components were evaluated in young and older cigarette smokers and nonsmokers. Participants ( n = 49) were categorized by smoking and age into 4 groups: (a) older smokers, (b) older nonsmokers, (c) young smokers, and (d) young nonsmokers. Monaural, 2-channel AMLRs were acquired from Fz and Cz electrodes with 3 stimuli (clicks, 500 Hz, and 3000 Hz). Group differences included significantly higher V-Na amplitude in young adults and shorter Pb latency in older nonsmokers. Young smokers had a significantly higher Nb-Pb amplitude and shorter Nb latency than other groups. Toneburst stimuli yielded significantly longer V, Na, and Pa latencies compared to clicks. Pb latency was shorter at Fz than at Cz. Relative amplitudes were significantly higher at Fz than at Cz overall; Pa-Nb and Nb-Pb were significantly lower for 3000 Hz than for 500 Hz and clicks. Responses from young smokers revealed a higher amplitude and shorter latency for later AMLR waves, reflecting an arousal effect of smoking in cortical and subcortical generators. AMLR differences in older adults may be due to age-related neurochemical changes in the central nervous system. Stimulus and electrode differences plus smoking and aging effects can guide neurodiagnostic AMLR protocols, especially in young adult smokers.	\N	\N
24026024	To standardize the information for families of children having functional surgery for middle ear malformations, we describe the audiometric results of the subgroup of patients with the most favorable anatomic conditions: viable auditory canal, intact tympanic membrane, mobile stapes, and corresponding to a Jahrsdoerfer score of 8 or higher. Case series, tertiary referral center. Charts of patients undergoing functional surgery for congenital middle ear malformations were reviewed for demographic data, preoperative Jahrsdoerfer score, ossicular chain status, type of ossiculoplasty, and audiometric data before and 6 months postsurgery. Eighteen consecutive interventions were performed on 13 patients (average age of 9 years, 8 girls and 5 boys) between 2004 and 2011. The ossiculoplasties performed were as follows: incus repositioning (4), double-layer tragal cartilage (5), intact native chain reconstruction (3), and partial ossicular prosthesis (6). Mean air bone gap (ABG) was 40.8 ± 12.4 dB preoperatively and 20.9 ± 12.9 dB postoperatively (p < 0.0001). Preoperative and postoperatively mean air conduction PTA thresholds were 49.9 ± 9.5 and 30.0 ± 14.1 dB, respectively (p < 0.0001). All ears operated on except one had air conduction improvement. There were no complications. Functional surgery for congenital middle ear malformations gives variable hearing outcomes. In this study, with the most favorable anatomic conditions, 12 ears (67%) of 18 had air conduction improvement below 30 dB.	\N	\N
24028890	Most hearing aid prescriptions focus on the optimization of a metric derived from the long-term average spectrum of speech, and do not consider how the prescribed values might distort the temporal envelope shape. A growing body of evidence suggests that such distortions can lead to systematic errors in speech perception, and therefore hearing aid prescriptions might benefit by including preservation of the temporal envelope shape in their rationale. To begin to explore this possibility, we designed a genetic algorithm (GA) to find the multiband compression settings that preserve the shape of the original temporal envelope while placing that envelope in the listener's audiometric dynamic range. The resulting prescription had a low compression threshold, short attack and release times, and a combination of compression ratio and gain that placed the output signal within the listener's audiometric dynamic range. Initial behavioral tests of individuals with impaired hearing revealed no difference in speech-in-noise perception between the GA and the NAL-NL2 prescription. However, gap detection performance was superior with the GA in comparison to NAL-NL2. Overall, this work is a proof of concept that consideration of temporal envelope distortions can be incorporated into hearing aid prescriptions.	\N	\N
24041778	Congenital amusia is a neuro-developmental disorder of music perception and production. Recent findings have demonstrated that this deficit is linked to an impaired short-term memory for tone sequences. As it has been shown before that non-musicians' implicit knowledge of musical regularities can improve short-term memory for tone information, the present study investigated if this type of implicit knowledge could also influence amusics' short-term memory performance. Congenital amusics and their matched controls, who were non-musicians, had to indicate whether sequences of five tones, presented in pairs, were the same or different; half of the pairs respected musical regularities (tonal sequences) and the other half did not (atonal sequences). As previously reported for non-musician participants, the control participants showed better performance (as measured with d') for tonal sequences than for atonal ones. While this improvement was not observed in amusics, both control and amusic participants showed faster response times for tonal sequences than for atonal sequences. These findings suggest that some implicit processing of tonal structures is potentially preserved in congenital amusia. This observation is encouraging as it strengthens the perspective to exploit implicit knowledge to help reducing pitch perception and memory deficits in amusia.	\N	\N
24043402	Our previous studies using fMRI have demonstrated that activations in human auditory cortex (AC) are strongly dependent on the characteristics of the task. The present study tested whether source estimation of scalp-recorded event-related potentials (ERPs) can be used to investigate task-dependent AC activations. Subjects were presented with frequency-varying two-part tones during pitch discrimination, pitch n-back memory, and visual tasks identical to our previous fMRI study (Rinne et al., J Neurosci 29:13338-13343, 2009). ERPs and their minimum-norm source estimates in AC were strongly modulated by task at 200-700 ms from tone onset. As in the fMRI study, the pitch discrimination and pitch memory tasks were associated with distinct AC activation patterns. In the pitch discrimination task, increased activity in the anterior AC was detected relatively late at 300-700 ms from tone onset. Therefore, this activity was probably not associated with enhanced pitch processing but rather with the actual discrimination process (comparison between the two parts of tone). Increased activity in more posterior areas associated with the pitch memory task, in turn, occurred at 200-700 ms suggesting that this activity was related to operations on pitch categories after pitch analysis was completed. Finally, decreased activity associated with the pitch memory task occurred at 150-300 ms consistent with the notion that, in the demanding pitch memory task, spectrotemporal analysis is actively halted as soon as category information has been obtained. These results demonstrate that ERP source analysis can be used to complement fMRI to investigate task-dependent activations of human AC.	\N	\N
24043565	What conditions, if any, can fully prevent attentional capture (i.e., involuntary allocation of spatial attention to an irrelevant object) has been a matter of debate. In a previous study, Folk, Ester, and Troemel (Psychonomic Bulletin & Review 16:127-132, 2009) suggested that attentional capture can be blocked entirely when attention is already engaged in a different object. This conclusion relied on the finding that in a search for a known-color target in a rapid serial visual presentation stream, a peripheral distractor with the target color did not further impair target identification performance when a distractor also with the target color that appeared in the stream had already captured attention. In the present study, we argue that this conclusion is unwarranted, because the effects of the central and peripheral distractors could not be disentangled. In order to isolate the effect of the peripheral distractor, we introduced a distractor-target letter compatibility manipulation. Our results showed that the peripheral distractor summoned attention, irrespective of whether attention had just been engaged. We conclude that neither spatially focused attention nor attentional engagement is sufficient to prevent attentional capture.	\N	\N
24055624	This study investigated the perceptual relationship between acoustic and electric stimuli presented to CI users with functional contralateral hearing. Fourteen subjects with unilateral profound deafness implanted with a MED-EL CI scaled the perceptual differences between pure tones presented to the acoustic hearing ear and electric biphasic pulse trains presented to the implanted ear. The differences were analyzed with a multidimensional scaling (MDS) analysis. Additionally, speech performance in noise was tested using sentence material presented in different spatial configurations while patients listened with both their acoustic hearing and implanted ears. Results of alternating least squares scaling (ALSCAL) analysis consistently demonstrate that a change in place of stimulation is in the same perceptual dimension as a change in acoustic frequency. However, the relative perceptual differences between the acoustic and the electric stimuli varied greatly across subjects. A degree of perceptual separation between acoustic and electric stimulation (quantified by relative dimensional weightings from an INDSCAL analysis) was hypothesized that would indicate a change in perceptual quality, but also be predictive of performance with combined acoustic and electric hearing. Perceptual separation between acoustic and electric stimuli was observed for some subjects. However, no relationship between the degree of perceptual separation and performance was found.	\N	\N
24059596	To establish the reliability and validity of an automated hearing screening test system for children. Cross-sectional within a comparative study of subjects. Subjects were 325 first-grade and second-grade children (6-10 years old) from primary schools in Shenzhen, China. Using the conventional pure-tone screening test with the pass/refer criterion set as 25 dB HL, as the 'gold standard", the sensitivity and specificity of the automated hearing screening test was 0.63 and 0.82, respectively. No specific pattern in the failure rates was observed to relate to the students' grade. There was no statistically significant age effect or gender effect. The results suggest that with further improvement in terms of its sensitivity and specificity, it may be feasible to use the automated hearing screening test system to conduct routine school hearing screenings.	\N	\N
24067501	To confirm an increased susceptibility to informational masking among individuals with single-sided deafness (SSD). To demonstrate a reduction in informational masking when SSD is treated with an integrated bone conduction hearing aid (IBC). To identify the acoustic cues that contribute to IBC-aided masking release. To determine the effects of device experience on the IBC advantage. Informational masking was evaluated with the coordinate-response measure. Participants performed the task by reporting color and number coordinates that changed randomly within target sentences. The target sentences were presented in free field accompanied by zero to three distracting sentences. Target and distracting sentences were spoken by different talkers and originated from different source locations, creating two sources of information for auditory streaming. Susceptibility to informational masking was inferred from the error rates of unaided SSD patients relative to normal controls. These baseline measures were derived by testing inexperienced IBC users without the device on the day of their initial fitting. The benefits of IBC-aided listening were assessed by measuring the aided performance of users who had at least 3 months' device experience. The acoustic basis of the listening advantage was isolated by correlating response errors with the voice pitch and location of distracting sentences. The effects of learning on cue effectiveness were evaluated by comparing the error rates of experienced and inexperienced users. Unaided SSD participants (inexperienced users) performed as well as normal controls when tested without distracting sentences but produced significantly higher error rates when tested with distracting sentences. Most errors involved responding with coordinates that were contained in distracting sentences. This increased susceptibility to informational masking was significantly reduced when experienced IBC users were tested with the device. The listening advantage was most strongly correlated with the availability of voice pitch cues, although performance was also influenced by the location of distracting sentences. Directional asymmetries appear to be dictated by location-dependent cues that are derived from the distinctive transmission characteristics of IBC stimulation. Experienced users made better use of these cues than inexperienced users. These results suggest that informational masking is a significant source of communication impairment among individuals with SSD. Despite the lateralization of auditory function, unaided SSD subjects experience informational masking when distractors occur in either the deaf or normal spatial hemifield. Restoration of aural sensitivity in the deaf hemifield with an IBC enhances speech intelligibility under complex listening conditions, presumably by providing additional sound-segregation cues that are derived from voice pitch and spatial location. The optimal use of these cues is not immediate, but a significant listening advantage is observed after 3 months of unstructured use.	\N	\N
24071587	Stereo vision has a well-known anisotropy: At low frequencies, horizontally oriented sinusoidal depth corrugations are easier to detect than vertically oriented corrugations (both defined by horizontal disparities). Previously, Serrano-Pedraza and Read (2010) suggested that this stereo anisotropy may arise because the stereo system uses multiple spatial-frequency disparity channels for detecting horizontally oriented modulations but only one for vertically oriented modulations. Here, we tested this hypothesis using the critical-band masking paradigm. In the first experiment, we measured disparity thresholds for horizontal and vertical sinusoids near the peak of the disparity sensitivity function (0.4 cycles/°), in the presence of either broadband or notched noise. We fitted the power-masking model to our results assuming a channel centered on 0.4 cycles/°. The estimated channel bandwidths were 2.95 octaves for horizontal and 2.62 octaves for vertical corrugations. In our second experiment we measured disparity thresholds for horizontal and vertical sinusoids of 0.1 cycles/° in the presence of band-pass noise centered on 0.4 cycles/° with a bandwidth of 0.5 octaves. This mask had only a small effect on the disparity thresholds, for either horizontal or vertical corrugations. We simulated the detection thresholds using the power-masking model with the parameters obtained in the first experiment and assuming either single-channel and multiple-channel detection. The multiple-channel model predicted the thresholds much better for both horizontal and vertical corrugations. We conclude that the human stereo system must contain multiple independent disparity channels for detecting horizontally oriented and vertically oriented depth modulations.	\N	\N
24073696	To investigate the effects of emotional music on visual processes, we analyzed visual evoked magnetic fields (VEF) on listening to emotional music in 14 healthy subjects. Positive and negative pieces of music were delivered during VEF recording following stimulation by emotionally neutral pictures of faces and landscapes. VEF components at 100 (M100) and 150 (M170)ms after stimulus onset were analyzed, and the estimated current strength for M170 following face stimulation was enhanced with negative compared to positive music in the right hemisphere. The equivalent current dipole for M100 and M170 was estimated in the primary visual cortex (V1) and inferior temporal area (IT), respectively. The present results indicate that background music showed a top-down control of the visual processes in IT, which is a core site responsible for the interpretation of facial expression. The emotional contents of music could alter visual processes, especially those involving the face.	\N	\N
24076424	For much of the past 30 years, investigations of auditory perception and language have been enhanced or even driven by the use of functional neuroimaging techniques that specialize in localization of central responses. Beginning with investigations using positron emission tomography (PET) and gradually shifting primarily to usage of functional magnetic resonance imaging (fMRI), auditory neuroimaging has greatly advanced our understanding of the organization and response properties of brain regions critical to the perception of and communication with the acoustic world in which we live. As the complexity of the questions being addressed has increased, the techniques, experiments and analyses applied have also become more nuanced and specialized. A brief review of the history of these investigations sets the stage for an overview and analysis of how these neuroimaging modalities are becoming ever more effective tools for understanding the auditory brain. We conclude with a brief discussion of open methodological issues as well as potential clinical applications for auditory neuroimaging. This article is part of a Special Issue entitled Human Auditory Neuroimaging.	\N	\N
24076425	Harmonic complexes that generate highly modulated temporal envelopes on the basilar membrane (BM) mask a tone less effectively than complexes that generate relatively flat temporal envelopes, because the non-linear active gain of the BM selectively amplifies a low-level tone in the dips of a modulated masker envelope. The present study examines a similar effect in speech recognition. Speech reception thresholds (SRTs) were measured for a voice masked by harmonic complexes with partials in sine phase (SP) or in random phase (RP). The masker's fundamental frequency (F0) was 50, 100 or 200 Hz. SRTs were considerably lower for SP than for RP maskers at 50-Hz F0, but the two converged at 100-Hz F0, while at 200-Hz F0, SRTs were a little higher for SP than RP maskers. The results were similar whether the target voice was male or female and whether the masker's spectral profile was flat or speech-shaped. Although listening in the masker dips has been shown to play a large role for artificial stimuli such as Schroeder-phase complexes at high levels, it contributes weakly to speech recognition in the presence of harmonic maskers with different crest factors at more moderate sound levels (65 dB SPL).	\N	\N
24086676	The auditory illusory perception "scale illusion" occurs when a tone of ascending scale is presented in one ear, a tone of descending scale is presented simultaneously in the other ear, and vice versa. Most listeners hear illusory percepts of smooth pitch contours of the higher half of the scale in the right ear and the lower half in the left ear. Little is known about neural processes underlying the scale illusion. In this magnetoencephalographic study, we recorded steady-state responses to amplitude-modulated short tones having illusion-inducing pitch sequences, where the sound level of the modulated tones was manipulated to decrease monotonically with increase in pitch. The steady-state responses were decomposed into right- and left-sound components by means of separate modulation frequencies. It was found that the time course of the magnitude of response components of illusion-perceiving listeners was significantly correlated with smooth pitch contour of illusory percepts and that the time course of response components of stimulus-perceiving listeners was significantly correlated with discontinuous pitch contour of stimulus percepts in addition to the contour of illusory percepts. The results suggest that the percept of illusory pitch sequence was represented in the neural activity in or near the primary auditory cortex, i.e., the site of generation of auditory steady-state response, and that perception of scale illusion is maintained by automatic low-level processing.	\N	\N
24089491	The strategies by which the central nervous system decodes the properties of sensory stimuli, such as sound source location, from the responses of a population of neurons are a matter of debate. We show, using the average firing rates of neurons in the inferior colliculus (IC) of awake rabbits, that prevailing decoding models of sound localization (summed population activity and the population vector) fail to localize sources accurately due to heterogeneity in azimuth tuning across the population. In contrast, a maximum-likelihood decoder operating on the pattern of activity across the population of neurons in one IC accurately localized sound sources in the contralateral hemifield, consistent with lesion studies, and did so with a precision consistent with rabbit psychophysical performance. The pattern decoder also predicts behavior in response to incongruent localization cues consistent with the long-standing "duplex" theory of sound localization. We further show that the pattern decoder accurately distinguishes two concurrent, spatially separated sources from a single source, consistent with human behavior. Decoder detection of small amounts of source separation directly in front is due to neural sensitivity to the interaural decorrelation of sound, at both low and high frequencies. The distinct patterns of IC activity between single and separated sound sources thereby provide a neural correlate for the ability to segregate and localize sources in everyday, multisource environments.	\N	\N
24095845	Pitch is derived by the auditory system through complex spectrotemporal processing. Pitch extraction is thought to depend on both spectral cues arising from lower harmonics that are resolved by cochlear filters in the inner ear, and on temporal cues arising from the pattern of action potentials contained in the cochlear output. Adults are capable of extracting pitch in the absence of robust spectral cues, taking advantage of the temporal cues that remain. However, recent behavioral evidence suggests that infants have difficulty discriminating between stimuli with different pitches when resolvable spectral cues are absent. In the current experiments, we used the mismatch negativity (MMN) component of the event related potential derived from electroencephalographic (EEG) recordings to examine a cortical representation of pitch discrimination for iterated rippled noise (IRN) stimuli in 4- and 8-month-old infants. IRN stimuli are pitch-evoking sounds generated by repeatedly adding a segment of white noise to itself at a constant delay. We created IRN stimuli (delays of 5 and 6ms creating pitch percepts of 200 and 167Hz) and high-pass filtered them to remove all resolvable spectral pitch cues. In experiment 1, we did not find EEG evidence that infants could detect the change in the pitch of these IRN stimuli. However, in Experiment 2, after a brief period of pitch-priming during which we added a sine wave component to the IRN stimulus at its perceived pitch, infants did show significant MMN in response to pitch changes in the IRN stimuli with sine waves removed. This suggests that (1) infants can use temporal cues to process pitch, although such processing is not mature and (2) that a short amount of pitch-priming experience can alter pitch representations in auditory cortex during infancy.	\N	\N
24105268	This study examined the ability of click auditory brainstem response (ABR) undertaken below the age of 6 months (from expected date of delivery) to differentiate between conductive and sensorineural hearing loss (SNHL), using the latency of wave V measured 20 dB above threshold. Subjects were recruited if they had an ABR threshold of ≥ 40 dB nHL and ≤ 70 dB nHL in one or both ears measured below the age of 6 months and they had also attended follow-up appointments for behavioral assessment of their hearing in which the type of hearing loss had been confirmed. Forty-five children (84 ears) with SNHL, 82 children (141 ears) with temporary conductive hearing loss (TCHL), and 5 children (10 ears) with permanent conductive hearing loss (PCHL) were recruited. The differences between mean wave V latencies measured 20 dB above ABR threshold were examined using the independent t-test for the groups of cases with SNHL, TCHL, and PCHL. Signal-detection theory was used to examine the relationship between sensitivity and specificity when the latency of wave V 20 dB above threshold was used to identify the presence of SNHL. Receiver operating characteristics were generated and the coordinates of the curve examined for the best compromise between sensitivity and false-alarm rate. The specificity, positive predictive value, and probability of missing a true case were determined for the most promising criteria. There were significant differences between the two groups with SNHL and TCHL. The mean latency of wave V 20 dB above threshold was 1 msec shorter in those with SNHL compared with those with TCHL. There were significant differences between children with PCHL and SNHL but no difference between those with PCHL and TCHL. When a criterion of < 7.6 msec was chosen to predict the presence of SNHL the test sensitivity was 0.98, test specificity 0.71, and positive predictive value was 0.66. Nine out of 10 of those with a latency 20 dB above threshold of < 7.0 msec had an SNHL. The latency of wave V 20 dB above threshold measured using click ABR is a useful indicator of the type of hearing loss in babies referred from newborn hearing screening.	\N	\N
24108804	Synchronizing movements with rhythmic inputs requires tight coupling of sensory and motor neural processes. Here, using a novel approach based on the recording of steady-state-evoked potentials (SS-EPs), we examine how distant brain areas supporting these processes coordinate their dynamics. The electroencephalogram was recorded while subjects listened to a 2.4-Hz auditory beat and tapped their hand on every second beat. When subjects tapped to the beat, the EEG was characterized by a 2.4-Hz SS-EP compatible with beat-related entrainment and a 1.2-Hz SS-EP compatible with movement-related entrainment, based on the results of source analysis. Most importantly, when compared with passive listening of the beat, we found evidence suggesting an interaction between sensory- and motor-related activities when subjects tapped to the beat, in the form of (1) additional SS-EP appearing at 3.6 Hz, compatible with a nonlinear product of sensorimotor integration; (2) phase coupling of beat- and movement-related activities; and (3) selective enhancement of beat-related activities over the hemisphere contralateral to the tapping, suggesting a top-down effect of movement-related activities on auditory beat processing. Taken together, our results are compatible with the view that rhythmic sensorimotor synchronization is supported by a dynamic coupling of sensory and motor related activities.	\N	\N
24110502	Bone-conducted ultrasound (BCU) is perceived even by the profoundly sensorineural deaf. A novel hearing aid using the perception of amplitude-modulated BCU (BCU hearing aid: BCUHA) has been developed. However, there is room for improvement particularly in terms of articulation and sound quality. BCU speech is accompanied by a strong high-pitched tone and contain some distortion. In this study, transposed modulation, that can be expected to reduce the high-pitched tone was newly employed as a modulation method in the BCUHA, and its resulting articulation, intelligibility and sound quality were evaluated. The results showed that transposed modulation showed nearly equal articulation and intelligibility scores to and better sound quality than the existing method, DSB-TC modulation. These results provide useful information for further development of the BCUHA.	\N	\N
24111102	Auditory Brainstem Responses (ABRs) are commonly used in clinical practice to determine hearing impairments and hearing thresholds. Although many research groups work on automatic recognition of ABRs - in order to decrease the acquisition times - measures to determine the quality of ABR measurements objectively are still missing. In fact, recently released new standards for electroencephalographic measurements in auditory examinations require an objective measurement quality assessment for neurodiagnostic devices. Thus there is a pressing need for the development and evaluation of such a quality control. In this study, we propose (a) a novel technique for the assessment of the ABR measurement quality and (b) evaluate and compare this technique to two other approaches which have been suggested in literature as required by the new standards.	\N	\N
24116424	Speech reception thresholds were obtained in normally hearing listeners for sentence targets masked by harmonic complexes constructed with different phase relationships. Maskers had either a constant fundamental frequency (F0), or had F0 changing over time, following a pitch contour extracted from natural speech. The median F0 of the target speech was very similar to that of the maskers. In experiment 1 differences in the masking produced by Schroeder positive and Schroeder negative phase complexes were small (around 1.5 dB) for moderate levels [60 dB sound pressure level (SPL)], but increased to around 6 dB for maskers at 80 dB SPL. Phase effects were typically around 1.5 dB larger for maskers that had naturally varying F0 contours than for maskers with constant F0. Experiment 2 showed that shaping the long-term spectrum of the maskers to match the target speech had no effect. Experiment 3 included additional phase relationships at moderate levels and found no effect of phase. Therefore, the phase relationship within harmonic complexes appears to have only minor effects on masking effectiveness, at least at moderate levels, and when targets and maskers are in the same F0 range.	\N	\N
24121087	Functional hemispheric differences for speech and language processing have been traditionally studied by using verbal dichotic-listening paradigms. The commonly observed right-ear preference for the report of dichotically presented syllables is taken to reflect the left hemispheric dominance for speech processing. However, the results of recent functional imaging studies also show that both hemispheres - not only the left - are engaged by dichotic listening, suggesting a more complex relationship between behavioral laterality and functional hemispheric activation asymmetries. In order to more closely examine the hemispheric differences underlying dichotic-listening performance, we report an analysis of functional magnetic resonance imaging (fMRI) data of 104 right-handed subjects, for the first time combining an interhemispheric difference and conjunction analysis. This approach allowed for a distinction of homotopic brain regions which showed symmetrical (i.e., brain region significantly activated in both hemispheres and no activation difference between the hemispheres), relative asymmetrical (i.e., activated in both hemispheres but significantly stronger in one than the other hemisphere), and absolute asymmetrical activation patterns (i.e., activated only in one hemisphere and this activation is significantly stronger than in the other hemisphere). Symmetrical activation was found in large clusters encompassing temporal, parietal, inferior frontal, and medial superior frontal regions. Relative and absolute left-ward asymmetries were found in the posterior superior temporal gyrus, located adjacent to symmetrically activated areas, and creating a lateral-medial gradient from symmetrical towards absolute asymmetrical activation within the peri-Sylvian region. Absolute leftward asymmetry was also found in the post-central and medial superior frontal gyri, while rightward asymmetries were found in middle temporal and middle frontal gyri. We conclude that dichotic listening engages a bihemispheric cortical network, showing a symmetrical and mostly leftward asymmetrical pattern. The here obtained functional (a)symmetry map might serve as a basis for future studies which - by studying the relevance of the here identified regions - clarify the relationship between behavioral laterality measures and hemispheric asymmetry.	\N	\N
24121711	The purpose of this study was to investigate the influence of contingent auditory feedback on the development of infant reaching. Eleven full-term infants were observed biweekly from the age of 10 weeks to 16 weeks, and their arm kinematics were recorded. Auditory feedback that was contingent on arm kinematics was provided in the form of: (a) the mother's voice; and (b) musical tones. Results showed that providing auditory feedback (mother's voice or musical tones): (i) increased the amplitude of exploratory arm movements before the onset of reaching; and (ii) increased the number of reaches at the onset of reaching. These results show that infants are able to use contingent auditory feedback to explore the relevant possibilities for action that are subsequently shaped into goal-directed movements.	\N	\N
24122619	To determine the effectiveness of simultaneous versus sequential bilateral cochlear implantation on postoperative outcomes in children with bilateral deafness and to evaluate the impact of the inter-implant interval and age at second implantation on postoperative outcomes in children who already received their first cochlear implant. PubMed, Embase, and Web of Science. All studies comparing the effects of simultaneous with sequential bilateral cochlear implantation on postoperative outcomes and those evaluating the impact of the inter-implant interval and age at second implantation were retrieved. Four studies compared the effects of simultaneous with sequential bilateral cochlear implantation. All studies lacked randomization. Of these, three reported better speech perception and expressive language development at one year of bilateral experience for simultaneous cochlear implantation. Of the nineteen publications on the impact of the inter-implant interval on postoperative outcomes, the risk of bias was low-moderate for seven studies which were derived from five different study populations. In two of these populations no impact of the inter-implant interval was found, while in three a longer inter-implant interval was associated with poorer speech and language development. Observational studies suggest that simultaneous implantation in children may be associated with improved speech and language development, and that a prolonged inter-implant interval between both implantations may have a negative impact on these postoperative outcomes. Randomized trials are, however, needed to demonstrate whether simultaneous implantation indeed is superior to sequential bilateral implantation in children with bilateral deafness. NA.	\N	\N
24125574	It is not unusual to find it stated as a fact that the left hemisphere is specialized for the processing of rapid, or temporal aspects of sound, and that the dominance of the left hemisphere in the perception of speech can be a consequence of this specialization. In this review we explore the history of this claim and assess the weight of this assumption. We will demonstrate that instead of a supposed sensitivity of the left temporal lobe for the acoustic properties of speech, it is the right temporal lobe which shows a marked preference for certain properties of sounds, for example longer durations, or variations in pitch. We finish by outlining some alternative factors that contribute to the left lateralization of speech perception.	\N	\N
24125858	Auditory verbal hallucinations (AVHs) are the experience of hearing voices in the absence of any speaker, often associated with a schizophrenia diagnosis. Prominent cognitive models of AVHs suggest they may be the result of inner speech being misattributed to an external or non-self source, due to atypical self- or reality monitoring. These arguments are supported by studies showing that people experiencing AVHs often show an externalising bias during monitoring tasks, and neuroimaging evidence which implicates superior temporal brain regions, both during AVHs and during tasks that measure verbal self-monitoring performance. Recently, efficacy of noninvasive neurostimulation techniques as a treatment option for AVHs has been tested. Meta-analyses show a moderate effect size in reduction of AVH frequency, but there has been little attempt to explain the therapeutic effect of neurostimulation in relation to existing cognitive models. This article reviews inner speech models of AVHs, and argues that a possible explanation for reduction in frequency following treatment may be modulation of activity in the brain regions involving the monitoring of inner speech.	\N	\N
24132709	Three cross-modal priming experiments examined the influence of preexposure to pictures and printed words on the speed of spoken word recognition. Targets for auditory lexical decision were spoken Dutch words and nonwords, presented in isolation (Experiments 1 and 2) or after a short phrase (Experiment 3). Auditory stimuli were preceded by primes, which were pictures (Experiments 1 and 3) or those pictures' printed names (Experiment 2). Prime-target pairs were phonologically onset related (e.g., pijl-pijn, arrow-pain), were from the same semantic category (e.g., pijl-zwaard, arrow-sword), or were unrelated on both dimensions. Phonological interference and semantic facilitation were observed in all experiments. Priming magnitude was similar for pictures and printed words and did not vary with picture viewing time or number of pictures in the display (either one or four). These effects arose even though participants were not explicitly instructed to name the pictures and where strategic naming would interfere with lexical decision making. This suggests that, by default, processing of related pictures and printed words influences how quickly we recognize spoken words.	\N	\N
24165303	Distortion-product otoacoustic emissions (DPOAEs) collected after sound pressure level (SPL) calibration are susceptible to standing waves that affect measurements at the plane of the probe microphone due to overlap of incident and reflected waves. These standing-wave effects can be as large as 20 dB, and may affect frequencies both above and below 4 kHz. It has been shown that forward pressure level (FPL) calibration minimizes standing-wave effects by isolating the forward-propagating component of the stimulus. Yet, previous work has failed to demonstrate more than a small difference in test performance and behavioral-threshold prediction with DPOAEs after SPL and FPL calibration. One potential limitation in prior studies is that measurements were restricted to octave and interoctave frequencies; as a consequence, data were not necessarily collected at the standing-wave null frequency. In the present study, DPOAE responses were measured with f2 set to each participant's standing-wave frequency in an effort to increase the possibility that differences in test performance and threshold prediction would be observed for SPL and FPL calibration methods. Data were collected from 42 normal-hearing participants and 93 participants with hearing loss. DPOAEs were measured with f2 set to 4 kHz and at each participant's notch frequency after SPL and FPL calibration. DPOAE input/output functions were obtained from -10 to 80 dB in 5 dB steps for each calibration/stimulus condition. Test performance was evaluated using clinical decision theory. Both area under receiver operating characteristic curves for all stimulus levels and cumulative distributions when L2 = 50 dB (a level at which the best performance was observed regardless of calibration method) were used to evaluate the accuracy with which auditory status was determined. A bootstrap procedure was used to evaluate the significance of the differences in test performance between SPL and FPL calibrations. DPOAE predictions of behavioral threshold were evaluated by correlating actual behavioral thresholds and predicted thresholds using a multiple linear regression model. First, larger DPOAE levels were measured after SPL calibration than after FPL calibration, which demonstrated the expected impact of standing waves. Second, for both FPL and SPL calibration, test performance was best for moderate stimulus levels. Third, differences in test performance between calibration methods were evident at low- and high-stimulus levels. Fourth, there were small but statistically significant improvements in test performance after FPL calibration for clinically relevant conditions. Fifth, calibration method had no effect on threshold prediction. Standing waves after SPL calibration have an impact on DPOAE levels. Although the effect of calibration method on test performance was small, test performance was better after FPL calibration than after SPL calibration. There was no effect of calibration method on predictions of behavioral threshold.	\N	\N
24167235	A phonological deficit is thought to affect most individuals with developmental dyslexia. The present study addresses whether the phonological deficit is caused by difficulties with perceptual learning of fine acoustic details. A demanding test of nonverbal auditory memory, "noise learning," was administered to both adults with dyslexia and control adult participants. On each trial, listeners had to decide whether a stimulus was a 1-s noise token or 2 abutting presentations of the same 0.5-s noise token (repeated noise). Without the listener's knowledge, the exact same noise tokens were presented over many trials. An improved ability to perform the task for such "reference" noises reflects learning of their acoustic details. Listeners with dyslexia did not differ from controls in any aspect of the task, qualitatively or quantitatively. They required the same amount of training to achieve discrimination of repeated from nonrepeated noises, and they learned the reference noises as often and as rapidly as the control group. However, they did show all the hallmarks of dyslexia, including a well-characterized phonological deficit. The data did not support the hypothesis that deficits in basic auditory processing or nonverbal learning and memory are the cause of the phonological deficit in dyslexia.	\N	\N
24174656	Despite the prevalence of poverty worldwide, little is known about how early socioeconomic adversity affects auditory brain function. Socioeconomically disadvantaged children are underexposed to linguistically and cognitively stimulating environments and overexposed to environmental toxins, including noise pollution. This kind of sensory impoverishment, we theorize, has extensive repercussions on how the brain processes sound. To characterize how this impoverishment affects auditory brain function, we compared two groups of normal-hearing human adolescents who attended the same schools and who were matched in age, sex, and ethnicity, but differed in their maternal education level, a correlate of socioeconomic status (SES). In addition to lower literacy levels and cognitive abilities, adolescents from lower maternal education backgrounds were found to have noisier neural activity than their classmates, as reflected by greater activity in the absence of auditory stimulation. Additionally, in the lower maternal education group, the neural response to speech was more erratic over repeated stimulation, with lower fidelity to the input signal. These weaker, more variable, and noisier responses are suggestive of an inefficient auditory system. By studying SES within a neuroscientific framework, we have the potential to expand our understanding of how experience molds the brain, in addition to informing intervention research aimed at closing the achievement gap between high-SES and low-SES children.	\N	\N
24180796	This article investigates the relationship between the shape of the mouthpiece and its acoustical properties in brass instruments. The hypothesis is that not only different volumes but also particular cup shapes affect the embouchure and the tone quality in both a physical and perceivable way. Three professional trumpet players were involved, and two different internal cup contours characterized by a "U" and a "V" shape with two types of throat junction (round and sharp) were chosen, based on a Vincent Bach 1 [1/2] C medium mouthpiece. A third intermediate contour was designed as a combination of these. Over 600 sound samples were produced under controlled conditions, the study involving four different stages: (1) Simulation of air-flow, (2) analysis of the sound spectra, (3) study of the players' subjective responses, and (4) perceptual analysis of their timbral differences. Results confirm the U shape is characterized by a stronger air recirculation and produces stronger spectral components above 8 kHz, compared to the V shape. A round throat junction may also be preferable to a sharp one in terms of playability. There is moderate agreement on the aural perception of these differences although the verbal attributes used to qualify these are not shared.	\N	\N
24181980	The role of visual cues in native listeners' perception of speech produced by nonnative speakers has not been extensively studied. Native perception of English sentences produced by native English and Korean speakers in audio-only and audiovisual conditions was examined. Korean speakers were rated as more accented in audiovisual than in the audio-only condition. Visual cues enhanced word intelligibility for native English speech but less so for Korean-accented speech. Reduced intelligibility of Korean-accented audiovisual speech was associated with implicit visual biases, suggesting that listener-related factors partially influence the efficiency of audiovisual integration for nonnative speech perception.	\N	\N
24184174	Expert musicians are able to time their actions accurately and consistently during a musical performance. We investigated how musical expertise influences the ability to reproduce auditory intervals and how this generalises across different techniques and sensory modalities. We first compared various reproduction strategies and interval length, to examine the effects in general and to optimise experimental conditions for testing the effect of music, and found that the effects were robust and consistent across different paradigms. Focussing on a 'ready-set-go' paradigm subjects reproduced time intervals drawn from distributions varying in total length (176, 352 or 704 ms) or in the number of discrete intervals within the total length (3, 5, 11 or 21 discrete intervals). Overall, Musicians performed more veridical than Non-Musicians, and all subjects reproduced auditory-defined intervals more accurately than visually-defined intervals. However, Non-Musicians, particularly with visual stimuli, consistently exhibited a substantial and systematic regression towards the mean interval. When subjects judged intervals from distributions of longer total length they tended to regress more towards the mean, while the ability to discriminate between discrete intervals within the distribution had little influence on subject error. These results are consistent with a Bayesian model that minimizes reproduction errors by incorporating a central tendency prior weighted by the subject's own temporal precision relative to the current distribution of intervals. Finally a strong correlation was observed between all durations of formal musical training and total reproduction errors in both modalities (accounting for 30% of the variance). Taken together these results demonstrate that formal musical training improves temporal reproduction, and that this improvement transfers from audition to vision. They further demonstrate the flexibility of sensorimotor mechanisms in adapting to different task conditions to minimise temporal estimation errors.	\N	\N
24192718	Dexamethasone administered prior to cochlear implantation has been shown to reduce the loss of residual hearing in experimental settings. However, its effect on the tissue response around the implant has not been extensively studied. In this study dexamethasone sodium phosphate was administered to guinea pigs via local delivery to the round window (2% dexamethasone for 120 min prior to surgery, 'local 2/120', or 20% dexamethasone for 30 min prior to surgery) or intravenously (2 mg/kg dexamethasone for 60 min) prior to implantation. Auditory brainstem responses (ABR) were monitored for 3 months, after which the cochleae were embedded in Spurr's resin and sectioned. The extent of the tissue response and the survival of the neurosensory structures were analysed. Both local 2/120 and systemically delivered dexamethasone improved ABR thresholds when compared with control animals. Systemic dexamethasone also reduced the tissue response around the electrode. This suggests that whilst both locally and systemically administered dexamethasone can protect residual hearing after cochlear implantation, their effects upon the tissue response to implantation may differ.	\N	\N
24198087	Cognitive skills, such as processing speed, memory functioning, and the ability to divide attention, are known to diminish with aging. The present study shows that, despite these changes, older adults can successfully compensate for degradations in speech perception. Critically, the older participants of this study were not pre-selected for high performance on cognitive tasks, but only screened for normal hearing. We measured the compensation for speech degradation using phonemic restoration, where intelligibility of degraded speech is enhanced using top-down repair mechanisms. Linguistic knowledge, Gestalt principles of perception, and expectations based on situational and linguistic context are used to effectively fill in the inaudible masked speech portions. A positive compensation effect was previously observed only with young normal hearing people, but not with older hearing-impaired populations, leaving the question whether the lack of compensation was due to aging or due to age-related hearing problems. Older participants in the present study showed poorer intelligibility of degraded speech than the younger group, as expected from previous reports of aging effects. However, in conditions that induce top-down restoration, a robust compensation was observed. Speech perception by the older group was enhanced, and the enhancement effect was similar to that observed with the younger group. This effect was even stronger with slowed-down speech, which gives more time for cognitive processing. Based on previous research, the likely explanations for these observations are that older adults can overcome age-related cognitive deterioration by relying on linguistic skills and vocabulary that they have accumulated over their lifetime. Alternatively, or simultaneously, they may use different cerebral activation patterns or exert more mental effort. This positive finding on top-down restoration skills by the older individuals suggests that new cognitive training methods can teach older adults to effectively use compensatory mechanisms to cope with the complex listening environments of everyday life.	\N	\N
24198324	Temporal pole (TP) cortex is associated with higher-order sensory perception and/or recognition memory, as human patients with damage in this region show impaired performance during some tasks requiring recognition memory (Olson et al. 2007). The underlying mechanisms of TP processing are largely based on examination of the visual nervous system in humans and monkeys, while little is known about neuronal activity patterns in the auditory portion of this region, dorsal TP (dTP; Poremba et al. 2003). The present study examines single-unit activity of dTP in rhesus monkeys performing a delayed matching-to-sample task utilizing auditory stimuli, wherein two sounds are determined to be the same or different. Neurons of dTP encode several task-relevant events during the delayed matching-to-sample task, and encoding of auditory cues in this region is associated with accurate recognition performance. Population activity in dTP shows a match suppression mechanism to identical, repeated sound stimuli similar to that observed in the visual object identification pathway located ventral to dTP (Desimone 1996; Nakamura and Kubota 1996). However, in contrast to sustained visual delay-related activity in nearby analogous regions, auditory delay-related activity in dTP is transient and limited. Neurons in dTP respond selectively to different sound stimuli and often change their sound response preferences between experimental contexts. Current findings suggest a significant role for dTP in auditory recognition memory similar in many respects to the visual nervous system, while delay memory firing patterns are not prominent, which may relate to monkeys' shorter forgetting thresholds for auditory vs. visual objects.	\N	\N
24210181	A time interval between the onset and the offset of a continuous sound (filled interval) is often perceived to be longer than a time interval between two successive brief sounds (empty interval) of the same physical duration. The present study examined whether and how this phenomenon, sometimes called the filled duration illusion (FDI), occurs for short time intervals (40-520 ms). The investigation was conducted with the method of adjustment (Experiment 1) and the method of magnitude estimation (Experiment 2). When the method of adjustment was used, the FDI did not appear for the majority of the participants, but it appeared clearly for some participants. In the latter case, the amount of the FDI increased as the interval duration lengthened. The FDI was more likely to occur with magnitude estimation than with the method of adjustment. The participants who showed clear FDI with one method did not necessarily show such clear FDI with the other method.	\N	\N
24218156	Declarative memory evaluation is an essential step in the clinical and neuropsychological assessment of a variety of neurological disorders. It typically addresses the issue of normality/abnormality of an individual's performance. Another clinical application of the neuropsychological assessment of declarative memory is the longitudinal evaluation of an individual's performance change. In fact, in a variety of neurological conditions repeated assessments are needed to evaluate the modifications of a memory disorder as a function of time or in response to a pharmacological or rehabilitation treatment. This study was aimed at collecting data for measuring and interpreting performance change on a memory test for verbal material. For this purpose, we administered to 100 healthy subjects (age range 20-80 years; years of formal education range 8-17 years) three parallel forms of a test requiring the immediate and delayed recall of a 15-word list. The subjects performed the recall test three times (each time with a different list) at least 1 week apart. The order of the lists was randomized across subjects. Results revealed that performance on the three lists was highly correlated and did not vary as a function of the order of presentation. However, accuracy of recall was slightly better on a list compared to the others. Based on a method devised by Payne and Jones (J Clin Psychol 13:115-121, 1957), we provide normative data for establishing whether a discrepancy in recall accuracy on two versions of the test exceeds the discrepancy expected based on the performance of normal controls.	\N	\N
24218332	Sound localization is important for orienting and focusing attention and for segregating sounds from different sources in the environment. In humans, horizontal sound localization mainly relies on interaural differences in sound arrival time and sound level. Despite their perceptual importance, the neural processing of interaural time and level differences (ITDs and ILDs) remains poorly understood. Animal studies suggest that, in the brainstem, ITDs and ILDs are processed independently by different specialized circuits. The aim of the current study was to investigate whether, at higher processing levels, they remain independent or are integrated into a common code of sound laterality. For that, we measured late auditory cortical potentials in response to changes in sound lateralization elicited by perceptually matched changes in ITD and/or ILD. The responses to the ITD and ILD changes exhibited significant morphological differences. At the same time, however, they originated from overlapping areas of the cortex and showed clear evidence for functional coupling. These results suggest that the auditory cortex contains an integrated code of sound laterality, but also retains independent information about ITD and ILD cues. This cue-related information might be used to assess how consistent the cues are, and thus, how likely they would have arisen from the same source.	\N	\N
24224991	Today's compression hearing aids with noise reduction systems may not manage transient noises effectively because of the short duration of these sounds compared to the onset times of the compressors and/or noise reduction algorithms. The current study was designed to evaluate the effect of a transient noise reduction (TNR) algorithm on listening comfort, speech intelligibility in quiet, and preferred wearer gain in the presence of transients. A single-blinded, repeated-measures design was used. Thirteen experienced hearing aid users with bilaterally symmetrical (≤7.5 dB) sensorineural hearing loss participated in the study. Speech identification in quiet (no transient noise) was identical between the TNR On and the TNR Off conditions. The participants showed subjective preference for the TNR algorithm when "comfortable listening" was used as the criterion. Participants preferred less gain than the default prescription in the presence of transient noise sounds. However, the preferred gain was 2.9 dB higher when the TNR was activated than when it was deactivated. This translated to 12.1% improvement in phoneme identification over the TNR Off condition for soft speech. This study demonstrated that the use of the TNR algorithm would not negatively affect speech identification. The results also suggested that this algorithm may improve listening comfort in the presence of transient noise sounds and ensure consistent use of prescribed gain. Such an algorithm may ensure more consistent audibility across listening environments.	\N	\N
24225652	The aim of this study was to comprehensively evaluate the auditory phenotype in Niemann-Pick disease, type C1 (NPC1), to understand better the natural history of this complex, heterogeneous disorder, and to define further the baseline auditory deficits associated with NPC1 so that use of potentially ototoxic interventions (e.g., 2-hydroxypropyl-ß-cyclodextrin) may be more appropriately monitored and understood. Fifty patients with NPC1 ranging in age from 4 months to 21 years (mean = 9.3 years) enrolled in a natural history/observational study at the National Institutes of Health. The auditory test battery included, when possible, immittance audiometry, pure-tone and speech audiometry, otoacoustic emission testing, and a neurotologic auditory brainstem response study. Longitudinal data were collected on a subset of patients. Over half of the cohort exhibited hearing loss involving the high frequencies ranging from a slight to moderate degree, and 74% of patients presented with clinically significant hearing loss involving the frequencies most important to speech understanding (0.5, 1, 2, 4 kHz). Despite the heterogeneity of the sample, results among patients were sufficiently consistent to implicate retrocochlear dysfunction in the majority (66%) of individuals, with (22%) or without (44%) accompanying cochlear involvement. Some patients (10%) presented with a profile for auditory neuropathy spectrum disorder. The combination of cross-sectional and longitudinal data indicates these patients are at risk for a progressive decline in auditory function. This is the largest cohort of patients with NPC1 evaluated comprehensively for auditory dysfunction, and results implicate the pathological processes of NPC1 in the manifestation of hearing loss. Patients with NPC1 should be monitored audiologically throughout their lives, beginning at the time of diagnosis. Clinicians and researchers should be aware of this historically overlooked aspect of the phenotype.	\N	\N
24227733	Previous imaging studies of congenital blindness have studied individuals with heterogeneous causes of blindness, which may influence the nature and extent of cross-modal plasticity. Here, we scanned a homogeneous group of blind people with bilateral congenital anophthalmia, a condition in which both eyes fail to develop, and, as a result, the visual pathway is not stimulated by either light or retinal waves. This model of congenital blindness presents an opportunity to investigate the effects of very early visual deafferentation on the functional organization of the brain. In anophthalmic animals, the occipital cortex receives direct subcortical auditory input. We hypothesized that this pattern of subcortical reorganization ought to result in a topographic mapping of auditory frequency information in the occipital cortex of anophthalmic people. Using functional MRI, we examined auditory-evoked activity to pure tones of high, medium, and low frequencies. Activity in the superior temporal cortex was significantly reduced in anophthalmic compared with sighted participants. In the occipital cortex, a region corresponding to the cytoarchitectural area V5/MT+ was activated in the anophthalmic participants but not in sighted controls. Whereas previous studies in the blind indicate that this cortical area is activated to auditory motion, our data show it is also active for trains of pure tone stimuli and in some anophthalmic participants shows a topographic mapping (tonotopy). Therefore, this region appears to be performing early sensory processing, possibly served by direct subcortical input from the pulvinar to V5/MT+.	\N	\N
24230923	The Rey Auditory-Verbal Learning Test is an easy to administer test that assesses many memory domains and is, therefore, widely used in the area of clinical neuropsychology. The purpose of this study was to provide normative data for an elderly population living in Spain. The sample of this study was comprised of 156 volunteers over 60 years of age, which were grouped into six different age groups. These groups comprised of 10 participants between the ages of 61 and 65 in the first group, 23 participants (66-70) in the second, 28 participants (71-75) in the third, 35 participants (76-80) in the fourth, 32 participants (81-85)in the fifth and 28 participants (86-95) in the sixth group. Demographic data were collected and means, deviations, and ranges of all the measures were evaluated. Normative data were calculated from the percentiles, and then converted into age-corrected scaled scores with a mean of 10 and a standard deviation of 3.	\N	\N
24231418	In the basic sciences, many researchers now use gap pre-pulse inhibition of the acoustic startle reflex (GPIAS) to determine if an animal has tinnitus after exposure to an ototoxic drug or intense noise. Tinnitus is assumed to be present if the silent gap in an ongoing narrow band noise (NBN) fails to suppress the startle reflex response evoked by an intense noise burst. The lack of gap pre-pulse inhibition presumably occurs because tinnitus fills in the silent intervals in the background noise. To test the perceptual aspects of this hypothesis, we asked hearing impaired subjects with tinnitus if they could perceive 50 ms silent intervals presented in a NBN, which was located above, below or at the subject's tinnitus pitch. The same tests were performed on normal hearing subjects without tinnitus. All subjects, with and without tinnitus, could detect the 50 ms gaps. Thus, using the stimulus parameters similar to those employed in animal and human GPIAS studies, we found that the tinnitus percept does not fill in the silent interval in a perceptual gap detection task; however, these finding do not rule out the possibility that tinnitus interferes with pre-attentive filtering of sensory stimuli in the GPIAS sensorimotor gating paradigm.	\N	\N
24232066	Compare preoperative and postoperative performance in patients undergoing cochlear implantation (CI) for unilateral severe-to-profound sensorineural hearing loss (single-sided deafness, SSD). IRB-approved, prospective Tertiary center Twenty-nine patients have undergone CI for SSD. SSD was due to Ménière's disease (MD) in 10 subjects; these also suffered from recalcitrant vertigo spells and in these 10 patients along with 2 others the CI was placed simultaneous with a labyrinthectomy. CI with or without labyrinthectomy. CNC word and AzBio sentences in quiet were administered to the implanted ear. A multiple-loudspeaker sound localization test was administered in the bilateral listening condition. All data were collected preoperatively and 3, 6, and 12 months postoperatively with postoperative data available for 19 subjects. Additionally, a tinnitus handicap questionnaire is administered pre- and 12-months post-operatively. CNC word and AzBio sentence scores showed improvement in the implanted ear. Sound localization appeared to improve in an experience-dependent fashion in some patients. Most patients reported diminished tinnitus after cochlear implantation. All patients undergoing labyrinthectomy experienced resolution of vertigo attacks. CI restores auditory function to the deafened ear. Additionally, the binaural input appears to improve sound localization for most patients. In patients with severe hearing loss and recalcitrant vertigo attacks because of MD, simultaneous labyrinthectomy and CI effectively relieves vertigo attacks and improves auditory function.	\N	\N
24234167	Are listeners able to adapt to a foreign-accented speaker who has, as is often the case, an inconsistent accent? Two groups of native Dutch listeners participated in a cross-modal priming experiment, either in a consistent-accent condition (German-accented items only) or in an inconsistent-accent condition (German-accented and nativelike pronunciations intermixed). The experimental words were identical for both groups (words with vowel substitutions characteristic of German-accented speech); additional contextual words differed in accentedness (German-accented or nativelike words). All items were spoken by the same speaker: a German native who could produce the accented forms but could also pass for a Dutch native speaker. Listeners in the consistent-accent group were able to adapt quickly to the speaker (i.e., showed facilitatory priming for words with vocalic substitutions). Listeners in the inconsistent-accent condition showed adaptation to words with vocalic substitutions only in the second half of the experiment. These results indicate that adaptation to foreign-accented speech is rapid. Accent inconsistency slows listeners down initially, but a short period of additional exposure is enough for them to adapt to the speaker. Listeners can therefore tolerate inconsistency in foreign-accented speech.	\N	\N
24238764	Two experiments examined when monolingual, English-learning 19-month-old infants learn a second object label. Two experimenters sat together. One labeled a novel object with one novel label, whereas the other labeled the same object with a different label in either the same or a different language. Infants were tested on their comprehension of each label immediately following its presentation. Infants mapped the first label at above chance levels, but they did so with the second label only when requested by the speaker who provided it (Experiment 1) or when the second experimenter labeled the object in a different language (Experiment 2). These results show that 19-month-olds learn second object labels but do not readily generalize them across speakers of the same language. The results highlight how speaker and language spoken guide infants' acceptance of second labels, supporting sociopragmatic views of word learning.	\N	\N
24256043	The procedure maximally retains the physiological structure of the middle ear and external auditory canal, thus effectively improving the patient's hearing ability. We explored the clinical outcomes of treating chronic suppurative otitis media using improved intact canal wall radical mastoidectomy with sandwich graft tympanoplasty. We chose to perform intact canal wall radical mastoidectomy with sandwich graft tympanoplasty in patients with chronic suppurative otitis media. A total of 170 patients were included in the study. Statistical analysis was carried out using software SPSS18.0, adjusted with the chi-squared test. In all, 140 cases were shown to have been treated effectively (82.35%, 140/170). The increased auditory threshold of preoperative bone conduction was not related to the duration of disease and/or the presence of cholesteatoma (p > 0.05), but was associated with ossicular chain disruption or fixation (p < 0.05), specifically the ossicular chain destruction/absorption, granulation tissue wrapping, and consequent fixation. During the procedure, the sleeve-like pedicle flap of external auditory canal and tympanic membrane is covered with graft, allowing good fixation with maintenance of the tympanic membrane's natural shape. The auditory threshold test revealed equal or above normal levels (30 dB) for 126 cases (74.12%, 126/170). The primary healing rate of tympanic membrane achieved was 96.47% (164/170).	\N	\N
24258458	While bilateral cochlear implants (CIs) provide some binaural benefits, these benefits are limited compared to those observed in normal-hearing (NH) listeners. The large frequency-to-electrode allocation bandwidths (BWs) in CIs compared to auditory filter BWs in NH listeners increases the interaural fluctuation rate available for binaural unmasking, which may limit binaural benefits. The purpose of this work was to investigate the effect of interaural fluctuation rate on correlation change discrimination and binaural masking-level differences in NH listeners presented a CI simulation using a pulsed-sine vocoder. In experiment 1, correlation-change just-noticeable differences (JNDs) and tone-in-noise thresholds were measured for narrowband noises with different BWs and center frequencies (CFs). The results suggest that the BW, CF, and/or interaural fluctuation rate are important factors for correlation change discrimination. In experiment 2, the interaural fluctuation rate was systematically varied and dissociated from changes in BW and CF by using a pulsed-sine vocoder. Results indicated that the interaural fluctuation rate did not affect correlation change JNDs for correlated reference noises; however, slow interaural fluctuations increased correlation change JNDs for uncorrelated reference noises. In experiment 3, the BW, CF, and vocoder pulse rate were varied while interaural fluctuation rate was held constant. JNDs increased for increasing BW and decreased for increasing CF. In summary, relatively fast interaural fluctuation rates are not detrimental for detecting changes in interaural correlation. Thus, limiting factors to binaural benefits in CI listeners could be a result of other temporal and/or spectral deficiencies from electrical stimulation.	\N	\N
24260183	In the real world, human speech recognition nearly always involves listening in background noise. The impact of such noise on speech signals and on intelligibility performance increases with the separation of the listener from the speaker. The present behavioral experiment provides an overview of the effects of such acoustic disturbances on speech perception in conditions approaching ecologically valid contexts. We analysed the intelligibility loss in spoken word lists with increasing listener-to-speaker distance in a typical low-level natural background noise. The noise was combined with the simple spherical amplitude attenuation due to distance, basically changing the signal-to-noise ratio (SNR). Therefore, our study draws attention to some of the most basic environmental constraints that have pervaded spoken communication throughout human history. We evaluated the ability of native French participants to recognize French monosyllabic words (spoken at 65.3 dB(A), reference at 1 meter) at distances between 11 to 33 meters, which corresponded to the SNRs most revealing of the progressive effect of the selected natural noise (-8.8 dB to -18.4 dB). Our results showed that in such conditions, identity of vowels is mostly preserved, with the striking peculiarity of the absence of confusion in vowels. The results also confirmed the functional role of consonants during lexical identification. The extensive analysis of recognition scores, confusion patterns and associated acoustic cues revealed that sonorant, sibilant and burst properties were the most important parameters influencing phoneme recognition. . Altogether these analyses allowed us to extract a resistance scale from consonant recognition scores. We also identified specific perceptual consonant confusion groups depending of the place in the words (onset vs. coda). Finally our data suggested that listeners may access some acoustic cues of the CV transition, opening interesting perspectives for future studies.	\N	\N
24271979	Integrating visual and auditory language information is critical for reading. Suppression and congruency effects in audiovisual paradigms with letters and speech sounds have provided information about low-level mechanisms of grapheme-phoneme integration during reading. However, the central question about how such processes relate to reading entire words remains unexplored. Using ERPs, we investigated whether audiovisual integration occurs for words already in beginning readers, and if so, whether this integration is reflected by differences in map strength or topography (aim 1); and moreover, whether such integration is associated with reading fluency (aim 2). A 128-channel EEG was recorded while 69 monolingual (Swiss)-German speaking first-graders performed a detection task with rare targets. Stimuli were presented in blocks either auditorily (A), visually (V) or audiovisually (matching: AVM; nonmatching: AVN). Corresponding ERPs were computed, and unimodal ERPs summated (A + V = sumAV). We applied TANOVAs to identify time windows with significant integration effects: suppression (sumAV-AVM) and congruency (AVN-AVM). They were further characterized using GFP and 3D-centroid analyses, and significant effects were correlated with reading fluency. The results suggest that audiovisual suppression effects occur for familiar German and unfamiliar English words, whereas audiovisual congruency effects can be found only for familiar German words, probably due to lexical-semantic processes involved. Moreover, congruency effects were characterized by topographic differences, indicating that different sources are active during processing of congruent compared to incongruent audiovisual words. Furthermore, no clear associations between audiovisual integration and reading fluency were found. The degree to which such associations develop in beginning readers remains open to further investigation.	\N	\N
24278326	The purpose of this study was to design and to verify a new hearing-aid fitting strategy (Aescu HRL-1) based on the acoustic features of Mandarin. The subjective and objective outcomes were compared to those fitted with NAL-NL1 (National Acoustic Laboratory Non-Linear, version1) in Mandarin-speaking hearing-aid users. Fifteen subjects with sensorineural hearing loss participated in this preliminary study. Each subject wore a pair of four-channel hearing aids fitted with the Aescu HRL-1 and NAL-NL1 prescriptions alternatively for 1 month. Objective and subjective tests including the Mandarin Monosyllable Recognition Test (MMRT), Mandarin Hearing in Noise Test (MHINT), International Outcome Inventory for Hearing Aids (IOI-HA), and a sound-quality questionnaire were used to evaluate the performance of the two prescriptions. The mean MMRT scores were 79.9% and 81.1% for NAL-NL1 and Aescu HRL-1 respectively. They are not statistically different. The corresponding MHINT signal-to-noise ratios were 0.87 and 0.85 dB, also, no significant difference was found between these two strategies. However, in subjective questionnaires, overall, the sound-quality and IOI-HA scores were higher for Aescu HRL-1. The speech recognition performance based on Aescu HRL-1 is as good as that of NAL-NL1 for Mandarin-speaking hearing-aid users. Moreover, the subjects generally responded that Aescu HRL-1 provides a more natural, richer, and better sound quality than does NAL-NL1.	\N	\N
24296543	The acoustic basis of intelligibility associated with varied clear speech instructions was studied. Twelve healthy speakers read 18 sentences in 'habitual', 'clear', 'hearing impaired' and 'overenunciate' conditions. The latter 3 conditions are varieties of clear speech. Acoustic measures included tense and lax vowel space area, a measure of vowel spectral change, articulation rate and sentence-level vocal intensity. Sentences were mixed with multitalker babble to prevent ceiling effects and were orthographically transcribed by 40 listeners. Percent-correct scores were obtained for each speaker and condition. Regression analyses were used to quantify relationships between acoustic measures and intelligibility. Univariate regressions indicated that greater magnitudes of acoustic change in nonhabitual conditions were associated with greater increases in intelligibility. Multivariate regression analysis further indicated that lax vowel space, articulation rate and vocal intensity were significant predictors of intelligibility. Acoustic variables associated with intelligibility differed depending on whether relationships were examined using univariate or multivariate statistics. Multivariate statistics indicated that articulation rate was the strongest predictor of improvements in intelligibility above and beyond all other variables studied. The findings have implications for optimizing therapeutic use of clear speech for clinical populations.	\N	\N
24302571	The activity of sensory neural populations carries information about the environment. This may be extracted from neural activity using different strategies. In the auditory brainstem, a recent theory proposes that sound location in the horizontal plane is decoded from the relative summed activity of two populations in each hemisphere, whereas earlier theories hypothesized that the location was decoded from the identity of the most active cells. We tested the performance of various decoders of neural responses in increasingly complex acoustical situations, including spectrum variations, noise, and sound diffraction. We demonstrate that there is insufficient information in the pooled activity of each hemisphere to estimate sound direction in a reliable way consistent with behavior, whereas robust estimates can be obtained from neural activity by taking into account the heterogeneous tuning of cells. These estimates can still be obtained when only contralateral neural responses are used, consistently with unilateral lesion studies. DOI: http://dx.doi.org/10.7554/eLife.01312.001.	\N	\N
24311693	Dyslexia is a severe and persistent reading and spelling disorder caused by impairment in the ability to manipulate speech sounds. We combined functional magnetic resonance brain imaging with multivoxel pattern analysis and functional and structural connectivity analysis in an effort to disentangle whether dyslexics' phonological deficits are caused by poor quality of the phonetic representations or by difficulties in accessing intact phonetic representations. We found that phonetic representations are hosted bilaterally in primary and secondary auditory cortices and that their neural quality (in terms of robustness and distinctness) is intact in adults with dyslexia. However, the functional and structural connectivity between the bilateral auditory cortices and the left inferior frontal gyrus (a region involved in higher-level phonological processing) is significantly hampered in dyslexics, suggesting deficient access to otherwise intact phonetic representations.	\N	\N
24312408	Nucleus cochlear implant systems incorporate a fast-acting front-end automatic gain control (AGC), sometimes called a compression limiter. The objective of the present study was to determine the effect of replacing the front-end compression limiter with a newly proposed envelope profile limiter. A secondary objective was to investigate the effect of AGC speed on cochlear implant speech intelligibility. The envelope profile limiter was located after the filter bank and reduced the gain when the largest of the filter bank envelopes exceeded the compression threshold. The compression threshold was set equal to the saturation level of the loudness growth function (i.e. the envelope level that mapped to the maximum comfortable current level), ensuring that no envelope clipping occurred. To preserve the spectral profile, the same gain was applied to all channels. Experiment 1 compared sentence recognition with the front-end limiter and with the envelope profile limiter, each with two release times (75 and 625 ms). Six implant recipients were tested in quiet and in four-talker babble noise, at a high presentation level of 89 dB SPL. Overall, release time had a larger effect than the AGC type. With both AGC types, speech intelligibility was lower for the 75 ms release time than for the 625 ms release time. With the shorter release time, the envelope profile limiter provided higher group mean scores than the front-end limiter in quiet, but there was no significant difference in noise. Experiment 2 measured sentence recognition in noise as a function of presentation level, from 55 to 89 dB SPL. The envelope profile limiter with 625 ms release time yielded better scores than the front-end limiter with 75 ms release time. A take-home study showed no clear pattern of preferences. It is concluded that the envelope profile limiter is a feasible alternative to a front-end compression limiter.	\N	\N
24317426	Previous research demonstrates that meaningfully related sounds enhance visual sensitivity to point-light displays of human movement. Here we report two psychophysical studies that investigated whether, and if so when, this facilitation is modulated by the temporal relationship between auditory and visual stimuli. In Experiment 1, participants detected point-light walkers in masks while listening to footsteps that were either synchronous or out-of-phase with point-light footfalls. The relative timing of auditory and visual walking did not impact performance. Experiment 2 further tested the importance of multisensory timing by disrupting the rhythm of the auditory and visual streams. Participants detected point-light walkers while listening to footstep or tone sounds that were either synchronous or temporally random with regards to point-light footfalls. Heard footsteps improved visual sensitivity over heard tones regardless of timing. Taken together, these results suggest that during the detection of others' actions, the perceptual system makes use of meaningfully related sounds whether or not they are synchronous. These results are discussed in relation to the unity assumption theory as well as recent empirical data that suggest that temporal correspondence is not always a critical factor in multisensory perception and integration.	\N	\N
24329490	To link outcome measures used in audiological research to the ICF classification and thereby describe audiological research from the ICF perspective. Through a peer-reviewed or a joint linking procedure, link outcome measures to the ICF classification system using standardized ICF linking rules. Additional linking rules were developed in combination with the established rules to overcome difficulties when connecting audiological data to ICF. Absolute and relative frequencies of ICF categories were reported. The identified outcome measures from the previous study (Part I) constituted the empirical material. In total, 285 ICF categories were identified. The most prevalent categories were related to listening, hearing functions, auditory perceptions, emotions and the physical environment, such as noise and hearing aids. Categories related to communication showed lower relative frequencies, as did categories related to the social and attitudinal environment. Based on the linked outcome measures, communication as a research topic is subordinated to other research topics. The same conclusion can be drawn for research targeting the social and attitudinal environment of adults with HL. Difficulties in the linking procedure were highlighted and discussed, and suggestions for future revisions of the ICF from the audiological perspective were described.	\N	\N
24333301	Mutations in the connexin 26 gene (GJB2) are the most common genetic cause of deafness, leading to congenital bilateral non-syndromic sensorineural hearing loss. Here we report the generation of a mouse model for a connexin 26 (Cx26) mutation, in which cre-Sox10 drives excision of the Cx26 gene from non-sensory cells flanking the auditory epithelium. We determined that these conditional knockout mice, designated Gjb2-CKO, have a severe hearing loss. Immunocytochemistry of the auditory epithelium confirmed absence of Cx26 in the non-sensory cells. Histology of the organ of Corti and the spiral ganglion neurons (SGNs) performed at ages 1, 3, or 6 months revealed that in Gjb2-CKO mice, the organ of Corti began to degenerate in the basal cochlear turn at an early stage, and the degeneration rapidly spread to the apex. In addition, the density of SGNs in Rosenthal's canal decreased rapidly along a gradient from the base of the cochlea to the apex, where some SGNs survived until at least 6 months of age. Surviving neurons often clustered together and formed clumps of cells in the canal. We then assessed the influence of brain derived neurotrophic factor (BDNF) gene therapy on the SGNs of Gjb2-CKO mice by inoculating Adenovirus with the BDNF gene insert (Ad.BDNF) into the base of the cochlea via the scala tympani or scala media. We determined that over-expression of BDNF beginning around 1 month of age resulted in a significant rescue of neurons in Rosenthal's canal of the cochlear basal turn but not in the middle or apical portions. This data may be used to design therapies for enhancing the SGN physiological status in all GJB2 patients and especially in a sub-group of GJB2 patients where the hearing loss progresses due to ongoing degeneration of the auditory nerve, thereby improving the outcome of cochlear implant therapy in these ears.	\N	\N
24342151	The purpose of the study was to identify structural brain differences in school-age children with residual speech sound errors. Voxel based morphometry was used to compare gray and white matter volumes for 23 children with speech sound errors, ages 8;6-11;11, and 54 typically speaking children matched on age, oral language, and IQ. We hypothesized that regions associated with production and perception of speech sounds would differ between groups. Results indicated greater gray matter volumes for the speech sound error group relative to typically speaking controls in bilateral superior temporal gyrus. There was greater white matter volume in the corpus callosum for the speech sound error group, but less white matter volume in right lateral occipital gyrus. Results may indicate delays in neuronal pruning in critical speech regions or differences in the development of networks for speech perception and production.	\N	\N
24344364	Previous studies in both humans and animals have documented improved performance following discrimination training. This enhanced performance is often associated with cortical response changes. In this study, we tested the hypothesis that long-term speech training on multiple tasks can improve primary auditory cortex (A1) responses compared to rats trained on a single speech discrimination task or experimentally naïve rats. Specifically, we compared the percent of A1 responding to trained sounds, the responses to both trained and untrained sounds, receptive field properties of A1 neurons, and the neural discrimination of pairs of speech sounds in speech trained and naïve rats. Speech training led to accurate discrimination of consonant and vowel sounds, but did not enhance A1 response strength or the neural discrimination of these sounds. Speech training altered tone responses in rats trained on six speech discrimination tasks but not in rats trained on a single speech discrimination task. Extensive speech training resulted in broader frequency tuning, shorter onset latencies, a decreased driven response to tones, and caused a shift in the frequency map to favor tones in the range where speech sounds are the loudest. Both the number of trained tasks and the number of days of training strongly predict the percent of A1 responding to a low frequency tone. Rats trained on a single speech discrimination task performed less accurately than rats trained on multiple tasks and did not exhibit A1 response changes. Our results indicate that extensive speech training can reorganize the A1 frequency map, which may have downstream consequences on speech sound processing.	\N	\N
24344815	Dyslexia is commonly attributed to a phonological deficit, but whether it effectively compromises the phonological grammar or lower level systems is rarely explored. To address this question, we gauge the sensitivity of dyslexics to grammatical phonological restrictions on spoken onset clusters (e.g., bl in block). Across languages, certain onsets are preferred to others (e.g., blif ≻ bnif ≻ bdif, where ≻ indicates a preference). Here, we show that dyslexic participants (adult native speakers of Hebrew) are fully sensitive to these phonological restrictions, and they extend them irrespective of whether the onsets are attested in their language (e.g., bnif vs. bdif) or unattested (e.g., mlif vs. mdif). Dyslexics, however, showed reduced sensitivity to phonetic contrasts (e.g., blif vs. belif; ba vs. pa). Together, these results suggest that the known difficulties of dyslexics in speech processing could emanate not from the phonological grammar, but rather from lower level impairments to acoustic/phonetic encoding, lexical storage, and retrieval.	\N	\N
24349414	The diagnosis of tinnitus relies on self-report. Psychoacoustic measurements of tinnitus pitch and loudness are essential for assessing claims and discriminating true from false ones. For this reason, the quantification of tinnitus remains a challenging research goal. We aimed to: (1) assess the precision of a new tinnitus likeness rating procedure with a continuous-pitch presentation method, controlling for music training, and (2) test whether tinnitus psychoacoustic measurements have the sensitivity and specificity required to detect people faking tinnitus. Musicians and non-musicians with tinnitus, as well as simulated malingerers without tinnitus, were tested. Most were retested several weeks later. Tinnitus pitch matching was first assessed using the likeness rating method: pure tones from 0.25 to 16 kHz were presented randomly to participants, who had to rate the likeness of each tone to their tinnitus, and to adjust its level from 0 to 100 dB SPL. Tinnitus pitch matching was then assessed with a continuous-pitch method: participants had to match the pitch of their tinnitus to an external tone by moving their finger across a touch-sensitive strip, which generated a continuous pure tone from 0.5 to 20 kHz in 1-Hz steps. The predominant tinnitus pitch was consistent across both methods for both musicians and non-musicians, although musicians displayed better external tone pitch matching abilities. Simulated malingerers rated loudness much higher than did the other groups with a high degree of specificity (94.4%) and were unreliable in loudness (not pitch) matching from one session to the other. Retest data showed similar pitch matching responses for both methods for all participants. In conclusion, tinnitus pitch and loudness reliably correspond to the tinnitus percept, and psychoacoustic loudness matches are sensitive and specific to the presence of tinnitus.	\N	\N
24350693	To investigate the predicted threshold shift associated with the use of nonlinear hearing aids fitted to the NAL-NL2 or the DSL m[i/o] prescription for children with the same audiograms. For medium and high input levels, we asked: (1) How does predicted asymptotic threshold shifts (ATS) differ according to the choice of prescription? (2) How does predicted ATS vary with hearing level for gains prescribed by the two prescriptions? A mathematical model consisting of the modified power law combined with equations for predicting temporary threshold shift (Macrae, 1994b) was used to predict ATS. Predicted threshold shift were determined for 57 audiograms at medium and high input levels. For the 57 audiograms, DSL m[i/o] gains for high input levels were associated with increased risk relative to NAL-NL2. The variation of ATS with hearing level suggests that NAL-NL2 gains became unsafe when hearing loss > 90 dB HL. The gains prescribed by DSL m[i/o] became unsafe when hearing loss > 80 dB HL at a medium input level, and > 70 dB HL at a high input level. There is a risk of damage to hearing for children using nonlinear amplification. Vigilant checking for threshold shift is recommended.	\N	\N
24357104	Middle ear disease is the primary cause of hearing loss in children and has a significant impact on language development and academic performance. Multiple prognostic factors have previously been examined, but there is little published data regarding frequency-specific hearing outcomes. To examine the relationship between type I tympanoplasty in a pediatric population and frequency-specific hearing changes, as well as the relationship between several prognostic factors and graft retention. Retrospective medical chart review (February 2006 to October 2011) of 492 consecutive pediatric otolaryngology patients undergoing type I tympanoplasty for tympanic membrane (TM) perforation of any etiology at a tertiary-care pediatric otolaryngology practice. Type I tympanoplasty. Preoperative and postoperative audiometric data were collected for patients undergoing successful TM repair. It was hypothesized before data collection that conductive hearing would improve at all frequencies with no significant change in sensorineural hearing. Data collected included air conduction at 250 to 8000 Hz, speech reception thresholds, bone conduction at 500 to 4000 Hz, and air-bone gap at 500 to 4000 Hz. Demographic data obtained included sex, age, size, mechanism, location of perforation, and operative repair technique. Of 492 patients, 320 were excluded; results were thus examined for 172 patients. Surgery was successful for 73.8% of patients. Perforation size was significantly associated with repair success (mean [SD] surgical success rate of 38.6% [15.3%] vs surgical failure rate of 31.4% [15.0%]; P < .01); however, mean (SD) age (9.02 [3.89] years [surgical success] vs 8.52 [3.43] years [surgical failure]; P > .05) and repair technique (medial [73.08%] vs lateral [76.47%] graft success; P > .99) were not. Air conduction significantly improved from 250 to 2000 Hz (P < .001), did not significantly improve at 4000 Hz (P = .08), and there was a nonsignificant decline at 8000 Hz (P = .12). Speech reception threshold significantly improved (20 vs 15 dB; P < .001). This large review found an association of TM perforation size with surgical success and an improvement in speech reception threshold, air conduction at 250 to 2000 Hz, air-bone gap at 500 to 2000 Hz, and worsening bone conduction at 4000 Hz. Patients with high-frequency hearing loss due to TM perforation should not anticipate significant recovery from type I tympanoplasty. Hearing loss at higher frequencies may require postoperative hearing rehabilitation.	\N	\N
24364392	Previous research has shown that damage to the left temporal pole (LTP) is associated with impaired retrieval of words for unique entities, including names of famous people and landmarks. However, it is not known whether retrieving names for famous melodies is associated with the LTP. The aim of this study was to investigate the hypothesis that damage to the LTP would be associated with impaired naming of famous musical melodies. A Melody Naming Test was administered to patients with LTP damage, brain damaged comparison (BDC) patients, and normal comparison participants (NC). The test included various well-known melodies (e.g., "Pop Goes the Weasel"). After hearing each melody, participants were asked to rate their familiarity with the melody and identify it by name. LTP patients named significantly fewer melodies than BDC and NC participants. Recognition of melodies did not differ significantly between groups. The findings suggest that LTP supports retrieval of names for famous melodies. More broadly, these results extend support for the theoretical notion that LTP is important for retrieving proper names for unique concepts, irrespectively of stimulus modality or category.	\N	\N
24366693	The visual cues involved in auditory speech processing are not restricted to information from lip movements but also include head or chin gestures and facial expressions such as eyebrow movements. The fact that visual gestures precede the auditory signal implicates that visual information may influence the auditory activity. As visual stimuli are very close in time to the auditory information for audiovisual syllables, the cortical response to them usually overlaps with that for the auditory stimulation; the neural dynamics underlying the visual facilitation for continuous speech therefore remain unclear. In this study, we used a three-word phrase to study continuous speech processing. We presented video clips with even (without emphasis) phrases as the frequent stimuli and with one word visually emphasized by the speaker as the non-frequent stimuli. Negativity in the resulting ERPs was detected after the start of the emphasizing articulatory movements but before the auditory stimulus, a finding that was confirmed by the statistical comparisons of the audiovisual and visual stimulation. No such negativity was present in the control visual-only condition. The propagation of this negativity was observed between the visual and fronto-temporal electrodes. Thus, in continuous speech, the visual modality evokes predictive coding for the auditory speech, which is analysed by the cerebral cortex in the context of the phrase even before the arrival of the corresponding auditory signal.	\N	\N
24372066	In this study, 35 young, healthy adults were tested on whether speech-like stimuli evoke a unique response in the auditory efferent system. To this end, descending cortical influences on medial olivocochlear (MOC) activity were indirectly evaluated by studying the effects of contralateral suppression on distortion product otoacoustic emissions (DPOAEs) under four conditions: (a) in the absence of any contralateral noise (Baseline), (b) presence of contralateral broadband noise (Noise Baseline), (c) vowel discrimination-in-noise task (VDN) and (d) tone discrimination-in-noise (TDN) task. A statistically significant release from suppression was evident across all tested DPOAE frequencies (1, 1.5 and 2 kHz) only for the VDN task (p < 0.05), which yielded greater release from suppression than the TDN task. These findings indicate that during active listening in the presence of noise, the MOC activity may be differentially modulated depending on the type of stimulus (vowel vs. tone). Specifically, in the presence of background noise, vowels may show a greater release from suppression in the cochlea than frequency, intensity and duration matched tones.	\N	\N
24376601	During sentence production, linguistic information (semantics, syntax, phonology) of words is retrieved and assembled into a meaningful utterance. There is still debate on how we assemble single words into more complex syntactic structures such as noun phrases or sentences. In the present study, event-related potentials (ERPs) were used to investigate the time course of syntactic planning. Thirty-three volunteers described visually animated scenes using naming formats varying in syntactic complexity: from simple words ('W', e.g., "triangle", "red", "square", "green", "to fly towards"), to noun phrases ('NP', e.g., "the red triangle", "the green square", "to fly towards"), to a sentence ('S', e.g., "The red triangle flies towards the green square."). Behaviourally, we observed an increase in errors and corrections with increasing syntactic complexity, indicating a successful experimental manipulation. In the ERPs following scene onset, syntactic complexity variations were found in a P300-like component ('S'/'NP'>'W') and a fronto-central negativity (linear increase with syntactic complexity). In addition, the scene could display two actions - unpredictable for the participant, as the disambiguation occurred only later in the animation. Time-locked to the moment of visual disambiguation of the action and thus the verb, we observed another P300 component ('S'>'NP'/'W'). The data show for the first time evidence of sensitivity to syntactic planning within the P300 time window, time-locked to visual events critical of syntactic planning. We discuss the findings in the light of current syntactic planning views.	\N	\N
24376662	Previous research suggests that deficits in attention-emotion interaction are implicated in schizophrenia symptoms. Although disruption in auditory processing is crucial in the pathophysiology of schizophrenia, deficits in interaction between emotional processing of auditorily presented language stimuli and auditory attention have not yet been clarified. To address this issue, the current study used a dichotic listening task to examine 22 patients with schizophrenia and 24 age-, sex-, parental socioeconomic background-, handedness-, dexterous ear-, and intelligence quotient-matched healthy controls. The participants completed a word recognition task on the attended side in which a word with emotionally valenced content (negative/positive/neutral) was presented to one ear and a different neutral word was presented to the other ear. Participants selectively attended to either ear. In the control subjects, presentation of negative but not positive word stimuli provoked a significantly prolonged reaction time compared with presentation of neutral word stimuli. This interference effect for negative words existed whether or not subjects directed attention to the negative words. This interference effect was significantly smaller in the patients with schizophrenia than in the healthy controls. Furthermore, the smaller interference effect was significantly correlated with severe positive symptoms and delusional behavior in the patients with schizophrenia. The present findings suggest that aberrant interaction between semantic processing of negative emotional content and auditory attention plays a role in production of positive symptoms in schizophrenia. (224 words).	\N	\N
24384081	Large variations in perceptual directional microphone benefit, which far exceed the variation expected from physical performance measures of directional microphones, have been reported in the literature. The cause for the individual variation has not been systematically investigated. To determine the factors that are responsible for the individual variation in reported perceptual directional benefit. A correlational study. Physical performance measures of the directional microphones obtained after they had been fitted to individuals, cognitive abilities of individuals, and measurement errors were related to perceptual directional benefit scores. Fifty-nine hearing-impaired adults with varied degrees of hearing loss participated in the study. All participants were bilaterally fitted with a Motion behind-the-ear device (500 M, 501 SX, or 501 P) from Siemens according to the National Acoustic Laboratories' non-linear prescription, version two (NAL-NL2). Using the Bamford-Kowal-Bench (BKB) sentences, the perceptual directional benefit was obtained as the difference in speech reception threshold measured in babble noise (SRTn) with the devices in directional (fixed hypercardioid) and in omnidirectional mode. The SRTn measurements were repeated three times with each microphone mode. Physical performance measures of the directional microphone included the angle of the microphone ports to loudspeaker axis, the frequency range dominated by amplified sound, the in situ signal-to-noise ratio (SNR), and the in situ three-dimensional, articulation-index weighted directivity index (3D AI-DI). The cognitive tests included auditory selective attention, speed of processing, and working memory. Intraparticipant variation on the repeated SRTn's and the interparticipant variation on the average SRTn were used to determine the effect of measurement error. A multiple regression analysis was used to determine the effect of other factors. Measurement errors explained 52% of the variation in perceptual directional microphone benefit (95% confidence interval [CI]: 34-78%), while another 37% of variation was explained primarily by the physical performance of the directional microphones after they were fitted to individuals. The most contributing factor was the in situ 3D AI-DI measured across the low frequencies. Repeated SRTn measurements are needed to obtain a reliable indication of the perceptual directional benefit in an individual. Further, to obtain optimum benefit from directional microphones, the effectiveness of the microphones should be maximized across the low frequencies.	\N	\N
24386719	Listener retention of silent, gap-length duration was studied. Just noticeable differences (JNDs) for gap length within standard and comparison stimuli were obtained for intervals with and without intervening noise bursts, including a condition with gapped intervening bursts. Outcomes indicate that gap duration itself can be determinant. Also, JNDs were similar whether intervening stimuli were present or absent, differing from results reported for pitch, loudness, and timbre retention. The latter suggests additional/alternative cortical resources might be employed for retention of auditory-temporal information.	\N	\N
24408329	To investigate the auditory behavior of patients with chronic renal failure (CRF) undergoing kidney transplantation. Thirty patients were evaluated, 10 (33.33%) females and 20 (66.67%) males, aging from 13 to 26 years (average, 16.97 years; standard deviation, 3.60 years). Patients underwent the following procedures: anamnesis, otolaryngological examination, audiological evaluation (pure tone and high frequency), acoustic impedance measurements and central auditory processing evaluation. A control group was used to compare the high-frequency audiometry results. The following observations were made: absence of auditory complaints at the time of anamnesis; pure-tone audiometry was predominantly normal; patients presented lower hearing levels at the high-frequency audiometry, when compared to the control group, and as for the acoustic impedance measurements, curves of the type A were predominant; there was a change of the central auditory processing for 14 patients (46.67%) in the Staggered Spondaic Word Test (SSW); there was a significant difference between the age variable and the result of the pure-tone audiometry, that is, hearing sensitivity in thresholds from 250Hz to 8,000Hz decreased with advancing age; and the relation between the type of donor and the SSW test result was significant. Rates were higher when the patients had been transplanted from deceased donors compared to living donors. There were no changes in conventional audiological and high-frequency evaluation, or in the central auditory processing. Professionals involved in the care of kidney transplantation recipients must be better informed about the care, prevention, and early identification of auditory disorders.	\N	\N
24408330	The objective of this research was to assess the auditory abilities of Portuguese children and compare such abilities to the score of the Scale of Auditory Behaviors (SAB). Fifty-one children were evaluated with audiometry, speech audiometry, acoustic immittance measures, and eight behavioral tests involving dichotic listening, monotic listening, temporal processing, and sound localization. Their parents filled in the SAB questionnaire adapted to European A. SAB scores and auditory tests scores were submitted to Pearson's correlation coefficient. There is significant correlation between the score on SAB questionnaire and the auditory processing tests. The greatest coefficient was observed in temporal processing test (p=0.000). There was correlation between the score of SAB and the performance in auditory processing tests, suggesting that the SAB may be used for auditory processing screening.	\N	\N
24413019	The neural underpinnings of auditory information processing have often been investigated using the odd-ball paradigm, in which infrequent sounds (deviants) are presented within a regular train of frequent stimuli (standards). Traditionally, this paradigm has been applied using either high temporal resolution (EEG) or high spatial resolution (fMRI, PET). However, used separately, these techniques cannot provide information on both the location and time course of particular neural processes. The goal of this study was to investigate the neural correlates of auditory processes with a fine spatio-temporal resolution. A simultaneous auditory evoked potentials (AEP) and functional magnetic resonance imaging (fMRI) technique (AEP-fMRI), together with an odd-ball paradigm, were used. Six healthy volunteers, aged 20-35 years, participated in an odd-ball simultaneous AEP-fMRI experiment. AEP in response to acoustic stimuli were used to model bioelectric intracerebral generators, and electrophysiological results were integrated with fMRI data. fMRI activation evoked by standard stimuli was found to occur mainly in the primary auditory cortex. Activity in these regions overlapped with intracerebral bioelectric sources (dipoles) of the N1 component. Dipoles of the N1/P2 complex in response to standard stimuli were also found in the auditory pathway between the thalamus and the auditory cortex. Deviant stimuli induced fMRI activity in the anterior cingulate gyrus, insula, and parietal lobes. The present study showed that neural processes evoked by standard stimuli occur predominantly in subcortical and cortical structures of the auditory pathway. Deviants activate areas non-specific for auditory information processing.	\N	\N
24419006	Three experiments investigated the role of memory and rehearsal in a dichotic emotion recognition task by manipulating the response procedure as well as the interval between encoding and retrieval while taking into account order of report. For all experiments, right-handed undergraduates were presented with dichotic pairs of the words bower, dower, power, and tower pronounced in a sad, angry, happy, or neutral tone of voice. Participants were asked to report the two emotions presented on each trial by clicking on the corresponding drawings or words on a computer screen, either following no delay or a five second delay. Experiment 1 applied the delay conditions as a between-subjects factor whereas it was a within-subject factor in Experiment 2. In Experiments 1 and 2, more correct responses occurred for the left than the right ear, reflecting a left ear advantage (LEA) that was slightly larger with a nonverbal than a verbal response. The LEA was also found to be larger with no delay than with the 5s delay. In addition, participants typically responded first to the left ear stimulus. In fact, the first response produced a LEA whereas the second response produced a right ear advantage. Experiment 3 involved a concurrent task during the delay to prevent rehearsal. In Experiment 3, the pattern of results supported the claim that rehearsal could account for the findings of the first two experiments. The findings are interpreted in the context of the role of rehearsal and memory in models of dichotic listening.	\N	\N
24429136	How humans solve the cocktail party problem remains unknown. However, progress has been made recently thanks to the realization that cortical activity tracks the amplitude envelope of speech. This has led to the development of regression methods for studying the neurophysiology of continuous speech. One such method, known as stimulus-reconstruction, has been successfully utilized with cortical surface recordings and magnetoencephalography (MEG). However, the former is invasive and gives a relatively restricted view of processing along the auditory hierarchy, whereas the latter is expensive and rare. Thus it would be extremely useful for research in many populations if stimulus-reconstruction was effective using electroencephalography (EEG), a widely available and inexpensive technology. Here we show that single-trial (≈60 s) unaveraged EEG data can be decoded to determine attentional selection in a naturalistic multispeaker environment. Furthermore, we show a significant correlation between our EEG-based measure of attention and performance on a high-level attention task. In addition, by attempting to decode attention at individual latencies, we identify neural processing at ∼200 ms as being critical for solving the cocktail party problem. These findings open up new avenues for studying the ongoing dynamics of cognition using EEG and for developing effective and natural brain-computer interfaces.	\N	\N
24429520	Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere. Although various theories have been proposed to unite perception and production, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system. Although recent evidence indicates that speech perception occurs bilaterally, prevailing models maintain that the speech sensory-motor system is left lateralized and facilitates the transformation from sensory-based auditory representations to motor-based production representations. However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging. Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural responses during both perception and production in an overt word-repetition task. Using a non-word transformation task, we show that bilateral sensory-motor responses can perform transformations between speech-perception- and speech-production-based representations. These results establish a bilateral sublexical speech sensory-motor system.	\N	\N
24431427	The new DSM-5 diagnostic criteria for autism spectrum disorders (ASDs) include sensory disturbances in addition to the well-established language, communication, and social deficits. One sensory disturbance seen in ASD is an impaired ability to integrate multisensory information into a unified percept. This may arise from an underlying impairment in which individuals with ASD have difficulty perceiving the temporal relationship between cross-modal inputs, an important cue for multisensory integration. Such impairments in multisensory processing may cascade into higher-level deficits, impairing day-to-day functioning on tasks, such as speech perception. To investigate multisensory temporal processing deficits in ASD and their links to speech processing, the current study mapped performance on a number of multisensory temporal tasks (with both simple and complex stimuli) onto the ability of individuals with ASD to perceptually bind audiovisual speech signals. High-functioning children with ASD were compared with a group of typically developing children. Performance on the multisensory temporal tasks varied with stimulus complexity for both groups; less precise temporal processing was observed with increasing stimulus complexity. Notably, individuals with ASD showed a speech-specific deficit in multisensory temporal processing. Most importantly, the strength of perceptual binding of audiovisual speech observed in individuals with ASD was strongly related to their low-level multisensory temporal processing abilities. Collectively, the results represent the first to illustrate links between multisensory temporal function and speech processing in ASD, strongly suggesting that deficits in low-level sensory processing may cascade into higher-order domains, such as language and communication.	\N	\N
24437771	Auditory deprivation and stimulation can change the threshold of the acoustic middle ear reflex as well as loudness in adult listeners. However, it has remained unclear whether changes in these measures are due to the same mechanism. In this study, deprivation was achieved using a monaural earplug that was worn by listeners for 7 days. Acoustic reflex thresholds (ARTs) and categorical loudness ratings were measured using a blinded design in which the experimenter was unaware of which ear had been plugged. Immediately after terminating unilateral deprivation, ARTs were obtained at a lower sound pressure level in the ear that had been fitted with an earplug and at a higher sound pressure level in the control ear. In contrast, categorical judgments of loudness changed in the same direction in both ears with a given stimulus level reported as louder after unilateral deprivation. The relationship between changes to the ART and loudness judgments was not statistically significant. For both the ARTs and the categorical loudness judgments, most of the changes had disappeared within 24 h after earplug removal. The changes in ARTs, as a consequence of unilateral sound deprivation, are consistent with a gain control mechanism; however, the lack of relationship with the categorical loudness judgments, and the different pattern of findings for each measure, suggests the possibility of multiple gain mechanisms.	\N	\N
24437774	The discrimination of interaural phase differences (IPDs) requires accurate binaural temporal processing and has been used as a measure of sensitivity to temporal envelope and temporal fine structure (TFS). Previous studies found that TFS-IPD discrimination declined with age and with sensorineural hearing loss (SNHL), but age and SNHL have often been confounded. The aim of this study was to determine the independent contributions of age and SNHL to TFS and envelope IPD discrimination by using a sample of adults with a wide range of ages and SNHL. A two-interval, two-alternative forced-choice procedure was used to measure IPD discrimination thresholds for 20-Hz amplitude-modulated tones with carrier frequencies of 250 or 500 Hz when the IPD was in either the stimulus envelope or TFS. There were positive correlations between absolute thresholds and TFS-IPD thresholds, but not envelope-IPD thresholds, when age was accounted for. This supports the idea that SNHL affects TFS processing independently to age. Age was positively correlated with envelope-IPD thresholds at both carrier frequencies and TFS-IPD thresholds at 500 Hz, when absolute thresholds were accounted for. These results suggest that age negatively affects the binaural processing of envelope and TFS at some frequencies independently of SNHL.	\N	\N
24441742	Abnormal hearing tests have been noted in human immunodeficiency virus (HIV)-infected patients in several studies, but the nature of the hearing deficit has not been clearly defined. The authors performed a cross-sectional study of both HIV+ and HIV- individuals in Tanzania by using an audiological test battery. The authors hypothesized that HIV+ adults would have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls. In addition, they anticipated that the prevalence of abnormal hearing assessments would increase with antiretroviral therapy (ART) use and treatment for tuberculosis (TB). Pure-tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and a gap-detection test were performed using a laptop-based hearing testing system on 751 subjects (100 HIV- in the United States, plus 651 in Dar es Salaam, Tanzania, including 449 HIV+ [130 ART- and 319 ART+], and 202 HIV-, subjects. No U.S. subjects had a history of TB treatment. In Tanzania, 204 of the HIV+ and 23 of the HIV- subjects had a history of TB treatment. Subjects completed a video and audio questionnaire about their hearing, as well as a health history questionnaire. HIV+ subjects had reduced DPOAE levels compared with HIV- subjects, but their hearing thresholds, tympanometry results, and gap-detection thresholds were similar. Within the HIV+ group, those on ART reported significantly greater difficulties understanding speech in noise, and were significantly more likely to report that they had difficulty understanding speech than the ART- group. The ART+ group had a significantly higher mean gap-detection threshold compared with the ART- group. No effects of TB treatment were seen. The fact that the ART+/ART- groups did not differ in measures of peripheral hearing ability (DPOAEs, thresholds), or middle ear measures (tympanometry), but that the ART+ group had significantly more trouble understanding speech and had higher gap-detection thresholds indicates a central processing deficit. These data suggest that: (1) hearing deficits in HIV+ individuals could be a CNS side effect of HIV infection, (2) certain ART regimens might produce CNS side effects that manifest themselves as hearing difficulties, and/or (3) some ART regimens may treat CNS HIV inadequately, perhaps due to insufficient CNS drug levels, which is reflected as a central hearing deficit. Monitoring of central hearing parameters could be used to track central effects of either HIV or ART.	\N	\N
24447236	This discussion paper aims to synthesise the literature on patient-centred care from a range of health professions and to relate this to the field of rehabilitative audiology. Through review of the literature, this paper addresses five questions: What is patient-centred care? How is patient-centred care measured? What are the outcomes of patient-centred care? What are the factors contributing to patient-centred care? What are the implications for audiological rehabilitation? Literature review and synthesis. Publications were identified by structured searches in PubMed, Cinahl, Web of Knowledge, and PsychInfo, and by inspecting the reference lists of relevant articles. Few publications from within the audiology profession address this topic and consequently a review and synthesis of literature from other areas of health were used to answer the proposed questions. This paper concludes that patient-centred care is in line with the aims and scope of practice for audiological rehabilitation. However, there is emerging evidence that we still need to inform the conceptualisation of patient-centred audiological rehabilitation. A definition of patient-centred audiological rehabilitation is needed to facilitate studies into the nature and outcomes of it in audiological rehabilitation practice.	\N	\N
24456399	Crossmodal integration of auditory and visual information, such as phonemes and graphemes, is a critical skill for fluent reading. Previous work has demonstrated that white matter connectivity along the arcuate fasciculus (AF) is predicted by reading skill and that crossmodal processing particularly activates the posterior STS (pSTS). However, the relationship between this crossmodal activation and white matter integrity has not been previously reported. We investigated the interrelationship of crossmodal integration, both in terms of behavioral performance and pSTS activity, with AF tract coherence using a rhyme judgment task in a group of 47 children with a range of reading abilities. We demonstrate that both response accuracy and pSTS activity for crossmodal (auditory-visual) rhyme judgments was predictive of fractional anisotropy along the left AF. Unimodal (auditory-only or visual-only) pSTS activity was not significantly related to AF connectivity. Furthermore, activity in other reading-related ROIs did not show the same AV-only AF coherence relationship, and AV pSTS activity was not related to connectivity along other language-related tracts. This study is the first to directly show that crossmodal brain activity is specifically related to connectivity in the AF, supporting its role in phoneme-grapheme integration ability. More generally, this study helps to define an interdependent neural network for reading-related integration.	\N	\N
24488957	In categorical perception (CP), continuous physical signals are mapped to discrete perceptual bins: mental categories not found in the physical world. CP has been demonstrated across multiple sensory modalities and, in audition, for certain over-learned speech and musical sounds. The neural basis of auditory CP, however, remains ambiguous, including its robustness in nonspeech processes and the relative roles of left/right hemispheres; primary/nonprimary cortices; and ventral/dorsal perceptual processing streams. Here, highly trained musicians listened to 2-tone musical intervals, which they perceive categorically while undergoing functional magnetic resonance imaging. Multivariate pattern analyses were performed after grouping sounds by interval quality (determined by frequency ratio between tones) or pitch height (perceived noncategorically, frequency ratios remain constant). Distributed activity patterns in spheres of voxels were used to determine sound sample identities. For intervals, significant decoding accuracy was observed in the right superior temporal and left intraparietal sulci, with smaller peaks observed homologously in contralateral hemispheres. For pitch height, no significant decoding accuracy was observed, consistent with the non-CP of this dimension. These results suggest that similar mechanisms are operative for nonspeech categories as for speech; espouse roles for 2 segregated processing streams; and support hierarchical processing models for CP.	\N	\N
24489819	This study tested the hypothesis that the previously reported advantage of musicians over non-musicians in understanding speech in noise arises from more efficient or robust coding of periodic voiced speech, particularly in fluctuating backgrounds. Speech intelligibility was measured in listeners with extensive musical training, and in those with very little musical training or experience, using normal (voiced) or whispered (unvoiced) grammatically correct nonsense sentences in noise that was spectrally shaped to match the long-term spectrum of the speech, and was either continuous or gated with a 16-Hz square wave. Performance was also measured in clinical speech-in-noise tests and in pitch discrimination. Musicians exhibited enhanced pitch discrimination, as expected. However, no systematic or statistically significant advantage for musicians over non-musicians was found in understanding either voiced or whispered sentences in either continuous or gated noise. Musicians also showed no statistically significant advantage in the clinical speech-in-noise tests. Overall, the results provide no evidence for a significant difference between young adult musicians and non-musicians in their ability to understand speech in noise.	\N	\N
24490946	Studies of face recognition in older adults (60 years of age and older) report increases in false alarms over younger adults (usually 18-30 years of age), but no age differences in hits. To examine this phenomenon, we compared older and younger adults in categorical perception of faces. We hypothesized that face representations in older adults would be broadly tuned, resulting in overlapping representations, manifested by a shallower slope in identity categorization than in younger adults, and age-related reductions in the advantage for between-categories, as compared with within-category, face discrimination. We morphed faces to change linearly from one identity to another. We used familiar or unfamiliar faces in separate conditions to examine the role of familiarity. Categorical perception was assessed in an identity-classification task and a discrimination task. Older adults showed a shallower slope and poorer discrimination compared with younger adults, and both groups exhibited better performance with familiar than unfamiliar faces. Enhanced discriminability for between-categories as compared with within-category faces was seen for both familiar and unfamiliar faces in younger adults, but only for familiar faces in older adults. The more broadly tuned representations of unfamiliar faces in older adults may lead to misidentification and greater false alarms for unfamiliar faces, but not for familiar faces.	\N	\N
24496288	This study evaluated effects of nonlinear frequency compression (NLFC) processing in children with hearing loss for consonant identification in quiet and for spondee identification in competing noise or speech. It was predicted that participants would benefit from NLFC for consonant identification in quiet when access to high-frequency information was critical, but that NLFC would be less beneficial, or even detrimental, when identification relied on mid-frequency cues. Further, it was hypothesized that NLFC could result in greater susceptibility to masking in the spondee task. The rationale for these predictions is that improved access to high-frequency information comes at the cost of decreased spectral resolution. A repeated-measures design compared speech-perception outcomes in 17 pediatric hearing aid users (9 to 17 years of age) wearing Naida V SP "laboratory" hearing aids with NLFC on and off. Data were also collected in an initial baseline session in which children wore their personal hearing aids. Children with a wide range of audiometric configurations were included, but all participants were full-time users of hearing aids with active NLFC. For each hearing aid condition, speech perception was assessed in the sound field by using a closed-set 12-alternative consonant-vowel identification measure in quiet, and a closed-set four-alternative spondee-identification measure in a speech-shaped noise or in a two-talker speech masker. No significant differences in performance were observed between laboratory hearing aid conditions with NLFC activated or deactivated for either speech-perception measure. An unexpected finding was that the majority of participants had no difficulty identifying the high-frequency consonant /s/ even when NLFC was deactivated. Investigation into individual differences revealed that subjects with a greater difference in audible bandwidth with NLFC on versus NLFC off were less likely to demonstrate improvements in high-frequency consonant identification in quiet, but were more likely to demonstrate improvements in spondee identification in speech-shaped noise. Group results observed in the initial baseline assessment using personal aids fitted with more aggressive NLFC settings than used in laboratory aids indicated better consonant identification accuracy in quiet. However, spondee identification in the two-talker masker was poorer with personal compared with laboratory hearing aids. Comparisons across personal and laboratory hearing aids are tempered, however, by the potential of an order effect. The observation of comparable performance with NLFC on and NLFC off in the laboratory aids provides evidence that NLFC is neither detrimental nor advantageous when modest in strength. Results with personal hearing aids fitted with stronger compression settings than laboratory aids (NLFC on) highlight the critical need for further research to determine the impact of NLFC processing on speech perception for a wider range of speech-perception measures and compression settings.	\N	\N
24503772	The bone-anchored hearing device (BAHD) was not introduced in China until 2010. To our knowledge, this is the first study to assess the efficacy of Chinese Mandarin-speaking patients with bilateral aural atresia. To evaluate the speech recognition of Chinese Mandarin-speaking patients with BAHDs as well as patients' satisfaction using 2 questionnaires. A retrospective case review of 16 patients with bilateral aural atresia conducted at a tertiary referral center. A BAHD was implanted during auricle reconstruction surgery or after the auricle was rebuilt. A surgical method to combine the BAHD implantation with the second stage of ear reconstruction was introduced. Speech audiometry test and mean pure-tone threshold results were compared among patients with unaided hearing and those with BAHDs. Scores from the BAHD user questionnaire and Glasgow Children's Benefit Inventory (GCBI) were used to measure patients' satisfaction and subjective health benefit. The mean (SD) speech discrimination scores measured in a sound field with a presentation level of 45 dB HL (hearing level) were 6.7% (7.4%) unaided and 86.5% (4.4%) with a BAHD. Scores with a presentation level of 65 dB HL were 56.5% (7.4%) unaided and 90.1% (3.4%) with a BAHD. The speech reception threshold was 60.6 (7.5) dB HL unaided and 24.7 (5.0) dB HL with a BAHD. The mean (SD) pure-tone threshold of the patients was 61.6 (7.8) dB HL unaided and 23.8 (5.9) dB HL with a BAHD. The BAHD application questionnaire demonstrated excellent patient satisfaction. The mean (SD) benefit score of GCBI was 45.6 (14.4). For aural atresia, the BAHD has been one of the most reliable methods of auditory rehabilitation. It can improve the patient's word recognition performance and quality of life. The technique of BAHD implantation combined with auricular reconstruction in a 2-stages-in-1 surgery and the modified incision of patients with reconstructed auricle proved to be safe and effective.	\N	\N
24508369	Acoustic communication requires gathering, transforming, and interpreting diverse sound cues. To achieve this, all the spatial and temporal features of complex sound stimuli must be captured in the firing patterns of the primary sensory neurons and then accurately transmitted along auditory pathways for additional processing. The mammalian auditory system relies on several synapses with unique properties in order to meet this task: the auditory ribbon synapses, the endbulb of Held, and the calyx of Held. Each of these synapses develops morphological and electrophysiological characteristics that enable the remarkably precise signal transmission necessary for conveying the miniscule differences in timing that underly sound localization. In this article, we review the current knowledge of how these synapses develop and mature to acquire the specialized features necessary for the sense of hearing.	\N	\N
24508791	Amblyopia is a developmental disorder that results in both monocular and binocular deficits. Although traditional treatment in clinical practice (i.e., refractive correction, or occlusion by patching and penalization of the fellow eye) is effective in restoring monocular visual acuity, there is little information on how binocular function, especially stereopsis, responds to traditional amblyopia treatment. We aim to evaluate the effects of perceptual learning on stereopsis in observers with amblyopia in the current study. Eleven observers (21.1 ± 5.1 years, six females) with anisometropic or ametropic amblyopia were trained to judge depth in 10 to 13 sessions. Red-green glasses were used to present three different texture anaglyphs with different disparities but a fixed exposure duration. Stereoacuity was assessed with the Fly Stereo Acuity Test and visual acuity was assessed with the Chinese Tumbling E Chart before and after training. Averaged across observers, training significantly reduced disparity threshold from 776.7″ to 490.4″ (P < 0.01) and improved stereoacuity from 200.3″ to 81.6″ (P < 0.01). Interestingly, visual acuity also significantly improved from 0.44 to 0.35 logMAR (approximately 0.9 lines, P < 0.05) in the amblyopic eye after training. Moreover, the learning effects in two of the three retested observers were largely retained over a 5-month period. Perceptual learning is effective in improving stereo vision in observers with amblyopia. These results, together with previous evidence, suggest that structured monocular and binocular training might be necessary to fully recover degraded visual functions in amblyopia. Chinese Abstract.	\N	\N
24514158	This study analyses the meaning spaces of German pitch contours using two modes of melodic movement: continuous or in steps of sustained pitch. Both the continuous and stepped movements are represented by a set of five basic patterns, the latter being derived from the former. Thirty-six German native speakers judged the pattern sets on a 12-scale semantic differential. The semantic profiles confirm that stepped contours can be conceived of as stylized intonation, in a formal as well as in a functional sense. On the one hand, continuous (non-stylized) and stepped (stylized) contours are assigned different overall meanings (especially on the scales astonished - commonplace and interested - not interested). On the other hand, listeners organize the two contour sets in a similar fashion, which speaks in favour of parallel pattern inventories of continuous and stepped movement, respectively. However, the meaning space of the stylized patterns is affected by formal restrictions, for instance in the step transformation of continuous rises.	\N	\N
24525262	What are the temporal dynamics of perceptual sampling during visual search tasks, and how do they differ between a difficult (or inefficient) and an easy (or efficient) task? Does attention focus intermittently on the stimuli, or are the stimuli processed continuously over time? We addressed these questions by way of a new paradigm using periodic fluctuations of stimulus information during a difficult (color-orientation conjunction) and an easy (+ among Ls) search task. On each stimulus, we applied a dynamic visual noise that oscillated at a given frequency (2-20 Hz, 2-Hz steps) and phase (four cardinal phase angles) for 500 ms. We estimated the dynamics of attentional sampling by computing an inverse Fourier transform on subjects' d-primes. In both tasks, the sampling function presented a significant peak at 2 Hz; we showed that this peak could be explained by nonperiodic search strategies such as increased sensitivity to stimulus onset and offset. Specifically in the difficult task, however, a second, higher-frequency peak was observed at 9 to 10 Hz, with a similar phase for all subjects; this isolated frequency component necessarily entails oscillatory attentional dynamics. In a second experiment, we presented difficult search arrays with dynamic noise that was modulated by the previously obtained grand-average attention sampling function or by its converse function (in both cases omitting the 2 Hz component to focus on genuine oscillatory dynamics). We verified that performance was higher in the latter than in the former case, even for subjects who had not participated in the first experiment. This study supports the idea of a periodic sampling of attention during a difficult search task. Although further experiments will be needed to extend these findings to other search tasks, the present report validates the usefulness of this novel paradigm for measuring the temporal dynamics of attention.	\N	\N
24533757	The effect of deactivating indiscriminable cochlear implant (CI) electrodes for unilaterally implanted adults was evaluated using the BKB (Bamford-Kowal-Bench) sentence test in quiet and in pink noise (signal-to-noise ratio of +10dBA) and the adaptive Coordinate Response Measure (CRM). Each CI recipient who failed electrode differentiation (ED) in at least one electrode-pair, based on results of a pure-tone pitch-ranking task received two research programmes to try out in a cross-over study. Research programmes (RP) either employed discriminable electrodes only or the most discriminable two-thirds of the electrodes in the electrode array for CI recipients failing ED for more than a third of the electrodes. The participants were also asked to subjectively report improvement of or decline in sound quality in everyday listening situations. There was significant improvement in CRM speech reception thresholds (SRTs) (Z = -3.24, N = 15, P = 0.001), BKB sentence scores in quiet (t = 3.17, df = 24, P < 0.005) and also in pink noise (t = 2.26, df = 19, P < 0.005) after deactivating indiscriminable electrodes.	\N	\N
24548324	Not much is known about how people comprehend ironic utterances, and to date, most studies have simply compared processing of ironic versus non-ironic statements. A key aspect of the graded salience hypothesis, distinguishing it from other accounts (such as the standard pragmatic view and direct access view), is that it predicts differences between processing of familiar and unfamiliar ironies. Specifically, if an ironic utterance is familiar, then the ironic interpretation should be available without the need for extra inferential processes, whereas for unfamiliar ironies, the literal interpretation would be computed first, and a mismatch with context would lead to a re-interpretation of the statement as being ironic. We recorded participants' eye movements while they were reading (Experiment 1), and electrical brain activity while they were listening to (Experiment 2), familiar and unfamiliar ironies compared to non-ironic controls. Results show disruption to eye movements and an N400-like effect for unfamiliar ironies only, supporting the predictions of the graded salience hypothesis. In addition, in Experiment 2, a late positivity was found for both familiar and unfamiliar ironic materials, compared to non-ironic controls. We interpret this positivity as reflecting ongoing conflict between the literal and ironic interpretations of the utterance.	\N	\N
24557002	The rapidly evolving field of early diagnostics after the introduction of newborn hearing screening requires rapid, valid, and objective methods, which have to be thoroughly evaluated in adults before use in infants. The aim was to study cross-correlation analysis of interleaved auditory brainstem responses (ABRs) in a wide dynamic range in normal-hearing adults. Off-line analysis allowed for comparison with psychoacoustical click threshold (PCT), pure-tone threshold, and determination of ABR input/output function. Specifically, nonfiltered and band-pass filtered ABRs were studied in various time segments along with time elapsed for ensemble of sweeps reaching a specific detection criterion. Fourteen healthy normal-hearing subjects (18 to 35 years of age, 50% females) without any history of noise exposure participated. They all had pure-tone thresholds better than 20 dB HL (125 to 8000 Hz). ABRs were recorded in both ears using 100 μsec clicks, from 71.5 dB nHL down to -18.5 dB nHL, in 10 dB steps (repetition rate, 39 Hz; time window, 15 msec; filter, 30 to 8000 Hz). The number of sweeps increased from 2000 at 71.5 dB nHL, up to 30000 at -18.5 dB nHL. Each sweep was stored in a data base for off-line analysis. Cross-correlation analysis between two subaverages of interleaved responses was performed in the time domain for nonfiltered and digitally band-pass filtered (300 to 1500 Hz) entire and time-windowed (1 to 11 and 5 to 11 msec) responses. PCTs were measured using a Bekesy technique with the same insert phone and stimulus as used for the ABR (repetition rate, 20 Hz). Time elapsed (≈ number of accepted sweeps/repetition rate) for the ensemble of sweeps needed to reach a cross-correlation coefficient (ρ) of 0.70 (=3.7 dB signal-to-noise ratio [SNR]) was analyzed. Mean cross-correlation coefficients exceeded 0.90 in both ears at stimulus levels ≥11.5 dB nHL for the entire nonfiltered ABR. At 1.5 dB nHL, mean(SD) ρ was 0.53(0.32) and 0.44(0.40) for left and right ears, respectively (n = 14) (=0 dB SNR). In comparison, mean(SD) PCT was -1.9(2.9) and -2.5(3.2) dB nHL for left and right ears, respectively (n = 14), while mean pure-tone average (500 to 2000 Hz) was 2.5 dB HL (n = 28). Almost no effect of band-pass filtering or reduced analysis time window existed. Average time elapsed needed to reach ρ = 0.70 was approximately 20 seconds or less at stimulus levels ≥41.5 dB nHL, and ≈30 seconds at 31.5 dB nHL. The average (interpolated) stimulus level corresponding to ρ=0.70 for the entire nonfiltered ABR was 6.5 dB nHL (n = 28), which coincided with the estimated psychoacoustical threshold for single clicks. ABR could be identified in a short period of time using cross-correlation analysis between interleaved responses. The average stimulus level corresponding to 0 dB SNR in the entire nonfiltered ABR occurred at 1.5 dB nHL, 4 dB above the average PCT. The mean input/output function for the ensemble of sweeps required to reach ρ = 0.70 increased monotonically with increasing stimulus level, in parallel with the ABR based on all sweeps (≥1.5 dB nHL). Time domain cross-correlation analysis of ABR might form the basis for automatic response identification and future threshold-seeking procedures.	\N	\N
24564623	To evaluate the hearing of adolescents with diabetes mellitus type 1(DM1) by otoacoustic emissions (OAEs), and by comparing different tests with pure-tone audiometry to identify potential early cochlear impairments. Pure-tone audiometry, transient evoked otoacoustic emissions (TEOAEs), and distortion product otoacoustic emissions (DPOAEs) were performed in a group of adolescents with and without DM1. Clinical characteristics, disease duration, and glycated haemoglobin levels were studied. Participants were 40 adolescents with DM1 and 40 healthy subjects. Sensorineural hearing loss, affecting frequencies of 6000 and 8000 Hz, was found only in DM1 subjects when compared to the controls (7.7% vs. 0%, p < 0.05). A higher prevalence of cochlear damage was detected by DPOAE responses, 32% belonging from the diabetic group, vs. 3.7% in the control group. Absent TEOAE responses were observed in only three individuals, all from the diabetic group (5.1% of the tests performed in the diabetic group). Additionally, hearing thresholds were better in diabetic subjects with good control when compared to ones with regular or poor control (p = 0.00). Hearing thresholds were higher in poorly controlled diabetics when compared to subjects with good (p = 0.000) or regular control (p = 0.006). Early evidence of cochlear damage was detected in adolescents with DM1 leading to hearing loss at high frequencies. Abnormal DPOAEs responses were found more frequently than the alterations in TEOAEs and pure-tone audiometry, suggesting that DPOAEs evaluation is the most sensitive and it could be used for monitoring the progression of cochlear damage during the early stages of hearing impairment.	\N	\N
24564624	Detailed information on the hearing threshold levels (HTLs) of young Australians was gathered as part of a large-scale study of the relationship between HTL and leisure-noise exposure in young Australians. HTL data for the study population (18-35 year olds) was carefully collected, as well as otoscopy, tympanometry, contra-lateral acoustic reflexes, and otoacoustic emissions (transient and distortion product), together with a comprehensive hearing health history - both past and present. The sample cohort consisted of 1407 individuals, females and males. Prior to analysis, HTL data were filtered according to both a 'Low' and 'High' set of exclusion criteria. The results obtained for both high-screen and low-screen datasets were around +5 dB above the traditionally accepted values of audiometric zero. This is consistent with previous published reports. Comparison with 'ISO 7029 Acoustics: Statistical distribution of hearing thresholds as a function of age' indicated that threshold values for this dataset have a similar distribution to those of the Standard. This data provides a suitable reference HTL ('normative') database for young Australians.	\N	\N
24564688	To characterize the impulse noise exposure and auditory risk for youth recreational firearm users engaged in outdoor target shooting events. The youth shooting positions are typically standing or sitting at a table, which places the firearm closer to the ground or reflective surface when compared to adult shooters. Acoustic characteristics were examined and the auditory risk estimates were evaluated using contemporary damage-risk criteria for unprotected adult listeners and the 120-dB peak limit suggested by the World Health Organization (1999) for children. Impulses were generated by 26 firearm/ammunition configurations representing rifles, shotguns, and pistols used by youth. Measurements were obtained relative to a youth shooter's left ear. All firearms generated peak levels that exceeded the 120 dB peak limit suggested by the WHO for children. In general, shooting from the seated position over a tabletop increases the peak levels, LAeq8 and reduces the unprotected maximum permissible exposures (MPEs) for both rifles and pistols. Pistols pose the greatest auditory risk when fired over a tabletop. Youth should utilize smaller caliber weapons, preferably from the standing position, and always wear hearing protection whenever engaging in shooting activities to reduce the risk for auditory damage.	\N	\N
24568928	A new study reports that activations of superior temporal regions for speech are normal in dyslexia, although being less well connected to downstream frontal regions. These findings support the hypothesis of a deficit in the access to phonological representations rather than in the representations themselves.	\N	\N
24569986	Viewing behavior exhibits temporal and spatial structure that is independent of stimulus content and task goals. One example of such structure is horizontal biases, which are likely rooted in left-right asymmetries of the visual and attentional systems. Here, we studied the existence, extent, and mechanisms of this bias. Left- and right-handed subjects explored scenes from different image categories, presented in original and mirrored versions. We also varied the spatial spectral content of the images and the timing of stimulus onset. We found a marked leftward bias at the start of exploration that was independent of image category. This left bias was followed by a weak bias to the right that persisted for several seconds. This asymmetry was found in the majority of right-handers but not in left-handers. Neither low- nor high-pass filtering of the stimuli influenced the bias. This argues against mechanisms related to the hemispheric segregation of global versus local visual processing. Introducing a delay in stimulus onset after offset of a central fixation spot also had no influence. The bias was present even when stimuli were presented continuously and without any requirement to fixate, associated to both fixation- and saccade-contingent image changes. This suggests the bias is not caused by structural asymmetries in fixation control. Instead the pervasive horizontal bias is compatible with known asymmetries of higher-level attentional areas related to the detection of novel events.	\N	\N
24580021	To evaluate the impact on voice of 2 hours of continuous oral reading. Fifty normophonic women underwent two sessions of voice loading in which the required intensity level varied: 60-65 dB(A) for the first session, and 70-75 dB(A) for the second session. Ten expert judges evaluated the breathiness of one sentence recorded before and after each loading session. Pairs of stimuli were presented randomly to the judges, who were asked to designate the breathiest sample. A significant decrease in breathiness was observed following both sessions, suggesting an improvement of voice subsequent to loading. When comparing the two intensity levels, no difference was found for breathiness after vocal loading.	\N	\N
24584899	The ability of humans to echolocate has been recognized since the 1940s. Little is known about what determines individual differences in echolocation ability, however. Although hearing ability has been suggested as an important factor in blind people and sighted-trained echolocators, there is evidence to suggest that this may not be the case for sighted novices. Therefore, non-auditory aspects of human cognition might be relevant. Previous brain imaging studies have shown activation of the early 'visual', i.e. calcarine, cortex during echolocation in blind echolocation experts, and also during visual imagery in blind and sighted people. Therefore, here we investigated the relationship between echolocation ability and vividness of visual imagery (VVI). Twenty-four sighted echolocation novices completed Marks' (Br J Psychol 1:17-24, 1973) VVI questionnaire and they also performed an echolocation size-discrimination task. Furthermore, they participated in a battery of auditory tests that determined their ability to detect fluctuations in sound frequency and intensity, as well as hearing differences between the right and left ear. A correlational analysis revealed a significant relationship between participants' VVI and echolocation ability, i.e. participants with stronger VVI also had higher echolocation ability, even when differences in auditory abilities were taken into account. In terms of underlying mechanisms, we suggest that either the use of visual imagery is a strategy for echolocation, or that visual imagery and echolocation both depend on the ability to recruit calcarine cortex for cognitive tasks that do not rely on retinal input.	\N	\N
24588528	To investigate the occurrence of 27 chronic medical conditions in a cohort of adults with and without hearing impairment, and to examine the association between these conditions and hearing ability. The National Longitudinal Study on Hearing (NL-SH study) is a large prospective study among adults aged 18 to 70 years, conducted via the internet in the Netherlands. Hearing ability was measured with a digits-in-noise test and comorbidity was assessed through self-report. Cross-sectional data of 890 hearing-impaired and 975 normally-hearing adults were analyzed. Both descriptive statistics and multinomial logistic regression analyses were conducted. Of the NL-SH participants with insufficient or poor hearing ability, 78.5% reported to suffer from at least one additional chronic condition. This proportion was larger than in the normally-hearing group (68.6% with one or more chronic conditions and 37.7% with two or more). After adjustment for age and gender, 'dizziness causing falling', 'diabetes' and 'arthritis types other than osteoarthritis and rheumatic arthritis' were significantly associated with poor hearing ability. Our results show that some previously reported associations do not only occur in older age groups, but also in younger cohorts. Comorbidity is relevant in the rehabilitation (multi-disciplinary care) and the clinical encounter.	\N	\N
24598525	Changes in amplitude and frequency jointly determine much of the communicative significance of complex acoustic signals, including human speech. We have previously described responses of neurons in the core auditory cortex of awake rhesus macaques to sinusoidal amplitude modulation (SAM) signals. Here we report a complementary study of sinusoidal frequency modulation (SFM) in the same neurons. Responses to SFM were analogous to SAM responses in that changes in multiple parameters defining SFM stimuli (e.g., modulation frequency, modulation depth, carrier frequency) were robustly encoded in the temporal dynamics of the spike trains. For example, changes in the carrier frequency produced highly reproducible changes in shapes of the modulation period histogram, consistent with the notion that the instantaneous probability of discharge mirrors the moment-by-moment spectrum at low modulation rates. The upper limit for phase locking was similar across SAM and SFM within neurons, suggesting shared biophysical constraints on temporal processing. Using spike train classification methods, we found that neural thresholds for modulation depth discrimination are typically far lower than would be predicted from frequency tuning to static tones. This "dynamic hyperacuity" suggests a substantial central enhancement of the neural representation of frequency changes relative to the auditory periphery. Spike timing information was superior to average rate information when discriminating among SFM signals, and even when discriminating among static tones varying in frequency. This finding held even when differences in total spike count across stimuli were normalized, indicating both the primacy and generality of temporal response dynamics in cortical auditory processing.	\N	\N
24606277	While many studies have assessed the efficacy of similarity-based cues for auditory stream segregation, much less is known about whether and how the larger-scale structure of sound sequences support stream formation and the choice of sound organization. Two experiments investigated the effects of musical melody and rhythm on the segregation of two interleaved tone sequences. The two sets of tones fully overlapped in pitch range but differed from each other in interaural time and intensity. Unbeknownst to the listener, separately, each of the interleaved sequences was created from the notes of a different song. In different experimental conditions, the notes and/or their timing could either follow those of the songs or they could be scrambled or, in case of timing, set to be isochronous. Listeners were asked to continuously report whether they heard a single coherent sequence (integrated) or two concurrent streams (segregated). Although temporal overlap between tones from the two streams proved to be the strongest cue for stream segregation, significant effects of tonality and familiarity with the songs were also observed. These results suggest that the regular temporal patterns are utilized as cues in auditory stream segregation and that long-term memory is involved in this process.	\N	\N
24606289	For assessing hearing aid algorithms, a method is sought to shift the threshold of a speech-in-noise test to (mostly positive) signal-to-noise ratios (SNRs) that allow discrimination across algorithmic settings and are most relevant for hearing-impaired listeners in daily life. Hence, time-compressed speech with higher speech rates was evaluated to parametrically increase the difficulty of the test while preserving most of the relevant acoustical speech cues. A uniform and a non-uniform algorithm were used to compress the sentences of the German Oldenburg Sentence Test at different speech rates. In comparison, the non-uniform algorithm exhibited greater deviations from the targeted time compression, as well as greater changes of the phoneme duration, spectra, and modulation spectra. Speech intelligibility for fast Oldenburg sentences in background noise at different SNRs was determined with 48 normal-hearing listeners. The results confirmed decreasing intelligibility with increasing speech rate. Speech had to be compressed to more than 30% of its original length to reach 50% intelligibility at positive SNRs. Characteristics influencing the discrimination ability of the test for assessing effective SNR changes were investigated. Subjective and objective measures indicated a clear advantage of the uniform algorithm in comparison to the non-uniform algorithm for the application in speech-in-noise tests.	\N	\N
24606291	The present study investigated the importance of overall segment amplitude and intrinsic segment amplitude modulation of consonants and vowels to sentence intelligibility. Sentences were processed according to three conditions that replaced consonant or vowel segments with noise matched to the long-term average speech spectrum. Segments were replaced with (1) low-level noise that distorted the overall sentence envelope, (2) segment-level noise that restored the overall syllabic amplitude modulation of the sentence, and (3) segment-modulated noise that further restored faster temporal envelope modulations during the vowel. Results from the first experiment demonstrated an incremental benefit with increasing resolution of the vowel temporal envelope. However, amplitude modulations of replaced consonant segments had a comparatively minimal effect on overall sentence intelligibility scores. A second experiment selectively noise-masked preserved vowel segments in order to equate overall performance of consonant-replaced sentences to that of the vowel-replaced sentences. Results demonstrated no significant effect of restoring consonant modulations during the interrupting noise when existing vowel cues were degraded. A third experiment demonstrated greater perceived sentence continuity with the preservation or addition of vowel envelope modulations. Overall, results support previous investigations demonstrating the importance of vowel envelope modulations to the intelligibility of interrupted sentences.	\N	\N
24606310	Musicians have been shown to better perceive pitch and timbre cues in speech and music, compared to non-musicians. It is unclear whether this "musician advantage" persists under conditions of spectro-temporal degradation, as experienced by cochlear-implant (CI) users. In this study, gender categorization was measured in normal-hearing musicians and non-musicians listening to acoustic CI simulations. Recordings of Dutch words were synthesized to systematically vary fundamental frequency, vocal-tract length, or both to create voices from the female source talker to a synthesized male talker. Results showed an overall musician effect, mainly due to musicians weighting fundamental frequency more than non-musicians in CI simulations.	\N	\N
24606491	This research employed a forward-masking paradigm to estimate the current spread of monopolar (MP) and bipolar (BP) maskers, with current amplitudes adjusted to elicit the same loudness. Since the spatial separation between active and return electrodes is smaller in BP than in MP configurations, the BP current spread is more localized and presumably superior in terms of speech intelligibility. Because matching the loudness requires higher current in BP than in MP stimulation, previous forward-masking studies show that BP current spread is not consistently narrower across subjects or electrodes within a subject. The present forward-masking measures of current spread differ from those of previous studies by using the same BP probe electrode configuration for both MP and BP masker configurations, and adjusting the current levels of the MP and BP maskers so as to match them in loudness. With this method, the estimate of masker current spread would not be contaminated by differences in probe current spread. Forward masking was studied in four cochlear implant patients, two females and two males, with speech recognition scores higher than 50%; that is, their auditory-nerve survival status was more than adequate to carry out the experiments. The data showed that MP and BP masker configurations produce equivalent masking patterns (and current spreads) in three participants. A fourth participant displayed asymmetrical patterns with enhancement rather than masking in some cases, especially when the probe and masker were at the same location. This study showed equivalent masking patterns for MP and BP maskers when the BP masker current amplitude was increased to match the loudness of the MP masker, and the same BP probe configuration is used with both maskers. This finding could help to explain why cochlear implant users often fail to accrue higher speech intelligibility benefit from BP stimulation.	\N	\N
24610168	Longitudinal analysis of audiometric data of a large population of noise-exposed workers provides insight into the development of noise-induced hearing loss (NIHL) as a function of noise exposure and age, particularly during the first decade of noise exposure. Data of pure-tone audiometry of 17,930 construction workers who underwent periodic occupational hearing screening at least twice during a 4-year period were available for analysis. These concerned all follow-up measurements of the baseline cohort described by Leensen et al. (Int Arch Occup Environ Health 84:577-590, 2011). Linear mixed models explored the relationship between the annual rate of change in hearing and noise exposure level, exposure duration, and age. Data of 3,111 workers who were tested on three occasions were used to investigate the pattern of hearing loss development. The mean annual deterioration in hearing in this study population was 0.54 dB/yr, and this became larger with increasing noise exposure level and increasing age. Remarkably, during the first decade of noise exposure, an improvement in hearing threshold levels (HTLs) was observed. The change in hearing over three measurements showed a concave development of hearing loss as a function of time, which corresponds to NIHL development. Overall, hearing deteriorated over the measurement period. Because HTLs at follow-up were better than those obtained at baseline, no statement can be made about the NIHL development during the first decade of noise exposure. This improvement in HTLs rather resembles the result of measurement variation in occupational screening audiometry than an actual improvement in hearing ability.	\N	\N
24611446	The role in which two tones are first encountered in an unattended oddball sequence affects how deviance detection, reflected by mismatch negativity, treats them later when the roles reverse: a "primacy bias." We tested whether this effect is modulated by previous behavioral relevance assigned to the two tones. To this end, sequences in which the roles of the two tones alternated were preceded by a go/no-go task in which tones were presented with equal probability. Half of the participants were asked to respond to the short sounds, the other half to long sounds. Primacy bias was initially abolished but returned dependent upon the go-stimulus that the participant was assigned. Results demonstrate a long-term impact of prior learning on deviance detection, and that even when prior importance/equivalence is learned, the bias ultimately returns. Results are discussed in terms of persistent go-stimulus specific changes in responsiveness to sound.	\N	\N
24616979	The aim of this study is to evaluate the development of auditory performance and speech intelligibility within the first year after hearing aid fitting in children with moderate or severe hearing loss, investigate the effects of hearing level on auditory performance and speech intelligibility and provide a clinical database for their hearing and speech habilitation. Twenty-nine children participated in this study, ranging in age at hearing aid fitting from 3 to 8 years old with a mean of 5. 6 years old. 19 were boys and 10 were girls. According to their hearing level, they were divided into two groups. 14 children were in group of moderate hearing loss (41-60 dB HL). 15 children were in group of severe hearing loss (61-80 dB HL). The categories of auditory performance (CAP) and speech intelligibility rating (SIR) were used to evaluate their auditory performance and speech intelligibility. The evaluation was performed before hearing aid fitting and 1, 3, 6, 9, 12 months after fitting. There was significant difference in mean score of CAP between group of moderate hearing loss and severe hearing loss before hearing aid fitting (P < 0.05). However, no significant differences were observed between these two groups at 1, 3, 6, 9, 12 months after fitting (P > 0.05). There was also significant difference in mean score of SIR between group of moderate hearing loss and severe hearing loss before hearing aid fitting (P < 0.05). How ever, no significant differences were also observed between these two groups at 1, 3, 6, 9, 12 months after fitting (P > 0.05). The mean scores of CAP for group of moderate hearing loss at 6, 9, 12 months after fitting were significantly superior in comparison with the score before hearing aid fitting (P < 0.05). The mean scores of SIR for group of moderate hearing loss at 6, 9, 12 months after fitting were significantly superior in comparison with the score before hearing aid fitting (P < 0.05); the mean score at 12 months after fitting was also significantly superior in comparison with the score at 1 month after fitting (P < 0.05). The mean scores of CAP for group of severe hearing loss at 3, 6, 9, 12 months after fitting were significantly superior in comparison with the score before hearing aid fitting (P < 0.05); the mean scores at 9,12 months after fitting were significantly superior in comparison with the score at 1 month after fitting (P < 0.05). The mean scores of SIR for group of severe hearing loss at 3, 6, 9, 12 months after fitting were significantly superior in comparison with the score before hearing aid fitting (P < 0.05); the mean scores at 6, 9, 12 months after fitting were also significantly superior in comparison with the score at 1 month after fitting (P < 0.05). Auditory performance and speech intelligibility in children with moderate or severe hearing loss improved significantly within the first year after hearing aid fitting. The development followed different trajectory.	\N	\N
24621149	Since being approved in 2009, bilateral simultaneous cochlear implantation (CI) has been the standard treatment for children in the UK who meet the criteria for CI. The aim was to report surgical outcomes of bilateral CI in the UK. Between January 2010 and December 2011, 14 UK CI centres collected data prospectively: demographics, aetiology, use of imaging, device type, surgery duration, use of intra-operative electrophysiology, length of stay, and post-operative complications. 1397 CI procedures in 961 CI recipients were included; 436 bilateral simultaneous, 394 bilateral sequential, and 131 unilateral. The majority (85%) were congenitally deaf. The commonest causes of acquired deafness were meningitis and cytomegalovirus infection. The median age for congenitally deaf bilateral simultaneous CI was 2.2 years, mean surgical duration 4.5 hours. 6.3% surgeries were day case procedures. Eight cases (2.0%) of planned bilateral CI had unilateral surgery. The overall major complication rate was 1.6% (0.9% excluding device failures), including explantation due to infection (0.2%), cerebrospinal fluid leak (0.2%), and meningitis (0.1%). There were no permanent facial nerve palsies and no deaths. Sixty-two (6.5%) immediate minor complications included 12 (1.3%) children with significant vestibular impairment. The complication rate was similar following bilateral CI compared to sequential and unilateral CI, and is comparable to other published series. This prospective multi-centre audit provides evidence that bilateral paediatric CI is a safe procedure in the UK, thus endorsing its role as a major therapeutic intervention in childhood deafness.	\N	\N
24626890	Auditory steady-state responses (ASSR) are an important tool to detect objectively frequency-specific hearing thresholds. Pure-tone audiometry is the gold-standard for hearing evaluation, although sometimes it may be inconclusive, especially in children and uncooperative adults. Compare pure tone thresholds (PT) with ASSR thresholds in normal hearing subjects. In this prospective cross-sectional study we included 26 adults (n = 52 ears) of both genders, without any hearing complaints or otologic diseases and normal puretone thresholds. All subjects had clinical history, otomicroscopy, audiometry and immitance measurements. This evaluation was followed by the ASSR test. The mean pure-tone and ASSR thresholds for each frequency were calculated. The mean difference between PTand ASSR thresholdswas 7,12 for 500 Hz, 7,6 for 1000 Hz, 8,27 for 2000 Hz and 9,71 dB for 4000 Hz. There were no difference between PT and ASSR means at either frequency. ASSR thresholds were comparable to pure-tone thresholds in normal hearing adults. Nevertheless it should not be used as the only method of hearing evaluation.	\N	\N
24627225	The goal of this study was to tease apart the roles of phonological awareness (pA) and phonological short-term memory (pSTM) in sentence comprehension, sentence production, and word reading. Children 6- to 10-years of age (N = 377) completed standardized tests of pA ('Elision') and pSTM ('Nonword Repetition') from the Comprehensive Test of Phonological Processing. Concepts and Following Directions (CFD) and Formulated Sentences (FS) were taken from the Clinical Evaluation of Language Fundamentals-Fourth Edition, as measures of sentence comprehension and production, respectively. Children also completed the Word Identification (Word Id) and Word Attack (Word Att) subtests of the Woodcock Reading Mastery Test-Third Edition. Hierarchical multiple regression analyses controlling for age and nonverbal IQ revealed that Elision was the only significant predictor of CFD and FS. While Elision was the strongest predictor of Word Id and Word Att, Nonword Repetition accounted for additional variance in both reading measures. These results emphasize the usefulness of breaking down phonological processing into multiple components and they also have implications language and reading disordered populations.	\N	\N
24630052	To investigate the clinical usefulness of the LS-chirp auditory brainstem response for estimation of behavioral thresholds in young children with mild to severe hearing losses. 68 infants (136 ears) aged 6-12 months (mean age=9.2 months) with bilateral mild to severe hearing losses were studied at Children's Hospital of Fudan University. In all cases, the children were referred for LS-chirp ABR and visual reinforcement audiometric (VRA) measurements. The low-frequency band chirp (LF-chirp) thresholds (frequency band=0.1-0.85kHz) were compared to the average VRA thresholds (frequency band=0.25-0.5kHz), whereas the high-frequency band chirp (HF-chirp) thresholds (frequency band=1-10kHz) were compared to the average VRA thresholds (frequency band=1-4kHz) using statistical correlation coefficient values. The LS-chirp ABR thresholds are very close to behavioral hearing levels. The mean differences between chirp-ABR and VRA thresholds were within 5dBHL for all measurements. The smallest mean threshold difference (<3dBHL) was obtained for the severe hearing loss group. The correlation coefficient values (r) were 0.97 at low-frequency and high-frequency bands. For each carrier frequency, the best correlations between chirp-ABR thresholds and VRA thresholds were obtained at VRA frequency of 0.25kHz/LF-chirp (r=0.98) and VRA frequency of 1kHz/HF-chirp (r=0.98). This study demonstrates the effectiveness using chirp-ABR predicted frequency-specific thresholds, especially of low and middle frequencies. LS-chirp ABR thresholds determined behavioral thresholds in patients with severe hearing losses were better than for mild hearing losses. The use of a chirp-ABR testing ensures higher sensitivity and accuracy than that of auditory stead-state evoked response (ASSR) for measuring frequency-specific thresholds in young children.	\N	\N
24631260	The left anterior temporal lobe (LATL) is robustly implicated in semantic processing by a growing body of literature. However, these results have emerged from two distinct bodies of work, addressing two different processing levels. On the one hand, the LATL has been characterized as a 'semantic hub׳ that binds features of concepts across a distributed network, based on results from semantic dementia and hemodynamic findings on the categorization of specific compared to basic exemplars. On the other, the LATL has been implicated in combinatorial operations in language, as shown by increased activity in this region associated with the processing of sentences and of basic phrases. The present work aimed to reconcile these two literatures by independently manipulating combination and concept specificity within a minimal MEG paradigm. Participants viewed simple nouns that denoted either low specificity (fish) or high specificity categories (trout) presented in either combinatorial (spotted fish/trout) or non-combinatorial contexts (xhsl fish/trout). By combining these paradigms from the two literatures, we directly compared the engagement of the LATL in semantic memory vs. semantic composition. Our results indicate that although noun specificity subtly modulates the LATL activity elicited by single nouns, it most robustly affects the size of the composition effect when these nouns are adjectivally modified, with low specificity nouns eliciting a much larger effect. We conclude that these findings are compatible with an account in which the specificity and composition effects arise from a shared mechanism of meaning specification.	\N	\N
24632323	This study investigated audiovisual synchrony perception in a rhythmic context, where the sound was not consequent upon the observed movement. Participants judged synchrony between a bouncing point-light figure and an auditory rhythm in two experiments. Two questions were of interest: (1) whether the reference in the visual movement, with which the auditory beat should coincide, relies on a position or a velocity cue; (2) whether the figure form and motion profile affect synchrony perception. Experiment 1 required synchrony judgment with regard to the same (lowest) position of the movement in four visual conditions: two figure forms (human or non-human) combined with two motion profiles (human or ball trajectory). Whereas figure form did not affect synchrony perception, the point of subjective simultaneity differed between the two motions, suggesting that participants adopted the peak velocity in each downward trajectory as their visual reference. Experiment 2 further demonstrated that, when judgment was required with regard to the highest position, the maximal synchrony response was considerably low for ball motion, which lacked a peak velocity in the upward trajectory. The finding of peak velocity as a cue parallels results of visuomotor synchronization tasks employing biological stimuli, suggesting that synchrony judgment with rhythmic motions relies on the perceived visual beat.	\N	\N
24636747	Similar to other zona pellucida mutations in the alpha-tectorin (TECTA) gene, the p.Y1870C alteration in DFNA8/12 causes prelingual, nonsyndromic, autosomal dominant hearing loss. Here we investigated the effect of p.Y1870C on reverse transduction by audiometric studies in the family. Pure tone audiometry, brainstem evoked response audiometry, the Freiburger test for speech understanding and transient evoked and distortion product otoacoustic emissions were assessed in three available affected members bearing p.Y1870C. Pure tone audiometry showed U-shaped curves with moderate to severe degrees of hearing impairment confirmed by brainstem evoked response audiometry. Transient evoked and distortion product otoacoustic emissions were completely absent in all affected family members whereas word recognition scores were up to 95%. Although the missense p.Y1870C TECTA mutation leads to complete failure of the cochlear amplifier in humans, very high speech perception scores can be achieved with appropriate therapy.	\N	\N
24639033	Although individuals with autism are known to have significant communication problems, the cellular mechanisms responsible for impaired communication are poorly understood. Valproic acid (VPA) is an anticonvulsant that is a known risk factor for autism in prenatally exposed children. Prenatal VPA exposure in rats causes numerous neural and behavioral abnormalities that mimic autism. We predicted that VPA exposure may lead to auditory processing impairments which may contribute to the deficits in communication observed in individuals with autism. In this study, we document auditory cortex responses in rats prenatally exposed to VPA. We recorded local field potentials and multiunit responses to speech sounds in primary auditory cortex, anterior auditory field, ventral auditory field. and posterior auditory field in VPA exposed and control rats. Prenatal VPA exposure severely degrades the precise spatiotemporal patterns evoked by speech sounds in secondary, but not primary auditory cortex. This result parallels findings in humans and suggests that secondary auditory fields may be more sensitive to environmental disturbances and may provide insight into possible mechanisms related to auditory deficits in individuals with autism.	\N	\N
24647432	Different brain areas integrate information over different timescales, and this capacity to accumulate information increases from early sensory areas to higher order perceptual and cognitive areas. It is currently unknown whether the timescale capacity of each brain area is fixed or whether it adaptively rescales depending on the rate at which information arrives from the world. Here, using functional MRI, we measured brain responses to an auditory narrative presented at different rates. We asked whether neural responses to slowed (speeded) versions of the narrative could be compressed (stretched) to match neural responses to the original narrative. Temporal rescaling was observed in early auditory regions (which accumulate information over short timescales) as well as linguistic and extra-linguistic brain areas (which can accumulate information over long timescales). The temporal rescaling phenomenon started to break down for stimuli presented at double speed, and intelligibility was also impaired for these stimuli. These data suggest that 1) the rate of neural information processing can be rescaled according to the rate of incoming information, both in early sensory regions as well as in higher order cortexes, and 2) the rescaling of neural dynamics is confined to a range of rates that match the range of behavioral performance.	\N	\N
24657592	Fragile X syndrome (FXS) is a common inherited cause of intellectual disability that results from a CGG repeat expansion in the FMR1 gene. Large repeat expansions trigger both transcriptional and translational suppression of Fragile X protein (FMRP) production. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is an allelic neurodegenerative disease caused by smaller "pre-mutation" CGG repeat expansions that enhance FMR1 transcription but lead to translational inefficiency and reduced FMRP expression in animal models. Sensorimotor gating as measured by pre-pulse inhibition (PPI) is altered in both FXS patients and Fmr1 knock out (KO) mice. Similarly, FXTAS patients have demonstrated PPI deficits. Recent work suggests there may be overlapping synaptic defects between Fmr1 KO and CGG knock-in premutation mouse models (CGG KI). We therefore sought to interrogate PPI in CGG KI mice. Using a quiet PPI protocol more akin to human testing conditions, we find that Fmr1 KO animals have significantly impaired PPI. Using this same protocol, we find CGG KI mice demonstrate an age-dependent impairment in PPI compared to wild type (WT) controls. This study describes a novel phenotype in CGG KI mice that can be used in future therapeutic development targeting premutation associated symptoms.	\N	\N
24660803	This study investigates the extent to which age-related language processing difficulties are due to a decline in sensory processes or to a deterioration of cognitive factors, specifically, attentional control. Two facets of attentional control were examined: inhibition of irrelevant information and divided attention. Younger and older adults were asked to categorize the initial phoneme of spoken syllables ("Was it m or n?"), trying to ignore the lexical status of the syllables. The phonemes were manipulated to range in eight steps from m to n. Participants also did a discrimination task on syllable pairs ("Were the initial sounds the same or different?"). Categorization and discrimination were performed under either divided attention (concurrent visual-search task) or focused attention (no visual task). The results showed that even when the younger and older adults were matched on their discrimination scores: (1) the older adults had more difficulty inhibiting lexical knowledge than did younger adults, (2) divided attention weakened lexical inhibition in both younger and older adults, and (3) divided attention impaired sound discrimination more in older than younger listeners. The results confirm the independent and combined contribution of sensory decline and deficit in attentional control to language processing difficulties associated with aging. The relative weight of these variables and their mechanisms of action are discussed in the context of theories of aging and language.	\N	\N
24663012	The present study aimed to vocally assess a group of rock singers who use growl voice and reinforced falsetto. A group of 21 rock singers and a control group of 18 pop singers were included. Singing and speaking voice was assessed through acoustic, perceptual, functional and laryngoscopic analysis. No significant differences were observed between groups in most of the analyses. Acoustic and perceptual analysis of the experimental group demonstrated normality of speaking voice. Endoscopic evaluation showed that most rock singers presented during singing voice a high vertical laryngeal position, pharyngeal compression and laryngeal supraglottic compression. Supraglottic activity during speaking voice tasks was also observed. However, overall vocal fold integrity was demonstrated in most of the participants. Slightly abnormal observations were demonstrated in few of them. Singing voice handicap index revealed that the most affected variable was the physical sphere, followed by the social and emotional spheres. Although growl voice and reinforced falsetto represent laryngeal and pharyngeal hyperfunctional activity, they did not seem to contribute to the presence of any major vocal fold disorder in our subjects. Nevertheless, we cannot rule out the possibility that more evident vocal fold disorders could be found in singers who use these techniques more often and during a longer period of time.	\N	\N
24672005	The inner ear receives two types of efferent feedback from the brainstem: one pathway provides gain control on outer hair cells' contribution to cochlear amplification, and the other modulates the excitability of the cochlear nerve. Although efferent feedback can protect hair cells from acoustic injury and thereby minimize noise-induced permanent threshold shifts, most prior studies focused on high-intensity exposures (>100 dB SPL). Here, we show that efferents are essential for long-term maintenance of cochlear function in mice aged 1 year post-de-efferentation without purposeful acoustic overexposure. Cochlear de-efferentation was achieved by surgical lesion of efferent pathways in the brainstem and was assessed by quantitative analysis of immunostained efferent terminals in outer and inner hair cell areas. The resultant loss of efferent feedback accelerated the age-related amplitude reduction in cochlear neural responses, as seen in auditory brainstem responses, and increased the loss of synapses between hair cells and the terminals of cochlear nerve fibers, as seen in confocal analysis of the organ of Corti immunostained for presynaptic and postsynaptic markers. This type of neuropathy, also seen after moderate noise exposure, has been termed "hidden hearing loss", because it does not affect thresholds, but can be seen in the suprathreshold amplitudes of cochlear neural responses, and likely causes problems with hearing in a noisy environment, a classic symptom of age-related hearing loss in humans. Since efferent reflex strength varies among individuals and can be measured noninvasively, a weak reflex may be an important risk factor, and prognostic indicator, for age-related hearing impairment.	\N	\N
24681401	Voice control is critical to communication. To date, studies have used behavioral, electrophysiological and functional data to investigate the neural correlates of voice control using perturbation tasks, but have yet to examine the interactions of these neural regions. The goal of this study was to use structural equation modeling of functional neuroimaging data to examine network properties of voice with and without perturbation. Results showed that the presence of a pitch shift, which was processed as an error in vocalization, altered connections between right STG and left STG. Other regions that revealed differences in connectivity during error detection and correction included bilateral inferior frontal gyrus, and the primary and pre motor cortices. Results indicated that STG plays a critical role in voice control, specifically, during error detection and correction. Additionally, pitch perturbation elicits changes in the voice network that suggest the right hemisphere is critical to pitch modulation.	\N	\N
24681402	Converging evidence suggests that understanding our first-language (L1) results in reactivation of experiential sensorimotor traces in the brain. Surprisingly, little is known regarding the involvement of these processes during second-language (L2) processing. Participants saw L1 or L2 words referring to entities with a typical location (e.g., star, mole) (Experiment 1 & 2) or to an emotion (e.g., happy, sad) (Experiment 3). Participants responded to the words' ink color with an upward or downward arm movement. Despite word meaning being fully task-irrelevant, L2 automatically activated motor responses similar to L1 even when L2 was acquired rather late in life (age >11). Specifically, words such as star facilitated upward, and words such as root facilitated downward responses. Additionally, words referring to positive emotions facilitated upward, and words referring to negative emotions facilitated downward responses. In summary our study suggests that reactivation of experiential traces is not limited to L1 processing.	\N	\N
24684405	We sought to determine whether the results of audiological tests and tinnitus characteristics, particularly tinnitus pitch and minimum masking level (MML), depend on tinnitus etiology, and what other etiology-specific tinnitus characteristics there are. The patients answered questions concerning tinnitus laterality, duration, character, aggravation, alleviation, previous treatment, and circumstances of onset. The results of tympanometry, pure-tone audiometry, distortion-product otoacoustic emissions, tinnitus likeness spectrum, MML, and uncomfortable loudness level were evaluated. Patients with several tinnitus etiological factors were excluded. The remaining participants were divided into groups according to medical history: acute acoustic trauma: 67 ears; chronic acoustic trauma: 82; prolonged use of oral estrogen and progesterone contraceptives: 46; Ménière's disease: 25; congenital hearing loss: 19; sensorineural sudden deafness: 40; dull head trauma: 19; viral labyrinthitis: 53; stroke: 6; presbycusis: 152. Data of 509 ears were analysed. Tinnitus pitch was highest in patients with acute acoustic trauma and lowest in patients receiving estrogen and progesterone. MML was lowest after acute acoustic trauma and in congenital hearing loss, and highest after a stroke and in the case of presbytinnitus. Tinnitus pitch and MML are etiology dependent.	\N	\N
24686520	PURPOSE The purpose of this study was to investigate how linguistic knowledge interacts with indexical knowledge in older children's perception under demanding listening conditions created by extensive talker variability. METHOD Twenty-five 9- to 12-year-old children, 12 from North Carolina (NC) and 13 from Wisconsin (WI), identified 12 vowels in isolated /hVd/ words produced by 120 talkers representing the 2 dialects (NC and WI), both genders, and 3 age groups (generations) of residents from the same geographic locations as the listeners. RESULTS Identification rates were higher for responses to talkers from the same dialect as the listeners and for female speech. Listeners were sensitive to systematic positional variations in vowels and their dynamic structure (formant movement) associated with generational differences in vowel pronunciation resulting from sound change in a speech community. Overall identification rate was 71.7%, which is 8.5% lower than for the adults responding to the same stimuli in Jacewicz and Fox (2012). CONCLUSION Typically developing older children were successful in dealing with both phonetic and indexical variation related to talker dialect, gender, and generation. They were less consistent than the adults, most likely because of less efficient encoding of acoustic-phonetic information in the speech of multiple talkers and relative inexperience with indexical variation.	\N	\N
24686901	PURPOSE The aim of this study was to evaluate the understanding of English sentences produced by native (English) and nonnative (Spanish) talkers by listeners with normal hearing (NH) and listeners with cochlear implants (CIs). METHOD Sentence recognition in noise was measured in adult subjects with CIs and subjects with NH, all of whom were native talkers of American English. Test sentences were from the Hearing in Noise Test (HINT) database and were produced in English by four native and eight nonnative talkers. Subjects also rated the intelligibility and accent for each talker. RESULTS The speech recognition thresholds in noise of subjects with CIs and subjects with NH were 4.23 dB and 1.32 dB poorer with nonnative talkers than with native talkers, respectively. Performance was significantly correlated with talker intelligibility and accent ratings for subjects with CIs but only correlated with talker intelligibility ratings for subjects with NH. For all subjects, performance with individual nonnative talkers was significantly correlated with talkers' number of years of residence in the United States. CONCLUSION CI users exhibited a larger deficit in speech understanding with nonnative talkers than did subjects with NH, relative to native talkers. Nonnative talkers' experience with native culture contributed strongly to speech understanding in noise, intelligibility ratings, and accent ratings of both listeners with NH and listeners with CIs.	\N	\N
24686915	The purpose of this study was to develop a task to evaluate children's English and Spanish speech perception abilities in either noise or competing speech maskers. Eight bilingual Spanish-English and 8 age-matched monolingual English children (ages 4.9-16.4 years) were tested. A forced-choice, picture-pointing paradigm was selected for adaptively estimating masked speech reception thresholds. Speech stimuli were spoken by simultaneous bilingual Spanish-English talkers. The target stimuli were 30 disyllabic English and Spanish words, familiar to 5-year-olds and easily illustrated. Competing stimuli included either 2-talker English or 2-talker Spanish speech (corresponding to target language) and spectrally matched noise. For both groups of children, regardless of test language, performance was significantly worse for the 2-talker than for the noise masker condition. No difference in performance was found between bilingual and monolingual children. Bilingual children performed significantly better in English than in Spanish in competing speech. For all listening conditions, performance improved with increasing age. Results indicated that the stimuli and task were appropriate for speech recognition testing in both languages, providing a more conventional measure of speech-in-noise perception as well as a measure of complex listening. Further research is needed to determine performance for Spanish-dominant listeners and to evaluate the feasibility of implementation into routine clinical use.	\N	\N
24687018	Although a number of questionnaires are available to assess hearing aid benefit and general hearing disability, relatively few investigate spatial hearing ability in more complex listening situations. The aim of this study was to document the performance of individuals with normal hearing using the Spatial Hearing Questionnaire (SHQ; Tyler, Perreau, & Ji, 2009) and to compare performance with published data from cochlear implant (CI) users. Fifty-one participants with normal hearing participated. All participants completed the 24-item SHQ. Also, a factor analysis and reliability tests were performed. Performance on the SHQ was high (87%) for the participants with normal hearing. Subjective ratings varied across different listening situations: Understanding speech in quiet (98%) was rated higher than sound localization (84%) and understanding speech in a background of noise (85%). Compared with previously published data (Tyler, Perreau, & Ji, 2009), listeners with normal hearing rated their spatial hearing ability significantly better than bilateral and unilateral CI users. Results confirmed that the SHQ is a reliable measure of spatial hearing ability for listeners with normal hearing. Overall, results indicated that the SHQ is able to capture expected differences between individuals with normal hearing and CI users. These new data can be used as targets following the provision of hearing devices.	\N	\N
24687041	To describe the inheritance patterns and auditory phenotype features of 3 Canadian families with mutations in 2 X-linked "deafness" genes (DFNX). Audiological, medical, and family histories were collected and family members interviewed to compare hearing thresholds and case histories between cases with mutations in SMPX versus POU3F4. The family pedigrees reveal characteristic X-linked inheritance patterns. Phenotypic features associated with the SMPX (DFNX4) mutation include early onset in males with rapid progression from mild and flat to sloping sensorineural loss, with highly variable onset and hearing loss severity in females. In contrast, phenotypic features associated with the POU3F4 (DFNX2) mutation are characterized by an early onset, mixed hearing loss with fluctuation in males, and a normal hearing phenotype reported for females. The study shows how this unique inheritance pattern and both gender and mutation-specific phenotype variations can alert audiologists to the presence of X-linked genetic etiologies in their clinical practice. By incorporating this knowledge into clinical decision making, audiologists can facilitate the early identification of X-linked hearing loss and contribute to the effective team management of affected families.	\N	\N
24704377	Perceptual synchrony and multisensory integration both vary as a function of stimulus onset asynchrony, but evidences from behavioral, patient, and lesion studies all support some dissociation between these two processes. Although it has been found that both perceptual synchrony and multisensory integration are recalibrated after exposure to asynchronous multisensory stimuli, no studies have directly compared these two recalibration patterns. We addressed this by using McGurk speech and requiring participants to perform simultaneity judgments and a syllable identification task in separate sessions. The results revealed that after exposure to asynchrony, both perceptual synchrony and McGurk fusion shifted toward the temporal lag. The recalibration aftereffects (i.e., the magnitude of shifts) of these two processes have no significant difference and correlation. In addition, McGurk fusion increased strongly at the direction of the temporal lag, which could not be fully explained by fusion shifts. Thus, the present research implies that recalibration patterns of explicit and implicit timing represented by perceptual synchrony and multisensory integration have both similarity and difference.	\N	\N
24709357	Although there is an extensive literature on the study of the neural correlates of consciousness (NCC) this is a subject that is far from being considered over. In this paper we present a novel experimental paradigm, based on binocular rivalry, to study internally and externally generated conscious experiences. We called this procedure bimodal rivalry. In addition, and assuming the non-linear nature of the EEG signals, we propose the use of fractal dimension to characterize the complexity of the EEG signal associated with each percept. Analysis of the data showed a significant difference in complexity between the internally generated and externally generated percepts. Moreover, EEG complexity was dissimilar for externally generated auditory and visual percepts. These results support fractal dimension analyses as a new tool to characterize conscious perception.	\N	\N
24715101	The current study investigated the mechanism underlying subliminal inhibition using the negative compatibility effect (NCE) paradigm. We hypothesized that a decrease in prime activation affects the subsequent inhibitory process, delaying onset of inhibition and reducing its strength. Two experiments tested this hypothesis using arrow stimuli as primes and targets. Two different irrelevant masks (i.e., a mask sharing no prime features) were presented in succession in each trial to not only ensure that primes were processed subliminally, but also avoid feature updating between primes and masks. Prime/target compatibility and prime background density were manipulated in Experiment 1. Results showed that under subliminal inhibitory condition, the NCE disappears when the density increases (i.e., pixel density in the prime's background of 25 %) in Experiment 1. However, when we fixed the prime's background at the density of 25 % and manipulated prime/target compatibility as well as inter-stimuli-interval (ISI) between mask and target in Experiment 2, behavioral results showed marginally significant NCEs in the 150-ms ISI condition. Electrophysiological evidence showed the lateralized readiness potential for compatible trials was significantly more positive than that for incompatible trials during the two consecutive time windows (i.e., 400-450 and 450-500 ms) in the 150-ms ISI condition. In addition, the NCE size was significant smaller in Experiment 2 than in Experiment 1. All of the results support predictions of the continuous subliminal inhibitory mechanism hypothesis which posits that decreases in prime activation strength lead to delay in inhibitory onset and decline in inhibitory strength.	\N	\N
24727491	The binaural cues used by terrestrial animals for sound localization in azimuth may not always suffice for accurate sound localization underwater. The purpose of this research was to examine the theoretical limits of interaural timing and level differences available underwater using computational and physical models. A paired-hydrophone system was used to record sounds transmitted underwater and recordings were analyzed using neural networks calibrated to reflect the auditory capabilities of terrestrial mammals. Estimates of source direction based on temporal differences were most accurate for frequencies between 0.5 and 1.75 kHz, with greater resolution toward the midline (2°), and lower resolution toward the periphery (9°). Level cues also changed systematically with source azimuth, even at lower frequencies than expected from theoretical calculations, suggesting that binaural mechanical coupling (e.g., through bone conduction) might, in principle, facilitate underwater sound localization. Overall, the relatively limited ability of the model to estimate source position using temporal and level difference cues underwater suggests that animals such as whales may use additional cues to accurately localize conspecifics and predators at long distances.	\N	\N
24735233	The dichotic listening task is typically administered by presenting a consonant-vowel (CV) syllable to each ear and asking the participant to report the syllable heard most clearly. The results tend to show more reports of the right ear syllable than of the left ear syllable, an effect called the right ear advantage (REA). The REA is assumed to be due to the crossing over of auditory fibres and the processing of language stimuli being lateralised to left temporal areas. However, the tendency for most dichotic listening experiments to use only CV syllable stimuli limits the extent to which the conclusions can be generalised to also apply to other speech phonemes. The current study re-examines the REA in dichotic listening by using both CV and vowel-consonant (VC) syllables and combinations thereof. Results showed a replication of the REA response pattern for both CV and VC syllables, thus indicating that the general assumption of left-side localisation of processing can be applied for both types of stimuli. Further, on trials where a CV is presented in one ear and a VC is presented in the other ear, the CV is selected more often than the VC, indicating that these phonemes have an acoustic or processing advantage.	\N	\N
24735850	To form a coherent percept of the environment, the brain needs to bind sensory signals emanating from a common source, but to segregate those from different sources [1]. Temporal correlations and synchrony act as prominent cues for multisensory integration [2-4], but the neural mechanisms by which such cues are identified remain unclear. Predictive coding suggests that the brain iteratively optimizes an internal model of its environment by minimizing the errors between its predictions and the sensory inputs [5,6]. This model enables the brain to predict the temporal evolution of natural audiovisual inputs and their statistical (for example, temporal) relationship. A prediction of this theory is that asynchronous audiovisual signals violating the model's predictions induce an error signal that depends on the directionality of the audiovisual asynchrony. As the visual system generates the dominant temporal predictions for visual leading asynchrony, the delayed auditory inputs are expected to generate a prediction error signal in the auditory system (and vice versa for auditory leading asynchrony). Using functional magnetic resonance imaging (fMRI), we measured participants' brain responses to synchronous, visual leading and auditory leading movies of speech, sinewave speech or music. In line with predictive coding, auditory leading asynchrony elicited a prediction error in visual cortices and visual leading asynchrony in auditory cortices. Our results reveal predictive coding as a generic mechanism to temporally bind signals from multiple senses into a coherent percept.	\N	\N
24736111	The aim of this study was to determine the relationship between serum albumin, affective prosody, and symptoms of attention-deficit hyperactivity disorder (ADHD) found coincidentally in a recently published study. Here, serum albumin levels were assessed as a covariate. Twenty healthy male adults (controls) and 20 adult male patients with ADHD participated in the study on two study days. Serum albumin levels and performance in an affective prosody task were assessed, and correlations were determined. Serum albumin had a significant correlation with performance on an affective prosody task on both of the 2 study days. The same correlations were not significant in the healthy control group. There was no difference in the serum albumin level between patients with ADHD and healthy controls. The association between serum albumin and affective prosody in adults with ADHD is a novel finding. However, to date, there is no clear theory that explains this association. Future research should analyze whether serum albumin influences causes changes in performance in affective prosody using experimental designs.	\N	\N
24736186	We investigated whether unattended visual, auditory and tactile stimuli compete for capacity-limited early sensory processing across senses. In three experiments, we probed competitive audio-visual, visuo-tactile and audio-tactile stimulus interactions. To this end, continuous visual, auditory and tactile stimulus streams ('reference' stimuli) were frequency-tagged to elicit steady-state responses (SSRs). These electrophysiological oscillatory brain responses indexed ongoing stimulus processing in corresponding senses. To induce competition, we introduced transient frequency-tagged stimuli in same and/or different senses ('competitors') during reference presentation. Participants performed a separate visual discrimination task at central fixation to control for attentional biases of sensory processing. A comparison of reference-driven SSR amplitudes between competitor-present and competitor-absent periods revealed reduced amplitudes when a competitor was presented in the same sensory modality as the reference. Reduced amplitudes indicated the competitor's suppressive influence on reference stimulus processing. Crucially, no such suppression was found when a competitor was presented in a different than the reference modality. These results strongly suggest that early sensory competition is exclusively modality-specific and does not extend across senses. We discuss consequences of these findings for modeling the neural mechanisms underlying intermodal attention.	\N	\N
24738537	Neuroscientific and musicological approaches to music cognition indicate that listeners familiarized in the Western tonal tradition expect a musical phrase boundary at predictable time intervals. However, phrase boundary prediction processes in music remain untested. We analyzed event-related potentials (ERPs) and event-related induced power changes at the onset and offset of a boundary pause. We made comparisons with modified melodies, where the pause was omitted and filled by tones. The offset of the pause elicited a closure positive shift (CPS), indexing phrase boundary detection. The onset of the filling tones elicited significant increases in theta and beta powers. In addition, the P2 component was larger when the filling tones started than when they ended. The responses to boundary omission suggest that listeners expected to hear a boundary pause. Therefore, boundary prediction seems to coexist with boundary detection in music segmentation.	\N	\N
24744448	Interest in the perception of the material of objects has been growing. While material perception is a critical ability for animals to properly regulate behavioral interactions with surrounding objects (e.g., eating), little is known about its underlying processing. Vision and audition provide useful information for material perception; using only its visual appearance or impact sound, we can infer what an object is made from. However, what material is perceived when the visual appearance of one material is combined with the impact sound of another, and what are the rules that govern cross-modal integration of material information? We addressed these questions by asking 16 human participants to rate how likely it was that audiovisual stimuli (48 combinations of visual appearances of six materials and impact sounds of eight materials) along with visual-only stimuli and auditory-only stimuli fell into each of 13 material categories. The results indicated strong interactions between audiovisual material perceptions; for example, the appearance of glass paired with a pepper sound is perceived as transparent plastic. Rating material-category likelihoods follow a multiplicative integration rule in that the categories judged to be likely are consistent with both visual and auditory stimuli. On the other hand, rating-material properties, such as roughness and hardness, follow a weighted average rule. Despite a difference in their integration calculations, both rules can be interpreted as optimal Bayesian integration of independent audiovisual estimations for the two types of material judgment, respectively.	\N	\N
24750038	Alarms are ubiquitous in anaesthetic practice, but their net effect on anaesthesiologists' performance and patient safety is debated. In this study, 27 anaesthesiologists performed two simulation sessions in random order; one session was programmed to include an alarm condition, with a standard, frequent, clearly audible alarm sound. During these sessions, adverse events were simulated and anaesthesiologists' response times to these events were recorded. Perceived workload was assessed with the NASA Task Load Index. Response times to adverse events and perceived workload were similar in both groups. Pooled response times to atrial fibrillation and desaturation were fast, with a median (range [IQR]) of 8 (4-14 [1-41]) s and 9 (6-16 [1-44]) s, respectively. Pooled response times to an ST segment elevation on the ECG and an obstructed intravenous line were significantly slower, with median (IQR[range]) times of 34 (21-76[4-300]) s and 227 (95-399 [2-600]) s, respectively (p < 0.001). This study shows that in a simulated anaesthesia environment, response times to adverse events are similar in the absence or presence of an audible alarm, and that response times to various critical events differ.	\N	\N
24751750	To prospectively evaluate hearing outcomes in patients with osteogenesis imperfecta undergoing primary stapes surgery and to isolate prognostic factors for success. A nonrandomized, open, prospective case series. A tertiary referral center. Twenty-five consecutive patients who underwent 32 primary stapedotomies for osteogenesis imperfecta with evidence of stapes fixation and available postoperative pure-tone audiometry. Primary stapedotomy with vein graft interposition and reconstruction with a regular Teflon piston or bucket handle-type piston. Preoperative and postoperative audiometric evaluation using conventional 4-frequency (0.5, 1, 2, and 4 kHz) audiometry. Air-conduction thresholds, bone-conduction thresholds, and air-bone gap were measured. The overall audiometric results as well as the results of audiometric evaluation at 3 months and at least 1 year after surgery were used. Overall, postoperative air-bone gap closure to within 10 dB was achieved in 88% of cases. Mean (standard deviation) gain in air-conduction threshold was 22 (9.4) dB for the entire case series, and mean (standard deviation) air-bone gap closure was 22 (9.0) dB. Backward multivariate logistic regression showed that a model with preoperative air-bone gap closure and intraoperatively established incus length accurately predicts success after primary stapes surgery. Stapes surgery is a feasible and safe treatment option in patients with osteogenesis imperfecta. Success is associated with preoperative air-bone gap and intraoperatively established incus length.	\N	\N
24754219	Diachronic velar palatalization is taken as the case study for modeling the emergence of a new phoneme category. The spread of a palatalized variant through the lexicon is treated as a stochastic classification task for the listener/learner. The model combines two measures of similarity to determine classification within an exemplar-theoretic framework: acoustic distance and phonotactic expectation. There are three model outcomes: contrast, allophony, or contextual neutralization between the plain and palatalized velars. It is shown, through a series of simulations, that these can be predicted from the distribution of sounds within the pre-change lexicons, namely, the ratio of the /k-vowel/ sequences containing naturally palatalizing vowels (i, I, e), to those containing non-palatalizers. "Unnatural" phonotactic associations can arise in individual lexicons, but are sharply limited due to the large size of the lexicon and the local nature of the phoneme changes. "Anti-natural" distributions, which categorically violate the proposed implicational relationship between palatalization and frontness/height, are absent. This work provides an explicit and restrictive model of phoneme change. The results also serve as an existence proof for an outcome-blind mechanism of avoiding over-generation.	\N	\N
24755208	A wide range of literature is available on the features of ataxic dysarthria, investigating segmental and prosodic characteristics by acoustic and perceptual means. However, very few studies have been published that look closely at the relationship between the observed phonetic disturbances and their perceptual sequelae, particularly in the area of prosody. The aim of the current study was therefore to examine the stress production of eight individuals with ataxic dysarthria and matched healthy controls, and to relate the results of phonological and perceptual evaluations to phonetic performances to better understand the relationship between these three components for speech outcomes. Speakers performed a sentence stress task which was analysed phonologically in terms of inventory, distribution, implementation and function of pitch accentuation. These data were then evaluated in relation to previously published phonetic and perceptual results on the same speaker group by the authors. Results indicated that the speakers with ataxia used a wide range of pitch patterns, but pitch-accented a higher number of words, and produced shorter phrases. The increased number of pitch accents per phrase was furthermore reflected in a reduced percentage of de-accented words in post-focal position. Perceptual results established this pattern as the main cause for listener errors in identifying the intended stressed item in an utterance. In addition, the performances of two speakers are discussed in greater detail. Although they were unable to de-accent, they nevertheless marked stress appropriately through phonetic compensatory strategies. After reading this article the reader will be able to (1) explain the relevance of phonology and phonetics in the perception of stress production in ataxic dysarthria; (2) describe the different levels of intonational analysis; and (3) understand the observed intonation patterns in ataxic dysarthria as well as the compensatory mechanisms speakers may adopt to produce stress.	\N	\N
24763046	Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI.	\N	\N
24764261	We investigated the relative effects of simple and complex auditory-visual discrimination training using an adapted alternating treatments design to establish derived stimulus relations in 2 children who had been diagnosed with autism and 1 typically developing peer. Emergence of untrained conditional relations was observed after training in both conditions, with a possible advantage of simple-sample training for 1 participant. Results of generalization and follow-up probes were mixed.	\N	\N
24769166	Although alterations of the limbic system have been linked to tinnitus persistence, the neural networks underlying such alteration are unclear. The present study investigated the effect of tinnitus on emotional processing in middle-aged adults using functional magnetic resonance imaging and stimuli from the International Affective Digital Sounds database. There were three groups of participants: bilateral hearing loss with tinnitus (TIN), age- and gender-matched controls with bilateral hearing loss without tinnitus (HL) and matched normal hearing controls without tinnitus (NH). In the scanner, subjects rated sounds as pleasant, unpleasant, or neutral. The TIN and NH groups, but not the HL group, responded faster to affective sounds compared to neutral sounds. The TIN group had elevated response in bilateral parahippocampus and right insula compared to the NH group, and left parahippocampus compared to HL controls for pleasant relative to neutral sounds. A region-of-interest analysis detected increased activation for NH controls in the right amygdala when responding to affective stimuli, but failed to find a similar heightened response in the TIN and HL groups. All three groups showed increased response in auditory cortices for the affective relative to neutral sounds comparisons. Our results suggest that the emotional processing network is altered in tinnitus to rely on the parahippocampus and insula, rather than the amygdala, and this alteration may maintain a select advantage for the rapid processing of affective stimuli despite the hearing loss. The complex interaction of tinnitus and the limbic system should be accounted for in development of new tinnitus management strategies.	\N	\N
24769280	Lexical access during speech comprehension comprises numerous computations, including activation, competition, and selection. The spatio-temporal profile of these processes involves neural activity in peri-auditory cortices at least as early as 200 ms after stimulation. Their oscillatory dynamics are less well understood, although reports link alpha band de-synchronization with lexical processing. We used magnetoencephalography (MEG) to examine whether these alpha-related oscillations reflect the speed of lexical access, as would be predicted if they index lexical activation. In an auditory semantic priming protocol, monosyllabic nouns were presented while participants performed a lexical decision task. Spatially-localizing beamforming was used to examine spectro-temporal effects in left and right auditory cortex time-locked to target word onset. Alpha and beta de-synchronization (10-20 Hz ERD) was attenuated for words following a related prime compared to an unrelated prime beginning about 270 ms after stimulus onset. This timing is consistent with how information about word identity unfolds incrementally in speech, quantified in information-theoretic terms. These findings suggest that alpha de-synchronization during auditory word processing is associated with early stages of lexical access.	\N	\N
24769430	In this study meaningful social stimuli were used as probes in a task requiring the judgment of semantic appropriateness to investigate contextual integration ability to test the ability of people with Williams syndrome (WS) to integrate information, as opposed to the use of meaningless syllables in audiovisual studies (the McGurk effect). Participants were presented with background auditory primes followed by targets that were either congruent or incongruent with the prime. Two modes of target were presented: a visual target (AV task) or an auditory target (AA task). Participants were asked to respond yes to contextually appropriate pairs and no to those that were contextually inappropriate. The congruency effect was measured as an index of successful central coherence. Similar to normally developing controls, people with WS showed shorter response latencies and greater accuracy in recognizing congruent pairs compared with incongruent pairs. Their performance did not differ from that of controls matched by mental age, but was inferior to that of controls matched by chronological age. The results revealed generalized contextual integration for auditory primes in both tasks, consistent with previous studies using visual presentation of social-related stimuli in people with WS (Hsu, 2013a, 2013c). Further demonstration of the presence of a modality effect on contextual coherence implies that cross-modal learning may be advantageous compared with unimodal learning.	\N	\N
24783989	To assist the human operator, modern auditory interfaces increasingly rely on sound spatialisation to display auditory information and warning signals. However, we often operate in environments that apply vibrations to the whole body, e.g. when driving a vehicle. Here, we report three experiments investigating the effect of sinusoidal vibrations along the vertical axis on spatial hearing. The first was a free-field, narrow-band noise localisation experiment with 5- Hz vibration at 0.88 ms(-2). The other experiments used headphone-based sound lateralisation tasks. Experiment 2 investigated the effect of vibration frequency (4 vs. 8 Hz) at two different magnitudes (0.83 vs. 1.65 ms(-2)) on a left-right discrimination one-interval forced-choice task. Experiment 3 assessed the effect on a two-interval forced-choice location discrimination task with respect to the central and two peripheral reference locations. In spite of the broad range of methods, none of the experiments show a reliable effect of whole-body vibrations on localisation performance. We report three experiments that used both free-field localisation and headphone lateralisation tasks to assess their sensitivity to whole-body vibrations at low frequencies. None of the experiments show a reliable effect of either frequency or magnitude of whole-body vibrations on localisation performance.	\N	\N
24809252	The aim of this work was to investigate perceived loudness change in response to melodies that increase (up-ramp) or decrease (down-ramp) in acoustic intensity, and the interaction with other musical factors such as melodic contour, tempo, and tonality (tonal/atonal). A within-subjects design manipulated direction of linear intensity change (up-ramp, down-ramp), melodic contour (ascending, descending), tempo, and tonality, using single ramp trials and paired ramp trials, where single up-ramps and down-ramps were assembled to create continuous up-ramp/down-ramp or down-ramp/up-ramp pairs. Twenty-nine (Exp 1) and thirty-six (Exp 2) participants rated loudness continuously in response to trials with monophonic 13-note piano melodies lasting either 6.4s or 12s. Linear correlation coefficients >.89 between loudness and time show that time-series loudness responses to dynamic up-ramp and down-ramp melodies are essentially linear across all melodies. Therefore, 'indirect' loudness change derived from the difference in loudness at the beginning and end points of the continuous response was calculated. Down-ramps were perceived to change significantly more in loudness than up-ramps in both tonalities and at a relatively slow tempo. Loudness change was also greater for down-ramps presented with a congruent descending melodic contour, relative to an incongruent pairing (down-ramp and ascending melodic contour). No differential effect of intensity ramp/melodic contour congruency was observed for up-ramps. In paired ramp trials assessing the possible impact of ramp context, loudness change in response to up-ramps was significantly greater when preceded by down-ramps, than when not preceded by another ramp. Ramp context did not affect down-ramp perception. The contribution to the fields of music perception and psychoacoustics are discussed in the context of real-time perception of music, principles of music composition, and performance of musical dynamics.	\N	\N
24809744	Since Köhler's experiments in the 1920s, researchers have demonstrated a correspondence between words and shapes. Dubbed the "Bouba-Kiki" effect, these auditory-visual associations extend across cultures and are thought to be universal. More recently the effect has been shown in other modalities including taste, suggesting the effect is independent of vision. The study presented here tested the "Bouba-Kiki" effect in the auditory-haptic modalities, using 2D cut-outs and 3D models based on Köhler's original drawings. Presented with shapes they could feel but not see, sighted participants showed a robust "Bouba-Kiki" effect. However, in a sample of people with a range of visual impairments, from congenital total blindness to partial sight, the effect was significantly less pronounced. The findings suggest that, in the absence of a direct visual stimulus, visual imagery plays a role in crossmodal integration.	\N	\N
24811450	Mice are emerging as an important behavioral model for studies of auditory perception and acoustic communication. These mammals frequently produce ultrasonic vocalizations, although the details of how these vocalizations are used for communication are not entirely understood. An important step in determining how they might be differentiating their calls is to measure discrimination and identification of the dimensions of various acoustic stimuli. Here, behavioral operant conditioning methods were employed to assess frequency difference limens for pure tones. We found that their thresholds were similar to those in other rodents but higher than in humans. We also asked mice, in an identification paradigm, whether they would use frequency or duration differences to classify stimuli varying on those two dimensions. We found that the mice classified the stimuli based on frequency rather than duration.	\N	\N
24815249	Personal audio refers to the creation of a listening zone within which a person, or a group of people, hears a given sound program, without being annoyed by other sound programs being reproduced in the same space. Generally, these different sound zones are created by arrays of loudspeakers. Although these devices have the capacity to achieve different sound zones in an anechoic environment, they are ultimately used in normal rooms, which are reverberant environments. At high frequencies, reflections from the room surfaces create a diffuse pressure component which is uniform throughout the room volume and thus decreases the directional characteristics of the device. This paper shows how the reverberant performance of an array can be modeled, knowing the anechoic performance of the radiator and the acoustic characteristics of the room. A formulation is presented whose results are compared to practical measurements in reverberant environments. Due to reflections from the room surfaces, pressure variations are introduced in the transfer responses of the array. This aspect is assessed by means of simulations where random noise is added to create uncertainties, and by performing measurements in a real environment. These results show how the robustness of an array is increased when it is designed for use in a reverberant environment.	\N	\N
24815280	Recent studies on binary masking techniques make the assumption that each time-frequency (T-F) unit contributes an equal amount to the overall intelligibility of speech. The present study demonstrated that the importance of each T-F unit to speech intelligibility varies in accordance with speech content. Specifically, T-F units are categorized into two classes, speech-present T-F units and speech-absent T-F units. Results indicate that the importance of each speech-present T-F unit to speech intelligibility is highly related to the loudness of its target component, while the importance of each speech-absent T-F unit varies according to the loudness of its masker component. Two types of mask errors are also considered, which include miss and false alarm errors. Consistent with previous work, false alarm errors are shown to be more harmful to speech intelligibility than miss errors when the mixture signal-to-noise ratio (SNR) is below 0 dB. However, the relative importance between the two types of error is conditioned on the SNR level of the input speech signal. Based on these observations, a mask-based objective measure, the loudness weighted hit-false, is proposed for predicting speech intelligibility. The proposed objective measure shows significantly higher correlation with intelligibility compared to two existing mask-based objective measures.	\N	\N
24815292	Behind-the-ear (BTE) processors of cochlear implant (CI) devices offer little to almost no protection from wind noise in most incidence angles. To assess speech intelligibility, eight CI recipients were tested in 3 and 9 m/s wind. Results indicated that speech intelligibility decreased substantially when the wind velocity, and in turn the wind sound pressure level, increased. A two-microphone wind noise suppression strategy was developed. Scores obtained with this strategy indicated substantial gains in speech intelligibility over other conventional noise reduction strategies tested.	\N	\N
24820112	This study aimed to propose an ototoxicity grading system sensitive to the effect of ototoxicity on specific daily life situations like speech intelligibility and the perception of ultra-high sounds and to test its feasibility compared to current criteria. Pure tone averages (PTAs) for speech perception (1-2-4 kHz) and ultra-high frequencies (8-10-12.5 kHz) were incorporated. Threshold shift and hearing level posttreatment were taken into account. Criteria were tested on head and neck cancer patients treated with (chemo-)radiotherapy ([C]RT) and compared with the Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) and the American Speech-Language-Hearing Association criteria (ASHA). Grades 1 and 2 were based on threshold shifts from baseline (in dB) and subjective complaints. Grades 3 and 4 were defined as treatment-induced hearing loss of ≥ 35 dB at PTA 1-2-4 kHz and ≥ 70 dB at PTA 1-2-4 kHz, respectively. In high-dose cisplatin CRT incidences by the new criteria, CTCAEv4 and ASHA were comparable (78%-88%). In RT and low-dose cisplatin CRT, incidences were 36% to 39% in the new criteria versus 22% to 53% in CTCAEv4 and ASHA. The new criteria show an increased sensitivity to ototoxicity compared to CTCAEv4 and ASHA and provide insight into the effect of hearing loss on certain daily life situations. The new grading system seems feasible for clinic and research purposes.	\N	\N
24834939	Our results indicated that electric acoustic stimulation (EAS) is beneficial for Japanese-speaking patients, including those with less residual hearing at lower frequencies. Comparable outcomes for the patients with less residual hearing indicated that current audiological criteria for EAS could be expanded. Successful hearing preservation results, together with the progressive nature of loss of residual hearing in these patients, mean that minimally invasive full insertion of medium/long electrodes in cochlear implantation (CI) surgery is a desirable solution. The minimally invasive concepts that have been obtained through EAS surgery are, in fact, crucial for all CI patients. This study was conducted to evaluate hearing preservation results and speech discrimination outcomes of hearing preservation surgeries using medium/long electrodes. A total of 32 consecutive minimally invasive hearing preservation CIs (using a round window approach with deep insertion of a flexible electrode) were performed in 30 Japanese patients (two were bilateral cases), including patients with less residual hearing. Hearing preservation rates as well as speech discrimination/perception scores were investigated on a multicenter basis. Postoperative evaluation after full insertion of the flexible electrodes (24 mm, 31.5 mm) showed that residual hearing was well preserved in all 32 ears. In all patients, speech discrimination and perception scores were improved postoperatively.	\N	\N
24840132	Helmets provide soldiers with ballistic and fragmentation protection but impair auditory spatial processing. Missed auditory information can be fatal for a soldier; therefore, helmet design requires compromise between protection and optimal acoustics. Twelve soldiers localised two sound signals presented from six azimuth angles and three levels of elevation presented at two intensity levels and with three background noises. Each participant completed the task while wearing no helmet and with two U.S. Army infantry helmets - the Personnel Armor System for Ground Troops (PASGT) helmet and the Advanced Combat Helmet (ACH). Results showed a significant effect of helmet type on the size of both azimuth and elevation error. The effects of level, background noise, azimuth and elevation were found to be significant. There was no effect of sound signal type. As hypothesised, localisation accuracy was greatest when soldiers did not wear helmet, followed by the ACH. Performance was worst with the PASGT helmet.	\N	\N
24840711	Test data were used to explore the neurocognitive processing of a group of children with cochlear implants (CIs) whose language development is below expectations. This cross-sectional study examines the relationship between neurocognitive processing, as assessed by the Kaufman Assessment Battery for Children-Second Edition, and verbal language standard scores, assessed using either the Comprehensive Assessment of Spoken Language or the Clinical Evaluation of Language Fundamentals in 22 school-age children with CIs. Processing scores of CI recipients with language scores below expectations were compared to those of children meeting or exceeding language expectations. Multiple linear regression estimated the associations of simultaneous and sequential processing with language scores. Though simultaneous processing scores between the two groups were similar, the mean sequential processing score (91.2) in the below expectations group (n = 13) was significantly lower (P = 0.002) than that of children (n = 9) meeting expectations (110.8). After adjusting for age at implantation, a 10-point higher sequential processing score was associated with a 7.4 higher language score (P = 0.027). Simultaneous processing capacity was at least within the average range of cognitive performance, and was not associated with language performance in children with CIs. Conversely, reduced sequential processing capacity was significantly associated with lower language scores. Neurocognitive skills, specifically cognitive sequencing, serial ordering, and auditory-verbal memory may be targets for therapeutic intervention. Intensive cognitive and educational habilitation and in milieu intervention may improve language learning in children with CIs.	\N	\N
24841996	Auditory objects, like their visual counterparts, are perceptually defined constructs, but nevertheless must arise from underlying neural circuitry. Using magnetoencephalography (MEG) recordings of the neural responses of human subjects listening to complex auditory scenes, we review studies that demonstrate that auditory objects are indeed neurally represented in auditory cortex. The studies use neural responses obtained from different experiments in which subjects selectively listen to one of two competing auditory streams embedded in a variety of auditory scenes. The auditory streams overlap spatially and often spectrally. In particular, the studies demonstrate that selective attentional gain does not act globally on the entire auditory scene, but rather acts differentially on the separate auditory streams. This stream-based attentional gain is then used as a tool to individually analyze the different neural representations of the competing auditory streams. The neural representation of the attended stream, located in posterior auditory cortex, dominates the neural responses. Critically, when the intensities of the attended and background streams are separately varied over a wide intensity range, the neural representation of the attended speech adapts only to the intensity of that speaker, irrespective of the intensity of the background speaker. This demonstrates object-level intensity gain control in addition to the above object-level selective attentional gain. Overall, these results indicate that concurrently streaming auditory objects, even if spectrally overlapping and not resolvable at the auditory periphery, are individually neurally encoded in auditory cortex, as separate objects.	\N	\N
24847936	False physiologic monitor alarms are extremely common in the hospital environment. High false alarm rates have the potential to lead to alarm fatigue, leading nurses to delay their responses to alarms, ignore alarms, or disable them entirely. Recent evidence from the U.S. Food and Drug Administration (FDA) and The Joint Commission has demonstrated a link between alarm fatigue and patient deaths. Yet, very little scientific effort has focused on the rigorous quantitative measurement of alarms and responses in the hospital setting. We developed a system using multiple temporarily mounted, minimally obtrusive video cameras in hospitalized patients' rooms to characterize physiologic monitor alarms and nurse responses as a proxy for alarm fatigue. This allowed us to efficiently categorize each alarm's cause, technical validity, actionable characteristics, and determine the nurse's response time. We describe and illustrate the methods we used to acquire the video, synchronize and process the video, manage the large digital files, integrate the video with data from the physiologic monitor alarm network, archive the video to secure servers, and perform expert review and annotation using alarm "bookmarks." We discuss the technical and logistical challenges we encountered, including the root causes of hardware failures as well as issues with consent, confidentiality, protection of the video from litigation, and Hawthorne-like effects. The description of this video method may be useful to multidisciplinary teams interested in evaluating physiologic monitor alarms and alarm responses to better characterize alarm fatigue and other patient safety issues in clinical settings.	\N	\N
24848460	Behavioral and neural findings demonstrate that animals can locate low-frequency sounds along the azimuth by detecting microsecond interaural time differences (ITDs). Information about ITDs is also available in the amplitude modulations (i.e., envelope) of high-frequency sounds. Since medial superior olivary (MSO) neurons encode low-frequency ITDs, we asked whether they employ a similar mechanism to process envelope ITDs with high-frequency carriers, and the effectiveness of this mechanism compared with the process of low-frequency sound. We developed a novel hybrid in vitro dynamic-clamp approach, which enabled us to mimic synaptic input to brain-slice neurons in response to virtual sound and to create conditions that cannot be achieved naturally but are useful for testing our hypotheses. For each simulated ear, a virtual sound, computer generated, was used as input to a computational auditory-nerve model. Model spike times were converted into synaptic input for MSO neurons, and ITD tuning curves were derived for several virtual-sound conditions: low-frequency pure tones, high-frequency tones modulated with two types of envelope, and speech sequences. Computational models were used to verify the physiological findings and explain the biophysical mechanism underlying the observed ITD coding. Both recordings and simulations indicate that MSO neurons are sensitive to ITDs carried by spectrotemporally complex virtual sounds, including speech tokens. Our findings strongly suggest that MSO neurons can encode ITDs across a broad-frequency spectrum using an input-slope-based coincidence-detection mechanism. Our data also provide an explanation at the cellular level for human localization performance involving high-frequency sound described by previous investigators.	\N	\N
24851353	The purpose of this chapter is to describe the vocabulary development and promising, evidence-based vocabulary interventions for English learners (ELs) from preschool through second grade. To achieve this purpose, we have taken six steps. First, we describe the elements of language development in the native language (L1) and a second language (L2) and how these elements relate to three phases of reading development (i.e., the prereading phase, the learning to read phase, and the reading to learn phase). We contend that in order for ELs to succeed in school, they need a strong language foundation prior to entering kindergarten. This language foundation needs to continue developing during the "learning to read" and "reading to learn" phases. Second, we describe the limitations of current practice in preschool for ELs related to vocabulary instruction and to family involvement to support children's language development. Third, we report curricular challenges faced by ELs in early elementary school, and we relate these challenges to the increase in reading and language demands outlined in the Common Core State Standards (CCSS). Specific language activities that can help meet some of the demands are provided in a table. Fourth, we synthesize the research on evidence-based vocabulary instruction and intervention and discuss implications for practice with ELs. Fifth, we describe two intervention projects under development that have the potential to improve EL vocabulary and language proficiency in the early grades. We conclude with a summary of the chapter and provide additional resources on the topic.	\N	\N
24856412	The objective of this study was to examine the relationship between perceived discrimination and psychotic experiences (PE) using validated measures of discrimination and a racially/ethnically diverse population-level sample. Data were drawn from two population-level surveys (The National Latino and Asian American Survey and The National Survey of American Life), which were analyzed together using survey weights and stratification variables. The analytic sample (N=8990) consisted of Latino, Asian, African-American, and Afro-Caribbean adults living in the United States. Separate unadjusted and adjusted multivariable logistic regression models were used, first to examine the crude bivariate relationship between perceived discrimination and PE, and second to examine the relationship adjusting for demographic variables. Adjusted logistic regression models were also used to examine the relationships between perceived discrimination and specific sub-types of PE (auditory and visual hallucinatory experiences, and delusional ideation). When compared to individuals who did not report any discrimination, those who reported the highest levels of discrimination were significantly more likely to report both 12-month PE (Adjusted OR=4.590, p<0.001) and lifetime PE (adjusted OR=4.270, p<0.001). This held true for visual hallucinatory experiences (adjusted OR=3.745, p<0.001), auditory hallucinatory experiences (adjusted OR=5.649, p<0.001), and delusional ideation (adjusted OR=7.208, p<0.001). Perceived discrimination is associated with the increased probability of reporting psychotic experiences in a linear Fashion in the US general population.	\N	\N
24861540	Considerable evidence suggests that performance across a variety of cognitive tasks is effectively supported by the use of verbal and nonverbal strategies. Studies exploring the usefulness of such strategies in children with specific language impairment (SLI) are scarce and report inconsistent findings. To examine the effects of induced labelling and auditory cues on the performance of children with and without SLI during a categorization task. Sixty-six school-age children (22 with SLI, 22 age-matched controls, 22 language-matched controls) completed three versions of a computer-based categorization task: one baseline, one requiring overt labelling and one with auditory cues (tones) on randomized trial blocks. Labelling had no effect on performance for typically developing children but resulted in lower accuracy and longer reaction time in children with SLI. The presence of tones had no effect on accuracy but resulted in faster reaction time and post-error slowing across groups. Verbal strategy use was ineffective for typically developing children and negatively affected children with SLI. All children showed faster performance and increased performance monitoring as a result of tones. Overall, effects of strategy use in children appear to vary based on task demands, strategy domain, age and language ability. Results suggest that children with SLI may benefit from auditory cues in their clinical intervention but that further research is needed to determine when and how verbal strategies might similarly support performance in this population.	\N	\N
24867743	The prevalence of deformational plagiocephaly has risen dramatically in recent years, now affecting 15 percent or more of infants. Prior research using developmental scales suggests that these children may be at elevated risk for developmental delays. However, the low positive predictive value of such instruments in identifying long-term impairment, coupled with their poor reliability in infants, warrants the development of methods to more precisely measure brain function in craniofacial patients. Event-related potentials offer a direct measure of cortical activity that is highly applicable to young populations and has been implemented in other disorders to predict long-term cognitive functioning. The current study used event-related potentials to contrast neural correlates of auditory perception in infants with deformational plagiocephaly and typically developing children. Event-related potentials were recorded while 16 infants with deformational plagiocephaly and 18 nonaffected controls passively listened to speech sounds. Given prior research suggesting their association with subsequent functioning, analyses focused on the P150 and N450 event-related potential components. Deformational plagiocephaly patients and normal controls showed comparable cortical responses to speech sounds at both auditory event-related potential components. Children with deformational plagiocephaly demonstrate neural responses to language that are consistent with normative expectations and comparable to those of typical children. These results indicate that head shape deformity secondary to supine sleep is not associated with impairments in auditory processing. The applicability of the current methods in early infancy suggests that electrophysiologic brain recordings represent a promising method of monitoring brain development in children with cranial disorders. Risk, II.	\N	\N
24869441	Hearing preservation surgery requires specially a traumatic technique. Having some preoperative anatomical data of the size of patient's cochlea surgeon can design his or her insertion depth. In the study we have evaluated a relation between hearing preservation rate and angular insertion depth estimated intraoperatively and postoperatively having measured insertion angle from radiological assessment and calculations given by Escude. There has not been no statistically significant difference between insertion depth angle, either estimated intraoperatively and measured and calculated post-operatively, and hearing preservation rate in the group. This analysis confirms a traumaticy of insertion in hearing preservation surgery.	\N	\N
24869443	To establish whether complex signal processing is beneficial for users of bone anchored hearing aids. Review and analysis of two studies from our own group, each comparing a speech processor with basic digital signal processing (either Baha Divino or Baha Intenso) and a processor with complex digital signal processing (either Baha BP100 or Baha BP110 power). The main differences between basic and complex signal processing are the number of audiologist accessible frequency channels and the availability and complexity of the directional multi-microphone noise reduction and loudness compression systems. Both studies show a small, statistically non-significant improvement of speech understanding in quiet with the complex digital signal processing. The average improvement for speech in noise is +0.9 dB, if speech and noise are emitted both from the front of the listener. If noise is emitted from the rear and speech from the front of the listener, the advantage of the devices with complex digital signal processing as opposed to those with basic signal processing increases, on average, to +3.2 dB (range +2.3 … +5.1 dB, p ≤ 0.0032). Complex digital signal processing does indeed improve speech understanding, especially in noise coming from the rear. This finding has been supported by another study, which has been published recently by a different research group. When compared to basic digital signal processing, complex digital signal processing can increase speech understanding of users of bone anchored hearing aids. The benefit is most significant for speech understanding in noise.	\N	\N
24908093	Inconsistent information from different modalities can be delusive for perception. This phenomenon can be observed with simultaneously presented inconsistent numbers of brief flashes and short tones. The conflict of bimodal information is reflected in double flash or fission, and flash fusion illusions, respectively. The temporal resolution of the vision system plays a fundamental role in the development of these illusions. As the parallel, dorsal and ventral pathways have different temporal resolution we presume that these pathways play different roles in the illusions. We used pathway-optimized stimuli to induce the illusions on separately driven visual streams. Our results show that both pathways support the double flash illusion, while the presence of the fusion illusion depends on the activated pathway. The dorsal pathway, which has better temporal resolution, does not support fusion, while the ventral pathway which has worse temporal resolution shows fusion strongly.	\N	\N
24909603	The current pupillometry study examined the impact of speech-perception training on word recognition and cognitive effort in older adults with hearing loss. Trainees identified more words at the follow-up than at the baseline session. Training also resulted in an overall larger and faster peaking pupillary response, even when controlling for performance and reaction time. Perceptual and cognitive capacities affected the peak amplitude of the pupil response across participants but did not diminish the impact of training on the other pupil metrics. Thus, we demonstrated that pupillometry can be used to characterize training-related and individual differences in effort during a challenging listening task. Importantly, the results indicate that speech-perception training not only affects overall word recognition, but also a physiological metric of cognitive effort, which has the potential to be a biomarker of hearing loss intervention outcome.	\N	\N
24911919	It is usually easy to understand speech, but when several people are talking at once it becomes difficult. The brain must select one speech stream and ignore distracting streams. We tested a theory about the neural and computational mechanisms of attentional selection. The theory is that oscillating signals in brain networks phase-lock with amplitude fluctuations in speech. By doing this, brain-wide networks acquire information from the selected speech, but ignore other speech signals on the basis of their non-preferred dynamics. Two predictions were supported: first, attentional selection boosted the power of neuroelectric signals that were phase-locked with attended speech, but not ignored speech. Second, this phase selectivity was associated with better recall of the attended speech.	\N	\N
24919347	Auditory stimuli often facilitate visual perception. Audiovisual integration requires spatial and/or temporal proximity between visual and auditory stimuli; additionally, sensory processing speed affects the audiovisual integration process. In the present study we examined the relationship between processing speed and the auditory facilitation effect on visual representations by manipulating dot quantity patterns. We hypothesized that the auditory facilitation effect would be observed in longer interstimulus interval conditions with more dot quantities. This is because more processing time would be required to integrate visual and auditory stimuli. During a backward masking paradigm used in experiment 1, the auditory facilitation effect depended on dot quantity among patterns and the interval between visual stimuli and masks. Moreover, differences in processing time required to integrate visual and auditory stimuli between dot quantities was confirmed from a same-different discrimination task in experiment 2. Therefore, dot quantity affects sensory processing time, and a longer processing time is required for integrating visual and auditory stimuli when visual dot quantity is high.	\N	\N
24920615	The human voice carries speech as well as important nonlinguistic signals that influence our social interactions. Among these cues that impact our behavior and communication with other people is the perceived emotional state of the speaker. A theoretical framework for the neural processing stages of emotional prosody has suggested that auditory emotion is perceived in multiple steps (Schirmer and Kotz, 2006) involving low-level auditory analysis and integration of the acoustic information followed by higher-level cognition. Empirical evidence for this multistep processing chain, however, is still sparse. We examined this question using functional magnetic resonance imaging and a continuous carry-over design (Aguirre, 2007) to measure brain activity while volunteers listened to non-speech-affective vocalizations morphed on a continuum between anger and fear. Analyses dissociated neuronal adaptation effects induced by similarity in perceived emotional content between consecutive stimuli from those induced by their acoustic similarity. We found that bilateral voice-sensitive auditory regions as well as right amygdala coded the physical difference between consecutive stimuli. In contrast, activity in bilateral anterior insulae, medial superior frontal cortex, precuneus, and subcortical regions such as bilateral hippocampi depended predominantly on the perceptual difference between morphs. Our results suggest that the processing of vocal affect recognition is a multistep process involving largely distinct neural networks. Amygdala and auditory areas predominantly code emotion-related acoustic information while more anterior insular and prefrontal regions respond to the abstract, cognitive representation of vocal affect.	\N	\N
24923315	The present study examines the articulation and acoustics of the typologically rare and understudied 'whistled' fricative sound in Xitsonga, a Southern Bantu language. Using ultrasound imaging and video recording, we examine the lingual and labial articulation of the whistled fricative. For the acoustic analysis, we employ the multitaper spectral analysis, which ensures reliable spectral estimates. The results revealed an interplay between multiple articulators involved in the production of the sound: the retroflex lingual gesture and the narrowing of the lower lip toward the upper teeth. Acoustically, the spectra of the whistled fricative are more peaked and compact than the acoustically similar palatoalveolar fricative, and the differences manifest themselves most clearly in two acoustic parameters, dynamic amplitude (Ad) and M2 (variance). The acoustic differences are also manifested in F2 and F3 in the surrounding vowels. Additionally, the 'whistled' fricative in Xitsonga is not quite whistled, contrary to the label given to the sound in previous studies. Building on the current articulatory and acoustic results, we discuss two different aerodynamic models for the whistled fricatives in Southern Bantu languages and conclude that the whistled fricative in Xitsonga is best characterized as a retroflex segment accompanied by weak whistling.	\N	\N
24923465	It has been suggested that high-frequency audiometry (HFA) could represent a useful preventive measure in exposed workers. The aim was to investigate the effects of age, ultrasound and noise on high-frequency hearing thresholds. We tested 24 industrial ultrasound-exposed subjects, 113 industrial noise-exposed subjects and 148 non-exposed subjects. Each subject was tested with both conventional-frequency (0.125-8 kHz) and high-frequency (9-18 kHz) audiometry. The hearing threshold at high frequency deteriorated as a function of age, especially in subjects more than 30 years old. The ultrasound-exposed subjects had significantly higher hearing thresholds than the non-exposed ones at the high frequencies, being greatest from 10 to 14 kHz. This hearing loss was already significantly evident in subjects with exposure <5 years and increased with years of exposure and advancing age. The noise exposure group had significantly higher hearing thresholds than the non-exposed group at the conventional frequencies 4 and 6 kHz and at the high frequency of 14 kHz. After stratification for age, there was a significant difference between the two groups at 9-10 and 14-15 kHz only for those under 30 years of age. Multivariate analysis indicated that age was the primary predictor, and noise and ultrasound exposure the secondary predictors of hearing thresholds in the high-frequency range. The results suggest that HFA could be useful in the early diagnosis of noise-induced hearing loss in younger groups of workers (under 30 years of age).	\N	\N
24923619	The investigators compared event-related potential (ERP) amplitudes and event-related oscillations across a broad frequency range during an auditory oddball task using a comprehensive analysis approach to describe shared and unique neural auditory processing characteristics among healthy subjects (HP), schizophrenia probands (SZ) and their first-degree relatives, and bipolar disorder I with psychosis probands (BDP) and their first-degree relatives. This Bipolar-Schizophrenia Network on Intermediate Phenotypes sample consisted of clinically stable SZ (n = 229) and BDP (n = 188), HP (n = 284), first-degree relatives of schizophrenia probands (n = 264), and first-degree relatives of bipolar disorder I with psychosis probands (n = 239). They were administered an auditory oddball task in the electroencephalography environment. Principal components analysis derived data-driven frequency bands evoked power. Spatial principal components analysis reduced ERP and frequency data to component waveforms for each subject. Clusters of time bins with significant group differences on response magnitude were assessed for proband/relative differences from HP and familiality. Nine variables survived a linear discriminant analysis between HP, SZ, and BDP. Of those, two showed evidence (deficit in relatives and familiality) as genetic risk markers more specific to SZ (N1, P3b), one was specific to BDP (P2) and one for psychosis in general (N2). This study supports for both shared and unique deficits in early sensory and late cognitive processing across psychotic diagnostic groups. Additional ERP and time-frequency component alterations (frontal N2/P2, late high, early, mid, and low frequency) may provide insight into deficits in underlying neural architecture and potential protective/compensatory mechanisms in unaffected relatives.	\N	\N
24933411	Cortical auditory evoked potentials (CAEPs) were obtained for vowel tokens presented in an oddball stimulus paradigm. Perceptual measures of vowel discrimination were obtained using a visually-reinforced head-turn paradigm. The hypothesis was that CAEP latencies and amplitudes would differ as a function of vowel type and be correlated with perceptual performance. Twenty normally hearing infants aged 4-12 months were evaluated. CAEP component amplitudes and latencies were measured in response to the standard, frequent token /a/ and for infrequent, deviant tokens /i/, /o/ and /u/, presented at rates of 1 and 2 tokens/s. The perceptual task required infants to make a behavioral response for trials that contained two different vowel tokens, and ignore those in which the tokens were the same. CAEP amplitudes were larger in response to the deviant tokens, when compared to the control condition in which /a/ served as both standard and deviant. This was also seen in waveforms derived by subtracting the response to standard /a/ from the responses to deviant tokens. CAEP component latencies in derived responses at 2/s also demonstrated some sensitivity to vowel contrast type. The average hit rate for the perceptual task was 68.5%, with a 25.7% false alarm rate. There were modest correlations of CAEP amplitudes and latencies with perceptual performance. The CAEP amplitude differences for vowel contrasts could be used as an indicator of the underlying neural capacity to encode spectro-temporal differences in vowel sounds. This technique holds promise for translation to clinical methods for evaluating speech perception.	\N	\N
24936778	To understand the third mobile window effect of chronic otitis media with cholesteatoma with inner ear fistula on the bone conduction threshold, we examined changes in the bone conduction audiogram after tympanoplasty with mastoidectomy for chronic otitis media with cholesteatoma with canal fistula. Retrospective case review. Tertiary referral center. According to the intraoperative classification of Dornhoffer and Milewski, we focused especially on Type IIa (anatomic bony fistula with no perilymph leak). We checked the bone conduction threshold at least 3 times: just before, just after, and 6 months after surgery in 20 ears with Type IIa lateral semicircular canal fistula. Tympanoplasty with mastoidectomy. Bone conduction thresholds before and after tympanoplasty with mastoidectomy. Compared with the preoperative bone conduction threshold, 6 cases were better, 12 cases were unchanged, and 2 cases were worse within the first postoperative week. Finally, 1 case was better, 15 cases were unchanged, and 4 cases were worse at the sixth postoperative month. Patients with a better bone conduction threshold in the low-tone frequencies immediately after surgery had a tendency to show no preoperative fistula symptoms. Postoperative spontaneous nystagmus had a tendency to be observed in patients with a worse bone conduction threshold in the high-tone frequencies. The better bone conduction threshold at low-tone frequencies immediately after tympanoplasty with mastoidectomy and no preoperative fistula symptoms might imply the third mobile window theory. The worse bone conduction threshold in high-tone frequencies with spontaneous nystagmus after surgery might indicate inner ear damage.	\N	\N
24937187	Change deafness is the failure to notice changes in an auditory scene. In this study, we sought to determine if change deafness is a perceptual error, rather than only a reflection of verbal memory limitations. We also examined how successful encoding of objects within a scene is related to successful detection of changes. Event-related potentials (ERPs) were recorded while listeners completed a change-detection and an object-encoding task with scenes composed of recognizable sounds or unrecognizable temporally scrambled versions of the recognizable sounds. More change deafness occurred for the unrecognizable, compared to recognizable sounds, indicating that change deafness is a perceptual error and not solely a product of verbal memory. ERPs from both the recognizable and unrecognizable scenes revealed an enhanced P3b (at PZ/1/2, POZ/3/4 from 350 to 750ms) to detected changes, a marker that conscious change detection has occurred. Recognizable scenes resulted in an enhanced T400 (at T8/TP8, C6/CP6 from 315 to 660ms) to detected changes, possibly indicating activation of established memory representations. Unrecognizable scenes elicited an enhanced P3a (at FCZ/1/2 from 280 to 600ms) to detected changes, indicating enhanced orienting to acoustic change. Performance on the object-encoding task revealed that change deafness was reduced, but not eliminated, when performance on the object-encoding task was accurate.	\N	\N
24937544	Executive functions (EF) are cognitive capacities that allow for planned, controlled behavior and strongly correlate with academic abilities. Several extracurricular activities have been shown to improve EF, however, the relationship between musical training and EF remains unclear due to methodological limitations in previous studies. To explore this further, two experiments were performed; one with 30 adults with and without musical training and one with 27 musically trained and untrained children (matched for general cognitive abilities and socioeconomic variables) with a standardized EF battery. Furthermore, the neural correlates of EF skills in musically trained and untrained children were investigated using fMRI. Adult musicians compared to non-musicians showed enhanced performance on measures of cognitive flexibility, working memory, and verbal fluency. Musically trained children showed enhanced performance on measures of verbal fluency and processing speed, and significantly greater activation in pre-SMA/SMA and right VLPFC during rule representation and task-switching compared to musically untrained children. Overall, musicians show enhanced performance on several constructs of EF, and musically trained children further show heightened brain activation in traditional EF regions during task-switching. These results support the working hypothesis that musical training may promote the development and maintenance of certain EF skills, which could mediate the previously reported links between musical training and enhanced cognitive skills and academic achievement.	\N	\N
24949818	During childhood, verbal learning and memory are important for academic performance. Recent functional MRI studies have reported on the functional correlates of verbal memory proficiency, but few have reported the underlying structural correlates. The present study sought to test the relationship between fronto-temporal white matter integrity and verbal memory proficiency in children. Diffusion weighted images were collected from 17 Black children (age 8-11 years) who also completed the California Verbal Learning Test. To index white matter integrity, fractional anisotropy values were calculated for bilateral uncinate fasciculus. The results revealed that low anisotropy values corresponded to poor verbal memory, whereas high anisotropy values corresponded to significantly better verbal memory scores. These findings suggest that a greater degree of myelination and cohesiveness of axonal fibers in uncinate fasciculus underlie better verbal memory proficiency in children.	\N	\N
24952106	This study evaluated the clinical effectiveness of wireless contralateral routing of offside signals hearing aids (CROS) in patients with severe to profound unilateral sensorineural hearing loss (USNHL). Twenty-one patients with USNHL were enrolled in this prospective study. The change of subjective satisfaction was evaluated using three questionnaires (K-HHIE, K-IOI-HA, K-SSQ). Changes in objective measurements were evaluated with sound localization test (SLT) and hearing in noise test (HINT). These tests were performed at pre-CROS fitting, 2 and 4 weeks after use of CROS. Subjects were grouped according to the age: young (<40 years) vs. old (≥40 years) group. The average K-HHIE and K-SSQ scores significantly improved with the use of CROS. SLT result revealed that hit rate and error degree improved in the young group and lateralization ability improved in both groups. In quiet environments, the reception threshold for speech also indicated a significant benefit in the young group. When the noise was presented to the normal ear, HINT revealed benefit of CROS, while loss of performance with CROS use was significant when noise was presented to the impaired ear. Wireless CROS provided increased satisfaction and overall improvement of localization and hearing. Although true binaural hearing cannot be obtained, CROS is a practical option for rehabilitation of USNHL.	\N	\N
24959621	Accurate and effective voice activity detection (VAD) is a fundamental step for robust speech or speaker recognition. In this study, we proposed a hierarchical framework approach for VAD and speech enhancement. The modified Wiener filter (MWF) approach is utilized for noise reduction in the speech enhancement block. For the feature selection and voting block, several discriminating features were employed in a voting paradigm for the consideration of reliability and discriminative power. Effectiveness of the proposed approach is compared and evaluated to other VAD techniques by using two well-known databases, namely, TIMIT database and NOISEX-92 database. Experimental results show that the proposed method performs well under a variety of noisy conditions.	\N	\N
24960432	Research on unconscious or unaware vision has demonstrated that unconscious processing can be flexibly adapted to the current goals of human agents. The present review focuses on one area of research, masked visual priming. This method uses visual stimuli presented in a temporal sequence to lower the visibility of one of these stimuli. In this way, a stimulus can be masked and even rendered invisible. Despite its invisibility, a masked stimulus if used as a prime can influence a variety of executive functions, such as response activation, semantic processing, or attention shifting. There are also limitations on the processing of masked primes. While masked priming research demonstrates the top-down dependent usage of unconscious vision during task-set execution it also highlights that the set-up of a new task-set depends on conscious vision as its input. This basic distinction captures a major qualitative difference between conscious and unconscious vision.	\N	\N
24961249	The sound-induced flash illusion (SIFI) is a multisensory perceptual phenomenon in which the number of brief visual stimuli perceived by an observer is influenced by the number of concurrently presented sounds. While the strength of this illusion has been shown to be modulated by the temporal congruence of the stimuli from each modality, there is conflicting evidence regarding its dependence upon their spatial congruence. We addressed this question by examining SIFIs under conditions in which the spatial reliability of the visual stimuli was degraded and different sound localization cues were presented using either free-field or closed-field stimulation. The likelihood of reporting a SIFI varied with the spatial cue composition of the auditory stimulus and was highest when binaural cues were presented over headphones. SIFIs were more common for small flashes than for large flashes, and for small flashes at peripheral locations, subjects experienced a greater number of illusory fusion events than fission events. However, the SIFI was not dependent on the spatial proximity of the audiovisual stimuli, but was instead determined primarily by differences in subjects' underlying sensitivity across the visual field to the number of flashes presented. Our findings indicate that the influence of auditory stimulation on visual numerosity judgments can occur independently of the spatial relationship between the stimuli.	\N	\N
24972303	Groove-based rhythm is a basic and much appreciated feature of Western popular music. It is commonly associated with dance, movement and pleasure and is characterized by the repetition of a basic rhythmic pattern. At various points in the musical course, drum breaks occur, representing a change compared to the repeated pattern of the groove. In the present experiment, we investigated the brain response to such drum breaks in a repetitive groove. Participants were scanned with functional magnetic resonance imaging (fMRI) while listening to a previously unheard naturalistic groove with drum breaks at uneven intervals. The rhythmic pattern and the timing of its different parts as performed were the only aspects that changed from the repetitive sections to the breaks. Differences in blood oxygen level-dependent activation were analyzed. In contrast to the repetitive parts, the drum breaks activated the left cerebellum, the right inferior frontal gyrus (RIFG), and the superior temporal gyri (STG) bilaterally. A tapping test using the same stimulus showed an increase in the standard deviation of inter-tap-intervals in the breaks versus the repetitive parts, indicating extra challenges for auditory-motor integration in the drum breaks. Both the RIFG and STG have been associated with structural irregularity and increase in musical-syntactical complexity in several earlier studies, whereas the left cerebellum is known to play a part in timing. Together these areas may be recruited in the breaks due to a prediction error process whereby the internal model is being updated. This concurs with previous research suggesting a network for predictive feed-forward control that comprises the cerebellum and the cortical areas that were activated in the breaks.	\N	\N
24972535	The aim of this study was to establish a multiparameter voice assessment profile using objective multiparameter test and subjective voice quality assessment. We assessed 50 patients with voice disorders before and after operation. The assessment incorporates (1) subjective voice quality assessment, (2) patients' self-assessment, and (3) objective acoustic analysis. The subjective voice quality assessment uses GRABS system to evaluates the grade of hoarseness (G), proposed by the Japanese Society for Logopedics and Phoniatrics. Patients' self-assessment is modified based on the Chinese version of voice handicap index (VHI) scale, composed of functional (F), physiological (P), emotional (E) part, and a total score (T). The acoustical analysis evaluate the patients' voice sample by voice analysis software "Dr. Speech". Three parameters, jitter (J), shimmer(S), and normalized noise energy (NNE), were taken in analysis. We observed high correlations among subentries F, P, and the total score TvH of the VHI scale in patients' subjective assessment. Parameter E does not correlate well with other assessed parameters. The Chinese version of VHI, which incorporate multifactors including age, education, and especially the cultural difference may account for the inconsistent correction in parameter E. In the objective acoustic analysis, high correlation among the three parameters J, S, and NNE is observed. Systemic assessment combining a subjective voice quality assessment, an objective acoustic analysis, and a self-assessment is helpful in clinical practice in the diagnosis and treatment for voice disorders. The E component in VHI scale assessment may not be a reliable parameter to evaluate treatment outcome.	\N	\N
24975453	The Hearing Implant Sound Quality Index (HISQUI19) seems to be a valid tool for quantifying the self-perceived level of auditory benefit that cochlear implant (CI) users experience in everyday listening situations. Additional research is, however, required. To develop and validate a user-friendly instrument for quantifying the self-perceived level of auditory benefit that CI users experience in everyday listening situations. This was an explorative, uncontrolled, single-group, cross-sectional study. Items for the HISQUI19 were decided upon using user input and verified by professionals. The HISQUI19 was assessed on 75 CI users from hearing implant centres in Germany and Austria to determine the questions. The HISQUI19, consisting of 19 items scored on a 7-point Likert scale, was validated. Subjects older than 60 years at time of implantation did not have significantly higher mean values than subjects younger than 60 years. Gender and whether subjects are unilateral or bilateral implant CI users did not influence self-perceived functioning. Subjects with ≤20 years of hearing loss reported no significantly higher functioning than those with >20 years of hearing loss.	\N	\N
24980742	The motivation for infants' non-word vocalizations in the second half of the first year of life and later is unclear. This study of hearing infants and infants with profound hearing loss with and without cochlear implants addressed the hypothesis that vocalizations are primarily motivated by auditory feedback. Early access to cochlear implants has created unique conditions of auditory manipulation that permit empirical tests of relations between auditory perception and infant behavior. Evidence from two separate tests of the research hypothesis showed that, before cochlear implantation, infants with profound hearing loss vocalized significantly less often than hearing infants; however, soon after cochlear implantation, they vocalized at levels commensurate with hearing peers. In contrast, vocal behaviors that are typically considered reflexive or emotion-based signals (e.g., crying) were infrequent overall and did not vary with auditory access. These results support the hypothesis that auditory feedback is a critical component motivating early vocalization frequency.	\N	\N
24990679	The human music faculty might have evolved from rudimentary components that occur in non-human animals. The evolutionary history of these rudimentary perceptual features is not well understood and rarely extends beyond a consideration of vertebrates that possess a cochlea. One such antecedent is a preferential response to what humans perceive as consonant harmonic sounds, which are common in many animal vocal repertoires. We tested the phonotactic response of female túngara frogs (Physalaemus pustulosus) to variations in the frequency ratios of their harmonically structured mating call to determine whether frequency ratio influences attraction to acoustic stimuli in this vertebrate that lacks a cochlea. We found that the ratio of frequencies present in acoustic stimuli did not influence female response. Instead, the amount of inner ear stimulation predicted female preference behaviour. We conclude that the harmonic relationships that characterize the vocalizations of these frogs did not evolve in response to a preference for frequency intervals with low-integer ratios. Instead, the presence of harmonics in their mating call, and perhaps in the vocalizations of many other animals, is more likely due to the biomechanics of sound production rather than any preference for 'more musical' sounds.	\N	\N
24993544	Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category- exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1), and this occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech are discussed.	\N	\N
24993633	To compare the Naida CI UltraZoom adaptive beamformer and T-Mic settings in a real life environment. Speech reception thresholds (SRTs) were measured in a moderately reverberant room, using the German Oldenburger sentence test. The speech signal was always presented from the front loudspeaker at 0° azimuth and fixed masking noise was presented either simultaneously from all eight loudspeakers around the subject at 0°, ±45°, ±90°, ±135°, and 180° azimuth or from five loudspeakers positioned at ±70°, ±135°, and 180° azimuth. In the third test setup, an additional roving noise was added to the six loudspeaker arrangement. There was a significant difference in mean SRTs between the Naida CI T-Mic and UltraZoom in each of the three test setups. The largest improvements were seen in the six speaker roving and fixed noise conditions. Adding ClearVoice to the Naida CI T-Mic setting significantly improved the SRT in both fixed noise conditions, but not in the roving noise condition. In each setup, the lowest SRTs were obtained with the UltraZoom plus ClearVoice setting. The degree of improvement was consistent with previous beamforming studies. In the most challenging listening situation, with noise from eight speakers and speech and noise presented coincidentally from the front, UltraZoom still provided a significant benefit. When a moving noise source was added, the improvement in SRT provided by UltraZoom was maintained. When tested in challenging and realistic noise environments, the Naida CI UltraZoom adaptive beamformer resulted in significantly lower mean SRTs than when the T-Mic alone was used.	\N	\N
24995902	Neuroplasticity (NPL), neuromodulation (NM), and neuroprotection (NPT) are ongoing biophysiological processes that are linked together in sensory systems, the goal being the maintenance of a homeostasis of normal sensory function in the central nervous system. It is hypothesized that when the balance between excitatory - inhibitory action is broken in sensory systems, predominantly due to neuromodulatory activity with reduced induced inhibition and excitation predominates, sensory circuits become plastic with adaptation at synaptic levels to environmental inputs(1). Tinnitus an aberrant auditory sensation, for all clinical types, is clinically considered to reflect a failure of NPL, NM, and NPT to maintain normal auditory function at synaptic levels in sensory cortex and projected to downstream levels in the central auditory system in brain and sensorineural elements in ear. Clinically, the tinnitus sensation becomes behaviorally manifest with varying degrees of annoyance, reflecting a principle of sensory physiology that each sensation has components, i.e. sensory, affect/behavior, psychomotor and memory. Modalities of tinnitus therapies, eg instrumentation, pharmacology, surgery, target a particular component of tinnitus, with resultant activation of neuromodulators at multiple neuromodulatory centers in brain and ear. Effective neuromodulation at sensory neuronal synaptic levels results in NPL in sensory cortex, NPT and tinnitus relief. Functional brain imaging, metabolic (PET brain) and electrophysiology quantitative electroencephalography (QEEG) data in a cochlear implant soft failure patient demonstrates what is clinically considered to reflect NPL, NM, NPT. The reader is provided with a rationale for tinnitus diagnosis and treatment, with a focus on ES, reflecting the biology underlying NPL, NM, NPT.	\N	\N
25013945	Music as alternate engagement (MAE) can be used effectively to distract children during painful or anxiety-provoking medical procedures. For such interventions to be successful, it would seem important to assess the degree to which a child can attend to musical stimuli. The purposes of this study were as follows: (a) To establish construct validity by determining the extent to which the Music Attentiveness Screening Assessment (MASA) measures auditory attention; and (b) to gather evidence regarding MASA test-retest and inter-observer reliability. The Auditory Attention (AA) subtest from the NEPSY-II (NEPSY, Second Edition) and the two items from MASA were administered to a nonclinical sample of children (N = 50) aged 5 to 9 years. There was a statistically significant proportion of AA score variance shared with MASA (both items), R (2) = .21, F(2, 47) = 6.34, p = .004. Test-retest reliability on the first MASA item was moderately high (Pearson r = .84) while on the second item it was lower (r = .63). Similarly, interobserver agreement was high for Item I (intraclass correlation coefficient [ICC] = .95) and lower for Item II (ICC = .71). Evidence suggests that MASA measures, at least in part, auditory attention. Despite this finding, a large proportion of unexplained variance remains. Furthermore, reliability estimates (test-retest and interobserver agreement) differ between both items. These findings are discussed with particular attention paid to the ways in which MASA should be revised and further study conducted.	\N	\N
25016092	Lesion and neuroimaging studies indicate that the insula mediates motor aspects of speech production, specifically, articulatory control. Although it has direct connections to Broca's area, the canonical speech production region, the insula is also broadly connected with other speech and language centres, and may play a role in coordinating higher-order cognitive aspects of speech and language production. The extent of the insula's involvement in speech and language processing was assessed using the Activation Likelihood Estimation (ALE) method. Meta-analyses of 42 fMRI studies with healthy adults were performed, comparing insula activation during performance of language (expressive and receptive) and speech (production and perception) tasks. Both tasks activated bilateral anterior insulae. However, speech perception tasks preferentially activated the left dorsal mid-insula, whereas expressive language tasks activated left ventral mid-insula. Results suggest distinct regions of the mid-insula play different roles in speech and language processing.	\N	\N
25026154	The purpose of this study was to compare 3 T and 1.5 T fMRI results during emotional music listening. Stimuli comprised of psychoacoustically balanced instrumental musical pieces, with three different affective expressions (fear, neutral, joy). Participants (N=32) were split into two groups, one subjected to fMRI scanning using 3 T and another group scanned using 1.5 T. Whole brain t-tests (corrected for multiple comparisons) compared joy and fear in each of the two groups. The 3 T group showed significant activity differences between joy and fear localized in bilateral superficial amygdala, bilateral hippocampus and bilateral auditory cortex. The 1.5 T group showed significant activity differences between joy and fear localized in bilateral auditory cortex and cuneus. This is the first study to compare results obtained under different field strengths with regard to affective processes elicited by means of auditory/musical stimulation. The findings raise concern over false negatives in the superficial amygdala and hippocampus in affective studies conducted under 1.5 T and caution that imaging improvements due to increasing magnetic field strength can be influenced by region-specific characteristics.	\N	\N
25031365	The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive.	\N	\N
25032683	Categorization is an important cognitive process. However, the correct categorization of a stimulus is often challenging because categories can have overlapping boundaries. Whereas perceptual categorization has been extensively studied in vision, the analogous phenomenon in audition has yet to be systematically explored. Here, we test whether and how human subjects learn to use category distributions and prior probabilities, as well as whether subjects employ an optimal decision strategy when making auditory-category decisions. We asked subjects to classify the frequency of a tone burst into one of two overlapping, uniform categories according to the perceived tone frequency. We systematically varied the prior probability of presenting a tone burst with a frequency originating from one versus the other category. Most subjects learned these changes in prior probabilities early in testing and used this information to influence categorization. We also measured each subject's frequency-discrimination thresholds (i.e., their sensory uncertainty levels). We tested each subject's average behavior against variations of a Bayesian model that either led to optimal or sub-optimal decision behavior (i.e. probability matching). In both predicting and fitting each subject's average behavior, we found that probability matching provided a better account of human decision behavior. The model fits confirmed that subjects were able to learn category prior probabilities and approximate forms of the category distributions. Finally, we systematically explored the potential ways that additional noise sources could influence categorization behavior. We found that an optimal decision strategy can produce probability-matching behavior if it utilized non-stationary category distributions and prior probabilities formed over a short stimulus history. Our work extends previous findings into the auditory domain and reformulates the issue of categorization in a manner that can help to interpret the results of previous research within a generative framework.	\N	\N
25033791	Noise has the potential to impair cognitive performance. For nonnative speakers, the effect of noise on performance is more severe than their native counterparts. What remains unknown is the effectiveness of countermeasures such as noise attenuating devices in such circumstances. Therefore, the main aim of the present research was to examine the effectiveness of active noise attenuating countermeasures in the presence of simulated aircraft noise for both native and nonnative English speakers. Thirty-two participants, half native English speakers and half native German speakers completed four recognition (cued) recall tasks presented in English under four different audio conditions, all in the presence of simulated aircraft noise. The results of the research indicated that in simulated aircraft noise at 65 dB(A), performance of nonnative English speakers was poorer than for native English speakers. The beneficial effects of noise cancelling headphones in improving the signal to noise ratio led to an improved performance for nonnative speakers. These results have particular importance for organizations operating in a safety-critical environment such as aviation.	\N	\N
25046122	Behavioral investigations of the acquisition of some have shown that children favor its logical interpretation (some and possibly all). Adults, however, use the pragmatic interpretation (some but not all) derived by a scalar implicature. Certain experimental manipulations increase children's rates of adult-like responses, indicating that children are capable of computing implicatures. A functional MRI (fMRI) study examining adults linked the left inferior frontal gyrus (IFG) to implicature computation, and prefrontal regions, the left middle frontal gyrus (MFG), and medial frontal gyrus (MeFG), to processing the mismatch between implicatures and the context in which they were presented. In the current fMRI study, we aimed to determine whether children's failure to give pragmatic interpretations to some results from a failure in implicature computation or in implicature-mismatch processing. We explored children's brain activations with the same experimental task administered to adults. In a region-of-interest analysis, children showed an activational pattern similar to the one observed in adults in the left IFG with increased activations for the implicature conditions. By contrast, in the left MFG, children showed decreased activation for the mismatched implicatures compared with matched and no implicature conditions. No difference between the conditions was observed in the MeFG. For both implicature conditions, no activation in the left IFG was observed when comparing adults and children directly. However, for mismatched implicatures, adults showed greater activation in the prefrontal regions compared with children. Our results suggest that children may have an adult-like computation of implicatures (even when their behavior does not necessarily indicate that), but they fail in resolving implicature-mismatch situations.	\N	\N
25056109	There is converging evidence for the notion that pain affects a broad range of attentional domains. This study investigated the influence of pain on the involuntary capture of attention as indexed by the P3a component in the event-related potential derived from the electroencephalogram. Participants performed in an auditory oddball task in a pain-free and a pain condition during which they submerged a hand in cold water. Novel, infrequent and unexpected auditory stimuli were presented randomly in a series of frequent standard and infrequent target tones. P3a and P3b amplitudes were observed to novel, unexpected and target-related stimuli, respectively. Both electrophysiological components were characterized by reduced amplitudes in the pain compared with the pain-free condition. Hit rate and reaction time to target stimuli did not differ between the two conditions presumably because the experimental task was not difficult enough to exceed attentional capacities under pain conditions. These results indicate that voluntary attention serving the maintenance and control of ongoing information processing (reflected by the P3b amplitude) is impaired by pain. In addition, the involuntary capture of attention and orientation to novel, unexpected information (measured by the P3a) is also impaired by pain. Thus, neurophysiological measures examined in this study support the theoretical positions proposing that pain can reduce attentional processing capacity. These findings have potentially important implications at the theoretical level for our understanding of the interplay of pain and cognition, and at the therapeutic level for the clinical treatment of individuals experiencing ongoing pain.	\N	\N
25064434	The present magnetoencephalography study used the cortically constrained minimum-norm estimates of human brain activity to elucidate functional roles of neural generators for detecting different magnitudes of lexical tones changes. A multiple-deviant oddball paradigm was used in which the syllable "yi" with a low-dipping tone (T3) was the common standard sound and the same syllable with a high-level tone (T1) or a high-rising tone (T2) were the large and small deviant sounds, respectively. The data revealed a larger magnetic mismatch field (MMNm) for large deviant in the left hemisphere. The source analysis also confirmed that the MMNm to lexical tone changes was generated in bilateral superior temporal gyri and only the large deviant revealed left lateralization. A set of frontal generators was activated at a later time and revealed differential sensitivities to the degree of deviance. The left anterior insula, the right anterior cingulate cortex, and the right ventral orbital frontal cortex were activated when detecting a large deviant, whereas the right frontal-opercular region was sensitive to the small deviant. These frontal generators were thought to be associated with various top-down mechanisms for attentional modulation. The time frequency (TF) analysis showed that large deviants yielded large theta band (5-7Hz) activity over the left anterior scalp and the left central scalp, while small deviants yielded large alpha band activity (9-11Hz) over the posterior scalp. The results of TF analyses implied that mechanisms of working memory and functional inhibition involved in the processes of acoustic change detection.	\N	\N
25074900	Studies of visual masking have provided a wide range of important insights into the processes involved in visual coding. However, very few of these studies have employed natural scenes as masks. Little is known on how the particular features found in natural scenes affect visual detection thresholds and how the results obtained using unnatural masks relate to the results obtained using natural masks. To address this issue, this paper describes a psychophysical study designed to obtain local contrast detection thresholds for a database of natural images. Via a three-alternative forced-choice experiment, we measured thresholds for detecting 3.7 cycles/° vertically oriented log-Gabor noise targets placed within an 85 × 85-pixels patch (1.9° patch) drawn from 30 natural images from the CSIQ image database (Larson & Chandler, Journal of Electronic Imaging, 2010). Thus, for each image, we obtained a masking map in which each entry in the map denotes the root mean squared contrast threshold for detecting the log-Gabor noise target at the corresponding spatial location in the image. From qualitative observations we found that detection thresholds were affected by several patch properties such as visual complexity, fineness of textures, sharpness, and overall luminance. Our quantitative analysis shows that except for the sharpness measure (correlation coefficient of 0.7), the other tested low-level mask features showed a weak correlation (correlation coefficients less than or equal to 0.52) with the detection thresholds. Furthermore, we evaluated the performance of a computational contrast gain control model that performed fairly well with an average correlation coefficient of 0.79 in predicting the local contrast detection thresholds. We also describe specific choices of parameters for the gain control model. The objective of this database is to provide researchers with a large ground-truth dataset in order to further investigate the properties of the human visual system using natural masks.	\N	\N
25080602	In an ever-changing environment, selecting appropriate responses in conflicting situations is essential for biological survival and social success and requires cognitive control, which is mediated by dorsomedial prefrontal cortex (DMPFC) and dorsolateral prefrontal cortex (DLPFC). How these brain regions communicate during conflict processing (detection, resolution, and adaptation), however, is still unknown. The Stroop task provides a well-established paradigm to investigate the cognitive mechanisms mediating such response conflict. Here, we explore the oscillatory patterns within and between the DMPFC and DLPFC in human epilepsy patients with intracranial EEG electrodes during an auditory Stroop experiment. Data from the DLPFC were obtained from 12 patients. Thereof four patients had additional DMPFC electrodes available for interaction analyses. Our results show that an early θ (4-8 Hz) modulated enhancement of DLPFC γ-band (30-100 Hz) activity constituted a prerequisite for later successful conflict processing. Subsequent conflict detection was reflected in a DMPFC θ power increase that causally entrained DLPFC θ activity (DMPFC to DLPFC). Conflict resolution was thereafter completed by coupling of DLPFC γ power to DMPFC θ oscillations. Finally, conflict adaptation was related to increased postresponse DLPFC γ-band activity and to θ coupling in the reverse direction (DLPFC to DMPFC). These results draw a detailed picture on how two regions in the prefrontal cortex communicate to resolve cognitive conflicts. In conclusion, our data show that conflict detection, control, and adaptation are supported by a sequence of processes that use the interplay of θ and γ oscillations within and between DMPFC and DLPFC.	\N	\N
25090306	It is widely acknowledged that individuals with elevated depressive symptoms exhibit deficits in inter-personal communication. Research has primarily focused on speech production in individuals with elevated depressive symptoms. Little is known about speech perception in individuals with elevated depressive symptoms, especially in challenging listening conditions. Here, we examined speech perception in young adults with low- or high-depressive (HD) symptoms in the presence of a range of maskers. Maskers were selected to reflect various levels of informational masking (IM), which refers to cognitive interference due to signal and masker similarity, and energetic masking (EM), which refers to peripheral interference due to signal degradation by the masker. Speech intelligibility data revealed that individuals with HD symptoms did not differ from those with low-depressive symptoms during EM, but they exhibited a selective deficit during IM. Since IM is a common occurrence in real-world social settings, this listening deficit may exacerbate communicative difficulties.	\N	\N
25092665	What do we hear when someone speaks and what does auditory cortex (AC) do with that sound? Given how meaningful speech is, it might be hypothesized that AC is most active when other people talk so that their productions get decoded. Here, neuroimaging meta-analyses show the opposite: AC is least active and sometimes deactivated when participants listened to meaningful speech compared to less meaningful sounds. Results are explained by an active hypothesis-and-test mechanism where speech production (SP) regions are neurally re-used to predict auditory objects associated with available context. By this model, more AC activity for less meaningful sounds occurs because predictions are less successful from context, requiring further hypotheses be tested. This also explains the large overlap of AC co-activity for less meaningful sounds with meta-analyses of SP. An experiment showed a similar pattern of results for non-verbal context. Specifically, words produced less activity in AC and SP regions when preceded by co-speech gestures that visually described those words compared to those words without gestures. Results collectively suggest that what we 'hear' during real-world speech perception may come more from the brain than our ears and that the function of AC is to confirm or deny internal predictions about the identity of sounds.	\N	\N
25096108	The summation of loudness across ears is often studied by measuring the level difference required for equal loudness (LDEL) of monaural and diotic sounds. Typically, the LDEL is ∼5-6 dB, consistent with the idea that a diotic sound is ∼1.5 times as loud as the same sound presented monaurally at the same level, as predicted by the loudness model of Moore and Glasberg [J. Acoust. Soc. Am. 121, 1604-1612 (2007)]. One might expect that the LDEL would be <5-6 dB for hearing-impaired listeners, because loudness recruitment leads to a more rapid change of loudness for a given change in level. However, previous data sometimes showed similar LDEL values for normal-hearing and hearing-impaired listeners. Here, the LDEL was measured for hearing-impaired listeners using narrowband and broadband noises centered at 500 Hz, where audiometric thresholds were near-normal, and at 3000 or 4000 Hz, where audiometric thresholds were elevated. The mean LDEL was 5.6 dB at 500 Hz and 4.2 dB at the higher center frequencies. The results were predicted reasonably well by an extension of the loudness model of Moore and Glasberg.	\N	\N
25096138	The effects of audiovisual versus auditory training for speech-in-noise identification were examined in 60 young participants. The training conditions were audiovisual training, auditory-only training, and no training (n = 20 each). In the training groups, gated consonants and words were presented at 0 dB signal-to-noise ratio; stimuli were either audiovisual or auditory-only. The no-training group watched a movie clip without performing a speech identification task. Speech-in-noise identification was measured before and after the training (or control activity). Results showed that only audiovisual training improved speech-in-noise identification, demonstrating superiority over auditory-only training.	\N	\N
25113242	This study investigates the influence of rhythmic expectancies on language processing. It is assumed that language rhythm involves an alternation of strong and weak beats within a linguistic domain. Hence, in some contexts rhythmically induced stress shifts occur in order to comply with the Rhythm Rule. In English, this rule operates to prevent clashes of stressed adjacent syllables or lapses of adjacent unstressed syllables. While previous studies investigated effects on speech production and perception, this study focuses on brain responses to structures either obeying or deviating from this rule. Event-related potentials show that rhythmic regularity is relevant for language processing: rhythmic deviations evoked different ERP components reflecting the deviance from rhythmic expectancies. An N400 effect found for shifted items reflects higher costs in lexical processing due to stress deviation. The overall results disentangle lexical and rhythmical influences on language processing and complement the findings of previous studies on rhythmical processing.	\N	\N
25118042	To compare the fitting time requirements and the efficiency in achieving improvements in speech perception during the first 6 months after initial stimulation of computer-assisted fitting with the Fitting to Outcome eXpert' (FOX) and a standard clinical fitting procedure. Twenty-seven post-lingually deafened adults, newly implanted recipients of the Advanced Bionics HiRes 90K™ cochlear implant from Germany, the UK, and France took part in a controlled, randomized, clinical study. Speech perception was measured for all participants and fitting times were compared across groups programmed using FOX and conventional programming methods. The fitting time for FOX was significantly reduced at 14 days (P < 0.001) but equivalent over the 6-month period. The groups were not well matched for duration of deafness; therefore, speech perception could not be compared across groups. Despite including more objective measures of performance than a standard fitting approach and the adjustment of a greater range of parameters during initial fitting, FOX did not add to the overall fitting time when compared to the conventional approach. FOX significantly reduced the fitting time in the first 2 weeks and by providing a standard fitting protocol, reduced variability across centres. FOX computer-assisted fitting can be successfully used at switch on, in different clinical environments, reducing fitting time in the first 2 weeks and is efficient at providing a usable program.	\N	\N
25121623	The current study provides evidence that the absence of a syntactically expected item leads to a sustained cognitive processing demand. Event-related potentials were measured at the omission of a syntactically expected object argument in a speech sequence. English monolingual adults listened to paired sentences. The first sentence in the pair established a context. The second sentence provided a response to the first sentence that was either grammatically correct by containing an overt object argument in the form of a pronoun, or was syntactically unacceptable by omitting the expected object pronoun. Event-related potentials measured at the omission of the object argument showed a prolonged positivity for 100-600 ms with a broad scalp distribution, and for 600-1000 ms with a focus in the anterior region. This observed omitted stimulus potential may contain characteristics of the P300 component, associated with the detection of the deviation of an expected stimulus, and the classical P600 related to syntactic reanalysis. Further, the late anterior P600 may indicate an increased memory demand in sentence comprehension. Thus, this linguistic omitted stimulus potential is a cognitive indicator of language processing that can be used to investigate the organization of linguistic knowledge.	\N	\N
25126691	To evaluate the relationship between conductive hearing loss and maxillary constriction. A total of 120 people, aged from 7 to 40 years, who were referred to an audiologist when taking out health insurance or for school pre-registration check-up, were selected for this study. A total of 60 participants who had hearing threshold levels greater than 15 dB in both ears were chosen as the conductive hearing loss group. The remaining 60, with normal hearing thresholds of less than 15 dB, were used as the control group. All participants were referred to an orthodontic clinic. Participants who had a posterior crossbite and high palatal vault were considered to suffer from maxillary constriction. There were no significant differences between the sex ratios and mean ages of the groups. However, participants with conductive hearing loss were 3.5 times more likely than controls to suffer from maxillary constriction. Patients who suffer from conductive hearing loss are likely to show a maxillary abnormality when examined by an orthodontist.	\N	\N
25139422	We investigated global integration (wrap-up) processes at the boundaries of musical phrases by comparing the effects of well and non-well formed phrases on event-related potentials time-locked to two boundary points: the onset and the offset of the boundary pause. The Closure Positive Shift, which is elicited at the boundary offset, was not modulated by the quality of phrase structure (well vs. non-well formed). In contrast, the boundary onset potentials showed different patterns for well and non-well formed phrases. Our results contribute to specify the functional meaning of the Closure Positive Shift in music, shed light on the large-scale structural integration of musical input, and raise new hypotheses concerning shared resources between music and language.	\N	\N
25150964	Timbre is an important attribute of sound both in music and nature. Previously, using an operant conditioning paradigm, we found that black-capped chickadees and humans show similar response patterns in discriminating triadic chords of the same timbre and transferred this discrimination to a novel key center (novel absolute pitch). The current study examined how varying the timbre of the chords influenced discrimination. Using a similar operant conditioning procedure, we trained humans (Experiment 1) and chickadees (Experiments 2 and 3) to discriminate a major chord from 6 other chord types that had semitone deviations from the major chord. The pattern of errors of the 2 species replicated our previous findings. We then tested participants with novel timbres. We found that humans readily transferred their discrimination to novel timbres, suggesting they were attending to triadic pitch relations. The chickadees failed to transfer to novel timbres, suggesting they were using a different strategy to perform the original chord discrimination. We conducted an acoustic analysis examining frequency ranges that are biologically relevant to chickadees. We found that the relative intensity within each chord of the frequencies used in black-capped chickadee song significantly correlated with chickadees' percent response during probe testing. In Experiment 3, we trained a new set of chickadees by including either expanded pitch or timbre training before testing. Although chickadees showed some transfer to novel chords following this expanded training, we found that neither type of expanded training helped the chickadees when probe tested with novel stimuli.	\N	\N
25151640	Congenital amusia has been described as a lifelong deficit of music perception and production, notably including amusic individuals' difficulties to recognize a familiar tune without the aid of lyrics. The present study aimed to evaluate whether amusic individuals might have acquired long-term knowledge of familiar music, and to test for the minimal amount of acoustic information necessary to access this knowledge (if any) in amusia. Segments of familiar and unfamiliar instrumental musical pieces were presented with increasing duration (250, 500, 1000 msec etc.), and participants provided familiarity judgments for each segment. Results showed that amusic individuals succeeded in differentiating familiar from unfamiliar excerpts with as little acoustic information as did control participants (i.e., within 500 msec). The findings reveal that amusic individuals have stored musical pieces in long-term memory (LTM), and, together with other recent findings, they suggest that congenital amusia might impair conscious access to music processing rather than music processing per se.	\N	\N
25158372	Cortical auditory-evoked potentials (CAEPs), an objective measure of human speech encoding in individuals with normal or impaired auditory systems, can be used to assess the outcomes of hearing aids and cochlear implants in infants, or in young children who cannot co-operate for behavioural speech discrimination testing. The current study aimed to determine whether naturally produced speech stimuli /m/, /g/ and /t/ evoke distinct CAEP response patterns that can be reliably recorded and differentiated, based on their spectral information and whether the CAEP could be an electrophysiological measure to differentiate between these speech sounds. CAEPs were recorded from 18 school-aged children with normal hearing, tested in two groups: younger (5 - 7 years) and older children (8 - 12 years). Cortical responses differed in their P1 and N2 latencies and amplitudes in response to /m/, /g/ and /t/ sounds (from low-, mid- and high-frequency regions, respectively). The largest amplitude of the P1 and N2 component was for /g/ and the smallest was for /t/. The P1 latency in both age groups did not show any significant difference between these speech sounds. The N2 latency showed a significant change in the younger group but not in the older group. The N2 latency of the speech sound /g/ was always noted earlier in both groups. This study demonstrates that spectrally different speech sounds are encoded differentially at the cortical level, and evoke distinct CAEP response patterns. CAEP latencies and amplitudes may provide an objective indication that spectrally different speech sounds are encoded differently at the cortical level.	\N	\N
25158615	To evaluate methods for measuring long-term benefits of cochlear implantation in a patient with single-sided deafness (SSD) with respect to spatial hearing and to document improved quality of life because of reduced tinnitus. A single adult male with profound right-sided sensorineural hearing loss and normal hearing in the left ear who underwent right-sided cochlear implantation. The subject was evaluated at 6, 9, 12, and 18 months after implantation on speech intelligibility with specific target-masker configurations, sound localization accuracy, audiologic performance, and tinnitus handicap. Testing conditions involved the acoustic (NH) ear only, the cochlear implant (CI) ear (acoustic ear plugged), and the bilateral condition (CI+NH). Measures of spatial hearing included speech intelligibility improvement because of spatial release from masking (SRM) and sound localization. In addition, traditional measures known as "head shadow," "binaural squelch," and "binaural summation" were evaluated. The best indicator for improved speech intelligibility was SRM, in which both ears are activated, but the relative locations of target and masker(s) are manipulated. Measures that compare performance with a single ear to performance using bilateral auditory input indicated evidence of the ability to integrate inputs across the ears, possibly reflecting early binaural processing, with 12 months of bilateral input. Sound localization accuracy improved with addition of the implant, and a large improvement with respect to tinnitus handicap was observed. Cochlear implantation resulted in improved sound localization accuracy when compared with performance using only the NH ear, and reduced tinnitus handicap was observed with use of the implant. The use of SRM addresses some of the current limitations of traditional measures of spatial and binaural hearing, as spatial cues related to target and maskers are manipulated, rather than the ear(s) tested. Sound testing methods and calculations described here are therefore recommended for assessing performance of a larger sample size of individuals with SSD who receive a CI.	\N	\N
25167217	Objective To investigate the effect of increasing phase duration (pulse width, T-pulse) using a biphasic pulse composed of an initial anodic active phase followed by a balancing cathodic phase on the electrically evoked auditory brainstem responses (eABRs) recorded at the time of cochlear implantation. Design eABRs recorded during 188 surgeries for cochlear implantation from 1999 to 2006 in a single center were retrospectively reviewed by two independent observers. All patients were fitted with a NEURELEC cochlear implant (CI) device, initially DIGISONIC(®) then DIGISONIC SP(®) (2004-2006). Result Immediately following cochlear implantation, stimulation by the CI resulted in reliable wave III and V eABR waveforms (mean wave III latency 2.23 ± 0.38 ms SD and wave V latency 4.28 ± 0.42 ms SD). Latencies followed an apical to basal gradient (0.32 ms increase in mean eV latency and 0.12 ms for eIII latency). With increasing phase duration, wave III and wave V latencies significantly decreased in association with a shortening of the eIII-eV interwave gap, while amplitudes of both waves increased. Conclusion The impact of increasing phase duration on latency and amplitude of brainstem responses in a large set of patients implanted with NEURELEC CIs was reported.	\N	\N
25170794	The neural resonance theory of musical meter explains musical beat tracking as the result of entrainment of neural oscillations to the beat frequency and its higher harmonics. This theory has gained empirical support from experiments using simple, abstract stimuli. However, to date there has been no empirical evidence for a role of neural entrainment in the perception of the beat of ecologically valid music. Here we presented participants with a single pop song with a superimposed bassoon sound. This stimulus was either lined up with the beat of the music or shifted away from the beat by 25% of the average interbeat interval. Both conditions elicited a neural response at the beat frequency. However, although the on-the-beat condition elicited a clear response at the first harmonic of the beat, this frequency was absent in the neural response to the off-the-beat condition. These results support a role for neural entrainment in tracking the metrical structure of real music and show that neural meter tracking can be disrupted by the presentation of contradictory rhythmic cues.	\N	\N
25176617	Verbal memory is a fundamental prerequisite for language learning. This study investigated 7-month-olds' (N = 62) ability to remember the identity and order of elements in a multisyllabic word. The results indicate that infants detect changes in the order of edge syllables, or the identity of the middle syllables, but fail to encode the order of middle syllables. This suggests that the representational format of multisyllabic words is determined by core mnemonic biases, which favor accurate encoding of edges and limits the encoding of temporal order for internal segments. The studies support accounts proposing that content and order are encoded separately; in addition, the data show that this dissociation occurs early in development.	\N	\N
25185802	In two studies based on Stanley Milgram's original pilots, we present the first systematic examination of cyranoids as social psychological research tools. A cyranoid is created by cooperatively joining in real-time the body of one person with speech generated by another via covert speech shadowing. The resulting hybrid persona can subsequently interact with third parties face-to-face. We show that naïve interlocutors perceive a cyranoid to be a unified, autonomously communicating person, evidence for a phenomenon Milgram termed the "cyranic illusion." We also show that creating cyranoids composed of contrasting identities (a child speaking adult-generated words and vice versa) can be used to study how stereotyping and person perception are mediated by inner (dispositional) vs. outer (physical) identity. Our results establish the cyranoid method as a unique means of obtaining experimental control over inner and outer identities within social interactions rich in mundane realism.	\N	\N
25188354	Although active listening is an influential behavior, which can affect the social responses of others, the neural correlates underlying its perception have remained unclear. Sensing active listening in social interactions is accompanied by an improvement in the recollected impressions of relevant experiences and is thought to arouse positive feelings. We therefore hypothesized that the recognition of active listening activates the reward system, and that the emotional appraisal of experiences that had been subject to active listening would be improved. To test these hypotheses, we conducted functional magnetic resonance imaging (fMRI) on participants viewing assessments of their own personal experiences made by evaluators with or without active listening attitude. Subjects rated evaluators who showed active listening more positively. Furthermore, they rated episodes more positively when they were evaluated by individuals showing active listening. Neural activation in the ventral striatum was enhanced by perceiving active listening, suggesting that this was processed as rewarding. It also activated the right anterior insula, representing positive emotional reappraisal processes. Furthermore, the mentalizing network was activated when participants were being evaluated, irrespective of active listening behavior. Therefore, perceiving active listening appeared to result in positive emotional appraisal and to invoke mental state attribution to the active listener.	\N	\N
25190323	In a standard center cueing paradigm, participants are asked to identify a target object presented either to the left or the right of a center cue (e.g., eye gaze, head-turn, arrow, etc.). When the center cue is non-predictive (e.g., the arrow points to the correct location of the target only 50 % of the time), the target can still be identified faster at the validly cued location than at the invalidly cued location. However, the abrupt onset of an object can elicit reflexive attention orientation. It is important to investigate whether this abrupt onset effect interferes with the cueing effect elicited by center cues because this interference effect, if it exists, should be controlled for in order to improve the test validity of the center cueing task. In an attentional cueing paradigm, we examined how the abrupt appearance of an exogenous target object mitigates the influence of center cues involving either a head turn (Experiment 1) or an arrow (Experiment 2). In Experiment 1, a non-predictive head-turn cue was followed by a target object (circle or square) presented in the left or right visual field. In the non-distractor condition, the target object was presented by itself. In this case, it is assumed that the sudden appearance of the target provides an orienting cue to the observer. To equalize the cueing effect of the target object, we presented a competing distractor object (triangle) in the opposite visual field to the target object. The participant's task was to categorize the target object as either a circle or square while ignoring the non-target triangle object in the opposite visual field. In Experiment 2, the arrow version of the cued recognition task was used, in which a single-headed arrow pointed to the object. The results from both experiments showed that both the non-predictive head-turn and arrow cues produced a reliable cueing effect in the distractor and non-distractor conditions. However, the magnitude of the cueing effect was greater in the distractor condition than in the non-distractor condition, suggesting that the abrupt onset of the target object acts like an exogenous signal, thereby reducing the impact of the internal head turn and arrow cues.	\N	\N
25190394	Factors that might affect perceptual pitch match between acoustic and electric stimulation were examined in 25 bimodal listeners using magnitude estimation. Pre-operative acoustic thresholds in both ears, and duration of severe-profound loss, were first examined as correlates with degree of match between the measured pitch and that predicted by the spiral ganglion frequency-position model. The degree of match was examined with respect to (1) the ratio between the measured and predicted pitch percept on the most apical electrode and (2) the ratio between the slope of the measured and predicted pitch function. Second, effect of listening experience was examined to assess whether adaptation occurred over time to match the frequency assignment to electrodes. Pre-experience pitch estimates on the apical electrode were within the predicted range in only 28% of subjects, and the slope of the electrical pitch function was lower than predicted in all except one subject. Subjects with poorer hearing tended to have a lower pitch and a shallower electrical pitch function than predicted by the model. Pre-operative hearing thresholds in the contralateral ear and hearing loss duration were not correlated with the degree of pitch match, and there was no significant group effect of listening experience.	\N	\N
25190407	Normal-hearing (NH) listeners make use of context, speech redundancy and top-down linguistic processes to perceptually restore inaudible or masked portions of speech. Previous research has shown poorer perception and restoration of interrupted speech in CI users and NH listeners tested with acoustic simulations of CIs. Three hypotheses were investigated: (1) training with CI simulations of interrupted sentences can teach listeners to use the high-level restoration mechanisms more effectively, (2) phonemic restoration benefit, an increase in intelligibility of interrupted sentences once its silent gaps are filled with noise, can be induced with training, and (3) perceptual learning of interrupted sentences can be reflected in clinical speech audiometry. To test these hypotheses, NH listeners were trained using periodically interrupted sentences, also spectrally degraded with a noiseband vocoder as CI simulation. Feedback was presented by displaying the sentence text and playing back both the intact and the interrupted CI simulation of the sentence. Training induced no phonemic restoration benefit, and learning was not transferred to speech audiometry measured with words. However, a significant improvement was observed in overall intelligibility of interrupted spectrally degraded sentences, with or without filler noise, suggesting possibly better use of restoration mechanisms as a result of training.	\N	\N
25194209	Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way.	\N	\N
25196041	Cognitive enhancement resulting from nicotinic acetylcholine receptor stimulation may be evidenced by increased efficiency of the auditory-frontal cortex network of auditory discrimination, which is impaired in schizophrenia, a cognitive disorder associated with excessive tobacco use. Investigating automatic (preattentive) detection of acoustic change with the mismatch negativity (MMN) brain event-related potential in response to nicotine in individuals with varying baseline levels of auditory discrimination may provide useful insight into the cholinergic regulation of this neural network and its potential amelioration with novel nicotinic agents. Sixty healthy, non-smoking male volunteers were presented with an 'optimal' multi-feature MMN paradigm in a randomized, placebo controlled double-blind design with 6 mg of nicotine gum. Participants with low, medium, and high baseline amplitudes responded differently to nicotine (vs. placebo), and nicotine response was feature specific. Whereas MMN in individuals with high amplitudes was diminished by nicotine, MMN increased in those with low amplitudes. Nicotine effects were not shown in medium amplitude participants. These findings provide preliminary support for the role of nicotinic neurotransmission in sensory memory processing of auditory change and suggest that nicotinic receptor modulation can both enhance and diminish change detection, depending on baseline MMN and its eliciting stimulus feature.	\N	\N
25201816	Evidence suggests that deafness-induced changes in visual perception, cognition and attention may compensate for a hearing loss. Such alterations, however, may also negatively influence adaptation to a cochlear implant. This study investigated whether involuntary attentional capture by salient visual stimuli is altered in children who use a cochlear implant. Thirteen experienced implant users (aged 8-16 years) and age-matched normally hearing children were presented with a rapid sequence of simultaneous visual and auditory events. Participants were tasked with detecting numbers presented in a specified color and identifying a change in the tonal frequency whilst ignoring irrelevant visual distractors. Compared to visual distractors that did not possess the target-defining characteristic, target-colored distractors were associated with a decrement in visual performance (response time and accuracy), demonstrating a contingent capture of involuntary attention. Visual distractors did not, however, impair auditory task performance. Importantly, detection performance for the visual and auditory targets did not differ between the groups. These results suggest that proficient cochlear implant users demonstrate normal capture of visuospatial attention by stimuli that match top-down control settings.	\N	\N
25208843	When an action produces an effect, both events are perceived to be shifted in time toward each other. This shift is called Intentional Binding (IB) effect. First evidence shows that this shift does not depend on the statistical predictability of the produced effect's identity (Desantis, Hughes, & Waszak, 2012). We confirm this result by comparing the perceived duration of action-effect intervals before valid and invalid action effects using the method of constant stimuli. The perceived duration of action-effect intervals did not differ for valid and invalid effects. This result was true for different durations of the action-effect interval (Experiments 1-4: 250 ms, Experiments 1 & 2: 400 ms), different effect modalities (Experiments 1 & 3: visual, Experiments 2-4: auditive), and two types of validity variations (Experiments 1 & 2: 80% valid, Experiments 3 & 4: 100% valid vs. random). We validated our results by using a clock paradigm and a numerical duration estimation task (Experiment 4). We conclude that the IB effect is not the result of internal prediction due to action-effect bindings, but might rely on higher-order processes.	\N	\N
25214304	Prior studies of spatial negative priming indicate that distractor-assigned keypress responses are inhibited as part of visual, but not auditory, processing. However, recent evidence suggests that static keypress responses are not directly activated by spatially presented sounds and, therefore, might not call for an inhibitory process. In order to investigate the role of response inhibition in auditory processing, we used spatially directed responses that have been shown to result in direct response activation to irrelevant sounds. Participants localized a target sound by performing manual joystick responses (Experiment 1) or head movements (Experiment 2B) while ignoring a concurrent distractor sound. Relations between prime distractor and probe target were systematically manipulated (repeated vs. changed) with respect to identity and location. Experiment 2A investigated the influence of distractor sounds on spatial parameters of head movements toward target locations and showed that distractor-assigned responses are immediately inhibited to prevent false responding in the ongoing trial. Interestingly, performance in Experiments 1 and 2B was not generally impaired when the probe target appeared at the location of the former prime distractor and required a previously withheld and presumably inhibited response. Instead, performance was impaired only when prime distractor and probe target mismatched in terms of location or identity, which fully conforms to the feature-mismatching hypothesis. Together, the results suggest that response inhibition operates in auditory processing when response activation is provided but is presumably too short-lived to affect responding on the subsequent trial.	\N	\N
25215617	Previous studies of frequency discrimination training (FDT) for tinnitus used repetitive task-based training programmes relying on extrinsic factors to motivate participation. Studies reported limited improvement in tinnitus symptoms. To evaluate FDT exploiting intrinsic motivations by integrating training with computer-gameplay. Sixty participants were randomly assigned to train on either a conventional task-based training, or one of two interactive game-based training platforms over six weeks. Outcomes included assessment of motivation, tinnitus handicap, and performance on tests of attention. Participants reported greater intrinsic motivation to train on the interactive game-based platforms, yet compliance of all three groups was similar (∼ 70%) and changes in self-reported tinnitus severity were not significant. There was no difference between groups in terms of change in tinnitus severity or performance on measures of attention. FDT can be integrated within an intrinsically motivating game. Whilst this may improve participant experience, in this instance it did not translate to additional compliance or therapeutic benefit. ClinicalTrials.gov NCT02095262.	\N	\N
25218167	Knowing the context of a discourse is an essential prerequisite for comprehension. Here we used functional magnetic resonance imaging (fMRI) to disclose brain networks supporting context-dependent speech comprehension. During fMRI, 20 participants listened to 1-min spoken narratives preceded by pictures that were either contextually matching or mismatching with the narrative. Matching pictures increased narrative comprehension, decreased hemodynamic activity in Broca׳s area, and enhanced its functional connectivity with left anterior superior frontal gyrus, bilateral inferior parietal cortex, as well as anterior and posterior cingulate cortex. Further, the anterior (BA 45) and posterior (BA 44) portions of Broca׳s area differed in their functional connectivity patterns. Both BA 44 and BA 45 have shown increased connectivity with right angular gyrus and supramarginal gyrus. Whereas BA 44 showed increased connectivity with left angular gyrus, left inferior/middle temporal gyrus and left postcentral gyrus, BA 45 showed increased connectivity with right posterior cingulate cortex, right anterior inferior frontal gyrus, lateral occipital cortex and anterior cingulate cortex. Our results suggest that a fronto-parietal functional network supports context-dependent narrative comprehension, and that Broca׳s area is involved in resolving ambiguity from speech when appropriate contextual cues are lacking.	\N	\N
25223106	A sound's duration provides important information about the event producing it. Although many of the sounds we hear every day are 'percussive' in nature (ie resulting from two objects impacting) and therefore exhibit decaying/damped amplitude envelopes, perceptual experiments frequently use tones synthesized with 'flat' or abruptly ending envelopes. Such sounds afford an estimation strategy involving calculating the elapsed time between tone onset and offset--a strategy that would be problematic for ecologically pervasive decaying sounds. Here we compare duration judgments for tones with percussive (ie gradually decaying) and flat (ie abruptly ending) amplitude envelopes, finding evidence for the use of different strategies. This result is discussed in terms of its implications for dominant theories and models of sensory perception that are often assessed using artificial sounds (ie 'flat tones') affording strategies that may not be optimal or even available for everyday listening.	\N	\N
25224031	In human and nonhuman primates, the cortical motor system comprises a collection of brain areas primarily related to motor control. Existing evidence suggests that no other mammalian group has the number, extension, and complexity of motor-related areas observed in the frontal lobe of primates. Such diversity is probably related to the wide behavioral flexibility that primates display. Indeed, recent comparative anatomical, psychophysical, and neurophysiological studies suggest that the evolution of the motor cortical areas closely correlates with the emergence of high cognitive abilities. Advances in understanding the cortical motor system have shown that these areas are also related to functions previously linked to higher-order associative areas. In addition, experimental observations have shown that the classical distinction between perceptual and motor functions is not strictly followed across cortical areas. In this paper, we review evidence suggesting that evolution of the motor system had a role in the shaping of different cognitive functions in primates. We argue that the increase in the complexity of the motor system has contributed to the emergence of new abilities observed in human and nonhuman primates, including the recognition and imitation of the actions of others, speech perception and production, and the execution and appreciation of the rhythmic structure of music.	\N	\N
25226375	We seek to determine the extent of age-related decline in speech perception performance among cochlear implant recipients as quantified by various metrics. Retrospective chart review. Tertiary referral center. The records of 70 postlingually deafened adults who received cochlear implants between 2004 and 2013 were reviewed. Unilateral cochlear implantation. Postoperative AzBio and Consonant-Nucleus-Consonant (CNC) scores at greater than 3 months postactivation. Group analyses comparing patients aged 65 years and older (elderly) with younger adult patients (control). In addition, multivariate linear regression analyses were performed that incorporated preoperative pure-tone audiograms, duration of deafness, duration of follow-up, sex, and laterality of the implanted ear to quantitate the dependence of AzBio and CNC results on age at implantation (AAI). Performance on AzBio for the control and elderly groups were 74.6% ± 4.1% and 59.5% ± 4.5% (p = 0.032), respectively. Performance on CNC scores were 63.9% ± 3.4% and 55.3% ± 3.3% (p = 0.098), respectively. Multiple linear regression showed a significant correlation of AzBio with AAI, whereas CNC did not correlate significantly (correlation coefficients = -0.006 and -0.003, p = 0.019 and 0.081, respectively). Patients implanted at a later age performed more poorly on AzBio sentences. A similar trend was noted with CNC scores although not significant. The variability in correlation coefficients and significance between both speech perception tests and AAI suggests that, as patients age, their performance on each individual test will be affected to a varying degree.	\N	\N
25234731	Mandarin Chinese is a lexical tone language that has four tones, with a change in tone denoting a change in lexical meaning. There are few studies regarding lexical tone identification abilities in deafened children using either cochlear implants (CIs) or hearing aids (HAs). Furthermore, no study has compared the lexical tone identification abilities of deafened children with their hearing devices turned on and off. The present study aimed to investigate the lexical tone identification abilities of deafened children with CIs or HAs. Forty prelingually deafened children (20 with CIs and 20 with HAs) participated in the study. In the HA group, 20 children were binaurally aided. In the CI group, all of the children were unilaterally implanted. All of the subjects completed a computerized lexical tone pairs test with their hearing devices turned on and off. The correct answers of all items were recorded as the total score and the correct answers of the tone pairs were recorded as subtotal scores. No significant differences in the tone pair identification scores were found between the CI group and HA group either with the devices turned on or off (t=1.62, p=0.11; t=1.863, p=0.07, respectively). The scores in the aided condition were higher than in the unaided condition regardless of the device used (t=22.09, p<0.001, in the HA group; t=20.20, p<0.001, in the CI group). Significantly higher scores were found in the tone pairs that contained tone 4. Age at fitting of the devices was correlated with tone identification abilities in both the CI and HA groups. Other demographic factors were not correlated with tone identification ability. The hearing device, whether a hearing aid or cochlear implant, is beneficial for tone identification. The lexical tone identification abilities were similar regardless of whether the subjects wore a HA or CI. Lexical tone pairs with different durations and dissimilar tone contour patterns are more easily identified. Receiving devices at earlier age tends to produce better lexical tone identification abilities in prelingually deafened children.	\N	\N
25234885	This study examined the ability of listeners to utilize syntactic structure to extract a target stream of speech from among competing sounds. Target talkers were identified by voice or location, which was held constant throughout a test utterance, and paired with correct or incorrect (random word order) target sentence syntax. Both voice and location provided reliable cues for identifying target speech even when other features varied unpredictably. The target sentences were masked either by predominantly energetic maskers (noise bursts) or by predominantly informational maskers (similar speech in random word order). When the maskers were noise bursts, target sentence syntax had relatively minor effects on identification performance. However, when the maskers were other talkers, correct target sentence syntax resulted in significantly better speech identification performance than incorrect syntax. Furthermore, conformance to correct syntax alone was sufficient to accurately identify the target speech. The results were interpreted as supporting the idea that the predictability of the elements comprising streams of speech, as manifested by syntactic structure, is an important factor in binding words together into coherent streams. Furthermore, these findings suggest that predictability is particularly important for maintaining the coherence of an auditory stream over time under conditions high in informational masking.	\N	\N
25235005	The contribution of recovered envelopes (RENVs) to the utilization of temporal-fine structure (TFS) speech cues was examined in normal-hearing listeners. Consonant identification experiments used speech stimuli processed to present TFS or RENV cues. Experiment 1 examined the effects of exposure and presentation order using 16-band TFS speech and 40-band RENV speech recovered from 16-band TFS speech. Prior exposure to TFS speech aided in the reception of RENV speech. Performance on the two conditions was similar (∼50%-correct) for experienced listeners as was the pattern of consonant confusions. Experiment 2 examined the effect of varying the number of RENV bands recovered from 16-band TFS speech. Mean identification scores decreased as the number of RENV bands decreased from 40 to 8 and were only slightly above chance levels for 16 and 8 bands. Experiment 3 examined the effect of varying the number of bands in the TFS speech from which 40-band RENV speech was constructed. Performance fell from 85%- to 31%-correct as the number of TFS bands increased from 1 to 32. Overall, these results suggest that the interpretation of previous studies that have used TFS speech may have been confounded with the presence of RENVs.	\N	\N
25243615	It is well established that categorising the emotional content of facial expressions may differ depending on contextual information. Whether this malleability is observed in the auditory domain and in genuine emotion expressions is poorly explored. We examined the perception of authentic laughter and crying in the context of happy, neutral and sad facial expressions. Participants rated the vocalisations on separate unipolar scales of happiness and sadness and on arousal. Although they were instructed to focus exclusively on the vocalisations, consistent context effects were found: For both laughter and crying, emotion judgements were shifted towards the information expressed by the face. These modulations were independent of response latencies and were larger for more emotionally ambiguous vocalisations. No effects of context were found for arousal ratings. These findings suggest that the automatic encoding of contextual information during emotion perception generalises across modalities, to purely non-verbal vocalisations, and is not confined to acted expressions.	\N	\N
25247311	Neonatal necrotizing enterocolitis (NEC) is associated with an increased incidence of poor neurodevelopment. The knowledge of underlying neurophysiology is very limited, and the influence of NEC on the preterm brainstem is very poorly understood. To assess the effect of NEC on the immature auditory brainstem by excluding any possible confounding effect of preterm birth. We recorded and analyzed brainstem auditory evoked response (BAER) at different click rates in preterm babies (30-34 weeks gestation) after NEC. The results were compared with those in age-matched healthy preterm babies who had no NEC. At click rate 21/s, the latencies of BAER waves I and III in the preterm NEC babies were similar to those babies without NEC. However, wave V latency was longer in the NEC babies than in those without NEC. The I-V interpeak interval was also longer in the NEC babies than in those without NEC. These abnormalities were persistent at higher click rates 51 and 91/s. Wave I amplitude in the preterm NEC babies did not differ significantly from that in those without NEC, but wave III and V amplitudes were smaller than in those without NEC at all 21-91/s clicks. Compared with healthy preterm babies, preterm babies after NEC showed a major increase in wave V latency and I-V interval at all 21-91/s clicks. Brainstem auditory function is impaired in preterm NEC babies after excluding the possible confounding effect of preterm birth. Neonatal NEC and associated perinatal conditions adversely affect the premature brainstem.	\N	\N
25248101	Using an auditory variant of task switching, we examined the ability to intentionally switch attention in a dichotic-listening task. In our study, participants responded selectively to one of two simultaneously presented auditory number words (spoken by a female and a male, one for each ear) by categorizing its numerical magnitude. The mapping of gender (female vs. male) and ear (left vs. right) was unpredictable. The to-be-attended feature for gender or ear, respectively, was indicated by a visual selection cue prior to auditory stimulus onset. In Experiment 1, explicitly cued switches of the relevant feature dimension (e.g., from gender to ear) and switches of the relevant feature within a dimension (e.g., from male to female) occurred in an unpredictable manner. We found large performance costs when the relevant feature switched, but switches of the relevant feature dimension incurred only small additional costs. The feature-switch costs were larger in ear-relevant than in gender-relevant trials. In Experiment 2, we replicated these findings using a simplified design (i.e., only within-dimension switches with blocked dimensions). In Experiment 3, we examined preparation effects by manipulating the cueing interval and found a preparation benefit only when ear was cued. Together, our data suggest that the large part of attentional switch costs arises from reconfiguration at the level of relevant auditory features (e.g., left vs. right) rather than feature dimensions (ear vs. gender). Additionally, our findings suggest that ear-based target selection benefits more from preparation time (i.e., time to direct attention to one ear) than gender-based target selection.	\N	\N
25255036	In human face-to-face communication, language comprehension is a multi-modal, situated activity. However, little is known about how we combine information from different modalities during comprehension, and how perceived communicative intentions, often signaled through visual signals, influence this process. We explored this question by simulating a multi-party communication context in which a speaker alternated her gaze between two recipients. Participants viewed speech-only or speech+gesture object-related messages when being addressed (direct gaze) or unaddressed (gaze averted to other participant). They were then asked to choose which of two object images matched the speaker's preceding message. Unaddressed recipients responded significantly more slowly than addressees for speech-only utterances. However, perceiving the same speech accompanied by gestures sped unaddressed recipients up to a level identical to that of addressees. That is, when unaddressed recipients' speech processing suffers, gestures can enhance the comprehension of a speaker's message. We discuss our findings with respect to two hypotheses attempting to account for how social eye gaze may modulate multi-modal language comprehension.	\N	\N
25261772	Amazing progress has been made in providing useful hearing to hearing-impaired individuals using cochlear implants, but challenges remain. One such challenge is understanding the effects of partial degeneration of the auditory nerve, the target of cochlear implant stimulation. Here we review studies from our human and animal laboratories aimed at characterizing the health of the implanted cochlea and the auditory nerve. We use the data on cochlear and neural health to guide rehabilitation strategies. The data also motivate the development of tissue-engineering procedures to preserve or build a healthy cochlea and improve performance obtained by cochlear implant recipients or eventually replace the need for a cochlear implant. This article is part of a Special Issue entitled <Lasker Award>.	\N	\N
25263528	Although children can use social categories to intelligently select informants, children's preference for in-group informants has not been consistently demonstrated across age and context. This research clarifies the extent to which children use social categories to guide learning by presenting participants with a live or video-recorded action demonstration by a linguistic in-group and/or out-group model. Participants' (N = 104) propensity to imitate these actions was assessed. Nineteen-month-olds did not selectively imitate the actions of the in-group model in live contexts, though in-group preferences were found after watching the demonstration on video. Three-year-olds selectively imitated the actions demonstrated by the in-group member regardless of context. These results indicate that in-group preferences have a more nuanced effect on social learning than previous research has indicated.	\N	\N
25269621	Despite the fact that no invariant acoustic property corresponds to a single stop consonant coupled with different vowels (e.g., [da], [de], and [du]), adults effortlessly identify the same consonant embedded in different syllables. In so doing, they solve the invariance problem. Can 3- and 6-month-olds solve it as well? To answer this question, we developed a novel methodology based on pupillometry. In Experiment 1, we demonstrated for the first time that infants are sensitive to the distinction between frequent and infrequent acoustic stimuli, showing greater pupil dilation in response to infrequent stimuli. Building on this effect, in Experiment 2, we showed that 6-month-olds, but not 3-month-olds, solve the invariance problem. Moreover, this ability develops before, and therefore independently of, the ability to produce well-formed syllables.	\N	\N
25275862	To compare within-subject bilateral-binaural and bimodal complementary abilities between bimodal (cochlear implant and hearing aid; CI/HA) and bilateral CI hearing (CI/CI), thereby enabling better-informed counseling of experienced CI/HA users contemplating contralateral implantation. Comparative within-subject case review. Outpatient hearing clinic. Ten experienced adult CI/HA users with severe-to-profound hearing loss in the HA ear, who converted to CI/CI between 2 and 11 years after initial implantation. Task-specific testing of bilateral-binaural hearing (sound lateralization, binaural summation/redundancy/unmasking, head-shadow effect), bimodal complementary benefit (contribution of low-frequency information), and a self-report Speech, Spatial, and Qualities of Hearing (SSQ) questionnaire, all before and 1 year after contralateral cochlear implantation. Test result differences between CI/HA and CI/CI conditions. CI/CI hearing was better than CI/HA for speech lateralization and for perception of semantically unpredictable sentences in speech noise with speech at 0 degrees and noise at +90 degrees azimuth on the old CI side. CI/HA was better than CI/CI only for differences between perception of natural prosody speech and of speech with flattened fundamental frequency (F0) contour with speech and noise in front (at 0 degrees azimuth). Total scores on the SSQ questionnaire were higher in CI/CI than in CI/HA users. Counseling regarding contralateral implantation for CI/HA users with severe-to-profound hearing loss in the HA ear, though generally positive, should consider individual functional needs, and cover expectations about the expected trade-off between gaining improved understanding and speech lateralization in challenging listening conditions and losing some low-frequency cues still available with CI/HA hearing.	\N	\N
25280122	Both psychological stress and predictive signals relating to expected sensory input are believed to influence perception, an influence which, when disrupted, may contribute to the generation of auditory hallucinations. The effect of stress and semantic expectation on auditory perception was therefore examined in healthy participants using an auditory signal detection task requiring the detection of speech from within white noise. Trait anxiety was found to predict the extent to which stress influenced response bias, resulting in more anxious participants adopting a more liberal criterion, and therefore experiencing more false positives, when under stress. While semantic expectation was found to increase sensitivity, its presence also generated a shift in response bias towards reporting a signal, suggesting that the erroneous perception of speech became more likely. These findings provide a potential cognitive mechanism that may explain the impact of stress on hallucination-proneness, by suggesting that stress has the tendency to alter response bias in highly anxious individuals. These results also provide support for the idea that top-down processes such as those relating to semantic expectation may contribute to the generation of auditory hallucinations.	\N	\N
25281311	Interactions between ourselves and the external world are mediated by a multisensory representation of the space surrounding the body, i.e. the peripersonal space (PPS). In particular, a special interplay is observed among tactile stimuli delivered on a body part, e.g. the hand, and visual or auditory external inputs presented close, but not far, from the same body part, e.g. within hand PPS. This coding of multisensory stimuli as a function of their distance from the hand has a role in upper limb actions. However, it remains unclear whether PPS representation affects the motor system only when stimuli occur specifically at the hand location or when they move within a continuous portion of space where the hand can potentially act. Here, in order to study these two alternatively hypotheses, we assessed the critical distance at which moving sounds have a direct effect on hand corticospinal excitability by using Transcranial Magnetic Stimulation (TMS). Specifically, TMS single pulses were delivered when a sound source was perceived at six different positions in space: from very close to subjects' hand (15 cm) to far away (90 cm). Moreover, sound direction was manipulated to test if stimuli approaching and receding from the hand might have the same relevance for the motor system. MEPs amplitude was enhanced when sounds were delivered within a limited distance from the hand (around 60 cm) as compared to when the sounds were beyond this space. This effect captures the spatial boundaries within which PPS representation modulates hand cortico-motor excitability. This spatially-dependent modulation of corticospinal activity was not further affected by the sound direction. Such findings support a strict link between the multisensory representation of the space around the body and the motor representation of potential approaching or defensive acts within that space.	\N	\N
25282057	A fundamental question in language development is how infants start to assign meaning to words. Here, using three Electroencephalogram (EEG)-based measures of brain activity, we establish that preverbal 11-month-old infants are sensitive to the non-arbitrary correspondences between language sounds and concepts, that is, to sound symbolism. In each trial, infant participants were presented with a visual stimulus (e.g., a round shape) followed by a novel spoken word that either sound-symbolically matched ("moma") or mismatched ("kipi") the shape. Amplitude increase in the gamma band showed perceptual integration of visual and auditory stimuli in the match condition within 300 msec of word onset. Furthermore, phase synchronization between electrodes at around 400 msec revealed intensified large-scale, left-hemispheric communication between brain regions in the mismatch condition as compared to the match condition, indicating heightened processing effort when integration was more demanding. Finally, event-related brain potentials showed an increased adult-like N400 response - an index of semantic integration difficulty - in the mismatch as compared to the match condition. Together, these findings suggest that 11-month-old infants spontaneously map auditory language onto visual experience by recruiting a cross-modal perceptual processing system and a nascent semantic network within the first year of life.	\N	\N
25301567	Previous research has shown that the human auditory system continuously monitors its acoustic environment, detecting a variety of irregularities (e.g., deviance from prior stimulation regularity in pitch, loudness, duration, and (perceived) sound source location). Detection of irregularities can be inferred from a component of the event-related brain potential (ERP), referred to as the mismatch negativity (MMN), even in conditions in which participants are instructed to ignore the auditory stimulation. The current study extends previous findings by demonstrating that auditory irregularities brought about by a change in room acoustics elicit a MMN in a passive oddball protocol (acoustic stimuli with differing room acoustics, that were otherwise identical, were employed as standard and deviant stimuli), in which participants watched a fiction movie (silent with subtitles). While the majority of participants reported no awareness for any changes in the auditory stimulation, only one out of 14 participants reported to have become aware of changing room acoustics or sound source location. Together, these findings suggest automatic monitoring of room acoustics.	\N	\N
25305712	The pathophysiology of nonfluent primary progressive aphasia (nfvPPA) remains poorly understood. Here, we compared quantitatively speech parameters in patients with nfvPPA versus healthy older individuals under altered auditory feedback, which has been shown to modulate normal speech output. Patients (n=15) and healthy volunteers (n=17) were recorded while reading aloud under delayed auditory feedback [DAF] with latency 0, 50 or 200 ms and under DAF at 200 ms plus 0.5 octave upward pitch shift. DAF in healthy older individuals was associated with reduced speech rate and emergence of speech sound errors, particularly at latency 200 ms. Up to a third of the healthy older group under DAF showed speech slowing and frequency of speech sound errors within the range of the nfvPPA cohort. Our findings suggest that (in addition to any anterior, primary language output disorder) these key features of nfvPPA may reflect distorted speech input signal processing, as simulated by DAF. DAF may constitute a novel candidate pathophysiological model of posterior dorsal cortical language pathway dysfunction in nfvPPA.	\N	\N
25306203	Reduced auditory P300 amplitude is a robust schizophrenia deficit exhibiting the qualities of a viable genetic endophenotype. These include heritability, test-retest reliability, and trait-like stability. Recent evidence suggests that P300 may also serve as a predictive biomarker for transition to psychosis during the schizophrenia prodrome. Historically, the utility of the P300 has been limited by its clinical nonspecificity, cross-site measurement variability, and required EEG expertise. The Consortium on the Genetics of Schizophrenia (COGS-2) study provided an opportunity to examine the consistency of the measure across multiple sites with varying degrees of EEG experience, and to identify important modulating factors that contribute to measurement variability. Auditory P300 was acquired from 649 controls and 587 patients at 5 sites. An overall patient deficit was observed with effect size 0.62. Each site independently observed a significant patient deficit, but site differences also existed. In patients, site differences reflected clinical differences in positive symptomatology and functional capacity. In controls, site differences reflected differences in racial stratification, smoking and substance use history. These factors differentially suppressed the P300 response, but only in control subjects. This led to an attenuated patient-control difference among smokers and among African Americans with history of substance use. These findings indicate that the P300 can be adequately assessed quantitatively, across sites, without substantial EEG expertise. Measurements are suitable for both genetic endophenotype analyses and studies of psychosis risk and conversion. However, careful attention must be given to selection of appropriate comparison samples to avoid misleading false negative results.	\N	\N
25313714	Perception of spoken language requires attention to acoustic as well as visible phonetic information. This article reviews the known differences in audiovisual speech perception in children with autism spectrum disorders (ASD) and specifies the need for interventions that address this construct. Elements of an audiovisual training program are described. This researcher-developed program delivered via an iPad app presents natural speech in the context of increasing noise, but supported with a speaking face. Children are cued to attend to visible articulatory information to assist in perception of the spoken words. Data from four children with ASD ages 8-10 are presented showing that the children improved their performance on an untrained auditory speech-in-noise task.	\N	\N
25319676	Subjective tinnitus is the perception of sound in the absence of a corresponding external sound for which there is no known medical etiology. For a minority of individuals with tinnitus, the condition impacts their ability to lead a normal lifestyle and is severely debilitating. There is no known cure for tinnitus, so current therapy focuses on reducing the effect of tinnitus on the patient's quality of life. Tinnitus retraining therapy (TRT) uses nonpsychiatric tinnitus-specific educational counseling and sound therapy in a habituation-based protocol to reduce the patient's tinnitus-evoked negative reaction to, and awareness of, the tinnitus, with the ultimate goal of reducing the tinnitus impact on the patient's quality of life. Some studies support the efficacy of TRT, but no trial to date has compared TRT with the current standard of care or evaluated the separate contributions of TRT counseling and sound therapy. The Tinnitus Retraining Therapy Trial (TRTT) is a randomized, double-blind, placebo-controlled, multicenter trial for individuals with intolerable tinnitus. The TRTT is enrolling active-duty and retired military personnel and their dependents with functionally adequate hearing sensitivity and severe tinnitus at US Air Force, Navy, and Army medical centers. Eligible study participants are randomized to TRT, partial TRT, or standard care to determine the efficacy of TRT and its components (TRT counseling and sound therapy). The primary outcome is change in score on the Tinnitus Questionnaire assessed longitudinally between baseline and follow-up (3, 6, 12, and 18 months following treatment). Secondary outcomes include subscale score changes in the Tinnitus Questionnaire, overall and subscale score changes in the Tinnitus Functional Index and Tinnitus Handicap Inventory, and change in the visual analog scale of the TRT Interview Form. Audiological outcomes include tinnitus pitch and loudness match and measures of loudness discomfort levels. The incidence of depression as a safety measure is assessed at each visit using the Beck Depression Inventory Fast Screen. Clinicaltrials.gov NCT01177137.	\N	\N
25324150	Recent literature reviews have highlighted the need to better understand the relation between speaker and listener behavior when teaching learners with autism spectrum disorders (ASD). The current study used a modified parallel-treatments design to compare directly the degree to which tact and listener behavior emerged during instruction in the opposite relation for 4 children with ASD. Results showed tact training to be either equally or more efficient than listener training for all participants. However, varied patterns of emergent responding across participants indicate a need for further research. Data on collateral responding during instruction did not suggest that the presence or absence of overt collateral behaviors were predictive of emergence. The results highlight the importance for clinicians and educators to assess emergent tact and listener repertoires periodically.	\N	\N
25324726	Our concepts of sound localization in the vertebrate brain are widely based on the general assumption that both the ability to detect air-borne sounds and the neuronal processing are homologous in archosaurs (present day crocodiles and birds) and mammals. Yet studies repeatedly report conflicting results on the neuronal circuits and mechanisms, in particular the role of inhibition, as well as the coding strategies between avian and mammalian model systems. Here we argue that mammalian and avian phylogeny of spatial hearing is characterized by a convergent evolution of hearing air-borne sounds rather than by homology. In particular, the different evolutionary origins of tympanic ears and the different availability of binaural cues in early mammals and archosaurs imposed distinct constraints on the respective binaural processing mechanisms. The role of synaptic inhibition in generating binaural spatial sensitivity in mammals is highlighted, as it reveals a unifying principle of mammalian circuit design for encoding sound position. Together, we combine evolutionary, anatomical and physiological arguments for making a clear distinction between mammalian processing mechanisms and coding strategies and those of archosaurs. We emphasize that a consideration of the convergent nature of neuronal mechanisms will significantly increase the explanatory power of studies of spatial processing in both mammals and birds.	\N	\N
25325783	Visual crowding is generally thought to affect recognition mostly or only at the level of feature combination. Calling this assertion into question, recent studies have shown that if a target object and its flankers belong to different categories crowding is weaker than if they belong to the same category. Nevertheless, these results can be explained in terms of featural differences between categories. The current study tests if category-level (i.e., high-level) interference in crowding occurs when featural differences are controlled for. First, replicating previous results, we found lower critical spacing for targets and flankers belonging to different categories. Second, we observed the same, albeit weaker, category-specific effect when objects in both categories had the exact same feature set, suggesting that category-specific effects persist even when featural differences are fully controlled for. Third, we manipulated the semantic content of the flankers while keeping their feature set constant, by using upright or rotated objects, and found that meaning modulated crowding. An exclusively feature-based account of crowding would predict no differences due to such changes in meaning. We conclude that crowding results from not only the well-documented feature-level interactions but also additional interactions at a level where objects are grouped by meaning.	\N	\N
25326606	What is the perceptual fate of invisible stimuli-are they processed at all and does their processing have consequences for the perception of other stimuli? As has been shown previously in the somatosensory system, even stimuli that are too weak to be consciously detected can influence our perception: Subliminal stimulation impairs perception of near-threshold stimuli and causes a functional deactivation in the somatosensory cortex. In a recent study, we showed that subliminal visual stimuli lead to similar responses, indicated by an increase in alpha-band power as measured with electroencephalography (EEG). In the current study, we investigated whether a behavioral inhibitory mechanism also exists within the visual system. We tested the detection of peripheral visual target stimuli under three different conditions: Target stimuli were presented alone or embedded in a concurrent train of subliminal stimuli either at the same location as the target or in the opposite hemifield. Subliminal stimuli were invisible due to their low contrast, not due to a masking procedure. We demonstrate that target detection was impaired by the subliminal stimuli, but only when they were presented at the same location as the target. This finding indicates that subliminal, low-intensity stimuli induce a similar inhibitory effect in the visual system as has been observed in the somatosensory system. In line with previous reports, we propose that the function underlying this effect is the inhibition of spurious noise by the visual system.	\N	\N
25332098	Development and evolution of auditory hindbrain nuclei are two major unsolved issues in hearing research. Recent characterization of transgenic mice identified the rhombomeric origins of mammalian auditory nuclei and unraveled genes involved in their formation. Here, we provide an overview on these data by assembling them into rhombomere-specific gene regulatory networks (GRNs), as they underlie developmental and evolutionary processes. To explore evolutionary mechanisms, we compare the GRNs operating in the mammalian auditory hindbrain with data available from the inner ear and other vertebrate groups. Finally, we propose that the availability of genomic sequences from all major vertebrate taxa and novel genetic techniques for non-model organisms provide an unprecedented opportunity to investigate development and evolution of the auditory hindbrain by comparative molecular approaches. The dissection of the molecular mechanisms leading to auditory structures will also provide an important framework for auditory processing disorders, a clinical problem difficult to tackle so far. These data will, therefore, foster basic and clinical hearing research alike.	\N	\N
25344346	It is increasingly recognized that motor routines dynamically shape the processing of sensory inflow (e.g., when hand movements are used to feel a texture or identify an object). In the present research, we captured the shaping of auditory perception by movement in humans by taking advantage of a specific context: music. Participants listened to a repeated rhythmical sequence before and after moving their bodies to this rhythm in a specific meter. We found that the brain responses to the rhythm (as recorded with electroencephalography) after body movement were significantly enhanced at frequencies related to the meter to which the participants had moved. These results provide evidence that body movement can selectively shape the subsequent internal representation of auditory rhythms.	\N	\N
25346316	In the United States, falls are the leading cause of accidental deaths in adults aged over 65 years. Epidemiologic studies indicate that there is a correlation between hearing loss and the risk of falling among older people. The vestibular, proprioceptive, and visual systems are known to contribute to postural stability, but the contribution of audition to maintaining balance has not yet been determined. Cross-sectional study to measure postural stability in bilateral hearing-aid users aged over 65 years in aided and unaided conditions. Balance was assessed using the Romberg on foam test and the tandem stance test. Tests were administered in the presence of a point-source broadband white-noise sound (0-4 kHz) source in both unaided and aided conditions in the dark. Subjective measures of balance were made using the Activities-specific Balance Confidence Scale. Performance was significantly better in the aided than the unaided condition (P = 0.005 for both tests). No statistically significant relationship between improvement in balance, and hearing was identified. Participants did not report that they perceived a difference in balance between the two conditions. These results indicate that hearing aids are a novel treatment modality for imbalance in older adults with hearing loss and suggest that wearing hearing aids may offer a significant public-health benefit for avoiding falls in this population.	\N	\N
25350757	This study used event-related potentials (ERPs) to assess effects of low-level prenatal lead exposure on auditory recognition memory in 2-month-old infants. Infants were divided into four groups according to cord-blood lead concentration: (1) <2.00 μ g/dL, (2) 2.00-2.99 μ g/dL, (3) 3.0-3.7 μ g/dL, and (4) ≥3.7 μ g/dL. The first group showed the normally expected differences in P2, P750, and late slow wave (LSW) amplitudes elicited by mothers' and strangers' voices. These differences were not observed for one or more ERP components in the other groups. Thus, there was electrophysiological evidence of poorer auditory recognition memory at 2 months with cord-blood lead ≥2.00 μ g/dL.	\N	\N
25358027	To evaluate a speech-processing strategy in which the lowest frequency channel is conveyed using an asymmetric pulse shape and "phantom stimulation", where current is injected into one intra-cochlear electrode and where the return current is shared between an intra-cochlear and an extra-cochlear electrode. This strategy is expected to provide more selective excitation of the cochlear apex, compared to a standard strategy where the lowest-frequency channel is conveyed by symmetric pulses in monopolar mode. In both strategies all other channels were conveyed by monopolar stimulation. Within-subjects comparison between the two strategies. Four experiments: (1) discrimination between the strategies, controlling for loudness differences, (2) consonant identification, (3) recognition of lowpass-filtered sentences in quiet, (4) sentence recognition in the presence of a competing speaker. Eight users of the Advanced Bionics CII/Hi-Res 90k cochlear implant. Listeners could easily discriminate between the two strategies but no consistent differences in performance were observed. The proposed method does not improve speech perception, at least in the short term.	\N	\N
25358716	Information processing of all acoustic stimuli involves temporal lobe regions referred to as auditory cortices, which receive direct afferents from the auditory thalamus. However, the perception of music (as well as speech or spoken language) is a complex process that also involves secondary and association cortices that conform a large functional network. Using different analytical techniques and stimulation paradigms, several studies have shown that certain areas are particularly sensitive to specific acoustic characteristics inherent to music (e.g., rhythm). This chapter reviews the functional anatomy of the auditory cortices, and highlights specific experiments that suggest the existence of distinct cortical networks for the perception of music and speech.	\N	\N
25373970	Otoacoustic emission (OAE) tests of the medial-olivocochlear reflex (MOCR) in humans were assessed for viability as clinical assays. Two reflection-source OAEs [TEOAEs: transient-evoked otoacoustic emissions evoked by a 47 dB sound pressure level (SPL) chirp; and discrete-tone SFOAEs: stimulus-frequency otoacoustic emissions evoked by 40 dB SPL tones, and assessed with a 60 dB SPL suppressor] were compared in 27 normal-hearing adults. The MOCR elicitor was a 60 dB SPL contralateral broadband noise. An estimate of MOCR strength, MOCR%, was defined as the vector difference between OAEs measured with and without the elicitor, normalized by OAE magnitude (without elicitor). An MOCR was reliably detected in most ears. Within subjects, MOCR strength was correlated across frequency bands and across OAE type. The ratio of across-subject variability to within-subject variability ranged from 2 to 15, with wideband TEOAEs and averaged SFOAEs giving the highest ratios. MOCR strength in individual ears was reliably classified into low, normal, and high groups. SFOAEs using 1.5 to 2 kHz tones and TEOAEs in the 0.5 to 2.5 kHz band gave the best statistical results. TEOAEs had more clinical advantages. Both assays could be made faster for clinical applications, such as screening for individual susceptibility to acoustic trauma in a hearing-conservation program.	\N	\N
25385771	The ability to perceive a regular beat in music and synchronize to this beat is a widespread human skill. Fundamental to musical behaviour, beat and meter refer to the perception of periodicities while listening to musical rhythms and often involve spontaneous entrainment to move on these periodicities. Here, we present a novel experimental approach inspired by the frequency-tagging approach to understand the perception and production of rhythmic inputs. This approach is illustrated here by recording the human electroencephalogram responses at beat and meter frequencies elicited in various contexts: mental imagery of meter, spontaneous induction of a beat from rhythmic patterns, multisensory integration and sensorimotor synchronization. Collectively, our observations support the view that entrainment and resonance phenomena subtend the processing of musical rhythms in the human brain. More generally, they highlight the potential of this approach to help us understand the link between the phenomenology of musical beat and meter and the bias towards periodicities arising under certain circumstances in the nervous system. Entrainment to music provides a highly valuable framework to explore general entrainment mechanisms as embodied in the human brain.	\N	\N
25385777	Physiological rhythms are sensitive to social interactions and could contribute to defining social rhythms. Nevertheless, our knowledge of the implications of breathing in conversational turn exchanges remains limited. In this paper, we addressed the idea that breathing may contribute to timing and coordination between dialogue partners. The relationships between turns and breathing were analysed in unconstrained face-to-face conversations involving female speakers. No overall relationship between breathing and turn-taking rates was observed, as breathing rate was specific to the subjects' activity in dialogue (listening versus taking the turn versus holding the turn). A general inter-personal coordination of breathing over the whole conversation was not evident. However, specific coordinative patterns were observed in shorter time-windows when participants engaged in taking turns. The type of turn-taking had an effect on the respective coordination in breathing. Most of the smooth and interrupted turns were taken just after an inhalation, with specific profiles of alignment to partner breathing. Unsuccessful attempts to take the turn were initiated late in the exhalation phase and with no clear inter-personal coordination. Finally, breathing profiles at turn-taking were different than those at turn-holding. The results support the idea that breathing is actively involved in turn-taking and turn-holding.	\N	\N
25401380	Interference between a target and simultaneous maskers occurs both at the cochlear level through energetic masking and more centrally through informational masking (IM). Hence, quantifying the amount of IM requires a strict control of the energetic component. Presenting target and maskers on different sides (i.e., dichotically) reduces energetic masking but provides listeners with important lateralization cues that also drastically reduce IM. The main purpose of this study (Experiment 1) was to evaluate a "switch" manipulation aiming at restoring most of the IM despite dichotic listening. Experiment 2 was designed to investigate the source of the difficulty induced by this switching dichotic condition. In Experiment 1, the authors presented 60 normal-hearing young adults with a detection task in which a regularly repeating target was embedded in a randomly varying background masker. The authors evaluated spatial masking release induced by three different dichotic listening conditions in comparison with a diotic baseline. Dichotic stimuli were presented in either a nonswitching or a switching condition. In the latter case, the presentation sides of dichotic target and maskers alternated several times throughout 10 sec sequences. The impact of the number of switches on IM was investigated parametrically, with both pure and complex tone sequences. In Experiment 2, the authors compared performance of 13 young, normal-hearing listeners in a monotic and dichotic version of the rapidly switching condition, using pure-tone sequences. When target and maskers switched rapidly within sequences, IM was significantly stronger than in nonswitching dichotic sequences and was comparable with the masking effect induced by diotic sequences. Furthermore, Experiment 2 suggests that rapidly switching target and maskers prevent listeners from relying on lateralization cues inherent to the dichotic condition, hence preserving important amounts of IM. This paradigm thus provides an original tool to isolate IM in signal and maskers having overlapping spectra.	\N	\N
25412406	Speech comprehension studies have generally focused on the isolation and function of regions with positive blood oxygen level dependent (BOLD) signals with respect to a resting baseline. Although regions with negative BOLD signals in comparison to a resting baseline have been reported in language-related tasks, their relationship to regions of positive signals is not fully appreciated. Based on the emerging notion that the negative signals may represent an active function in language tasks, the authors test the hypothesis that negative BOLD signals during receptive language are more associated with comprehension than content-free versions of the same stimuli. Regions associated with comprehension of speech were isolated by comparing responses to passive listening to natural speech to two incomprehensible versions of the same speech: one that was digitally time reversed and one that was muffled by removal of high frequencies. The signal polarity was determined by comparing the BOLD signal during each speech condition to the BOLD signal during a resting baseline. As expected, stimulation-induced positive signals relative to resting baseline were observed in the canonical language areas with varying signal amplitudes for each condition. Negative BOLD responses relative to resting baseline were observed primarily in frontoparietal regions and were specific to the natural speech condition. However, the BOLD signal remained indistinguishable from baseline for the unintelligible speech conditions. Variations in connectivity between brain regions with positive and negative signals were also specifically related to the comprehension of natural speech. These observations of anticorrelated signals related to speech comprehension are consistent with emerging models of cooperative roles represented by BOLD signals of opposite polarity.	\N	\N
25415467	To determine differences in speech perception outcomes for patients who received a CI422 and a Contour cochlear implant. Retrospective case review. Tertiary referral center. Thirty-two adults who underwent cochlear implantation. Cochlear implantation using a CI422 or Contour device. Bamford-Kowal-Bench (BKB) speech perception scores at 3 and 9 months after activation. The mean BKB scores at 3 months for the CI422 device were 86.0% in quiet and 55.1% in noise. This compares with 86.0% in quiet and 62.3% in noise for the Contour device. At 9 months, the mean BKB scores were 85.9% in quiet and 67.1% in noise for the CI422 and 90.1% in quiet and 77.6% in noise for the Contour device. There was no statistically significant difference (p > 0.05) between speech perception outcomes at 3 or 9 months. This study suggests that CI422 and Contour electrode both improve speech perception outcomes postoperatively, and there does not appear to be any significant difference in outcome between the two types of devices.	\N	\N
25415938	Embodied music cognition stresses the role of the human body as mediator for the encoding and decoding of musical expression. In this paper, we set up a low dimensional functional model that accounts for 70% of the variability in the expressive body movement responses to music. With the functional principal component analysis, we modeled individual body movements as a linear combination of a group average and a number of eigenfunctions. The group average and the eigenfunctions are common to all subjects and make up what we call the commonalities. An individual performance is then characterized by a set of scores (the individualities), one score per eigenfunction. The model is based on experimental data which finds high levels of coherence/consistency between participants when grouped according to musical education. This shows an ontogenetic effect. Participants without formal musical education focus on the torso for the expression of basic musical structure (tempo). Musically trained participants decode additional structural elements in the music and focus on body parts having more degrees of freedom (such as the hands). Our results confirm earlier studies that different body parts move differently along with the music.	\N	\N
25421408	Individuals lip read themselves more accurately than they lip read others when only the visual speech signal is available (Tye-Murray et al., Psychonomic Bulletin & Review, 20, 115-119, 2013). This self-advantage for vision-only speech recognition is consistent with the common-coding hypothesis (Prinz, European Journal of Cognitive Psychology, 9, 129-154, 1997), which posits (1) that observing an action activates the same motor plan representation as actually performing that action and (2) that observing one's own actions activates motor plan representations more than the others' actions because of greater congruity between percepts and corresponding motor plans. The present study extends this line of research to audiovisual speech recognition by examining whether there is a self-advantage when the visual signal is added to the auditory signal under poor listening conditions. Participants were assigned to sub-groups for round-robin testing in which each participant was paired with every member of their subgroup, including themselves, serving as both talker and listener/observer. On average, the benefit participants obtained from the visual signal when they were the talker was greater than when the talker was someone else and also was greater than the benefit others obtained from observing as well as listening to them. Moreover, the self-advantage in audiovisual speech recognition was significant after statistically controlling for individual differences in both participants' ability to benefit from a visual speech signal and the extent to which their own visual speech signal benefited others. These findings are consistent with our previous finding of a self-advantage in lip reading and with the hypothesis of a common code for action perception and motor plan representation.	\N	\N
25436670	Sound waves emitted by two or more simultaneous sources reach the ear as one complex waveform. Auditory scene analysis involves parsing a complex waveform into separate perceptual representations of the sound sources [Bregman, A. S. Auditory scene analysis: The perceptual organization of sounds. London: MIT Press, 1990]. Harmonicity provides an important cue for auditory scene analysis. Normally, harmonics at integer multiples of a fundamental frequency are perceived as one sound with a pitch corresponding to the fundamental frequency. However, when one harmonic in such a complex, pitch-evoking sound is sufficiently mistuned, that harmonic emerges from the complex tone and is perceived as a separate auditory object. Previous work has shown that the percept of two objects is indexed in both children and adults by the object-related negativity component of the ERP derived from EEG recordings [Alain, C., Arnott, S. T., & Picton, T. W. Bottom-up and top-down influences on auditory scene analysis: Evidence from event-related brain potentials. Journal of Experimental Psychology: Human Perception and Performance, 27, 1072-1089, 2001]. Here we examine the emergence of object-related responses to an 8% harmonic mistuning in infants between 2 and 12 months of age. Two-month-old infants showed no significant object-related response. However, in 4- to 12-month-old infants, a significant frontally positive component was present, and by 8-12 months, a significant frontocentral object-related negativity was present, similar to that seen in older children and adults. This is in accordance with previous research demonstrating that infants younger than 4 months of age do not integrate harmonic information to perceive pitch when the fundamental is missing [He, C., Hotson, L., & Trainor, L. J. Maturation of cortical mismatch mismatch responses to occasional pitch change in early infancy: Effects of presentation rate and magnitude of change. Neuropsychologia, 47, 218-229, 2009]. The results indicate that the ability to use harmonic information to segregate simultaneous sounds emerges at the cortical level between 2 and 4 months of age.	\N	\N
25445239	In this study we validate passive language fMRI protocols designed for clinical application in pediatric epilepsy surgical planning as they do not require overt participation from patients. We introduced a set of quality checks that assess reliability of noninvasive fMRI mappings utilized for clinical purposes. We initially compared two fMRI language mapping paradigms, one active in nature (requiring participation from the patient) and the other passive in nature (requiring no participation from the patient). Group-level analysis in a healthy control cohort demonstrated similar activation of the putative language centers of the brain in the inferior frontal (IFG) and temporoparietal (TPG) regions. Additionally, we showed that passive language fMRI produced more left-lateralized activation in TPG (LI=+0.45) compared to the active task; with similarly robust left-lateralized IFG (LI=+0.24) activations using the passive task. We validated our recommended fMRI mapping protocols in a cohort of 15 pediatric epilepsy patients by direct comparison against the invasive clinical gold-standards. We found that language-specific TPG activation by fMRI agreed to within 9.2mm to subdural localizations by invasive functional mapping in the same patients, and language dominance by fMRI agreed with Wada test results at 80% congruency in TPG and 73% congruency in IFG. Lastly, we tested the recommended passive language fMRI protocols in a cohort of very young patients and confirmed reliable language-specific activation patterns in that challenging cohort. We concluded that language activation maps can be reliably achieved using the passive language fMRI protocols we proposed even in very young (average 7.5 years old) or sedated pediatric epilepsy patients.	\N	\N
25449865	Utilizing the high temporal resolution of event-related potentials (ERPs), we examined the effects of temporal reliability of sounds on visual detection. Significantly faster reaction times to visual target stimuli were observed when reliable temporal information was provided by a task-irrelevant auditory stimulus. Three main ERP components related to the effects of auditory temporal reliability were found: the first at 180-240 ms over a wide central area, the second at 300-400 ms over an anterior area, and the third at 300-380 ms over bilateral temporal areas. Our results support the hypothesis that temporal reliability affects visual detection and indicate that auditory facilitation of visual detection is partly due to spread of attention and thus results from implicit temporal linking of auditory and visual information at a relatively late processing stage.	\N	\N
25473957	To examine the differences in quality of life for vestibular schwannoma patients undergoing conservative management, gamma knife, and surgery. Vestibular schwannoma patients without a diagnosis of NF2. Vestibular schwannoma treatment or conservative management. Penn Acoustic Neuroma Quality of Life (PANQOL) survey scores (0-100). One hundred eighty-six patients (98 conservative, 49 gamma knife, 39 surgery) were included. Mean patient age (years) of the surgery group (49 ± 14) was significantly younger than both the conservative (58 ± 13) and gamma knife group (59 ± 12) (p < 0.001). Mean follow-up time was 2.6 years.Tumor size (mm) was found to be significantly different between the conservative (8 ± 4.8), gamma knife (18 ± 5.9), and surgery (22 ± 8.3) groups (p < 0.001). Speech recognition threshold and speech discrimination percentage were significantly better for the conservative group compared to the gamma knife or surgery groups (p < 0.001).The hearing domain scores seemed better for the conservative group (62 ± 26) when compared to the surgery group (47 ± 25). The general and total domain scores were similar for all treatment groups, whereas the quality-of-life scores for gamma knife and surgery were similar. Although surgery groups' significantly larger tumors and worse hearing were apparent in specific PANQOL domains, all patients achieved a similar general level of quality of life.	\N	\N
25474416	One of the major complaints of people with a single-sided deafness is the inability to localize sound sources. Evidence suggests that subjects with a hearing loss can benefit from the use of a cochlear implant (CI) in sound localization. This study aimed to determine the effect of CI use on localization ability in unilaterally deafened subjects. Sixteen adult subjects with postlingual unilateral deafness, fitted with a CI on the deaf side, were included in this study. The auditory speech sounds evaluation (A§E) localization test was used to determine localization with a CI on (binaural) and a CI off (monaural). The root mean square error was used as a measure of the subject's localization performance. Stratified analyses were performed to test the influence of gender, age of implantation (<55 years and >55 years), and the duration of deafness (<10 years and >10 years) on localization ability. Subjects with a CI on localized significantly better than without a CI. Gender, age, and the duration of deafness had no effect on the localization ability of the subjects. Cochlear implantation is effective in improving localization abilities in subjects with unilateral deafness. The root mean square error dropped significantly with binaural hearing compared to monaural hearing.	\N	\N
25477777	For multimodal Human-Computer Interaction (HCI), it is very useful to identify the modalities on which the user is currently processing information. This would enable a system to select complementary output modalities to reduce the user's workload. In this paper, we develop a hybrid Brain-Computer Interface (BCI) which uses Electroencephalography (EEG) and functional Near Infrared Spectroscopy (fNIRS) to discriminate and detect visual and auditory stimulus processing. We describe the experimental setup we used for collection of our data corpus with 12 subjects. On this data, we performed cross-validation evaluation, of which we report accuracy for different classification conditions. The results show that the subject-dependent systems achieved a classification accuracy of 97.8% for discriminating visual and auditory perception processes from each other and a classification accuracy of up to 94.8% for detecting modality-specific processes independently of other cognitive activity. The same classification conditions could also be discriminated in a subject-independent fashion with accuracy of up to 94.6 and 86.7%, respectively. We also look at the contributions of the two signal types and show that the fusion of classifiers using different features significantly increases accuracy.	\N	\N
25480056	Mounting evidence suggests that listeners perceptually compensate for the adverse effects of reverberation in rooms when listening to speech monaurally. However, it is not clear whether the underlying perceptual mechanism would be at all effective in the high levels of stimulus uncertainty that are present in everyday listening. Three experiments investigated monaural compensation with a consonant identification task in which listeners heard different speech on each trial. Consonant confusions frequently arose when a greater degree of reverberation was added to a test-word than to its surrounding context, but compensation became apparent in conditions where the context reverberation was increased to match that of the test-word; here, the confusions were largely resolved. A second experiment shows that information from the test-word itself can also effect compensation. Finally, the time course of compensation was examined by applying reverberation to a portion of the preceding context; consonant identification improves as this portion increases in duration. These findings indicate a monaural compensation mechanism that is likely to be effective in everyday listening, allowing listeners to recalibrate as their reverberant environment changes.	\N	\N
25486827	Temporal summation in masking has been measured simultaneously with a resolution of the masker's spectral structure to find psychoacoustic characteristics for estimation of speech intelligibility, to detect the manifestation of peripheral processes in auditory perception in humans. For this, detection thresholds of a test signal with different durations were determined. The test signal was pulse with a Gaussian envelope and a sine-wave carrier. It was presented simultaneously with a noise masker. The minimal pulse duration was inversely proportional to width of the critical bands of hearing, formed at the pulse's center frequency. The maximal pulse duration always was 50 ms. We adopted pulses with duration of 1-10 ms as a model of consonants and pulses with duration of 20-50 ms as a model of vowels. The band pass noises with rippled structure of the amplitude spectrum of two types were used as maskers. The central frequency of one masker coincided with a spectral hump and the central frequency of the other--with the spectral failure. If the pulses and maskers central frequencies were equal, the first and second maskers were called on- and - off- maskers. If the auditory system could discriminate the rippled structure of the masker's spectra, the difference in the detection thresholds of the pulses, which was presented with each of the maskers, was not equal to zero. The difference in the detection thresholds allows us to estimate resolution of the masker's spectra, i.e. frequency selectivity. Changes in the pulse's and masker's central frequencies allow us to evaluate the hearing ability in certain frequency domain. Changes in the masker's levels allow us to find influence of nonlinear dynamic properties of cochlea on temporal summation and frequency selectivity. This paper presents the results of measurements of temporal summation in masking, obtained in two frequency domains 2 and 4 kHz, in 4 subjects with normal hearing and in 1 subject with age-related hearing loss, who complained about deterioration of speech intelligibility. It has been found an increasing temporal summation and an improving the resolution of the rippled structure of the amplitude spectra for the maskers with average levels. We believe, the reasons could be found in the properties of the peripheral pulse coding, such as (1) the stabilization zones of excitation of the basilar.membrane, the range of the characteristic frequencies and the number of excited auditory nerve fibers and the number ofspikes, generated by fibers, due to the nonlinearity of the dynamic properties of the cochlea, (2) increasing synchronization of a reaction of the excited fibers and shortening in time of this reaction, due to thefiber's refractory properties.	\N	\N
25514452	Temporal processing ability has been linked to speech understanding ability and older adults often complain of difficulty understanding speech in difficult listening situations. Temporal processing can be evaluated using gap detection procedures. There is some research showing that gap detection can be evaluated using an electrophysiological procedure. However, there is currently no research establishing gap detection threshold using the N1-P2 response. The purposes of the current study were to 1) determine gap detection thresholds in younger and older normal-hearing adults using an electrophysiological measure, 2) compare the electrophysiological gap detection threshold and behavioral gap detection threshold within each group, and 3) investigate the effect of age on each gap detection measure. This study utilized an older adult group and younger adult group to compare performance on an electrophysiological and behavioral gap detection procedure. The subjects in this study were 11 younger, normal-hearing adults (mean = 22 yrs) and 11 older, normal-hearing adults (mean = 64.36 yrs). All subjects completed an adaptive behavioral gap detection procedure in order to determine their behavioral gap detection threshold (BGDT). Subjects also completed an electrophysiologic gap detection procedure to determine their electrophysiologic gap detection threshold (EGDT). Older adults demonstrated significantly larger gap detection thresholds than the younger adults. However, EGDT and BGDT were not significantly different in either group. The mean difference between EGDT and BGDT for all subjects was 0.43 msec. Older adults show poorer gap detection ability when compared to younger adults. However, this study shows that gap detection thresholds can be measured using evoked potential recordings and yield results similar to a behavioral measure.	\N	\N
25517630	Auditory processing disorder patients may have deficits in auditory temporal resolution. This study explored: (1) the ear specific norms for young adults using the adaptive tests of temporal resolution (ATTR); (2) the reliability of ATTR using two different modes of stimuli presentation; and (3) the concurrent validity of ATTR with reference to the gaps-in-noise (GIN) test. GIN and ATTR were administered through a standard audiometer and headphones. As ATTR can also be completed using a computer with commercially available headphones, thresholds from these two variants were compared. Thirty normal-hearing young adults were recruited. The mean ATTR gap detection thresholds (GDTs) derived under audiometer administration were 4.60 ms (SD 1.49) and 4.97 ms (SD 1.98) for the left and right ear, respectively. The approximated threshold (A. th.), an equivalent measure to the GDT in the GIN, mean values were 5.37 ms (SD 0.98) and 5.33 ms (SD 1.07) for left and right ears, respectively. No significant threshold difference was found between the ATTR variants. A positive, moderate correlation was found, and Bland-Altman plot analysis revealed good agreement, between GDT and A.th. ATTR and GIN results were moderately associated. Moreover, the ATTR was found to have high test-retest reliability and high specificity for the current participants.	\N	\N
25521593	A new approach for the segregation of monaural sound mixtures is presented based on the principle of temporal coherence and using auditory cortical representations. Temporal coherence is the notion that perceived sources emit coherently modulated features that evoke highly-coincident neural response patterns. By clustering the feature channels with coincident responses and reconstructing their input, one may segregate the underlying source from the simultaneously interfering signals that are uncorrelated with it. The proposed algorithm requires no prior information or training on the sources. It can, however, gracefully incorporate cognitive functions and influences such as memories of a target source or attention to a specific set of its attributes so as to segregate it from its background. Aside from its unusual structure and computational innovations, the proposed model provides testable hypotheses of the physiological mechanisms of this ubiquitous and remarkable perceptual ability, and of its psychophysical manifestations in navigating complex sensory environments.	\N	\N
25534365	The temporal masking curve (TMC) method is a behavioral technique for inferring human cochlear compression. The method relies on the assumptions that in the absence of compression, forward-masking recovery is independent of masker level and probe frequency. The present study aimed at testing the validity of these assumptions. Masking recovery was investigated for eight listeners with sensorineural hearing loss carefully selected to have absent or nearly absent distortion product otoacoustic emissions. It is assumed that for these listeners basilar membrane responses are linear, hence that masking recovery is independent of basilar membrane compression. TMCs for probe frequencies of 0.5, 1, 2, 4, and 6 kHz were available for these listeners from a previous study. The dataset included TMCs for masker frequencies equal to the probe frequencies plus reference TMCs measured using a high-frequency probe and a low, off-frequency masker. All of the TMCs were fitted using linear regression, and the resulting slope and intercept values were taken as indicative of masking recovery and masker level, respectively. Results for on-frequency TMCs suggest that forward-masking recovery is generally independent of probe frequency and of masker level and hence that it would be reasonable to use a reference TMC for a high-frequency probe to infer cochlear compression at lower frequencies. Results further show, however, that reference TMCs were sometimes shallower than corresponding on-frequency TMCs for identical probe frequencies, hence that compression could be overestimated in these cases. We discuss possible reasons for this result and the conditions when it might occur.	\N	\N
25536846	We explored the functional units of speech segmentation in Japanese using dichotic presentation and a detection task requiring no intentional sublexical analysis. Indeed, illusory perception of a target word might result from preattentive migration of phonemes, morae, or syllables from one ear to the other. In Experiment I, Japanese listeners detected targets presented in hiragana and/or kanji. Phoneme migrations did occur, suggesting that orthography-independent sublexical constituents play some role in segmentation. However, syllable and especially mora migrations were more numerous. This pattern of results was not observed in French speakers (Experiment 2), suggesting that it reflects native segmentation in Japanese. To control for the intervention of kanji representations (many words are written in kanji, and one kanji often corresponds to one syllable), in Experiment 3, Japanese listeners were presented with target loanwords that can be written only in katakana. Again, phoneme migrations occurred, while the first mora and syllable led to similar rates of illusory percepts. No migration occurred for the second, "special" mora (/J/ or/N/), probably because this constitutes the latter part of a heavy syllable. Overall, these findings suggest that multiple units, such as morae, syllables, and even phonemes, function independently of orthographic knowledge in Japanese preattentive speech segmentation.	\N	\N
25546030	A study was conducted to determine whether modifications to input compression and input frequency response characteristics can improve music-listening satisfaction in cochlear implant users. Experiment 1 compared three pre-processed versions of music and speech stimuli in a laboratory setting: original, compressed, and flattened frequency response. Music excerpts comprised three music genres (classical, country, and jazz), and a running speech excerpt was compared. Experiment 2 implemented a flattened input frequency response in the speech processor program. In a take-home trial, participants compared unaltered and flattened frequency responses. Ten and twelve adult Nucleus Freedom cochlear implant users participated in Experiments 1 and 2, respectively. Experiment 1 revealed a significant preference for music stimuli with a flattened frequency response compared to both original and compressed stimuli, whereas there was a significant preference for the original (rising) frequency response for speech stimuli. Experiment 2 revealed no significant mean preference for the flattened frequency response, with 9 of 11 subjects preferring the rising frequency response. Input compression did not alter music enjoyment. Comparison of the two experiments indicated that individual frequency response preferences may depend on the genre or familiarity, and particularly whether the music contained lyrics.	\N	\N
25556198	The auditory steady-state response, which measures the ability of neural ensembles to entrain to rhythmic auditory stimuli, has been used in human electroencephalogram studies to assess sensory processing and electrical oscillatory deficits. Patients with schizophrenia show a deficit in auditory steady-state response at 40 Hz, and therefore this may be a useful biomarker to study this disorder. We used auditory steady-state response recordings from the primary auditory cortex, hippocampus, and vertex electroencephalogram sites in awake behaving rats to determine whether pharmacological impairment of excitatory or inhibitory neurotransmission mimics auditory steady-state response abnormalities in schizophrenia. We found the most robust response to auditory stimuli in the primary auditory cortex, in line with previous studies suggesting this region is the primary generator of the auditory steady-state response in humans. Acute MK-801 (0.1mg/kg i.p.) increased primary auditory cortex intertrial coherence during auditory steady-state response at 20 and 40 Hz. Chronic MK-801 (21-day exposure at this daily dose) had no significant effect on 40-Hz auditory steady-state response. Furthermore, we found no effect of acute or chronic picrotoxin (a GABA-A antagonist) on intertrial coherence. Our data indicate that acute N-methyl-d-aspartate receptor antagonism increases synchronous activity in the primary auditory cortex in a frequency-specific manner, supporting the widely held view that acute N-methyl-d-aspartate antagonism augments gamma oscillations. Thus, rodent auditory steady-state response could be a valuable method to study the cortical ability to support synchronous activity at specific frequencies.	\N	\N
25561538	Some of the psychological abilities that underlie human speech are shared with other species. One hallmark of speech is that linguistic context affects both how speech sounds are categorized into phonemes, and how different versions of phonemes are produced. We here confirm earlier findings that swamp sparrows categorically perceive the notes that constitute their learned songs and then investigate how categorical boundaries differ according to context. We clustered notes according to their acoustic structure, and found statistical evidence for clustering into 10 population-wide note types. Examining how three related types were perceived, we found, in both discrimination and labeling tests, that an "intermediate" note type is categorized with a "short" type when it occurs at the beginning of a song syllable, but with a "long" type at the end of a syllable. In sum, three produced note-type clusters appear to be underlain by two perceived categories. Thus, in birdsong, as in human speech, categorical perception is context-dependent, and as is the case for human phonology, there is a complex relationship between underlying categorical representations and surface forms. Our results therefore suggest that complex phonology can evolve even in the absence of rich linguistic components, like syntax and semantics.	\N	\N
25565661	The objective of this study was to examine the hypothesis that between-channel gap detection, which includes between-frequency and between-ear gap detection, and perception of stop consonants, which is mediated by the length of voice-onset time (VOT), share common mechanisms, namely relative-timing operation in monitoring separate perceptual channels. The authors measured gap detection thresholds and identification functions of /ba/ and /pa/ along VOT in 49 native young adult Japanese listeners. There were three gap detection tasks. In the between-frequency task, the leading and trailing markers differed in terms of center frequency (Fc). The leading marker was a broadband noise of 10 to 20,000 Hz. The trailing marker was a 0.5-octave band-passed noise of 1000-, 2000-, 4000-, or 8000-Hz Fc. In the between-ear task, the two markers were spectrally identical but presented to separate ears. In the within-frequency task, the two spectrally identical markers were presented to the same ear. The /ba/-/pa/ identification functions were obtained in a task in which the listeners were presented synthesized speech stimuli of varying VOTs from 10 to 46 msec and asked to identify them as /ba/ or /pa/. The between-ear gap thresholds were significantly positively correlated with the between-frequency gap thresholds (except those obtained with the trailing marker of 4000-Hz Fc). The between-ear gap thresholds were not significantly correlated with the within-frequency gap thresholds, which were significantly correlated with all the between-frequency gap thresholds. The VOT boundaries and slopes of /ba/-/pa/ identification functions were not significantly correlated with any of these gap thresholds. There was a close relation between the between-ear and between-frequency gap detection, supporting the view that these two types of gap detection share common mechanisms of between-channel gap detection. However, there was no evidence for a relation between the perception of stop consonants and the between-frequency/ear gap detection in native Japanese speakers.	\N	\N
25571013	Binaural beat (BB) illusions are experienced as continuous central pulsations when two sounds with slightly different frequencies are delivered to each ear. It has been shown that steady-state auditory evoked potentials (AEPs) to BBs can be captured and investigated. The authors recently developed a new method of evoking transient AEPs to binaural beats using frequency modulated stimuli. This methodology was able to create single BBs in predetermined intervals with varying carrier frequencies. This study examines the effects of the BB duration and the frequency modulating component of the stimulus on the binaural beats and their evoked potentials. Normal hearing subjects were tested with a set of four durations (25, 50, 100, and 200 ms) with two stimulation configurations, binaural dichotic (binaural beats) and diotic (frequency modulation). The results obtained from the study showed that out of the given durations, the 100 ms beat, was capable of evoking the largest amplitude responses. The frequency modulation effect showed a decrease in peak amplitudes with increasing beat duration until their complete disappearance at 200 ms. Even though, at 200 ms, the frequency modulation effects were not present, the binaural beats were still perceived and captured as evoked potentials.	\N	\N
25571287	The pathologic auditory sensation in decompensated tinnitus patients is accompanied by the inability to habituate even temporary to this sound. This disability might originate from simultaneous activation of brain areas for the appraisal of the stimulus valence as, e.g., the limbic system. This coactivation of limbic areas is likely to modulate the degree and persistence of selective attention assigned to the tinnitus stream, which in turn could also explain interindividual differences in tinnitus loudness perception. Preliminary studies demonstrate that the amount of allocated attention and the habituation deficit can be mapped to changes in auditory late evoked responses (ALRs). Utilizing a numerical model for the simulation of ALRs we were able to predict a general habituation behavior in two patient groups with different degrees of tinnitus severity. Evaluating the instantaneous phase of simulated and measured ALRs by its von Mises concentration parameter, we verify a habituation deficit relative to the degree of decompensation and thus provide additional support for our neurofunctional model of limbic influences on neural processing of sensory information.	\N	\N
25577901	People with one eye show altered sensory processing. Such changes might reflect a central reweighting of sensory information that might impact on how multisensory cues are integrated. We assessed whether people who lost an eye early in life differ from controls with respect to audiovisual integration. In order to quantify the relative weightings assigned to each sensory system, participants were asked to spatially localize audiovisual events that have been previously shown to be optimally combined and perceptually fused from the point of view of location in a normal population, where the auditory and visual components were spatially disparate. There was no difference in the variability of localizing unimodal visual and auditory targets by people with one eye compared to controls. People with one eye did however, demonstrate slower reaction times to localize visual stimuli compared to auditory stimuli and were slower than binocular and eye-patched control groups. When localizing bimodal targets, the weightings assigned to each sensory modality in both people with one eye and controls were predictable from their unimodal performance, in accordance with Maximum Likelihood Estimation and the time it took all three groups to localize the bimodal targets was faster than for vision alone. Regardless of demonstrating a longer response time to visual stimuli, people with one eye appear to integrate the auditory and visual components of multisensory events optimally when determining spatial location.	\N	\N
25597464	There is a paucity of published studies examining how children with hearing loss understand speech over the telephone. Previous studies on adults with hearing aids have suggested that adults with bilateral hearing aids experience significant difficulty recognizing speech on the telephone when listening with one ear, but the provision of telephone input to both ears substantially improved speech understanding. The objectives of this study were to measure speech recognition in quiet and in noise for a group of older children with hearing loss over the telephone and to evaluate the effects of binaural hearing (e.g., DuoPhone) on speech recognition over the telephone. A cross-sectional, repeated-measures design was used in this study. A total of 14 children, ages 6-14 yr, participated in the study. Participants were obtained using convenience sampling from a nonprofit clinic population. Speech recognition in quiet and in noise with binaural versus monaural telephone input was compared in pediatric participants. Monosyllabic word recognition was assessed in quiet and classroom noise set at 50 dBA in conditions with monaural and binaural (DuoPhone) telephone input. The children's speech recognition in quiet and in noise was significantly better with binaural telephone input relative to monaural telephone input. To obtain optimal performance on the telephone, the following considerations may apply: (1) use of amplification with binaural streaming capabilities (e.g., DuoPhone), (2) counseling of family and children on how to best use the telephone, (3) provision of telecoil with microphone attenuation for improved signal-to-noise ratio, and (4) use of probe tube measures to verify the appropriateness of the telephone programs.	\N	\N
25597465	In order to differentiate between a conductive hearing loss (CHL) and a sensorineural hearing loss (SNHL) in the hearing-impaired individual, we compared thresholds to air conduction (AC) and bone conduction (BC) auditory stimulation. The presence of a gap between these thresholds (an air-bone gap) is taken as a sign of a CHL, whereas similar threshold elevations reflect an SNHL. This is based on the assumption that BC stimulation directly excites the inner ear, bypassing the middle ear. However, several of the classic mechanisms of BC stimulation such as ossicular chain inertia and the occlusion effect involve middle ear structures. An additional mode of auditory stimulation, called soft tissue conduction (STC; also called nonosseous BC) has been demonstrated, in which the clinical bone vibrator elicits hearing when it is applied to soft tissue sites on the head, neck, and thorax. The purpose of this study was to assess the relative contributions of threshold determinations to stimulation by STC, in addition to AC and osseous BC, to the differential diagnosis between a CHL and an SNHL. Baseline auditory thresholds were determined in normal participants to AC (supra-aural earphones), BC (B71 bone vibrator at the mastoid, with 5 N application force), and STC (B71 bone vibrator) to the submental area and to the submandibular triangle with 5 N application force) stimulation in response to 0.5, 1.0, 2.0, and 4.0 kHz tones. A CHL was then simulated in the participants by means of an ear plug. Separately, an SNHL was simulated in these participants with 30 dB effective masking. STUDY SAMPLE consisted of 10 normal-hearing participants (4 males; 6 females, aged 20-30 yr). AC, BC, and STC thresholds were determined in the initial normal state and in the presence of each of the simulations. The earplug-induced CHL simulation led to a mean AC threshold elevation of 21-37 dB (depending on frequency), but not of BC and STC thresholds. The masking-induced SNHL led to a mean elevation of AC, BC, and STC thresholds (23-36 dB, depending on frequency). In each type of simulation, the BC threshold shift was similar to that of the STC threshold shift. These results, which show a similar threshold shift for STC and for BC as a result of these simulations, together with additional clinical and laboratory findings, provide evidence that BC thresholds likely represent the threshold of the nonosseous BC (STC) component of multicomponent BC at the BC stimulation site, and thereby succeed in clinical practice to contribute to the differential diagnosis. This also provides evidence that STC (nonosseous BC) stimulation at low intensities probably does not involve components of the middle ear, represents true cochlear function, and therefore can also contribute to a differential diagnosis (e.g., in situations where the clinical bone vibrator cannot be applied to the mastoid or forehead with a 5 N force, such as in severe skull fracture).	\N	\N
25605693	Tetramethylpyrazine has been suggested to have a therapeutic effect on impaired hearing that is induced by aminoglycoside antibiotics. However, its effectiveness on streptomycin ototoxicity and its cellular mechanisms are relatively unknown. Here we investigate the protective effect of tetramethylpyrazine on streptomycin-induced ototoxicity in guinea pig cochlea. Prospective randomized laboratory study. Hearing Research Laboratory of China Medical University. Adult guinea pigs were randomized to 4 groups. Hearing sensitivity of guinea pigs was tested by auditory brainstem response measurements before streptomycin exposure and again 10 days later. The cochlear tissues were prepared for electron microscopy and immunohistochemical staining of heat shock protein 70 (HSP70). The effect of tetramethylpyrazine on streptomycin-induced activation of caspase-3 was evaluated by Western blotting. Co-therapy with tetramethylpyrazine reduced a profound streptomycin-induced auditory threshold shift compared with streptomycin treatment alone (P = .0002 or P = .00008). Tetramethylpyrazine also attenuated the structural disruption in streptomycin-treated outer hair cells and marginal cells of vascular stria by transmission electronic microscopy and scanning electronic microscopy, respectively. Moreover, tetramethylpyrazine decreased the streptomycin-stimulated expressions of HSP70 and caspase-3. The correlation analysis demonstrated that HSP70 expression had a positive correlation with auditory brainstem response thresholds (|R| = 0.6-0.9, P = .0073 or P = .0169). Our data suggest that the protective effect of tetramethylpyrazine on hearing function is associated with the reduction of stress response and inhibition of apoptosis. Tetramethylpyrazine may have therapeutic potential for patients with ototoxicity diseases.	\N	\N
25611857	This study reviewed whether advanced age should be a consideration when revision cochlear implantation is warranted. To examine whether age at revision cochlear implantation is related to postrevision speech perception performance. A retrospective analysis was performed in an academic tertiary care center. Participants included 14 younger adults (<65 years) and 15 older adults (≥65 years) who underwent revision cochlear implantation. Revision cochlear implantation. Speech perception performance, as measured with consonant-nucleus-consonant [CNC] words in quiet, at the best prerevision interval as well as the 3- and 6-month postrevision intervals were compared between the 2 cohorts. The CNC word test consists of 10 lists of 50 phonemically balanced monosyllabic words, scored with a range of 0% to 100% correct. Both cohorts experienced a restoration in speech perception scores after revision cochlear implantation compared with their best performance before the revision (mean [SD] CNC word test scores for the younger cohort: 43.9% [25.6%] before revision and 47.7% [21.3%] at 3 months and 47.6% [19.8%] at 6 months after revision; for the older cohort: 36.3% [19.1%] before revision and 35.3% [17.2%] at 3 months and 39.9% [16.3%] at 6 months after revision; F₂,₅₄= 0.93; P = .40). There was no interaction between age at revision surgery and speech perception performance at each assessment interval (F₂,₅₄= 0.51; P = .60). In this study, age at revision cochlear implantation was not related to postrevision speech perception performance. Advanced age should not be considered a contraindication to revision cochlear implantation.	\N	\N
25613931	To study electrical stimulation, auditory functionality, and language development in patients with inner ear malformations involving the anterior labyrinth who underwent cochlear implantation. Retrospective case review. Reference hospital for cochlear implantation. Review of 14 cases of severe hearing loss with major (common cavity deformity and cochlear hypoplasia) or minor (e.g., incomplete partition and basal turn aplasia) malformations. After cochlear implantation, data were gathered on the threshold (THR) and maximum comfort level (MCL) of the electrical stimulation and the number of functioning electrodes. Auditory responses to speech (EARS protocol) subtests were used to evaluate auditory functionality and language acquisition at 6, 12, and 24 months post-implantation. Tests used were: LIP profile, MTP (3, 6 and 12 words), OLD (open set test) and CLD (close set test). Results were compared with findings in a control group of 28 cochlear implantation patients without these malformations and with congenital hearing loss. The mean THR was 11.02μC in patients with malformations versus 3.5μC in those without, a significant difference. The THR also significantly differed between groups with major and minor malformations. Fewer functioning electrodes were used in patients with malformations. Auditory functionality scores were best in controls than in patients with malformations, who scored ≤50%, finding the lowest scores in those with major malformations. Patients with inner ear malformations undergoing cochlear implantation require greater stimuli to obtain an auditory response and have worse auditory functionality outcomes; these differences are greater in those with major versus minor malformations Nevertheless, cochlear implantation appears to be beneficial for all patients with these malformations to a greater or lesser extent.	\N	\N
25617593	We examined 4- and 6-month-old infants' sensitivity to the perceptual association between pitch and object size. Crossmodal correspondence effects were observed in 6-month-old infants but not in younger infants, suggesting that experience and/or further maturation is needed to fully develop this crossmodal association.	\N	\N
25618049	An acoustic survey of secondary schools in England has been undertaken. Room acoustic parameters and background noise levels were measured in 185 unoccupied spaces in 13 schools to provide information on the typical acoustic environment of secondary schools. The unoccupied acoustic and noise data were correlated with various physical characteristics of the spaces. Room height and the amount of glazing were related to the unoccupied reverberation time and therefore need to be controlled to reduce reverberation to suitable levels for teaching and learning. Further analysis of the unoccupied data showed that the introduction of legislation relating to school acoustics in England and Wales in 2003 approximately doubled the number of school spaces complying with current standards. Noise levels were also measured during 274 lessons to examine typical levels generated during teaching activities in secondary schools and to investigate the influence of acoustic design on working noise levels in the classroom. Comparison of unoccupied and occupied data showed that unoccupied acoustic conditions affect the noise levels occurring during lessons. They were also related to the time spent in disruption to the lessons (e.g., students talking or shouting) and so may also have an impact upon student behavior in the classroom.	\N	\N
25618071	Listeners can use pitch changes in speech to identify talkers. Individuals exhibit large variability in sensitivity to pitch and in accuracy perceiving talker identity. In particular, people who have musical training or long-term tone language use are found to have enhanced pitch perception. In the present study, the influence of pitch experience on talker identification was investigated as listeners identified talkers in native language as well as non-native languages. Experiment 1 was designed to explore the influence of pitch experience on talker identification in two groups of individuals with potential advantages for pitch processing: musicians and tone language speakers. Experiment 2 further investigated individual differences in pitch processing and the contribution to talker identification by testing a mediation model. Cumulatively, the results suggested that (a) musical training confers an advantage for talker identification, supporting a shared resources hypothesis regarding music and language and (b) linguistic use of lexical tones also increases accuracy in hearing talker identity. Importantly, these two types of hearing experience enhance talker identification by sharpening pitch perception skills in a domain-general manner.	\N	\N
25618091	This study reports a finding about vocal expressions of emotion in Mandarin Chinese. Production and perception experiments used the same tone and mixed tone sequences to test whether pitch variation is restricted due to the presence of lexical tones. Results showed that the restriction of pitch variation occurred in all high level tone sequences (tone 1 group) with the expression of happiness but did not happen for other dynamic tone groups. However, perception analysis revealed that all the emotions in every tone group received high identification rates; this indicates that listeners used other cues for encoding happiness in the tone 1 group. This study demonstrates that the restriction of pitch variation does not affect the perception of vocal emotions.	\N	\N
25618101	Speech perception studies generally focus on the acoustic information present in the frequency regions below 6 kHz. Recent evidence suggests that there is perceptually relevant information in the higher frequencies, including information affecting speech intelligibility. This experiment examined whether listeners are able to accurately identify a subset of vowels and consonants in CV-context when only high-frequency (above 5 kHz) acoustic information is available (through high-pass filtering and masking of lower frequency energy). The findings reveal that listeners are capable of extracting information from these higher frequency regions to accurately identify certain consonants and vowels.	\N	\N
25628152	The aim of the present study was to investigate whether the saliency effect for word beginnings reported in children with dyslexia (Marshall & Van der Lely, 2009) can be found also in typically developing children. Thirty-four typically developing Italian children aged 8-10 years completed two specifically designed tasks: a production task and a perception task. Both tasks used nonwords containing clusters consisting of plosive plus liquid (e.g. pl). Clusters could be either in a stressed or in an unstressed syllable and could be either in initial position (first syllable) or in medial position (second syllable). In the production task, children were asked to repeat the nonwords. In the perception task, the children were asked to discriminate between two nonwords differing in one phoneme belonging to a cluster by reporting whether two repetitions were the same or different. Results from the production task showed that children are more accurate in repeating stressed than unstressed syllables, but there was no difference with respect to position of the cluster. Results from the perception task showed that children performed more accurately when discriminating word initial contrasts than when discriminating word medial contrasts, especially if the cluster was unstressed. Implications of this finding for clinical assessments are discussed.	\N	\N
25630393	The objective of this study was to test if stimulating multiple electrodes can improve temporal pitch ranking performance at low and high stimulation rates. Temporal pitch cues are usually based on modifying the stimulation rate of the implant and thereby provide a continuum of pitches on a single electrode up to approximately 300 Hz. Ten cochlear implant subjects were asked to pitch rank stimuli presented with direct electrical stimulation. The pulses were applied on one, three, six, or eleven electrodes. In one of the conditions the current amplitude of each pulse was randomly varied between 0 and 100%. Their frequency ranged from 100 up to 500 pps. Listeners showed the previously reported performance pattern in most conditions with very good performance at the lowest standard rates and deteriorating performance to near chance level at the highest rate tested. Performance with eleven electrodes was significantly better than performance with one electrode at 500 pps. Stimulating on multiple electrodes can improve temporal pitch perception.	\N	\N
25634776	To compare some perceptual and acoustic characteristics of the voices of children who use the advanced combination encoder (ACE) or fine structure processing (FSP) speech coding strategies, and to investigate whether these characteristics differ from children with normal hearing. Acoustic analysis of the sustained vowel /a/ was performed using the multi-dimensional voice program (MDVP). Analyses of sequential and spontaneous speech were performed using the real time pitch. Perceptual analyses of these samples were performed using visual-analogic scales of pre-selected parameters. Seventy-six children from three years to five years and 11 months of age participated. Twenty-eight were users of ACE, 23 were users of FSP, and 25 were children with normal hearing. Although both groups with CI presented with some deviated vocal features, the users of ACE presented with voice quality more like children with normal hearing than the users of FSP. Sound processing of ACE appeared to provide better conditions for auditory monitoring of the voice, and consequently, for better control of the voice production. However, these findings need to be further investigated due to the lack of comparative studies published to understand exactly which attributes of sound processing are responsible for differences in performance.	\N	\N
25636271	The major purpose of this study was to explore the changes in the local/global gamma-band neural synchronies during target/non-target processing due to task difficulty under an auditory three-stimulus oddball paradigm. Multichannel event-related potentials (ERPs) were recorded from fifteen healthy participants during the oddball task. In addition to the conventional ERP analysis, we investigated the modulations in gamma-band activity (GBA) and inter-regional gamma-band phase synchrony (GBPS) for infrequent target and non-target processing due to task difficulty. The most notable finding was that the difficulty-related changes in inter-regional GBPS (33-35 Hz) at P300 epoch (350-600 ms) completely differed for target and non-target processing. As task difficulty increased, the GBPS significantly reduced for target processing but increased for non-target processing. This result contrasts with the local neural synchrony in gamma-bands, which was not affected by task difficulty. Another major finding was that the spatial patterns of functional connectivity were dissociated for target and non-target processing with regard to the difficult task. The spatial pattern for target processing was compatible with the top-down attention network, whereas that for the non-target corresponded to the bottom-up attention network. Overall, we found that the inter-regional gamma-band neural synchronies during target/non-target processing change significantly with task difficulty and that this change is dissociated between target and non-target processing. Our results indicate that large-scale neural synchrony is more relevant for the difference in information processing between target and non-target stimuli.	\N	\N
25638938	When one hears footsteps in the hall, one is able to instantly recognise it as a person: this is an everyday example of auditory biological motion perception. Despite the familiarity of this experience, research into this phenomenon is in its infancy compared with visual biological motion perception. Here, two experiments explored sensitivity to, and recognition of, auditory stimuli of biological and nonbiological origin. We hypothesised that the cadence of a walker gives rise to a temporal pattern of impact sounds that facilitates the recognition of human motion from auditory stimuli alone. First a series of detection tasks compared sensitivity with three carefully matched impact sounds: footsteps, a ball bouncing, and drumbeats. Unexpectedly, participants were no more sensitive to footsteps than to impact sounds of nonbiological origin. In the second experiment participants made discriminations between pairs of the same stimuli, in a series of recognition tasks in which the temporal pattern of impact sounds was manipulated to be either that of a walker or the pattern more typical of the source event (a ball bouncing or a drumbeat). Under these conditions, there was evidence that both temporal and nontemporal cues were important in recognising theses stimuli. It is proposed that the interval between footsteps, which reflects a walker's cadence, is a cue for the recognition of the sounds of a human walking.	\N	\N
25646513	Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing.	\N	\N
25653354	Perceptual phase entrainment improves speech intelligibility by phase-locking the brain's high-excitability and low-excitability phases to relevant or irrelevant events in the speech input. However, it remains unclear whether phase entrainment to speech can be explained by a passive "following" of rhythmic changes in sound amplitude and spectral content or whether entrainment entails an active tracking of higher-level cues: in everyday speech, rhythmic fluctuations in low-level and high-level features always covary. Here, we resolve this issue by constructing novel speech/noise stimuli with intelligible speech but without systematic changes in sound amplitude and spectral content. The probability of detecting a tone pip, presented to human listeners at random moments during our speech/noise stimuli, was significantly modulated by the rhythmic changes in high-level information. Thus, perception can entrain to the speech rhythm even without concurrent fluctuations in sound amplitude or spectral content. Strikingly, the actual entrainment phase depended on the tone-pip frequency, with tone pips within and beyond the principal frequency range of the speech sound modulated in opposite fashion. This result suggests that only those neural populations processing the actually presented frequencies are set to their high-excitability phase, whereas other populations are entrained to the opposite, low-excitability phase. Furthermore, we show that the perceptual entrainment is strongly reduced when speech intelligibility is abolished by presenting speech/noise stimuli in reverse, indicating that linguistic information plays an important role for the observed perceptual entrainment.	\N	\N
25656953	This study investigated the sensitivity of 9-month-old infants to the alignment between prosodic and gesture prominences in pointing-speech combinations. Results revealed that the perception of prominence is multimodal and that infants are aware of the timing of gesture-speech combinations well before they can produce them.	\N	\N
25665752	This study compared the timing of appearance of three components of age-related hearing loss that determine the pattern and severity of presbycusis: the functional and structural pathologies of sensory cells and neurons and changes in gap detection (GD), the latter as an indicator of auditory temporal processing. Using UM-HET4 mice, genetically heterogeneous mice derived from four inbred strains, we studied the integrity of inner and outer hair cells by position along the cochlear spiral, inner hair cell-auditory nerve connections, spiral ganglion neurons (SGN), and determined auditory thresholds, as well as pre-pulse and gap inhibition of the acoustic startle reflex (ASR). Comparisons were made between mice of 5-7, 22-24 and 27-29 months of age. There was individual variability among mice in the onset and extent of age-related auditory pathology. At 22-24 months of age a moderate to large loss of outer hair cells was restricted to the apical third of the cochlea and threshold shifts in the auditory brain stem response were minimal. There was also a large and significant loss of inner hair cell-auditory nerve connections and a significant reduction in GD. The expression of Ntf3 in the cochlea was significantly reduced. At 27-29 months of age there was no further change in the mean number of synaptic connections per inner hair cell or in GD, but a moderate to large loss of outer hair cells was found across all cochlear turns as well as significantly increased ABR threshold shifts at 4, 12, 24 and 48 kHz. A statistical analysis of correlations on an individual animal basis revealed that neither the hair cell loss nor the ABR threshold shifts correlated with loss of GD or with the loss of connections, consistent with independent pathological mechanisms.	\N	\N
25669257	Individual factors beyond the audiogram, such as age and cognitive abilities, can influence speech intelligibility and speech quality judgments. This paper develops a neural network framework for combining multiple subject factors into a single model that predicts speech intelligibility and quality for a nonlinear hearing-aid processing strategy. The nonlinear processing approach used in the paper is frequency compression, which is intended to improve the audibility of high-frequency speech sounds by shifting them to lower frequency regions where listeners with high-frequency loss have better hearing thresholds. An ensemble averaging approach is used for the neural network to avoid the problems associated with overfitting. Models are developed for two subject groups, one having nearly normal hearing and the other mild-to-moderate sloping losses.	\N	\N
25673838	Critical periods are developmental windows during which the stimuli an animal encounters can reshape response properties in the affected system to a profound degree. Despite this window's importance, the neural mechanisms that regulate it are not completely understood. Pioneering studies in visual cortex initially indicated that norepinephrine (NE) permits ocular dominance column plasticity during the critical period, but later research has suggested otherwise. More recent work implicating NE in experience-dependent plasticity in the adult auditory cortex led us to re-examine the role of NE in critical period plasticity. Here, we exposed dopamine β-hydroxylase knock-out (Dbh(-/-)) mice, which lack NE completely from birth, to a biased acoustic environment during the auditory cortical critical period. This manipulation led to a redistribution of best frequencies (BFs) across auditory cortex in our control mice, consistent with prior work. By contrast, Dbh(-/-) mice failed to exhibit the expected redistribution of BFs, even though NE-deficient and NE-competent mice showed comparable auditory cortical organization when reared in a quiet colony environment. These data suggest that while intrinsic tonotopic patterning of auditory cortical circuitry occurs independently from NE, NE is required for critical period plasticity in auditory cortex.	\N	\N
25685775	The aim of this research was to analyze temporal auditory processing and phonological awareness in school-age children with benign childhood epilepsy with centrotemporal spikes (BECTS). Patient group (GI) consisted of 13 children diagnosed with BECTS. Control group (GII) consisted of 17 healthy children. After neurological and peripheral audiological assessment, children underwent a behavioral auditory evaluation and phonological awareness assessment. The procedures applied were: Gaps-in-Noise test (GIN), Duration Pattern test, and Phonological Awareness test (PCF). Results were compared between the groups and a correlation analysis was performed between temporal tasks and phonological awareness performance. GII performed significantly better than the children with BECTS (GI) in both GIN and Duration Pattern test (P < 0.001). GI performed significantly worse in all of the 4 categories of phonological awareness assessed: syllabic (P = 0.001), phonemic (P = 0.006), rhyme (P = 0.015) and alliteration (P = 0.010). Statistical analysis showed a significant positive correlation between the phonological awareness assessment and Duration Pattern test (P < 0.001). From the analysis of the results, it was concluded that children with BECTS may have difficulties in temporal resolution, temporal ordering, and phonological awareness skills. A correlation was observed between auditory temporal processing and phonological awareness in the suited sample.	\N	\N
25693304	When we interact with objects in our environment, as a general rule we are not aware of the proximal stimulation they provide, but we directly experience the external object. This process of assigning an external cause is known as distal attribution. It is extremely difficult to measure how distal attribution emerges because it arises so early in life and appears to be automatic. Sensory substitution systems give us the possibility to measure the process as it occurs online. With these devices, objects in our environment produce novel proximal stimulation patterns and individuals have to establish the link between the proximal stimulation and the distal object. This review disentangles the contributing factors that allow the nervous system to assign a distal cause, thereby creating the experience of an external world. In particular, it highlights the role of the assumption of a stable world, the role of movement, and finally that of calibration. From the existing sensory substitution literature it appears that distal attribution breaks down when one of these principles is violated and as such the review provides an important piece to the puzzle of distal attribution.	\N	\N
25698006	The present study investigated the possibility that the human auditory system demonstrates frequency selectivity to spectro-temporal amplitude modulations. Threshold modulation depth for detecting sinusoidal spectro-temporal modulations was measured using a generalized masked threshold pattern paradigm with narrowband masker modulations. Four target spectro-temporal modulations were examined, differing in their temporal and spectral modulation frequencies: a temporal modulation of -8, 8, or 16 Hz combined with a spectral modulation of 1 cycle/octave and a temporal modulation of 4 Hz combined with a spectral modulation of 0.5 cycles/octave. The temporal center frequencies of the masker modulation ranged from 0.25 to 4 times the target temporal modulation. The spectral masker-modulation center-frequencies were 0, 0.5, 1, 1.5, and 2 times the target spectral modulation. For all target modulations, the pattern of average thresholds for the eight normal-hearing listeners was consistent with the hypothesis of a spectro-temporal modulation filter. Such a pattern of modulation-frequency sensitivity was predicted on the basis of psychoacoustical data for purely temporal amplitude modulations and purely spectral amplitude modulations. An analysis of separability indicates that, for the present data set, selectivity in the spectro-temporal modulation domain can be described by a combination of a purely spectral and a purely temporal modulation filter function.	\N	\N
25721795	Music and speech are skills that require high temporal precision of motor output. A key question is how humans achieve this timing precision given the poor temporal resolution of somatosensory feedback, which is classically considered to drive motor learning. We hypothesise that auditory feedback critically contributes to learn timing, and that, similarly to visuo-spatial learning models, learning proceeds by correcting a proportion of perceived timing errors. Thirty-six participants learned to tap a sequence regularly in time. For participants in the synchronous-sound group, a tone was presented simultaneously with every keystroke. For the jittered-sound group, the tone was presented after a random delay of 10-190 ms following the keystroke, thus degrading the temporal information that the sound provided about the movement. For the mute group, no keystroke-triggered sound was presented. In line with the model predictions, participants in the synchronous-sound group were able to improve tapping regularity, whereas the jittered-sound and mute group were not. The improved tapping regularity of the synchronous-sound group also transferred to a novel sequence and was maintained when sound was subsequently removed. The present findings provide evidence that humans engage in auditory feedback error-based learning to improve movement quality (here reduce variability in sequence tapping). We thus elucidate the mechanism by which high temporal precision of movement can be achieved through sound in a way that may not be possible with less temporally precise somatosensory modalities. Furthermore, the finding that sound-supported learning generalises to novel sequences suggests potential rehabilitation applications.	\N	\N
25724819	Older adults, even with clinically normal hearing sensitivity, often report difficulty understanding speech in the presence of background noise. Part of this difficulty may be related to age-related degradations in the neural representation of speech sounds, such as formant transitions. Frequency-following responses (FFRs), which are dependent on phase-locked neural activity, were elicited using sounds consisting of linear frequency sweeps, which may be viewed as simple models of formant transitions. Eighteen adults (ten younger, 22-24 years old, and nine older, 51-67 years old) were tested. FFRs were elicited by tonal sweeps in six conditions. Two directions of frequency change, rising or falling, were used for each of three rates of frequency change. Stimulus-to-response cross correlations revealed that older adults had significantly poorer representation of the tonal sweeps, and that FFRs became poorer for faster rates of change. An additional FFR signal-to-noise ratio analysis based on time windows revealed that across the FFR waveforms and rates of frequency change, older adults had smaller (poorer) signal-to-noise ratios. These results indicate that older adults, even with clinically-normal hearing sensitivity, have degraded phase-locked neural representations of dynamic frequency.	\N	\N
25726264	Speech is a complex acoustic signal showing a quasiperiodic structure at several timescales. Integrated neural signals recorded in the cortex also show periodicity at different timescales. In this chapter we outline the neural mechanisms that potentially allow the auditory cortex to segment and encode continuous speech. This chapter focuses on how the human auditory cortex uses the temporal structure of the acoustic signal to extract phonemes and syllables, the two major constituents of connected speech. We argue that the quasiperiodic structure of collective neural activity in auditory cortex represents the ideal mechanical infrastructure to fractionate continuous speech into linguistic constituents of variable sizes.	\N	\N
25726287	Neural disorders of the auditory nerve are associated with particular disorders of auditory perceptions dependent on processing of acoustic temporal cues. These include: (1) speech perception; (2) localizing a sound's origin in space; and (3) identifying sounds in background noise. Auditory neuropathy (AN) is a consequence of: (1) presynaptic disorders affecting inner hair cell ribbon synapses; (2) postsynaptic disorders of auditory nerve dendrites; and (3) postsynaptic disorders of auditory nerve axons. The etiologies of these disorders are diverse, similar to other cranial or peripheral neuropathies. The pathologies cause attenuated and dyssynchronous auditory nerve discharges. Therapies and management of patients with AN are reviewed.	\N	\N
25726290	Neglect is a neurologic disorder, typically associated with lesions of the right hemisphere, in which patients are biased towards their ipsilesional - usually right - side of space while awareness for their contralesional - usually left - side is reduced or absent. Neglect is a multimodal disorder that often includes deficits in the auditory domain. Classically, auditory extinction, in which left-sided sounds that are correctly perceived in isolation are not detected in the presence of synchronous right-sided stimulation, has been considered the primary sign of auditory neglect. However, auditory extinction can also be observed after unilateral auditory cortex lesions and is thus not specific for neglect. Recent research has shown that patients with neglect are also impaired in maintaining sustained attention, on both sides, a fact that is reflected by an impairment of auditory target detection in continuous stimulation conditions. Perhaps the most impressive auditory symptom in full-blown neglect is alloacusis, in which patients mislocalize left-sided sound sources to their right, although even patients with less severe neglect still often show disturbance of auditory spatial perception, most commonly a lateralization bias towards the right. We discuss how these various disorders may be explained by a single model of neglect and review emerging interventions for patient rehabilitation.	\N	\N
25730449	To assess whether recombinant growth factor (hGH) therapy has an effect on cochlear implant (CI) performance. Two pediatric CI recipients (S1, S2) who underwent treatment with hGH for short stature were identified for review. S1 has bilateral labyrinthine dysplasia and received implants at ages 10 months (right) and 4 years 3 months (left). S2 was diagnosed with severe to progressive sensorineural hearing loss bilaterally and received a CI at age 9 years 10 months (left). Case series. Cochlear implant, hGH, and speech perception data were collected. Phonetically Balanced Kindergarten (PBK) and Consonant Nucleus Consonant (CNC) word recognition scores were reviewed to assess auditory perception. Electrode impedances, threshold levels, and comfort levels were also reviewed. After 4 months of hGH, word recognition scores for S1 were observed to decrease from 90 to 72% (right) and were stable at 40% (left). Despite troubleshooting, performance continued to decline bilaterally to 52% (right) and 28% (left), and the decision was made to discontinue hGH. One month after cessation of hGH, word recognition scores began improving to 74% (right) and 68% (left). Word recognition scores for S2 were observed to have decreased from 92% the previous year to 82% after taking hGH for 2 months. Given both our previous experience with S1 and discussions with S2's parents, hGH was discontinued after 10 months of therapy. Two months after cessation of hGH, S2's word recognition had improved to 86% (left). Our case studies illustrate that implanted children undergoing treatment with hGH may experience a decrease in speech perception, which recovers after the cessation of treatment. Since hGH use has become more prevalent in recent years, it is important to inquire whether children undergoing, or who have undergone, implantation are receiving hGH so that they may be appropriately monitored.	\N	\N
25731581	While potentially improving audibility for listeners with considerable high frequency hearing loss, the effects of implementing nonlinear frequency compression (NFC) for listeners with moderate high frequency hearing loss are unclear. The purpose of this study was to investigate the effects of activating NFC for listeners who are not traditionally considered candidates for this technology. Participants wore study hearing aids with NFC activated for a 3-4 week trial period. After the trial period, they were tested with NFC and with conventional processing on measures of consonant discrimination threshold in quiet, consonant recognition in quiet, sentence recognition in noise, and acceptableness of sound quality of speech and music. Seventeen adult listeners with symmetrical, mild to moderate sensorineural hearing loss participated. Better ear, high frequency pure-tone averages (4, 6, and 8 kHz) were 60 dB HL or better. Activating NFC resulted in lower (better) thresholds for discrimination of /s/, whose spectral center was 9 kHz. There were no other significant effects of NFC compared to conventional processing. These data suggest that the benefits, and detriments, of activating NFC may be limited for this population.	\N	\N
25731582	To evaluate wideband amplification and non-linear frequency compression (NLFC) as a means to improve speech recognition for children with mild/moderate hearing loss. Randomized within-subject design with repeated measures across test conditions. Eleven children with mild to moderate hearing loss were evaluated with: (1) Phonak BTE without NLFC, (2) Phonak BTE with NLFC, and (3) Oticon BTE with wideband response extending to 8000 Hz. Use of NLFC provided better detection and recognition of high-frequency stimuli (e.g. /sh/ and /s/). No difference in performance between conditions was observed for speech recognition when measured with the University of Western Ontario (UWO) plurals test and the UWO distinctive features difference test. Finally, there were no differences between conditions on the BKB-SIN test. Children with mild to moderate hearing loss have good access to high-frequency phonemes presented at fixed levels (e.g. 50 to 60 dBA) with both wideband and NLFC technology. Similarly, sentence recognition in noise was similar with wideband and NLFC. Adaptive test procedures that probe performance at lower input levels showed small but significant improvements in the detection and recognition of the phonemes /s/ and /sh/ with NLFC condition when compared to the NLFC Off and wideband conditions.	\N	\N
25733362	With the growing number of older adults receiving cochlear implants (CI), there is general agreement that substantial benefits can be gained. Nonetheless, variability in speech perception performance is high, and the relative contribution and interactions among peripheral, central-auditory, and cognitive factors are not fully understood. The goal of the present study was to compare auditory-cognitive processing in older-adult CI recipients with that of older normal-hearing (NH) listeners by means of behavioral and electrophysiologic manifestations of a high-load cognitive task. Auditory event-related potentials (AERPs) were recorded from 9 older postlingually deafened adults with CI (age at CI >60) and 10 age-matched listeners with NH, while performing an auditory Stroop task. Participants were required to classify the speaker's gender (male/female) that produced the words 'mother' or 'father' while ignoring the irrelevant congruent or incongruent word meaning. Older CI and NH listeners exhibited comparable reaction time, performance accuracy, and initial sensory-perceptual processing (i.e. N1 potential). Nonetheless, older CI recipients showed substantially prolonged and less efficient perceptual processing (i.e. P3 potential). Congruency effects manifested in longer reaction time (i.e. Stroop effect), execution time, and P3 latency to incongruent versus congruent stimuli in both groups in a similar fashion; however, markedly prolonged P3 and shortened execution time were evident in older CI recipients. Collectively, older adults (CI and NH) employed a combined perceptual and postperceptual conflict processing strategy; nonetheless, the relative allotment of perceptual resources was substantially enhanced to maintain adequate performance in CI recipients. In sum, the recording of AERPs together with the simultaneously obtained behavioral measures during a Stroop task exposed a differential time course of auditory-cognitive processing in older CI recipients that was not manifested in the behavioral end products of processing. These data may have implications regarding clinical evaluation and rehabilitation procedures that should be tailored specifically for this unique group of patients.	\N	\N
25734571	This study assesses attention and response control through visual and auditory stimuli in a primary care pediatric sample. The sample consisted of 191 participants aged between 7 and 13 years old. It was divided into 2 groups: (a) 90 children with ADHD, according to diagnostic (DSM-IV-TR) (APA, 2002) and clinical (ADHD Rating Scale-IV) (DuPaul, Power, Anastopoulos, & Reid, 1998) criteria, and (b) 101 children without a history of ADHD. The aims were: (a) to determine and compare the performance of both groups in attention and response control, (b) to identify attention and response control deficits in the ADHD group. Assessments were carried out using the Integrated Visual and Auditory Continuous Performance Test (IVA/CPT, Sandford & Turner, 2002). Results showed that the ADHD group had visual and auditory attention deficits, F(3, 170) = 14.38; p < .01, deficits in fine motor regulation (Welch´s t-test = 44.768; p < .001) and sensory/motor activity (Welch'st-test = 95.683, p < .001; Welch's t-test = 79.537, p < .001). Both groups exhibited a similar performance in response control, F(3, 170) = .93, p = .43.Children with ADHD showed inattention, mental processing speed deficits, and loss of concentration with visual stimuli. Both groups yielded a better performance in attention with auditory stimuli.	\N	\N
25740521	Speech recognition in noise can be challenging for older adults and elicits elevated activity throughout a cingulo-opercular network that is hypothesized to monitor and modify behaviors to optimize performance. A word recognition in noise experiment was used to test the hypothesis that cingulo-opercular engagement provides performance benefit for older adults. Healthy older adults (N = 31; 50-81 years of age; mean pure tone thresholds <32 dB HL from 0.25 to 8 kHz, best ear; species: human) performed word recognition in multitalker babble at 2 signal-to-noise ratios (SNR = +3 or +10 dB) during a sparse sampling fMRI experiment. Elevated cingulo-opercular activity was associated with an increased likelihood of correct recognition on the following trial independently of SNR and performance on the preceding trial. The cingulo-opercular effect increased for participants with the best overall performance. These effects were lower for older adults compared with a younger, normal-hearing adult sample (N = 18). Visual cortex activity also predicted trial-level recognition for the older adults, which resulted from discrete decreases in activity before errors and occurred for the oldest adults with the poorest recognition. Participants demonstrating larger visual cortex effects also had reduced fractional anisotropy in an anterior portion of the left inferior frontal-occipital fasciculus, which projects between frontal and occipital regions where activity predicted word recognition. Together, the results indicate that older adults experience performance benefit from elevated cingulo-opercular activity, but not to the same extent as younger adults, and that declines in attentional control can limit word recognition.	\N	\N
25770375	Arthur Lessac developed a voice training approach that concentrated on three energies: structural action, tonal action, and consonant action. In Lessac-Madsen Resonant Voice Therapy (LMRVT), speech-language pathologists help patients achieve a resonant voice through structural posturing and awareness of tonal changes. However, LMRVT many not necessarily include the third component of Lessac's approach: consonant action.This study examines the effect that increased effort on consonant production has on the speaking voice-particularly regarding vocal loudness and projection. Audio samples were collected from eight actor participants who read a monologue using three distinct styles: normal articulation, poor articulation (elicited using a bite block), and overarticulation (elicited using a Lessac-based training intervention). Twenty graduate students of speech-language pathology listened to speech samples from the different conditions and made comparative judgments regarding articulation, loudness, and projection. Group results showed a strong correlation between the articulatory condition and the level of perceived loudness and projection. That is, as precision of articulation increased, the ratings of perceived loudness and projection increased, as well. These findings indicate that articulation treatment may have a positive influence on the perception of vocal loudness and projection. This has implications for future directions in expanding voice therapy modalities.	\N	\N
25773636	Most people derive pleasure from music. Neuroimaging studies show that the reward system of the human brain is central to this experience. Specifically, the dorsal and ventral striatum release dopamine when listening to pleasurable music, and activity in these structures also codes the reward value of musical excerpts. Moreover, the striatum interacts with cortical mechanisms involved in perception and valuation of musical stimuli. Recent studies have begun to explore individual differences in the way that this complex system functions. Development of a questionnaire for music reward experiences has allowed the identification of separable factors associated with musical pleasure, described as music-seeking, emotion-evocation, mood regulation, sensorimotor, and social factors. Applying this questionnaire to a large sample uncovered approximately 5% of the population with low sensitivity to musical reward in the absence of generalized anhedonia or depression. Further study of this group revealed that there are individuals who respond normally both behaviorally and psychophysiologically to rewards other than music (e.g., monetary value) but do not experience pleasure from music despite normal music perception ability and preserved ability to identify intended emotions in musical passages. This specific music anhedonia bears further study, as it may shed light on the function and dysfunction of the reward system.	\N	\N
25774428	The perception of near-threshold visual stimuli has been shown to depend in part on the phase (i.e., time in the cycle) of ongoing alpha (8-13 Hz) oscillations in the visual cortex relative to the onset of that stimulus. However, it is currently unknown whether the phase of the ongoing alpha activity can be manipulated by top-down factors such as attention or expectancy. Using three variants of a cross-modal attention paradigm with constant predictable stimulus onsets, we examined if cues signaling to attend to either the visual or the auditory domain influenced the phase of alpha oscillations in the associated sensory cortices. Importantly, intermixed in all three experiments, we included trials without a target to estimate the phase at target presentation without contamination from the early evoked responses. For these blank trials, at the time of expected target and distractor onset, we examined (1) the degree of the uniformity in phase angles across trials, (2) differences in phase angle uniformity compared with a pretarget baseline, and (3) phase angle differences between visual and auditory target conditions. Across all three experiments, we found that, although the cues induced a modulation in alpha power in occipital electrodes, neither the visual condition nor the auditory cue condition induced any significant phase-locking across trials during expected target or distractor presentation. These results suggest that, although alpha power can be modulated by top-down factors such as attention and expectation, the phase of the ongoing alpha oscillation is not under such control.	\N	\N
25774653	The effect of stimulation history on the perception of a current event can yield two opposite effects, namely: adaptation or hysteresis. The perception of the current event thus goes in the opposite or in the same direction as prior stimulation, respectively. In audiovisual (AV) synchrony perception, adaptation effects have primarily been reported. Here, we tested if perceptual hysteresis could also be observed over adaptation in AV timing perception by varying different experimental conditions. Participants were asked to judge the synchrony of the last (test) stimulus of an AV sequence with either constant or gradually changing AV intervals (constant and dynamic condition, respectively). The onset timing of the test stimulus could be cued or not (prospective vs. retrospective condition, respectively). We observed hysteretic effects for AV synchrony judgments in the retrospective condition that were independent of the constant or dynamic nature of the adapted stimuli; these effects disappeared in the prospective condition. The present findings suggest that knowing when to estimate a stimulus property has a crucial impact on perceptual simultaneity judgments. Our results extend beyond AV timing perception, and have strong implications regarding the comparative study of hysteresis and adaptation phenomena.	\N	\N
25781179	Lifestyle including smoking, noise exposure with MP3 player and drinking alcohol are considered as risk factors for affecting hearing synergistically. However, little is known about the association of cigarette smoking with hearing impairment among subjects who carry a lifestyle without using MP3 player and drinking alcohol. We showed here the influence of smoking on hearing among Bangladeshi subjects who maintain a lifestyle devoid of using MP3 player and drinking alcohol. A total of 184 subjects (smokers: 90; non-smokers: 94) were included considering their duration and frequency of smoking for conducting this study. The mean hearing thresholds of non-smoker subjects at 1, 4, 8 and 12 kHz frequencies were 5.63 ± 2.10, 8.56±5.75, 21.06 ± 11.06, 40.79 ± 20.36 decibel (dB), respectively and that of the smokers were 7 ± 3.8, 13.27 ± 8.4, 30.66 ± 12.50 and 56.88 ± 21.58 dB, respectively. The hearing thresholds of the smokers at 4, 8 and 12 kHz frequencies were significantly (p<0.05) higher than those of the non-smokers, while no significant differences were observed at 1 kHz frequency. We also observed no significant difference in auditory thresholds among smoker subgroups based on smoking frequency. In contrast, subjects smoked for longer duration (>5 years) showed higher level of auditory threshold (62.16 ± 19.87 dB) at 12 kHz frequency compared with that (41.52 ± 19.21 dB) of the subjects smoked for 1-5 years and the difference in auditory thresholds was statistically significant (p<0.0002). In this study, the Brinkman Index (BI) of smokers was from 6 to 440 and the adjusted odds ratio showed a positive correlation between hearing loss and smoking when adjusted for age and body mass index (BMI). In addition, age, but not BMI, also played positive role on hearing impairment at all frequencies. Thus, these findings suggested that cigarette smoking affects hearing level at all the frequencies tested but most significantly at extra higher frequencies.	\N	\N
25786320	The spatial specificity of auditory approaching and withdrawing aftereffects was investigated in an anechoic chamber. The adapting and testing stimuli were presented from loudspeakers located in front of the subject at the distance of 1.1 m (near) and 4.5 m (far) from the listener's head. Approach and withdrawal of stimuli were simulated by increasing or decreasing the amplitude of the wide-noise impulse sequence. The listeners were required to determine the movement direction of test stimulus following each 5-s adaptation period. The listeners' "withdrawal" responses were used for psychometric functions plotting and for quantitative assessment of auditory aftereffect. The data summarized for all 8 participants indicated that the asymmetry of approaching and withdrawing aftereffects depended on spatial localization of adaptor and test. The asymmetry of aftereffects was largest when adaptor and test were presented from the same loudspeaker (either near or far). Adaptation to the approach induced a directionally dependent displacement of the psychometric functions relative to control condition without adaptation and adaptation to the withdrawal was not. The magnitude of approaching aftereffect was greater when adaptor and test were located in near spatial domain than when they came from far domain. When adaptor and test were presented from the distinct loudspeakers, magnitude approaching aftereffect was decreasing in comparison to the same spatial localization, but after adaptation to withdrawal it was increasing. As a result, the directionally dependent displacements of the psychometric functions relative to control condition were observed after adaptation as to approach and to withdrawal. The discrepancy of the psychometric functions received after adaptation to approach and to withdrawal at near and far spatial domains was greater under the same localization of adaptor and test in comparison to their distinct localization. We assume that the peculiarities of approaching and withdrawing aftereffects observed reflect their spatial specificity. It is possible that spatial peculiarities of approaching and withdrawing aftereffects can be associated with specialized mechanisms for analysis of motion at the different distance from subject.	\N	\N
25786957	Performing a secondary task while listening to speech has a detrimental effect on speech processing, but the locus of the disruption within the speech system is poorly understood. Recent research has shown that cognitive load imposed by a concurrent visual task increases dependency on lexical knowledge during speech processing, but it does not affect lexical activation per se. This suggests that "lexical drift" under cognitive load occurs either as a post-lexical bias at the decisional level or as a secondary consequence of reduced perceptual sensitivity. This study aimed to adjudicate between these alternatives using a forced-choice task that required listeners to identify noise-degraded spoken words with or without the addition of a concurrent visual task. Adding cognitive load increased the likelihood that listeners would select a word acoustically similar to the target even though its frequency was lower than that of the target. Thus, there was no evidence that cognitive load led to a high-frequency response bias. Rather, cognitive load seems to disrupt sublexical encoding, possibly by impairing perceptual acuity at the auditory periphery.	\N	\N
25788705	Spatial crowding refers to impaired target identification when the target is surrounded by other stimuli in space temporal crowding refers to impaired target identification when the target is surrounded by other stimuli in time previously, when spatial and temporal crowding were measured in the fovea they were interrelated with amblyopic observers but almost absent with normal observers bonneh, sagi, & polat, 2007. In the current study we examined whether reliable temporal crowding can be found for normal observers with peripheral presentation 9° of eccentricity, and whether similar relations between temporal and spatial crowding will emerge to that end, we presented a sequence of three displays separated by a varying interstimulus interval (ISI). Each display included either one letter : experiments 1a ,: 1b ,: 1c or three letters separated by a varying interletter spacing: Experiments 2a ,: 2b). One of these displays included an oriented T. Observers indicated the T's orientation. As expected, we found spatial crowding: accuracy improved as the interletter spacing increased. Critically, we also found temporal crowding: in all experiments accuracy increased as the ISI increased, even when only stimulus-onset asynchronies (SOAs) larger than 150 ms were included, ensuring this effect does not reflect mere ordinary masking. Thus, with peripheral presentation, temporal crowding also emerged for normal observers. However, only a weak interaction between temporal and spatial crowding was found.	\N	\N
25798581	Contralateral masking is the phenomenon where a masker presented to one ear affects the ability to detect a signal in the opposite ear. For normal hearing listeners, contralateral masking results in masking patterns that are both sharper and dramatically smaller in magnitude than ipsilateral masking. The goal of this study was to investigate whether medial olivocochlear (MOC) efferents are needed for the sharpness and relatively small magnitude of the contralateral masking function. To do this, bilateral cochlear implant patients were tested because, by directly stimulating the auditory nerve, cochlear implants circumvent the effects of the MOC efferents. The results indicated that, as with normal hearing listeners, the contralateral masking function was sharper than the ipsilateral masking function. However, although there was a reduction in the magnitude of the contralateral masking function compared to the ipsilateral masking function, it was relatively modest. This is in sharp contrast to the results of normal hearing listeners where the magnitude of the contralateral masking function is greatly reduced. These results suggest that MOC function may not play a large role in the sharpness of the contralateral masking function but may play a considerable role in the magnitude of the contralateral masking function.	\N	\N
25816820	The Fukuda stepping test is commonly used to assess peripheral vestibular function. It has, however, been suggested that its maximal sensitivity and specificity are 70 per cent and 50 per cent, respectively. This study was undertaken to evaluate environmental factors that may influence the reliability of this assessment and hence to 'sharpen' its use in a clinical setting. Forty-four participants aged between 20 and 43 years were asked to perform the Fukuda stepping test in both a standard clinic room and a soundproofed room under the following conditions in a randomised order: on the floor versus on foam; with and without a sound-localising source; and with and without ear defenders. Significant differences in the extent of rotation were found when comparing the results obtained in several settings, including standing on the floor in a standard room versus a soundproofed room (p = 0.036), and standing on foam in a standard room versus a soundproofed room (p = 0.015). Our results suggest that certain alterations to the test environment may improve the sensitivity of this clinical examination.	\N	\N
25832187	Previous studies have shown that discrimination sensitivity in 2AFC tasks depends on the presentation order of the standard and comparison stimulus. The present study examined whether this so-called Type B effect generalizes across different standard magnitudes. Therefore, Experiment 1 employed an auditory duration discrimination task with short (100 ms) and long (1,000 ms) standard durations and a constant interstimulus interval (ISI) of 1,000 ms. For both standard durations, a clear Type B effect emerged. In Experiment 2, discrimination sensitivity was assessed for short (300 ms) and long (1,000 ms) ISIs and a constant standard duration of 100 ms, in order to examine whether the Type B effect diminishes or even reverses when both stimuli are presented in rapid succession, as was suggested by previous studies. In the short, but not the long ISI condition, the Type B effect was virtually eliminated. Taken together, the present experiments suggest that the Type B effect is robust across standard magnitude, but diminishes when the time interval between both stimuli is reduced. This result pattern is discussed within the framework of the Internal Reference Model and the Sensation Weighting Model. It is also demonstrated that both models provide a quantitative account of the present results.	\N	\N
25878263	Amplitude modulations are fundamental features of natural signals, including human speech and nonhuman primate vocalizations. Because natural signals frequently occur in the context of other competing signals, we used a forward-masking paradigm to investigate how the modulation context of a prior signal affects cortical responses to subsequent modulated sounds. Psychophysical "modulation masking," in which the presentation of a modulated "masker" signal elevates the threshold for detecting the modulation of a subsequent stimulus, has been interpreted as evidence of a central modulation filterbank and modeled accordingly. Whether cortical modulation tuning is compatible with such models remains unknown. By recording responses to pairs of sinusoidally amplitude modulated (SAM) tones in the auditory cortex of awake squirrel monkeys, we show that the prior presentation of the SAM masker elicited persistent and tuned suppression of the firing rate to subsequent SAM signals. Population averages of these effects are compatible with adaptation in broadly tuned modulation channels. In contrast, modulation context had little effect on the synchrony of the cortical representation of the second SAM stimuli and the tuning of such effects did not match that observed for firing rate. Our results suggest that, although the temporal representation of modulated signals is more robust to changes in stimulus context than representations based on average firing rate, this representation is not fully exploited and psychophysical modulation masking more closely mirrors physiological rate suppression and that rate tuning for a given stimulus feature in a given neuron's signal pathway appears sufficient to engender context-sensitive cortical adaptation.	\N	\N
25885195	To verify the effect of long-term use of hearing aids with frequency compression for verbal behavior tests and daily activities. Thirty-two adults, aged between 30 and 60 years old, with moderate to severe sensorineural hearing loss at high frequencies with steeply sloping configuration were divided into two groups: 16 with hearing aids with frequency compression algorithm enabled and 16 not enabled. All participants underwent the detection tests of consonant sounds, monosyllable recognition in quiet environments, identification of fricative monosyllables, and Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire in five times throughout a 12-month trial. Detection of consonant sounds, recognition of monosyllables in quiet environments and identification of fricative monosyllables improved significantly with frequency compression enabled. Participants had their APHAB scores improved whether they were adapted to the frequency compression or not. Frequency compression provides the anticipated improvement in audibility, detection of high-frequency consonant sounds, and recognition of monosyllables.	\N	\N
25913551	Since 1972, the World Health Organization (WHO) has declared noise as a pollutant. Over the last decades, the quality of the urban environment has attracted the interest of researchers due to the growing urban sprawl, especially in developing countries. The objective of this study was to evaluate the effects of noise exposure in six urban soundscapes: Areas with high and low levels of noise in scenarios of leisure, work, and home. Cross-sectional study. The study was conducted in two steps: Evaluation of noise levels, with the development of noise maps, and health related inquiries. 180 individuals were interviewed, being 60 in each scenario, divided into 30 exposed to high level of noise and 30 to low level. Chi-Square test and Ordered Logistic Regression Model (P < 0,005). 70% of the interviewees reported noticing some source of noise in the selected scenarios and it was observed an association between exposure and perception of some source of noise (P < 0.001). 41.7% of the interviewees reported some degree of annoyance, being that this was associated with exposure (P < 0.001). There was also an association between exposure in different scenarios and reports of poor quality of sleep (P < 0.001). In the scenarios of work and home, the chance of reporting annoyance increased when compared with the scenario of leisure. We conclude that the use of this sort of assessment may clarify the relationship between urban noise exposure and health.	\N	\N
25914528	The possible relationship between audiometric hearing thresholds and cognitive performance on language tests was analyzed in a cross-sectional cohort of older adults aged ≥65 years (N=98) with different degrees of cognitive impairment. Participants were distributed into two groups according to Reisberg's Global Deterioration Scale (GDS): a normal/predementia group (GDS scores 1-3) and a moderate/moderately severe dementia group (GDS scores 4 and 5). Hearing loss (pure-tone audiometry) and receptive and production-based language function (Verbal Fluency Test, Boston Naming Test, and Token Test) were assessed. Results showed that the dementia group achieved significantly lower scores than the predementia group in all language tests. A moderate negative correlation between hearing loss and verbal comprehension (r=-0.298; P<0.003) was observed in the predementia group (r=-0.363; P<0.007). However, no significant relationship between hearing loss and verbal fluency and naming scores was observed, regardless of cognitive impairment. In the predementia group, reduced hearing level partially explains comprehension performance but not language production. In the dementia group, hearing loss cannot be considered as an explanatory factor of poor receptive and production-based language performance. These results are suggestive of cognitive rather than simply auditory problems to explain the language impairment in the elderly.	\N	\N
25920851	Broadened auditory filters associated with sensorineural hearing loss have clearly been shown to diminish speech recognition in noise for adults, but far less is known about potential effects for children. This study examined speech recognition in noise for adults and children using simulated auditory filters of different widths. Specifically, 5 groups (20 listeners each) of adults or children (5 and 7 yrs), were asked to recognize sentences in speech-shaped noise. Seven-year-olds listened at 0 dB signal-to-noise ratio (SNR) only; 5-yr-olds listened at +3 or 0 dB SNR; and adults listened at 0 or -3 dB SNR. Sentence materials were processed both to smear the speech spectrum (i.e., simulate broadened filters), and to enhance the spectrum (i.e., simulate narrowed filters). Results showed: (1) Spectral smearing diminished recognition for listeners of all ages; (2) spectral enhancement did not improve recognition, and in fact diminished it somewhat; and (3) interactions were observed between smearing and SNR, but only for adults. That interaction made age effects difficult to gauge. Nonetheless, it was concluded that efforts to diagnose the extent of broadening of auditory filters and to develop techniques to correct this condition could benefit patients with hearing loss, especially children.	\N	\N
25994736	A follow-up experiment to those conducted by Brown and Yost [(2011). J. Acoust. Soc. Am. 130, 358-364; (2013). Basic Aspects of Hearing: Physiology and Perception (Springer, London, UK)] examined interaural time difference (ITD) discrimination for a low-frequency target noise band flanked by monotic noise bands that were either lower-frequency than the target band, higher-frequency, or both. The flanking bands were either spectrally contiguous with the target band or spectrally separated. Significant interference in ITD processing occurred in the presence of the high-frequency flanking band. Results are discussed by way of a comparison of the conditions in the present study to those in studies of binaural interference. The possible role of attention is also discussed.	\N	\N
25997868	In cochlear implant (CI) recipients with unilateral hearing loss (UHL) and normal hearing (NH) in the contralateral ear, the central auditory system receives signals of different auditory modalities, i.e. electrically via the CI ear as well as acoustically via the NH ear. The present study investigates binaural integration of bimodal stimulation in the central auditory system of 10 CI subjects with UHL by applying a modified version of the Rapidly Alternating Speech Perception (RASP) test to characterise speech recognition ability under monotic and dichotic listening arrangements. Subsequently, the results for each monotic and dichotic test condition were compared to quantify the binaural benefit from CI usage. The study results demonstrate significantly improved speech recognition under dichotic compared to monotic listening conditions, providing evidence that there is binaural integration of acoustically and electrically transmitted speech segments in the central nervous system at brainstem and cortical levels. In contrast to more commonly used tests of binaural integration, such as localisation, the RASP test provides the clinical option to investigate binaural integration involving structures at the cortical level.	\N	\N
25998097	Recommendation for cochlear implant (CI) treatment for individuals with severe to profound single-sided deafness (SSD) and asymmetrical hearing loss (AHL) is on the rise. This raises the need for greater consistency in the definition of CI candidacy for these cases and in the assessment methods of patient-related benefits to permit effective comparison and interpretation of the outcomes with both conventional and implantable options across studies. During a dedicated seminar on implant treatment in AHL patients, the panellists of the closing round table reviewed the clinical experience presented with the aim to define clear audiometric characteristics for both AHL and SSD cases, as well as a common data set enabling consistent evaluation of hearing benefits in this population. The panellists agreed on a clear differentiation between AHL and SSD CI candidates, defining average pure-tone thresholds up to 4 kHz for better and poorer ears. Agreement was reached on a minimum set of assessment procedures, and included the necessity of trials with conventional CROS/BICROS hearing aids and bone conduction devices before considering CI treatment. Objective assessment of sound localisation abilities was identified as the most relevant criterion to quantify performance before and after treatment. In parallel, subjective assessment of overall hearing ability was recommended via the Speech, Spatial and Qualities of hearing questionnaire. Longitudinal follow-up of these parameters and the hours of daily use were considered essential to reflect the potential treatment benefits for this population. The consistency in the data collection and its report will further support health authorities in their decision on acceptable gains from available hearing loss treatment options.	\N	\N
26017796	To compare the efficacy and feasibility of teleaudiometry with that of sweep audiometry in elementary school children, using pure-tone audiometry as the gold standard. A total of 243 students with a mean age of 8.3 years participated in the study. Of these, 118 were boys, and 125 were girls. The following procedures were performed: teleaudiometry screening with software that evaluates hearing at frequencies of 1,000, 2000 and 4000 Hz at 25 dBHL; sweep audiometry screening in an acoustic booth (20 dBHL at the same frequencies); pure-tone audiometry thresholds in an acoustic booth (frequencies of 500, 1000, 2000 and 4000 Hz); and acoustic immittance measurements. The diagnostic capacities of the teleaudiometry/sweep audiometry screening methods were as follows: sensitivity  ϝ  58%/65%; specificity  ϝ  86%/99%; positive predictive value  ϝ  51%/91%; negative predictive value  ϝ  89%/92%; and accuracy  ϝ  81%/92%. Teleaudiometry and sweep audiometry showed moderate agreement. Furthermore, the use of these methods in series with immittance testing improved the specificity, whereas parallel testing improved the sensitivity. Teleaudiometry was found to be reliable and feasible for screening hearing in school children. Moreover, teleaudiometry is the preferred method for remote areas where specialized personnel and specific equipment are not available, and its use may reduce the costs of hearing screening programs.	\N	\N
26025759	Our fMRI study investigates auditory rhyme processing in spoken language to further elucidate the topic of functional lateralization of language processing. During scanning, 14 subjects listened to four different types of versed word strings and subsequently performed either a rhyme or a meter detection task. Our results show lateralization to auditory-related temporal regions in the right hemisphere irrespective of task. As for the left hemisphere we report responses in the supramarginal gyrus as well as in the opercular part of the inferior frontal gyrus modulated by the presence of regular meter and rhyme. The interaction of rhyme and meter was associated with increased involvement of the superior temporal sulcus and the putamen of the right hemisphere. Overall, these findings support the notion of right-hemispheric specialization for suprasegmental analyses during processing of spoken sentences and provide neuroimaging evidence for the influence of metrics on auditory rhyme processing.	\N	\N
26055197	The timely diagnosis and treatment of acquired hearing loss in the pediatric population has significant implications for a child's development. Audiological assessment in children, however, carries both technological and logistical challenges. Typically, specialized methods (such as play audiometry) are required to maintain the child's attention and can be resource intensive. These challenges were previously addressed by a novel, calibrated, interactive play audiometer for Apple(®) iOS(®) called "ShoeBOX Audiometry". This device has potential applications for deployment in environments where traditional clinical audiometry is either unavailable or impractical. The objective of this study was to assess the screening capability of the tablet audiometer in an uncontrolled environment using consumer ear-bud headphones. Consecutive patients presenting to the Audiology Clinic at the Children's Hospital of Eastern Ontario (ages 4 and older) were recruited. Participants' hearing was evaluted using the tablet audiometer calibrated to Apple(®) In-Ear headphones. The warble tone thresholds obtained were compared to gold standard measurements taken with a traditional clinical audiometer inside a soundbooth. 80 patients were enrolled. The majority of participants were capable of completing an audiologic assessment using the tablet computer. Due to ambient noise levels outside a soundbooth, thresholds obtained at 500Hz were not consistent with traditional audiometry. Excluding 500Hz threholds, the tablet audiometer demonstrated strong negative predictive value (89.7%) as well as strong sensitivity (91.2%) for hearing loss. Thresholds obtained in an uncontrolled setting are not reflective of diagnostic thresholds due to the uncalibrated nature of the headphones and variability of the setting without a booth. Nevertheless, the tablet audiometer proved to be both a valid and sensitive instrument for unsupervised screening of warble-tone thresholds in children.	\N	\N
26065403	To date, there have been less than 30 cases of cochlear implantation (CI) in patients with superficial siderosis (SS) reported in the literature. The primary objective of the current study is to evaluate CI outcomes in six additional patients (seven ears) with SS and sensorineural hearing loss (SNHL) and to perform a systematic review of the literature. Case series and systematic review of the literature. Two tertiary academic CI centers. All patients with SS who underwent CI between 2007 and 2014. Cochlear implantation. Pre- and post-implantation speech perception scores and durability of benefit. A total of seven ears (four males; median age 52 yr) with SS and SNHL met inclusion criteria. All patients developed progressive bilateral SNHL that was no longer amenable to conventional hearing aids. Additional presenting symptoms included vestibulopathy (n = 4), cerebellar ataxia (n = 3), mild dementia (n = 1), and myelopathy (n = 1). All patients underwent uncomplicated CI, and intraoperative device telemetry revealed normal responses in all electrodes. The median postoperative auditory threshold average was 32.5 dB HL (range 16-36 dB) and the median postoperative CNC word score was 51% (range 46-64%). The median duration of follow-up was 15.5 months (range 3-64 mo). All patients demonstrated initial improvement in speech perception testing. Two patients had performance decline and worsening dementia resulting from progressive SS. Cochlear implantation is a viable strategy for auditory rehabilitation in patients with SS and associated SNHL. Most individuals enjoy benefit from CI; however, patients should be counseled regarding the risks of performance decline with progressive SS.	\N	\N
26093425	Natural auditory scenes often consist of several sound sources overlapping in time, but separated in space. Yet, location is not fully exploited in auditory grouping: spatially separated sounds can get perceptually fused into a single auditory object and this leads to difficulties in the identification and localization of concurrent sounds. Here, the brain mechanisms responsible for grouping across spatial locations were explored in magnetoencephalography (MEG) recordings. The results show that the cortical representation of a vowel spatially separated into two locations reflects the perceived location of the speech sound rather than the physical locations of the individual components. In other words, the auditory scene is neurally rearranged to bring components into spatial alignment when they were deemed to belong to the same object. This renders the original spatial information unavailable at the level of the auditory cortex and may contribute to difficulties in concurrent sound segregation.	\N	\N
26093429	Sound focusing is to create a concentrated acoustic field in the region surrounded by a loudspeaker array. This problem was tackled in the previous research via the Helmholtz integral approach, brightness control, acoustic contrast control, etc. In this paper, the same problem was revisited from the perspective of beamforming. A source array model is reformulated in terms of the steering matrix between the source and the field points, which lends itself to the use of beamforming algorithms such as minimum variance distortionless response (MVDR) and linearly constrained minimum variance (LCMV) originally intended for sensor arrays. The beamforming methods are compared with the conventional methods in terms of beam pattern, directional index, and control effort. Objective tests are conducted to assess the audio quality by using perceptual evaluation of audio quality (PEAQ). Experiments of produced sound field and listening tests are conducted in a listening room, with results processed using analysis of variance and regression analysis. In contrast to the conventional energy-based methods, the results have shown that the proposed methods are phase-sensitive in light of the distortionless constraint in formulating the array filters, which helps enhance audio quality and focusing performance.	\N	\N
26093435	Working memory capacity has been linked to performance on many higher cognitive tasks, including the ability to perceive speech in noise. Current efforts to train working memory have demonstrated that working memory performance can be improved, suggesting that working memory training may lead to improved speech perception in noise. A further advantage of working memory training to improve speech perception in noise is that working memory training materials are often simple, such as letters or digits, making them easily translatable across languages. The current effort tested the hypothesis that working memory training would be associated with improved speech perception in noise and that materials would easily translate across languages. Native Mandarin Chinese and native English speakers completed ten days of reversed digit span training. Reading span and speech perception in noise both significantly improved following training, whereas untrained controls showed no gains. These data suggest that working memory training may be used to improve listeners' speech perception in noise and that the materials may be quickly adapted to a wide variety of listeners.	\N	\N
26093448	Physiological measures of neural activity in the auditory cortex have revealed plasticity following unilateral deafness. Central projections from the remaining ear reorganize to produce a stronger cortical response than normal. However, little is known about the perceptual consequences of this increase. One possibility is improved sound intensity discrimination. Intensity difference limens were measured in 11 individuals with unilateral deafness that were previously shown to exhibit increased cortical activity to sounds heard by the intact ear. Significantly smaller mean difference limens were observed compared with controls. These results provide evidence of the perceptual consequences of plasticity in humans following unilateral deafness.	\N	\N
26107084	To examine the voice and personality characteristics of patients diagnosed with organic dysphonia secondary to vocal fold immobility. The study comprised patients of both genders, attending the Clinic School of Speech Therapy of the Federal University of Paraíba, with otorhinolaryngological diagnosis of vocal fold immobility and speech therapy diagnosis of dysphonia. The self-assessment of voice was measured through a Vocal Screening Protocol and Voice Symptoms Scale (VoiSS), the voice was collected for auditory-perceptive evaluation, and the Factorial Personality Battery (FPB) was used. Descriptive statistical analysis was performed to determine the frequency, mean, and standard deviation of the studied variables. Eight patients participated in the study, of both genders, with average age of 40.4 ± 16.9 years. The more frequent risk factors were the personal ones (4.7 ± 2.1). In the VoiSS, the patients presented a higher average in the limitation score (34.1 ± 15.7). From the auditory-perceptive evaluation, moderate intensity of vocal deviation was obtained, with predominant vocal roughness (57.7 ± 25.2). In the FPB, the patients had an average higher than the cutoff scores in neuroticism (3.8 ± 1.4) and accomplishment (5.2 ± 1.0). The predominant vocal parameter was roughness. The patients referred to a few risk factors that compromise the vocal behavior and presented the neuroticism and realization factors as a highlight in their personality. Thus, individuals with vocal fold immobility show personality characteristics that may be a reflection of their voice disorder, not a factor that determines their dysphonia.	\N	\N
26121827	To assess the clinical effeetiveness of prelingually deaf children after cochlear implantation at different ages so as to provide reasonable expectations for the patients and guidance for the clinical treatment. Electronic databases PubMed, YZ365. COM, WANFANG DATA, CMJD, CHKD, CNKI were searched using relevant keywords. Extracted data included author, year of publication, diagnosis, et al. Reported treatment outcomes were clustered into speech discrimination and hearing abilities. Meta-analyses were performed on studies with numerical results using random or fixed effects model. There were eight randomized control studies including 442 patients. Comparing speech perception of prelingually deaf children after cochlear implantation younger than three years old (experimental group) and 3-6 years old (control group), three and six months after operation showed that experimental group performed significantly worse than control group; 12 months after operation showed that experimental group performed significantly better than control group. Comparing hearing abilities, three and six months after operation showed that experimental group performed significantly worse than control group; 12 months after operation showed showed that experimental group performed significantly better than control group. Comparing speech perception of younger or older than 4. 5 years old children showed that after 1.5-2 years of operation children implanted younger than 4.5 years of age performed significantly better than children implanted older than 4.5 years old. Comparing speech perception of 7-12 years old children showed that after 3, 6, 12 months of operation patients of 7-12 years old performed significantly better than those children older than 12 years old. Comparing speech perception of implantation younger or older than 18 years old (7-14 yeas old was group A, > 14-18 yeas old was group B, older than 18 yeas old was group C) showed that after one and four years of operation A > B > C, and there were significant differences among them. Comparing warble tone threshold average (WTA) showed that after one year of operation A < B < C, and there were significant differences among them. However, after four years of operation, there was no significant difference among them. Prelinguistically deafened patients younger than three years old with cochlear implantation, insisting on scienctific rehabilitation training for a long period of time can receive the optimal recovery effect. The older patients are suggested as early as possible receiving cochlear implantation. The longer they are implanted, the better results they will receive. Moreover, the younger age they are implanted, the faster postoperative language progress they will receive. Further controlled studies with longer follow-up periods and more person included may make the effectiveness of cochlear implantaion more reliable.	\N	\N
26152053	During the first years of life, sensory modalities communicate with each other. This process is fundamental for the development of unisensory and multisensory skills. The absence of one sensory input impacts on the development of other modalities. Since 2008 we have studied these aspects and developed our cross-sensory calibration theory. This theory emerged from the observation that children start to integrate multisensory information (such as vision and touch) only after 8-10 years of age. Before this age the more accurate sense teaches (calibrates) the others; when one calibrating modality is missing, the other modalities result impaired. Children with visual disability have problems in understanding the haptic or auditory perception of space and children with motor disabilities have problems in understanding the visual dimension of objects. This review presents our recent studies on multisensory integration and cross-sensory calibration in children and adults with and without sensory and motor disabilities. The goal of this review is to show the importance of interaction between sensory systems during the early period of life in order to correct perceptual development to occur.	\N	\N
26152058	Echolocation can be used by blind and sighted humans to navigate their environment. The current study investigated the neural activity underlying processing of path direction during walking. Brain activity was measured with fMRI in three blind echolocation experts, and three blind and three sighted novices. During scanning, participants listened to binaural recordings that had been made prior to scanning while echolocation experts had echolocated during walking along a corridor which could continue to the left, right, or straight ahead. Participants also listened to control sounds that contained ambient sounds and clicks, but no echoes. The task was to decide if the corridor in the recording continued to the left, right, or straight ahead, or if they were listening to a control sound. All participants successfully dissociated echo from no echo sounds, however, echolocation experts were superior at direction detection. We found brain activations associated with processing of path direction (contrast: echo vs. no echo) in superior parietal lobule (SPL) and inferior frontal cortex in each group. In sighted novices, additional activation occurred in the inferior parietal lobule (IPL) and middle and superior frontal areas. Within the framework of the dorso-dorsal and ventro-dorsal pathway proposed by Rizzolatti and Matelli (2003), our results suggest that blind participants may automatically assign directional meaning to the echoes, while sighted participants may apply more conscious, high-level spatial processes. High similarity of SPL and IFC activations across all three groups, in combination with previous research, also suggest that all participants recruited a multimodal spatial processing system for action (here: locomotion).	\N	\N
26177161	Code-blends (simultaneous words and signs) are a unique characteristic of bimodal bilingual communication. Using fMRI, we investigated code-blend comprehension in hearing native ASL-English bilinguals who made a semantic decision (edible?) about signs, audiovisual words, and semantically equivalent code-blends. English and ASL recruited a similar fronto-temporal network with expected modality differences: stronger activation for English in auditory regions of bilateral superior temporal cortex, and stronger activation for ASL in bilateral occipitotemporal visual regions and left parietal cortex. Code-blend comprehension elicited activity in a combination of these regions, and no cognitive control regions were additionally recruited. Furthermore, code-blends elicited reduced activation relative to ASL presented alone in bilateral prefrontal and visual extrastriate cortices, and relative to English alone in auditory association cortex. Consistent with behavioral facilitation observed during semantic decisions, the findings suggest that redundant semantic content induces more efficient neural processing in language and sensory regions during bimodal language integration.	\N	\N
26185045	Discourse structure enables us to generate expectations based upon linguistic material that has already been introduced. The present magnetoencephalography (MEG) study addresses auditory perception of test sentences in which discourse coherence was manipulated by using presuppositions (PSP) that either correspond or fail to correspond to items in preceding context sentences with respect to uniqueness and existence. Context violations yielded delayed auditory M50 and enhanced auditory M200 cross-correlation responses to syllable onsets within an analysis window of 1.5s following the PSP trigger words. Furthermore, discourse incoherence yielded suppression of spectral power within an expanded alpha band ranging from 6 to 16Hz. This effect showed a bimodal temporal distribution, being significant in an early time window of 0.0-0.5s following the PSP trigger and a late interval of 2.0-2.5s. These findings indicate anticipatory top-down mechanisms interacting with various aspects of bottom-up processing during speech perception.	\N	\N
26185046	A number of studies have shown that from an early age, bilinguals outperform their monolingual peers on executive control tasks. We previously found that bilingual children and adults also display greater attention to unexpected language switches within speech. Here, we investigated the effect of a bilingual upbringing on speech perception in one language. We recorded monolingual and bilingual toddlers' event-related potentials (ERPs) to spoken words preceded by pictures. Words matching the picture prime elicited an early frontal positivity in bilingual participants only, whereas later ERP amplitudes associated with semantic processing did not differ between groups. These results add to the growing body of evidence that bilingualism increases overall attention during speech perception whilst semantic integration is unaffected.	\N	\N
26200250	Event-related brain potentials (ERPs) demonstrate that human auditory cortical responses are sensitive to changes in static pitch as indexed by the pitch onset response (POR), a negativity generated at the initiation of acoustic periodicity. Yet, it is still unclear if this brain signature is sensitive to dynamic, time-varying properties of pitch more characteristic of those found in naturalistic speech and music. Neuroelectric PORs were recorded in response to contrastive pitch patterns differing in their pitch height, time-variance, and directionality (i.e., rise vs. fall). Broadband noise followed by contiguous iterated rippled noise (producing salient pitch sweeps) was used to temporally separate neural activity coding the onset of acoustic energy from the onset of time-varying pitch. Analysis of PORs revealed distinct modulations in response latency that distinguished static from time-varying pitch contours (steady-state<dynamic) and pitch height (high<low). However, PORs were insensitive to the direction of pitch sweeps (rise=fall). Our findings suggest that the POR signature provides a useful neural index of auditory cortical pitch processing for some, but not all pitch-evoking stimuli.	\N	\N
26222937	To analyze the occurrence of acoustic reflex and its threshold on newborns using the 226 and 1,000 Hz probes. Thirty-six newborns with "PASS" results in newborn hearing screening and tympanogram with one or two peaks for both probe tones were included. Group I comprised 20 full-term newborns without risk indicator for hearing loss, and Group II comprised 16 newborns with at least one risk indicator. The study about ipsilateral acoustic reflex thresholds was conducted in 500, 1,000, 2,000, and 4,000 Hz. The groups presented the acoustic reflex thresholds between 50 and 100 dB for both probe tones. In the comparison between the probes, there were differences in all frequencies evaluated in Group I, with the lowest threshold mean for the 1,000 Hz probe. In Group II, differences were detected at 2,000 Hz. The mean acoustic reflex thresholds were similar in both groups for the 226 Hz probe. There was a difference for the 1,000 Hz probe in all tested frequencies. The percentage of response was higher in both groups for the 1,000 Hz probe. The kappa test showed extremely poor agreement in the comparison of results between both probes. The occurrence of acoustic reflex was higher in newborns and its thresholds were lower with the 1,000 Hz probe both for healthy newborns and for newborns at risk.	\N	\N
26290244	Plasticity in the visual cortex of blind individuals provides a rare window into the mechanisms of cortical specialization. In the absence of visual input, occipital ("visual") brain regions respond to sound and spoken language. Here, we examined the time course and developmental mechanism of this plasticity in blind children. Nineteen blind and 40 sighted children and adolescents (4-17 years old) listened to stories and two auditory control conditions (unfamiliar foreign speech, and music). We find that "visual" cortices of young blind (but not sighted) children respond to sound. Responses to nonlanguage sounds increased between the ages of 4 and 17. By contrast, occipital responses to spoken language were maximal by age 4 and were not related to Braille learning. These findings suggest that occipital plasticity for spoken language is independent of plasticity for Braille and for sound. We conclude that in the absence of visual input, spoken language colonizes the visual system during brain development. Our findings suggest that early in life, human cortex has a remarkably broad computational capacity. The same cortical tissue can take on visual perception and language functions. Studies of plasticity provide key insights into how experience shapes the human brain. The "visual" cortex of adults who are blind from birth responds to touch, sound, and spoken language. To date, all existing studies have been conducted with adults, so little is known about the developmental trajectory of plasticity. We used fMRI to study the emergence of "visual" cortex responses to sound and spoken language in blind children and adolescents. We find that "visual" cortex responses to sound increase between 4 and 17 years of age. By contrast, responses to spoken language are present by 4 years of age and are not related to Braille-learning. These findings suggest that, early in development, human cortex can take on a strikingly wide range of functions.	\N	\N
26323201	To determine if differences between dyslexic and typical readers in their reading scores and verbal IQ are evident as early as first grade and whether the trajectory of these differences increases or decreases from childhood to adolescence. The subjects were the 414 participants comprising the Connecticut Longitudinal Study, a sample survey cohort, assessed yearly from 1st to 12th grade on measures of reading and IQ. Statistical analysis employed longitudinal models based on growth curves and multiple groups. As early as first grade, compared with typical readers, dyslexic readers had lower reading scores and verbal IQ, and their trajectories over time never converge with those of typical readers. These data demonstrate that such differences are not so much a function of increasing disparities over time but instead because of differences already present in first grade between typical and dyslexic readers. The achievement gap between typical and dyslexic readers is evident as early as first grade, and this gap persists into adolescence. These findings provide strong evidence and impetus for early identification of and intervention for young children at risk for dyslexia. Implementing effective reading programs as early as kindergarten or even preschool offers the potential to close the achievement gap.	\N	\N
26336746	Dynamics of activity in the frequency band of theta waves during of procedures, listening of the acoustic image of the own EEG was investigated. The formation of the acoustic image EEG was performed with a significant reduction of musical properties. It is shown that the increase in activity in the theta range depends on the level of synchronization and consistency of the presentation of the acoustic image own EEG relative to the current bioelectrical activity of the brain. The maximum increase in activity in the theta range was observed with minimum time delay and maximum consistency requirements of sounds with the current EEG. It is concluded that the increase in activity in the range of theta waves in the listening environment acoustic image own EEG is determined by the correlation of sounds with the current bioelectric activity of the brain.	\N	\N
26377472	Human cortex is comprised of specialized networks that support functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity offer unique insights into this question. In congenitally blind individuals, "visual" cortex responds to auditory and tactile stimuli. Remarkably, recent evidence suggests that occipital areas participate in language processing. We asked whether in blindness, occipital cortices: (1) develop domain-specific responses to language and (2) respond to a highly specialized aspect of language-syntactic movement. Nineteen congenitally blind and 18 sighted participants took part in two fMRI experiments. We report that in congenitally blind individuals, but not in sighted controls, "visual" cortex is more active during sentence comprehension than during a sequence memory task with nonwords, or a symbolic math task. This suggests that areas of occipital cortex become selective for language, relative to other similar higher-cognitive tasks. Crucially, we find that these occipital areas respond more to sentences with syntactic movement but do not respond to the difficulty of math equations. We conclude that regions within the visual cortex of blind adults are involved in syntactic processing. Our findings suggest that the cognitive function of human cortical areas is largely determined by input during development. Human cortex is made up of specialized regions that perform different functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity show that cortical areas can change function from one sensory modality to another. Here we demonstrate that input during development can alter cortical function even more dramatically. In blindness a subset of "visual" areas becomes specialized for language processing. Crucially, we find that the same "visual" areas respond to a highly specialized and uniquely human aspect of language-syntactic movement. These data suggest that human cortex has broad functional capacity during development, and input plays a major role in determining functional specialization.	\N	\N
26380997	The usage of personal listening devices (PLDs) is associated with risks of hearing loss. The aim of this study is to evaluate the effects of music exposure from these devices on high-frequency hearing thresholds of PLD users. A total of 282 young adults were questioned regarding their listening habits and symptoms associated with PLD listening. Their audiogram thresholds were determined at high (3-8 kHz) frequencies and extended high frequencies (EHFs, 9-16 kHz). The preferred listening volumes of PLD users were used to compute their overall 8-h equivalent music exposure levels (LAeq8h). Approximately 80% of the subjects were regular PLD users. Of these, 20.1% had LAeq8h of ≥75 dBA, while 4.4% of them had LAeq8h of ≥85 dBA, which carries a high risk of hearing damage. Compared with those exposed to LAeq8h of <75 dBA, subjects who had LAeq8h of ≥75 dBA reported a significantly higher incidence of tinnitus and difficulty in hearing others immediately after using PLDs. PLD users who were exposed to LAeq8h of ≥75 dBA and had been using their devices for ≥4 years also showed significantly higher mean audiogram thresholds compared with non-users at most EHFs tested. In addition, the thresholds of PLD users at EHFs showed a weak but significant positive correlation with their LAeq8h. The present findings suggest that excessive exposure to music among PLD users may lead to initial effects on their hearing at very high frequencies.	\N	\N
26536965	It has been shown that musicians are at risk of noise-induced hearing loss. The aim of the study has been to evaluate the temporary changes of hearing in the case of orchestral musicians after group rehearsals. The study group comprised 18 orchestral musicians, aged 30-58 years old (mean: 40 years old) having 12-40 years (mean: 22 years) of professional experience. The temporary changes in hearing after group rehearsals were determined using transient-evoked otoacoustic emissions (TEOAEs). Noise exposures during group rehearsals were also evaluated. Musicians' hearing threshold levels were higher (worse) than expected for the equivalent non-noise-exposed population. Moreover, the high frequency notched audiograms were observed in some of them. After rehearsals, during which musicians were exposed to orchestral noise at A-weighted equivalent-continuous sound pressure level (normalized to 8-h working day) varied from 75.6-83.1 dB (mean: 79.4 dB). The significant post-exposure reductions of TEOAE amplitudes (approx. 0.7 dB) both for the total response and frequency bands of 2000 and 3000 Hz were noted. However, there were no significant differences between pre- and postexposure reproducibility of TEOAE. Obtained results have confirmed that orchestral musicians are at risk of hearing loss due to their professional activities, even at exposures to orchestral noise less than the limit values for occupational noise.	\N	\N
26538659	Deficits in auditory emotion recognition (AER) are a core feature of schizophrenia and a key component of social cognitive impairment. AER deficits are tied behaviorally to impaired ability to interpret tonal ("prosodic") features of speech that normally convey emotion, such as modulations in base pitch (F0M) and pitch variability (F0SD). These modulations can be recreated using synthetic frequency modulated (FM) tones that mimic the prosodic contours of specific emotional stimuli. The present study investigates neural mechanisms underlying impaired AER using a combined event-related potential/resting-state functional connectivity (rsfMRI) approach in 84 schizophrenia/schizoaffective disorder patients and 66 healthy comparison subjects. Mismatch negativity (MMN) to FM tones was assessed in 43 patients/36 controls. rsfMRI between auditory cortex and medial temporal (insula) regions was assessed in 55 patients/51 controls. The relationship between AER, MMN to FM tones, and rsfMRI was assessed in the subset who performed all assessments (14 patients, 21 controls). As predicted, patients showed robust reductions in MMN across FM stimulus type (p = 0.005), particularly to modulations in F0M, along with impairments in AER and FM tone discrimination. MMN source analysis indicated dipoles in both auditory cortex and anterior insula, whereas rsfMRI analyses showed reduced auditory-insula connectivity. MMN to FM tones and functional connectivity together accounted for ∼50% of the variance in AER performance across individuals. These findings demonstrate that impaired preattentive processing of tonal information and reduced auditory-insula connectivity are critical determinants of social cognitive dysfunction in schizophrenia, and thus represent key targets for future research and clinical intervention. Schizophrenia patients show deficits in the ability to infer emotion based upon tone of voice [auditory emotion recognition (AER)] that drive impairments in social cognition and global functional outcome. This study evaluated neural substrates of impaired AER in schizophrenia using a combined event-related potential/resting-state fMRI approach. Patients showed impaired mismatch negativity response to emotionally relevant frequency modulated tones along with impaired functional connectivity between auditory and medial temporal (anterior insula) cortex. These deficits contributed in parallel to impaired AER and accounted for ∼50% of variance in AER performance. Overall, these findings demonstrate the importance of both auditory-level dysfunction and impaired auditory/insula connectivity in the pathophysiology of social cognitive dysfunction in schizophrenia.	\N	\N
26562889	Visual search is an essential task for many lifesaving professions; airport security personnel search baggage X-ray images for dangerous items and radiologists examine radiographs for tumors. Accuracy is critical for such searches; however, there are potentially negative influences that can affect performance; for example, the displays can be cluttered and can contain multiple targets. Previous research has demonstrated that clutter can hurt search performance and a second target is less likely to be detected in a multiple-target search after a first target has been found, which raises a concern-how does clutter affect multiple-target search performance? The current study explored clutter in a multiple-target search paradigm, where there could be one or two targets present, and targets appeared in varying levels of clutter. There was a significant interaction between clutter and target number: Increasing levels of clutter did not affect single-target detection but did reduce detection of a second target. Multiple-target search accuracy is known to be sensitive to contextual influences, and the current results reveal a specific effect wherein clutter disproportionally affected multiple-target search accuracy. These results suggest that the detection and processing of a first target might enhance the masking effects of clutter around a second target.	\N	\N
26575193	We examined short-term memory for sequences of visual stimuli embedded in varying multisensory contexts. In two experiments, subjects judged the structure of the visual sequences while disregarding concurrent, but task-irrelevant auditory sequences. Stimuli were eight-item sequences in which varying luminances and frequencies were presented concurrently and rapidly (at 8 Hz). Subjects judged whether the final four items in a visual sequence identically replicated the first four items. Luminances and frequencies in each sequence were either perceptually correlated (Congruent) or were unrelated to one another (Incongruent). Experiment 1 showed that, despite encouragement to ignore the auditory stream, subjects' categorization of visual sequences was strongly influenced by the accompanying auditory sequences. Moreover, this influence tracked the similarity between a stimulus's separate audio and visual sequences, demonstrating that task-irrelevant auditory sequences underwent a considerable degree of processing. Using a variant of Hebb's repetition design, Experiment 2 compared musically trained subjects and subjects who had little or no musical training on the same task as used in Experiment 1. Test sequences included some that intermittently and randomly recurred, which produced better performance than sequences that were generated anew for each trial. The auditory component of a recurring audiovisual sequence influenced musically trained subjects more than it did other subjects. This result demonstrates that stimulus-selective, task-irrelevant learning of sequences can occur even when such learning is an incidental by-product of the task being performed.	\N	\N
26753216	The stress response has been well documented in past music therapy literature. However, hypometabolism, or the relaxation response, has received much less attention. Music therapists have long utilized various music-assisted relaxation techniques with both live and recorded music to elicit such a response. The ongoing proliferations of relaxation music through commercial media and the dire lack of evidence to support such claims warrant attention from healthcare professionals and music therapists. The purpose of these 3 studies was to investigate the correlational relationships between 12 psychophysical properties of music, preference, familiarity, and degree of perceived relaxation in music. Fourteen music therapists recommended and analyzed 30 selections of relaxation music. A group of 80 healthy adults then rated their familiarity, preference, and degree of perceived relaxation in the music. The analysis provided a detailed description of the intrinsic properties in music that were perceived to be relaxing by listeners. These properties included tempo, mode, harmonic, rhythmic, instrumental, and melodic complexities, timbre, vocalization/lyrics, pitch range, dynamic variations, and contour. In addition, music preference was highly correlated with listeners' perception of relaxation in music for both music therapists and healthy adults. The correlation between familiarity and degree of relaxation reached significance in the healthy adult group. Results from this study provided an in-depth operational definition of the intrinsic parameters in relaxation music and also highlighted the importance of preference and familiarity in eliciting the relaxation response.	\N	\N
26891543	PROBLEM/OBJECTIVES: Maxillary constriction and high palatal arch are associated with increased risk of chronic eustachian tube dysfunction and conductive hearing loss (CHL) due to chronic effusion. However, this relationship has not been clearly demonstrated. This study assessed CHL in school children with a narrowed maxilla and deep palatal vault. Thirty-two children with maxillary constriction were randomly selected for the study group and 28 children with normal transverse maxillary development were selected for the control group. Pure-tone audiograms were obtained for all children, and hearing levels and air-bone gaps were measured. Air-bone gap measurements in the control group ranged from 5.50 to 14.50 decibels (dB), and in the study group they were between 5.00 and 24.00 dB. In the study group, 14 (43.8%) children had slight CHL, and the remaining 18 (56.2%) children had normal hearing levels. In the control group, all of the children had normal hearing levels. Hearing levels and air-bone gaps were greater in the study group than the control group. This study showed that children with a narrowed maxilla and deep palatal vault may have slight CHL. Therefore, the onset of CHL should be followed with hearing screening programs.	\N	\N
26941686	Actions that produce sounds infuse our daily lives. Some of these sounds are a natural consequence of physical interactions (such as a clang resulting from dropping a pan), but others are artificially designed (such as a beep resulting from a keypress). Although the relationship between actions and sounds has previously been examined, the frame of reference of these associations is still unknown, despite it being a fundamental property of a psychological representation. For example, when an association is created between a keypress and a tone, it is unclear whether the frame of reference is egocentric (gesture-sound association) or exocentric (key-sound association). This question is especially important for artificially created associations, which occur in technology that pairs sounds with actions, such as gestural interfaces, virtual or augmented reality, and simple buttons that produce tones. The frame of reference could directly influence the learnability, the ease of use, the extent of immersion, and many other factors of the interaction. To explore whether action-sound associations are egocentric or exocentric, an experiment was implemented using a computer keyboard's number pad wherein moving a finger from one key to another produced a sound, thus creating an action-sound association. Half of the participants received egocentric instructions to move their finger with a particular gesture. The other half of the participants received exocentric instructions to move their finger to a particular number on the keypad. All participants were performing the same actions, and only the framing of the action varied between conditions by altering task instructions. Participants in the egocentric condition learned the gesture-sound association, as revealed by a priming paradigm. However, the exocentric condition showed no priming effects. This finding suggests that action-sound associations are egocentric in nature. A second part of the same session further confirmed the egocentric nature of these associations by showing no change in the priming effect after moving to a different starting location. Our findings are consistent with an egocentric representation of action-sound associations, which could have implications for applications that utilize these associations.	\N	\N
22619989	The paper involves exposure to noise of the State Police officers connected with the use of firearms. The noise generated by these weapons is of short duration and high intensity. The research was carried out during the sessions of firearm training of State Police officers to assess exposure to noise. The values of the various investigations, both audiometric and phonometric, carried out made it possible to demonstrate a significant exposure and a temporary increase in the threshold, above the frequency of 6000 Hz. Even taking account of the abatement from use of headphones, an exposure was demonstrated that was above the statutory limits, as was confirmed by the temporary hearing threshold shift.	\N	\N
19616325	A patient with ankylosing spondylitis, migraine, Parkinson syndrome, renal insufficiency and myopathy, received an implantable-cardioverter-defibrillator because of asymptomatic left ventricular hypertrabeculation/noncompaction as primary prophylaxis against sudden cardiac death. Inadvertently the ventricular lead was placed in a cardiac vein, the patient suffered from pericardial effusion and it was impossible to remove the lead. Implantation of an implantable-cardioverter-defibrillator simply upon the presence of LVHT appears not justified and may be more harmful than beneficial. Studies about the risk of SCD in adults with LVHT are necessary and will hopefully clarify if primary prevention of SCD is indicated.	\N	\N
19770797	FX06 is a naturally occurring fibrin-derived peptide demonstrated to confer cytoprotection in the setting of primary percutaneous coronary intervention. Because the effect of FX06 on human platelet, coagulation, and fibrinolysis biomarkers (PCFB) is unknown but is important for further clinical development, we evaluated how FX06 affects PCFB. The in vitro effects of the whole-blood pre-incubation with escalating concentrations of FX06 (4, 25, and 75 μg/mL) were assessed in aspirin-naïve healthy volunteers (n = 10), those with multiple risk factors for vascular disease (n = 10), and patients with documented coronary artery disease (n = 10). The last two groups were treated with aspirin (81 mg/daily). Thirty-two variables of PCFB were measured with the vehicle and for each chosen FX06 dose. Pretreatment of blood samples with FX06 resulted in a moderate but significant and mostly dose-dependent increases of platelet aggregation induced by adenosine diphosphate and collagen. Similarly, the closure time was reduced, suggesting share-induced activation, PECAM-1, GP Ib, GP IIb/IIIa activity, and vitronectin receptors, which were also up-regulated. In contrast, P-selectin and GPIIb antigen expression were reduced after FX06. All other PCFB were predominantly unaffected by FX06, with the exception of the increased plasminogen, decreased protein C activity, and activated von Willebrand factor. We conclude that in the therapeutic range, FX06 in vitro mildly affects hemostasis by way of mostly activating platelets. Applying moderate concomitant antiplatelet strategies should be considered for the adequate protection from vascular thrombotic events in patients treated with FX06. Similar ex vivo study in patients receiving aspirin and clopidogrel is warranted.	\N	\N
19854042	Upper urinary tract urothelial carcinoma (UUTUC) is relatively rare, occurring in only 5% of all urothelial cancers. It has not been as extensively studied and reviewed as carcinoma of the bladder. UUTUC has a propensity for multifocality, local recurrence, and development of metastases, which argues for an aggressive treatment approach. Open radical nephroureterectomy (ORNU) with removal of an ipsilateral bladder cuff still remains the gold standard treatment for patients with UUTUC and a normal contralateral kidney, which, however, is being challenged by minimally invasive approaches, such as endoscopic and laparoscopic approaches. They are rapidly evolving as reasonable alternatives of care depending on grade and stage of disease. Adjuvant therapy seems to be safe, although its efficacy is debatable. Immunotherapy appears to be most effective in patients with upper-tract carcinoma in situ. Chemotherapy and radiotherapy also show some improvement in recurrence rates, but there have been no randomized, prospective trials. Gene and molecular-targeted therapy is expected. Several controversies remain in our management, including a selection of endoscopic versus laparoscopic approaches, management strategies on the distal ureter, the role of lymphadenectomy, and the value of immunotherapy, chemotherapy, radiotherapy and genetics and molecular markers in UUTUC. Aims of this paper are to critically review the treatment of UUTUC.	\N	\N
20049455	Relapsing polychondritis (RP) is a rare disease which presents chondritis in multiple organs. Characteristic features include auricular chondritis, arthritis, nasal chondritis, ocular inflammation, respiratory tract involvement and audiovestibular damage. Fifty percent of cases of RP are associated with inner ear symptoms such as dizziness and hearing loss. We have recently encountered a case of RP in a 34-year-old man who had recurrent chondritis of both auricles and progressive bilateral profound sensorineural hearing loss; he had been treated many times with steroids, immunosuppressants, plasmapheresis treatments. We perfomed a successful cochlear implant surgery on the left ear of this patient. This raises the possibility of using cochlear implants in treating patients with immune-mediated inner ear disease as well as such RP patients.	\N	\N
20373123	Juvenile dermatomyositis (JDM) is a rare childhood disease with autoimmune association. Environmental factors are known to trigger JDM in genetically susceptible individuals (Schmieder et al., Dermatol Online 6:3, 2009). Calcinosis is a well-established complication of JDM. Prevalence is higher in children (30-70%; Özkaya et al., Erciyes Med J 30(1):40-43, 2008). Hyperimmunoglobulin E syndrome is a primary immunodeficiency syndrome with multiple recurrent abscess formation and raised serum immunoglobulin E levels. We report a case of JDM with calcinosis cutis universalis with hyperimmunoglobulin E syndrome. With a previous similar case report (Min et al., Korean J Intern Med 14:95-98, 1999), this could well be a new sequence syndrome where abscesses are the trigger for the onset of JDM.	\N	\N
20390341	The estrogen signal is mediated by the estrogen receptor (ER). The specific role of ER-beta, a second ER, in breast carcinogenesis is not known. A number of association studies have been carried out to investigate the relationship between polymorphic sites in the ESR2 gene and breast cancer risk, however, the results are inconsistent. We searched PubMed, Medline, and Web of Science database (updated to 10 January 2010) and identified 13 relevant case-control studies, and approximately 28 single-nucleotide polymorphisms (SNPs) and one micro-satellite marker were reported in the literature. The median number of study subjects was 776 (range 158-13,550). Three genetic variants [(CA)n, rs2987983, and rs4986938] showed significant overall associations with breast cancer, and rs4986938 was reported twice. Because rs4986938 and rs1256049 were the most extensively studied polymorphisms, we subsequently conducted a meta-analysis to evaluate their relationship with breast cancer risk (9 studies of 10,837 cases and 16,021 controls for rs4986938; 8 studies of 11,652 cases and 15,726 controls for rs1256049). For rs4986938, the women harboring variant allele seemed to be associated with a decreased risk either in the dominant model [pooled OR = 0.944, 95% confidence interval (95% CI) 0.897-0.993, fixed-effects] or in the co-dominant model (AG vs. GG) (OR = 0.944, 95% CI 0.895-0.997, fixed-effects). rs1256049 was not associated with breast cancer risk in any model. Five studies had investigated the effect of haplotypes in the ESR2 gene on breast cancer risk, and four of them had positive outcomes. In summary, the present systematic review suggests that SNP rs4986938 as well as haplotypes in the ESR2 gene might be associated with breast cancer. The need for additional studies examining these issues seems of vital importance.	\N	\N
20434804	The pathophysiology of tinnitus is obscure and its treatment is therefore elusive. Significant progress in this field can only be achieved by determining the mechanisms of tinnitus generation, and thus, histopathologic findings of the cochlea in presbycusis with tinnitus become crucial. We revealed the histopathologic findings of the cochlea in subjects with presbycusis and tinnitus. The subjects were divided into 2 groups, presbycusis with tinnitus (tinnitus) group and presbycusis without tinnitus (control) group, with each group comprising 8 temporal bones from 8 subjects. We quantitatively analyzed the number of spiral ganglion cells, loss of cochlear inner and outer hair cells, and areas of the stria vascularis and spiral ligament. There was a significantly greater loss of outer hair cells in the tinnitus group compared with the control group in the basal and upper middle turns. The stria vascularis was more atrophic in the tinnitus group compared with the control group in the basal turn. Tinnitus is more common in patients with presbycusis who have more severe degeneration of outer hair cells and stria vascularis.	\N	\N
20512338	Hoarseness due to left recurrent laryngeal nerve paralysis (LRLN) caused by identifiable cardiovascular disease is described as Ortner's syndrome or cardiovocal syndrome. This was first reported by Ortner in 1897 to describe left recurrent laryngeal nerve palsy secondary to mitral stenosis. This case report describe a patient with giant cell arteritis with initial presentation of Ortner's syndrome.	\N	\N
20579773	Oligomeric β-amyloid (Aβ) has recently been linked to synaptic plasticity deficits, which play a major role in progressive cognitive decline in Alzheimer's disease (AD). Here we present evidence that chronic oral administration of carvedilol, a nonselective β-adrenergic receptor blocker, significantly attenuates brain oligomeric β-amyloid content and cognitive deterioration in 2 independent AD mouse models. We found that carvedilol treatment significantly improved neuronal transmission, and that this improvement was associated with the maintenance of number of the less stable "learning" thin spines in the brains of AD mice. Our novel observation that carvedilol interferes with the neuropathologic, biochemical, and electrophysiological mechanisms underlying cognitive deterioration in AD supports the potential development of carvedilol as a treatment for AD.	\N	\N
20678147	Psoriasis is today generally considered a systemic disease. Systemic therapies are used frequently. In Germany fumaric acid esters - FAE (Fumaderm(®) ) - are employed in more than 50 % of the patients requiring such therapy. We report for the first time the development of melanoma in two patients during their treatment with FAE. The logical question is - are the tumors coincidental or might they be treatment-related? Further investigations of pathways and immunologic effects as well as careful reports of side effects are necessary to estimate the risks of malignancy of FAE.	\N	\N
20696610	This study investigates the relationship between neck muscle coactivation, neck strength and perceived pain and disability in women with neck pain. Surface electromyography (EMG) was acquired from the sternocleidomastoid (SCM) and splenius capitis (SC) muscles of 13 women with chronic neck pain and 10 controls as they performed 1) maximal voluntary contractions (MVC) in flexion, extension and left and right lateral flexion, 2) ramped contractions from 0% to 50% MVC in flexion and extension and 3) circular contractions in the horizontal plane at 15N and 30N force. Higher values of EMG amplitude were observed for the SC (antagonist) during ramped neck flexion and for the SCM during ramped extension in the patient group (P<0.05). The patients displayed reduced values of directional specificity in the surface EMG of the SCM and SC for the circular contractions (P<0.05). The EMG amplitude of SC during cervical flexion was positively correlated with the patients' pain (R² =0.35, P<0.05) and perceived disability (R² 0.53, P<0.01). An inverse correlation was evident between the amount of activation of SC during cervical flexion and strength (R² =0.54, P<0.01). These observations indicate a relationship between alterations in neuromuscular control in patients with neck pain and functional consequences, including impaired motor performance and increased levels of perceived disability.	\N	\N
20733020	To report the clinical course, treatment response and prognosis of eight cases which developed acute-onset postoperative endophthalmitis over a 1-month period. 8 patients who were operated on over a period of 1 month and developed acute postoperative endophthalmitis were evaluated. Five of the patients had cataract surgery, one had cataract surgery combined with silicone extraction, and two patients had pars plana vitrectomy (PPV). Clinical patterns were observed, intraocular cultures were obtained, and the source of the organisms causing the epidemic was investigated. All patients had intravitreal antibiotic injections, three had PPV, and in two patients anterior chamber irrigation was performed. Vitreous cultures showed Cellulosimicrobium cellulans in three cases and Stenotrophomonas maltophilia in one case. Four of the cases were culture negative. Stenotrophomonas maltophilia were also isolated from unused bottles of irrigating solutions. The final visual acuity of the patients ranged between HM and 7/10. All three patients with Cellulosimicrobium cellulans had a final visual acuity of ≥ 5/10. The available irrigating solutions were changed, and the endophthalmitis did not recur. The authors are unaware of any previous reports of postoperative endophthalmitis associated with Cellulosimicrobium cellulans. Prompt management with microbiological support, intravitreal antibiotics and PPV when needed were the key to good visual outcomes in this endophthalmitis outbreak.	\N	\N
20849277	The ability for public/veterinary health agencies to assess the risks posed by tick-borne pathogens is reliant on an understanding of the main tick vector species. Crucially, the status, distribution, and changing trends in tick distribution and abundance are implicit requirements of any risk assessment; however, this is contingent on the quality of tick distribution data. Since 2005 the Health Protection Agency has promoted an enhanced tick surveillance program. Through engagement with a variety of public and veterinary health agencies and practitioners (e.g., clinicians and veterinarians), wildlife groups (deer society, zoos, animal refuge centers, and academics), and amateur entomologists, >4000 ticks from 900 separate records across Great Britain have been submitted, representing 14 tick species (Ixodes ricinus, Ixodes hexagonus, Ixodes acuminatus, Ixodes arboricola, Ixodes canisuga, Ixodes frontalis, Ixodes lividus, Ixodes trianguliceps, Ixodes ventalloi, Carios vespertilionis, Dermacentor reticulatus, Haemaphysalis punctata, Hyalomma marginatum, and Amblyomma species). The majority of ticks submitted were I. ricinus (81%), followed by I. hexagonus (10%) and I. frontalis (2.5%). Predominant host groups include companion animals (411 records), humans (198 records), wild birds (111 records), and large wild mammals (88 records), with records also from small/medium wild mammals, livestock, the environment and domestic/aviary birds. The scheme has elucidated the detection of two nonnative tick species, the expansion of previously geographically restricted D. reticulatus and produced ground data on the spread of I. ricinus in southwest England. It has also provided a forum for submission of ticks from the concerned public and particularly those infected with Lyme borreliosis, thus raising awareness among public health agencies of the increased peri-urban tick problem in Britain. Our results demonstrate that it is possible to run a cost-effective nationwide surveillance program to successfully monitor endemic tick species, identify subtle changes in their distribution, and detect the arrival and presence of exotic species.	\N	\N
20853354	We report our 10-year experience with percutaneous closure of adult congenital and acquired (non-post-infarct) ventricular septal defects (VSDs) using different types of Amplatzer occluder devices. Adult congenital and acquired VSDs may produce significant morbidity and mortality. Furthermore, such VSDs pose a significant surgical challenge. Between February 2000 and August 2009, data were retrospectively reviewed from 28 patients who underwent 29 procedures for percutaneous device closure of hemodynamically significant VSDs. Seventeen had unrepaired congenital VSDs, 10 had post-operative VSDs (5 with residual patch-margin defects, 4 post-aortic valve replacement, 1 post-myomectomy), and one had an acquired traumatic VSD. INDICATIONS FOR CLOSURE INCLUDED: symptoms related to significant shunt (dyspnea on exertion); unexplained deterioration of LV function, and/or LV dilation; recurrent endocarditis, and pulmonary hypertension. Outcome parameters were procedural success, procedure-related complications, evidence of residual shunt by echocardiography, and improvement in the signs/symptoms for which the procedure was performed. The mean follow-up interval was 68 months. Of the 28 patients studied, a single VSD was present in 26 patients, while one patient had two defects, and one patient had one defect on the LV side with three openings at the RV side. The median size of the defects by echocardiography was 6 mm. A device was successfully implanted in 28 of 29 (97%) procedures and 28 of 28 (100%) patients. PROCEDURE-RELATED COMPLICATIONS OCCURRED IN TWO CASES: one involving an access site hematoma not requiring transfusion as well as nonsustained ventricular tachycardia that resolved spontaneously and the other involving acute mitral regurgitation due to inadvertent trapping of the anterior mitral valve leaflet between the left ventricular disk and the septum that was resolved by recapturing of the disk. There was immediate complete closure in 20 patients (71%). In six cases there was trivial residual shunt and in two patients the residual shunt was mild. At the latest follow-up, four of the eight with a residual shunt had no shunt and in the remaining four the residual shunt was trivial. Among symptomatic patients 18 (64%), there was marked improvement in symptoms and for those patients 17 (61%) for whom the procedure was performed to address left ventricular enlargement, there was reduction or stabilization in LV size on serial echoes. Percutaneous closure of VSDs in the adult patient appears to be safe and effective.	\N	\N
20853359	A significant proportion (~ 20%) of patients with complex tibial artery occlusions cannot be treated using a conventional antegrade approach. We report our experience using the retrograde approach for the treatment of complex tibial artery occlusive disease using retrograde pedal/tibial access in 13 limbs from 12 patients. Retrograde pedal/tibial access was achieved in all cases (facilitated by surgical cutdown in one case), and procedural success was achieved in 11 of 13 limbs (85%). Based on this experience, a discussion of clinical and technical aspects of the retrograde pedal/tibial approach is provided, and a new classification for tibial artery occlusive disease is proposed.	\N	\N
20878712	Endoscopic evaluation plays a pivotal role in the assessment of treatment response in ulcerative colitis (UC). This study aimed to determine the interobserver agreement (IOA) for assessment of mucosal lesions, and to determine lesions predictive of global assessment of endoscopic severity (GAES). Fifty-one UC patients had digital videorecording of their colonoscopic examinations, edited into videoclips representative of five colonic segments (rectum, sigmoid, descending, transverse, ascending/cecum). Seven gastroenterologists specializing in inflammatory bowel disease (IBD) independently and blindly rated individual lesions and endoscopic severity for each segment and globally. Edema, erythema, stricture, loss of haustral folds, rigidity, and pseudopolyps were scored as absent or present while vascular pattern, granularity, ulceration, and bleeding-friability were scored using a predefined severity scale. The GAES was based on a 4-point scale and a 10-cm visual analog scale (VAS). The IOA among raters was estimated using Lin's concordance correlation coefficient (CCC). Strength of agreement was categorized as excellent (0.81-1.00), good (0.61-0.80), moderate (0.41-0.60), and fair (0.21-0.40). Linear regression analysis was used to identify lesions predictive of overall endoscopic severity and develop a scoring system for clinical use. Granularity, vascular pattern, ulceration, bleeding/friability, and pseudopolyps had good IOA in most segments. There was excellent agreement for VAS and good agreement for GAES and the VAS was significantly associated with GAES (P < 0.001). Granularity, vascular pattern, ulceration, and bleeding-friability were significant predictors of overall endoscopic severity. Granularity, vascular pattern, ulceration, and bleeding-friability demonstrated good reproducibility and were predictors of the GAES in UC patients.	\N	\N
20881290	Mutations in PITX2 are associated with Axenfeld-Rieger syndrome (ARS), which involves ocular, dental, and umbilical abnormalities. Identification of cis-regulatory elements of PITX2 is important to better understand the mechanisms of disease. Conserved noncoding elements surrounding PITX2/pitx2 were identified and examined through transgenic analysis in zebrafish; expression pattern was studied by in situ hybridization. Patient samples were screened for deletion/duplication of the PITX2 upstream region using arrays and probes. Zebrafish pitx2 demonstrates conserved expression during ocular and craniofacial development. Thirteen conserved noncoding sequences positioned within a gene desert as far as 1.1 Mb upstream of the human PITX2 gene were identified; 11 have enhancer activities consistent with pitx2 expression. Ten elements mediated expression in the developing brain, four regions were active during eye formation, and two sequences were associated with craniofacial expression. One region, CE4, located approximately 111 kb upstream of PITX2, directed a complex pattern including expression in the developing eye and craniofacial region, the classic sites affected in ARS. Screening of ARS patients identified an approximately 7600-kb deletion that began 106 to 108 kb upstream of the PITX2 gene, leaving PITX2 intact while removing regulatory elements CE4 to CE13. These data suggest the presence of a complex distant regulatory matrix within the gene desert located upstream of PITX2 with an essential role in its activity and provides a possible mechanism for the previous reports of ARS in patients with balanced translocations involving the 4q25 region upstream of PITX2 and the current patient with an upstream deletion.	\N	\N
20936300	In Huntington's disease (HD) atrophy of the caudate nucleus and putamen has been described many years before clinical manifestation. Volume changes of the pallidum, thalamus, brainstem, accumbens nucleus, hippocampus, and amygdala are less well investigated, or reported with contradicting results. The aim of our study is to provide a more precise view of the specific atrophy of the subcortical grey matter structures in different stages of Huntington's disease, and secondly to investigate how this influences the clinical manifestations. All TRACK-HD subjects underwent standardised T1-weighted 3T MRI scans encompassing 123 manifest HD (stage 1, n = 77; stage 2, n = 46), 120 premanifest HD (close to onset n = 58, far from onset n = 62) and 123 controls. Using FMRIB's FIRST and SIENAX tools the accumbens nucleus, amygdala, brainstem, caudate nucleus, hippocampus, pallidum, putamen, thalamus and whole brain volume were extracted. Results showed that volumes of the caudate nucleus and putamen were reduced in premanifest HD far from predicted onset (>10.8 years). Atrophy of accumbens nucleus and pallidum was apparent in premanifest HD in the close to onset group (0-10.8 years). All other structures were affected to some degree in the manifest group, although brainstem, thalamus and amygdala were relatively spared. The accumbens nucleus, putamen, pallidum and hippocampus had a strong significant correlation with functional and motor scores. We conclude that volume changes may be a sensitive and reliable measure for early disease detection and in this way serve as a biomarker for Huntington's disease. Besides the caudate nucleus and putamen, the pallidum and the accumbens nucleus show great potential in this respect.	\N	\N
20938704	We describe an outbreak of Bacillus cereus bacteremia that occurred at Jichi Medical University Hospital in 2006. This study aimed to identify the source of this outbreak and to implement appropriate control measures. We reviewed the charts of patients with blood cultures positive for B. cereus, and investigated B. cereus contamination within the hospital environment. Genetic relationships among B. cereus isolates were analyzed. Eleven patients developed B. cereus bacteremia between January and August 2006. The hospital linens and the washing machine were highly contaminated with B. cereus, which was also isolated from the intravenous fluid. All of the contaminated linens were autoclaved, the washing machine was cleaned with a detergent, and hand hygiene was promoted among the hospital staff. The number of patients per month that developed new B. cereus bacteremia rapidly decreased after implementing these measures. The source of this outbreak was B. cereus contamination of hospital linens, and B. cereus was transmitted from the linens to patients via catheter infection. Our findings demonstrated that bacterial contamination of hospital linens can cause nosocomial bacteremia. Thus, blood cultures that are positive for B. cereus should not be regarded as false positives in the clinical setting.	\N	\N
20950346	Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone receptor blockade has been shown to reduce morbidity and mortality in human patients with advanced congestive left ventricular heart failure. This study was designed to assess the efficacy and tolerance of long-term low-dose spironolactone when added to conventional heart failure treatment in dogs with advanced heart failure. Eighteen client-owned dogs with advanced congestive heart failure due to either degenerative valve disease (n=11) or dilated cardiomyopathy (n=7) were included in this prospective, placebo-controlled, double-blinded, randomized clinical study. After initial stabilization including furosemide, angiotensin-converting enzyme inhibitors, pimobendan and digoxin, spironolactone at a median dose of 0.52 mg/kg (range 0.49-0.8 mg/kg) once daily (n=9) or placebo (n=9) was added to the treatment, and the dogs were reassessed 3 and 6 months later. Clinical scoring, echocardiography, electrocardiogram, systolic blood pressure measurement, thoracic radiography, sodium, potassium, urea, creatinine, alanine aminotransferase, aldosterone and aminoterminal atrial natriuretic propeptide were assessed at baseline, 3 and 6 months. Survival times were not significantly different between the two treatment groups. Spironolactone was well tolerated when combined with conventional heart failure treatment.	\N	\N
20981578	Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to slow neuronal loss in several brain regions. It is characterised by the presence of cerebral senile plaques comprised of aggregated amyloid-β peptides. Transcriptional regulation of the γ-secretase complex, which cleaves the β-amyloid precursor protein to produce Aβ-peptides, could modulate the pathological phenotype of AD patients. This study investigates whether rosuvastatin, an HMG-CoA reductase inhibitor, modulates the expression of genes involved in the function of the γ-secretase complex, in a human cellular model for Aβ peptide accumulation. In particular, we analysed the effect of the statin combined with apoptotic induction. Experimental apoptosis was induced by thapsigargin treatment, a drug that depletes intracellular calcium stores via inhibition of the calcium ATPase pump. Notably, systemic calcium dysregulation accompanies almost all of the brain pathology processes observed in AD. We found differential transcriptional regulation of some γ-secretase cofactors relative to rosuvastatin treatment, in cells expressing Swedish mutant APP. Interestingly, this statin down-regulated the transcription of some enzyme cofactors, similar to treatment with thapsigargin. However, rosuvastatin neither affected the basal Aβ levels nor counteracted APP processing or Aβ over-production triggered by the thapsigargin. Our results provide evidence that rosuvastatin alters gene expression of the γ-secretase complex without affecting enzyme activity.	\N	\N
21040232	Febrile seizures (FSs) relatively represent the most common form of childhood seizures. FSs are not thought of as a true epileptic disease but rather as a special syndrome characterized by its provoking factor (fever) and a typical range of 3 months to 5 years. Although specific genes affecting the majority of FS cases have not been identified yet, several genetic loci for FSs have been reported recently. The aim of this report is to search for the gene responsible for FSs in six affected Tunisian families. A microsatellite marker analysis was performed on the known FS and generalized epilepsy with febrile seizures plus (GEFS+) loci. According to the results obtained by statistical analyses for the six studied families and in agreement with the involvement of SCN1B gene in the GEFS+ syndrome in previous studies, SCN1B on GEFS+1 locus was considered as one of the potential candidate genes and was tested for mutations by direct sequencing. A sequencing analysis of the SCN1B gene revealed a novel mutation (c.374G>T) that changed an arginine residue with leucine at position 125 of the protein. We consider that the variation R125L may affect the protein structure and stability by the loss of hydrogen bonding. Two identified single nucleotide polymorphisms that are located in a neighboring hypothetical polyadenylation were assumed to compose a putative disease-associated haplotype. Our results support that SCN1B is the gene responsible in one amongst the six FS Tunisian families studied and might contribute to the FS susceptibility for the five others.	\N	\N
21055462	Environmental factors have a significant impact on biology. Therefore, environmental toxicants through similar mechanisms can modulate biological systems to influence physiology and promote disease states. The majority of environmental toxicants do not have the capacity to modulate DNA sequence, but can alter the epigenome. In the event an environmental toxicant such as an endocrine disruptor modifies the epigenome of a somatic cell, this may promote disease in the individual exposed, but not be transmitted to the next generation. In the event a toxicant modifies the epigenome of the germ line permanently, then the disease promoted can become transgenerationaly transmitted to subsequent progeny. The current review focuses on the ability of environmental factors such as endocrine disruptors to promote transgenerational phenotypes.	\N	\N
21073934	Two mouse models, the Coch(G88E/G88E) or "knock-in" and the Coch(-/-) or "knock-out" (Coch null), have been developed to study the human late-onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. This disorder results from missense and in-frame deletion mutations in COCH (coagulation factor C homology), encoding cochlin, the most abundantly detected protein in the inner ear. We have performed hearing and vestibular analyses by auditory brainstem response (ABR) and vestibular evoked potential (VsEP) testing of the Coch(-/-) and Coch(G88E/G88E) mouse models. Both Coch(-/-) and Coch(G88E/G88E) mice show substantially elevated ABRs at 21 months of age, but only at the highest frequency tested for the former and all frequencies for the latter. At 21 months, 9 of 11 Coch(-/-) mice and 4 of 8 Coch(G88E/G88E) mice have absent ABRs. Interestingly Coch(-/+) mice do not show hearing deficits, in contrast to Coch(G88E/+), which demonstrate elevated ABR thresholds similar to homozyotes. These results corroborate the DFNA9 autosomal dominant mode of inheritance, in addition to the observation that haploinsufficiency of Coch does not result in impaired hearing. Vestibular evoked potential (VsEP) thresholds were analyzed using a two factor ANOVA (Age X Genotype). Elevated VsEP thresholds are detected in Coch(-/-) mice at 13 and 21 months, the two ages tested, and as early as seven months in the Coch(G88E/G88E) mice. These results indicate that in both mouse models, vestibular function is compromised before cochlear function. Analysis and comparison of hearing and vestibular function in these two DFNA9 mouse models, where deficits occur at such an advanced age, provide insight into the pathology of DFNA9 and age-related hearing loss and vestibular dysfunction as well as an opportunity to investigate potential interventional therapies.	\N	\N
21084426	We performed a three-stage genome-wide association study (GWAS) to identify common Parkinson's disease (PD) risk variants in the European population. The initial genome-wide scan was conducted in a French sample of 1039 cases and 1984 controls, using almost 500 000 single nucleotide polymorphisms (SNPs). Two SNPs at SNCA were found to be associated with PD at the genome-wide significance level (P < 3 × 10(-8)). An additional set of promising and new association signals was identified and submitted for immediate replication in two independent case-control studies of subjects of European descent. We first carried out an in silico replication study using GWAS data from the WTCCC2 PD study sample (1705 cases, 5200 WTCCC controls). Nominally replicated SNPs were further genotyped in a third sample of 1527 cases and 1864 controls from France and Australia. We found converging evidence of association with PD on 12q24 (rs4964469, combined P = 2.4 × 10(-7)) and confirmed the association on 4p15/BST1 (rs4698412, combined P = 1.8 × 10(-6)), previously reported in Japanese data. The 12q24 locus includes RFX4, an isoform of which, named RFX4_v3, encodes brain-specific transcription factors that regulate many genes involved in brain morphogenesis and intracellular calcium homeostasis.	\N	\N
21085051	The Centers for Disease Control and Prevention recommend hospitals develop guidelines for the appropriate use of vancomycin as part of comprehensive antimicrobial stewardship. The objective of this study was to evaluate the effectiveness and safety of a guideline to restrict vancomycin use in the neonatal intensive care unit (NICU). A vancomycin use guideline was introduced in 2 tertiary care NICUs with low incidences of methicillin-resistant Staphylococcus aureus infections. We compared all infants >72 hours of age who were evaluated for late-onset infection before and after implementation of this guideline. Vancomycin start rates were reduced from 6.9 to 4.5 per 1000 patient-days (35% reduction; P = 0.01) at Brigham and Women's Hospital, and from 17 to 6.4 per 1000 patient-days (62% reduction; P < 0.0001) at Massachusetts General Hospital. The number of infants exposed to vancomycin decreased from 5.2 to 3.1 per 1000 patient-days (40% reduction; P = 0.008) at Brigham and Women's Hospital, and 10.8 to 5.5 per 1000 patient-days (49% reduction; P = 0.009) at Massachusetts General Hospital. Causes of infection, duration of bacteremia, and incidence of complications or deaths attributable to late-onset infection did not change significantly at either institution. Implementation of a NICU vancomycin use guideline significantly reduced exposure of newborns to vancomycin without adversely affecting short-term patient safety. Further studies are required to evaluate the long-term effect of vancomycin restriction on NICU patient safety and microbial ecology, particularly among institutions with higher rates of methicillin-resistant Staphylococcus aureus infections.	\N	\N
21102561	Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the potential to differentiate into all cell lineages, including hepatocytes, in vitro. Induced hepatocytes have a wide range of potential application in biomedical research, drug discovery, and the treatment of liver disease. However, the existing protocols for hepatic differentiation of PSCs are not very efficient. In this study, we developed an efficient method to induce hepatoblasts, which are progenitors of hepatocytes, from human ESCs and iPSCs by overexpression of the HEX gene, which is a homeotic gene and also essential for hepatic differentiation, using a HEX-expressing adenovirus (Ad) vector under serum/feeder cell-free chemically defined conditions. Ad-HEX-transduced cells expressed α-fetoprotein (AFP) at day 9 and then expressed albumin (ALB) at day 12. Furthermore, the Ad-HEX-transduced cells derived from human iPSCs also produced several cytochrome P450 (CYP) isozymes, and these P450 isozymes were capable of converting the substrates to metabolites and responding to the chemical stimulation. Our differentiation protocol using Ad vector-mediated transient HEX transduction under chemically defined conditions efficiently generates hepatoblasts from human ESCs and iPSCs. Thus, our methods would be useful for not only drug screening but also therapeutic applications.	\N	\N
21104183	Crohn disease is a chronic granulomatous inflammatory disorder that most commonly affects the gastrointestinal tract, particularly the distal small bowel and colon. While certain extraintestinal manifestations of Crohn disease are relatively common and well-known, others, such as metastatic cutaneous involvement, are quite rare and may be difficult to recognize, particularly in the pediatric population. This case report illustrates the magnetic resonance imaging (MRI) appearance of vulvar region cutaneous Crohn disease in an 11-year-old girl.	\N	\N
21106231	The purpose of this study was (1) to investigate the association between BMI self-reported at three time points (during their 20s, 5 years before diagnosis, and post-diagnosis) and mortality among 388 women with newly diagnosed epithelial ovarian cancer and (2) weight change between these 3 time points and mortality. Women completed interview-administered questionnaires on average 9 months post-diagnosis. Women were followed 5 years after diagnosis or until death, whichever came first. Cox proportional hazard regression was used to estimate associations between BMI during the 20s, BMI 5 years prior to diagnosis, BMI post-diagnosis (i.e., at the time of interview) and weight changes between these time points and mortality. The 5-year survival rate was 54% (178 deaths, 146 from ovarian cancer). BMI measured continuously at all three time points was associated with a higher risk of ovarian cancer mortality (P≤0.05). The strongest association was observed with BMI in the 20s and all-cause mortality comparing women with BMI≥25 kg/m(2) to BMI<25 kg/m(2) (HR=1.82; 95% CI, 1.02-3.27; P for trend=0.045). For weight change from the 20s to 5 years prior to diagnosis and ovarian cancer specific mortality, we observed a 68% higher risk of ovarian cancer mortality (HR=1.68; 95% CI, 1.11-2.55; P for trend=0.015, comparing women with <10 lbs weight gain to women with ≥10 lbs weight gain). BMI prior to and after diagnosis and weight gain throughout adulthood is associated with ovarian cancer mortality.	\N	\N
21135704	To study the role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis (AP). Bacterial translocation has been implicated in infective complications in AP, which has been shown to be prevented by probiotics. A double-blind, randomized placebo-controlled trial was conducted. Consecutive patients with AP presenting within 72 hours after the onset of abdominal pain or who had been nil orally at the time of presentation for up to 5 days were included in the study. The probiotic group received 4 sachets of Probiotics (2.5 billion bacteria per sachet) whereas the placebo group received 4 sachets of placebo for 7 days. Primary outcome measures were effect on gut permeability [assessed by lactulose/mannitol (L/M) excretion in urine] and endotoxemia assessed by endotoxin-core antibody types IgG and IgM (EndoCab IgG and IgM). Secondary outcome measures were mortality, total hospital/intensive care unit stay, abdominal discomfort, organ failure, C-reactive protein, and prealbumin levels. The study was prematurely stopped after the publication of probiotic prophylaxis in patients with predicted severe acute pancreatitis trial. From March 2007 to May 2008, 50 patients with AP were included in the study (26 in placebo group and 24 in probiotic group). There was no difference after intervention in gut permeability, whereas values of C-reactive protein and immunoglobulins decreased significantly [IgG: 140 (20-920) to 90 (20-600) GGU/mL and IgM: 65 (13-230) to 51 (9-240) GMU/mL] in the probiotic group. No difference was observed in prealbumin values, duration of hospital/intensive care unit stay, and mortality in both the groups. No significant trend was identified for an effect of probiotics on gut permeability or endotoxemia in AP. However, the study was underpowered owing to premature study termination.	\N	\N
21172349	Visceral leishmaniasis (VL) is a health issue in Sudan. Our aim was to investigate the involvement of eosinophils and neutrophils in VL by serum and plasma measurements of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) and some key cytokines and chemokines. Blood was collected from 125 VL patients and 181 healthy Sudanese controls from the same rural area. Results showed reduced eosinophil and neutrophil counts in the VL group (P=0.0001 and P=0.002, respectively). Serum-ECP levels were higher in the controls (P<0.0001), while plasma MPO levels were higher in the VL group (P<0.0001). Levels of IL-5, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-17 were increased among the VL group (P<0.0001, P=0.017 and P=0.03, respectively), whereas eotaxin and IL-8 levels were reduced (P<0.0001 and P=0.002, respectively). Positive correlations were found between IL-8 and ECP/MPO (P<0.0001). We conclude that eosinophil and neutrophil turnover and activity are increased in subjects in rural areas of Sudan. In VL the turnover was further increased, but the relatively low secretory activity of eosinophils and neutrophils in VL may relate to the reduced production and availability of the chemokines eotaxin and IL-8. The combined assay of ECP and MPO in serum and plasma provides further insight into the mechanisms of eosinophil and neutrophil involvement in disease and constitutes a novel approach to the study of disease processes.	\N	\N
21184197	The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level and whether it might have differential effects on brain function due to the presence of APOE ε 4 allele(s) in HIV-infected patients are unknown. However, APOE ε 4 allele has been associated with greater incidence of HIV-associated dementia and accelerated progression of HIV infection. Here, we show further evidence for the role of APOE ε 4 in promoting cognitive impairment. We measured the APOE levels in the CSF of HIV-infected individuals. HIV+ subjects showed lower CSF APOE proteins than SN controls (-19%, p= 0.03). While SN subjects with or without ε 4 allele showed no difference in CSF APOE levels, ε 4+ HIV+ subjects had similar levels to the SN subjects but higher levels than ε 4- HIV+ subjects (+34%, p= 0.01). Furthermore, while HIV+ subjects with ε 2 or ε 3 allele(s) showed a positive relationship between their CSF APOE levels and cognitive performance on the speed of processing domain (r= +0.35, p= 0.05), ε 4+ HIV+ subjects, in contrast, exhibited a negative relationship such that those with higher levels of CSF APOE(4) performed worse on the HIV Dementia Scale (r= -0.61, p= 0.02), had lower Global Cognitive Scores (r= -0.57, p= 0.03), and had poorer performance on tests involving learning (ε 4 allele x [APOE] interaction, p = 0.01). Our findings also suggest that the relatively higher levels of CSF APOE in ε 4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the ε 4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.	\N	\N
21190758	Assuming selective vulnerability of short association U-fibers in early Alzheimer's disease (AD), we quantified demyelination of the surface white matter (dSWM) with magnetization transfer ratio (MTR) in 15 patients (Clinical Dementia Rating Scale [CDR] 0.5-1; Functional Assessment Staging [FAST]: 3-4) compared with 15 controls. MTRs were computed for 39 areas in each hemisphere. We found a bilateral MTR decrease in the temporal, cingulate, parietal, and prefrontal areas. With linear discriminant analysis, we successfully classified all the participants with 3 variates including the cuneus, parahippocampal, and superior temporal regions of the left hemisphere. The pattern of dSWM changed with the age of AD onset. In early onset patients, we found bilateral posterior demyelination spreading to the temporal areas in the left hemisphere. The late onset patients showed a distributed bilateral pattern with the temporal and cingulate areas strongly affected. A correlation with Mini Mental State Examination (MMSE), Lexis, and memory tests revealed the dSWM impact on cognition. A specific landscape of dSWM in early AD shows the potential of MTR imaging as an in vivo biomarker superior to currently used techniques.	\N	\N
21211565	Nuclear receptors (NRs) are ligand-activated transcriptional factors that are involved in various physiological, developmental, and toxicological processes. Farnesoid X receptor (FXR) is a NR that belongs to the NR superfamily. The endogenous ligands of FXR are bile acids. FXR is essential in regulating a network of genes involved in maintaining bile acid and lipid homeostasis. It is clear that FXR is critical for liver and intestinal function. In mice FXR deficiency leads to the development of cholestasis, gallstone disease, nonalcoholic steatohepatitis, liver tumor, and colon tumor. Using mouse models where FXR is deleted either in the whole-body, or selectively in hepatocytes or enterocytes, we start to reveal the importance of tissue-specific FXR function in regulating bile acid and lipid homeostasis. However, a great challenge exists for developing tissue-specific FXR modulators to prevent and treat diseases associated with bile acid or lipid disorders. With further understanding of FXR function in both rodents and humans, this nuclear receptor may emerge as a novel target to prevent and treat liver, gastrointestinal and systemic diseases.	\N	\N
21220035	We retrospectively compared the outcomes of 225 patients with adult acquired aplastic anemia (AA) who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) from matched related donors (MRDs), and those treated by alloHSCT from alternative donors (ADs). Univariate and multivariate analyses of factors associated with survival were performed. Multivariate analysis showed that age at alloHSCT of ≤ 31 years, MRD, successful engraftment, absence of acute graft-versus-host disease (aGVHD), and platelet engraftment at ≤ 21 days, were independent predictors of longer survival. In addition, time to aGVHD and cumulative nonrelapse mortality (NRM) were better in MRD than in AD recipients. Using propensity score matching (PSM), we performed a case-control study comparing 25 patients in each group who underwent alloHSCT from MRDs and ADs. Pretransplantation clinical factors were well balanced in either group. Median survival time was similar, and no statistically significant difference in transplantation outcomes was apparent when MRD and AD recipients were compared. In conclusion, our results suggest that alloHSCT from an AD should be considered earlier in adult patients with AA who do not have an MRD.	\N	\N
21224840	Despite little supporting data, thiopurine use is common in pediatric ulcerative colitis (UC). Our aim was to determine outcome following thiopurine use in a multicenter inception cohort of children diagnosed with UC. Data were obtained from a prospective observational study of newly diagnosed children <16 years of age. Data are recorded at diagnosis, 30 days, and quarterly. Patients are managed by physician dictates not protocol. Disease activity is classified by physician global assessment. The primary outcome was corticosteroid (CS)-free inactive UC at 1 year following thiopurine initiation without the need for rescue therapy (infliximab, calcineurin inhibitors, or colectomy). Of 1,490 patients in our registry, 394 have UC (mean age at diagnosis 11.3±3.7 years); 197 (50%) received thiopurine (49% ≤3 months from diagnosis). Also, 84% were receiving CSs and 60% 5-aminosalicylates at thiopurine start. Of the 197 patients, there was insufficient follow-up (41), previous or concomitant use of infliximab (16), or calcineurin inhibitor (7), leaving 133 patients evaluable at 1 year. Of these, 65 (49%) had CS-free inactive UC without rescue therapy. CS-free inactive disease at 1 year after initiating thiopurine was not affected by starting thiopurine ≤3 months vs. >3 months from diagnosis, gender, age, or concomitant treatment with 5-aminosalicylates. Kaplan-Meier analysis showed that the likelihood of remaining free of rescue therapy in the thiopurine-treated patients was 73% at 1 year. Approximately 50% of children with UC starting thiopurine without previous or concomitant biologic or calcineurin inhibitor therapy have CS-free inactive disease 1 year later without the need for rescue therapy.	\N	\N
21240517	We investigated whether there exists a hierarchical vulnerability of subcortical structures with respect to the severity of Alzheimer's disease (AD). A total of 236 subjects (179 with AD and 57 with normal cognition) underwent 1.5-T magnetic resonance (MR) imaging. The volumes of the five subcortical structures (amygdala, thalamus, putamen, globus pallidus, and caudate nucleus) and hippocampus were analyzed using a large deformation diffeomorphic metric mapping algorithm. The volume changes were evaluated according to the Clinical Dementia Rating (CDR). Correlation between the volumes of the subcortical structures and scores of the cognitive domain-specific neuropsychological tests were evaluated. Volume loss of the amygdala occurred even in the very mild stage of AD (CDR 0.5), as did volume loss in the hippocampus. Similar reductions in volume occurred in the thalamus and putamen, however during the mild (CDR 1) and moderate (CDR 2) stages of AD, respectively. The globus pallidus and caudate nucleus remained devoid of changes until the moderate stage of AD (p < 0.01). Volume loss in those subcortical structures correlated with the neuropsychological test scores (p < 0.01). Our results suggest that there is a hierarchical vulnerability in subcortical structures according to the clinical severity of AD and that subcortical volume reductions correlate with cognitive impairment.	\N	\N
21242863	A retrospective clinical and radiographic study was performed. The purpose of this study was to compare outcomes of patients with degenerative spondylolisthesis and a preexisting degenerative L5-S1 disc treated with a lumbar floating fusion (LFF) versus lumbosacral fusion (LSF). Fusion for treatment of degenerative spondylolisthesis often ends at the L5 level. These patients usually had a preexisting L5-S1 disc degeneration; however, no literature mentions the role of prophylactic LSF in degenerative spondylolisthesis associated with L5-S1 disc degeneration. A total of 107 patients with a minimum 5-year follow-up who had lumbosacral or LFF with pedicle instrumentation for degenerative spondylolisthesis were included. UCLA (University of California, Los Angeles) classification was used to evaluate the radiographic results of the L5-S1 segment. The Oswestry Disability Index (ODI) and modified Brodsky's criteria were used to evaluate patients' clinical results. The incidence of adjacent segment disease (ASD) (includes radiographic and clinical ASD) of both ends was recorded. There were no statistically significant differences in sex, age distribution, or amount of follow-up between the LFF and LSF groups. The LSF group had a higher percentage of patients that underwent total L5 laminectomy with loss of L5-S1 posterior ligament integrity (LSF = 92% vs. LFF = 67%, P = 0.019). The higher incidence of cephalic ASD in the LSF group was statistically significant (LSF = 25% vs. LFF = 9.7%, P = 0.049). Although no patient in the LSF group developed L5-S1 ASD, need for L5-S1 segment revision surgery was not prevented with LSF. Clinical outcomes on the basis of the success rate (LFF = 85.5% vs.LSF = 70.8%, P = 0.103) and ODI difference (LFF = 28.97 ± 15.82 vs. LSF = 23.04 ± 10.97, P = 0.109), there were no statistically significant difference between these two groups. Posterior instrumentation with posterolateral LFF for the treatment of degenerative spondylolisthesis with concomitant L5-S1 disc degeneration results in a high percentage of satisfactory clinical results. Extended fusion to the sacrum did not provide a better clinical result. LSF could not reduce the incidence of revision surgery at the L5-S1 segment and involved greater incidence of cephalic ASD.	\N	\N
21246519	Concurrent inhibition of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) is an active and well tolerated regimen in recurrent head and neck cancer (HNC). In the current phase 1 trial, the authors sought to determine the maximum tolerated dose (MTD) and efficacy of concurrent erlotinib and celecoxib as a radiosensitizing regimen. Fourteen patients with previously irradiated HNC with no distant metastases who required reirradiation were eligible. Treatment consisted of daily erlotinib 150 mg and twice daily celecoxib (escalated from 200 mg to 600 mg using a 3 + 3 design with an expanded cohort at the MTD) starting on Day 1 and was continued during radiation. Daily radiation was started on Day 15, and maintenance erlotinib was recommended. The recommended phase 2 dose of celecoxib was 400 mg. Three dose-limiting toxicities included late in-field orocutaneous fistula (Dose Level 2), osteonecrosis (Dose Level 3), and trismus (Dose Level 3). Acute grade ≥ 3 toxicities were uncommon and included mucositis (21%) and dermatitis (14%). At a median follow-up of 11 months, the 1-year locoregional control, progression-free survival, and overall survival rates were 60%, 37%, and 55%, respectively. Concurrent erlotinib, celecoxib, and reirradiation was a feasible and clinically active regimen in a population of patients with recurrent HNC who had a poor prognosis.	\N	\N
21251542	In recent years, a common strategy for the prevention of postsurgical intra-abdominal adhesions has been intrasurgical placement of adhesion barriers into the peritoneal cavity. Osmotic agents, such as various polysaccharides, frequently are used as antiadhesive materials. The effects of these materials on kidney function have not yet been studied. We report a case of an individual with pre-existing chronic kidney disease who developed acute kidney injury after surgical placement of an antiadhesive barrier of macromolecular polysaccharides. A kidney biopsy, performed because of persistent kidney failure, showed tubular cell lesions compatible with osmotic nephrosis lesions. This case suggests that use of polysaccharide-containing antiadhesive barriers can induce severe kidney damage. Such barriers should be used with caution in patients with abnormal kidney function to prevent irreversible damage.	\N	\N
21262922	A 2005 report from the Centers for Medicare and Medicaid Services and the Centers for Disease Control Surgical Infection Prevention program indicated that only 41% of prophylactic antibacterials were correctly stopped within 24 h of the end of surgery. Electronic order sets have shown promise as a means of integrating guideline information with electronic order entry systems and facilitating safer, more effective care. The aim was to study the effectiveness of a computer-based antibacterial order set on increasing the proportion of patients who have antibacterial wound prophylaxis discontinued in the appropriate time frame. The authors conducted a quasi-experimental interrupted time-series analysis over an 8-month study period with the implementation of a computer-based order system designed to prevent excessive duration of surgical prophylaxis antibacterials. The primary outcome was the proportion of surgeries with antibacterials discontinued in the appropriate time frame. Additionally, we evaluated the percent of surgeries after implementation of the electronic intervention with chart documentation of infection among surgeries where the prescriber indicated the reason for antibacterial therapy was treatment. The computer-based order intervention significantly improved the proportion of surgeries with timely discontinuation of antibacterials from 38.8% to 55.7% (p < 0.001) in the intervention hospital, while the control hospital remained at 56-57% (p = 0.006 for the difference between treated and control hospitals). In surgeries after intervention implementation where a prescriber indicated the reason for antibacterial therapy was treatment, the prevalence of chart documented infection was only 14%. A computer-based electronic order set intervention increased timely discontinuation of postoperative antibacterials.	\N	\N
21278729	Optogenetics is a technique for controlling subpopulations of neurons in the intact brain using light. This technique has the potential to enhance basic systems neuroscience research and to inform the mechanisms and treatment of brain injury and disease. Before launching large-scale primate studies, the method needs to be further characterized and adapted for use in the primate brain. We assessed the safety and efficiency of two viral vector systems (lentivirus and adeno-associated virus), two human promoters (human synapsin (hSyn) and human thymocyte-1 (hThy-1)) and three excitatory and inhibitory mammalian codon-optimized opsins (channelrhodopsin-2, enhanced Natronomonas pharaonis halorhodopsin and the step-function opsin), which we characterized electrophysiologically, histologically and behaviorally in rhesus monkeys (Macaca mulatta). We also introduced a new device for measuring in vivo fluorescence over time, allowing minimally invasive assessment of construct expression in the intact brain. We present a set of optogenetic tools designed for optogenetic experiments in the non-human primate brain.	\N	\N
21291294	We have assessed gastroduodenal, endoscopical and histopathological findings in a series of patients with microscopic colitis (MC). We studied 75 patients with MC, 27 with collagenous colitis (CC) and 48 with lymphocytic colitis (LC), and 60 controls. Data of endoscopical findings were collected and biopsies were assessed. Helicobacter pylori infection rate was 15% in MC and 28% in the controls (p = 0.088). Age at diagnosis of MC was higher in H. pylori positive than negative patients (63.4 ± 9.6 vs. 54.4 ± 13.1 years; p = 0.034). Gastric endoscopic erosions were more prevalent in CC than in LC (25.9% vs. 6.2%; p = 0.030) and associated with thick body glands and antral predominance of gastritis in H. pylori positive patients. Rates of focal gastritis (5.6% vs. 6.9%) and lymphocytic gastritis (5.6% vs. 10%) were similar in MC and controls. LC was associated with gastric epithelial lymphocytosis and lymphocytic gastritis. Fifteen patients (20%) had celiac disease. Unlike LC, CC is associated with endoscopic erosions, likely related with the high acid secretion capacity as indicated by the ample body glands and antral predominance of gastritis in H. pylori associated cases of CC. The presence of some divergent gastroduodenal features in LC and CC, and in comparison with those reported in inflammatory bowel disease (IBD), supports the concept that these two conditions differ not only from IBD but also from each other. The findings also suggest the presence of pathogenetic links between colorectal and gastroduodenal abnormalities.	\N	\N
21297177	Moderate chronic kidney disease (CKD) (defined by an estimated glomerular filtration rate of 30-60 ml/min) is associated with mild hypertriglyceridemia related to delayed catabolism of triglyceride-rich lipoprotein particles. Altered apolipoprotein C-III (apoC-III) metabolism may contribute to dyslipidemia in CKD. To further characterize the dyslipidemia of CKD, we investigated the kinetics of plasma apoC-III in 7 nonobese, nondiabetic, non-nephrotic CKD subjects and 7 age- and sex-matched healthy controls, using deuterated leucine ([5, 5, 5, ²H₃]leucine), gas chromatography-mass spectrometry, and multicompartmental modeling. Compared with controls, CKD subjects had higher concentrations of plasma and VLDL triglycerides and plasma and VLDL apoC-III (P < 0.05). The increased plasma apoC-III concentration was associated with a decreased apoC-III fractional catabolic rate (FCR) (1.21 ± 0.15 vs. 0.74 ± 0.12 pools/day, P = 0.03). There were no differences between apoC-III production rates of controls and those of CKD subjects. In CKD subjects, plasma apoC-III concentration was significantly and negatively correlated with apoC-III FCR (r = -0.749, P = 0.05) but not with apoC-III production rate. Plasma apoC-III concentration was positively correlated with plasma and VLDL triglycerides and VLDL apoB concentrations and negatively correlated with VLDL apoB FCR (P < 0.05 for all). ApoC-III FCR was negatively correlated with plasma and VLDL triglycerides and VLDL apoB concentration and positively correlated with VLDL apoB FCR (P < 0.05 for all). Altered plasma apoC-III metabolism is a feature of dyslipidemia in moderate CKD. Modification of apoC-III catabolism may be an important therapeutic target for reducing cardiovascular disease risk in moderate CKD.	\N	\N
21303529	Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program. Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire. Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase. This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP. ClinicalTrials.gov: NCT00566930.	\N	\N
21305298	Spondyloarthritis (SpA) are diseases with increased gut inflammation. To search for (anti-Saccharomyces cerevisiae) ASCA IgA, ASCA IgG, and anti-endomysial antibodies (EmA-IgA) in a cohort of 70 patients with SpA, we found 18.6% (13/70) positive for IgA-ASCA in the SpA group and 3/57 (5.2%) in the control group (P = 0.031). ASCA IgG and EmA-IgA were found at the same frequency in SpA and controls. No relationship of ASCA IgA positivity could be established with disease activity (measured by ESR, C-reactive protein, and BASDAI), presence of uveitis, or peripheral arthritis neither with functional status measured by BASFI. SpA patients present an increase in the IgA-ASCA positivity without any relationship to disease activity, functional index, clinical profile or the presence of HLA-B27. There is no evidence of higher prevalence of EmA-IgA in SpA patients in the studied sample.	\N	\N
21307778	Vitamin D deficiency is a global health problem that has various adverse consequences. Vitamin D is mainly synthesized in the skin by sunlight (UV light) irradiation; therefore, vitamin D status is influenced by geographic locations, seasonal changes, and skin pigmentations. The kidney is involved in the biosynthesis of 1,25-dihydroxyvitamin D and the reuptake of filtered 25-hydroxyvitamin D from the proximal tubules, thus, vitamin D deficiency is highly prevalent in patients with kidney disease who have renal insufficiency. There is a growing body of epidemiological and clinical evidence in the literature that links vitamin D deficiency to cardiovascular disease. The discovery of the vitamin D hormone functioning as an endocrine inhibitor of the renin-angiotensin system provides an explanation for this association. This review will discuss the mechanism underlying the connection between vitamin D and cardiovascular disease and its physiological and therapeutic implications.	\N	\N
21312278	Abnormal repetitive behaviors have been reported in Parkinson's disease (PD) during dopamine replacement therapy (DRT) and associated with individual predisposing features, including impulsivity. However, impulsivity and compulsive symptoms have never been explored in PD patients before initiation of DRT. We previously reported a 20% of impulse control disorders (ICD) in an Italian cohort. 103 consecutive newly diagnosed drug-naïve PD patients (means: age = 60.5 ± 9.2 years; duration = 15.4 ± 15.3 months) were screened for compulsive sexual behavior, compulsive buying, intermittent explosive disorder (Minnesota Impulsive Disorders Interview, MIDI), and pathological gambling (South Oaks Gambling Screen, SOGS). Barratt Impulsiveness Scale (BIS-11) and Maudsley Obsessional-Compulsive Questionnaire (MOCQ/R) assessed impulsivity, obsessive-compulsive symptoms, respectively. Depression (GDS-15) and general cognitive status were additionally assessed. We also compared ICDs frequency with our healthy controls. 17.5% of PD patients screened positive for at least one ICD at MIDI (17/103) and SOGS (1/103), though none had a disorder based on DSM-IV criteria. These frequencies were similar to healthy controls. There was a trend toward higher scores in BIS-11 attentive-impulsivity subscale (15.2 ± 4.8 vs. 18.7 ± 4.9; P = 0.007) and in MOCQ/R-Doubting subscale (0.67 ± 1.1 vs. 1.5 ± 1.2; P = 0.007) in PD with ICD. We also observed a positive correlation between GDS-15 and BIS-11. Similar to our healthy control population, we found a significant proportion of early PD patients positive for ICDs before starting treatment. We also found a relationship between impulsivity and depression. A detailed behavioral assessment before starting dopaminergic therapy is recommended.	\N	\N
21316322	The role of oxidative stress in patients with chronic kidney disease (CKD) as a potential marker of morbidity and mortality remains poorly evaluated. The aim of the present study aims was thus: to determine plasma levels of malondialdehyde (MDA), end product of lipid peroxidation in patients at different CKD stages (predialysis and dialysis); to evaluate the association between plasma MDA levels and vascular disease or overall and cardiovascular mortality. Plasma MDA levels evaluated by HPLC, pulse wave velocity, aortic calcification score were evaluated in 94 CKD patients (67±13 years, 54% males, 29% at CKD stages 2-3, 32% at stages 4-5, 39% at stage 5D) prospectively followed for mortality. We observed that the plasma MDA levels were increased in patient with CKD and augmented progressively with CKD stages. However, we did not find any independent association between plasma levels of MDA and pulse wave velocity, aortic calcification score, or overall and cardiovascular mortality. Our results suggest that plasma MDA is not a useful biomarker in CKD patients.	\N	\N
21317510	Many studies document racial variation, gender differences, and socioeconomic status (SES) patterning in cardiovascular disease (CVD) risk factors but few studies have investigated heterogeneity in SES differences by race/ethnicity or gender. Using data from the Multi-Ethnic Study of Atherosclerosis (N=6,814) and stratified regression models, we investigated race/ethnic differences in the SES patterning of diabetes, hypertension, smoking, and body mass index (BMI). Inverse socioeconomic gradients in hypertension, diabetes, smoking, and BMI were observed in White and Black women but associations were weaker or absent in Hispanic and Chinese women (except in the case of diabetes for Hispanic women). Even greater heterogeneity in social patterning of risk factors was observed in men. In White men all four risk factors were inversely associated with socioeconomic position, although often associations were only present or were stronger for education than for income. The inverse socioeconomic patterning was much less consistent in men of other races/ethnic groups, and higher SES was associated with higher BMI in non-White men. These findings have implications for understanding the causes of social patterning, for the analysis of SES adjusted race/ethnic differences, and for the targeting of interventions.	\N	\N
21327566	A synergistic effect of alcohol and hypertension has been suggested to increase the risk for stroke. However, the contribution of alcohol-induced hypertension to stroke morbidity and mortality may be greater than observed, because the effects of different drinking patterns have not been separately investigated. Alcohol-induced transient peaks in systolic blood pressure may predispose to stroke. Recent studies have measured time trends of blood pressure elevations in relation to alcohol consumption. They found a significant morning surge in blood pressure, which was related to alcohol intake in a dose-dependent manner and was independent of smoking. Men with a severe form of hypertension showed a 12-fold increased risk for cardiovascular disease mortality associated with heavy binge drinking. Binge drinking is a significant risk factor for stroke. Hypertensive patients should be warned about the risks of alcohol and urged to avoid binge drinking because of an increased risk for all subtypes of stroke.	\N	\N
21329838	We sought to study whether patients with right ventricular failure (RVF) secondary to chronic thromboembolic pulmonary hypertension (CTEPH) have reduced left ventricular (LV) mass, and whether LV mass reduction is caused by atrophy. The LV in patients with CTEPH is underfilled (unloaded). LV unloading may cause atrophic remodeling that is associated with diastolic and systolic dysfunction. We studied LV mass using cardiac magnetic resonance imaging (MRI) in 36 consecutive CTEPH patients (before/after pulmonary endarterectomy [PEA]) and 11 healthy volunteers selected to match age and sex of patients. We studied whether LV atrophy is present in monocrotaline (MCT)-injected rats with RVF or controls by measuring myocyte dimensions and performing in situ hybridization. At baseline, CTEPH patients with RVF had significantly lower LV free wall mass indexes than patients without RVF (35 ± 6 g/m(2) vs. 44 ± 7 g/m(2), p = 0.007) or volunteers (42 ± 6 g/m(2), p = 0.006). After PEA, LV free wall mass index increased (from 38 ± 6 g/m(2) to 44 ± 9 g/m(2), p = 0.001), as right ventricular (RV) ejection fraction improved (from 31 ± 8% to 56 ± 12%, p < 0.001). Compared with controls, rats with RVF had reduced LV free wall mass and smaller LV free wall myocytes. Expression of atrial natriuretic peptide was higher, whereas that of α-myosin heavy chain and sarcoplasmic reticulum calcium ATPase-2 were lower in RVF than in controls, both in RV and LV. RVF in patients with CTEPH is associated with reversible reduction in LV free wall mass. In a rat model of RVF, myocyte shrinkage due to atrophic remodeling contributed to reduction in LV free wall mass.	\N	\N
21332905	• To describe a multicentre experience with preoperative platinum-based chemotherapy before radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) with loco-regional nodal metastases. • We identified 313 patients from the UTUC Collaboration (over 1200 patients), who underwent RNU with concomitant retroperitoneal lymph node dissection between 1990 and 2007 and met the inclusion criteria for one of three groups. • Group 1 comprised patients who received chemotherapy before RNU because of biopsy-proven loco-regional nodal metastases. • Group 2 consisted of patients who underwent primary RNU and were found to have metastatic nodal disease on final pathological review (node-positive). • Group 3 comprised a comparative cohort of patients treated with primary RNU for invasive or locally advanced (pT2/pT4) node-negative (N0) UTUC. • Groups 1, 2 and 3 included 18, 120 and 175 patients, respectively. The 5-year disease-free survival rates were 49%, 30% and 64%, whereas the 5-year cancer-specific survival rates were 44%, 36% and 69% in groups 1, 2 and 3, respectively. • In group 1, on final pathological evaluation, nine patients were pN0, six patients were pT0 and five patients had pT0N0 disease. Kaplan-Meier survival analyses showed similar recurrence and survival rates in group 1 compared with group 3 (P= 0.14 and P= 0.06, respectively). • Meanwhile, group 2 had significantly lower disease-free and cancer-specific survival rates compared with group 3 (P < 0.001 and P < 0.001, respectively) and compared with group 1 (P= 0.04 and P= 0.06, respectively). • Preoperative chemotherapy followed by aggressive surgical consolidation may yield favourable oncological outcomes in patients with UTUC with loco-regional nodal metastases. • These data support further evaluation of neoadjuvant systemic therapy in patients at risk for locally advanced UTUC.	\N	\N
21342667	In Belgium, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the national schedule in 2007. The early impact of PCV7 vaccination on paediatric invasive disease was estimated by comparing pre- and post-vaccination incidence from national surveillance. In children <2 year-olds, vaccine-serotype incidence declined by 96% but non-vaccine-types increased 2-3-fold. Overall invasive disease decreased by 23-46%, depending on adjustment for under-reporting and pre-vaccine trends. Non-vaccine-types 1 and 19A had increased before PCV7 use, suggesting the contribution of other factors. Estimation of PCV7 impact comparing pre- and post-vaccination data should adjust for pre-vaccine trends, and serotype dynamics need further exploration.	\N	\N
21349334	The intestinal microbiota is an ecosystem formed by a variety of ecological niches, made of several bacterial species and a very large amount of strains. The microbiota is in close contact with the intestinal mucosa or epithelial interface which is, after the respiratory area, the largest surface of the body, occupying approximately 250-400 m(2). The physiological activities of the microbiota are manifold and are just being unraveled. Based on the observations of the multiple roles played by the microbiota in health and disease, the notion of modifying it with appropriate formulations, i.e. probiotics, is being tested in several settings. This review summarizes the current knowledge on probiotics and discusses both limitations and acquired evidence to support their use in preventive and therapeutic medicine.	\N	\N
21350933	This study used data mining techniques to investigate disease forms in various administrative areas and to analyze the differences among various administrative areas in order to further draw up a disease distribution map. It is hoped that may help formulate future public health strategies and to allocate medical resources more appropriately. The major disease forms for residents under the age of 60 were hypertension, hyperglycemia and hyperlipidemia. In regard to the neighboring areas, three neighboring areas, A1, A3, and B9, shared the same disease problems with A4, A5, and B3, while two mountain-area cities, B7 and C10, experienced higher instances of liver function impairment. In terms of the clustering phenomenon among municipally graded administrative areas, the major health problems in Grade A cities were hypertension, hyperglycemia, and hyperlipidemia. The health problems such as liver function impairment and renal dysfunction were more frequently observed in Grade B and Grade C cities.	\N	\N
21352090	Autologous chondrocyte implantation (ACI) is considered a promising choice for the treatment of cartilage defects. However, the application of ACI to osteoarthritic patients is, in general, contraindicated. The purpose of this study is to evaluate the efficiency of three-dimensionally structured ACI (3D-ACI; CaReS) in a rat model of knee osteoarthritis (OA). OA-like degenerative changes in the articular cartilage were created by transecting the anterior cruciate ligament (ACLT) in athymic nude rats. Two weeks later, CaReS was transplanted at the cartilage injury sites created by micro-drilling in the patella groove (Chondrocyte-implanted (CI) group: CaReS collagen with human chondrocytes; Collagen group: CaReS collagen without cells; and Sham group: sham operation; n = 15/group). Reverse Transcription Polymerase Chain Reaction (RT-PCR) analysis demonstrated the expression of human-specific type 2 collagen and Sry-type high-mobility-group box 9 (SOX9) in the CI group-not in the other groups-throughout the study period. Double immunohistochemistry for human-specific type 2 collagen and human leukocyte antigen-abacavir (HLA-ABC) at week 4 showed positive staining in the CI group only. Macroscopic assessment showed better repair at the cartilage defect sites in the CI group, compared to the other groups. Histological assessment with toluidine blue staining showed that the thickness of the articular cartilage and semi-quantitative histological scores were higher in the CI group than in the other groups up to week 20. We demonstrate, for the first time, that 3D-ACI is effective in repairing cartilage defects in a rat model of ACLT-induced OA.	\N	\N
21354253	Molecular rotors are a form of fluorescent intramolecular charge-transfer complexes that can undergo intramolecular twisting motion upon photoexcitation. Twisted-state formation leads to non-radiative relaxation that competes with fluorescence emission. In bulk solutions, these molecules exhibit a viscosity-dependent quantum yield. On the molecular scale, the fluorescence emission is a function of the local free volume, which in turn is related to the local micro-viscosity. Membrane viscosity, and the inverse; fluidity, are characteristic terms used to describe the ease of movement withing the membrane. Often, changes in membrane viscosity govern intracellular processes and are indicative of a disease state. Molecular rotors have been used to investigate viscosity changes in liposomes and cells, but accuracy is affected by local concentration gradients and sample optical properties. We have developed self-calibrating ratiometric molecular rotors to overcome this challenge and integrated the new molecules into a DLPC liposome model exposed to the membrane-fluidizing agent propanol. We show that the ratiometric emission intensity linearly decreases with the propanol exposure and that the ratiometric intensity is widely independent of the total liposome concentration. Conversely, dye concentration inside liposomes influences the sensitivity of the system. We suggest that the new self-calibrating dyes can be used for real-time viscosity sensing in liposome systems with the advantages of lifetime measurements, but with low-cost steady-state instrumentation.	\N	\N
21357888	This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD), which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure), were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils), dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life) and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.	\N	\N
21360500	In addition to inducing a self-limited myopathy, statin use is associated with an immune-mediated necrotizing myopathy (IMNM), with autoantibodies that recognize ∼200-kd and ∼100-kd autoantigens. The purpose of this study was to identify these molecules to help clarify the disease mechanism and facilitate diagnosis. The effect of statin treatment on autoantigen expression was addressed by immunoprecipitation using sera from patients. The identity of the ∼100-kd autoantigen was confirmed by immunoprecipitation of in vitro-translated 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) protein. HMGCR expression in muscle was analyzed by immunofluorescence. A cohort of myopathy patients was screened for anti-HMGCR autoantibodies by enzyme-linked immunosorbent assay and genotyped for the rs4149056 C allele, a predictor of self-limited statin myopathy. Statin exposure induced expression of the ∼200-kd/∼100-kd autoantigens in cultured cells. HMGCR was identified as the ∼100-kd autoantigen. Competition experiments demonstrated no distinct autoantibodies recognizing the ∼200-kd protein. In muscle biopsy tissues from anti-HMGCR-positive patients, HMGCR expression was up-regulated in cells expressing neural cell adhesion molecule, a marker of muscle regeneration. Anti-HMGCR autoantibodies were found in 45 of 750 patients presenting to the Johns Hopkins Myositis Center (6%). Among patients ages 50 years and older, 92.3% had taken statins. The prevalence of the rs4149056 C allele was not increased in patients with anti-HMGCR. Statins up-regulate the expression of HMGCR, the major target of autoantibodies in statin-associated IMNM. Regenerating muscle cells express high levels of HMGCR, which may sustain the immune response even after statins are discontinued. These studies demonstrate a mechanistic link between an environmental trigger and the development of sustained autoimmunity. Detection of anti-HMGCR autoantibodies may facilitate diagnosis and direct therapy.	\N	\N
21362127	Type 3 von Willebrand disease (VWD) is an autosomal recessive bleeding disorder, characterized by virtually undetectable plasma von Willebrand factor (VWF) and consequently reduced plasma factor VIII levels. Genetic mutations responsible for type 3 VWD are very heterogeneous, scattered throughout the VWF gene and show high variability among different populations. Twenty-five severe VWD patients were studied by direct sequencing of the 51 coding exons of the VWF gene. The total number of VWD type 3 families in Hungary is 24, of which 23 were investigated. Fifteen novel mutations were identified in 31 alleles, five being nonsense mutations (p.Q1238X, p.Q1898X, p.Q1931X, p.S2505X and p.S2568X), four small deletions and insertions resulting in frame shifts (c.1992insC, c.3622delT, c.5315insGA and c.7333delG), one a large partial deletion (delExon1-3) of the 5'-region, four candidate missense mutations (p.C35R, p.R81G, p.C295S, p.C623T) and one a candidate splice site mutation (c.1730-10C>A). Six previously described mutations were detected in 17 alleles, including the repeatedly found c.2435delC, p.R1659X and p.R1853X. Only one patient developed alloantibodies to VWF, carrying a homozygous c.3622delT. We report the genetic background of the entire Hungarian type 3 VWD population. A large novel deletion, most probably due to a founder effect, seems to be unique to Hungarian type 3 VWD patients with high allele frequency. In contrast to previous reports, none of the five patients homozygous for the large partial deletion developed inhibitors to VWF. This discrepancy raises the possibility of selection bias in some of the reports.	\N	\N
21363991	Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in Shandong Province, China. In this study, we combined ecologic niche modeling with geographic information systems (GIS) and remote sensing techniques to identify the risk factors and affected areas of hantavirus infections in rodent hosts. Land cover and elevation were found to be closely associated with the presence of hantavirus-infected rodent hosts. The averaged area under the receiver operating characteristic curve was 0.864, implying good performance. The predicted risk maps based on the model were validated both by the hantavirus-infected rodents' distribution and HFRS human case localities with a good fit. These findings have the applications for targeting control and prevention efforts.	\N	\N
21397153	Epidermolysis bullosa acquisita (EBA) is the rarest of the autoimmune bullous diseases (AIBD). It is defined as an AIBD secondary to production of antibodies directed against type VII collagen and then binding to anchoring fibrils in the basal membrane zone (BMZ) of the skin and the Malpighian mucosa. To evaluate risk factors, different clinical forms and diagnostic methods, and the efficacy of treatments. The articles were identified by a search of PubMed and Embase from the initial creation of these databases through to March 2009. We selected generalised reviews and meta-analyses, cases involving unusual and/or serious clinical presentations, studies of immunological tests and homogeneous retrospective series regarding therapy. Of the 206 articles analysed, only two were of an adequate level of proof, with four of intermediate level, and all the others of only low level. EBA affects all age groups (from newborn infants to the very elderly) with a slight predominance in female subjects. Diagnosis must be considered in subjects with black skin of African origin. A drug-induced origin of the disease was reported in 11% of cases of IgA-EBA. Classical EBA (30 to 50% of cases), resembles epidermolysis bullosa hereditaria (EBH), with fragile skin, non-inflammatory bullae, dystrophic scars and milia. Numerous atypical and misleading forms exist. Evocative signs are the presence of mucosal lesions and/or scars. The severity of EBA is determined by the extent of cutaneous lesions, and ophthalmological, ENT and/or oesophageal involvement. Crohn's disease is associated in 25% of cases of EBA. Unequivocal diagnosis is provided by direct immunoelectron microscopy (IEM). Therapeutic efficacy has been reported for dapsone, sulphapyridine and colchicine in milder forms, and for cyclosporine, mycophenolate mofetil, rituximab, intravenous immunoglobulins and extracorporeal photochemotherapy in resistant and severe forms. A number of authors have reported inefficacy of systemic corticosteroids, even in high-dose regimens, with the development of corticosteroid dependence in certain cases. In the absence of any therapeutic trials, it is difficult to select optimal treatment; however, the benefit/risk ratio of systemic corticosteroid treatment is unfavourable.	\N	\N
21397734	In this paper we introduce a new technical development of branching processes that can potentially model spread of epidemics by including various stages of infection. In fact, we present an epidemic model that the disease spreads from an individual to another one in such a way that the ability of individual u to infect a susceptible individual depends only on how long u has been infected. For analysis of this model, we introduce a new and special model of the Crump-Mode-Jagers branching processes in discrete time and obtain some of its fundamental properties.	\N	\N
21404106	To confirm the efficacy and toxicity of Erlotinib in combination with Gemcitabine and Capecitabine when used as a first-line therapy in metastatic/recurrent pancreatic cancer (PC). Locally advanced PC was excluded. Erlotinib was given at a dose of 100 mg daily from D1 to D28. 1000 mg/m(2) of gemcitabine was given on D1,8,15 and 1660 mg/m(2)/day of capecitabine was given from D1 to 21, repeated every 4 weeks. Response was assessed every 8 weeks. A total of 47 patients were enrolled. Response rate and disease control rate was 32.6% (95% CI, 18.6-46.6%) and 83.7% (95% CI, 72.7-94.7%) respectively. The PFS was 6.5 months (95% CI, 3.4-9.7) and OS was 12.0 months (95% CI, 8.6-15.9). The Gr 3/4 toxicities were: neutropenia (6.8%), thrombocytopenia (3.2%), anemia (1.6%). nausea (1.6%), vomiting (1.6%), anorexia (5.3%), rash (2.4%). The EGFR expression was associated with shorter OS and ERCC2 expression was associated with longer PFS and OS. PFS and OS were not different according to K-RAS mutation or polymorphism of RRM1 and CDA. Erlotinib, gemcitabine and capecitabine combination showed promising efficacy and good tolerability in metastatic PC. This efficacy was observed irrespective of K-RAS mutation, and EGFR expression was poor prognostic factor for OS.	\N	\N
21415164	Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor-negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase α), ELOVL1 (elongation of very long chain fatty acid-like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element-binding protein cleavage-activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone-responsive protein)] indicated that silencing of multiple lipid metabolism-regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment.	\N	\N
21418090	To investigate associations between fasting plasma glucose level and the prevalence of acquired colour vision impairment in type 2 diabetes patients without diabetic retinopathy. Participants in this cross-sectional study of male officials aged 20-60 yr in the Japanese Self Defence Force, underwent colour vision testing, ophthalmic examination, a standardized interview and examination of venous blood samples. Ishihara plates, a Lanthony 15-hue desaturated panel and Standard Pseudoisochromatic Plates Part 2 were used to examine colour vision. The Farnsworth-Munsell 100-hue test was performed to define acquired colour vision impairment. Cardiovascular disease risk factors were determined from serum blood samples, physical records and an interview. We performed logistic regression analysis adjusted for age, diagnosed hypertension, dyslipidaemia, cataract, glaucoma, being overweight, smoking status and alcohol intake. Crude and adjusted odds ratios were calculated for three glucose levels, which included normal fasting glucose, impaired fasting glucose and diabetes. Out of a total of 1042 men enrolled, 872 were eligible for the study, and 31 were diagnosed with acquired colour vision impairment. As compared with the subjects with normal fasting glucose (< 5.6 mmol/l), the crude odds ratio for acquired colour vision impairment was 0.93 (95% CI 0.32-2.74) for the subjects with impaired fasting glucose (5.6-6.9 mmol/l) and 8.07 (95% CI 2.48-26.22) for the patients with type 2 diabetes. The multiple-adjusted odds ratios were 0.77 (95% CI 0.25-2.34) for the subjects with impaired fasting glucose and 5.89 (95% CI 1.55-22.40) for the patients with type 2 diabetes. Our findings suggest that there is a dramatically increased prevalence of acquired colour vision impairment in type 2 diabetes patients without diabetic retinopathy which might be attributable to another pathogenesis associated with diabetic retinopathy.	\N	\N
21421095	Appendectomy remains one of the most common emergency surgical procedures encountered throughout the United States. With improvements in diagnostic techniques, the efficiency of diagnosis has increased over the years. However, the entity of negative appendectomies still poses a dilemma because these are associated with unnecessary risks and costs to both patients and institutions. This study was conducted to show current statistics and trends in negative appendectomy rates in the United States. A retrospective analysis was conducted using data from the National Inpatient Sample from 1998 to 2007. Adult patients (>18 y) having undergone appendectomies were identified by the appropriate International Classification of Diseases 9th revision codes. Patients with incidental appendectomy and those with appendiceal pathologies, also identified by relevant International Classification of Diseases 9th revision codes, were excluded. The remaining patients represent those who underwent an appendectomy without appendiceal disease. The patients then were stratified according to sex, women were classified further into younger (18-45 y) and older (>45 y) based on child-bearing age. The primary diagnoses subsequently were categorized by sex to identify the most common conditions mistaken for appendiceal disease in the 2 groups. Between 1998 and 2007, there were 475,651 cases of appendectomy that were isolated. Of these, 56,252 were negative appendectomies (11.83%). There was a consistent decrease in the negative appendectomy rates from 14.7% in 1998 to 8.47% in 2007. Women accounted for 71.6% of cases of negative appendectomy, and men accounted for 28.4%. The mortality rate was 1.07%, men were associated with a higher rate of mortality (1.93% vs .74%; P < .001). Ovarian cyst was the most common diagnosis mistaken for appendicitis in younger women, whereas malignant disease of the ovary was the most common condition mistaken for appendiceal disease in women ages 45 and older. The most common misdiagnosis in men was diverticulitis of the colon. There has been a consistent decline in the rates of negative appendectomy. This trend may be attributed to better diagnostics. Gynecologic conditions involving the ovary are the most common to be misdiagnosed as appendiceal disease in women.	\N	\N
21422948	This study was designed to characterize the energy metabolism in the patients with acute-on-chronic liver failure (ACLF). Protein-energy malnutrition usually occurs in the patients with chronic liver disease and is exacerbated during the progression of liver failure. Unfortunately, there is limited study to fully elucidate the energy metabolism in the patients with ACLF. A retrospective cohort was designed with a total of 282 patients (100 patients with ACLF, 100 with liver cirrhosis, and 82 with chronic hepatitis B). Resting energy expenditure and the oxidation rates of glucose, lipid, and protein were assessed by indirect heat measurement using the critical care monitor and desktop analysis system, nutritive metabolic investigation system. Survival rate was estimated with the Kaplan-Meier method. There was no significant difference in resting energy expenditure among the patients with ACLF, the liver cirrhosis, and the chronic hepatitis (1402.05±480.07 kcal/d in patients with ACLF, 1274.27±316.36 kcal/d in patients with liver cirrhosis, and 1396.77±384.80 kcal/d in patients with chronic hepatitis). Respiratory quotient (RQ) was significantly lower in the patients with ACLF than those in the liver cirrhosis and the chronic hepatitis B (P=0.000). In patients with ACLF, RQ of the nonsurvival group was significantly lower than the survival group (P=0.000). It is identified from receiver operating characteristic curve analysis that a RQ cutoff value of 0.83 (area under the receiver operating characteristic curve, 0.760) is favorable to predict good prognosis in patients with liver failure, which has a sensitivity of 73.68%, a specificity of 74.42%, and positive predictive value of 79.2% and negative predictive value of 68.1%. In patients with ACLF, RQ was significantly lower in the nonsurvival group than the survival group, thus suggesting that RQ may be used as an indicator of prognosis of liver failure.	\N	\N
21426326	To investigate for the first time the natural history and long-term evolution of "familial cortical tremor, myoclonus, and epilepsy." We evaluated the clinical, electrophysiologic, and treatment data of 14 patients from three families linked to 2p11.1-q12.2. A simplified scale was used to score myoclonus severity. Electroencephalography (EEG) studies were reviewed for the evaluation of background activity, paroxysmal abnormalities, and photoparoxysmal response. Data were organized for age groups. Correlation and logistic regression analysis were performed. Patients' mean age was 47.8 ± 22.0 years (range 20-86 years). Mean age at disease onset was 20.2 ± 7.8 years (range 11-40 years); mean follow-up duration was 14.0 ± 5.8 years (range 7-28 years). Evaluation at different age groups revealed a gradual, progressive worsening of the myoclonus in 10 patients (71.4%). Two subjects aged >80 years showed myoclonus interfering with autonomous walking. Myoclonus severity was correlated with disease duration (p<0.001) and patients' age (p=0.001). Six patients (42.8%) experienced seizures, usually between the second and sixth decades of life. Evaluation of EEG long-term evolution revealed progressive slowing of background activity in parallel with the gradual worsening of myoclonus. In contrast, paroxysmal activity and photosensitivity were particularly evident during the intermediate phases of the disease. In addition, psychiatric and neuropsychological dysfunction occurred in more than one third of the patients. We provide data for a slight age-dependent progression and the presence of neuropsychiatric and neuropsychological dysfunction in this unique syndrome, for which the definition of familial or autosomal dominant cortical tremor, myoclonus, and epilepsy (FCTME/ADCME) seems to be, therefore, more appropriate.	\N	\N
21429534	Familial combined hyperlipidemia (FCH) is a genetic model of atherogenic dyslipidemia with insulin resistance and early coronary disease. Our objective was to evaluate the presence of carotid alterations as a marker of systemic atherosclerosis in subjects with FCH and assess the effect of 80 mg of atorvastatin per day in carotid plaque thickness after 2 years. 100 non diabetic subjects with FCH in primary prevention were consecutively included. Clinical and biochemical parameters and carotid ultrasonography were performed. Subjects with carotid plaque started treatment with 80 mg of atorvastatin per day for 2 years. 29% of subjects had carotid plaques. We did not find significant differences in any of the parameters between subjects with presence or absence of carotid plaques. Twenty subjects with carotid plaques accepted/agreed to participate in the interventional study. Two years follow-up showed a significant reduction in LDLc (30%) and carotid plaque thickness (10%). Carotid ultrasonography is useful to detect subclinical atherosclerosis in high risk cardiovascular patients such as subjects with FCH. Treatment with high doses of atorvastatin induces the regression of carotid plaque thickness after 2 years follow-up. Our results suggest that intensive treatment with atorvastatin could be useful to reduce the development of cardiovascular disease in this group of patients.	\N	\N
21430371	The aim of this study was to evaluate the impact of clinical variables and biologic features on response rate (RR), overall survival (OS) and progression-free survival (PFS) in 111 patients with de novo diffuse large B cell lymphoma (DLBCL). Fifty-three patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and 58 patients were treated with R-CHOP (rituximab + CHOP). The variables predictive of RR in the CHOP group were B symptoms, age, clinical stage, bone marrow involvement, bulky disease, International Prognostic Index (IPI) and Bcl-2; in the R-CHOP group, these variables were bulky disease, bone marrow involvement, IPI and Ki67 expression >80%. Multivariate analysis showed that in patients treated with CHOP, the independent prognostic factors associated with PFS were age, bulky disease, IPI and Bcl-2 and those associated with OS were performance status, clinical stage, IPI and bone marrow involvement. In contrast, in patients treated with R-CHOP, the variable shown by multivariate analysis to be an independent prognostic factor associated with PFS was bulky disease, whereas Ki67 expression >80% was associated with OS and PFS. Our data show that a high Ki67 expression and bulky disease could represent possible predictive factors of poor prognosis, which would help to identify a high-risk subgroup of newly diagnosed DLBCL.	\N	\N
21437774	The enormous abundance of lipid molecules in the central nervous system (CNS) suggests that their role is not limited to be structural and energetic components of cells. Over the last decades, some lipids in the CNS have been identified as intracellular signalers, while others are known to act as neuromodulators of neurotransmission through binding to specific receptors. Neurotransmitters of lipidic nature, currently known as neurolipids, are synthesized during the metabolism of phospholipid precursors present in cell membranes. Therefore, the anatomical identification of each of the different lipid species in human CNS by imaging mass spectrometry (IMS), in association with other biochemical techniques with spatial resolution, can increase our knowledge on the precise metabolic routes that synthesize these neurolipids and their localization. The present study shows the lipid distribution obtained by MALDI-TOF IMS in human frontal cortex, hippocampus, and striatal area, together with functional autoradiography of cannabinoid and LPA receptors. The combined application of these methods to postmortem human brain samples may be envisioned as critical to further understand neurological diseases, in general, and particularly, the neurodegeneration that accompanies Alzheimer's disease.	\N	\N
21438696	To test the hypothesis of a significant association between resting heart rate (RHR) and coronary artery calcium (CAC). This is a cross-sectional study of a subset of women enrolled in the estrogen-alone clinical trial of the Women's Health Initiative (WHI). We used a longitudinal study that enrolled 998 postmenopausal women with a history of hysterectomy between the ages of 50 and 59 at enrollment at 40 different clinical centers. RHR was measured at enrollment and throughout the study, and CAC was determined approximately 7 years after the baseline clinic visit. The mean (standard deviation [SD]) age was 55 (2.8) years. With adjustment for age and ethnicity, a 10-unit increment in RHR was significantly associated with CAC (SD 1.18, 95% confidence interval [CI] 1.01-1.38), but this was no longer significant after adjustment for body mass index (BMI), income, education, dyslipidemia, diabetes, smoking, and hypertension (SD 1.06, 95% CI 0.90-1.25). In a fully adjusted multivariable model, however, there was a significant interaction (p=0.03) between baseline RHR and systolic blood pressure (SBP) for the presence of any CAC. Compared to women with an RHR < 80 beats per minute (BPM) and an SBP < 140 mm Hg, those who had an RHR ≥ 80 BPM and an SBP ≥ 140 mm Hg had 2.66-fold higher odds (1.08-6.57) for the presence of any CAC. Compared to those with normal BP and RHR, postmenopausal, hysterectomized women with an elevated SBP and RHR have a significantly higher odds for the presence of calcified coronary artery disease.	\N	\N
21438811	Hepatic steatosis, considered the first step in the pathophysiologic continuum of non-alcoholic fatty liver disease, is estimated to afflict 30% of the US population and over 75% of patients with Type 2 diabetes. Given the expected rise in the prevalence of obesity and Type 2 diabetes in the following decades, hepatic steatosis will, if not already, become an epidemic. The consequences of hepatic steatosis are numerous, and range from progression to chronic liver disease, with its associated morbidity and mortality, to worsening insulin resistance and Type 2 diabetes, as well as being an independent contributor to cardiovascular disease. All such consequences are more likely to occur in patients with Type 2 diabetes who are already at high risk of cardiovascular events. In this article we review the evidence behind the available therapeutic options for hepatic steatosis, and identify challenges and unmet needs in the field.	\N	\N
21439159	The influence of respiratory infections on asthma has not been fully understood. Acute viral and bacterial infections often lead to exacerbations. Less is known about the role of chronic infections, particularly with atypical pathogens. The aim of this study was to evaluate the impact of Chlamydophila pneumoniae and Mycoplasma pneumoniae infections on the control and severity of asthma. Spirometry, skin-prick tests as well as measurement of immunoglobulin G (IgG), IgM, and IgA against C. pneumoniae and M. pneumoniae (ELISA) were performed in 95 patients with persistent asthma and 58 healthy controls. Additionally, in the selected group of asthmatic patients, presence of C. pneumoniae and M. pneumoniae genetic material was tested in induced sputum (polymerase chain reaction [PCR]). IgA against C. pneumoniae was found in 42 (44.2%) asthmatic patients and 17 (29.3%) controls (p < 0.05). It was found more often in the group with uncontrolled asthma (p = 0.001) as well as in nonatopic asthmatic patients (p < 0.05). IgG was detected in 58 asthmatic patients (61%) and 21 (36.2%) controls, more often in cases of uncontrolled (p < 0.05) and nonatopic asthma patients (p < 0.05). Such correlations were not found in relation to M. pneumoniae infections. C. pneumoniae was detected by means of PCR in respiratory secretions of eight asthmatic patients (40%), and M. pneumoniae was detected in two asthmatic patients (10%). In conclusion, C. pneumoniae infections are more frequent in asthmatic patients compared with healthy individuals and in nonatopic asthmatic patients compared to atopic patients. Chronic infection is associated with poor control of asthma.	\N	\N
21443521	The inherited disorders of hemoglobin synthesis are the most common monogenic disorders worldwide. They include thalassemias, hemoglobin variants, and hereditary persistence of fetal hemoglobin. β-thalassemia is the most common monogenic disorder in India. Clinical manifestations of β-thalassemia are extremely variable in severity. The reasons for this heterogeneity are not very well understood. Previous studies have shown that the genetic variants that modulate HbF levels have a very strong impact on ameliorating the clinical phenotype. In the present study, 5570 blood samples from suspected cases were analyzed using HPLC, amplification refractory mutation system-PCR and reverse dot blot techniques. Of 5570 individuals, we found 676 cases of β-thalassemia disease. Molecular analysis revealed the presence of different β-thalassemia mutations in the population under study. Patients with β-thalassemia were classified into mild, moderate, and severe according to severity score based on Hb level, age of onset, age at which patients received their first blood transfusion, degree of growth retardation and splenectomy. Patients with β-thalassemia were analyzed for zinc finger and homeoboxes 2 (ZHX2) G779A polymorphism, and the association between ZHX2 gene polymorphism and severity of β-thalassemia was evaluated. We did not find a significant difference in genotypic and allelic frequency of ZHX2 gene between mild and moderate, mild and severe, and moderate and severe cases. There was no significant difference in high and low percentage of HbF in GG, GA, and AA bearing individuals showing that ZHX2 gene variant has no role in ameliorating the severity of β-thalassemia major in the South Indian population from Andhra Pradesh.	\N	\N
21458394	Encapsulating peritoneal sclerosis (EPS) is a rare but life-threatening complication of peritoneal sclerosis (PD). In 2000, the International Society for Peritoneal Dialysis outlined diagnostic guidelines and a clinical definition of EPS. Over the intervening years, new evidence was published and several centers became more experienced managing patients with EPS. Although, further networking was initiated (European EPS Working Group), evidence regarding therapy and diagnosis of EPS is still lacking. Multicenter trials are needed to establish evidence regarding the management of EPS. Risk factors for EPS are identified and patients at risk should be monitored closely. In case of emerging signs of EPS, patients should be referred to an EPS-center before initiation of therapy. Morphology and immunohistochemistry will play a central role in the near future. Nowadays, most pathologists are not sophisticated in the pathology of peritoneal biopsies. Clear histological criteria are warranted. For the outcome of the patient, it is crucial that an EPS experienced surgeon conducts surgery.	\N	\N
21463281	Dravet syndrome (DS) is an epileptic encephalopathy related mainly to mutations in the SCN1A gene, encoding for neuronal sodium channels. Patients with DS have a high risk of sudden unexpected death in epilepsy (SUDEP). In this study we investigated whether patients with DS present abnormalities in electrical and autonomic cardiac function. To this aim we assessed ventricular repolarization and heart rate variability (HRV) on standard electrocardiography (ECG) and on 24-h ECG Holter monitoring, respectively, in 20 patients affected by DS (6.8 ± 4 years, 11 female). As age- and sex-matched control groups, we also studied 20 patients with other epileptic syndromes receiving antiepileptic drugs (ES/AED, 6.0 ± 5 years, 12 female), 20 patients with other epileptic syndromes without treatment (ES/no-AED, 6.7 ± 4 years, 10 female), and 20 healthy children (HC, 7.2 ± 5 years, 11 females). Data analysis showed that patients with DS had depressed HRV variables compared to both ES patients (ES/AED and ES/no-AED) and HC control group, whereas no significant differences in HRV variables were found between ES patients (with and without treatment) and HC. There was no significant difference between patients with DS and all the other control groups in RR intervals, QT, and QTc interval analysis. In conclusion, DS patients display an imbalance of cardiac autonomic function toward a relative predominance of adrenergic tone compared to both healthy children and patients with other forms of epilepsy, independent of antiepileptic therapy. Follow-up studies should clarify the clinical significance of this autonomic impairment and whether HRV analysis can be helpful in predicting the risk of sudden death in patients with DS.	\N	\N
21463368	Oral lichen planus (OLP) is generally accepted as a chronic and T-cell-mediated autoimmune disease, whose immunopathogenesis may involve antigen presentation, T-cell activation and migration as well as, possibly, tumor necrosis factor-alpha (TNF-α)-induced keratinocytes apoptosis. However, present treatment options for OLP are far from being satisfactory. Recent advances in understanding the pathogenesis of OLP, progress in biologics, and the success of biologic therapies in OLP indicate that biologic agents are facing expanding indications in OLP. In this review, we mainly discuss the role of T cells in the pathogenesis of OLP and several biologic therapies that directly and/or indirectly target T cells to treat OLP.	\N	\N
21467169	Purpose. To compare the properties of the visual field index (VFI) to those of mean deviation (MD) in patients with glaucoma. Methods. MD and VFI were calculated in data obtained from an ongoing longitudinal study in which patients with glaucoma (N = 109, 204 eyes) were observed for 9.8 years (median, 21 tests) with static automated perimetry. MD and VFI were compared in one test of each eye, and a subset of 30 tests were selected to compare the VFI with the judgments of eight experts who judged the percentage of the remaining visual field. In series of tests obtained over time, rates of change, statistical significance, evidence of nonlinearity, and variability were compared between both indices. Results. In single tests, MD and VFI were closely related (r = 0.88, P < 0.001). The relationship between both indices appeared linear, except in visual fields with MDs better than -5.0 dB where 29 (22%) of 129 eyes exhibited a ceiling effect (VFI = 100%). Based on this relationship, the predicted VFIs for visual fields with MDs of -5, -10, and -15 dB were 91%, 76%, and 60%, respectively. The percentage of remaining visual field suggested by the VFI exceeded the range of the experts' subjective judgments in 16 (53%) of 30 eyes. In series of tests obtained over time, rates of change with the two indices were closely related (r = 0.79, P < 0.001), and statistically significant reductions over time (P < 0.05) occurred in a similar number of eyes (92 [45%] with MD, and 87 [43%] with VFI). Of the 105 eyes with statistically significant (P < 0.05) negative trend in either MD or VFI, 74 (70%) showed such trends with both indices (κ = 0.69). The variability of MD and VFI increased with damage, and there was no evidence that change over time was more linear with VFI than with MD. Conclusions. The VFI provides a simple and understandable metric of visual field damage, but its estimates of remaining visual field were more optimistic than those of the experts. Rates of change over time with both indices were closely related, but the reliance of the VFI on pattern deviation probability maps caused a ceiling effect that may have reduced its sensitivity to change in eyes with early damage. In this group of patients there was no evidence to suggest that the VFI is either superior or inferior to the MD as a summary measure of visual field damage.	\N	\N
21468585	Basic transcription element-binding protein 2 (BTEB2) is a regulator of the proliferation and phenotypic changes of vascular smooth muscle cells (SMCs). The aim of the present study was to determine whether or not BTEB2 knockdown inhibits balloon injury-induced neointimal hyperplasia attributed to the proliferation and phenotypic changes of vascular SMCs. We found that the knockdown of BTEB2 with antisense oligonucleotides (Ad-As-BTEB2) significantly reduced the intima/media ratio compared to uninjured arteries and vessels treated with Ad-LacZ. Knockdown of BTEB2 suppresses the proliferation of cultured vascular SMCs, concurrent with the down-regulation of proliferating cell nuclear antigen, angiotensin II type 1 receptor and platelet-derived growth factor BB. In addition, BTEB2 knockdown caused the up-regulation of the differentiation marker smooth muscle α-actin and down-regulation of the dedifferentiation marker embryonic smooth muscle myosin heavy chain. The present study provides direct evidence that BTEB2 plays a critical role in balloon injury-induced neointimal hyperplasia, which is closely linked to vascular SMC proliferation and phenotypic modulation. This study highlights the fact that BTEB2 may be a potential target for the prevention of restenosis after vascular intervention.	\N	\N
21473920	Diffusion imaging of post mortem brains has great potential both as a reference for brain specimens that undergo sectioning, and as a link between in vivo diffusion studies and "gold standard" histology/dissection. While there is a relatively mature literature on post mortem diffusion imaging of animals, human brains have proven more challenging due to their incompatibility with high-performance scanners. This study presents a method for post mortem diffusion imaging of whole, human brains using a clinical 3-Tesla scanner with a 3D segmented EPI spin-echo sequence. Results in eleven brains at 0.94 × 0.94 × 0.94 mm resolution are presented, and in a single brain at 0.73 × 0.73 × 0.73 mm resolution. Region-of-interest analysis of diffusion tensor parameters indicate that these properties are altered compared to in vivo (reduced diffusivity and anisotropy), with significant dependence on post mortem interval (time from death to fixation). Despite these alterations, diffusion tractography of several major tracts is successfully demonstrated at both resolutions. We also report novel findings of cortical anisotropy and partial volume effects.	\N	\N
21474147	Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the gold standard surgical treatment for chronic ulcerative colitis. More recently, this procedure is being performed laparoscopically assisted. Postoperatively, small bowel obstruction (SBO) is one of the more common associated complications. However, it is unknown whether the addition of a laparoscopic approach has changed this risk. This study aims to assess and compare the incidence of SBOs after both open and laparoscopic restorative proctocolectomy. All subjects who underwent restorative proctocolectomy from 1998-2008 were identified from a prospective Colorectal Surgery Database. Medical records were reviewed for all cases of SBO, confirmed by a combination of clinical symptoms and radiologic evidence. Comparisons were made between laparoscopic and open approaches. The incidence of SBO was also subdivided into pre-ileostomy takedown, early post-ileostomy takedown (30 d post), and late post-ileostomy takedown (30 d to 1 y post). Several potential risk factors were also evaluated. Statistical analysis was performed utilizing Fisher's exact (for incidence) or t-tests (for means). Significance was defined as P < 0.05 A total of 290 open cases and 100 laparoscopic cases were identified during this time period. The overall incidence of SBO at 1 y post-ileostomy takedown was 14% (n = 42) in the open group and 16% (n = 16) laparoscopic (P = NS). In the pre-ileostomy takedown period the incidence of SBO was 7% (n = 21) open and 13% (n = 13) laparoscopic (P = NS). While in the post-takedown period, the early incidence was 4% (n = 12) open and 1% (n = 1) laparoscopic and late incidence was 3% (n = 9) open and 2% (n = 2) laparoscopic (P = NS). Factors associated with an increased risk of SBO include coronary artery disease, prior appendectomy and W and J pouch configurations. The burden of postoperative small bowel obstruction after restorative proctocolectomy is not changed with a laparoscopic approach. Most cases occur in the early postoperative period, especially prior to ileostomy reversal.	\N	\N
21475985	To investigate the nationwide prevalence of hepatitis E virus (HEV) infection and to characterize HEV genomes among Japanese wild boars (Sus scrofa leucomystax), 578 boars captured in 25 prefectures from 2003 to 2010 were studied. Anti-HEV IgG was detected in 8.1%, and HEV RNA in 3.3% of boars. Among the 19 boar HEV isolates obtained from infected boars, 14 isolates (74%) were classified as genotype 3, 4 isolates (21%) as genotype 4, and the remaining isolate (wbJOY_06) was distantly related to all known HEV isolates of genotypes 1-4, differing by 18.4-25.0% and 18.0-24.3% within the 412-nucleotide sequence of ORF1 and ORF2, respectively. A genotype 4 boar HEV isolate (wbJGF_08-1) obtained herein shared 98.6% identity over the entire genome with a human HEV isolate obtained from a patient who developed acute hepatitis after consuming undercooked wild boar meat, suggesting that wild boars are also reservoirs for genotype 4 HEV in humans.	\N	\N
21476292	The performance of a latex agglutination test (Mediace TPLA) in the detection of anti-treponemal antibody was evaluated in comparison with chemical luminescence tests (LumipulsII-N and Architect TPAb) in 346 cases. Anti-treponemal antibody was further determined by immunochromatography and immunoblotting tests and additionally evaluated by a serological test for syphilis with lipoidal antigens. The total concordance rate between the latex agglutination test and chemical luminescence tests ranged from 96% to 97%: the positive concordance rate ranged from 96% to 97%, and the negative concordance rate, from 97% to 98%. The latex agglutination test showed two false positive cases, and each chemical luminescence test showed two false positive cases, respectively. In eight cases, only the latex agglutination test showed negative results; all specimens contained anti-treponemal antibodies. However, none of these was considered to be a false positive and each was treated as syphilis based on the results of confirmatory analysis with immunochromatography and immunoblotting tests and a serological test for syphilis. The discordant results in the latex agglutination test and chemical luminescence tests may be caused by the different antigenisity of each test. With detailed analysis of those sera treated as syphilis, each specimen was found to contain various antibodies against syphilitic antigens, suggesting that there was a different specificity of native and recombinant antigens. Based on the present results for the comparison between the latex agglutination test and chemical luminescence tests, it was considered that further investigation is necessary to clarify the anti-treponemal antibody profile of syphilis at the disease stage.	\N	\N
21477408	Ideally putative disease-modifying therapies for Alzheimer's disease (AD) should be tested in patients who have minimal morbidity. Current barriers to such trials in early disease include the lack of disease-specific early biomarkers, insensitivity of quantitative cognitive outcome measures, and expensive trial designs requiring large sample sizes and long duration. This paper describes principles and progress towards a novel trial design that overcomes these problems, utilizing wide-scale cognitive performance screening to define pre-trial cognitive decline trajectories which can serve as trial outcome measures to assess AD disease-modifying efficacy. Theoretical principles important for the detection of intra-individual cognitive decline and a practical example are described. Serial evaluations of community-based volunteers demonstrate how a screening tool method to detect subtle cognitive decline can predict in vivo amyloid pathology as a trigger for etiological evaluation. Trajectories of decline appear consistent over at least two years, suggesting they could be used as a trial inclusion criterion and ameliorable outcome measure together with other AD biomarkers. Informative trial durations could be 6-12 months, or extend to incorporate staggered random withdrawal or start designs, with as few as 20 individuals per treatment arm. This trial methodology offers significant advantages over current AD trial designs, including treatment at earlier stages of disease, shorter trial duration, obviation of informed consent difficulties, smaller sample sizes, reduced cost and--given adequate screening programs--sufficient subjects for multiple simultaneous trials. Importantly, it allows the rapid evaluation of putative treatments that may only be efficacious in pre-dementia states.	\N	\N
21478119	The impact of drug-eluting stents (DES) has not been extensively investigated in patients with moderate to severe renal dysfunction, as these patients are consistently excluded from randomised studies. We sought to assess prospectively the effectiveness and safety of the new-generation DES in patients with moderate chronic kidney disease (CKD) and an isolated de novo lesion in the proximal segment of the left anterior descending artery (pLAD). We evaluated 400 consecutive patients with a pLAD lesion. There were 96 patients with moderate CKD (estimated glomerular filtration rate 59 ml/min/1.73 m2) and 304 without CKD. Major adverse cardiac events (MACE) were defined as death, non-fatal myocardial infarction and target lesion revascularisation (TLR). Clinical or telephone follow up was performed. There was a significantly higher incidence of mortality in patients with CKD (n=4) as compared with non-CKD (n=2) (4.16% versus 0.65%, respectively, p=0.03). The rate of non-fatal myocardial infarction was similar in the 2 cohorts (p=0.59), as was the TLR rate (p=0.99). Overall, there were no significant differences regarding MACE between the 2 groups of patients (p=0.19) during the 13.62 ± 6.22 month follow-up period. The rate of angiographic stent thrombosis was 2.08% in the CKD group versus 0.98% in the non-CKD group (p=0.59). New generation DES implantation in patients with CKD and a pLAD lesion is effective and safe, with rates of TLR and stent thrombosis comparable to those in patients with normal renal function. However, the higher mortality in patients with CKD needs further evaluation.	\N	\N
21481900	Non-Hodgkin lymphomas are common cancers that can develop in the upper aero-digestive tract. We describe a case of a large B-cell palatine lymphoma with spontaneous clinical regression. A 58-year-old female patient presented with a sub-mucosal lesion of the hard palate. CT scan and magnetic resonance imaging revealed a lesion invading the right posterior palatine canal. At the second consultation, 15 days after performing the biopsy, the lesion had disappeared. PET scan proved the absence of lesion. Lymph node biopsy supported the diagnosis of large B-cell lymphoma. Large B-cell lymphoma of the hard palate is a rare disease. Only 27 cases have been described in the international literature. The anatomopathological analysis is often difficult to perform. The final diagnosis is often made by immunochemistry. The usual treatment is R-CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, prednisone combined to rituximab) with a 5-year survival rate at 55%.	\N	\N
21484828	Anterior interosseous nerve syndrome (AINS) has not been widely recognized as a possible complication following peripheral catheterization. Herein we present a retrospective review of patients with AINS over the last 5 years. Six cases were identified, 4 associated with catheterization. AINS may be a rare complication of catheterization. Magnetic resonance imaging (MRI) may serve as an adjunct diagnostic modality to conventional electromyography (EMG) and nerve conduction studies, especially in patients who are intolerant of pain.	\N	\N
21485204	This paper presents a novel matching method of vessels in 3D reconstruction of heart vessel. The directed binary tree was used to describe the topological structure of heart vessel tree's skeleton. Based on topological property and epipolar property, the branch-points and end-points of each branch level could be automatically matched along the direction of blood stream. Thereupon it is easy to couple the corresponding vessels segments of two angiograms projected in different directions. The 3D heart vessel tree was successfully reconstructed from clinic coronary angiograms, which validates the presented method.	\N	\N
21489314	The standard treatment for patients with advanced transitional cell carcinoma of the bladder is platin based chemotherapy. Only approximately 50% of the patients respond to chemotherapy. Therefore, molecular predictive markers for identification of chemotherapy sensitive subgroups of patients are highly needed. We selected the transcription factor TFAP2α from a previously identified gene expression signature for chemotherapy response. TFAP2α expression and localization was assessed by immunohistochemistry using a tissue microarray (TMA) containing 282 bladder cancer tumors from patients with locally advanced (pT2-T4(b) and N(1-3)) or metastatic (M(1)) disease. All patients had received cisplatin containing chemotherapy. Furthermore, QPCR analysis of three TFAP2α isoforms was performed on tumor specimens of advanced muscle invasive bladder cancers (T2-4). Using the bladder cell lines T24 and SW780 the relation of TFAP2α and cisplatin and gemcitabine sensitivity as well as cell proliferation was examined using siRNA directed TFAP2α knockdown. TFAP2α protein expression was analyzed on a TMA with cores from 282 advanced bladder cancer tumors from patients treated with cisplatin based combinational chemotherapy. TFAP2α was identified as a strong independent predictive marker for a good response and survival after cisplatin-containing chemotherapy in patients with advanced bladder cancer. Strong TFAP2α nuclear and cytoplasmic staining predicted good response to chemotherapy in patients with lymph node metastasis, whereas weak TFAP2α nuclear staining predicted good response in patients without lymph node metastasis. In vitro studies showed that siRNA mediated knockdown of TFAP2α increased the proliferation of SW780 cells and rendered the cells less sensitive to cisplatin and gemcitabine. In contrast to that T24 bladder cells with mutated p53 showed to be more drug sensitive upon TFAP2α depletion. High levels of nuclear and cytoplasmic TFAP2α protein were a predictor of increased overall survival and progression free survival in patients with advanced bladder cancer treated with cisplatin based chemotherapy. TFAP2α knockdown increased the proliferation of the SW780 bladder cells and reduced cisplatin and gemcitabine induced cell death. The inverse effect was observed in the TP53 mutated T24 cell line where TFAP2α silencing augmented cisplatin and gemcitabine sensitivity and did not stimulate proliferation.	\N	\N
21493631	Data on right ventricle (RV) regional function in adults with interatrial shunt are scarce. The aim of the study was to assess the regional RV deformation in the population of adults with uncorrected atrial left-to-right shunt and to establish a potential relationship between its magnitude and RV regional deformation. We studied 40 adults (30F/10M; mean age 39.2 years) with atrial septal defect (ASD) [average pulmonary-to-systemic blood flow ratio (Qp/Qs) 2.1 ± 0.7]. Standard echocardiographic evaluation was completed with right ventricular dimensions, parameters of its global [tricuspid annular plane systolic excursion (TAPSE), fractional area change, myocardial performance index], and regional [strain/strain rate (ε/SR)] function. Among echocardiographic indices describing RV global function, only TAPSE was increased when compared with healthy subjects. No differences in RV deformation data (ε/SR) between ASD patients and control group were found. Non-linear relationship between the differing Qp/Qs and maximal ε in the mid-segments of the RV free wall was observed. In patients with moderate shunt, maximal ε values were higher when compared with the values obtained in mild and large shunts. Regional RV deformation (ε/SR) does not differ significantly in the group of patients with various degrees of the left-to-right shunts when compared with healthy subjects. However, a non-linear correlation between Qp/Qs and ε could be observed. The affected region of the RV wall is the mid-segment and the highest values of ε were recorded in patients with moderate left-to-right shunts.	\N	\N
21493742	The risk of a posttransplant recurrence of secondary glomerulonephritis (GN) is quite variable. Histologic recurrence is frequent in lupus nephritis, but the lesions are rarely severe and usually do not impair the long-term graft outcome. Patients with Henoch-Schonlein nephritis have graft survival similar to that of other renal diseases, although recurrent Henoch-Schonlein nephritis with extensive crescents has a poor prognosis. Amyloid light-chain amyloidosis recurs frequently in renal allografts but it rarely causes graft failure. Amyloidosis secondary to chronic inflammation may also recur, but this is extremely rare in patients with Behcet's disease or in those with familial Mediterranean fever, when the latter are treated with colchicine. Double organ transplantation (liver/kidney; heart/kidney), chemotherapy, and autologous stem cell transplantation may be considered in particular cases of amyloidosis, such as hereditary amyloidosis or multiple myeloma. There is little experience with renal transplantation in light-chain deposition disease, fibrillary/immunotactoid GN, or mixed cryoglobulinemic nephritis but successful cases have been reported. Diabetic nephropathy often recurs but usually only after many years. Recurrence in patients with small vessel vasculitis is unpredictable but can cause graft failure. However, in spite of recurrence, patient and graft survival rates are similar in patients with small vessel vasculitis compared with those with other renal diseases. Many secondary forms of GN no longer represent a potential contraindication to renal transplantation. The main issues in transplantation of patients with secondary GN are the infectious, cardiovascular, or hepatic complications associated with the original disease or its treatment.	\N	\N
21496186	Certainty is seen as the 'Holy Grail' of science, despite the fact that all science is based in doubt, and that good scientists always leave a door open for an alternative explanation of their findings. Certainty also is a human desire providing comfort and surety. How can these two notions coexist? The way we perceive is the way we see and understand. Perception, however, is not objective; the way we 'know' what the sensory input we receive means arises from matching it against stored images of prior experiences, or put differently, the way we perceive the world depends on successfully predicting our own sensory status. Only large mismatches create new awareness resulting in new learning. At large we are prisoners of our own making, and awareness of the boundaries of our understanding will help to expand our horizon. The four papers of this edition attempt to expand the boundaries of 'common certainty' in terms of statistical interpretation, management of individual patients, disease management and health policy.	\N	\N
21498295	Patients suffering from hereditary hyperlipidemia have a high risk for premature cardiovascular disease and death as a consequence of accelerated atherosclerosis. To prospectively and intra-individually compare image quality and detectability of stenoses in contrast enhanced whole-body MRA (WBMRA) at 1.5 and 3 Tesla (T) in patients with hereditary hyperlipidemia. Twenty-seven patients with hereditary hyperlipidemia received a 1.5 and 3 T gadopentetate dimeglumine contrast-enhanced WBMRA. Twenty-three defined arterial segments were analyzed regarding depiction of target vessels and image quality according to a 5-point-scale ('not evaluable' to 'excellent'). Wilcoxon matched pair test was performed for comparison. Forty-three defined arterial segments were analyzed for the degree of stenosis (0%, 1-49%, 50-99% and 100%) as well as vessel alterations such as aneurysms. Chi-square test was performed for comparison. 1.5 T and 3 T scans yielded WBMRA with diagnostic quality in all patients. In seven of 23 arterial segments (30.4%) image quality was rated significantly higher at 3 T, whereas there was no significant difference in the remaining 16 segments between WBMRA at 1.5 T and 3 T. All relevant stenoses (n = 5), occlusions (n = 6), and aneurysms (n = 3) were evaluated similarly at both field strengths. WBMRA can be performed at 1.5 T and 3 T with diagnostic image quality. Image quality was significantly higher at 3 T than at 1.5 T in only 30.4% of the arterial segments. In order to effectively take advantage of the higher field strength, further optimization of sequence parameters and injection protocols for WBMRA at 3 T is necessary.	\N	\N
21503392	The rate of transient dilatation can be determined by exercise testing or pharmacological stress test. It is unknown whether the type of stress has an impact on average transient dilatation index values. To compare average transient dilation index values in 99mTc-sestamibi scintigraphy in patients undergoing treadmill stress test, versus dipyridamole stress test. The secondary purpose was to evaluate the impact on the average index value by demographic characteristics, risk factors for coronary artery disease and severity of ischemia. The cross-sectional study included 200 patients between 40 and 70 years old, with or without risk factors for ischemic heart disease, with or without a previous diagnosis of ischemic heart disease. The separation between groups was sequential. The software 4D-MSPECT calculated the transient dilatation index and provided a scoring system for perfusion analysis. The average transient dilation index value of the group undergoing exercise stress test was 1.06 (±0.23). For the group undergoing the dipyridamole stress test, it was 1.10 (±0.22); (p = 0.200). There was no association between the type of stress and the average transient dilatation index values. An association was found between the average index values and age only for those patients from the exercise test group (p = 0.009). The results of our study demonstrate that the transient dilation index does not differ when patients undergo exercise stress test on a treadmill or pharmacological stress by dipyridamole.	\N	\N
21506835	Rapid and reliable detection and identification of coccidian oocysts are essential for animal health and foodborne disease outbreak investigations. Traditional microscopy and morphological techniques can identify large and unique oocysts, but they are often subjective and require parasitological expertise. The objective of this study was to develop a real-time quantitative PCR (qPCR) assay using melting curve analysis (MCA) to detect, differentiate, and identify DNA from coccidian species of animal health, zoonotic, and food safety concern. A universal coccidia primer cocktail was designed and employed to amplify DNA from Cryptosporidium parvum, Toxoplasma gondii, Cyclospora cayetanensis, and several species of Eimeria, Sarcocystis, and Isospora using qPCR with SYBR Green detection. MCA was performed following amplification, and melting temperatures (T(m)) were determined for each species based on multiple replicates. A standard curve was constructed from DNA of serial dilutions of T. gondii oocysts to estimate assay sensitivity. The qPCR assay consistently detected DNA from as few as 10 T. gondii oocysts. T(m) data analysis showed that C. cayetanensis, C. parvum, Cryptosporidium muris, T. gondii, Eimeria bovis, Eimeria acervulina, Isospora suis, and Sarcocystis cruzi could each be identified by unique melting curves and could be differentiated based on T(m). DNA of coccidian oocysts in fecal, food, or clinical diagnostic samples could be sensitively detected, reliably differentiated, and identified using qPCR with MCA. This assay may also be used to detect other life-cycle stages of coccidia in tissues, fluids, and other matrices. MCA studies on multiple isolates of each species will further validate the assay and support its application as a routine parasitology screening tool.	\N	\N
21507892	Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare condition defined by eyelid colobomas, cryptophthalmos and anophthalmia/microphthalmia, an aberrant hairline, a bifid or broad nasal tip, and gastrointestinal anomalies such as omphalocele and anal stenosis. Autosomal recessive inheritance had been assumed because of consanguinity in the Oji-Cre population of Manitoba and reports of affected siblings, but no locus or cytogenetic aberration had previously been described. This study shows that MOTA syndrome is caused by mutations in FREM1, a gene previously mutated in bifid nose, renal agenesis, and anorectal malformations (BNAR) syndrome. MOTA syndrome and BNAR syndrome can therefore be considered as part of a phenotypic spectrum that is similar to, but distinct from and less severe than, Fraser syndrome. Re-examination of Frem1(bat/bat) mutant mice found new evidence that Frem1 is involved in anal and craniofacial development, with anal prolapse, eyelid colobomas, telecanthus, a shortened snout and reduced philtral height present in the mutant mice, similar to the human phenotype in MOTA syndrome. The milder phenotypes associated with FREM1 deficiency in humans (MOTA syndrome and BNAR syndrome) compared to that resulting from FRAS1 and FREM2 loss of function (Fraser syndrome) are also consistent with the less severe phenotypes resulting from Frem1 loss of function in mice. Together, Fraser, BNAR and MOTA syndromes constitute a clinically overlapping group of FRAS-FREM complex diseases.	\N	\N
21508333	c-Src is a non-receptor tyrosine kinase whose activity is induced by phosphorylation at Y418 and translocation from the cytoplasm to the cell membrane. Increased activity of c-Src has been associated with cell proliferation, matrix adhesion, motility, and apoptosis in tumors. Immunohistochemistry suggested that activated (pY(418))-Src activity is increased in cyst-lining autosomal dominant polycystic kidney disease (ADPKD) epithelial cells in human and mouse ADPKD. Western blot analysis showed that SKI-606 (Wyeth) is a specific inhibitor of pY(418)-Src without demonstrable effects on epidermal growth factor receptor or ErbB2 activity in renal epithelia. In vitro studies on mouse inner medullary collecting duct (mIMCD) cells and human ADPKD cyst-lining epithelial cells showed that SKI-606 inhibited epithelial cell proliferation over a 24-h time frame. In addition, SKI-606 treatment caused a striking statistically significant decrease in adhesion of mIMCD and human ADPKD to extracellular collagen matrix. Retained viability of unattached cells was consistent with a primary effect on epithelial cell anchorage dependence mediated by the loss of extracellular matrix (ECM)-attachment due to α(2)β(1)-integrin function. SKI-606-mediated attenuation of the human ADPKD hyperproliferative and hyper-ECM-adhesive epithelial cell phenotype in vitro was paralleled by retardation of the renal cystic phenotype of Pkd1 orthologous ADPKD heterozygous mice in vivo. This suggests that SKI-606 has dual effects on cystic epithelial cell proliferation and ECM adhesion and may have therapeutic potential for ADPKD patients.	\N	\N
21537035	To determine if time to diagnosis is associated with stage of disease at diagnosis or survival among women with symptomatic ovarian cancer. A representative sample of Australian women (n = 1,463) with ovarian cancer diagnosed between 2002 and 2005 who participated in a population-based case-control study were interviewed regarding the events leading to their diagnosis and were observed for mortality for 5 years. Of the 1,318 women (90%) who presented to a medical practitioner with symptoms, 55% presented within 1 month, 70% in less than 2 months, and 92% within 6 months of symptom onset. There were no significant differences in the time from symptom onset to first medical practitioner consultation (P = .19) or symptom onset to diagnosis (P = .64) among women with borderline, early (International Federation of Gynecology and Obstetrics [FIGO] stages I to II) or late (FIGO stages III to IV) disease. There was also no association between time to diagnosis and survival; adjusted hazard ratio for long delay (> 12 months from symptom onset to diagnosis) versus short delay (≤ 1 month) was 0.94 (95% CI, 0.68 to 1.30). Women who had asymptomatic cancers diagnosed incidentally (n = 145) were younger and were more likely to have borderline or stage I disease compared with women who had symptomatic ovarian cancer. The results of this study suggest that, once ovarian cancer is symptomatic, reducing the time to diagnosis would not greatly alter stage of disease at diagnosis or survival.	\N	\N
21542809	Endometriosis-associated infertility results in reduced ovarian response, fewer oocytes available for fertilization, compromised oocyte quality and higher miscarriage rates. A consistent proportion of women with endometriosis require in vitro fertilization. We sought to clarify the impact of deep infiltrating pelvic disease on antral follicle count and ovarian response to follicle-stimulating hormone (FSH) stimulation in patients with severe endometriosis. Retrospective cohort study. University hospital. Patients with severe endometriosis (stages III-IV; n=51) were divided into two groups regarding localization of endometriosis during surgical staging: ovarian (n=27) and both ovarian and deep infiltrating disease (n=24). A total of 73 long-protocol ovulation induction cycles with recombinant FSH for an intracytoplasmic sperm injection program were given. On day 3 of the cycle, measurements of FSH and luteinizing hormone and an ultrasound evaluation of antral follicle count were performed. Number of oocytes collected at ovum pick up, number of mature oocytes, number of embryos transferred and clinical pregnancy rate. Ovarian reserve in terms of antral follicle count was damaged in both groups but, if adjusted for age, it was significantly lower in the ovarian and pelvic infiltrating group compared with patients having only ovarian endometriosis. Pelvic deep infiltrating disease significantly impacted on the number of oocytes collected at pick up when adjusted for age. Deep infiltrating pelvic disease can negatively affect ovarian reserve in terms of antral follicle count and number of oocytes retrieved. Mechanisms underlying this phenomenon need to be elucidated.	\N	\N
21545837	The proteasome is an enzyme complex responsible for targeted intracellular proteolysis. Alterations in proteasome-mediated protein clearance have been implicated in the pathogenesis of aging, Alzheimer's disease (AD) and Parkinson's disease (PD). In such diseases, proteasome inhibition may contribute to formation of abnormal protein aggregates, which in turn activate intracellular unfolded protein responses that cause oxidative stress and apoptosis. In this study, we investigated the protective effect of Insulin-like Growth Factor-I (IGF-1) for neural SH-SY5Y cells treated with the proteasomal inhibitor, Epoxomicin. In SH-SY5Y cells, Epoxomicin treatment results in accumulation of intracellular ubiquitinated proteins and cytochrome c release from damaged mitochondria, leading to cell death, in Epoxomicin time- and dose-dependent manner. In cells treated with small amounts of IGF-1, the same dosages of Epoxomicin reduced both mitochondrial damage (cytochrome c release) and reduced caspase-3 activation and PARP cleavage, both of which are markers of apoptosis. Notably, however, IGF-1-treated SH-SY5Y cells still contained ubiquitinated protein aggregates. This result indicates that IGF-1 blocks the downstream apoptotic consequences of Epoxomicin treatment leading to decreased proteasome function. Clues as to the mechanism for this protective effect come from (a) increased AKT phosphorylation observed in IGF-1-protected cells, vs. cells exposed to Epoxomicin without IGF-1, and (b) reduction of IGF-1 protection by pretreatment of the cells with LY294002 (an inhibitor of PI3-kinase). Together these findings suggest that activation of PI3/AKT pathways by IGF-1 is involved in IGF-1 neuroprotection against apoptosis following proteasome inhibition.	\N	\N
21547907	Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes. Of those, pancreatobiliary and oncocytic types are recently recognized and relatively uncommon, and usually exhibit high-grade dysplasia. The biological properties and molecular characteristics of these two types have not been well documented. The few molecular studies of the oncocytic type showed absence of KRAS mutations commonly seen in the other subtypes, raising the possibility that the oncocytic type is distinct from the other subtypes. Thus, we examined clinicopathological features and molecular alterations of the two subtypes. The study cohort consisted of 12 pancreatobiliary and 18 oncocytic IPMN cases. KRAS, BRAF, and PIK3CA mutations and TP53, SMAD4, and β-catenin expression were analysed, and the results of molecular and clinicopathological profiles were compared between the two subtypes. KRAS mutations were identified in the oncocytic type, but less frequently than the pancreatobiliary type (17% versus 58%, p = 0.048). BRAF mutation was found in a single oncocytic tumour, and no PIK3CA mutations were seen in any of the study cohort. TP53 overexpression was less frequent in the oncocytic type than in the pancreatobiliary type (11% versus 58%, p = 0.013). Invasive components were present in 50% of the oncocytic and 92% of the pancreatobiliary types, with lymph node metastasis more frequently seen in the latter, corresponding to better outcomes in the former (5-year survival rates: 93% versus 32%, p = 0.014). Our demonstration of KRAS and BRAF mutations in the oncocytic-type IPMN supports a role for the activation of the RAS-MAPK pathway in this tumour type. However, the less frequent TP53 overexpression associated with the significantly lower rates of invasion and nodal disease in the oncocytic type correlates with better outcomes compared to the pancreatobiliary type.	\N	\N
21565878	Excessive dynamic airway collapse (EDAC) refers to abnormal and exaggerated bulging of the posterior wall within the airway lumen during exhalation. This condition is pathological if the reduced airway lumen is <50% of the normal. It is a relatively new disease entity that is recognised more easily now with the increased use of multi-detector row CT. EDAC is often asymptomatic and diagnosed incidentally. Although the term excessive dynamic airway collapse is often used interchangeably with tracheobronchomalacia, both entities represent morphologically and physiologically distinct processes. Considering the confusion between the two entities, the prevalence of stand-alone EDAC remains unclear. The prevalence of tracheobronchomalacia and EDAC depends upon the patient population, associated comorbidities and underlying aetiologies, diagnostic tools used and criteria used to define the airway collapse. This review defines EDAC and describes its pathophysiology, precipitating factors, associated symptoms and potential treatments.	\N	\N
21571478	To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis. Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis. Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity. Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.	\N	\N
21572511	The epidemiology of Chagas disease, until recently confined to areas of continental Latin America, has undergone considerable changes in recent decades due to migration to other parts of the world, including Spain. We studied the prevalence of Chagas disease in Latin American patients treated at a health center in Barcelona and evaluated its clinical phase. We make some recommendations for screening for the disease. We performed an observational, cross-sectional prevalence study by means of an immunochromatographic test screening of all continental Latin American patients over the age of 14 years visiting the health centre from October 2007 to October 2009. The diagnosis was confirmed by serological methods: conventional in-house ELISA (cELISA), a commercial kit (rELISA) and ELISA using T cruzi lysate (Ortho-Clinical Diagnostics) (oELISA). Of 766 patients studied, 22 were diagnosed with T. cruzi infection, showing a prevalence of 2.87% (95% CI, 1.6-4.12%). Of the infected patients, 45.45% men and 54.55% women, 21 were from Bolivia, showing a prevalence in the Bolivian subgroup (n=127) of 16.53% (95% CI, 9.6-23.39%). ALL THE INFECTED PATIENTS WERE IN A CHRONIC PHASE OF CHAGAS DISEASE: 81% with the indeterminate form, 9.5% with the cardiac form and 9.5% with the cardiodigestive form. All patients infected with T. cruzi had heard of Chagas disease in their country of origin, 82% knew someone affected, and 77% had a significant history of living in adobe houses in rural areas. We found a high prevalence of T. cruzi infection in immigrants from Bolivia. Detection of T. cruzi-infected persons by screening programs in non-endemic countries would control non-vectorial transmission and would benefit the persons affected, public health and national health systems.	\N	\N
21575881	Mesalazine remains the first line treatment for the induction and the maintenance of remission in mild to moderate ulcerative colitis (UC). Its efficacy as a maintenance treatment after a first flare treated with corticosteroids has not been specifically studied. The aims of our work were to study a cohort of UC patients treated with mesalazine after a course of oral systemic corticosteroids and to identify predictive factors of relapse and of colectomy. We studied retrospectively a cohort of 143 UC patients, who never received immunosuppressive drugs, and treated for the first time with oral corticosteroids for a flare. Among patients responding to corticosteroids, we studied the group treated by mesalazine after the flare. Fifty% (n=52) achieved a complete clinical remission with steroid weaning. In this group, 67% (n=35) received oral mesalazine. Seventy-five % of patients treated by mesalazine relapsed (median 29 months, range: 1-156). Fourteen % required a colectomy (median 11 months, range: 1-24). Kaplan Meier curve showed a relapse rate and a colectomy rate over one year of 26% and 11% respectively. In multivariate analysis, male gender and short duration of disease were predictive factors of the time-to-relapse. No factor was predictive of time-to-colectomy. Maintenance efficacy of mesalazine over one year after a first course of corticosteroids for a disease flare is reasonably high. The longer-term relapse rate becomes higher in male patients with a short disease duration. An immunosuppressive treatment could be discussed in case of further relapse despite improved medication-adherence. Medication-adherence should first be assessed and promoted. An immunosuppressive treatment could be discussed in case of further relapse despite improved medication-adherence.	\N	\N
21576904	Mutations in IRAK4 have been associated with recurrent Gram-positive infections in children. Given the central role of IRAK4 in innate immunity signaling, we hypothesized that common genetic variants of IRAK4 may be associated with prevalence of Gram-positive infection in critically ill adults. Haplotype clade tag single nucleotide polymorphisms (SNPs) of the IRAK4 gene were selected and genotyped in a cohort of 1,029 critically ill patients with systemic inflammatory response syndrome (SIRS). We found that a haplotype clade tagged by the A allele of the htSNP G29429A (Ala428Thr) was associated with increased relative risk of Gram-positive infection at admission to ICU (RR = 1.2, p < 0.05). Furthermore, the 29429A allele was associated with decreased lymphoblastoid cell response to CpG (as measured by IL-6 production) (raw values ± 95% CI 40.3 ± 32.3 vs. 85.8 ± 29.4 pg/ml; log-transformed values ± 95% CI 1.13 ± 0.37 vs. 1.55 ± 0.18, p < 0.04). We also found that IRAK4-deficient fibroblasts transfected with an IRAK4 expression plasmid containing the 29429A allele produced less IL-6 in response to lipopolysaccharide (p = 0.07). Our data suggest that the IRAK4 haplotype clade marked by 29429A (428Thr) alters susceptibility to Gram-positive bacteria, by decreasing cellular response to TLR ligands.	\N	\N
21585286	β-site APP-cleaving enzyme (BACE1) cleaves the wild type (WT) β-site very slowly (k(cat)/K(m): 46.6 m(-1) s(-1)). Therefore we searched for additional β-secretases and identified three cathepsins that split the WT β-site much faster. Human cathepsin S cleaves the WT β-site (k(cat)/K(m): 54 700 m(-1) s(-1)) 1170-fold faster than BACE1 and cathepsins B and L are 440- and 74-fold faster than BACE1, respectively. These cathepsins split two bonds flanking the WT β-site (K-MD-A), where the K-M bond (85%) is cleaved more efficiently than the D-A bond (15%). Cleavage at the major K-M bond yields Aβ (amyloid β-peptide) extended by N-terminal Met that should be removed to generate Aβ initiated by Asp1. The activity of cytosol and microsomal aminopeptidases on relevant peptides revealed rapid removal of N-terminal Met but not N-terminal Asp. Brain aminopeptidases showed similar specificity. Thus, aminopeptidases would convert Aβ extended by Met into regular Aβ (Asp1) found in amyloid plaques. Earlier studies indicate that Aβ is likely produced in the endosome and lysosome system where cathepsins S, B and L are localized and cysteine cathepsin inhibitors reduce the level of Aβ in cells and animals. Taken together, cathepsins S, B and L deserve further evaluation as therapeutic targets to develop disease modifying drugs to treat Alzheimer's disease.	\N	\N
21596857	Femoral and lumbar bone mineral densities (BMDs) were measured in 159 adults enrolled in the Leucémies de l'Enfant et de l'Adolescent program, a French prospective multicentric cohort of childhood leukemia survivors. BMDs were expressed as Z-scores, and multivariate linear regression analyses were used to construct association models with potential risk factors. Mean age at evaluation and follow-up was 23 and 14.7 years, respectively. In the whole cohort, mean femoral Z-score was -0.19 ± 0.08. Two factors were associated with lower femoral BMD transplantation (-0.49 ± 0.15 vs -0.04 ± 0.10 in the chemotherapy group; P = .006) and female sex (-0.34 ± 0.10 vs -0.03 ± 0.13; P = .03). Among patients who received a transplant, the only significant risk factor was hypogonadism (-0.88 ± 0.16 vs -0.10 ± 0.23; P = .04). A slight reduction in lumbar BMD (mean Z-score, -0.37 ± 0.08) was detected in the whole cohort without difference between the transplantation and chemotherapy groups. Among patients who received a transplant, younger age at transplantation was correlated with a low lumbar BMD (P = .03). We conclude that adults who had received only chemotherapy for childhood leukemia have a slight reduction in their lumbar BMD and a normal femoral BMD. Patients who received a transplant with gonadal deficiency have a reduced femoral BMD which might increase the fracture risk later in life.	\N	\N
21601991	Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Due to either infection or disease activity, elevated levels of inflammatory markers and up-regulation of the autoimmune process can contribute to the development of atherosclerosis in SLE patients. Periodontal diseases are among the most prevalent chronic infections in humans and are characterized by pathogen-induced oral inflammatory disease affecting the supporting tissues of teeth. Several cytokines capable of inducing systemic effects are produced during the course of this infection. The presence of these cytokines can be verified by changes in the levels of C-reactive protein (CRP). Periodontal disease is a well-known risk factor for atherosclerosis. The potential for beneficial prevention of CVD events through the use of periodontal treatment has been previously recommended. This review reinforces the hypothesis that periodontal infection could be a risk factor for CVD in patients diagnosed with SLE, and suggests that by reducing the progression of this oral infection, levels of inflammatory markers common to both diseases (SLE and periodontal disease) would likely decrease.	\N	\N
21603646	Miniature pigs are useful model animals for humans because they have similar anatomy and digestive physiology to humans and are easy to breed and handle. In this study, whole blood microarray analyses were conducted to evaluate variations of correlation among individuals and ages using specific pathogen-free (SPF) Clawn miniature pigs. Whole blood RNA is easy to handle compared to isolated white blood cell RNA and can be used for health and disease monitoring and animal control. In addition, whole blood is a heterogeneous mixture of subpopulation cells. Once a great change occurs in composition and expressing condition of subpopulations, their associated change will be reflected on whole blood RNA. From 12 to 30 weeks of age, fractions of lymphocytes, monocytes, neutrophils, eosinophils, and basophils in white blood cells showed insignificant differences with age as a result of ANOVA analysis. This study attempted to identify characteristics of age-related gene expression by taking into account the change in the number of expressed genes by age and similarities of gene expression intensity between individuals. As a result, the number of expressed genes was less in fetal stage and infancy period but increased with age, reaching a steady state of gene expression after 20 weeks of age. Variation in gene expression intensity within the same age was great in fetal stage and infancy period, but converged with age. The variation between 20 and 30 weeks of age was comparable to that among 30 weeks individuals. These results indicate that uniformity of laboratory animals is expected for miniature pigs after 20 weeks of age. Furthermore, a possibility was shown that whole blood RNA analysis is applicable to evaluation of physiological state.	\N	\N
21607722	It has been only 5 years since the identification of TDP-43 as the major protein component of the ubiquitinated inclusions in FTLD-U. At that time, there were approximately a dozen papers about TDP-43; today, a "TDP-43" search reveals almost 600 papers. It is now clear that the majority of FTLD cases containing tau- and alpha-synuclein-negative, ubiquitin-positive inclusions (FTLD-U) are FTLD-TDP. The spectrum of TDP-43 proteinopathies includes FTLD-TDP with or without ALS, with or without mutations in GRN, VCP, or TARDBP, with or without chromosome 9p linkage, and sporadic and non-SOD1 familial ALS with or without FTLD-TDP. There are four sub-types of FTLD-TDP, and these correlate with specific clinical and genetic profiles. Sub-types are determined by the presence, predominance, and distribution of the various TDP-43 immunopositive insoluble aggregates-neuronal cytoplasmic inclusions, neuronal intranuclear inclusions, and dystrophic neurites. In this paper, FTLD-TDP pathologic sub-types will be described, and examples of each sub-type will be shown, and implications for future research will be discussed.	\N	\N
21609376	Differentiating between benign and malignant causes of obstructive jaundice can be challenging, even with the advanced imaging and endoscopic techniques currently available. In patients with obstructive jaundice, the predictive accuracy of bilirubin levels at presentation was examined in order to determine whether such data could be used to differentiate between malignant and benign disease. A total of 1,026 patients with obstructive jaundice were identified. Patients were divided into benign and malignant groups. The benign patients were subgrouped into those with choledocholithiasis and those with inflammatory strictures of the biliary tree. Bilirubin levels at presentation and other demographic data were obtained from case records. Area under the curve (AUC) values for bilirubin as a predictor of malignancy were highly significant for all benign presentations and for those with benign biliary strictures (AUC: 0.8 for both groups; P < 0.001). A bilirubin level > 100 µmol/l was determined to provide the optimum sensitivity and specificity for malignancy in all patients and in those without choledocholithiasis (71.9% and 86.9%, 71.9% and 88.0%, respectively). The application of a bilirubin level > 250 µmol/l achieved specificities of 97.1% and 98.0% in each subgroup of patients, respectively. In patients with obstructive jaundice, bilirubin levels in isolation represent an important tool for discriminating between benign and malignant underlying causes.	\N	\N
21621489	The aim of this study is to develop a standardized LC-MS/MS method for accurate measurement of desmosine (DES) and isodesmosine (IDS) in all body fluids as biomarkers for in vivo degradation of matrix tissue elastin in man and animals. A reproducible three-step analytical procedure: (1) sample hydrolysis in 6N HCl, (2) SPE by a CF1 cartridge with addition of acetylated pyridinoline as internal standard (IS), and (3) LC/MSMS analysis by SRM monitoring of transition ions; DES or IDS (m/z 526-481+397) and IS (m/z 471-128) was developed. The method achieves accurate measurements of DES/IDS in accessible body fluids (i.e. urine, plasma, and sputum). LOQ of DES/IDS in body fluids is 0.1 ng/ml. The % recoveries and reproducibility from urine, plasma, and sputum samples are above 99 ± 8% (n = 3), 94 ± 9% (n = 3) and 87 ± 11% (n = 3), with imprecision 8%, 9% and 10%, respectively. The proposed method was applied to measure DES/IDS in body fluids of patients with chronic obstructive pulmonary disease (COPD) and healthy controls. Total DES/IDS in sputum and plasma is increased over normal controls along with the free DES/IDS in urine in patients. DES/IDS can be used to study the course of COPD and the response to therapy. This practical and reliable LC-MS/MS method is proposed as a standardized method to measure DES and IDS in body fluids. This method can have wide application for investigating diseases which involve elastic tissue degradation.	\N	\N
21626540	The Movement Disorder Society (MDS) developed out of a merger with two short-lived organizations, the Movement Disorder Society, primarily organized to develop a journal for the subspecialty, and the International Society of Motor Disturbances, primarily organized to develop international congresses. The formal merger of the Movement Disorder Society and the International Society of Motor Disturbances into the Movement Disorder Society took place at the 2nd International Congress of Movement Disorders in Munich, Germany, in June 1992. Whereas the journal, Movement Disorders, and the annual International Congress of Parkinson's Disease and Movement Disorders remain the anchors of the society, the goals now include the development of regional symposia, regional sections, Web-based educational programs, and outreach efforts to include young investigators, wide international membership, and inclusion of non-neurologists, including basic scientists, neurosurgeons, and nonphysician health professionals. Movement Disorders has a continuingly growing subscribership and rising impact factor.	\N	\N
21630606	Renal biopsy is the definitive diagnostic test in patients with renal parenchymal disease. Renal biopsy registry is an important tool which can provide valuable data concerning early and correct epidemiological description and clinical correlations of renal diseases. Records of 326 adult renal biopsies performed at our hospital from January 1991 till the end of December 2006 were retrospectively examined. Overall, secondary glomerular diseases (SGD) were predominant (39.9%), followed by primary glomerular diseases (PGD) (30.4%), vascular diseases (13.2%) and TIN (6.7%). Total sclerosis of the kidney did not allow histopathological diagnosis in 5.8% of all biopsied kidneys. Focal and Segmental Glomerular Sclerosis (FSGS), IgA Nephropathy (IgAGN) and Minimal Change Disease (MCD) and Membranous Glomerulopathy (MGN) were the most common PGD, altogether representing 75.7% of all PGD. FSGS was the most frequent (30.3%), followed by IgAGN (21.2%), MCD (19.1%) and MGN in 15.1%. Vasculitis, HIVAN, diabetic nephropathy and amyloidosis were the most common SGD, altogether representing 90% of all SGD. Immune Mediated Glomerulonephritis (IMGN) were the most frequent (32.3%), followed by HIVAN (16.9%), diabetic nephropathy (14.6%) and amyloidosis (10%). Nephroangiosclerosis (benign and malignant nephroangiosclerosis) was the most frequent vascular nephropathy responsible for 79% of all vascular diseases. Thrombotic microangiopathy was seen in 9.3% and atherothrombotic disease in 7% of all vascular diseases. Concerning tubular diseases, chronic TIN accounted for 63.6% of all tubular diseases, followed by light chain-cast nephropathy (22.7%) and acute TIN (13.6%). Because of lack of material, 3.4% of all biopsies could not be analyzed. These data demonstrate that the distribution of biopsy-proved renal diseases in a Belgian population of the Brussels area is strongly influenced by the indications of renal biopsy. Harmonization of these indications might reflect with more accuracy the actual incidence of different nephropathies in a given population. Nation and worldwide renal biopsy registers are important to follow patterns of renal diseases in different populations. This information is important not only for health organizations in order to plan health budget but also for helping clinicians to provide a better care to patients.	\N	\N
21641369	Although very late stent thrombosis occurs several years after implantation of sirolimus-eluting stent (SES), the morphologic changes of the stent beyond 2 years have not yet been systematically studied in living patients. The late vascular response to SES was therefore evaluated by serial angioscopic studies at 2 and 5 years after stent implantation. A total of 17 patients with 17 SES underwent a repeated angioscopy procedure at 2 and 5 years. Neointimal stent coverage (NSC) was classified as follows: grade 0, presence of uncovered struts; grade 1, visible struts through a thin neointima; or grade 2, complete neointimal coverage without visible struts. For each patient, the minimum and maximum NSC grade and the existence of in-stent thrombus were recorded. The minimum and maximum NSC grade did not increase between the 2 and 5 years (0.59 ± 0.51 vs 0.88 ± 0.70, P = .17, and 1.82 ± 0.39 vs 1.94 ± 0.24, P = .30, respectively). The prevalence of patients with uncovered struts did not significantly decrease from 2 to 5 years (41% vs 29%, P = .49). During the follow-up period, 3 of 6 thrombi disappeared, whereas new thrombus formation was found in 3 patients without any clinical symptoms. In-stent thrombus did not decrease (35% vs 35%, P > .99). The current serial angioscopic study suggests that incomplete NSC and the prevalence of latent thrombus within the SES segments did not decrease from 2 to 5 years. The risk of stent thrombosis related to incomplete healing of SES may continue for an extended period.	\N	\N
21645024	Retinol-binding protein 4 (RBP4), produced by adipocytes and hepatocytes, contributes to an unfavourable lipid profile and insulin resistance, which can contribute to the development of coronary artery disease (CAD). Recently, several studies have shown that epicardial adipose tissue (EAT) differs from subcutaneous adipose tissue (SAT) and plays a role on the physiopathology of CAD because of its proximity to the coronary arteries. We aimed to study the expression and secretion levels of RBP4 in both fat tissues and explore its possible association with CAD. Fifty-eight patients undergoing heart surgery were included in the study. We analysed RBP4 mRNA expression by real-time PCR, protein expression by Western blot and immunohistochemistry, and secretion of EAT and SAT explants from CAD and non-CAD patients by Enzyme Immunoassay. Retinol-binding protein 4 is expressed at similar levels in EAT and SAT, mainly from adipocytes. Protein levels were higher in EAT from CAD than non-CAD patients (0·63 ± 0·09 arbitrary units (a.u).; n = 10) vs (0·41 ± 0·04 a.u.; n = 13, P = 0·039). In contrast, GLUT4 mRNA levels were lower in EAT from CAD than non-CAD patients (6·55 ± 0·16 a.u.; n = 13) vs (7·21 ± 0·18 a.u.; n = 14, P = 0·012). We also found differential expression in SAT between samples from CAD and non-CAD patients [(6·63 ± 0·16 a.u.; n = 14) vs (7·21 ± 0·14 a.u.; n = 14, P = 0·009)]. Besides, EAT releases higher RBP4 levels than SAT after 3, 6, 24 and 48 h of culture. These levels were independent of CAD but significantly higher in diabetic than nondiabetic patients. Retinol-binding protein 4 levels behave differently in EAT and SAT with respect to CAD. However, both adipose tissues have lower GLUT4 levels in patients with CAD. These findings suggest a differential regulation of RBP4 production in EAT and SAT that may be influenced by local factors.	\N	\N
21647871	In this phase 1 trial, the authors evaluated sunitinib combined with radiation therapy (RT) for the treatment of primary or metastatic central nervous system (CNS) malignancies. Eligible patients had CNS malignancies that required a (minimum) 2-week course of RT. Sunitinib (37.5 mg) was administered daily for the duration of RT with optional treatment extension of 1 month. Urine was collected at 3 time points for correlative biomarker studies. The primary endpoint was acute toxicity defined according to Common Toxicity Criteria version 3. Fifteen patients were enrolled (12 with CNS metastasis and 3 with primary tumors). RT doses ranged from 14 Gray (Gy) to 70 Gy (1.8-3.5 Gy per fraction). Acute toxicities included hematologic, nausea, hyperglycemia, fatigue, hypocalcemia, and diarrhea. Six patients (40%) developed grade ≤ 2 toxicities. Grade 3 toxicities occurred in 7 patients (47%) and included hematologic toxicity, fatigue, deep vein thrombosis, dysphasia, hyperglycemia, and hyponatremia. No grade 3 through 5 hypertensive events or intracerebral hemorrhages occurred. Two grade 5 adverse events attributed to disease progression occurred. The median follow-up was 34.2 months. Two patients (13%) achieved a partial response, 9 patients (60%) had stable disease, and 2 patients (13%) patients had progressive disease. The 6-month progression-free survival rate for patients who had brain metastasis was 58%. Grade 3 hematologic toxicity was correlated with greater changes in vascular endothelial growth factor levels changes between baseline and the completion of RT. Continuous 37.5-mg sunitinib combined with RT in patients who had CNS malignancies yielded acceptable toxicities and adverse events. The current results indicated that changes in urine vascular endothelial growth factor levels are associated with hematologic toxicity, and this association should be analyzed in a larger cohort. The feasibility, safety, and early response results warrant a phase 2 trial.	\N	\N
21653298	US estimates of the Clostridium difficile infection (CDI) burden have utilized International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Whether ICD-9-CM code rank order affects CDI prevalence estimates is important because the National Hospital Discharge Survey (NHDS) and the Nationwide Inpatient Sample (NIS) have varying limits on the number of ICD-9-CM codes collected. ICD-9-CM codes for CDI (008.45), C. difficile toxin assay results, and dates of admission and discharge were collected from electronic hospital databases for adult patients admitted to 4 hospitals in the United States from July 2000 through June 2006. CDI prevalence per 1000 discharges was calculated and compared for NHDS and NIS limits and toxin assay results from the same hospitals. CDI prevalence estimates were compared using the χ(2) test, and the test of equality was used to compare slopes. CDI prevalence measured by NIS criteria was significantly higher than that measured using NHDS criteria (10.7 cases per 1000 discharges versus 9.4 cases per 1000 discharges; P<.001) in the 4 hospitals. CDI prevalence measured by toxin assay results was 9.4 cases per 1000 discharges (P=.57 versus NHDS). However, the CDI prevalence increased more rapidly over time when measured according to the NHDS criteria than when measured according to toxin assay results (β=1.09 versus 0.84; P=.008). Compared with the NHDS definition, the NIS definition captured 12% more CDI cases and reported significantly higher CDI rates. Rates calculated using toxin assay results were not different from rates calculated using NHDS criteria, but CDI prevalence appeared to increase more rapidly when measured by NHDS criteria than when measured by toxin assay results.	\N	\N
21659502	Despite high vaccination coverage rates, there has been a gradual increase in reported pertussis cases. Although whooping cough affects all ages, young infants continue to suffer the greatest pertussis disease burden. Adolescents and adults are the primary source of infection for young babies. In this paper, we report two cases involving the likely transmission of pertussis from mothers to infants in Tunisia.	\N	\N
21665106	Radiating leg pain is a common symptom presenting in manual therapy practices. Although this symptom has been reported as a complication of endometriosis, its prevalence and characteristics have not been studied. We surveyed members of a national endometriosis support group with endometriosis using a self-administered, mailed questionnaire. The main outcome measures were the prevalence and characteristics of leg pain. Of 94 respondents, leg pain was reported by 48 women (51%), and was bilateral in 59% of these symptomatic women. The likelihood of experiencing leg pain was related to weight gain since age 18, age, and height. The most common treatments tried included exercise, over-the-counter medications, and massage therapy, all with variable results. These data support leg pain as a prevalent complication of endometriosis, and that the disease may affect multiple peripheral nerves. Manual therapists should remain aware to this possible etiology for radiating pain.	\N	\N
21674011	Intestinal luminal microbiota likely contribute to the etiology of necrotizing enterocolitis (NEC), a common disease in preterm infants. Microbiota development, a cascade of initial colonization events leading to the establishment of a diverse commensal microbiota, can now be studied in preterm infants using powerful molecular tools. Starting with the first stool and continuing until discharge, weekly stool specimens were collected prospectively from infants with gestational ages ≤32 completed weeks or birth weights≤1250 g. High throughput 16S rRNA sequencing was used to compare the diversity of microbiota and the prevalence of specific bacterial signatures in nine NEC infants and in nine matched controls. After removal of short and low quality reads we retained a total of 110,021 sequences. Microbiota composition differed in the matched samples collected 1 week but not <72 hours prior to NEC diagnosis. We detected a bloom (34% increase) of Proteobacteria and a decrease (32%) in Firmicutes in NEC cases between the 1 week and <72 hour samples. No significant change was identified in the controls. At both time points, molecular signatures were identified that were increased in NEC cases. One of the bacterial signatures detected more frequently in NEC cases (p<0.01) matched closest to γ-Proteobacteria. Although this sequence grouped to the well-studied Enterobacteriaceae family, it did not match any sequence in Genbank by more than 97%. Our observations suggest that abnormal patterns of microbiota and potentially a novel pathogen contribute to the etiology of NEC.	\N	\N
21674889	Awareness of the clinical importance of second-line chemotherapy for incurable gastric cancer has been increasing. To assess the clinical validity of the new concept that second-line chemotherapy following predetermined cycles of first-line chemotherapy would improve survival, we conducted a phase II study. Patients with pathologically proven incurable gastric adenocarcinoma and adequate organ functions were enrolled. S-1 or S-1 plus cisplatin was administered as first-line chemotherapy. The number of cycles of S-1-based chemotherapy was determined to be three as a maximum unless there was disease progression. The treatment was followed by weekly administration of paclitaxel. The primary endpoint was overall survival and the secondary endpoints were progression-free survival and safety. Thirty-seven patients were eligible for enrollment. Twenty-eight patients (76%) underwent the second-line chemotherapy with paclitaxel after completion of S-1-based chemotherapy or disease progression. Treatment-related grade 3 or 4 toxicity was noted in 14 patients during S-1-based chemotherapy, and in 6 patients during paclitaxel treatment. The median survival time was 455 days and the median progression-free survival was 229 days. Sequential set chemotherapy with three cycles of S-1-based chemotherapy followed by weekly paclitaxel is feasible. The survival results are equivalent to those of other current regimens using S-1.	\N	\N
21681643	Long-term central venous catheter (CVC) implantation has become more affordable in Taiwan since 1995. Surgical removal of the catheter may be the essential treatment for catheter-related bloodstream infections (CRBSI). The aim of this study was to evaluate the clinical features and microbial isolates in pediatric cancer patients with removal of CVC for CRBSI. The records of positive blood culture from hospitalized pediatric oncology patients between 1995 and 2004 were reviewed. One hundred and forty-three patients implanted with a long-term CVC were further identified. Seventeen catheters in 16 patients developed catheter-related bacteremia that needed catheter removal. The rate of catheter removal was 11.9%. The median device life was 7.7 months. Six catheters were removed within 3 months of insertion. Nine of the 17 catheters were removed from patient younger than 2 years. Eight infections occurred during severe neutropenia, and 6 patients had refractory or relapsed underlying disease. The cultural isolates were Gram-negative bacilli in 7, Gram-positive in 5, fungi in 5, and atypical mycobacterium in 1. The frequency of catheter removal for infection control was significantly higher in the first 5 years (1994-1999) compared to the last 5 years (2000-2004) (30.9 vs. 4.0%, p = 2.3 × 10(-4)). Factors such as microbiological isolates, age of infection, the status of malignancy, and neutropenia are related to catheter outcome. The reduction in patients with positive cultures needing removal of the catheters can be related to improved nursing care and more aggressive antibiotic therapy.	\N	\N
21685330	Lymphatic metastasis constitutes a critical route of disease dissemination, which limits the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). As lymphangiogenesis has been implicated in stimulation of lymphatic metastasis by vascular endothelial growth factor-C (VEGF-C) and VEGF-D, we studied the effect of the angioregulatory growth factor angiopoietin-2 (Ang-2) on PDAC progression. Ang-2 was found to be expressed in transformed cells of human PDAC specimens, with corresponding Tie-2 receptors present on blood and lymphatic endothelium. In vitro in PDAC cells, Ang-2 was subject to autocrine/paracrine TGF-β stimulation (2-fold induction, P=0.0106) acting on the -61- to +476-bp element of the human Ang-2 promoter. In turn, Ang-2 regulated the expression of genes involved in cell motility and tumor suppression. Orthotopic PDAC xenografts with forced expression of Ang-2, but not Ang-1, displayed increased blood and lymphatic vessel density, and an enhanced rate of lymphatic metastasis (6.7- to 9.1-fold, P<0.01), which was prevented by sequestration of Ang-2 via coexpression of soluble Tie-2. Notably, elevated circulating Ang-2 in patients with PDAC correlated with the extent of lymphatic metastasis. Furthermore, median survival was reduced from 28.4 to 7.7 mo in patients with circulating Ang-2 ≥ 75th percentile (P=0.0005). These findings indicate that Ang-2 participates in the control of lymphatic metastasis, constitutes a noninvasive prognostic biomarker, and may provide an accessible therapeutic target in PDAC.	\N	\N
21689845	To describe the number of urethral dilations, urethrotomies, and urethroplasties performed on men with a diagnosis of urethral stricture disease seeking care in the Veterans Affairs (VA) health care system in southern California and southern Nevada over a 5-year period. To date, few health services research studies have evaluated patterns of care for urethral stricture disease using national datasets. We analyzed stricture treatment for male veterans with an ICD-9 diagnosis code for urethral stricture in the National Patient Care Database (NPCD). Encounters for urethral stricture procedures performed were identified based on the presence of Physicians Current Procedural Terminology Coding System (4th edition, CPT-4) codes for treatments performed during the fiscal years 2002-2006. A total of 1457 men carried a diagnosis of urethral stricture disease during the index time period. Of these, 333 men (23%) underwent 431 procedures. Of the 216 men who underwent urethral dilations, 170 (79%) underwent only 1 procedure and 26 (12%) underwent 2 procedures. Of the 79 men who underwent urethrotomy, 76 (96%) underwent 1 procedure. Sixteen men (5%) underwent a urethroplasty, 8 of whom underwent a perineal urethrostomy. The vast majority of men treated for stricture disease underwent only 1 such procedure over a 5-year time period. Further research is required to investigate whether this is a quality-of-care issue or patients refusing intervention. It is possible that some patients may be temporized for a significant period with dilation/urethrotomy, whereas those with rapid recurrence require early urethroplasty.	\N	\N
21690452	Laparoscopy is increasingly used in colon and rectal procedures. However, little is known regarding the incidence of venous thromboembolism (VTE) in laparoscopic colorectal (LC) compared with that in open colorectal (OC) procedures. We aimed to compare the incidences and to highlight the risk factors of developing VTE after LC and OC surgery. Analysis of the Nationwide Inpatient Sample data from 2002 through 2006. National database. Patients who underwent elective LC and OC surgery from 2002 through 2006. Incidence of VTE during initial hospitalization after LC and OC surgery; VTE classified by surgical site, pathology type, and at-risk patient population. Over a 60-month period, 149,304 patients underwent LC or OC resection. Overall, the incidence of VTE was significantly higher in OC cases (2036 of 141,456 [1.44%]) compared with the incidence in LC cases (65 of 7848 [0.83%]) (P < .001). When stratified according to pathologic condition and surgical site, the overall rate of VTE was highest in patients with inflammatory bowel disease and in those undergoing rectal resections. Patients who underwent OC surgery were almost twice as likely to develop VTE compared with patients who underwent LC surgery. We also identified malignancy, obesity, and congestive heart failure as statistically significant (P < .05) risk factors for VTE in OC and LC surgery. On the basis of data from a large clinical data set, the incidence of perioperative VTE is lower after LC than after OC surgery. These findings may help colorectal surgeons use appropriate VTE prophylaxis for patients undergoing colorectal procedures.	\N	\N
21699733	Itch sensation is one of the major sensory experiences of human and animals. Recent studies have proposed that gastrin releasing peptide (GRP) is a key neurotransmitter for itch in spinal cord. However, no direct evidence is available to indicate that GRP actually mediate responses between primary afferent fibers and dorsal horn neurons. Here we performed integrative neurobiological experiments to test this question. We found that a small population of rat dorsal horn neurons responded to GRP application with increases in calcium signaling. Whole-cell patch-clamp recordings revealed that a part of superficial dorsal horn neurons responded to GRP application with the increase of action potential firing in adult rats and mice, and these dorsal horn neurons received exclusively primary afferent C-fiber inputs. On the other hands, few A(δ) inputs receiving cells were found to be GRP positive. Finally, we found that evoked sensory responses between primary afferent C fibers and GRP positive superficial dorsal horn neurons are mediated by glutamate but not GRP. CNQX, a blocker of AMPA and kainate (KA) receptors, completely inhibited evoked EPSCs, including in those Fos-GFP positive dorsal horn cells activated by itching. Our findings provide the direct evidence that glutamate is the principal excitatory transmitter between C fibers and GRP positive dorsal horn neurons. Our results will help to understand the neuronal mechanism of itch and aid future treatment for patients with pruritic disease.	\N	\N
21699956	The NMDA glutamate hypofunction model of schizophrenia is based in part upon acute effects of NMDA receptor blockade in humans and rodents. Several laboratories have reported glutamate system abnormalities following prenatal exposure to immune challenge, a known environmental risk factor for schizophrenia. Here we report indices of NMDA glutamate receptor hypofunction following prenatal immune activation, as well as the effects of treatment during periadolescence with the atypical antipsychotic medications risperidone and paliperidone. Pregnant Sprague-Dawley rats were injected with polyinosinic:polycytidylic acid (poly I:C) or saline on gestational day 14. Male offspring were treated orally via drinking water with vehicle, risperidone (0.01mg/kg/day), or paliperidone (0.01mg/kg/day) between postnatal days 35 and 56 (periadolescence) and extracellular glutamate levels in the prefrontal cortex were determined by microdialysis at PD 56. Consistent with decreased NMDA receptor function, MK-801-induced increases in extracellular glutamate concentration were markedly blunted following prenatal immune activation. Further suggesting NMDA receptor hypofunction, prefrontal cortex basal extracellular glutamate was significantly elevated (p<0.05) in offspring of poly I:C treated dams. Pretreatment with low dose paliperidone or risperidone (0.01mg/kg/day postnatal days 35-56) normalized prefrontal cortical basal extracellular glutamate (p<0.05 vs. poly I:C vehicle-treatment). Pretreatment with paliperidone and risperidone also prevented the acute MK-801-induced increase in extracellular glutamate. These observations demonstrate decreased NMDA receptor function and elevated extracellular glutamate, two key features of the NMDA glutamate receptor hypofunction model of schizophrenia, during periadolescence following prenatal immune activation. Treatment with the atypical antipsychotic medications paliperidone and risperidone normalized basal extracellular glutamate. Demonstration of glutamatergic abnormalities consistent with the NMDA glutamate receptor hypofunction model of schizophrenia as an early developmental consequence of prenatal immune action provides a model to identify novel early interventions targeting glutamatergic systems which play an important role in both positive and negative symptoms of schizophrenia.	\N	\N
21700931	Caloric restriction (CR) confers cardioprotection against ischemia/reperfusion injury. However, the exact mechanism(s) underlying CR-induced cardioprotection remain(s) unknown. Recent evidence indicates that Sirtuins, NAD(+)-dependent deacetylases, regulate various favorable aspects of the CR response. Thus, we hypothesized that deacetylation of specific mitochondrial proteins during CR preserves mitochondrial function and attenuates production of reactive oxygen species during ischemia/reperfusion. The objectives of the present study were (1) to investigate the effect of CR on mitochondrial function and mitochondrial proteome and (2) to investigate what molecular mechanisms mediate CR-induced cardioprotection. Male 26-week-old Fischer344 rats were randomly divided into ad libitum-fed and CR (40% reduction) groups for 6 months. No change was observed in basal mitochondrial function, but CR preserved postischemic mitochondrial respiration and attenuated postischemic mitochondrial H(2)O(2) production. CR decreased the level of acetylated mitochondrial proteins that were associated with enhanced Sirtuin activity in the mitochondrial fraction. We confirmed a significant decrease in the acetylated forms of NDUFS1 and cytochrome bc1 complex Rieske subunit in the CR heart. Low-dose resveratrol treatment mimicked the effect of CR on deacetylating them and attenuated reactive oxygen species production during anoxia/reoxygenation in cultured cardiomyocytes without changing the expression levels of manganese superoxide dismutase. Treatment with nicotinamide completely abrogated the effect of low-dose resveratrol. These results strongly suggest that CR primes mitochondria for stress resistance by deacetylating specific mitochondrial proteins of the electron transport chain. Targeted deacetylation of NDUFS1 and/or Rieske subunit might have potential as a novel therapeutic approach for cardioprotection against ischemia/reperfusion.	\N	\N
21703749	Few studies have focused on the full complement of cardiac arrest cases seen in hospital emergency departments (ED). The aims of our study were to describe cardiac arrest visits in the ED by using a nationally representative sample of U.S. adults. ED data from the 2001-2007 National Hospital Ambulatory Medical Care Survey (NHAMCS) were analyzed. Cardiac arrest visits were considered to be those with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 427.5 as the primary diagnosis. From 2001 to 2007, adults in the U.S. made an estimated 600,729,000 ED visits. Of those, 1,001,000 (0.17%) had a primary diagnosis of cardiac arrest. The majority of patients with such visits were dead on arrival or died in the ED (74.0%). The mean age for cardiac arrest visits was 66.7 years (95% confidence interval [CI], 64.6-68.8 years). Women had a lower rate of cardiac arrest visits than men (age-adjusted odds ratio [AOR], 0.6; 95% CI, 0.5-0.8), and the privately insured (AOR, 0.4; 95% CI, 0.2-0.7) and those with government insurance (AOR, 0.5; 95% CI, 0.3-0.9) had a lower proportion of cardiac arrest ED visits than uninsured persons. In addition, increasing age was a significant predictor of cardiac arrest visits. Cardiac arrest visits did not vary significantly by race, geographic region, or metropolitan statistical area. ED visits classified as cardiac arrest represent 1 in 600 visits and these visits differ by age, sex, payment source, and arrival time at the ED.	\N	\N
21704888	The safety of long-acting β2 agonists (LABA) for the treatment of persistent asthma remains a topic of ongoing debate. To evaluate the risk of serious asthma-related events among patients treated with formoterol, a meta-analysis of all Novartis-sponsored controlled clinical trials was conducted. Forty-five randomized, placebo- and active-controlled, parallel-group or crossover studies with formoterol were included. Background inhaled corticosteroid (ICS) use was permitted in all studies; however, in only 2 studies was ICS randomized as study medication. Sub-analyses of the pooled data were performed according to age (5-12; 13-18; >18 years), baseline ICS use, and lung function. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated between formoterol (twice-daily), albuterol (salbutamol) 4 times per day (active control), and placebo. Patients were randomized to formoterol (n = 5,367), placebo (n = 2,026), and albuterol (n = 976). Two deaths were reported, 1 each in the formoterol (asthma exacerbation) and the placebo (hemorrhagic pancreatitis) groups. No statistically significant differences in serious asthma exacerbations were observed compared with placebo in adolescents and adults. In children, a higher frequency of hospitalizations was observed among patients treated with formoterol compared with placebo (OR 8.4; 95% CI: 1.1-65.3). A trend toward fewer exacerbations was observed among subjects reporting concomitant ICS use at baseline. This analysis supports current guideline recommendations for the use of LABAs only as add-on therapy to ICS.	\N	\N
21706339	The prostate gland is the most common site of neoplastic disorders in men. The pathogenesis of inflammatory cells, prostatic intraepithelial neoplasia (PIN) lesions, and prostate cancer is still under investigation. Inflammatory cells by producing free radicals are considered as major and universal contributors to cancerogenesis. PIN is regarded as a precursor lesion to prostate cancer or a marker signaling the vulnerability of the epithelium to neoplastic transformation [1]. Differentiation markers that are frequently changed in early invasive carcinoma are also changed in PIN lesions. In this study, prostate tissue samples obtained during surgical operation and classified as various disease states (inflammation, PIN lesions, and cancer) were examined. The samples were measured by means of microbeam synchrotron-radiation-induced X-ray emission (micro-SRIXE). Special attention was paid to examine the relationship between the earlier-mentioned disorders and changes in relative concentrations of S, K, Ca, Fe, Cu, and Zn. Applying the image-processing program ImageJ enabled us to select the areas of interest from two-dimensional maps of various prostate samples according to the histopathologist's evaluation. Detailed analysis of micro-SRIXE spectra based on multivariate methods shows significant differences between elemental concentrations in inflammatory cells, PIN lesions, and cancerous tissues, which confirms that this method can be used to distinguish various pathological states in prostate tissues. Information obtained in this way may provide better understanding of the biochemistry of unhealthy prostate tissues, thus opening the way to find new medicines/treatments to prevent or slow down some harmful intracellular processes.	\N	\N
21712520	Data have shown that preprocedural statin therapy reduces periprocedural myocardial infarction after percutaneous coronary intervention (PCI). However, whether preprocedural statins improve clinical outcomes in patients with stable coronary artery disease (CAD) has not been established. We aimed to evaluate the clinical effectiveness of preprocedural statin therapy in patients with stable CAD undergoing PCI. We conducted an observational study of 12 980 patients, age >65 years with stable CAD, who underwent PCI from December 1, 2003, to March 31, 2008. Using propensity score-matching analysis, 3098 unique matched pairs (6196 patients) who had similar likelihood of receiving preprocedural statins were identified. Additional analyses adjusting for postprocedural statins as a time-varying variable were performed. The main outcome measure was a composite of death or recurrent acute coronary syndrome. In the propensity-matched cohort, at 90 days, the primary outcome of death and acute coronary syndrome occurred in 5.6% in the preprocedural statin group as compared with 7.4% in the no-pretreatment group (P=0.005). Improved clinical outcomes associated with preprocedural statins were still observed at 2 years (16.7% versus 19.3%, P=0.007). The effectiveness of preprocedural statins was most pronounced at 90 days after PCI (adjusted hazard ratio, 0.80; 95% confidence interval, 0.65 to 0.98) but was no longer significant at 1 year (adjusted hazard ratio, 0.92; 95% confidence interval, 0.79 to 1.07) after accounting for postprocedural statin therapy. Preprocedural statin therapy was associated with significant reduction in the risk of death or recurrent acute coronary syndrome in stable CAD patients after PCI. These findings support the routine use of preprocedural statins for suitable candidates.	\N	\N
21722500	To describe the MRI features of gout tophi in the soft-tissues or joints of the limbs by low-field extremity-dedicated MRI. Nine consecutive patients, 8M/1W, affected by chronic tophaceous gout were studied. Mean patients' age was 71.3±11.5 years, mean disease duration 98.1±44.9 months, and mean serum uric acid concentration 9.2±2.8 mg/L. Diagnosis was based on the ACR classification criteria for gout, and by identification of MSU crystals in the tophi and synovial fluid. Conventional radiograms and MRI with an extremity-dedicated system were obtained of the joint areas involved by tophi. At T1 weighted MRI images, all tophi showed a homogeneous intermediate signal intensity, similar to that of muscle. Conversely, in T2 weighted images, a wide spectrum of signal intensity patterns was observed. The pattern of contrast enhancement was variable from intense homogeneous to peripheral and heterogeneous. Capsulo-ligamentous structures were often thickened and degenerated and, on occasion, could be recognised as inhomogeneous, hypointense ribbon-shaped elements in the context of the tophus. In only two cases, tendons were infiltrated by tophaceous matter. Bone marrow oedema (BME) and erosions were seen in 8 out of 10 bones adjacent to tophi. The MRI appearance of gout tophi using an extremity-dedicated machine is similar to that described in the literature using whole body machines. BME adjacent to the tophus was a frequent finding. This technique may occasionally help in the differential diagnosis of nodules and in the follow-up of the disease. It also represents a useful tool to investigate the pathogenesis of gout and to better understand its clinical progression.	\N	\N
21726837	Data are lacking on the efficacy and safety of a loading dose (LD) of clopidogrel in elderly patients with acute myocardial infarction (AMI). FAST-MI is a nationwide registry that was carried out over a 1-month period in 2005 and included consecutive patients with AMI admitted to intensive care units <48 hours from symptom onset in 223 participating centers. We assessed the impact of a clopidogrel LD (≥300 mg) compared to a conventional dose (<300 mg) on bleeding, need for blood transfusion, and 30-day and 12-month survivals in 791 elderly patients (≥75 years old, mean age 81 ± 4 years, 48% women, 35% with ST-segment elevation MI) included in this registry. Fifty-nine percent (466 patients) received a clopidogrel LD. Follow-up was >99% complete. Major bleeding and blood transfusions were not significantly different in patients who received a clopidogrel LD (3.2% vs 3.7%, p = 0.72; 5.4% vs 6.2%, p = 0.64, respectively). Early mortality was also not significantly different (10.1 vs 10.8, p = 0.76). Using multivariate analyses, clopidogrel LD did not significantly affect major bleeding or transfusion (odds ratio 1.03, 95% confidence interval 0.49 to 2.17, p = 0.94) and 12-month mortality (hazard ratio 1.00, 95% confidence interval 0.72 to 1.40, p = 0.98). In conclusion, the present data showed that in elderly patients admitted for AMI, use of a LD of clopidogrel compared to a conventional dose was not associated with increased in-hospital bleeding, need for transfusion, or mortality. Large-scale randomized trials are still needed to identify the optimal LD of clopidogrel for elderly patients admitted for AMI.	\N	\N
21727012	The lung is the most common site for extrahepatic metastasis from hepatocellular carcinoma (HCC). We previously reported in a series of 20 patients that pulmonary metastasectomy for HCC is feasible in selected patients. The objective of this study was to re-evaluate the long-term outcomes and prognostic factors with an additional 25 patients. We retrospectively analyzed the records of 45 consecutive patients who underwent pulmonary metastasectomy due to HCC at our institution between 1990 and 2010. Thirty-nine patients underwent hepatectomy or liver transplantation, whereas six patients underwent locoregional therapy for primary liver lesions. Twenty-seven patients died during a median 17.6-month follow-up period. The 2-year disease-free survival (DFS) was 19.5%. The 5-year overall survival (OS) was 40.9%. History of recurrence and serum des-gamma-carboxy prothrombin (DCP) level >40 mAU ml(-1) at initial pulmonary resection were unfavorably associated with OS in univariate analysis. Pulmonary metastasectomy for HCC in selected patients resulted in relatively good outcomes with regard to OS. History of recurrence and serum DCP levels were shown to be candidates of prognostic factors for OS.	\N	\N
21735745	A 42-year-old Japanese woman was referred to our university hospital due to progressive anemia and bilateral hilar lymphadenopathy with diffuse ground-glass attenuation on chest computed tomography in December 2009. She had suffered from exertional dyspnea and fatigue for several months. Laboratory findings on admission demonstrated leukocytosis (10,950/ul), elevation of C-reactive protein (4.7 mg/dl), IL-6 (19.9 pg/ml), IgG4 (567 mg/dl) and polyclonal hyper gamma-globulinemia. Chest computed tomography represented mediastinal and bilateral hilar lymphadenopathy with diffuse centrilobular fine nodules and intralobular septal thickening. Histopathological findings of the specimens obtained by thoracoscopic lung and mediastinal lymph node biopsies revealed massive infiltration of IgG4-positive plasma cells in lung tissue and lymph nodes. Pathological findings and high levels of C-reactive protein and interleukin-6 suggested a diagnosis of multicentric Castleman's disease (MCD). In addition, pathological findings of peribronchiolar infiltration of IgG4-positive plasma cells and lymphoid follicles with infiltration of IgG4-positive plasma cells with a high level of IgG4 were indicative of the complication of IgG4-related lung disease. Radiological and serological findings improved rapidly soon after the initiation of oral corticosteroid treatment. It was speculated that this case indicated the close relationship between MCD and IgG4-related lung disease.	\N	\N
21737965	Bartonella henselae is the causative agent of cat scratch disease (CSD) in humans. Cats are the main reservoir of this bacterium and may infect humans through scratches and bites. The purpose of this study was to determine the B. henselae seroprevalence in cats in Turkey. A total of 298 cats blood samples were collected from six different provinces of Turkey. Sera were tested for the presence of anti-B. henselae IgG antibodies by indirect fluorescent antibody test (IFA). The seroprevalence of B. henselae was 27.9% (83/298) for the cats examined in this study. The seroprevalence of cats by province was significantly higher in Bursa (41.3%), Adana (33.9%), Aydin (27.5%) and Burdur (32.3%) than in Kayseri (17.9%) and Istanbul (12.5%). Statistically significant differences were not observed between cat sexes and living conditions of cats. The results revealed that B. henselae is an important zoonotic pathogen in Turkey.	\N	\N
21751546	Intravenous immunoglobulin (IVIG) products are derived from plasma pools of thousands of healthy donors. These immunoglobulin concentrates contain large number of antibodies as well trace levels various other immunologically active molecules. Therapeutic Ig formulations contain intact IgG molecules, with variable amounts of monomeric and dimeric form existing in a dynamic equilibrium. Paradoxically, IgG can exert both pro-and anti-inflammatory activities, depending on its concentration. IVIG have been used for the treatment of primary immunodeficiency disorders for more than 25 years. IVIG products are also effective in the treatment of autoimmune and inflammatory disorders; however, the precise mechanism (s) of action is not known. Clinical and laboratory studies have documented various mechanisms of action of IVIG. The complex network of immunological reactions resulting from the infusion of IVIG includes changes in several cytokines, interactions with dendritic cells, T-and B-cell effects, macrophage effects, mediated by distinct Fc-gamma receptors. IVIG is also a recently recognized modifier of complement activation and injury. The complement--scavenging ability of Ig implies expansion of the use of IVIG to all disease in which generation of complement fragments plays a crucial role in pathogenesis. Recent studies showed that the anti-inflammatory activity of IVIG result from a minor population of the pooled IgG molecules that contains terminal a-2,6 sialic acid linkages on their Fc-linked glycans. This fully processed glycan is found in 1-3% of IgG in IVIG, which may explain the requirement for a high dose of IVIG. Recent data demonstrate, that the anti-inflammatory properties of IVIG can be recapitulated with fully recombinant preparation of appropriately sialylated IgG Fc fragments. This recombinant preparation had a 35 fold enhanced activity and potentially could be used at much lower doses than IVIG preparation in the treatment of autoimmune disorders.	\N	\N
21764110	The impact of diffusion-weighted imaging (DWI) and apparent diffusion coefficients (ADCs) of MR imaging on the evaluation of residual Uterine Cervical Carcinoma after Radiation Therapy, in addition to conventional MR images. Fourty-nine women presenting with a uterine cervical cancer were examined with 1.5 T MRI and DWI, 8 (4-20) weeks after treatment. Treatment response was determined based on the histopathological results after therapy and was classified as a complete response (CR) or residual disease (RD). Post-treatment DWI and ADC results were compared. Five (11%) and 44 (89%) patients were considered as having histologically-proven RD or a CR respectively. The mean ADC of cervical tissue for all patients was 1.74±0.324×10(-3) mm(2)/s and the SD was 1.94±1.11×10(-4). The mean ADC was 1.62±0.21×10(-3) mm(2)/s (SD=1.45×10(-4)) for the 5 patients with RD versus 1.76±0.33×10(-3) mm(2)/s (SD=1.99×10(-4)) for the 44 patients with a CR (p=0.09). Using 1.7×10(-3) mm(2)/s as a radiological cut-off value for the ADC, all patients classified as having histologically-proven RD had a mean ADC of ≤1.7×10(-3). In 12 (25%) cases, RD was suspected on T2-weighted MRI images alone. Eight of these cases were considered as false positives compared to the histological results. Their mean ADC was 1.98×10(-3) mm(2)/s and none of them had an ADC of <1.7×10(-3) mm(2)/s. Although our results were not statistically significant, ADC values could potentially be used to predict and monitor the response of uterine cervical cancer.	\N	\N
21769106	Strong and unidirectional associations exist between the severity of cardiovascular calcifications and mortality in patients with advanced chronic kidney disease. In the past 10 years, a wealth of experimental and clinical information has been published on the key pathophysiological events that contribute to the development and progression of vascular and soft-tissue calcifications. These processes involve a sensitive balance of calcification inhibition, induction and removal. The traditional view of regarding secondary hyperparathyroidism and elevated calcium × phosphate product as the pivotal risk factors for calcification has been challenged by data demonstrating a role for other, more subtle and complex pathomechanisms. These mechanisms include the loss of endogenous calcification inhibitors, deficient clearance of calcified debris, effects of vitamin K and vitamin D, and the action of calcification inducers as in osteogenic transdifferentiation. In this Review, we describe our current knowledge of the factors involved in the passive and active regulation of extraosseous calcification processes, with an assessment of their importance as targets for future diagnostic and therapeutic interventions.	\N	\N
21776811	Tumor characterization employing a voxel-wise analysis of image signal facilitates the determination of the spatial distribution of tumor attributes, and when employed for therapy response assessment offers the promise of greater sensitivity to change than conventional approaches. However, the accuracy of a voxel-wise analysis of change is limited by local registration uncertainties that can disrupt the spatiotemporal correspondence between assessed voxels. We present a method for assessing voxel correspondence strength using a multiresolution local histogram-based measure of image structure similarity. When employed in a longitudinal tumor imaging context, a voxel similarity measure must be robust to intensity variations that can arise from the image acquisition, treatment effects, or changes in underlying disease processes. Consequently, the local histogram-based similarity measure is evaluated for sensitivity to structural change and robustness to intensity variation and is compared against normalized mutual information and normalized cross-correlation. T1-weighted (T1W) magnetic resonance (MR) images of glioblastoma acquired as part of a longitudinal response assessment study are first rigidly registered, and then similarity between spatially corresponding voxels is evaluated using multiresolution local histograms. Region-based and nonuniform intensity changes of varying magnitude as well as deformations to image structure are applied individually and in combination to the test images. Statistical analysis is used to test for interaction effects between the applied perturbations and the value of the local histogram similarity function. Pair-wise voxel similarity maps are computed for pairs of longitudinal clinical MR image volumes and compared with observed patterns of change on conventional imaging. The simulations demonstrated that the local histogram measure was robust to intensity modulations applied to increasing region sizes and exhibited a strong negative correlation with the magnitude of local deformation. No statistically significant interaction effects were observed upon the value of the local histogram similarity function when deformation was applied in conjunction with a nonuniform intensity change. Pair-wise voxel similarity maps were consistent with image change observed on T1W MR imaging and revealed patterns of change not apparent in conventional image sequences. A measure of local histogram image structure similarity can be used to assess the strength of voxel to voxel correspondences independently of intensity nonuniformities. The metric can provide a local estimate of the limits of achievable correspondence underlying the registration and voxel-wise comparison of signal in longitudinal imaging used for assessing tumor response to treatment.	\N	\N
21779916	Metastatic pulmonary calcification can be caused by a number of diseases, most common being end-stage renal disease. Most of the patients are asymptomatic, and imaging with computed tomography is useful in making a diagnosis. Demonstration of pulmonary and chest wall vessel calcification is characteristic. We report a case of a 60-year-old patient with chronic renal failure on dialysis, presenting with gradual onset dyspnea, who showed metastatic pulmonary calcification on chest imaging.	\N	\N
21784472	Long-term ketamine abuse in humans causes significant lower urinary tract symptoms. However, the etiology of ketamine associated cystitis is still not clear. We created a mouse model of ketamine induced lower urinary tract dysfunction to explore the pathogenesis of this condition. Female C57BL/6 mice randomly distributed into control and ketamine groups received daily intraperitoneal injection of saline and ketamine (100 mg/kg), respectively. Cystometry was done in each group at 4, 8 and 16 weeks. After sacrifice the bladders were harvested for isometric muscle tension recording and immunohistochemical examination. After 8 weeks of treatment body weight growth was significantly decreased in ketamine treated mice. Cystometry revealed a significantly decreased intercontraction interval (mean±SEM 237±9 vs 360±20 seconds, p<0.001) and decreased bladder capacity (0.1±0.004 vs 0.13±0.006 ml, p<0.001) in ketamine vs saline injected mice. Increased adenosine triphosphate evoked detrusor contraction developed in the ketamine group. Immunohistochemical examination revealed increased P2X1 receptor expression in ketamine treated mouse bladders while M2 and M3 receptor expression was unchanged. At 8 weeks mice treated with ketamine showed increased voiding frequency and decreased bladder capacity, the same symptoms that develop in human ketamine abusers. Enhanced noncholinergic contractions and P2X1 receptor expression in the ketamine bladder indicate that dysregulation of purinergic neurotransmission may underlie detrusor overactivity in cases of ketamine induced bladder dysfunction.	\N	\N
21785215	Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress. Here, we show that oxidized calmodulin kinase II (ox-CaMKII) is a biomarker for SND in patients and dogs and a disease determinant in mice. In wild-type mice, Ang II infusion caused sinoatrial nodal (SAN) cell oxidation by activating NADPH oxidase, leading to increased ox-CaMKII, SAN cell apoptosis, and SND. p47-/- mice lacking functional NADPH oxidase and mice with myocardial or SAN-targeted CaMKII inhibition were highly resistant to SAN apoptosis and SND, suggesting that ox-CaMKII-triggered SAN cell death contributed to SND. We developed a computational model of the sinoatrial node that showed that a loss of SAN cells below a critical threshold caused SND by preventing normal impulse formation and propagation. These data provide novel molecular and mechanistic information to understand SND and suggest that targeted CaMKII inhibition may be useful for preventing SND in high-risk patients.	\N	\N
21791221	This manuscript provides a survey of research findings catered to the development of effective countermeasures against nerve agent poisoning over the past decade. New neuropathophysiological distinctive features as regards organophosphate (OP) intoxication are presented. Such leading neuropathophysiological features include recent data on nerve agent-induced neuropathology, related peripheral or central nervous system inflammation and subsequent angiogenesis process. Hence, leading countermeasures against OP exposure are down-listed in terms of pre-treatment, protection or decontamination and emergency treatments. The final chapter focuses on the description of the self-repair attempt encountered in lesioned rodent brains, up to 3months after soman poisoning. Indeed, an increased proliferation of neuronal progenitors was recently observed in injured brains of mice subjected to soman exposure. Subsequently, the latter experienced a neuronal regeneration in damaged brain regions such as the hippocampus and amygdala. The positive effect of a cytokine treatment on the neuronal regeneration and subsequent cognitive behavioral recovery are also discussed in this review. For the first time, brain cell therapy and neuronal regeneration are considered as a valuable contribution towards delayed treatment against OP intoxication. To date, efficient delayed treatment was lacking in the therapeutic resources administered to patients contaminated by nerve agents.	\N	\N
21797955	The outcome of HCC after transplantation (OLT) in children is not well known. Unfavorable features based on adult reports may lead to contraindicate OLT even in children. We reviewed a cohort of children with cirrhosis and HCC to evaluate their outcome after primary transplantation. We considered children with cirrhosis and HCC who had a primary OLT. We retrospectively recorded demographic, medical and surgical features, and MC as predictors of outcome. Among 456 children transplanted in the last 15 yr, 10 (2%), median age at diagnosis 1.8 yr (range 0.5-7.2), had HCC in biliary atresia (3), BSEP deficiency (3), tyrosinemia type 1 (2), complications of choledocal cyst and glycogen storage disease type IV (1 each). At HCC discovery, median AFP was 2322 ng/mL (3-35,000), high or rising in 9/10 patients. Six patients were outside the MC. Median time on the waiting list was 38 days (1-152). Two patients died from early complications of OLT. In the other eight patients, there was no tumor recurrence after a median follow-up of four yr. Children with cirrhosis may develop HCC at a very young age. The outcome appears excellent even outside MC. Primary liver transplantation is advisable for children with cirrhosis, HCC, and no extrahepatic disease.	\N	\N
21802018	The cost associated with asthma impairment in children with severe asthma has not been determined. To assess the asthma cost burden in children with severe or difficult-to-treat asthma based on asthma impairment. Children aged 6 to 12 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study with available data at baseline (n = 628), month 12 (n = 385), and month 24 (n = 280) corresponding to the National Heart, Lung, and Blood Institute asthma guidelines' impairment domain were included. Children were categorized as either very poorly controlled (VPC), not well controlled (NWC), or well controlled (WC) and assessed cross-sectionally and longitudinally. Mean total asthma costs based on direct (medication usage, unscheduled office visits, emergency department visits, hospitalizations) and indirect (school/work days lost) asthma costs were assessed. Mean annual total asthma costs were more than twice as high in the VPC group compared with NWC and WC groups (baseline: $7,846, $3,526, $3,766.44, respectively; month 12: $7,326, $2,959, $2,043, respectively; month 24: $8,879, $3,308, $1,861, respectively (all P < .001). Indirect costs accounted for approximately half the total asthma costs for VPC asthma patients at each time point. Significantly lower costs were observed for patients whose impairment status improved or temporarily improved from VPC after baseline. The economic burden of severe or difficult-to-treat asthma in children is associated with VPC asthma and improvement in asthma control and is associated with reducing cost. Further attention to patients with poorly controlled asthma, through better management strategies or more effective medications, may significantly reduce this burden of illness.	\N	\N
21803694	The use of experimental model systems has expedited the elucidation of pathogenetic mechanisms of renal developmental disease in humans and the identification of genes that orchestrate developmental programming during nephrogenesis. We conducted studies to evaluate the role of AHR polymorphisms in the disruption of renal developmental programming by benzo(a)pyrene (BaP). We used metanephric cultures of C57BL/6J (C57) mice expressing the Ahr(b-1) allele and B6.D2N-Ahr(d)/J (D2N) mice expressing a mutant allele deficient in ligand binding (Ahr(d)) to investigate molecular mechanisms of renal development. Deficits in fetal programming were evaluated in the offspring of pregnant mice treated with BaP during nephrogenesis. Hydrocarbon challenge of metanephri from C57 mice altered Wilms' tumor suppressor gene (Wt1) mRNA splice variant ratios and reduced mRNAs of the Wt1 transcriptional targets syndecan-1 (Sdc1) paired box gene 2 (Pax2), epidermal growth factor receptor (Egfr), and retinoic acid receptor, alpha (Rarα). These changes correlated with down-regulation of effectors of differentiation [secreted frizzled-related sequence protein 1 (Sfrp1), insulin-like growth factor 1 receptor (Igf1r), wingless-related MMTV-integration site 4 (Wnt4), Lim homeobox protein 1 (Lhx1), E-cadherin]. In contrast, metanephri from D2N mice were spared hydrocarbon-induced changes in Wt1 splice variant ratios and deficits of differentiation. We observed similar patterns of dysmorphogenesis and progressive loss of renal function at postnatal weeks 7 and 52 in the offspring of pregnant C57 but not D2N mice gavaged with 0.1 or 0.5 mg/kg BaP on gestation days 10-13. These findings support a functional link between AHR and WT1 in the regulation of renal morphogenesis and raise important questions about the contribution of human AHR polymorphisms to the fetal origins of adult-onset kidney disease.	\N	\N
21804097	Proper understanding of the roles of, and interactions between genetic, lifestyle, environmental and psycho-social factors in determining the risk of development and/or progression of chronic diseases requires access to very large high-quality databases. Because of the financial, technical and time burdens related to developing and maintaining very large studies, the scientific community is increasingly synthesizing data from multiple studies to construct large databases. However, the data items collected by individual studies must be inferentially equivalent to be meaningfully synthesized. The DataSchema and Harmonization Platform for Epidemiological Research (DataSHaPER; http://www.datashaper.org) was developed to enable the rigorous assessment of the inferential equivalence, i.e. the potential for harmonization, of selected information from individual studies. This article examines the value of using the DataSHaPER for retrospective harmonization of established studies. Using the DataSHaPER approach, the potential to generate 148 harmonized variables from the questionnaires and physical measures collected in 53 large population-based studies (6.9 million participants) was assessed. Variable and study characteristics that might influence the potential for data synthesis were also explored. Out of all assessment items evaluated (148 variables for each of the 53 studies), 38% could be harmonized. Certain characteristics of variables (i.e. relative importance, individual targeted, reference period) and of studies (i.e. observational units, data collection start date and mode of questionnaire administration) were associated with the potential for harmonization. For example, for variables deemed to be essential, 62% of assessment items paired could be harmonized. The current article shows that the DataSHaPER provides an effective and flexible approach for the retrospective harmonization of information across studies. To implement data synthesis, some additional scientific, ethico-legal and technical considerations must be addressed. The success of the DataSHaPER as a harmonization approach will depend on its continuing development and on the rigour and extent of its use. The DataSHaPER has the potential to take us closer to a truly collaborative epidemiology and offers the promise of enhanced research potential generated through synthesized databases.	\N	\N
21813382	Living donor liver transplantation (LDLT) has recently emerged as an effective therapeutic alternative for patients with end-stage liver disease. In the meantime, the health-related quality of life (HRQoL) of the donors is becoming better appreciated. Here we aimed to review the current literature and summarize the effects of liver donation on the long-term HRQoL of living donors. A literature search of PubMed using "donors", "living donor liver transplantation", "health-related quality of life", and "donation" was performed, and all the information was collected. The varied postoperative outcomes of liver donors are attributive to the different evaluation instruments used. On the whole, donors experienced good long-term physical and mental well-being with a few complaining of compromised quality of life due to mild symptoms or psychiatric problems. The psychosocial dimension has received increasing attention with the vocational, interpersonal and financial impact of liver donation on donors mostly studied. Generally, donors have a good HRQoL after LDLT. Nevertheless, to achieve an ideal donor outcome, further work is necessary to minimize the negative effects as well as to incorporate recent progress in regenerative medicine.	\N	\N
21824495	Sandfly fever (SF) is an arthropod-borne disease, which has not yet been reported from Ankara. In the summer of 2007, the disease started to be seen in our region, surprisingly causing severe clinical presentations. This report reviews the clinical and laboratory findings of patients with sandfly virus infection of disease outbreaks in 2008 and 2009. A retrospective single-centre descriptive study was performed. Clinically suspected cases were defined on the basis of epidemiologic history and clinical and laboratory findings. The sera samples of the suspected patients were sent to Germany for diagnostic assistance. 50 patients were included in the study. Fever, headache, photophobia, conjunctivitis, myalgia, arthralgia, nausea, abdominal pain and anorexia were common symptoms. Although the fever lasted only 3-6 days, complete recovery required up to 30 days. Leukopenia, thrombocytopenia and elevated serum aspartate-aminotransferase and alanine-aminotransferase levels were remarkable findings. The viral-load of Sandfly fever Turkey Virus (SFTV) was detected in the serum of acute patients ranged from 3.19×10(6) to 2.79×10(9) viral RNA molecules/ml. As a result we want to underline that the new type of sandfly virus causes a severe clinical picture with elevated liver enzymes and thrombocytopenia, to an extent not described before in the literature, which might be due to the elevated viral-load observed.	\N	\N
21832975	In the United States, approximately one in three new human immunodeficiency virus (HIV) infections are transmitted via heterosexual contact. To monitor HIV risk behaviors and HIV prevalence among heterosexuals and other populations, CDC surveys persons in selected metropolitan statistical areas (MSAs), using the National HIV Behavioral Surveillance System (NHBS). This report summarizes data collected from heterosexuals in 24 MSAs with a high prevalence of acquired immunodeficiency syndrome (AIDS) that participated in NHBS during 2006-2007. Of 14,837 heterosexuals aged 18-50 years who were interviewed and tested, 2.0% were HIV infected. HIV prevalence was higher among those with lower socioeconomic status (SES). For example, HIV prevalence was 2.8% among participants with less than a high school education compared with 1.2% among those with more than a high school education, 2.6% among participants who were unemployed compared with 1.0% among those who were employed, and 2.3% among participants with annual household incomes at or below the poverty level compared with 1.0% among those with incomes above the poverty level. This association between HIV prevalence and SES could not be attributed to factors commonly associated with HIV infection risk in heterosexuals, such as using crack cocaine, exchanging sex for things such as money or drugs, or being diagnosed with a sexually transmitted disease (STD). Based on the association observed between HIV prevalence and SES, HIV prevention activities targeted at heterosexuals in urban areas with high AIDS prevalence should be focused on those with lower SES.	\N	\N
21835304	A fundamental challenge in analyzing exome-sequence data is distinguishing pathogenic mutations from background polymorphisms. To address this problem in the context of a genetically heterogeneous disease, retinitis pigmentosa (RP), we devised a candidate-gene prioritization strategy called cis-regulatory mapping that utilizes ChIP-seq data for the photoreceptor transcription factor CRX to rank candidate genes. Exome sequencing combined with this approach identified a homozygous nonsense mutation in male germ cell-associated kinase (MAK) in the single affected member of a consanguineous Turkish family with RP. MAK encodes a cilium-associated mitogen-activated protein kinase whose function is conserved from the ciliated alga, Chlamydomonas reinhardtii, to humans. Mutations in MAK orthologs in mice and other model organisms result in abnormally long cilia and, in mice, rapid photoreceptor degeneration. Subsequent sequence analyses of additional individuals with RP identified five probands with missense mutations in MAK. Two of these mutations alter amino acids that are conserved in all known kinases, and an in vitro kinase assay indicates that these mutations result in a loss of kinase activity. Thus, kinase activity appears to be critical for MAK function in humans. This study highlights a previously underappreciated role for CRX as a direct transcriptional regulator of ciliary genes in photoreceptors. In addition, it demonstrates the effectiveness of CRX-based cis-regulatory mapping in prioritizing candidate genes from exome data and suggests that this strategy should be generally applicable to a range of retinal diseases.	\N	\N
21846442	Cardiac rhabdomyoma (CR) is the cardiac tumour most commonly diagnosed in utero. Eighty percent of CRs are associated with tuberous sclerosis (TS). TS is a rare multi-system disease, with autosomal dominant genetic transmission. If the parents of an affected child do not have features of TS, then either one parent is mosaic for the TS gene mutation or the affected child is the result of a de novo germline mutation. We present a case of a dizygotic twin pregnancy complicated by CRs in both fetuses at 24 weeks. Twin A died in utero at 28 weeks. Preterm labour and delivery of twin B occurred at 33 weeks. Twin B had multiple small CRs and a large apical CR. At six weeks after delivery, the CRs had disappeared or reduced in size. Regression in the third trimester or postnatally is the natural course of CRs. Molecular testing for TS identified two variants in the TSC2 gene. The parents were clinically unaffected; however, the father was subsequently found on an MRI of the head to have cortical tubers, and he was found to carry the pathogenic TSC2 mutation. Since dizygotic twin pregnancy is akin to two consecutive pregnancies, the etiology in our case is due to one parent having subclinical TS. To the best of our knowledge, this is the first such case to be reported.	\N	\N
21852013	We compared the intergenerational variations of the clinical phenotype between 30 patients affected with multiple autoimmune syndrome (MAS) and their affected first- and second-degree relatives. Mean age at onset was always significantly higher in the previous generation than in probands for all the considered diseases.	\N	\N
21852664	Observational studies have reported an association between metabolic syndrome (MetS) and microalbuminuria or proteinuria and chronic kidney disease (CKD) with varying risk estimates. We aimed to systematically review the association between MetS, its components, and development of microalbuminuria or proteinuria and CKD. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS AND POPULATION: We searched MEDLINE (1966 to October 2010), SCOPUS, and the Web of Science for prospective cohort confidence interval (CI) studies that reported the development of microalbuminuria or proteinuria and/or CKD in participants with MetS. Risk estimates for eGFR <60 ml/min per 1.73 m(2) were extracted from individual studies and pooled using a random effects model. The results for proteinuria outcomes were not pooled because of the small number of studies. Eleven studies (n = 30,146) were included. MetS was significantly associated with the development of eGFR <60 ml/min per 1.73 m(2) (odds ratio, 1.55; 95% CI, 1.34, 1.80). The strength of this association seemed to increase as the number of components of MetS increased (trend P value = 0.02). In patients with MetS, the odds ratios (95% CI) for development of eGFR <60 ml/min per 1.73 m(2) for individual components of MetS were: elevated blood pressure 1.61 (1.29, 2.01), elevated triglycerides 1.27 (1.11, 1.46), low HDL cholesterol 1.23 (1.12, 1.36), abdominal obesity 1.19 (1.05, 1.34), and impaired fasting glucose 1.14 (1.03, 1.26). Three studies reported an increased risk for development of microalbuminuria or overt proteinuria with MetS. MetS and its components are associated with the development of eGFR <60 ml/min per 1.73 m(2) and microalbuminuria or overt proteinuria.	\N	\N
21855111	The EHF (Ets homologous factor) gene was previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared to malignant mesothelioma using gene expression arrays. The objective of this study was to validate this finding at the mRNA level in a larger series. We analyzed the diagnostic role of EHF in 98 ovarian serous carcinoma effusions, 23 malignant mesothelioma specimens (20 effusions, 3 surgical specimens), and 28 primary ovarian serous carcinomas using quantitative real-time polymerase chain reaction. Expression levels of EHF in ovarian carcinoma were additionally investigated for association with clinicopathologic parameters and survival. Quantitative real-time polymerase chain reaction analysis showed significantly higher expression of EHF mRNA in ovarian carcinoma effusions and in primary ovarian carcinoma compared to malignant mesothelioma effusions (P < .001 for both). EHF mRNA expression was additionally higher in primary ovarian carcinomas compared to effusions of this cancer (P < .001). In univariate analysis for all patients with effusions, higher EHF mRNA levels were associated with a trend for shorter progression-free survival (P = .066), which became significant in analysis of 45 patients with primary diagnosis pre-chemotherapy effusions (P = .01). In Cox multivariate analysis, EHF mRNA expression was an independent predictor of poor progression-free survival for all patients and patients with primary diagnosis pre-chemotherapy effusions (P = .033 and P = .009, respectively). EHF mRNA levels differentiate ovarian carcinoma from malignant mesothelioma and may thus be of diagnostic value in this setting. EHF may be a novel prognostic marker in ovarian carcinoma.	\N	\N
21872587	Decline in verbal fluency is the most consistent and persistent cognitive impairment documented after deep brain stimulation of the subthalamic nucleus in Parkinson's disease. The mechanisms of this deficit are unclear. We aimed to identify and characterise verbal fluency related processing within the subthalamic nucleus through analysis of local field potentials. Local field potentials were recorded from deep brain stimulation electrodes implanted in the subthalamic nuclei of 8 patients (16 sides) with Parkinson's disease, when patients were on medication. Patients performed phonemic and semantic verbal fluency tasks and a control word repetition task to control for the motor output involved in response generation. Significant increases in local field potential Power (p ≤ 0.05) were seen across a broad gamma frequency band (30-95 Hz) during both verbal fluency tasks, after controlling for motor output. Increases in gamma local field potential Power of +7.5% ± 2.3% (SEM) in the semantic fluency task and +6.9% ± 2.0% in the phonemic fluency task were derived when averaging across all electrode contact pairs. Gamma changes recorded from contacts lying in the left hemisphere (dominant in verbal fluency) correlated with average number of correct responses generated (r=0.81 p=0.015) and measures of 'switching' (r=0.79 p=0.020) particularly strongly in the semantic fluency task. Frequency specific power changes observed during task performance are consistent with involvement of the subthalamic nucleus in switching during verbal fluency. Antagonism of such task-related activity with high frequency stimulation of this nucleus may explain the impairments reported.	\N	\N
21876350	We proposed a new method to estimate dry weight (DW) using single frequency bioimpedance. We hypothesized that the change in whole body resistance at 50 kHz (R(50)) was proportional to the ultrafiltration volume (UFV) during a hemodialysis (HD) session. When the targeted resistance estimated in healthy subjects was reached, the patient achieved his/her DW. UFV and R(50) were monitored in 40 HD patients. Another 43 HD patients were stratified into 2 groups to validate this method. The change in whole body resistance was proportional to UFV in each of the 40 HD patients. In the DW(decrease) group, pre-dialysis systolic blood pressure (n = 29, 154.5 ± 22.8 vs. 146.9 ± 22.3, p < 0.05) and antihypertensive medicine (4.7 ± 3.6 vs. 3.3 ± 2.2, p < 0.05) decreased without adverse symptoms change. In the DW(increase) group, the number of adverse symptoms in 1 week (n = 14, 26 vs. 6, p < 0.05) decreased without a change in systolic blood pressure. This method may become a convenient and cheaper way to estimate DW in HD patients.	\N	\N
21884641	Breast cancer is a complex and heterogeneous disease. Gene expression profiling has contributed significantly to our understanding of this heterogeneity at a molecular level, refining taxonomy based on simple measures such as histological type, tumour grade, lymph node status and the presence of predictive markers like oestrogen receptor and human epidermal growth factor receptor 2 (HER2) to a more sophisticated classification comprising luminal A, luminal B, basal-like, HER2-positive and normal subgroups. In the laboratory, breast cancer is often modelled using established cell lines. In the present review we discuss some of the issues surrounding the use of breast cancer cell lines as experimental models, in light of these revised clinical classifications, and put forward suggestions for improving their use in translational breast cancer research.	\N	\N
21884662	Asthma is a frequent illness in young adults and is characterized by airway hyper responsiveness (AHR) and airway inflammation. Asthma is a complex disease and AHR as well as inflammation may be limited, although characteristic symptoms are present. The clinical experience in asthma treatment is that not all asthmatics have a satisfactory effect of the different drugs. Asthma has been found to develop from one disease to a multifaceted disease with numerous different possibilities. More research is needed in strategic asthma management in the search for tailored treatment strategy.	\N	\N
21889188	We report the sixth autopsy case of a patient with aceruloplasminemia. He was the younger brother of the first reported autopsy case of this disease. Among autopsy cases with aceruloplasminemia reported to date, he had the longest duration of neurologic disorders. The neuropathologic findings showed that the basal ganglia and dentate nuclei were most severely affected. The most striking finding in the present case was that marked iron deposition was evident in the cerebral cortex. Many enlarged or deformed astrocytes and globular structures, both of which were heavily iron loaded, were found in the cerebral cortex as well as in the basal ganglia. Pyramidal neurons in his cerebral cortex were fewer in number than observed in the previous reported cases. There was a negative correlation between the number of cortical pyramidal neurons and globular structures. The present case clearly indicates that the neuropathologic process in aceruloplasminemia extends beyond the basal ganglia to the cerebral cortex with time.	\N	\N
21889832	Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. Identify predictors of biochemical tumor control and distant metastases-free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. This retrospective analysis comprised 2551 patients with clinical stages T1-T3 PCa. Median follow-up was 8 yr, extending >20 yr. Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels < 70.2 Gy and 70.2-79.2 Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse-free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes. Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high-risk patients; however, an overall survival advantage was not observed.	\N	\N
21890816	A multicentre cohort follow-up study of a large number of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma was conducted to elucidate the long-term outcome of the disease after Helicobacter pylori eradication. 420 patients with gastric low-grade MALT lymphoma who had undergone successful H pylori eradication and been followed up for at least 3 years were registered from 21 participating institutes. Responders to treatment were defined as patients whose post-treatment biopsies showed complete histological response (ChR) or probable minimal residual disease (pMRD). Treatment failure was defined as the status of progressive disease or lymphoma relapse after ChR/pMRD. 323 patients (77%) responded to H pylori eradication. A logistic regression analysis showed that absence of H pylori, submucosal invasion determined by endoscopic ultrasonography and t(11;18)/API2-MALT1 were independent predictors of resistance to H pylori eradication. During the follow-up periods ranging from 3.0 to 14.6 years (mean 6.5 years, median 6.04 years), the disease relapsed in 10 of 323 responders (3.1%) while progressive disease was found in 27 of 97 non-responders (27%). Thus, 37 of 420 patients (8.8%) were regarded as treatment failures. Of these 37 patients, transformation into diffuse large B cell lymphoma occurred in nine patients. Among the non-responders and relapsed patients, 17 patients were subjected to a 'watch and wait' strategy while 90 patients underwent second-line treatments including radiotherapy (n=49), chemotherapy (n=26), surgical resection (n=6), chemoradiotherapy (n=5), antibiotic treatment (n=2), rituximab monotherapy (n=1) or endoscopic resection (n=1). Probabilities of freedom from treatment failure, overall survival and event-free survival after 10 years were 90%, 95% and 86%, respectively. Cox multivariate analysis revealed endoscopic non-superficial type to be an independent prognostic factor for adverse freedom from treatment failure, overall survival and event-free survival. The excellent long-term outcome of gastric MALT lymphoma after H pylori eradication was confirmed by this large-scale follow-up study.	\N	\N
21896508	The interaction between transcription factor (TF) and transcription factor binding site (TFBS) is essential for gene regulation. Mutation in either the TF or the TFBS may weaken their interaction and thus result in abnormalities. To maintain such vital interaction, a mutation in one of the interacting partners might be compensated by a corresponding mutation in its binding partner during the course of evolution. Confirming this co-evolutionary relationship will guide us in designing protein sequences to target a specific DNA sequence or in predicting TFBS for poorly studied proteins, or even correcting and rescuing disease mutations in clinical applications. Based on six, publicly available, experimentally validated TF-TFBS binding datasets for the basic Helix-Loop-Helix (bHLH) family, Homeo family, High-Mobility Group (HMG) family and Transient Receptor Potential channels (TRP) family, we showed that the evolutions of the TFs and their TFBSs are significantly correlated across eukaryotes. We further developed a mutual information-based method to identify co-evolved protein residues and DNA bases. This research sheds light on the dynamic relationship between TF and TFBS during their evolution. The same principle and strategy can be applied to co-evolutionary studies on protein-DNA interactions in other protein families. All the datasets, scripts and other related files have been made freely available at: http://jjwanglab.org/co-evo. junwen@uw.edu. Supplementary data are available at Bioinformatics online.	\N	\N
21904924	The distribution of complement component 4 (C4) gene copy number (GCN) has been validated in European populations. Meanwhile, C4 gene has been identified as a susceptibility gene for systemic lupus erythematosus (SLE). However, the association and the possible phenotype significance remain to be determined intensely in the Chinese population. This study was designed to validate the distribution of C4 GCNs in Chinese Han and the correlation between C4 GCNs and SLE using quantitative real-time polymerase chain reaction in 924 SLE patients and 1,007 controls. The results presented distribution of C4 GCNs in healthy populations and also showed that lower C4 GCN was a risk factor for SLE and higher C4 GCN was a protective factor against the disease susceptibility, which was similar to the report in the Caucasian population. Furthermore, we found the association between C4A GCN and disease subphenotypes of arthritis with SLE. We conclude that the association of C4 GCN with SLE was replicated in Chinese Han population, which highlighted the importance of C4 in SLE pathogenesis of diverse populations.	\N	\N
21912125	Women undergoing isolated coronary artery bypass graft (CABG) surgery have been previously shown to be at an independently increased risk for post-operative morbidity and mortality. However, there are considerably less data on whether this trend remains true in patients undergoing concomitant aortic valve replacement (AVR) and CABG surgery. The aim of our study was to investigate this pertinent issue. Data obtained between June 2001 and December 2009 by the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program were retrospectively analysed. Demographic, operative data and post-operative complications were compared between male and female patients using χ(2) and t tests. Long-term survival analysis was performed using Kaplan-Meier survival curves and the log-rank test. Independent risk factors for short- and long-term mortality were identified using binary logistic and Cox regression, respectively. Concomitant AVR and CABG surgery was undertaken in 2,563 patients; 31.8% were female. Female patients were older (mean age 76 vs. 73 years; p < 0.001) and presented more often with hypertension (p < 0.001) but less often with severely impaired ejection fraction (p < 0.001), peripheral vascular disease (p < 0.001) and triple vessel disease (p < 0.001). Women did not demonstrate an increased risk of 30-day mortality (4.8 vs. 3.3%) on univariate (p = 0.069) or multivariate (p = 0.236) analysis. Female gender was independently associated with post-operative myocardial infarction (p = 0.022) and red blood cell transfusion (p < 0.001). There was no difference in long-term survival between men and women on multivariate analysis (p = 0.413). Female gender is not associated with poorer short- or long-term outcomes after concomitant CABG and AVR surgery.	\N	\N
21913717	Hepatocellular carcinoma (HCC) is one of the leading causes of mortality from solid organ malignancy worldwide. Because of the complexity of proteins within liver cells and tissues, the discovery of therapeutic targets of HCC has been difficult. To investigate strategies for decreasing the complexity of tissue samples for detecting meaningful protein mediators of HCC, we employed subcellular fractionation combined with 1D-gel electrophoresis and liquid chromatography-tandem mass spectrometry analysis. Moreover, we utilized a statistical method, namely, the Power Law Global Error Model (PLGEM), to distinguish differentially expressed proteins in a duplicate proteomic data set. Mass spectrometric analysis identified 3045 proteins in nontumor and HCC from cytosolic, membrane, nuclear, and cytoskeletal fractions. The final lists of highly differentiated proteins from the targeted fractions were searched for potentially translocated proteins in HCC from soluble compartments to the nuclear or cytoskeletal compartments. This analysis refined our targets of interest to include 21 potential targets of HCC from these fractions. Furthermore, we validated the potential molecular targets of HCC, MATR3, LETM1, ILF2, and IQGAP2 by Western blotting, immunohistochemisty, and immunofluorescent microscopy. Here we demonstrate an efficient strategy of subcellular tissue proteomics toward molecular target discovery of one of the most complicated human disease, HCC.	\N	\N
21915990	Investigations of rare cell types in peripheral blood samples, such as tumor, fetal, and endothelial cells, represent an emerging field with several potentially valuable medical applications. Peripheral blood is a particularly attractive body fluid for the detection of rare cells as its collection is minimally invasive and can be repeated throughout the course of the disease. Because the number of rare cells in mononuclear cells can be very low (1 in 10 million), a large number of cells must be quickly screened, which places demanding requirements on the screening technology. While enrichment technology has shown promise in managing metastatic disease, enrichment can cause distortions of cell morphology that limit pathological identification, and the enrichment targeting adds additional constraints that can affect sensitivity. Here, we describe a new approach for detecting rare leukemia cells that does not require prior enrichment. We have developed an immunocytochemical assay for identification of leukemia cells spiked in peripheral blood samples, and a high-speed scanning instrument with high numerical aperture and wide field of view to efficiently locate these cells in large sample sizes. A multiplex immunoassay with four biomarkers was used to uniquely identify the rare cells from leukocytes and labeling artifacts. The cytometer preserves the cell morphology and accurately locates labeled rare cells for subsequent high resolution imaging. The sensitivity and specificity of the approach show promise for detection of a low number of leukemia cells in blood (1 in 10 million nucleated cells). The method enables rapid location of rare circulating cells (25 M cells/min), no specific enrichment step, and excellent imaging of cellular morphology with multiple immunofluorescent markers. The cell imaging is comparable to other imaging approaches such as laser scan cytometry and image flow cytometry, but the cell analysis rate is many orders of magnitude faster making this approach practical for detection of rare cells.	\N	\N
21916327	Serum dioxin studies of Vietnam (VN) veterans, military historical records of tactical herbicide use in Vietnam, and the compelling evidence of the photodegradation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aspects of environmental fate and low bioavailability of TCDD are consistent with few, if any, ground troop veterans being exposed to Agent Orange. That conclusion, however, is contrary to the presumption by the Department of Veterans Affairs (DVA) that military service in Vietnam anytime from January 9, 1962 to May 7, 1975 is a proxy for exposure to Agent Orange. The DVA assumption is inconsistent with the scientific principles governing determinations of disease causation. The DVA has nonetheless awarded Agent Orange-related benefits and compensation to an increasing number of VN veterans based on the presumption of exposure and the published findings of the Institute of Medicine that there is sufficient evidence of a "statistical association" (a less stringent standard than "causal relationship") between exposure to tactical herbicides or TCDD and 15 different human diseases. A fairer and more valid approach for VN veterans would have been to enact a program of "Vietnam experience" benefits for those seriously ill, rather than benefits based on the dubious premise of injuries caused by Agent Orange.	\N	\N
21917357	To know the relative weight of the diagnosis of detrusor overactivity (DO) in the Urodynamic Units of Spain and relate the prevalence of the overactive bladder (OB) syndrome. An epidemiological, descriptive, retrospective, multicenter, national study conducted according to registered data in 47 Urodynamic Units covering the Spanish geographic area in the different areas of health distributed among the regional communities. These data inform about the health care received by 35% of the Spanish population. Urodynamic diagnoses and related variables, recorded during 2007 and 2008, were collected. A mean of 346.45 (SD=304.03) and 349.72 (SD=296.49) urodynamics studies per care unit were performed in women during 2007 and 2008, respectively and 181.20 (SD=212.71) and 195.68 (SD=257.58) in men. The relative weight of the diagnosis of non-neurogenic DO in women per unit was 31.39% and 35.28%, in 2007 and 2008, and in men was 21.06% and 20.43%. The diagnostic capacity of DO was 19.28 new cases per 100,000 inhabitants/year. The diagnosis of non-neurogenic DO in the woman accounts for one third of all the urodynamic/year diagnoses and more than half of the diagnoses of DO. In men, DO accounts for 25% of the diagnoses, the most frequent one being that associated with benign prostatic hyperplasia, followed by that of neurogenic cause. Approximately half of the DO diagnoses in children correspond to non-neurogenic DO. The differences between the capacity of diagnosis of DO (ratio per 100,000 inhabitants) is far from many of the estimations of the prevalence of OB (relationship %). The doubt may exist about whether part of this quota is secondary and not-idiopathic, given the large difference between the frequency of OB and the capacity of diagnosis of DO.	\N	\N
21917441	Idiopathic pulmonary fibrosis (IPF) is a lethal lung disorder of unknown etiology. The disease is likely the result of complex interactions between genetic and environmental factors. Evidence suggests that certain environmental factors, such as cigarette smoking and metal dust exposures, or comorbidities like gastroesophageal reflux, and type 2 diabetes mellitus (DM2) may increase risk to develop IPF. Substantial uncertainty remains, however, regarding these and other putative risk factors for IPF. In this study we performed a case-control analysis including 100 patients with IPF and 263 controls matched for age sex and place of residence. We used a structured questionnaire to identify potential risk factors for IPF, including environmental and occupational exposures as well as the relevance of family history of pulmonary fibrosis. The multivariate analysis revealed that family history of pulmonary fibrosis [OR = 6.1, CI95% 2.3-15.9; p < 0.0001] was strongly associated with increased risk of IPF. Actually, 20% of the cases reported a parent or sibling with pulmonary fibrosis. Gastroesophageal reflux [OR = 2.9, CI: 1.3-6.6; p = 0.007], former cigarette smoking [OR = 2.5, CI: 1.4-4.6, p = 0.003], and past or current occupational exposure to dusts, smokes, gases or chemicals [OR = 2.8, CI: 1.5-5.5; p = 0.002] were also associated with the disease. Despite being a significant risk factor on univariate analysis DM2 was not significant in multivariate analysis. These findings indicate that family history of pulmonary fibrosis is a strong risk factor for IPF. Also, we confirmed that occupational exposures, gastroesophageal reflux and former smoking increase the risk for this disease.	\N	\N
21918487	Although the use of embryonic stem cells to treat disease has caused much controversy, one type of stem cell treatment has slowly and steadily shown promise but has not engendered negative ethical media attention: the use of umbilical stem cells. Umbilical cord blood (UCB) contains stem cells that have already successfully treated a variety of diseases, including leukemias, lymphomas, hemoglobinopathies, immunodeficiencies, and disorders of metabolism; ongoing research continues to explore additional diseases for potential treatment. Cord blood can be stored in private banks or public banks. Private cord blood banks save cord blood for use by the family only, at a cost. Public cord blood banks accept donations and the cord blood is then used for the general public and/or research. A review of the literature finds that public banking is the preferred recommendation over private unless there is a known family member with a disease that can currently be treated with cord blood. This article discusses cord blood banking options as well as the ethical issues and barriers facing both healthcare providers and patients when dealing with cord blood banking.	\N	\N
21924425	Recent genome-wide association studies (GWAS) have identified associations with myocardial infarction and coronary artery disease (CAD), but the mechanisms underlying these associations remain largely unclear. Carotid intima-media thickness (IMT) is a measure of early arterial remodeling and arteriosclerosis. Therefore, if CAD associated SNPs are also associated with carotid IMT; it suggests that they are acting via the early stages of the atherosclerotic process. In three large community based independent populations (CAPS, KORA and Young Finns) of European ancestry in which common carotid IMT had been measured (total 4961 individuals), we determined whether SNPs that have been associated with CAD in GWAS studies are also associated with carotid IMT. Associations with plaque were not examined. We identified 11 SNPs and one haplotype previously associated with CAD. None of these were associated with common carotid IMT. We found no evidence that SNPs associated with CAD on GWAS are also associated with carotid IMT. This suggests these genetic associations are not acting via early vessel remodeling or early arteriosclerosis.	\N	\N
21925097	The aim of this pilot study was to evaluate the feasibility of long-term subcutaneous application of low-dose IL-2 in children with malignancies at very high risk of relapse who underwent highly T cell and B cell depleted HLA-identical (MUD) or full haplotype mismatched related hematopoetic stem cell transplantation. We studied 11 patients with acute leukemias / myelodysplastic syndrome and juvenile myelomonocytic leukemia (active disease and/or second stem cell transplantation, n = 8; ≥CR 2, n = 2) and relapsed or progressive Ewing's sarcoma (n = 2) who received prophylactic IL-2 treatment for a high probability of disease recurrence after allo-HSCT. Toxicities from IL-2 were transient fever, fatigue and local inflammation. In one patient GvHD grade III with no clear association to IL-2 administration occurred. IL-2 administration was started at median day 57 (range 13-154) post-transplant for a mean duration of 28 days (range 15-250). IL-2 administration clearly increased NK cell activity. 3 of 11 patients (ALL, AML, multifocal Ewings sarcoma) survived with a follow-up of ten years. In conclusion, long-term low-dose IL-2 subcutaneous application is feasible in children due to a low side effect profile even after HLA mismatched transplantation and may be a strategy to prevent relapse in pediatric malignancies with extremely high risk of relapse.	\N	\N
21926372	Ryanodine receptor 1 (RyR1) is a Ca(2+) release channel located in the sarcoplasmic reticulum membrane of skeletal muscle. More than 200 variants in RyR1 have been identified in DNA from patients with malignant hyperthermia (MH) and congenital myopathies; only 30 have been sufficiently studied so as to be identified as MH-causative mutations. The Ala4894Thr RyR1 variant was found in a Japanese patient with susceptibility to MH, and the Ala4894Pro variant in a rare case of myopathy: congenital neuromuscular disease with uniform type 1 fiber (CNMDU1). We hypothesized that different Ala4894 variants of RyR1 cause different pathophysiological changes that are identifiable by having differing pharmacological sensitivities to RYR1 agonists. Expression vector with a mutation in RYR1 corresponding to the Ala4894Thr, Ala4894Pro, Ala4894Ser, or Ala 4894Gly variant of human RyR1 was transfected into human embryonic kidney 293 cells. At 72 hours after transfection, we determined the intracellular Ca(2+) changes induced by caffeine and 4-chloro-m-cresol (4CmC), in the presence or absence of dantrolene. Ala4894Thr-transfected cells and Ala4894Ser-transfected cells were more sensitive to caffeine than the wild type, and Ala4894Thr-transfected cells were also more sensitive to 4CmC than the wild type, whereas Ala4894Pro-transfected cells had no response to caffeine or 4CmC. Ala4894Gly-transfected cells were significantly less sensitive to caffeine than the wild type. In addition, the responses of Ala4894Thr-transfected cells and Ala4894Ser-transfected cells to caffeine were suppressed by dantrolene. We concluded that different Ala4894 variants of RyR1 lead to different agonist/antagonist sensitivities, which may predict differing RYR1 functionality during excitation-contraction coupling and sensitivity to MH. The hypersensitive Ala4894Thr-RyR1 is associated with MH and the poorly functional Ala4894Pro-RyR1 with CNMDU1.	\N	\N
21934067	The role of CRP as a regulator of inflammation is not fully understood. Structural rearrangement in CRP results in expression of potent proinflammatory actions. Proteolysis of CRP yields the C-terminal peptide Lys(201)-Pro-Gln-Leu-Trp-Pro(206). Here, we investigated the impact of this peptide on neutrophil interactions with endothelial cells and platelets, critical inflammatory events triggering acute coronary artery disease. CRP peptide 201-206 induced L-selectin shedding from human neutrophils and inhibited L-selectin-mediated neutrophil adhesion to TNF-α-activated HCAECs under nonstatic conditions. CRP peptide 201-206 also attenuated shear-induced up-regulation of platelet P-selectin expression, platelet capture of neutrophils, and subsequent homotypic neutrophil adhesion in human whole blood. Anti-CD32 but not anti-CD16 or anti-CD64 mAb effectively prevented the inhibitory actions of CRP peptide 201-206. Substitution of Lys(201), Gln(203), or Trp(205) with Ala in CRP peptide 201-206 resulted in loss of the biological activities, whereas peptides in which Pro(202), Leu(204), or Pro(206) was substituted with Ala retained biological activity. We identified amino acid residues involved in CRP peptide 201-206-FcγRII (CD32) interactions, which mediate potent antineutrophil and antiplatelet adhesion actions, and these findings open up new perspectives for limiting inflammation and thrombosis underlying coronary artery disease.	\N	\N
21935854	A 65-year-old woman presented with reduced general condition and dyspnoea that was progressive over the last months. Clinical findings revealed an exophthalmus on the right, xanthelasm and mild peripheral oedema. Previously, a pericardiocentesis had been performed due to a large pericardial effusion. A previous CT scan showed a mass attached to the pericardium extending through the atrio-ventricular groove and a thickened aorta. In addition, a retroperitoneal fibrosis and an occlusion of both Aa. iliacae internae were found. The ECG showed sinus rhythm. Laboratory findings demonstrated a microcytic anemia and a renal failure. Chest radiography showed a large cardiac silhouette, while the transthoracic echocardiography revealed a recurrent large pericardial effusion. A PET/CT scan of the chest and abdomen showed a tissue infiltration of the retroperitoneal structures, a mass surrounding the right coronary artery and the right orbita. Finally, a femur biopsy confirmed the diagnosis of Erdheim-Chester disease. With the diagnosis Erdheim-Chester disease we started a high dose immunsuppressive therapy using glucocorticoids and interferon-a. Tumour size slightly decreased during the following 2 months, however the patient developed a severe urosepsis and died from multiorgan failure. We report a case of an Erdheim-Chester disease with cardiovascular involvement primarily diagnosed due to a recurrent large pericardial effusion. In case of cardial tumors with interatrial septum or coronary artery involvement together with cerebral manifestations, an Erdheim-Chester disease should be taken into account.	\N	\N
21938677	Cyclosporine A is a potent immunosuppressant used to prevent organ transplant rejection and treat various autoimmune diseases. However, cyclosporine A can also induce gingival overgrowth, which is characterized by increased extracellular matrix due to an altered balance between collagen synthesis and degradation. This study proposed to verify whether trans-glutaminase 2, an enzyme thought to be responsible for the assembly and remodelling of extracellular matrix, plays any role in the pathogenesis of cyclosporine A-induced gingival overgrowth. Cyclosporine A-induced gingival overgrowths were collected from 21 liver transplant patients and case-controlled with 20 non-hyperplastic gingival biopsies from healthy patients who had previous periodontal treatment. In both groups, the presence and tissue distribution of transglutaminase 2 were determined by immunohistochemistry and analyzed in comparison with the tissue morphology and expression of lymphocyte-related antigens (CD3 and CD20) and a vessel-related marker (CD34). Transglutaminase 2 expression showed a significant increase (2.6-fold) in the stromal component of cyclosporine A-treated patients compared with controls (p<0.001), which suggested that transglutaminase 2 had a role in the pathogenesis of the disease. Further studies should investigate the therapeutic effect of anti-transglutaminase 2 drugs (putrescine or 1,4-diamino-butane) in these patients.	\N	\N
21946897	Genetic factors may play a role in fibrosis progression in patients with chronic hepatitis C (CHC). A cirrhosis risk score (CRS7) with seven single nucleotide polymorphisms was previously shown to correlate with cirrhosis in patients with CHC. This study aimed to assess the validity of CRS7 as a marker of fibrosis progression and cirrhosis and as a predictor of clinical outcomes in patients with CHC. A total of 938 patients (677 Caucasians, 165 African-Americans, and 96 Hispanic/Other) in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial were studied. CRS7 was categorized a priori as high risk (n=440), medium risk (n=310), or low risk (n=188). Patients were assessed for four possible outcomes: fibrosis progression, cirrhosis, clinical outcomes [decompensation or hepatocellular carcinoma (HCC)], or HCC alone. Twenty-nine percent (142/493) developed an increase in fibrosis score by greater than or equal to 2 points on follow-up biopsies, 58% had cirrhosis on one or more biopsies, 35% developed at least one clinical outcome, and 13% developed HCC. CRS7 (trend test) was associated with risk for fibrosis progression (P=0.04) with adjusted hazard ratio of 1.27 (95% confidence interval: 1.01-1.58) and with cirrhosis (P=0.05) with adjusted odds ratio of 1.19 (1.00-1.41). Rates of HCC and clinical outcomes were increased in patients with higher CRS7 scores, but were not statistically significant (P=0.12 clinical outcomes, and P=0.07 HCC). A single nucleotide polymorphism in AZIN1 was significantly associated with fibrosis progression. CRS7 was validated as a predictor of fibrosis progression and cirrhosis among Hepatitis C Antiviral Long-term Treatment against Cirrhosis patients, who all had advanced fibrosis. CRS7 was not predictive of clinical outcome.	\N	\N
21953291	Although tumor reduction via present-day prehepatectomy chemotherapy can render initially unresectable disease potentially resectable, little is known about the effects of such chemotherapy on liver metastases with known attachment to or invasion of major intrahepatic vessels. We histologically assessed the relationships of liver tumors to major intrahepatic vessels after chemotherapy. In 45 patients who underwent chemotherapy and hepatectomy with pretreatment images showing metastases attached to or invading major intrahepatic vessels, 77 metastases showed attachment to or invasion of 96 vessels. Using postchemotherapy imaging, 11 of 77 metastases (14.3%) appeared separated from 12 of 96 major hepatic vessels (12.5%). Among 83 vessels later examined pathologically, 29 showed direct invasion (35%) and 10 showed attachment (12%). Tumors involved another 9 vessels (11%) that were separated surgically from the tumor and preserved during hepatectomy. Tumor attachment that exceeded 25% of vessel circumferences via imaging after chemotherapy was a factor associated with pathological vascular invasion or attachment according to multivariate analysis (relative risk, 8.449; 95% confidence interval, 1.961-36.415; P = .0042). Liver metastasis attachment to or invasion of major intrahepatic vessels is difficult to eradicate even with otherwise effective chemotherapy.	\N	\N
21955617	Osteoarthritis (OA) is a degenerative joint disease characterized by progressive loss of articular cartilage, subchondral bone sclerosis, osteophyte formation, and synovial inflammation, causing substantial physical disability, impaired quality of life, and significant health care utilization. Traditionally, non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase (COX)-2 inhibitors, have been used to treat pain and inflammation in OA. Besides its anti-inflammatory properties, evidence is accumulating that celecoxib, one of the selective COX-2 inhibitors, has additional disease-modifying effects. Celecoxib was shown to affect all structures involved in OA pathogenesis: cartilage, bone, and synovium. As well as COX-2 inhibition, evidence indicates that celecoxib also modulates COX-2-independent signal transduction pathways. These findings raise the question of whether celecoxib, and potentially other coxibs, is more than just an anti-inflammatory and analgesic drug. Can celecoxib be considered a disease-modifying osteoarthritic drug? In this review, these direct effects of celecoxib on cartilage, bone, and synoviocytes in OA treatment are discussed.	\N	\N
21959310	We report 9 patients with pleural biopsies referred because of concern about infiltration of what appeared to be chest wall fat by pan-keratin-positive spindled cells, a finding that led to a consideration of desmoplastic mesothelioma. All patients showed pleural effusions/pleural thickening on computed tomographic scan. Pleural biopsy showed a greatly thickened and fibrotic paucicellular pleura with circular fat-like spaces and, sometimes, adjacent oblate spaces mostly deep in the fibrotic area. Indistinct, keratin-positive, spindle cells arranged parallel to the pleural surface coursed between these fat-like spaces. S-100 stains were negative around the fat-like spaces. Vimentin stains showed that the spaces did not have a cellular lining of any kind. Sometimes the spaces contained faintly hematoxyphilic material that was Alcian blue positive, and similar material was seen in the fibrotic stroma. Follow-up with periods ranging from 6 to 30 months revealed that 8 cases had stable disease on chest imaging or by clinical findings. One case had slowly progressive pleural thickening. These observations suggest that spaces resembling fat may be encountered in fibrotic pleurae and that horizontally oriented keratin-positive spindled cells between the fat-like spaces deep in the fibrotic portion of a thickened pleura represent a benign finding seen in some cases of organizing pleuritis/fibrothorax. The spaces themselves are probably artifacts derived from the biopsy procedure and/or cutting artifacts. In contrast, in true desmoplastic mesotheliomas there is downward, rather than horizontal, growth of keratin-positive spindled cells running between clearly definable fat cells.	\N	\N
21963153	Multimorbidity is increasing in frequency. It can be quantitatively measured and is a major correlate of high use of health services resources of all types, especially over time. The ACG System for characterizing multimorbidity is the only widely used method that is based on combinations of different TYPES of diagnoses over time, rather than the presence or absence of particular conditions or numbers of conditions. It incorporates administrative data (as from claims forms or medical records) on all types of encounters and is not limited to diagnoses captured during hospitalizations or other places of encounter. It can be employed in any one or combination of analytic models, and can incorporate medication use if desired. It is being used in clinical care, management of health services resources, in health services research to control for degree of morbidity, and in understanding morbidity patterns over time. In addition to its research uses, it is being employed in many countries in various applications as a policy to better understand health needs of populations and tailor health services resources to health needs.	\N	\N
21970661	Toxoplasma gondii is a major cause of chronic parasitic infection in the world. This protozoan can cause retino-choroiditis in newborns and in adults, both immunocompetent and immunodeficient. This disease tends to be recurrent and can lead to severe visual impairment. The authors review current knowledge on the role of parasite genetics in influencing susceptibility to ocular toxoplasmosis and on the immuno-pathogenesis of this disease.	\N	\N
21971930	The development of drug resistance represents a major complication in the effective treatment of breast cancer. Epigenetic therapy, through the use of histone deacetylase inhibitors (HDACi) or demethylation agents, is an emerging area of therapeutic targeting in a number of ontological entities, particularly in the setting of aggressive therapy-resistant disease. Using the well-described HDAC inhibitor trichostatin A (TSA) we demonstrate the suppression of in vitro clonogenicity in the previously described apoptosis-resistant MCF-7TN-R breast carcinoma cell line. Additionally, recent work has demonstrated that these agents can alter the expression profile of microRNA signatures in malignant cells. Using an unbiased microRNA microarray analysis, changes in miRNA expression of MCF-7TN-R cells treated with TSA for 24 h were analyzed. We observed significant up-regulation of 22 miRNAs and down-regulation of 10 miRNAs in response to TSA treatment. Our results demonstrate that the HDACi, TSA, exerts anticancer activity in the apoptosis-resistant MCF-7TN-R breast carcinoma cell line. This activity is correlated with TSA alteration of microRNA expression profiles indicative of a less aggressive phenotype.	\N	\N
21973247	Mortality level and cause of death trends are evaluated to chart the epidemiological transition in Fiji. IMPLICATIONS for current health policy are discussed. Published data for infant mortality rate (IMR), life expectancy (LE) and causes of death for 1940-2008 were assessed for quality, and compared with mortality indices generated from recent Ministry of Health death recording. Trends in credible mortality estimates are compared with trends in proportional mortality for cause of death. IMR declined from 60 deaths (per 1,000) in 1945 to below 20 by 2000. IMR for 2006-08 is estimated at 18-20 deaths per 1,000 live births. Excessive LE estimates arise by imputing from the IMR using inappropriate models. LE increased, but has been stable at 64 years for males and 69 years for females since the late 1980s and early 1990s respectively. Proportional mortality from diseases of the circulatory system has increased from around 20% in the 1960s to more than 45%. Extensive variation in published mortality estimates was indentified, including clearly incompatible ranges of IMR and LE. Mortality decline has stagnated. Relatively low IMR and proportional mortality trends suggest this is largely due to chronic diseases (especially cardiovascular) in adults. Reconciliation of mortality data in Fiji to reduce uncertainty is urgently needed. Fiji's health services and donor partners should place continued and increased emphasis on effective control strategies for cardiovascular disease.	\N	\N
21978795	Objective of this study was to evaluate the acute cardiovascular and respiratory effects of switching on the deep brain stimulation in the follow up of nine Parkinson's disease patients with subthalamic nucleus stimulation and six cluster headache patients with posterior hypothalamic area stimulation. Systolic and diastolic blood pressure, heart rate, and respiratory rate were monitored continuously during supine rest in both groups. Each patient was assessed in two conditions: resting supine with stimulator off and with stimulator on. In supine resting condition switching on the DBS induced no significant changes (p>0.05) in systolic and diastolic blood pressure as well as in heart rate and respiratory rate, in both groups of patients, either taking 1 min or 10 heartbeats as a sample for analysis. Switching on the DBS does not modify heart rate, blood pressure nor respiratory rate in both Parkinson and cluster headache patients under resting conditions.	\N	\N
21985741	Rarely, a patient presents to a surgeon for evaluation of an adrenal incidentaloma where the final pathology is primary malignancy. For primary adrenal lymphoma, fewer than 100 cases have been reported in the literature. We report a case of unilateral primary adrenal aggressive B cell lymphoma discovered incidentally in a 41-year-old female. Preoperative testing demonstrated the 6-cm mass to be biochemically silent. Subsequently, the patient underwent a laparoscopic adrenalectomy. Following pathologic diagnosis of B cell lymphoma, a metastatic workup was negative, and she underwent treatment with systemic chemotherapy. She is currently disease free 6 months postoperatively. Primary adrenal lymphoma should be considered in patients with unilateral adrenal incidentaloma. We believe that adherence to guidelines of resection of incidentalomas allowed for early surgical intervention and possible cure.	\N	\N
21986202	Parkinson's disease is a common neurodegenerative disorder characterized by α-synuclein (α-Syn)-containing Lewy body formation and selective loss of dopaminergic neurons in the substantia nigra. We have demonstrated the modulating effect of noopept, a novel proline-containing dipeptide drug with nootropic and neuroprotective properties, on α-Syn oligomerization and fibrillation by using thioflavin T fluorescence, far-UV CD, and atomic force microscopy techniques. Noopept does not bind to a sterically specific site in the α-Syn molecule as revealed by heteronuclear two-dimensional NMR analysis, but due to hydrophobic interactions with toxic amyloid oligomers, it prompts their rapid sequestration into larger fibrillar amyloid aggregates. Consequently, this process rescues the cytotoxic effect of amyloid oligomers on neuroblastoma SH-SY5Y cells as demonstrated by using cell viability assays and fluorescent staining of apoptotic and necrotic cells and by assessing the level of intracellular oxidative stress. The mitigating effect of noopept against amyloid oligomeric cytotoxicity may offer additional benefits to the already well-established therapeutic functions of this new pharmaceutical.	\N	\N
21987744	The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections.	\N	\N
21994137	Proctitis is a common problem and is most frequently associated with inflammatory bowel diseases. However, the incidence of infectious proctitis appears to be rising, especially in men who have sex with men. This may be due to the rise of people participating in receptive anal sex as well as the increase in sexually transmitted infections. The most frequently reported pathogens include Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, and herpes simplex. Symptoms of infectious proctitis can include rectal blood and mucous discharge, anorectal pain, ulcers, and occasionally lymphadenopathy and fever. History and physical examination are crucial in establishing a diagnosis, supported by endoscopy, histology, serology, culture and PCR. Treatment with antibiotics or antivirals is usually initiated, either empirically or after establishing a diagnosis. Co-infections, HIV testing, and treatment of sexual partners should always be considered.	\N	\N
22002662	The destruction of blood-brain barrier (BBB) and blood-nerve barrier (BNB) has been considered to be a key step in the disease process of a number of neurological disorders including cerebral ischemia, Alzheimer's disease, multiple sclerosis, and diabetic neuropathy. Although glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) facilitate neuronal or axonal regeneration in the brain or peripheral nerves, their action in the BBB and BNB remains unclear. The purpose of the present study was to elucidate whether these neurotrophic factors secreted from the brain or peripheral nerve pericytes increase the barrier function of the BBB or BNB, using our newly established human brain microvascular endothelial cell (BMEC) line or peripheral nerve microvascular endothelial cell (PnMEC) line. GDNF increased the expression of claudin-5 and the transendothelial electrical resistance (TEER) of BMECs and PnMECs, whereas BDNF did not have this effect. Furthermore, we herein demonstrate that the GDNF secreted from the brain and peripheral nerve pericytes was one of the key molecules responsible for the up-regulation of claudin-5 expression and the TEER value in the BBB and BNB. These results indicate that the regulation of GDNF secreted from pericytes may therefore be a novel therapeutic strategy to modify the BBB or BNB functions and promote brain or peripheral nerve regeneration.	\N	\N
22010196	The eukaryotic cell is organized into membrane-covered compartments that are characterized by specific sets of proteins and biochemically distinct cellular processes. The appropriate subcellular localization of proteins is crucial because it provides the physiological context for their function. In this Commentary, we give a brief overview of the different mechanisms that are involved in protein trafficking and describe how aberrant localization of proteins contributes to the pathogenesis of many human diseases, such as metabolic, cardiovascular and neurodegenerative diseases, as well as cancer. Accordingly, modifying the disease-related subcellular mislocalization of proteins might be an attractive means of therapeutic intervention. In particular, cellular processes that link protein folding and cell signaling, as well as nuclear import and export, to the subcellular localization of proteins have been proposed as targets for therapeutic intervention. We discuss the concepts involved in the therapeutic restoration of disrupted physiological protein localization and therapeutic mislocalization as a strategy to inactivate disease-causing proteins.	\N	\N
22011558	Although moderate alcohol drinkers have lower rates of incident coronary artery disease than abstainers, much less is known about the health effects of different patterns of alcohol use in women with established coronary artery disease. In the Determinants of Myocardial Infarction Onset Study, 1,253 women hospitalized for acute myocardial infarction (MI) at 64 centers nationwide from 1989 to 1996 were followed for mortality through December 31, 2007. Of the women, 761 (61%) reported abstention in the year before their MIs, 280 (22%) reported consumption of <1 serving/week, 75 (6%) reported consumption of 1 to 3 servings/week, and 137 (11%) reported consumption of ≥3 servings/week. Using Cox proportional-hazards models, the associations between total weekly volume of consumption, drinking days per week, drinks per drinking day, and beverage type with 10-year mortality were investigated, adjusting for clinical and socioeconomic potential confounders. Compared with abstention, adjusted hazard ratios were 0.66 (95% confidence interval 0.50 to 0.86) for <1 serving/week, 0.65 (95% confidence interval 0.38 to 1.11) for 1 to 3 servings/week, and 0.65 (95% confidence interval 0.38 to 1.11) for ≥3 servings/week (p for trend = 0.008). No differences were found by beverage type, and generally inverse associations of drinking frequency and quantity with mortality were found. In conclusion, in women who survive MI, moderate drinking is associated with a decreased risk for mortality, with no clear differences on the basis of pattern or beverage type. These results suggest that women who survive MI need not abstain from alcohol, but any derived benefit would appear to occur well below currently recommended limits in alcohol consumption.	\N	\N
22015458	Cholangitis arising from biliary infection dominates the prognosis in Caroli's disease. To clarify the influences of bacterial infection on the biliary cystogenesis, in vivo and in vitro studies were performed using the polycystic kidney (PCK) rat as an animal model of Caroli's disease. Cholangitis became a frequent histological finding in aged PCK rats, and neovascularization around the bile ducts also increased in aged PCK rats. Immunohistochemistry revealed that expression of vascular endothelial growth factor (VEGF) was increased in PCK rat biliary epithelium. In vitro, PCK cholangiocytes overexpressed VEGF, and the supernatant of cultured PCK cholangiocytes significantly increased the proliferative activity, migration, and tube formation of cultured rat vascular endothelial cells. Stimulation with lipopolysaccharide (LPS) further induced VEGF expression in PCK cholangiocytes, which might be mediated by signaling pathways involving phosphatidylinositol 3-kinase (PI3K)-Akt and c-Jun N-terminal kinase (JNK). Both LPS and VEGF increased cell proliferative activity in PCK cholangiocytes, and siRNA against VEGF significantly reduced LPS-induced cell proliferation. Thus, LPS-induced overexpression of VEGF in the biliary epithelium may lead to hypervascularity around the bile ducts; concurrently, LPS and VEGF act as cell proliferation factors for cholangiocytes. Biliary infection may thus exacerbate biliary cystogenesis in PCK rats.	\N	\N
22016594	We investigated the clinical characteristics and prognosis of elderly patients with acute lymphoblastic leukemia (ALL). We reviewed the clinical data, laboratory findings, bone marrow findings, and cytogenetic analysis of elderly patients (≥ 60 years) with ALL, and data of an additional 101 younger adult patients (< 60 years) with ALL were reviewed for comparison. Twenty-six elderly patients (≥ 60 years) and 101 younger adult patients (< 60 years) with ALL were retrospectively enrolled. The median follow-up duration was 6.0 months (range, 0.4 to 113.2) in the elderly patients and 21.7 months (range, 1.0 to 122.7) in the adult patients. In total, 34.6% (9 patients) of the elderly patients and 24.8% (25 patients) of the adult patients had Philadelphia chromosome positive ALL. The overall complete remission (CR) rate was much higher in the younger than in the elderly patients (94.1% vs. 57.7%, p < 0.001). The median overall survival (OS) of the younger patients (< 60 years) was 26.3 months, whereas that of the elderly patients (≥ 60 years) was 10.3 months (p = 0.003). In the elderly patients with ALL, T cell lineage and the presence of lymphadenopathy were significant prognostic factors for OS in a univariate analysis (p = 0.033 and 0.041, respectively). The outcomes of Korean elderly patients with ALL were poor, and the shorter OS was mainly due to the low CR rate. T-cell lineage and the presence of lymphadenopathy were significant prognostic factors in Korean elderly patients with ALL.	\N	\N
22017219	Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene. Key symptoms of mania were rated in two sets of medicated bipolar disorder patients (n=171 and n=475) at two specialized outpatient clinics for affective disorders and three regular psychiatric outpatient units in Sweden. The relationships between all manic symptoms according to DSM-IV were entered in a principal component analysis. We used a case-case model to reduce the genetic heterogeneity and tested associations between four factors related to manic symptoms and their association to four single nucleotide polymorphisms in the P2RX7 gene. The combination of the cognitive symptoms, distractibility, talkativeness, and thought disorder was significantly associated with rs1718119 in the P2RX7 gene in Set 1 [odds ratio (OR) = 1.78; p=0.011]. The association was re-tested in the second set (OR = 1.42; p=0.009). In the total sample, the association was even stronger (OR = 1.49; p<0.001). None of the other factors was associated with the P2RX7 gene. Within the first factor, the distractibility symptom accounted for a significant portion of the association to rs1718119 (p=0.016). There is an association between specific symptoms of bipolar disorder and the P2RX7 gene. This finding may open up new approaches to elucidating the neurobiology behind bipolar symptoms.	\N	\N
22018216	Although endoscopy and angiography have changed the management of lower gastrointestinal bleeding and the majority of patients respond to conservative treatment 10-20% of cases have no recognizable site of hemorrhage. About 10-30% of all patients will require operative intervation. A very rare case of massive lower gastrointestinal bleeding in a young patient who was found to suffer from two causes of gastrointestinal hemorrhage in the same time is reported. The patient had to undergo surgery for the control of bleeding. A 23 years old male Greek patient presented to the emergency department of our hospital because of three episodes of hematochezia during the last 10 hours. He was admitted to the surgical department for monitoring of his condition. In the next 10 hours the hematochezia continued and the patient although being transfused with three units of packed red blood cells, started to become unstable with his vital signs affected, having also a syncoptic episode. Emergent colonoscopy could not recognize the site of hemorrhage or any other pathology in the colon, but revealed an intestinal lumen full of blood from the anus to the cecum. It was decided that the patient should undergo operation to stop bleeding. An extensive right hemicolectomy was performed. After that the patient remained stable and showed no signs of hemorrage. The histopathological examination of the specimen showed an arteriovenous malformation but also lesions of the mucosa compatible with early inflammatory bowel disease. In young patients with massive lower gastrointestinal bleeding of unknown origin, extensive right hemicolectomy provides a good and safe therapeutic choice that will control hemorrhage in most cases with the advantage of lower mortality and morbidity rates compared to subtotal colectomy. Close monitoring of the patient postoperatively is essential.	\N	\N
22023956	Atherosclerotic carotid artery disease remains an important cause of cerebrovascular ischemic disease. We present a patient with residual stenosis of the distal internal carotid artery following carotid endarterectomy that was treated with stenting. The case highlights the potential complimentary benefits of carotid endarterectomy and carotid stenting.	\N	\N
22026553	Evidence suggests that occult adenoma remnants are responsible for persistent Cushing's disease (CD) following transsphenoidal surgery (TSS). To optimize the outcome, we have adapted our microsurgical concept. The influence of our surgical strategy on remission rate and pituitary function is presented. 83 patients undergoing TSS for newly diagnosed CD. An enlarged resection was performed in 36 patients. A modified exploration technique with radial incisions was performed in 19 patients in whom an adenoma was not readily detectable. The overall remission rate of primary surgery was 84·3% (70/83). A remission rate of 87·5% (63/72) was achieved in microadenomas. Six patients with microadenomas were re-operated for persistence, and hypercortisolism was corrected in five of them. With re-operation included, the overall remission rate for microadenomas was 94·4%. No procedure-related complications occurred in primary surgery. Of the patients in remission, 72·5% had early postoperative random cortisol levels below 2 μg/dl, 17·4% had cortisol levels between 2 and 5 μg/dl, and 10·1% had cortisol levels >5 μg/dl. 15·2% of the patients with microadenomas developed postoperative partial hypopituitarism and 3% diabetes insipidus. No increased rate of hypopituitarism was found with enlarged adenomectomy compared to selective adenomectomy. Only a slightly higher rate of partial hypopituitarism (23·1%) was found if extensive exploration was required. With our microsurgical concept, a high initial cure rate is achievable with minimal surgical morbidity. Enlarged adenomectomy has no adverse effect on the rate of postoperative hypopituitarism. Early repeat surgery is a successful option if CD persists.	\N	\N
22034985	Earlier, we identified proteins connecting different disease proteins in the human protein-protein interaction network and quantified their mediator role. An analysis of the networks of these mediators shows that proteins connecting heart disease and diabetes largely overlap with the ones connecting heart disease and obesity. We quantified their overlap, and based on the identified topological patterns, we inferred the structural disease-relatedness of several proteins. Literature data provide a functional look of them, well supporting our findings. For example, the inferred structurally important role of the PDZ domain-containing protein GIPC1 in diabetes is supported despite the lack of this information in the Online Mendelian Inheritance in Man database. Several key mediator proteins identified here clearly has pleiotropic effects, supported by ample evidence for their general but always of only secondary importance. We suggest that studying central nodes in mediator networks may contribute to better understanding and quantifying pleiotropy. Network analysis provides potentially useful tools here, as well as helps in improving databases.	\N	\N
22040839	Coronary artery disease (CAD) is the major cause of morbidity and mortality in type 2 diabetic patients. Severe vitamin D deficiency has been shown to predict cardiovascular mortality in type 2 diabetic patients. We investigated the association among severe vitamin D deficiency, coronary calcium score (CCS), and asymptomatic CAD in type 2 diabetic patients with elevated urinary albumin excretion rate (UAER) >30 mg/24 h. This was a cross-sectional study including 200 type 2 diabetic patients without a history of CAD. Severe vitamin D deficiency was defined as plasma 25-hydroxyvitamin D (p-25[OH]D3) <12.5 nmol/L. Patients with plasma N-terminal pro-brain natriuretic peptide >45.2 ng/L or CCS ≥400 were stratified as being high risk for CAD (n= 133). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109), computed tomography angiography (n = 20), or coronary angiography (CAG; n = 86). Patients' p-25(OH)D3 levels were determined by high-performance liquid chromatography/tandem mass spectrometry. The median (range) vitamin D level was 36.9 (3.8-118.6) nmol/L. The prevalence of severe vitamin D deficiency was 9.5% (19/200). MPI or CAG demonstrated significant CAD in 70 patients (35%). The prevalence of CCS ≥400 was 34% (68/200). Severe vitamin D deficiency was associated with CCS ≥400 (odds ratio [OR] 4.3, 95% CI [1.5-12.1], P = 0.005). This association persisted after adjusting for risk factors (4.6, 1.5-13.9, P = 0.007). Furthermore, severe vitamin D deficiency was associated with asymptomatic CAD (adjusted OR 2.9, 1.02-7.66, P = 0.047). In high-risk type 2 diabetic patients with elevated UAER, low levels of vitamin D are associated with asymptomatic CAD.	\N	\N
22047508	Hypertension is a common major risk factor for stroke and coronary heart disease. Little is known about how achievement of financially incentivised and non-incentivised indicators of quality of care varies with deprivation, or about the effect of financial incentives on health inequalities in hypertension. General practices in the UK have received financial incentives for high quality care since 2004. This study set out to assess the variations in achievement of incentivised and non-incentivised quality indicators for hypertension by patient area deprivation, before and after the introduction of financial incentives. Achievement of 14 quality indicators for hypertension in 304 patient participants in 18 general practices in Norfolk, England was assessed one year before (2003) and one year after (2005) the introduction of financial incentives. Four indicators were incentivised and 10 were non-incentivised. Each participant's postcode was linked to an index of multiple deprivation score. The range of achievement of incentivised quality indicators was 65-94% in the least deprived third of participants, and 77-94% in the most deprived third in 2003 and 2005 combined. For non-incentivised indicators, the range was 7-85% in the least deprived and 24-93% in the most deprived third.Achievement of incentivised quality indicators in 2003 and 2005 combined did not vary significantly by area deprivation. Achievement of three of 10 non-incentivised indicators was higher in participants from more deprived postcode areas: providing lifestyle advice (odds ratio 1.34, 95% confidence interval 1.00-1.79), assessment of peripheral vascular disease (1.54, 1.02-2.35) and electrocardiography (1.38, 1.04-1.82). Participants from more deprived areas received at least the same, and sometimes better, quality of care than those from less deprived areas. Quality of care for hypertension in general practice may not follow the inequitable distribution seen with some other conditions.	\N	\N
22050270	Vitiligo is a common acquired depigmentation disorder caused by the loss of melanocytes. Despite the numerous treatment modalities available for vitiligo, responses to treatment are still unsatisfactory. For this reason, new treatment modalities and approaches are needed. To investigate the effects of fractional carbon dioxide (CO(2) ) laser therapy followed by systemic narrowband ultraviolet B (NB-UVB) phototherapy on nonsegmental vitiligo (NSV) as a prospective and randomized left-right comparative study. Ten patients with NSV who presented symmetrical vitiligo lesions with no further improvement despite more than 1 year of conventional treatment were enrolled. Two sessions of half-body fractional CO(2) laser therapy were performed at a 2-month interval. NB-UVB phototherapy was then administered to the entire body 5 days after each fractional laser treatment twice a week, increasing the dose incrementally by 15% at each session. Objective clinical assessments were made by two blinded dermatologists using a quartile grading scale, and the patients' overall satisfaction was evaluated using a 10-point visual analogue scale. Two months after the last treatment, mean improvement scores, assessed by physicians, were significantly higher for those treated with half-body fractional CO(2) laser therapy followed by NB-UVB phototherapy, compared with those treated with NB-UVB alone (P=0·034). In addition, according to subjective assessment, the half-body laser treatment followed by NB-UVB showed significantly higher improvements compared with NB-UVB treatment alone (P=0·023). Noticeable adverse events, such as infection, scarring and Koebner phenomenon, were not found in any patient. This study suggests that fractional CO(2) laser therapy followed by NB-UVB phototherapy could be used effectively and safely as an alternative modality for the treatment of refractory vitiligo.	\N	\N
22054870	Age-related cognitive decline is likely promoted by accumulated brain injury due to chronic conditions of aging, including neurodegenerative and vascular disease. Because common neuronal mechanisms may mediate the adaptation to diverse cerebral insults, we hypothesized that susceptibility for age-related cognitive decline may be due in part to a shared genetic network. We have therefore performed a genome-wide association study using a quantitative measure of global cognitive decline slope, based on repeated measures of 17 cognitive tests in 749 subjects from the Religious Orders Study. Top results were evaluated in 3 independent replication cohorts, consisting of 2279 additional subjects with repeated cognitive testing. As expected, we find that the Alzheimer's disease (AD) susceptibility locus, APOE, is strongly associated with rate of cognitive decline (P(DISC) = 5.6 × 10(-9); P(JOINT)= 3.7 × 10(-27)). We additionally discover a variant, rs10808746, which shows consistent effects in the replication cohorts and modestly improved evidence of association in the joint analysis (P(DISC) = 6.7 × 10(-5); P(REP) = 9.4 × 10(-3); P(JOINT) = 2.3 × 10(-5)). This variant influences the expression of 2 adjacent genes, PDE7A and MTFR1, which are potential regulators of inflammation and oxidative injury, respectively. Using aggregate measures of genetic risk, we find that known susceptibility loci for cardiovascular disease, type 2 diabetes, and inflammatory diseases are not significantly associated with cognitive decline in our cohort. Our results suggest that intermediate phenotypes, when coupled with larger sample sizes, may be a useful tool to dissect susceptibility loci for age-related cognitive decline and uncover shared molecular pathways with a role in neuronal injury.	\N	\N
22054881	Lung cancer is a heterogeneous disease clinically, biologically, histologically, and molecularly. Understanding the molecular causes of this heterogeneity, which might reflect changes occurring in different classes of epithelial cells or different molecular changes occurring in the same target lung epithelial cells, is the focus of current research. Identifying the genes and pathways involved, determining how they relate to the biological behavior of lung cancer, and their utility as diagnostic and therapeutic targets are important basic and translational research issues. This article reviews current information on the key molecular steps in lung cancer pathogenesis, their timing, and clinical implications.	\N	\N
22067963	Lewy pathology in Parkinson disease (PD) extends well beyond the CNS, also affecting peripheral autonomic neuronal circuits, especially the enteric nervous system (ENS). The ENS is an integrative neuronal network also referred to as "the brain in the gut" because of its similarities to the CNS. We have recently shown that the ENS can be readily analyzed using routine colonic biopsies. This led us to propose that the ENS could represent a unique window to assess the neuropathology in living patients with PD. In this perspective, we discuss current evidence which indicates that the presence of ENS pathology may by exploited to improve our understanding and management of PD and likely other neurodegenerative disorders.	\N	\N
22068070	Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare adrenergically mediated arrhythmogenic disorder classically induced by exercise or emotional stress and found in structurally normal hearts. It is an important cause of cardiac syncope and sudden death in childhood. Catecholaminergic polymorphic ventricular tachycardia is a genetic cardiac channelopathy with known mutations involving genes affecting intracellular calcium regulation. We present a case of a 14-year-old boy who had cardiopulmonary arrest after an emotionally induced episode of CPVT while attempting to invite a girl to the school dance. Review of his presenting cardiac rhythm, induction of concerning ventricular arrhythmias during an exercise stress test, and genetic testing confirmed the diagnosis of CPVT. He recovered fully and was treated with β-blocker therapy and placement of an implantable cardioverter-defibrillator. In this report, we discuss this rare but important entity, including its molecular foundation, clinical presentation, basics of diagnosis, therapeutic options, and implications of genetic testing for family members. We also compare CPVT to other notable cardiomyopathic and channelopathic causes of sudden death in youth including hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, long QT syndrome, short QT syndrome, and Brugada syndrome.	\N	\N
22072024	Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include 'off-label' use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors' own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.	\N	\N
22072546	Recent genome wide association studies have identified susceptibility loci for adult testicular germ cell tumors (GCT) near KITLG, SPRY4, BAK1, and DMRT1. We evaluated variants in these four genes to determine whether these are also susceptibility loci for pediatric GCTs. DNA was isolated from 52 pediatric GCTs (ages 0-21 years) obtained from the Cooperative Human Tissue Network. Control DNA was isolated from de-identified dried blood spots from 141 white newborns. Genotyping was conducted using TaqMan assays (rs4474514) or by PCR and sequencing (rs4324715, rs210138, and rs755383). Associations between variants and GCT were evaluated using logistic regression with adjustment for sex. We also evaluated whether the associations differed by age at GCT diagnosis (0-9 years, 10-21 years), sex, and tumor location (gonadal, non-gonadal). We observed a significant association for rs210138 (BAK1) and pediatric GCT overall (odds ratio (OR) = 1.80, 95% confidence interval (CI) 1.10-2.95, P = 0.02) with non-significant associations similar in magnitude in both the pediatric (P = 0.09) and adolescent (P = 0.06) age groups. The KITLG (rs4474514) and SPRY4 (rs4324715) variants were significantly associated with GCT only in the adolescent age group (rs4474514: OR = 2.28, 95% CI 1.09-4.79, P = 0.03 and rs4324715: OR = 2.40, 95% CI 1.19-4.83, P = 0.01). Associations were mostly similar when stratified by sex. This is the first study to suggest that these loci may also be important in susceptibility to GCTs in the adolescent (KITLG, SPRY4, and BAK1) and pediatric (BAK1) age groups.	\N	\N
22078109	The aim of the present study was to examine abnormalities in the ankle-brachial index (ABI) and related risk factors in patients with type 2 diabetes. Between September 2003 and June 2010, the ABI was determined in 3924 outpatients attending the Diabetes Center of the People's Liberation Army 306th Hospital. In addition, demographic and laboratory data were collected. The risk factors for an abnormal ABI were determined using univariate and stepwise logistic regression analysis. The ABI was normal (0.91-1.3) in 93.1% of patients, low (<0.9) in 5.2%, and high (>1.3) in 1.7%. The prevalence of abnormal lower ABI was greater in elderly (≥ 65 years) patients (12.2%) than in younger (< 65 years) patients (3.6%). Using normal ABI as the reference, low ABI in younger patients was found to be independently associated with HbA1c, the urinary albumin:creatinine ratio, diabetic peripheral neuropathy, diabetic retinopathy, and cerebrovascular disease. A low ABI in elderly patients was found to be independently associated with age, smoking, HbA1c, uric acid, total cholesterol, diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy and cerebrovascular disease. A high ABI in younger patients was associated with being male. The prevalence of an abnormal ABI was high in patients with type 2 diabetes, especially elderly patients. Early identification and intensive treatment are needed to improve the quality of life and overall prognosis of patients with type 2 diabetes.	\N	\N
22079056	Cancer represents a complex group of heterogeneous diseases. While many cancers share fundamental biological processes (hallmarks of cancer) necessary for their development and progression, cancers also distinguish themselves by their dependence on distinct oncogenic pathways. Over the last decade, targeted therapies have been introduced to the clinic with variable success. In truth, single targeted therapies may be successful in only a subset of malignancies but insufficient to address malignancies that often rely on multiple pathways, thus evading single targeted agents. Investigators have recently identified potentially functional components of the human genome that were previously thought to have no biological function. This discovery has added to the already established complexity of gene regulation in the pathogenesis of cancer. Non-coding RNAs represent key regulators of gene expression. Improved knowledge of their biogenesis and function may in turn lead to a better understanding of the heterogeneity of malignancies and eventually be leveraged as diagnostic, prognostic and therapeutic targets. MicroRNAs (miRNAs or miRs) for example, have the capacity for the regulation of multiple genes and thus redirection or reprogramming of biological pathways. However, several other members of the non-coding RNA family may be of equal biological relevance. In this review, we provide a perspective on emerging concepts in the clinical application of miRNA and other non-coding RNAs as biomarkers in cancer with an eye on the eventual integration of both miRNA and other non-coding RNA biology into our understanding of cancer pathogenesis and treatment.	\N	\N
22082049	A growing number of prognostic indices for chronic obstructive pulmonary disease (COPD) is developed for clinical use. Our aim is to identify, summarize and compare all published prognostic COPD indices, and to discuss their performance, usefulness and implementation in daily practice. We performed a systematic literature search in both Pubmed and Embase up to September 2010. Selection criteria included primary publications of indices developed for stable COPD patients, that predict future outcome by a multidimensional scoring system, developed for and validated with COPD patients only. Two reviewers independently assessed the index quality using a structured screening form for systematically scoring prognostic studies. Of 7,028 articles screened, 13 studies comprising 15 indices were included. Only 1 index had been explored for its application in daily practice. We observed 21 different predictors and 7 prognostic outcomes, the latter reflecting mortality, hospitalization and exacerbation. Consistent strong predictors were FEV1 percentage predicted, age and dyspnoea. The quality of the studies underlying the indices varied between fairly poor and good. Statistical methods to assess the predictive abilities of the indices were heterogenic. They generally revealed moderate to good discrimination, when measured. We focused on prognostic indices for stable disease only and, inevitably, quality judgment was prone to subjectivity. We identified 15 prognostic COPD indices. Although the prognostic performance of some of the indices has been validated, they all lack sufficient evidence for implementation. Whether or not the use of prognostic indices improves COPD disease management or patients' health is currently unknown; impact studies are required to establish this.	\N	\N
22082649	INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients.	\N	\N
22092655	Immunomodulatory T cells are thought to influence development of allergy and asthma, but early life longitudinal data on their phenotype and function are lacking. As part of the Urban Environment and Childhood Asthma (URECA) study, we investigated the development of immunomodulatory T cell phenotype and function, and characterized their relation to allergic disease progression from birth through to 2 years of age. Immunomodulatory T cell phenotype and function in cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) at 1 and 2 years of age were characterized by analysing CD25(bright) and FoxP3(+) expression, proliferative responses and cytokine production. The relation of immunomodulatory T cell characteristics to allergic sensitization and disease at 1- and 2-years of age was investigated. The proportion of CD4(+)CD25(bright) and CD4(+)CD25(+)FoxP3(+)T cells (n = 114, 83, 82 at birth, 1- and 2-years respectively) increased significantly, whereas there were no significant changes in the suppressive function of CD25(+)T cells (n = 78, 71, 81 at birth, 1- and 2-years respectively). Birth immunomodulatory T cell characteristics were not related to subsequent allergic sensitization or disease. However, increases in the numbers of CD4(+)CD25(bright) cells and their ability to suppress lymphoproliferative responses at 1 year of age were associated with reduced allergic sensitization at 1 (P = 0.03) and 2 (P = 0.02) years of age. Production of the anti-inflammatory cytokine IL-10 by CD25(+)T cells appeared to mediate this protective suppressive function. In contrast, by 2 years of age, we observed the emergence of a positive association of CD4(+)CD25(+) FoxP3(+) T cell numbers with allergic sensitization (P = 0.05) and eczema (P = 0.02). These findings suggest that the relationship between immunomodulatory T cell subsets, allergic sensitization and eczema is developmentally regulated. In the first year of life, CD4(+)CD25(+) IL-10 producing T cells are associated with a reduced incidence of allergic sensitization. Once allergic sensitization or eczema is established, CD4(+)CD25(+)FoxP3(+)T-reg cells expand to potentially counteract the allergic inflammatory response. Understanding the relationship between development of immunoregulatory T cells and early onset atopy could lead to new preventive strategies for allergic diseases.	\N	\N
22104022	Bronchiolitis is the most common respiratory disease in children under 2 years-old and a major cause of hospitalization in young children, especially during the winter. To determine the prevalence and etiology of bronchiolitis in south-east of Spain. A prospective study was conducted during the bronchiolitis season (December-April). Children below 18 months-old admitted to the hospital for a first bronchiolitis episode were included. Nasopharyngeal aspirates were analysed by reverse transcription polymerase chain reaction (RT-PCR) respiratory syncytial virus. A total of 235 children were included during this period, and 235 RT-PCR were performed. A total of 287 viruses were detected in nasopharyngeal aspirates from 204 infants. Respiratory syncytial virus was the virus detected more frequently, followed by rhinovirus. Co-infections were found in the 36% of children. Respiratory viruses were detected in most of the children below 18 months-old hospitalised with bronchiolitis, and 36% of them showed a mixed infection.	\N	\N
22106694	HLA-DQA1, -DQB1, and -DRB1 gene polymorphism were analyzed to study type 1 DM susceptibility in Malay patients from Southeast Asia (Malaysia and Singapore). Patients showed significant increases in the occurrence of DQA1*0501 (50.7% vs. 20.4%; RR = 3.97; Pc < 0.01), DQB1*0201 (48% vs. 19.1%; RR = 3.86; Pc < 0.05), and DRB1*0301 (38.7 vs. 6.8%; RR = 8.36; 95% Pc < 0.05). Conversely, significant decreases were noted in the occurrence of DQA1*0601 (14.7% vs. 35.2%; RR = 0.33; Pc = 0.008) and DQB1*0601 (4% vs. 23.5%; RR = 0.16; Pc < 0.05) in type 1 DM patients. Using a logistic regression model, we derived a risk prediction model for type 1 DM in our indigenous Malay population based on the identified HLA genotypes. The RR for type 1 DM increases by a factor of 5.68 for every unit increase in the number of DRB1*0301 allele (P < 0.001), and decreases by a factor of 0.18 per unit increase in the number of DQB1*0601 allele (P < 0.001). After adjusting for these two HLA genotypes, DQA1*0501, DQB1*0201 and DQA1*0601 were not statistically significant as risk predictors. The lower incidence of type 1 DM in the Malay population may be contributed by the genotypic combinations of DR and DQ genes as well as the linkage disequilibria between susceptible and protective alleles.	\N	\N
22110167	A primary function of B lymphocytes is immunoglobulin production; however, the therapeutic benefit of B cell depletion in autoimmune diseases previously thought to be T cell mediated suggests that some B cells fulfill other roles in autoimmunity. We examined the recently identified human B1 cell population for T cell stimulatory activity. We found two kinds of B1 cells that are distinguished by multiple surface markers and distinct transcriptomic profiles. In both umbilical cord and adult peripheral blood, a CD11b(+) subset constitutes ~1 out of every 8-10 B1 cells, whereas a CD11b(-) subset constitutes the remaining B1 cells. These B1 cell populations differ functionally. CD11b(-) B1 cells spontaneously secrete much more IgM than CD11b(+) B1 cells. In contrast, CD11b(+) B1 cells express more CD86, and more efficiently stimulate allogeneic CD4(+) T cell expansion, than CD11b(-) B1 cells. The frequency of these CD11b(+) B1 cells is markedly elevated in lupus patients. CD11b(+) B1 cells in lupus patients express more CD86 and have increased T cell-stimulating activity in disease. This work distinguishes a novel, T cell-interacting B1 cell population whose abundance and activity may be a reflection of, and a therapeutic target in, autoimmune disease.	\N	\N
22112193	Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is one of the most common causes of chronic liver disease, worldwide. Lipoprotein-associated phospholipase A2 (Lp-PLA2) was recently characterized as a novel inflammatory biomarker that is correlated with several components constituting the metabolic syndrome. In this study, we determined the serum levels of Lp-PLA2 in patients with definite nonalcoholic steatohepatitis (NASH, n=25), borderline NASH (n=22), simple fatty liver (n=10), and healthy controls without evidence of liver disease (n=38). The levels of Lp-PLA2 were measured by enzyme-linked immunosorbent assay and compared in the four study groups. Moreover, concentrations of Lp-PLA2 were assessed in relation to the general characteristics of the study participants and the results of liver biopsy. Concentrations of Lp-PLA2 were significantly higher in patients with definite NASH (161.8±0.9 μg/L, P<0.001), borderline NASH (135.4±47.7 μg/L, P=0.001), and simple fatty liver (132.4±46.2 μg/L, P=0.042) compared with healthy controls (86.2±40.7 μg/L). Furthermore, the serum Lp-PLA2 level was strongly associated to histological steatosis scores in patients with NAFLD (β=0.32, t=2.50, P=0.016). Although subject to future confirmation, our data suggest that Lp-PLA2 levels are elevated in NAFLD.	\N	\N
22122455	PPAR agonists represent a heterogeneous group of compounds that have been used in the treatment of cardiovascular and metabolic diseases for over thirty years. While the primary indications for PPAR agonist therapy focus on hyperlipidemia and diabetes, there is a growing body of pre-clinical data that suggests they may be beneficial in the treatment of heart failure; a disease marked by abnormal myocardial metabolism, fibrosis and insulin insensitivity. PPAR agonist treatment in numerous animal models of systolic heart failure have demonstrated improvement in cardiac function with decreased fibrosis, improved contractility and endothelial function. However, considerable controversy exists on the cardiac safety profile of PPAR agonists, particularly concern for inducing lipotoxicty and precipitating or worsening heart failure. In addition during pre-clinical testing, many compounds have been associated with increased death and adverse cardiovascular outcomes casting a pall over their future use for treating disorders of myocardial function. This article will review cardiac pathways involved in PPAR activation and their potential regulation of maladaptive pathways involved in heart failure and highlight molecular mechanisms that may contribute to adverse events and raise safety concerns. Specific attention will be focused on PPAR alpha and gamma, subtypes for which commercially available PPAR agonists are currently available.	\N	\N
22122790	Atopic dermatitis (AD) is a kind of eczema with an inflammatory, relapsing, non-contagious, and pruritic skin disorder. It is associated with the local infiltration of T helper type 2 (Th2) cells that secrete interleukin (IL)-4 and IL-5. IL-21 is a member of IL-2 family cytokine mainly expressed by activated CD4+ T lymphocytes. Until now, there is no clinical research in the expression of IL-21 in patients with AD. We analyzed serum levels of total immunoglobulin E (IgE), allergen-specific IgE, and cytokines IL-4, IL-5, IFN-γ, IL-17, and IL-21 in AD cases and controls. In addition, cytokine levels in the culture supernatants of peripheral blood mononuclear cells stimulated with anti-CD3 and anti-CD28 Abs, phytohemagglutin (PHA), or pokeweed mitogen (PWM) were measured. We also assessed clinical skin severity by Scoring of Atopic Dermatitis (SCORAD) index. Our results showed that serum total IgE in the case group was significantly higher than that of control group (365.449 ± 52.945 and 39.243 ± 7.605 IU/ml, respectively). Logistic regression analysis system reveals serum levels of IL-21 and IFN-γ are significantly correlated. However, IL-21 and IL-4, IL-21 and IL-5, as well as IL-21 and IL-17 showed no correlation. A significantly decreased level of IL-21 was observed in children suffering with severe AD compared with controls, suggesting that IL-21 may play a role in AD.	\N	\N
22124677	Colonic ischemia following colorectal surgery is an unusual and serious complication. As it has been reported that the incidence of colonic ischemia was higher after laparoscopic surgery, the aim of this report was to document the clinical features of postoperative colonic ischemia following colorectal surgery. Among 1,201 surgeries for sigmoid colon and rectal cancer by a single surgeon from 2006 to 2010, 10 cases of postoperative colonic ischemia were retrospectively identified (0.83%). IMA high ligation was routinely made in all surgeries. The clinical findings and laboratory data of these 10 cases were evaluated. Of the 10 patients, 9 were male and 1 was female. The mean age was 66.9 years old. The mean BMI was 23.3. Three patients (30%) had a cardiovascular disease other than hypertension. Eight patients (80%) underwent laparoscopic surgery and two patients (20%) underwent open surgery. Intraoperative bleeding occurred in five patients (50%, mean 435 ml). The average day for occurrence of postoperative colonic ischemia was on the 5th day (range 2nd-10th day). A consistent postoperative fever was found in eight patients (80%). Mortality due to postoperative colonic ischemia was 10%. Postoperative colonic ischemia may be considered one of the more important complications of colorectal resection.	\N	\N
22129916	To evaluate the long-term safety and efficacy of etanercept treatment in Polish patients with juvenile idiopathic arthritis (JIA). The study involved patients, fulfilling the JIA criteria of the International League of Associations of Rheumatology (ILAR), who were started on etanercept therapy after methotrexate and other synthetic disease-modifying antirheumatic drugs (DMARDs) had proven ineffective. Patient data were collected in an electronic registry. Disease improvement was assessed based on Giannini's criteria. The statistical analysis involved 188 patients. Significant improvement was observed in all clinical and laboratory parameters after the first month of therapy and was maintained in the following months. ACR Pediatric 30, 50, 70, 90, and 100 improvement was observed in 81.4%, 65.9%, 27.5%, 16.2%, and 15%, respectively, of patients after 3 months and in 94.7%, 88.4%, 62.1%, 34.7%, and 26.3%, respectively, after 24 months of treatment. Throughout the 72-month safety observation period, 1162 adverse events were reported; the exposure-adjusted AE rate was 2.96 per patient per year. In patients with various subtypes of JIA resistant to conventional DMARD treatment, etanercept resulted in significant and long-lasting improvements in disease activity. Combination treatment with etanercept and a DMARD was well tolerated.	\N	\N
22133826	The purpose of clinical assessment of atherosclerosis in aorta is to detect early lesions that are associated with a substantial risk of cardiovascular disease, such as stroke, aortic aneurysm and dissection, and to develop a treatment strategy for reduction of the cardiovascular risk. The pulse wave velocity (PWV) and pulse wave analysis (augmentation index : AI) can reveal atherosclerotic functional vascular abnormalities. On the contrary, plain X-rays, ultrasound examination, computed tomography (CT) , and magnetic resonance imaging (MRI) can be employed to easily assess the severity of atherosclerotic vascular damage morphologically. In these examinations, only PWV, as an index of arterial stiffness, can detect early atherosclerotic change in aorta before organic change. So, considering the importance of detecting early lesion, PWV is the most useful examination of atherosclerosis in aorta.	\N	\N
22134016	In this review, the pitfalls that still exist with the surgical treatment of endometriosisassociatedpelvic pain have been discussed and the best evidence regarding various aspects of surgical techniques have been reviewed. When laparoscopy is performed to evaluate a woman with pelvic pain symptoms, it is important she be counseled that the primary function of the surgery is to confirm the presence (and allow surgical treatment) of endometriosis, and that it is not the penultimate diagnostic modality for her pelvic pain. There are many etiologies of pelvic pain that present with symptoms resembling those of endometriosis-associated pelvic pain that are not diagnosable with laparoscopy, such as interstitial cystitis and irritable bowel syndrome. It is unfortunate that many women are left with the belief that if a laparoscopy fails to provide a diagnosis of a pain generator, then it means there are no diagnoses other than that the “pain is in her head,” often disparagingly termed “supratentorial” byclinicians. In fact, the pain-related diagnoses that are amenable to and possibly require a laparoscopy are quite limited, a group of diagnoses that this author terms the “dirty dozen” because there are just 12, and only the first 4 have good evidence to clearly associate them with chronic pelvic pain:1. Endometriosis 2. Ovarian remnant syndrome 3. Pelvic inflammatory disease 4. Tuberculous salpingitis 5. Adhesions 6. Benign cystic mesothelioma 7. Postoperative peritoneal cysts 8. Adnexal cysts (nonendometriotic)9. Chronic ectopic pregnancy 10. Endosalpingiosis 11. Residual accessory ovary 12. Hernias: ventral, inguinal, femoral, spigelian.I would argue that diagnostic laparoscopy in modern gynecology has a limited, if any role, and that when laparoscopy is planned for women with chronic pelvic pain, it should be with a very high suspicion of a diagnosis and with plans to treat the disease operatively. In this era, a negative diagnostic laparoscopy should be a rare event.	\N	\N
22139583	Omics is the study of proteins, peptides, genes, and metabolites in living organisms. Systems biology aims to understand the system through the study of the relationship between elements such as genes and proteins in biological system. Recently, systems biology emerged as the result of the advanced development of high-throughput analysis technologies such as DNA sequencers, DNA arrays, and mass spectrometry for omics studies. Among a number of analytical tools and technologies, CE and CE coupled to MS are promising and relatively rapidly developing tools with the potential to provide qualitative and quantitative analyses of biological molecules. With an emphasis on CE for systems biology, this review summarizes the method developments and applications of CE for the genomic, transcriptomic, proteomic, and metabolomic studies focusing on the drug discovery and disease diagnosis and therapies since 2009.	\N	\N
22145272	The prognosis of multiple myeloma patients has significantly improved since the introduction of the novel agents thalidomide, bortezomib and lenalidomide. We report the data of a medical need programme with lenalidomide plus dexamethasone, conducted in Belgium between August 2007 and March 2008, and including 98 relapsed refractory multiple myeloma patients. In addition to chemotherapy and steroids, all patients had received prior treatment with bortezomib, and 84% of them had been exposed to thalidomide. In 52 patients response data could be retrieved by post-hoc analysis. A partial remission or better was achieved in 52% (49% partial and 3% complete response) of patients, despite a median of 5 previous anti-myeloma treatment lines. Responses were rapid while the majority of patients received lenalidomide with once weekly (also called low-dose) dexamethasone. Treatment with lenalidomide plus dexamethasone did prolong overall survival by nearly half a year in this population with end-stage myeloma. Overall response and quality of response were independent of previous response to thalidomide and bortezomib, although the time to progression tended to be shorter in thalidomide- and bortezomib-refractory patients. It can be concluded that lenalidomide plus dexamethasone is an effective and safe treatment regimen in highly refractory multiple myeloma patients, and that these responses are irrespective of previous exposure or sensitivity to thalidomide and bortezomib.	\N	\N
22153142	As important members of the health care team, patients and caregivers must be empowered to recognize their asthma status and to act accordingly. Education about asthma, complications, and successful management of asthma provide the best way to empower children and their caregivers. A Shared Medical Appointment (SMA) is a unique health care delivery approach that integrates disease management and patient education. The SMA described here is a 90-minute group appointment for four to nine patients who share a diagnosis of asthma, bronchospasm, or wheeze and their caregivers. The appointment includes a brief individual examination, health education delivered to the group, and the opportunity for interaction between group members. Because a supporting theoretic framework is not identified in the original design proposals for the SMA model or in the literature on its use, for the purposes of this project, Social Cognitive Theory is identified as the theoretical framework that best explains and reinforces the benefits of the SMA. The theoretic framework is important to direct the development and continued success of this treatment model. This project report describes the first nurse practitioner-led SMA as a tool for improving quality of care and service for children with asthma and their caregivers.	\N	\N
22153317	Oral ulcer is the cardinal clinical sign and increased neutrophilic activity is a part of the pathogenesis in Behcet's disease (BD). Saliva, as a part of the innate immune response, contains antimicrobial peptides (AMPs) that are derived from both oral epithelial cells and neutrophils. The aim of this study was to investigate the associations between salivary levels of AMPs HNP 1-3, LL-37 and S100 and disease course in patients with Behcet's disease (BD). Fifty-three patients with BD and 44 healthy controls (HC) were included in the study. Disease severity score reflecting organ involvement was calculated. Salivary HNP 1-3, LL-37 and S100 levels were measured in unstimulated saliva samples by ELISA. Salivary HNP 1-3 and S100 levels in BD patients (2715.2 ± 1333.4 μg/ml and 430.6 ± 203.9 ng/ml) were significantly higher compared to HC (1780.6 ± 933.2 μg/ml and 365.3 ± 84.7 ng/ml) (p = 0.000 and p = 0.004, respectively). Although LL-37 levels were also higher in BD than HC (190.9 ± 189.1 vs 143.1 ± 128.9 ng/ml), no significant difference was observed (p = 0.53). Salivary HNP 1-3 and LL-37 levels were associated with the severity of BD (mild disease: 1975.1 ± 1174.2 μg/ml and 115.9 ± 109.4 ng/ml vs severe disease: 2955.7 ± 1305.6 μg/ml and 215.3 ± 203.8 ng/ml, p=0.020 and p=0.031, respectively). Salivary LL-37 levels also correlated with the number of monthly oral ulcers (r = 0.5 p = 0.000). An increase in salivary HNP 1-3 and S100 levels might be associated with enhanced local and systemic innate responses in BD.	\N	\N
22156557	statin drugs may induce skeletal myopathy, but might also have the potential to improve rehabilitation outcomes by improving sarcopenia or by preventing intercurrent illness. We examined the association between statin use and functional outcomes in the rehabilitation of older people. retrospective cohort study using routinely collected clinical data. Admissions to Royal Victoria Hospital, Dundee for inpatient rehabilitation over a 10-year period were identified. Data were available regarding demographics, statin therapy, antiplatelet therapy, admission and discharge Barthel scores, length of stay and comorbid disease. Multivariate analyses were performed to examine the difference between admission and discharge Barthel score in patients taking statins compared with those not taking statins. a total of 3,422 patients were included. Mean age was 81.4 years; 40% were male. Baseline Barthel scores were similar in the statin/non-statin groups, respectively (10.4/20 versus 10.3/20, P = 0.57). Improvement in the Barthel score between admission and discharge was greater in the statin than non-statin group (3.59 versus 4.30 points, P < 0.001) after adjustment for age, sex, baseline Barthel score and comorbid disease. statin use was associated with improved Barthel scores on discharge from rehabilitation. This gain could contribute to improved outcomes as part of the rehabilitation package and requires further prospective investigation.	\N	\N
22156787	Spinal muscular atrophy is a relatively stable chronic disease. Patients may gradually experience declines in muscle strength and motor function over time. However, functional progression is difficult to document, and the mechanism remains poorly understood. An 11-year-old girl was diagnosed at 19 months and took a few steps without assistance at 25 months. She was evaluated for 54 months in a prospective multicenter natural history study. Outcome measures were performed serially. From 6 to 7.5 years, motor function improved. From 7.5 to 11 years, motor function declined with increasing growth. Manual muscle testing scores minimally decreased. Motor unit number estimation studies gradually increased over 4.5 years. Compared to the published natural history of spinal muscular atrophy type III, our patient lost motor function over time. However, she walked with assistance 2 years longer than expected. Our report highlights possible precipitating factors that could affect the natural history of spinal muscular atrophy type III.	\N	\N
22157156	Rhinitis is a common condition associated with significant under-recognized morbidity and impaired quality of life. The natural history of rhinitis is poorly characterized. Better understanding of its natural history and associated risk factors would improve the ability to effectively manage rhinitis in clinical practice. This review focuses on the current research findings on the natural history of rhinitis and how that is influenced by atopy and sex. Recent work from the Isle of Wight Birth Cohort Study has demonstrated that the prevalence of atopic rhinitis increases steadily in the first 18 years of life in both sexes. However, nonatopic rhinitis behaves differently during adolescence. Its prevalence decreases in boys but continues to increase in girls resulting in a female predominance after puberty. Numerous recent studies have proposed potential roles for sex-related and adipose-related hormonal changes in influencing the course of allergic disease. Further research is needed to establish mechanisms that could underlie such findings. Rhinitis becomes increasingly common through childhood, with prevalence during adolescence being mediated by differential effects of sex and atopy. Mechanisms to explain these findings await elucidation.	\N	\N
22174195	Early rheumatoid arthritis (RA) and very early RA are major targets of research and clinical practice. Remission has become a realistic goal in the management of RA, particularly in early disease. The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA classification criteria, the EULAR treatment recommendations for RA, and the EULAR recommendations for the management of early arthritis focus on early disease and translate the knowledge related to early RA into classification and management. Nevertheless, there is a need for further improvement and progress. Results from 6 recent studies are summarized, evaluating the performance of the 2010 ACR/EULAR RA classification criteria. The data show a significant risk of misclassification, and highlight that overdiagnosis and underdiagnosis may become important issues if the criteria recommend synthetic and biological disease-modifying antirheumatic drugs. Therefore, some considerations are presented on how the current problems and limitations could be overcome in clinical practice and future research. A consensus is needed to better define the early phase of RA and differentiate from other early arthritis. The possible effect of misclassification on spontaneous and drug-induced remission of early and very early RA awaits further elucidation. Such research will eventually lead to more reliable diagnostic and classification criteria for new-onset RA.	\N	\N
22174210	To compare clinical features of patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) and patients with polymyalgia rheumatica (PMR) and to explore the purported association between RS3PE and malignancy. We did a retrospective chart review of patients with RS3PE and PMR treated in a community-based hospital between January 2000 and December 2009. Outcomes assessed were clinical course of disease and associated malignancies. We identified 28 patients with RS3PE and 123 with pure PMR. All patients with RS3PE fulfilled PMR criteria as well. Age, comorbidity, erythrocyte sedimentation rate, duration and progression of symptoms, treatment response to initial low-dose steroids, and steroid complication rates were similar in both groups. Patients with RS3PE were more likely to be male (79% vs 41%; p = 0.001) and to have a history of smoking (39% vs 15%; p = 0.008) and a higher rate of depression (11% vs 2%; p = 0.044) at diagnosis. Among those with RS3PE, hip pain was less common (39% vs 74%; p = 0.001) than in the PMR group. No patients with RS3PE and 6 patients with pure PMR (4.9%) developed another rheumatological disease during followup. Seven of 9 patients (78%) with concurrent cancer presented slightly more frequently with systemic symptoms compared to patients without cancer (48%; p = 0.098), especially with fatigue (56% vs 22%; p = 0.037) and anorexia (33% vs 9.0%; p = 0.047). Despite rigorous cancer screening in patients with RS3PE, however, the rate of associated malignancy was not statistically different from that of patients with pure PMR [2 (7%) vs 7 (6%), respectively; p = 0.673]. Despite evidence that RS3PE is clinically distinct from PMR, we observed characteristics, treatment response, and outcomes like those expected in pure PMR. Compared to patients with pure PMR, patients with RS3PE are more likely to be male, to be depressed, and to smoke. Contrary to earlier studies, no clear association of RS3PE with malignancy was found despite rigorous cancer screening, although clinicians should be aware that patients with concurrent cancer may manifest more systemic signs and symptoms, as well as steroid resistance.	\N	\N
22179327	Population allele frequencies of apolipoprotein E (APOE) vary by geographic region. The purpose of this study is to summarize and evaluate published estimates for the prevalence of APOE e4 carrier status among the population diagnosed with Alzheimer's disease (AD) by geographic region and country. A systematic review of English-language publications from January 1, 1985, through May 31, 2010, was conducted. Studies reporting APOE e4 status for patients diagnosed with AD were included in the analysis; trials and autopsies were excluded. APOE e4 data were pooled, and prevalence and 95% confidence intervals (CIs) were calculated. Pooled estimates for APOE e4 carrier prevalence data were derived from 142 independent samples: 48.7% (95% CI: 46.5-51.0), and from 73 samples for e4/4 (homozygotes): 9.6% (95% CI: 8.4-10.8). The highest estimates were in Northern Europe: 61.3% (95% CI: 55.9-66.7), e4/4 prevalence: 14.1% (95% CI: 12.2-16.0). The lowest estimates were in Asia and Southern Europe. Substantial heterogeneity of these prevalence estimates was observed. APOE e4 genotype prevalence varies among AD patients by region and within each country. Further exploration is warranted to better understand the substantial heterogeneity of these prevalence estimates.	\N	\N
22183718	The gut epithelium is a barrier between the 'outside' and 'inside' world. The major function of the epithelium is to absorb nutrients, ions and water, yet it must balance these functions with that of protecting the 'inside' world from potentially harmful toxins, irritants, bacteria and other pathogens that also exist in the gut lumen. The health of an individual depends upon the efficient digestion and absorption of all required nutrients from the diet. This requires sensing of meal components by gut enteroendocrine cells, activation of neural and humoral pathways to regulate gastrointestinal motor, secretory and absorptive functions, and also to regulate food intake and plasma levels of glucose. In this way, there is a balance between the delivery of food and the digestive and absorptive capacity of the intestine. Maintenance of the mucosal barrier likewise requires sensory detection of pathogens, toxins and irritants; breakdown of the epithelial barrier is associated with gut inflammation and may ultimately lead to inflammatory bowel disease. However, disruption of the barrier alone is not sufficient to cause frank inflammatory bowel disease. Several recent studies have provided compelling new evidence to suggest that changes in epithelial barrier function and inflammation are associated with and may even lead to altered regulation of body weight and glucose homeostasis. This article provides a brief review of some recent evidence to support the hypothesis that changes in the gut microbiota and alteration of gut epithelial function will perturb the homeostatic humoral and neural pathways controlling food intake and body weight.	\N	\N
22184604	Assessing the medical history of patients before any treatment is an essential aspect of the dentist's responsibility; however, many dental practitioners assume that their patients are systemically healthy so their medical history is often overlooked. The objective of this study was to determine the prevalence of self-reported medical conditions among a sample of dental school patients at the Institute of Dental Sciences, Bareilly (Uttar Pradesh), India. Detailed medical histories were taken from 3,786 new dental patients in an outpatient setting. The demographic data, medical status, and use of medications from the charts were analyzed. Thirty-eight percent of the total patients had a positive finding in their medical history for at least one systemic condition. The most commonly reported systemic condition was hypertension (15.2 percent) followed by diabetes (11.4 percent), and 26 percent of the patients were taking at least one medication daily. The results of this study reflect the medical complexity of the increasingly aging population.	\N	\N
22185707	Acute pyelonephritis (APN) requires prompt diagnosis and immediate treatment. To develop a simple score to assist in diagnosing treatment deterioration in patients with serious APN. Using data from a retrospective cohort of 193 patients with APN, we developed scores based on multivariate logistic regression after the jackknife procedure. We validated the scores in a prospective cohort of 40 patients. Nine criteria were independently associated with our investigation: Abscess (adjusted odds ratio [OR], 19.8; 95% confidence interval [95% CI] 4.5-72.1), pyonephrosis with or without stone (18.3; 4.8-70.9), pelvicalyceal air (15.5; 3.2-26.9), poor global excretion of contrast (12.3; 2.9-68.5), tachycardia or hypotension (10.1; 2.5-28.0), obliteration of the renal sinus (9.6; 2.5-45.2), persistent fever or pyuria (9.8; 1.9-25.8), diabetes (9.4; 2.0-31.8), and global renal enlargement (7.5; 2.1-35.8). The APN score was based on these nine criteria. Low-risk and high-risk groups were derived from the score (probability, 3.5% [95% CI 0-7.5] and 67% [51-83]). Application of these criteria to the prospective cohort confirmed the diagnostic accuracy of the score (probability 0% [0-15] and 71% [25-100] in the low-risk and high-risk groups, respectively). This easy-to-calculate score may prove useful for diagnosing patients with serious APN who deteriorate with treatment.	\N	\N
22195084	There is increasing interest in leveraging electronic health data across disparate sources for a variety of uses. A fallacy often held by data consumers is that clinical data quality is homogeneous across sources. We examined one attribute of data quality, completeness, in the context of electronic laboratory reporting of notifiable disease information. We evaluated 7.5 million laboratory reports from clinical information systems for their completeness with respect to data needed for public health reporting processes. We also examined the impact of health information exchange (HIE) enhancement methods that attempt to improve completeness. The laboratory data were heterogeneous in their completeness. Fields identifying the patient and test results were usually complete. Fields containing patient demographics, patient contact information, and provider contact information were suboptimal. Data processed by the HIE were often more complete, suggesting that HIEs can support improvements to existing public health reporting processes.	\N	\N
22199325	There have been reports suggesting that continuous administration of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is advantageous for patients in which disease progression was observed after the establishment of clinical benefit from EGFR-TKIs. We retrospectively evaluated the clinical course of patients who received continuous administration of EGFR-TKIs after disease progression was detected solely in bone lesions. The medical records of patients administered gefitinib or erlotinib between 2002 and 2010 were reviewed. We evaluated the progression-free survival (PFS) and overall survival (OS) in patients who had bone metastases after the establishment of clinical benefit from EGFR-TKI and who received radiation therapy for the bone lesion and continuous treatment with EGFR-TKI. Ten patients were enrolled in this study. The median PFS and OS were 88 days and 330 days, respectively. Furthermore, a longer duration from the start of first EGFR-TKI to detection of bone metastases (p=0.0049) was identified as being significantly associated with a longer PFS. Our data suggest that continuous administration of EGFR-TKI is a treatment option for patients with bone metastases who previously benefited from therapy with EGFR-TKI.	\N	\N
22200856	Caveolin-1 (cav-1) has been implicated in the development of human cancers. However, the distribution of cav-1 in non-small cell lung cancer (NSCLC) and its signiﬁcance require further study. Real-time PCR and Western blot assays were performed to detect cav-1 mRNA and protein levels in tumor tissues (TT) and matched tumor-free tissues (TF). The protein expression in 115 paraffin-embedded blocks was examined by immunohistochemical staining (IHC). Correlations between cav-1 mRNA and protein expression by IHC and clinicopathological features were statistically evaluated. For the 136 patients examined, the levels of cav-1 mRNA and protein expression were significantly lower in lung TT compared to matched TF (P<0.05). High cav-1 expression was detected in 60 of 115 (52.2%) NSCLC tissues and this level was significantly lower than cav-1 expression in non-cancerous lung tissues (15 of 19, 78.9%, P<0.05). Up-regulation of cav-1 mRNA expression in lung adenocarcinoma (AC) (29.7%) was higher than that observed in lung squamous cell carcinoma (SCC) (15.8%). Statistical analysis of the correlation between cav-1 protein expression and clinical features showed a statistical association with poorer N-stage (P=0.032) and higher pathological TNM stage (P=0.012) in lung AC patients, that was not found in lung SCC patients. Moreover, lung AC patients with higher cav-1 expression showed significantly shorter life-spans than those with lower cav-1 expression (P=0.032, log-rank test). The levels of cav-1 mRNA and protein expression were significantly lower in lung cancers when compared to matched TF or non-cancerous lung tissues. The higher protein expression correlated with the advanced pathological stage and shorter survival rates in lung AC patients.	\N	\N
22201290	Integrins play myriad and vital roles in development and disease. They connect a cell with its surroundings and transmit chemical and mechanical signals across the plasma membrane to the cell's interior. Dissecting their roles in cell behavior is complicated by their overlapping ligand specificity and shared downstream signaling components. In principle, immobilized synthetic peptides can mimic extracellular matrix proteins by supporting integrin-mediated adhesion, but most short peptide sequences lack selectivity for one integrin over others. In contrast, synthetic integrin antagonists can be highly selective. We hypothesized that this selectivity could be exploited if antagonists, when immobilized, could support cellular adhesion and activate signaling by engaging specific cell-surface integrins. To investigate this possibility, we designed a bifunctional (RGD)-based peptidomimetic for surface presentation. Our conjugate combines a high affinity integrin ligand with a biotin moiety; the former engages the α(v)β(3) integrin, and the latter allows for presentation on streptavidin-coated surfaces. Surfaces decorated with this ligand promote both cellular adhesion and integrin activation. Moreover, the selectivity of these surfaces for the α(v)β(3) integrin can be exploited to capture a subset of cells from a mixed population. We anticipate that surfaces displaying highly selective small molecule ligands can reveal the contributions of specific integrin heterodimers to cell adhesion and signaling.	\N	\N
22211766	Retinol binding protein-4 (RBP-4) is a member of adipocytokines, which is potentially associated with fibrosis, vasodilation, and angiogenesis in addition to insulin resistance. To investigate the clinical significance of serum RBP4 levels in patients with systemic sclerosis (SSc), which is a systemic autoimmune disease characterized by fibrosis and vasculopathy. Serum RBP4 levels were determined by enzyme-linked immunosorbent assay in 62 SSc patients and 19 healthy controls. Similar to patients with chronic kidney disease, serum RBP4 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction. Therefore, analyses were carried out by excluding SSc patients with estimated glomerular filtration rate <60 mL/min/1.73 m(2) . Serum RBP4 levels were significantly lower in diffuse cutaneous SSc (dcSSc) than in control subjects [median (25-75 percentile); 25.8 μg/mL (19.6-47.0) vs. 43.1 μg/mL (31.7-53.4), P < 0.05], while there was no significant difference between limited cutaneous SSc (lcSSc) [28.0 μg/mL (25.4-43.3)] and control subjects. In both of dcSSc and lcSSc, patients with Raynaud's phenomenon had RBP4 levels significantly lower than those without. Furthermore, serum RBP4 levels inversely correlated with pulmonary function test results in dcSSc and with right ventricular systolic pressure in lcSSc. CONCLUSION  Decreased RBP4 levels are associated with the prevalence of Raynaud's phenomenon in dcSSc and lcSSc, with the severity of interstitial lung disease in dcSSc, and with the degree of pulmonary vascular involvement in lcSSc, suggesting the possible contribution of RBP4 to the pathological events in this disorder.	\N	\N
22215125	Primary hyperoxaluria type I is a rare inherited disease that presents a disturbed metabolism of glyoxylate. Consequently, patients suffer from hyperoxaluria, leading to renal failure and subsequent skeletal calcium oxalate deposition. Areas with high concentrations of calcium oxalate, so-called dense metaphyseal bands, are at risk for pathological fracturing. The primary disease is treated by combined liver-kidney transplantation, although pathological fracturing also occurs in the posttransplant period. In the current case, we present a 3-year-old boy with a pathological fracture of his right femur, 2 years after liver-kidney transplantation. We opted for a conservative regime, leading to good fracture healing. As there are limited data in the literature regarding treatment of fractures in these patients, it is important to notify the outcome of conservative treatment of pathological fractures in patients with primary hyperoxaluria type I.	\N	\N
22226887	Cystic fibrosis is a lethal autosomal recessive condition caused by a defect of the transmembrane conductance regulator gene that has a key role in cell homeostasis. A dysfunctional cystic fibrosis transmembrane conductance regulator impairs the efflux of cell anions such as chloride and bicarbonate, and also that of other solutes such as reduced glutathione. This defect produces an increased viscosity of secretions together with other metabolic defects of epithelia that ultimately promote the obstruction and fibrosis of organs. Recurrent pulmonary infections and respiratory dysfunction are main clinical consequences of these pathogenetic events, followed by pancreatic and liver insufficiency, diabetes, protein-energy malnutrition, etc. This complex comorbidity is associated with the extensive injury of different biomolecular targets by reactive oxygen species, which is the biochemical hallmark of oxidative stress. These biological lesions are particularly pronounced in the lung, in which the extent of oxidative markers parallels that of inflammatory markers between chronic events and acute exacerbations along the progression of the disease. Herein, an abnormal flux of reactive oxygen species is present by the sustained activation of neutrophils and other cystic fibrosis-derived defects in the homeostatic processes of pulmonary epithelia and lining fluids. A sub-optimal antioxidant protection is believed to represent a main contributor to oxidative stress and to the poor control of immuno-inflammatory pathways in these patients. Observed defects include an impaired reduced glutathione metabolism and lowered intake and absorption of fat-soluble antioxidants (vitamin E, carotenoids, coenzyme Q-10, some polyunsaturated fatty acids, etc.) and oligoelements (such as Se, Cu and Zn) that are involved in reactive oxygen species detoxification by means of enzymatic defenses. Oral supplements and aerosolized formulations of thiols have been used in the antioxidant therapy of this inherited disease with the main aim of reducing the extent of oxidative lesions and the rate of lung deterioration. Despite positive effects on laboratory end points, poor evidence was obtained on the side of clinical outcome so far. These aspects examined in this critical review of the literature clearly suggest that further and more rigorous trials are needed together with new generations of pharmacological tools to a more effective antioxidant and anti-inflammatory therapy of cystic fibrosis patients. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.	\N	\N
22237046	PTPN22 is involved in T-cell activation and its R620W single-nucleotide polymorphism (SNP) has been shown to predispose to different autoimmune diseases. The aims of this study were to investigate the role of the PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated vasculitides (AAVs), and to explore potential associations between the PTPN22 genotype and the disease manifestations. PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS)] and in 945 healthy controls. The frequency of the minor allele (620W) was significantly higher in GPA patients than in controls [P = 0.005, χ(2 )= 7.858, odds ratio (OR) = 1.91], while no statistically significant association was found with MPA or CSS. Among GPA patients, the 620W allele was particularly enriched in ANCA-positive patients as compared with controls (P = 0.00012, χ(2 )= 14.73, OR = 2.31); a particularly marked association was also found with ENT involvement (P = 0.0071, χ(2 )= 7.258, OR = 1.98), lung involvement (P = 0.0060, χ(2 )= 7.541, OR = 2.07) and skin manifestations of all kinds (P = 0.000047, χ(2 )= 16.567, OR = 3.73). The PTPN22 620W allele confers susceptibility to the development of GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.	\N	\N
22237792	Substantia nigra hyperechogenicity assessed by transcranial sonography is a typical finding in up to 90% of patients with idiopathic Parkinson's disease, although its value as a surrogate marker for disease progression in Parkinson's disease is controversial. (123) I-FP-CIT-single photon emission computed tomography (SPECT) represents an established paraclinical surrogate marker to quantify the nigrostriatal dopaminergic deficit in Parkinson's disease. Whereas most studies found no correlation between extent of substantia nigra echogenicity and the putaminal FP-CIT binding ratio, a more recent analysis reported opposite results. In 92 patients with Parkinson's disease the substantia nigra echogenicity was compared with the putaminal FP-CIT binding ratio using an investigator-independent SPECT analysis protocol and with several clinical parameters. No correlation was found between the substantia nigra hyperechogenicity and the FP-CIT binding ratio or the disease severity. Substantia nigra hyperechogenicity does not reflect the degree of the nigrostriatal degeneration or the clinical state of the disease progression.	\N	\N
22239875	Dual-energy x-ray absorptiometry (DEXA) is a safe, noninvasive, inexpensive tool for managing patients with neuromuscular diseases. Regional and whole-body DEXA can be used to guide clinical treatments, such as determining body composition to guide nutritional recommendations, as well as to monitor disease progression by assessing regional and whole-body lean tissue mass. DEXA can also be used as an outcome measure for clinical trials.	\N	\N
22239959	An inadequate level of bowel preparation can affect the efficacy and safety of colonoscopy. Although some factors have been associated with outcome, there is no strategy to identify patients at high risk for inadequate preparation. We searched for factors associated with an inadequate level of preparation and tested the validity of a predictive clinical rule based on these factors. We performed a prospective study of 2811 consecutive patients who underwent colonoscopy examinations at 18 medical centers; clinical and demographic data were collected before the colonoscopy. Bowel preparation was classified as adequate or inadequate; 925 patients (33%) were found to have inadequate preparation. Multivariate analysis was used to identify factors associated with inadequate preparation, which were expressed as odds ratio (OR) and used to build a predictive model. Factors associated with inadequate bowel preparation included being overweight (OR, 1.5), male sex (OR, 1.2), a high body mass index (OR, 1.1), older age (OR, 1.01), previous colorectal surgery (OR, 1.6), cirrhosis (OR, 5), Parkinson disease (OR, 3.2), diabetes (OR, 1.8), and positive results in a fecal occult test (OR, 0.6). These factors predicted which patients would have inadequate cleansing with 60% sensitivity, 59% specificity, 41% positive predictive value, and 76% negative predictive value; they had an under the receiver operating characteristic curve value of 0.63. Assuming 100% efficacy of a hypothetical regimen to address patients predicted to be at risk of inadequate preparation, the rate would decrease from 33% to 13%. We identified factors associated with inadequate bowel preparation for colonoscopy and used these to build an accurate predictive model.	\N	\N
22241793	Neointimal hyperplasia causes a high rate of hemodialysis synthetic graft failure. Thus, therapies that inhibit neointimal hyperplasia are urgently needed. The Coll-R is a sirolimus-eluting collagen matrix designed for intra-operative perivascular implantation around the graft-venous anastomosis. Sirolimus is an anti-proliferative drug that has proven clinical utility in suppressing neointimal tissue growth in coronary artery disease when delivered locally to the vascular wall by an endovascular drug eluting stent. A cohort of 12 chronic hemodialysis patients underwent surgical placement of 13 polytetrafluoroethylene grafts + Coll-R and were followed for up to 24 months. The primary endpoint was safety (freedom from device related adverse events). Secondary endpoints were pharmacokinetics of sirolimus release, success of Coll-R implantation and primary unassisted graft patency. There were no technical failures, infections, vascular anastomotic or wound-healing problems. Whole blood sirolimus levels rose to a mean peak of 4.8 ng/mL at 6 h and fell to <1 ng/mL at 1 week (n = 5). Twelve and 24-month primary unassisted patencies were 76 and 38%, respectively, and the thrombosis rate was 0.37/patient-year. Perivascular implantation of the Coll-R during graft surgery safely delivered sirolimus to the vascular wall. Systemic sirolimus levels were sub-therapeutic for immunosuppression. This small first-in-human study supports the concept that the Coll-R can safely deliver sirolimus to the graft-venous anastomosis. Safety and patency in this small study were sufficiently encouraging to justify randomized controlled trials to further test the efficacy of the Coll-R.	\N	\N
22248333	We assessed HIV prevalence and associated behaviors and risk factors among men who have sex with men (MSM) in Beijing, China. Five hundred MSM were recruited for a biological and behavioral survey using respondent-driven sampling (RDS) in 2009. Serologic specimens were tested for markers of HIV and syphilis infection. A computer-assisted personal interview (CAPI) administered questionnaire gathered information including demographic characteristics, sexual behaviors, HIV testing, and social norms concerning condom use. The adjusted HIV prevalence was 8.0%, syphilis 22.0%. HIV testing and disclosure was low; only 39.3% had HIV tested in the past 12 months, 49.7% knew their own HIV status and 22.8% knew their last male partner's HIV status. HIV infection was associated with syphilis, ever having sex with a woman, not knowing the HIV status of the most recent male partner, and never buying condoms in the past 12 months. Stronger endorsement of positive social norms around condom use strongly and predicted lower prevalence of HIV infection. Compared to surveys of similar design in the recent past, HIV continues to spread rapidly among Beijing's MSM. Our results identify points of intervention that, if addressed in time, may still alter the course of the epidemic including the promotion of HIV testing and partner disclosure, syphilis control and particularly changing social norms around condom use.	\N	\N
22249461	Kuru was the first human transmissible spongiform encephalopathy (TSE) or prion disease identified, occurring in the Fore linguistic group of Papua New Guinea. Kuru was a uniformly fatal cerebellar ataxic syndrome, usually followed by choreiform and athetoid movements. Kuru imposed a strong balancing selection on the Fore population, with individuals homozygous for the 129 Met allele of the gene (PRNP) encoding for prion protein (PrP) being the most susceptible. The decline in the incidence of kuru in the Fore has been attributed to the exhaustion of the susceptible genotype and ultimately by discontinuation of exposure via cannibalism. Neuropathologically, kuru-affected brains were characterized by widespread degeneration of neurons, astroglial and microglial proliferation, and the presence of amyloid plaques. These early findings have been confirmed and extended by recent immunohistochemical studies for the detection of the TSE-specific PrP (PrP). Confocal laser microscopy also showed the concentration of glial fibrillary acidic protein-positive astrocytic processes at the plaque periphery. The fine structure of plaques corresponds to that described earlier by light microscopy. The successful experimental transmission of kuru led to the awareness of its similarity to Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease and formed a background against which the recent epidemics of iatrogenic and variant Creutzfeldt-Jakob disease could be studied.	\N	\N
22252480	The objective is to evaluate the relationship between cholesterolemia, serum apolipoprotein B (apoB) level and blood pressure in a large sample of general population. The Brisighella Heart Study (BHS) is a prospective, population-based longitudinal epidemiological investigation. For this study, we analysed the data sampled in the 2008 BHS population survey, excluding those participants treated with antihypertensive and/or lipid lowering drugs (N: 2473). In a sex, BMI, smoking habit, physical activity level and serum creatinine adjusted model, low-density lipoprotein-cholesterol (LDL-C) appears to be significantly related to SBP (P < 0.001), DBP (P = 0.026), and pulse pressure (PP) (P < 0.001). In individuals aged less than 52 years, LDL-C was significantly associated to SBP and DBP (P < 0.001), but not PP. In the same model, apoB appears to be mildly but significantly related to SBP (P < 0.001), DBP (P < 0.001), and PP (P < 0.001). In individuals aged less than 52 years, apoB was significantly associated to SBP (P < 0.001), DBP (P < 0.001), and PP (P < 0.001). In individuals aged 52 or more, nor LDL-C neither apoB were significantly associated to blood pressure. Including in the same model LDL-C and apoB, apoB excluded the predicting role of LDL-C as it regards the blood pressure either in the whole population sample and in the younger individuals. On the basis of our observation, either serum LDL-C and apoB are significantly related to the blood pressure level in a large sample of individuals untreated with antihypertensive and lipid-lowering drugs. This association is stronger in younger individuals than in elderly. ApoB seems to be a stronger predictor of either SBP, DBP and PP than LDL-C.	\N	\N
22253312	During past decades, twin studies have played an important role in genetic epidemiology studies of complex traits. The strength of twin studies lies in the ability to disentangle genetic and environmental factors that contribute to a phenotype, by comparing genetically identical monozygotic twins to dizygotic twins, who share on average 50% of genetic variants. Twin studies now offer the opportunity to study epigenetic variation across the genome with two aims. First, twin studies can improve our understanding of the factors regulating epigenetic variability by assessing the heritability of epigenetic variants. Secondly, the use of twins in epigenetic research is increasingly recognized as an important approach to help unravel the complexities associated with human development and disease. The strategic use of identical twins discordant for complex disease has revealed the importance of linking epigenetic disruption to the disease-associated risk in humans. Lastly, we also discuss the possibility that epigenetic effects on disease may in part explain some of the missing heritability in genome-wide association studies. The study of human epigenetic factors in twins can inform the role of genetics, as well as in utero and postnatal environments to the establishment, maintenance and functional consequences of human epigenome variation.	\N	\N
22257051	Extracellular matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases involved in physiological and pathological processes, through the cleavage of extracellular matrix. MMPs are capable of degrading essentially all matrix components, which is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. The vertebrates MMP family includes at least 26 enzymes (23 have been known in humans) with only MMP-1, 2, and 7 experimentally validated as targets for antitumoral drug design. However, inhibition of MMP-1 has been hypothesized to be the cause of the clinically observed musculoskeletal syndrome when broad spectrum inhibitors are used. On the other hand, MMP-9 is a tricky enzyme, since its inhibition might be useful in treating patients with early-stage cancers, but MMP-9 is an anti-target in patients with advanced disease. So, MMP-9 inhibition should also be prevented. Therefore, selective MMP-2 inhibition arises as a pursued profile for MMP binders. Among them, hydroxamates have been extensively studied as small molecule drug candidates characterized by an effective zinc-binding group plus additional side chains responsible for the selectivity. This article pays particular attention to MMP-2 selectivity on hydroxamate-type inhibitors, especially against MMP-9, and their chemical structure, SAR, general synthetic methods, and molecular modelling studies are here reviewed in order to inspire further design of new effective anticancer agents.	\N	\N
22266119	The apicomplexan parasite Plasmodium vivax is responsible for causing more than 70% of human malaria cases in Central and South America, Southeastern Asia and the Indian subcontinent. The rising severity of the disease and the increasing incidences of resistance shown by this parasite towards usual therapeutic regimens have necessitated investigation of putative novel drug targets to combat this disease. The apicoplast, an organelle of procaryotic origin, and its circular genome carrying genes of possible functional importance, are being looked upon as potential drug targets. The genes on this circular genome are believed to be highly conserved among all Plasmodium species. Till date, the plastid genome of P. falciparum, P. berghei and P. chabaudi have been detailed while partial sequences of some genes from other parasites including P. vivax have been studied for identifying evolutionary positions of these parasites. The functional aspects and significance of most of these genes are still hypothetical. In one of our previous reports, we have detailed the complete sequence, as well as structural and functional characteristics of the Elongation factor encoding tufA gene from the plastid genome of P. vivax. We present here the sequences of large and small subunit rRNA (lsu and ssu rRNA) genes, sufB (ORF470) gene, RNA polymerase (rpo B, C) subunit genes and clpC (casienolytic protease) gene from the plastid genome of P. vivax. A comparative analysis of these genes between P. vivax and P. falciparum reveals approximately 5-16% differences. A codon usage analysis of major plastid genes has shown a high frequency of codons rich in A/T at any or all of the three positions in all the species. TTA, AAT, AAA, TAT, and ATA are the major preferred codons. The sequences, functional domains and structural analysis of respective proteins do not show any variations in the active sites. A comparative analysis of these Indian P. vivax plastid genome encoded genes has also been done to understand the evolutionary position of the Indian parasite in comparison to other Plasmodium species.	\N	\N
22267663	Oral candidiasis is often accompanied by severe inflammation, resulting in a decline in the quality of life of immunosuppressed individuals and elderly people. To develop a new oral therapeutic option for candidiasis, a nonpathogenic commensal oral probiotic microorganism, Streptococcus salivarius K12, was evaluated for its ability to modulate Candida albicans growth in vitro, and its therapeutic activity in an experimental oral candidiasis model was tested. In vitro inhibition of mycelial growth of C. albicans was determined by plate assay and fluorescence microscopy. Addition of S. salivarius K12 to modified RPMI 1640 culture medium inhibited the adherence of C. albicans to the plastic petri dish in a dose-dependent manner. Preculture of S. salivarius K12 potentiated its inhibitory activity for adherence of C. albicans. Interestingly, S. salivarius K12 was not directly fungicidal but appeared to inhibit Candida adhesion to the substratum by preferentially binding to hyphae rather than yeast. To determine the potentially anti-infective attributes of S. salivarius K12 in oral candidiasis, the probiotic was administered to mice with orally induced candidiasis. Oral treatment with S. salivarius K12 significantly protected the mice from severe candidiasis. These findings suggest that S. salivarius K12 may inhibit the process of invasion of C. albicans into mucous surfaces or its adhesion to denture acrylic resins by mechanisms not associated with the antimicrobial activity of the bacteriocin. S. salivarius K12 may be useful as a probiotic as a protective tool for oral care, especially with regard to candidiasis.	\N	\N
22270369	α-Dystroglycan (α-DG) is a membrane-associated glycoprotein that interacts with several extracellular matrix proteins, including laminin and agrin. Aberrant glycosylation of α-DG disrupts its interaction with ligands and causes a certain type of muscular dystrophy commonly referred to as dystroglycanopathy. It has been reported that a unique O-mannosyl tetrasaccharide (Neu5Ac-α2,3-Gal-β1,4-GlcNAc-β1,2-Man) and a phosphodiester-linked modification on O-mannose play important roles in the laminin binding activity of α-DG. In this study, we use several dystroglycanopathy mouse models to demonstrate that, in addition to fukutin and LARGE, FKRP (fukutin-related protein) is also involved in the post-phosphoryl modification of O-mannose on α-DG. Furthermore, we have found that the glycosylation status of α-DG in lung and testis is minimally affected by defects in fukutin, LARGE, or FKRP. α-DG prepared from wild-type lung- or testis-derived cells lacks the post-phosphoryl moiety and shows little laminin-binding activity. These results show that FKRP is involved in post-phosphoryl modification rather than in O-mannosyl tetrasaccharide synthesis. Our data also demonstrate that post-phosphoryl modification not only plays critical roles in the pathogenesis of dystroglycanopathy but also is a key determinant of α-DG functional expression as a laminin receptor in normal tissues and cells.	\N	\N
22276367	Evaluation of the fitness of an accused person to participate in legal proceedings is a classic forensic activity. Before the trial, the forensic expert will already assess any preexisting somatic and psychological illnesses and give a written expert opinion describing the condition of the accused at the time of the examination and assessing whether he is fit to stand trial. Nevertheless, decompensation or aggravation of a disease may occur--especially in stress situations as they are to be expected for an accused in the courtroom--so that apart from the current evaluation of the state of health of the accused, emergency treatment may occasionally become necessary in the courtroom. The article tries to answer the question how the expert can meet this challenge.	\N	\N
22280950	Endocardial lead-induced tricuspid regurgitation has not been well recognized, either clinically or echocardiographically, and yet it is likely a preventable iatrogenic disease. In severe cases, it can lead to right ventricular failure and require tricuspid valve surgery. This complication will become increasingly important, because the numbers of permanent pacemakers and implantable cardioverter-defibrillators are expected to increase because of the aging population and the expanding capabilities of these devices. Published studies are largely retrospective, and serial studies to assess the time course of the development of tricuspid regurgitation are lacking. The mechanisms and severity of tricuspid regurgitation may not be well evaluated by two-dimensional echocardiography. Real-time three-dimensional echocardiography appears to be a promising technique to evaluate the mechanism of tricuspid regurgitation and may allow the early detection of patients who will develop severe lead-induced tricuspid regurgitation. A better understanding of the mechanism of lead-induced tricuspid regurgitation will be essential to the development of preventive strategies, which can then be tested in future clinical trials.	\N	\N
22281228	Progressive multifocal leukoencephalopathy (PML) is a subacute central nervous system infection due to reactivation of the JC virus. Most reported cases occurred in HIV-infected patients (80% of cases), patients with lymphoid malignancies (13%) and transplant recipients taking immunosuppressants (5%). Less often, PML has been described in patients with chronic inflammatory joint diseases associated with autoimmune disorders (lupus, rheumatoid arthritis [RA] and vasculitis) (2%). Magnetic resonance imaging of the brain shows suggestive changes and confirmation of the diagnosis is obtained by performing PCR tests to identify the JC virus in the cerebrospinal fluid or, when necessary, a brain biopsy. No treatments have been proven effective. Most patients experience progressive disease that is fatal within a few months or induces incapacitating neurological impairments. The risk of PML is 0.4/100,000 in patients with RA. In the few case-reports of PML in RA patients, the treatments used included methotrexate (five cases) combined with a biological agent such as infliximab (one case), rituximab (four cases), or leflunomide (two cases including one with concomitant rituximab). PML is an extremely rare but devastating complication. Rituximab therapy is associated with an increased prevalence of PML in RA patients (4/100,000), who should be informed of this risk. In patients with lupus, the risk of PML is higher than in RA (4/100,000) and 40% of cases of PML occur during low-dose glucocorticoid therapy without immunosuppressive therapy.	\N	\N
22281918	Sporotrichosis is a subcutaneous fungal infection caused by Sporothrix schenckii and acquired by direct inoculation. Although the majority of cases consist of the classic lymphocutaneous presentation, the frequency of atypical and severe clinical forms of the disease has increased progressively. Systemic and disseminated cutaneous sporotrichosis constitute rare variants and such cases are generally associated with cellular immunodeficiency or debilitated states. The present paper describes the first published case of molluscum-like lesions in disseminated mucocutaneous sporotrichosis. Direct mycological examination and histopathology revealed numerous yeast cells.	\N	\N
22283575	Inhaled dry powder mannitol is well established for use in bronchial provocation testing. Inhaled mannitol also increases mucociliary clearance, and therefore could have a role in treating chronic suppurative lung disease. There have been a number of studies in cystic fibrosis and bronchiectasis. An international Phase III trial has just been published that suggests the use of regular inhaled mannitol increases lung function and reduces exacerbation frequency in cystic fibrosis. Inhaled mannitol exerts its effects in a number of ways, most importantly like hypertonic saline, setting up an osmotic gradient so water flows into the airway lumen, increasing mucus hydration and mucociliary clearance. Its formulation as a dry powder makes it quick and convenient to take.	\N	\N
22288822	Urinary schistosomiasis is caused by the digenetic trematode Schistosoma haematobium, characterized by accumulation of eggs in the genitourinary tract. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) can play an important role in parasitic infection due to its major role as a negative regulator of T-cell activation and proliferation. This study was performed in patients with schistosomiasis and healthy controls to analyze the allele and genotype frequencies of four CTLA-4 gene polymorphisms. The CTLA-4 gene was amplified using Taqman real-time polymerase chain reaction, and allele and genotypes of 49 patients with schistosomiasis were analyzed using allelic discrimination analysis followed by subsequent direct sequencing. The results were compared with healthy control subjects. The frequencies of CTLA-4 rs733618 A allele at position -1722 (p=0.001), rs11571316 C allele at position -1577 (p<0.001), and rs231775 A allele at position +49 (p=0.002) in the patient group were significantly higher than the control group. The rs733618 AA genotype (p=0.001), rs11571316 CC genotype (p<0.001), and rs231775 AA genotype (p=0.007) were also significantly overrepresented. Meanwhile, rs733618 AG genotype (p=0.001), rs11571316 CT genotype (p=0.02), and rs231775 GG genotype (p=0.029) were significantly decreased in the patients with schistosomiasis, as compared with the controls. No significant difference was observed in both allele and genotype of rs16841252. The results of this study suggest that the rs733618, rs11571316, and rs231775 polymorphisms in the CTLA-4 gene may influence susceptibility to schistosomiasis infection in the Gabonese children.	\N	\N
22289889	Accumulating evidence indicates that infiltrating stromal cells contribute directly and indirectly to tumor growth in a wide range of cancers. In follicular lymphoma (FL), malignant B cells are found admixed with heterogeneous lymphoid-like stromal cells within invaded lymph nodes and BM. In addition, mesenchymal stromal cells (MSCs) support in vitro FL B-cell survival, in particular after their engagement toward lymphoid differentiation. We show here that BM-MSCs obtained from patients with FL (FL-MSCs) display a specific gene expression profile compared with MSCs obtained from healthy age-matched donors (HD-MSCs). This FL-MSC signature is significantly enriched for genes associated with a lymphoid-like commitment. Interestingly, CCL2 could be detected at a high level within the FL-cell niche, is up-regulated in HD-MSCs by coculture with malignant B cells, and is overexpressed by FL-MSCs, in agreement with their capacity to recruit monocytes more efficiently than HD-MSCs. Moreover, FL-MSCs and macrophages cooperate to sustain malignant B-cell growth, whereas FL-MSCs drive monocyte differentiation toward a proangiogenic and lipopolysaccharide-unresponsive phenotype close to that of tumor-associated macrophages. Altogether, these results highlight the complex role of FL stromal cells that promote direct tumor B-cell growth and orchestrate FL-cell niche, thus emerging as a potential therapeutic target in this disease.	\N	\N
22299123	Abuse of methamphetamine (meth), a potent central nervous system stimulant, has been associated with significant dental disease. Current descriptions of "meth mouth" are limited in their scope and fail to illuminate the potential pathogenic mechanisms of meth for oral disease. The purpose of this pilot study was to characterize the oral health of subjects with a history of meth abuse as compared to nonabusing control subjects. A total of 28 meth abusers and 16 control subjects were enrolled. Interviews and surveys regarding meth abuse, dental history, oral hygiene, and diet were collected. A comprehensive oral cavity examination including salivary characterization was completed. We observed significantly higher rates of decayed surfaces, missing teeth, tooth wear, plaque, and calculus among meth abusers. No significant difference in salivary flow rates were noted, yet results showed significant trends for lower pH and decreased buffering capacity. These findings suggest that salivary quality may play a more important role in meth mouth than previously considered. Salivary analysis may be useful when managing a dental patient with history of methamphetamine abuse.	\N	\N
22299530	Traditional forms of treatment of the thyroid diseases: pharmacotherapy, radioiodine therapy and surgery can not always be applied. Intolerance, side effects of antithyroid drugs, low iodine uptake, high risk of surgery or disagreement with the proposed treatment was the reason for seeking alternative healing methods. With the development of interventional radiology, and gained experience in the use of arterial embolization, this method has become possible to use in treatment of thyroid diseases. The essence of this treatment is to shut down blood flow in major arteries of the thyroid by direct injection into the vessel's light of adequate size particles containing polyvinyl alcohol (PVA). The consequence of acute ischemia is septic necrosis of the glandular tissue in a field being supplied by this artery. Further repair processes and fibrosis lead to a reduction of active thyroid hormone synthesis and restriction of thyroid gland. Effects of embolization on angiogenesis, apoptosis and autoimmune reactions contribute to compensation thyroid function and significant reduction a goiter volume in course of Graves' disease. Preoperative selective embolization of a huge goiter or thyroid cancer improves surgery outcomes, reduces the risk of hemorrhage and damage to surrounding tissue. Palliative use of embolization in advanced stages of thyroid cancer reduces symptoms and improves quality of life. Little invasive nature of this procedure, the lack of serious undesirable coincidence makes embolization of thyroid arteries an attractive form of a therapy, which may become a therapeutic option in many difficult clinical situations and improve the clinical effectiveness of treatment of thyroid disease.	\N	\N
22299533	Objectification assess the health status of COPD patients poses numerous problems arising from the complexity of both the disease and medical co-operation with the patient. So far, the methods adopted do not correlate with the quality of life. Also, the discrepancy in the evaluation of their symptoms by patients leads to an underestimation of obtained information. Recently proposed a test study of COPD has been validated in many countries and can be implemented into daily practice.	\N	\N
22302706	Homozygous germline mutations of the PARK2 gene are responsible for the development of early-onset Parkinson's disease (PD). Homozygous PARK2 mutations have been also detected in lung adenocarcinoma (LADC). However, since heterozygous PARK2 germline mutations are present in a subset of non-PD individuals, the timing for the occurrence of two-hit PARK2 mutations in LADC progression is unclear. Therefore, we comprehensively analyzed mutations, expression and copy number variations of the PARK2 gene in 267 primary LADCs together with the corresponding noncancerous lung cells and 39 LADC cell lines. Heterozygous germline exonic deletions were detected in five patients with LADC, and loss of heterozygosity including the PARK2 locus was detected in 31/267 (11.6%) LADCs. However, homozygous PARK2 inactivation was not detected in any of them, including the five patients with germline mutations. Homozygous PARK2 inactivation was detected in 6/39 (15%) cell lines, two exonic deletions, one exonic duplication, and three point mutations, while heterozygous PARK2 inactivation was detected in two cell lines (both by exonic deletions). These results strongly indicate that somatic PARK2 mutations occur rarely (or do not occur) in LADC development and that germline PARK2 mutations could contribute to LADC progression but not to LADC development.	\N	\N
22304951	Coronary computed tomography angiography (CTA) is a highly accurate noninvasive test that is increasingly used in symptomatic patients primarily for the diagnosis of coronary artery disease (CAD). Beyond its proven accuracy, data have now clearly demonstrated the incremental prognostic information available from coronary CTA related to the presence, extent, and severity of obstructive and nonobstructive CAD across a variety of clinical settings and patient populations. Current evidence supports the use of coronary CTA not only for the diagnosis of CAD in appropriately selected symptomatic patients but also to further refine their cardiovascular risk assessment following testing.	\N	\N
22306387	Heart disease is one of the leading causes of death in the United States. With the increase in substance abuse, the incidence of acute myocardial infarction (MI) in younger population has been on the rise. Traditionally, cocaine has been blamed for acute MI; however, recently, there have been more incidences of marijuana as an inciting factor. We present a case of marijuana-induced acute MI and discuss the proposed mechanism.	\N	\N
22309448	The aetiology of female pattern hair loss (FPHL) is largely unknown. However, it is hypothesized that FPHL and male pattern baldness (AGA) share common susceptibility alleles. The two major susceptibility loci for AGA are the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X-chromosome, and a locus on chromosome 20p11, for which no candidate gene has yet been identified. To examine the role of the AR/EDA2R and 20p11 loci in the development of FPHL using 145 U.K. and 85 German patients with FPHL, 179 U.K. supercontrols and 150 German blood donors. Patients and controls were genotyped for 25 single nucleotide polymorphisms (SNPs) at the AR/EDA2R locus and five SNPs at the 20p11 locus. Analysis of the AR/EDA2R locus revealed no significant association in the German sample. However, a nominally significant association for a single SNP (rs1397631) was found in the U.K. sample. Subgroup analysis of the U.K. patients revealed significant association for seven markers in patients with an early onset (P = 0·047 after adjustment for the testing of multiple SNPs by Monte Carlo simulation). No significant association was obtained for the five 20p11 variants, either in the overall samples or in the analysis of subgroups. The observed association suggests that the AR/EDA2R locus confers susceptibility to early-onset FHPL. Our results do not implicate the 20p11 locus in the aetiology of FPHL.	\N	\N
22310615	Due to the severe shortage of deceased donors in Japan, ABO-incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved; the rates of graft survival among these patients are currently similar to those of recipients of ABO-compatible grafts. Our single-center experience describing the immunosuppressive protocols, complications, and grafts survivals is documented in this study. Among 123 patients with end-stage renal disease who underwent living donor kidney transplantation between January 1999 and December 2010, 25 cases were ABO-incompatible grafts. All of these patients were followed until August 2011. Analyzing these patients, we focused on their immunosuppressive protocols, complications, and graft survivals. Patient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and an intractable acute cellular rejection episode, 1 patient an antibody-mediated rejection, and 6 patients had acute cellular rejection episodes. However, there were no severe complications. Although ABO-incompatible kidney transplantation is a high-risk procedure, a short-term graft survival rate of 100% may be expected due to recent significant improvements in desensitization and recipient management.	\N	\N
22312826	Combination anti-HIV therapies revolutionized patient life expectancy in the mid-1990's. Afterwards, in the early 2000's, research focused on the adverse effects caused by HIV drugs. Among these, the most serious ones are myocardial infarction at young age, disturbances of kidney function, liver disorders, pancreatitis and osteoporosis. The worsening of prognosis, for instance in respect of cardiac diseases, observed approximately five years ago in patients due to pauses in HIV medication, has changed perspective. Currently it is being discussed whether the overall prognosis will be improved with HIV medication started as early as possible.	\N	\N
22318137	Herpes simplex virus 1 (HSV-1) and HSV-2 are medically significant pathogens. The development of an effective HSV vaccine remains a global public health priority. HSV-1 and HSV-2 immunodominant "asymptomatic" antigens (ID-A-Ags), which are strongly recognized by B and T cells from seropositive healthy asymptomatic individuals, may be critical to be included in an effective immunotherapeutic HSV vaccine. In contrast, immunodominant "symptomatic" antigens (ID-S-Ags) may exacerbate herpetic disease and therefore must be excluded from any HSV vaccine. In the present study, proteome microarrays of 88 HSV-1 and 84 HSV-2 open reading frames(ORFs) (ORFomes) were constructed and probed with sera from 32 HSV-1-, 6 HSV-2-, and 5 HSV-1/HSV-2-seropositive individuals and 47 seronegative healthy individuals (negative controls). The proteins detected in both HSV-1 and HSV-2 proteome microarrays were further classified according to their recognition by sera from HSV-seropositive clinically defined symptomatic (n = 10) and asymptomatic (n = 10) individuals. We found that (i) serum antibodies recognized an average of 6 ORFs per seropositive individual; (ii) the antibody responses to HSV antigens were diverse among HSV-1- and HSV-2-seropositive individuals; (iii) panels of 21 and 30 immunodominant antigens (ID-Ags) were identified from the HSV-1 and HSV-2 ORFomes, respectively, as being highly and frequently recognized by serum antibodies from seropositive individuals; and (iv) interestingly, four HSV-1 and HSV-2 cross-reactive asymptomatic ID-A-Ags, US4, US11, UL30, and UL42, were strongly and frequently recognized by sera from 10 of 10 asymptomatic patients but not by sera from 10 of 10 symptomatic patients (P < 0.001). In contrast, sera from symptomatic patients preferentially recognized the US10 ID-S-Ag (P < 0.001). We have identified previously unreported immunodominant HSV antigens, among which were 4 ID-A-Ags and 1 ID-S-Ag. These newly identified ID-A-Ags could lead to the development of an efficient "asymptomatic" vaccine against ocular, orofacial, and genital herpes.	\N	\N
22319048	Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.	\N	\N
22326991	After age, the second largest risk factor for Alzheimer's disease (AD) is apolipoprotein E (APOE) genotype, where APOE4 is associated with lower apoE protein levels, more severer brain pathology, enhanced inflammation and disease. Small peptides corresponding to the receptor-binding region of apoE mimic the anti-inflammatory activity of the apoE holoprotein. These apoE mimetics greatly improve behavioral outcomes and neuronal survival in head trauma models that display AD pathology and neuronal loss. To determine whether apoE mimetics change behavior, inflammation and pathology in CVND-AD (SwDI-APP/NOS2(-/-)) transgenic mice. Starting at 9 months, apoE peptides were subcutaneously administered 3 times per week for 3 months followed by behavioral, histochemical and biochemical testing. Treatment with apoE mimetics significantly improved behavior while decreasing the inflammatory cytokine IL-6, neurofibrillary tangle-like and amyloid plaque-like structures. Biochemical measures matched the visible pathological results. Treatment with apoE mimetics significantly improved behavior, reduced inflammation and reduced pathology in CVND-AD mice. These improvements are associated with apoE-mimetic-mediated increases in protein phosphatase 2A activity. Testing in additional AD models showed similar benefits, reinforcing this novel mechanism of action of apoE mimetics. These data suggest that the combination of anti-inflammatory and neuroprotective activities of apoE mimetics represents a new generation of potential therapeutics for AD.	\N	\N
22333444	To investigate the feasibility and safety of unilateral incision hybrid fixation using pedicle screws and a translaminar screw in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). From January to June 2010, 18 patients with single-level lumbar disc disease were treated with MIS-TLIF under METRx(TM) X-tube. After decompression and fixation using unilateral pedicle screws, a translaminar screw was inserted from the same incision to the other side. The results of perioperative parameters, radiographic images and clinical outcomes were assessed. All patients underwent MIS-TLIF were accomplished unilateral hybrid fixation without any neural complication. The average operative time was (107 ± 19) min, the average operative blood loss was (62 ± 21) ml, and the average postoperative ambulation time was (21 ± 5) h. The average length of translaminar facets screw was (52 ± 2) mm, and the postoperative images showed all screws penetrate through facets joint. During the follow-up the visual analogue scale and Oswestry disability index scores were significant improved compared with preoperative (F = 42.221 - 259.833, P < 0.01). Bilateral hybrid fixation could be completed through unilateral incision by pedicle screws and a translaminar screw in MIS-TLIF, and the advantage including less invasion, quickly recovery, short operative time, and saving fixation cost.	\N	\N
22335481	Optical imaging has seen significant developments over the past decade as an investigational tool for in-vivo visualization of cellular and sub-cellular events. With the recent addition of optoacoustic (photoacoustic) methods, in particular multi-spectral opto-acoustic tomography (MSOT), to the already rich armamentarium of photonic methods the capacity of optical molecular imaging across scales has widened significantly. MSOT brings unique features into optical imaging, namely high resolution optical imaging over several millimeters to centimeters of tissue depth and the ability to simultaneously resolve multiple tissue molecules and extrinsically administered optical or optoacoustic agents with physiological or molecular specificity. Here, we discuss the implications of utilizing MSOT in the context of drug discovery and review suitable optoacoustic agents against disease and drug efficacy biomarkers. The combination of existing knowledge on generating optical targeted contrast, with the high resolution deep tissue visualization offered by MSOT, allows for the development of next-generation biological optical imaging and corresponding drug discovery applications.	\N	\N
22337313	Rubella virus (RV) usually causes a mild disease. However, infection during the first trimester of pregnancy often leads to severe birth defects known as congenital rubella syndrome (CRS). Although wild-type RVs exist and circulate worldwide, their genotypes remain unknown in many countries. The aim of this study was to identify the molecular characteristics of RVs found in Vietnam during the years 2009-2010 and to provide the first data concerning RV genotypes in this country. Throat swab samples were collected between 2009 and 2010 from four CRS cases and nine rubella infection cases visiting one Children's Hospital and one outpatient clinic in Ho Chi Minh City. The 739-nucleotide coding region of the RV E1 gene recommended by the World Health Organization was amplified by reverse transcriptase PCR, and the resulting DNA fragments were then sequenced. Sequences were assigned to genotypes by phylogenetic analysis with RV reference strains. RV RNA was detected in 11 clinical specimens. Phylogenetic analysis of the sequences showed that all 11 strains belonged to 2B genotype. Several variations in amino acids were found, among which five changes were involved in the B and T cell epitopes. These data indicate that viruses of genotype 2B were circulating in Vietnam. The increasing information about RV genotype in Vietnam should aid in the control of rubella infection and CRS in this country.	\N	\N
22339380	Acute pancreatitis is an acute inflammatory condition of the pancreas, which might extend to local and distant extrapancreatic tissues. The global incidence varies between 17.5 and 73.4 cases per 100,000 and the pathogenesis recognizes alcohol exposure and biliary tract disease as the leading causes, ahead of post-endoscopic retrograde cholangiopancreatography, drugs and abdominal trauma. The diagnosis of acute pancreatitis is substantially based on a combination of clinical signs and symptoms, imaging techniques and laboratory investigations. Contrast-enhanced computed tomography is the reference standard for the diagnosis, as well as for establishing disease severity. The assessment of pancreatic enzymes, early released from necrotic tissue, is the cornerstone of laboratory diagnosis in this clinical setting. Although there is no single test that shows optimal diagnostic accuracy, most current guidelines and recommendations indicate that lipase should be preferred over total and pancreatic amylase. Although a definitive diagnostic threshold cannot be identified, cut-offs comprised between ≥ 2 and ≥ 4 times the upper limit of the reference interval are preferable. The combination of amylase and lipase has been discouraged as although it marginally improves the diagnostic efficiency of either marker alone, it increases the cost of investigation. Some interesting biomarkers have been also suggested (e.g., serum and urinary trypsinogen-1, -2 and -3, phospholipase A2, pancreatic elastase, procalcitonin, trypsinogen activated protein, activation peptide of carboxypeptidase B, trypsin-2-alpha1 antitrypsin complex and circulating DNA), but none of them has found widespread application for a variety of reasons, including the inferior diagnostic accuracy when compared with the traditional enzymes, the use of cumbersome techniques, or their recent discovery. The promising results of recent proteomics studies showed that this innovative technique might allow the identification of changes characterizing pancreatic tissue injury, thus highlighting new potential biomarkers of acute pancreatitis.	\N	\N
22353988	Several studies have reported that patients with essential tremor (ET) may also have mild cognitive impairment. Event-related potentials (ERPs) involve cognitive processes in the brain. No detailed investigation has been conducted into auditory ERPs (AERPs) to detect the subclinical cognitive dysfunction in patients with ET. Therefore, this study aimed to clarify the usefulness of AERPs in ET-related cognitive impairment. The AERPs were obtained by using an oddball paradigm in 27 patients with ET and 27 age-matched control subjects. The mean latency and amplitude of the ERPs were compared between the two groups. The correlation between disease duration and the mean values of all components of the potentials was assessed. The association between tremor severity and potentials was also evaluated. The patients with ET showed significant prolongation of all components of the ERP latencies at each electrode site. The N200 and P300 amplitudes were reduced in the ET group. Interestingly, the significant prolongation of N100 and N200 latencies correlated with disease duration, and N200 latencies appeared significantly longer in patients with severe tremor. Significant differences were found between the components of the AERPs and tremor severity and disease duration. This finding implies that ERPs may be useful in evaluating the cognitive functions in ET and that those AERP abnormalities may appear before clinical presentation.	\N	\N
22356008	A 22 year old female with valvular heart disease, moderate mitral valve insufficiency, moderate aortic insufficiency, extensive aneurysmal dilatation of the entire ascending aorta and arch, and segmental dilatation of descending aorta underwent entire anterior aortic replacement. We performed aortic root and valve replacement with a composite graft, followed by coronary artery reimplantation using the Bentall and De Bono technique. Simultaneously, we carried out a graft replacement of the transverse arch and descending aortic aneurysms with a woven Dacron graft using the Elephant Trunk technique. The goal of this surgery was to correct or optimally treat the multiple sites of aortic disease. To the best of our knowledge, there is no reported case from Pakistan with extensive aortic grafting from root to descending aorta using the Bentall and Elephant Trunk technique simultaneously.	\N	\N
22363380	The redox system is an important anti-oxidative system composed of thioredoxin, thioredoxin reductase, and peroxiredoxin (PRx). The fine details of PRx expression and its protective effects in various cells in cardiovascular tissue under oxidative stress created by hydrogen peroxide have not been fully elucidated. Oxidative stress was induced by adding hydrogen peroxide at 0.25 mM for 2 hours to rat neonatal cardiomyocytes (rCMCs), rat vascular smooth muscle cells (rVSMCs), and human umbilical vein endothelial cells (HUVECs). Apoptosis was quantified by flow cytometry and the expression patterns of the six PRx isoforms were evaluated by western blotting in the three cell lines after hydrogen peroxide stimulation. Apoptosis and the cell survival signal pathway were evaluated by PRx1 gene delivery using lentiviral vector in hydrogen peroxide stimulated rCMCs versus green fluorescence protein gene delivery. Hydrogen peroxide induced 25% apoptosis in rCMCs. Furthermore, the PRx1 and 5 isoforms were found to be overexpressed in hydrogen peroxide treated rCMCs, and PRx1 overexpression by gene delivery was found to reduce hydrogen peroxide induced rCMCs apoptosis significantly. In addition, this effect was found to originate from cell survival pathway modification. Hydrogen peroxide induced significant oxidative stress in rCMCs, rVSMCs, and HUVECs, and PRx1 overexpression using a lentiviral vector system significantly reduced hydrogen peroxide induced rCMCs apoptosis by upregulation of cell survival signals and downregulation of apoptotic signals. These findings suggest that PRx1 could be used as a treatment strategy for myocardial salvage in conditions of oxidative stress.	\N	\N
22363739	Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia. We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a "mild-to-moderate" pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as "avoidable" mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored. The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.	\N	\N
22365640	For an evaluation of the progress achieved in the field of kidney cancer care in the Netherlands in the last decades, we described trends in incidence, treatment, mortality and relative survival. All adult patients newly diagnosed with kidney cancer between 1989 and 2009 (N=32,545) were selected from the Netherlands Cancer Registry. Age-standardised incidence and mortality rates were calculated. Follow-up was completed until January 2010. In order to assess trends estimated annual percentages of change (EAPC) were estimated. The incidence of kidney cancer has been fairly stable between 1989 and 2001 with a European Standardised Rate of approximately 11 per 100,000 person years (PY). Since 2001 the incidence increased to 13 per 100,000 PY in 2009 (EAPC: 2.4%; 95%confidence interval (CI): 1.5 to 3.4%). The mortality rate decreased slightly over time, from 6.2 per 100,000 PY in 1989 to 5.6 in 2010. No changes in treatment were observed, except for the introduction of targeted therapies for stage IV disease, since 2005. The 5-year relative survival improved from 51% in 1989-1994 to 58% in 2005-2009 (EAPC: 0.9%; 95%CI 0.7 to 1.2%). Improvement in survival was especially seen in males, younger age groups and low stages. The incidence of kidney cancer has increased slightly, and survival improved modestly, resulting in a decreasing mortality. A positive effect of the introduction of targeted therapies for metastatic kidney cancer was observed in 1-year relative survival. For progress in kidney cancer care, effective prevention strategies and new therapies remain warranted.	\N	\N
22370242	This review describes the features of modern infrared imaging technology and the standardization protocols for thermal imaging in medicine. The technique essentially uses naturally emitted infrared radiation from the skin surface. Recent studies have investigated the influence of equipment and the methods of image recording. The credibility and acceptance of thermal imaging in medicine is subject to critical use of the technology and proper understanding of thermal physiology. Finally, we review established and evolving medical applications for thermal imaging, including inflammatory diseases, complex regional pain syndrome and Raynaud's phenomenon. Recent interest in the potential applications for fever screening is described, and some other areas of medicine where some research papers have included thermal imaging as an assessment modality. In certain applications thermal imaging is shown to provide objective measurement of temperature changes that are clinically significant.	\N	\N
22383586	To report the annual incidence of occupational diseases (ODs) in economic sectors in The Netherlands. In a 5-year prospective cohort study (2009-2013), occupational physicians were asked to participate in a sentinel surveillance system for OD notification. The inclusion criteria for participation were (1) covering a population of employees, (2) reporting the economic sectors and the size of their employee population and (3) willingness to report all diagnosed ODs. In this study, an OD was defined as a disease with a specific clinical diagnosis that was predominantly caused by work-related factors. The economic sectors (n=21) were defined according the NACE (Nomenclature des Activités Économiques dans la Communauté Européenne) classification. In a total working population of 514,590 employees, 1782 ODs were reported over 12 months in 2009. The estimated annual incidence for any OD was 346 (95% CI 330 to 362) per 100,000 worker-years. Of all the ODs, mental diseases were reported most frequently (41%), followed by musculoskeletal (39%), hearing (11%), infectious (4%), skin (3%), neurological (2%) and respiratory (2%) diseases. The four economic sectors with the highest annual incidences per 100,000 workers were construction (1127; 95% CI 1002 to 1253), mining and quarrying (888; 95% CI 110 to 1667), water and waste processing (832; 95% CI 518 to 1146) and transport and storage (608; 95% CI 526 to 690). ODs are reported in all economic sectors in The Netherlands. Up to 91% of all ODs are mental, musculoskeletal and hearing diseases. Efforts to increase the effective assessment of ODs and compliance in reporting activities enhance the usability of incidence figures for the government, employers and workers.	\N	\N
22394620	The longitudinal degradation mechanism of extracellular matrix (ECM) in the interbertebral disc remains unclear. Our objective was to elucidate catabolic and anabolic gene expression profiles and their balances in intervertebral disc degeneration using a static compression model. Forty-eight 12-week-old male Sprague-Dawley rat tails were instrumented with an Ilizarov-type device with springs and loaded statically at 1.3 MPa for up to 56 days. Experimental loaded and distal-unloaded control discs were harvested and analyzed by real-time reverse transcription-polymerase chain reaction (PCR) messenger RNA quantification for catabolic genes [matrix metalloproteinase (MMP)-1a, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5], anti-catabolic genes [tissue inhibitor of metalloproteinases (TIMP)-1, TIMP-2, and TIMP-3], ECM genes [aggrecan-1, collagen type 1-α1, and collagen type 2-α1], and pro-inflammatory cytokine genes [tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, and IL-6]. Immunohistochemistry for MMP-3, ADAMTS-4, ADAMTS-5, TIMP-1, TIMP-2, and TIMP-3 was performed to assess their protein expression level and distribution. The presence of MMP- and aggrecanase-cleaved aggrecan neoepitopes was similarly investigated to evaluate aggrecanolytic activity. Quantitative PCR demonstrated up-regulation of all MMPs and ADAMTS-4 but not ADAMTS-5. TIMP-1 and TIMP-2 were almost unchanged while TIMP-3 was down-regulated. Down-regulation of aggrecan-1 and collagen type 2-α1 and up-regulation of collagen type 1-α1 were observed. Despite TNF-α elevation, ILs developed little to no up-regulation. Immunohistochemistry showed, in the nucleus pulposus, the percentage of immunopositive cells of MMP-cleaved aggrecan neoepitope increased from 7 through 56 days with increased MMP-3 and decreased TIMP-1 and TIMP-2 immunopositivity. The percentage of immunopositive cells of aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with decreased TIMP-3 immunopositivity. In the annulus fibrosus, MMP-cleaved aggrecan neoepitope presented much the same expression pattern. Aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with increased ADAMTS-4 and ADAMTS-5 immunopositivity. This rat tail sustained static compression model mimics ECM metabolic imbalances of MMPs, aggrecanases, and TIMPs in human degenerative discs. A dominant imbalance of MMP-3/TIMP-1 and TIMP-2 relative to ADAMTS-4 and ADAMTS-5/TIMP-3 signifies an advanced stage of intervertebral disc degeneration.	\N	\N
22407767	Cryptic subtelomeric chromosomal aberrations are responsible for 5-10% of moderate/severe and 1% of mild intellectual disability. Unbalanced subtelomeric chromosomal rearrangements result in variable phenotypes which seem to be highly influenced by both the size of the duplication/deletion and the chromosomes involved in the translocation. We report on three related patients with moderate intellectual disability, language delay, hypotonia, facial dysmorphism, cardiac anomalies, scoliosis, and kyphosis in whom a familial (maternal) unbalanced submicroscopic translocation was found by subtelomeric fluorescence in situ hybridization (FISH). This rearrangement resulted in a partial trisomy 10pter and partial monosomy 21qter. The karyotype was 46,XY.ish der(21)t(10;21)(p14;q22.2). Confirmation of a 6.7 Mb size distal duplication of the p15.3-14 region of chromosome 10 and a 5.6 Mb distal deletion of the q22.2-22.3 region of chromosome 21 was obtained by array-CGH. To our best knowledge, such a composition of subtelomeric unbalanced translocations has not yet been published. Detection of this aberration in successive pregnancies of carrier members of the family by prenatal FISH could prevent the recurrence of the disease. Furthermore, detection of the rearrangements and identification of genes located in the chromosomal regions involved might be of interest.	\N	\N
22412958	This study identified sex differences in progression of cutaneous melanoma. Of 7,338 patients who were diagnosed as an invasive primary CM without clinically detectable metastases from 1976 to 2008 at the University of Tuebingen in Germany, 1,078 developed subsequent metastases during follow up. The metastatic pathways were defined in these patients and analyzed using the Kaplan-Meier method. Multivariate survival analysis was performed using Cox modeling. In 18.7% of men and 29.2% of women (P<0.001) the first metastasis following diagnosis of primary tumor was locoregional as satellite/in-transit metastasis. The majority of men (54.0%) and women (47.6%, P = 0.035) exhibited direct regional lymph node metastasis. Direct distant metastasis from the stage of the primary tumor was observed in 27.3% of men and 23.2% of women (P = 0.13). Site of first metastasis was the most important prognostic factor of survival after recurrence in multivariate analysis (HR:1.3; 95% CI: 1.0-1.6 for metastasis to the regional lymph nodes vs. satellite/in-transit recurrence, and HR:5.5; 95% CI: 4.2-7.1 for distant metastasis vs. satellite/in-transit recurrence, P<0.001). Median time to distant metastasis was 40.5 months (IQR, 58.75) in women and 33 months (IQR, 44.25) in men (P = 0.002). Five-year survival after distant recurrence probability was 5.2% (95% CI: 1.4-2.5) for men compared with 15.3% (95% CI: 11.1-19.5; P = 0.008) for women. Both, the pattern of metastatic spread with more locoregional metastasis in women, and the time course with retracted metastasis in women contributed to the more favorable outcome of women. Furthermore, the total rate of metastasis is increased in men. Interestingly, there is also a much more favorable long term survival of women after development of distant metastasis. It remains a matter of debate and of future research, whether hormonal or immunologic factors may be responsible for these sex differences.	\N	\N
22417127	In approximately 5-8% patients with primary ovarian insufficiency (POI), the disease is caused by an autoimmune process made evident by the appearance of autoantibodies against steroidogenic enzymes (SCA-POI). Anti-müllerian hormone (AMH) is the best marker of the residual follicular pool. To evaluate the rate of loss of the residual follicle pool in women with SCA-POI after clinical diagnosis. One hundred and thirty-two women with POI were tested for 21-hydroxylase autoantibodies, 17α-hydroxylase autoantibodies and P450scc autoantibodies, and 35 patients with SCA-POI were identified. AMH was analysed at the time of the first visit in all women with POI, and in follow-up, serum samples were taken 1-3 years after in 11 women with SCA-POI and detectable AMH. 12/35 (35%) women with SCA-POI had AMH levels within the normal range at the time of first sampling, as compared to 6/97 (6%) with idiopathic POI (P < 0·001). 11/17 (65%) women with SCA-POI with <6 years disease duration had normal serum AMH concentration. A progressive decline in AMH concentration was observed at longitudinal follow-up in all 11 AMH-positive women with SCA-POI, at an estimated average rate of 1·6 μg/l AMH/year (corresponding to an average 57% of preserved follicle pool/previous year) (R(2)  = 0·219, P = 0·028). After 6 years of disease duration, only 1/18 (6%) women with SCA-POI had detectable levels of AMH, similar to women with idiopathic POI (5/78, 6%). Most women with SCA-POI present at clinical diagnosis with a preserved follicle pool that is progressively lost within a few years.	\N	\N
22426166	Natural killer (NK) cells are the effector cells of innate immunity that respond to infection and tumor. Interactions between killer cell immunoglobulin like receptors (KIR) and human leukocyte antigen (HLA) class I molecules regulate NK cells responses to eliminate infected and transformed cells. To investigate the impact of KIR genes, HLA ligand genes, and KIR-HLA combinations on susceptibility to tuberculosis (TB) in Lur population of Iran. The genomic DNA of 50 patients with TB from Lorestan province of Iran was genotyped for sixteen KIR genes and their five major HLA class I ligands were determined by a polymerase chain reaction-sequence-specific primers (PCR-SSP) assay. The results were compared with those of 200 healthy unrelated Iranian individuals. In Lur population of Iran, a significant decrease in frequency of KIR3DS1 was found in TB patients compared to control group (24% vs. 44.5%, OR=0.394, CI=0.194-0.798, p=0.013). Also, among the three activating genes that may use HLA class I molecules as their ligands, a significant decrease was shown in frequency of KIR3DS1 with HLA-B Bw4Ile80 ligand in TB patients compared to control group (4% vs. 23%, OR=0.14, CI=0.033-0.596, p=0.004). These findings imply a genetic imbalance between activating and inhibitory KIR genes and KIR-HLA combinations in Lur TB patients. Low level of activating KIR3DS1 and its combination with HLA-B Bw4Ile80 ligand might have an influence on the susceptibility to TB in Lur population of Iran.	\N	\N
22433620	The aim of this study was to define body fat percentiles for German children and adolescents aged 3-16 years using the largest German database. The study population included 11,632 girls and 11,604 boys. Data were pooled from: i) Kiel Obesity Prevention Study (KOPS), acquisition period: 1996-2008, n = 12,237; ii) 'Better diet. More exercise. KINDERLEICHT-REGIONS', acquisition period: 2007, n = 9,405; and iii) examination of Jena schoolchildren, acquisition period: 2005, n = 1,594. Body fat mass was measured by bioelectrical impedance analysis using a population-specific algorithm. Data were weighted to achieve a representative sample for Germany. Percentile curves were constructed by the LMS method and proved by Worm plots and Q-statistic. In both genders, the higher body fat percentile curves sloped downwards to age 7 years, whereas the lower percentiles declined up to 8.5 years. Thereafter fat mass remained nearly constant with age in boys and increased in girls. The 10th percentile achieved a minimum of 10-11% body fat in both genders, whereas the 90th percentile curve fluctuated between 29 and 44% in boys or 30-43% in girls. The association between fat mass and blood pressure was too weak to define disease-related cut-offs. These body fat percentiles are suitable reference values for German children and adolescents.	\N	\N
22434759	The aim of our study was to evaluate the physical and sedentary activities and energy expenditure (EE) in a group of children affected by non-alcoholic fatty liver disease (NAFLD), compared with normal and obese subjects, using a physical activity questionnaire (PAQ) and a SenseWear armband (SWA). Forty NAFLD (10 females), 41 lean (NRM; 11 females) and 30 obese (OB; 10 females), age- and pubertal stage-matched, children were included. Sedentary activity (PAQ) was similar in NAFLD and NRM but less in OB, while SWA showed that NAFLD spent less time in physical activity and more in sedentary activities compared with NRM, but not with OB. Insulin sensitivity index result is related to active EE (cal kg(-1)  d(-1) ) in NAFLD, while homeostatic model assessment index result was negatively related to total EE in OB. Regular physical activity must be encouraged in all obese children affected by NAFLD or not, and SWA might be a possible valid tool for evaluating actual EE.	\N	\N
22458506	The roles of cysteine protease (CP) enzymes in the biochemistry and infectivity of the three trypanosomal parasitic infections, Chagas' disease, leishmaniasis and human African trypanosomiasis, which have been elucidated over the last three decades are summarized. Inhibitors of these enzymes, which act through trapping the active site cysteine with an electrophilic warhead, hold huge potential as therapeutic agents but the promise of these has yet to be realized in clinical studies. The article addresses aspects that ought to be considered in order to develop orally active CP inhibitors that are safe and effective therapies for trypanosomiasis. This article reviews learnings from CP research in the trypanosomal field and recent advances in developing cysteine protease inhibitors (CPIs) of human cathepsin K, a related enzyme. Considerations such as intra- and extracellular localization of the CPs, off-target activities against human cathepsin enzymes, basic versus neutral and potential pro-drug inhibitors are reviewed. A description of odanacatib, a cathepsin K inhibitor currently in late stage development, is made to illustrate the attributes of a clinically viable CPI. The emerging role of CPs in a wide array of parasitic diseases is highlighted with the vision that CP inhibitors could become the 'β-lactams' of anti-parasitic treatments in the coming decades. New CPI research will see the optimization of intra- and extracellular enzyme targeting, reduction of off-target activities and better understanding of pharmacokinetic-pharmacodynamic interactions which will all lead to compounds with much improved efficacy and viability as clinical therapies.	\N	\N
22458804	Over the past few years, there has been a rapid rise in the older segments of the world population, which has brought along with it a major health concern: dementia. Alzheimer's disease, considered to be the most common cause of dementia, has become a prospect feared by the elderly. Inflammation of the brain is strongly implicated in Alzheimer's disease which could be enhanced by systemic inflammation. Periodontitis being a chronic inflammatory condition, which can cause systemic inflammation, the question is whether chronic periodontitis can initiate or hasten the rate of progression of Alzheimer's disease in susceptible individuals. In this article, the authors outline the proposed oral systemic link between periodontitis and Alzheimer's disease.	\N	\N
22463746	Evaluation of peritoneal involvement in colonic cancer (CC) can be difficult. We studied pT4N0 cancers and their association with pathological prognostic markers, including tumour budding. Tumours were classified as (i) at the peritoneal surface or free in the peritoneal cavity (pT4a subgroup n = 44); (ii) directly invading adjacent organ (pT4b subgroup n = 8); or (iii) showing inflammatory involvement of the peritoneum (pT4I subgroup n = 25). A published pT3N0 cohort was used to compare Stage II subgroups. Standard pathological markers including tumour budding were assessed. Elastin staining was performed in the pT4I subgroup. Seventy-seven Stage II CCs met inclusion criteria. There was no significant difference in survival across subgroups. pT4b tumours were larger than pT4a tumours (P < 0.001). Over-represented features in pT4a versus pT4b tumours were tumour budding (P = 0.02) and infiltrative margin (P = 0.02). Tumour budding did not predict survival. Using multivariate analysis, neural invasion was the only parameter predictive of survival (hazard ratio = 2.8; 95% CI 1.2-6.4; P = 0.02). Stage II pT4I CCs have a similar outcome to T4a/b tumours. Elastin staining is useful in defining this group. Tumour budding may facilitate peritoneal invasion in pT4a tumours, but does not predict outcome in pT4N0 disease. Only neural invasion independently predicted poor outcome.	\N	\N
22466542	Most common type of head and neck malignant tumors is squamous cell carcinoma reaching 3% of all human cancers. Oral squamous cell carcinoma (OSCC) has tendency of increasing incidence and mortality worldwide with an overall 5 year survival rate of <60%. In order to explore this disease, different in vivo mouse models have been introduced. In this study we analyzed clinical and morphological characteristics of OSCC in vivo nude mouse model. 80% of mice which were injected with human oral squamous cancer cells developed orthotopic tumors with the mean volume of 146 mm(3), from which 62% exhibited metastatic spread. Morphology of the cancer tissue was characterized with invasive phenotype and inflammation. Proliferation activity rate of orthotopicly grown tumors were 55,7 ± 4,7 mitotic cells/optical field and displayed weakly developed vascular network. OSCC in vivo orthotopic nude mouse model can mimic pathological and clinical picture of the malignant disease and may be effectively used in oncology research.	\N	\N
22472026	Patients with Crohn's disease (CD) may need anti-inflammatory drugs for decades. Anti-TNF-α agents have good efficacy and adverse events similar to placebo in randomized controlled trials (RCTs), but there are still questions about long-term safety and efficacy. In this respect, reports from clinical practice may be useful. We currently report on the clinical experience with infliximab and adalimumab in a single-center cohort of patients with CD. Patients with CD treated with infliximab or adalimumab from 2000 to 2010 were reviewed. Patient and disease characteristics at start, reason for discontinuation, and adverse events were recorded retrospectively. Corticosteroid use, the need for hospitalization, and surgeries before and during anti-TNF-α therapy were recorded. Eighty-three patients had received anti-TNF-α treatment against CD, median treatment duration was 11.4 months (0.2-99.5), and follow-up time 59 months (8-135). Eighteen of 43 patients using corticosteroids at treatment start discontinued corticosteroids during TNF-α therapy. Need for hospitalizations (6.13 vs. 3.28 days/year, p < 0.001) and surgeries (0.56 vs. 0.16 operations/year, p < 0.001) were lower during anti-TNF-α therapy than before treatment. Twenty-six percent discontinued therapy due to adverse events and 26% due to lack or loss of response. Two of four deaths observed during follow-up were believed to be related to anti-TNF-α treatment. Anti-TNF-α therapy was beneficial in many patients with CD, but the majority of patients discontinued treatment during follow-up. Reports from clinical experience with anti-TNF-α treatment may be valuable for clinicians treating patients with CD.	\N	\N
22483567	Anti tumor necrosis factor alpha (TNFα) agents have become widely used in pediatric inflammatory bowel disease (IBD). So far, only few studies examined the long-term results of anti-TNFα treatment in children with IBD. The long-term outcome of pediatric patients with IBD was assessed retrospectively in a multicenter cohort of children treated with anti-TNFα beyond induction treatment. Short- and long-term response rates, predictors for loss of response, data on growth and laboratory parameters were assessed. 120 patients [101 crohn's disease (CD), 19 ulcerative colitis (UC) or indeterminate colitis (IC)] received either infliximab or adalimumab. The mean age at initiation of anti-TNFα was 13.4 ± 3.9 years and the median duration of anti-TNFα treatment was 15 months (range: 2-90). Overall, 89% of the cohort experienced short-term response following induction. Response was associated with improvement in weight and BMI Z-scores (p<0.001) but not with linear growth. Responders experienced a significant decrease in erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) during treatment (p<0.001). Albumin and hemoglobin both improved but only albumin increased significantly (p<0.001). The cumulative probability of losing response to anti-TNFα treatment was 17%, 38%, and 49% after 1, 3, and 5 years, respectively. Responders had a significantly lower weight and BMI Z-scores at initiation of anti-TNFα treatment in compared to non-responders (p=0.04 and 0.02 respectively). Our long term cohort supports the current evidence on the effectiveness and safety of anti-TNFα treatment in children with IBD. Response to treatment was interestingly associated with lower weight and BMI.	\N	\N
22484574	To determine the incidence of radiographic lumbar spondylosis (LS)and lower back pain, and their risk factors in Japan using a large-scale population from the nationwide cohort Research on Osteoarthritis/osteoporosis Against Disability (ROAD) Study. Participants in the ROAD study who had been recruited between 2005 and 2007 were followed up with lumbar spine radiography for 3 years. A total of 2,282 paired radiographs (75% of the original sample) were scored using Kellgren and Lawrence (KL) grades, and the incidence and progression rate of radiographic LS was analyzed. The incidence of lower back pain was also examined. In addition, associations between risk factors and incident and progressive radiographic LS as well as incident lower back pain were tested. Given a 3.3-year follow-up, the incidence of KL≥2 radiographic LS was 50.0% and 34.4% (15.3% and 10.5% per year), while that of KL≥3 LS was 15.3% and 23.7% (4.6% and 7.2% per year) in men and women, respectively. The progression rate of LS was 20.5% and 27.4% (6.2% and 8.3% per year) in men and in women, respectively. In addition, the incidence of lower back pain was 28.3% and 31.2% (8.6% and 9.5% per year) in men and women. Lower back pain was not significantly associated with incident radiographic LS, while a more severe KL grade at baseline was associated with incident lower back pain. The present longitudinal study revealed a high incidence of radiographic LS in Japan.	\N	\N
22484921	Sarcoidosis is a multi-systemic disease. A 21-year-old female patient was admitted to our department with lymphadenopathy, B symptoms, erythema nodosum and joint pain. Sarcoidosis showed a very atypical course, lacking any pulmonary symptoms or typical laboratory values. The diagnosis was finally confirmed histologically and thus various differential diagnoses such as microbiological and malignant diseases could be excluded. Oral steroid medication led to remission.	\N	\N
22484998	Populations living in poverty in the developing world suffer a heavy burden caused by infectious diseases, most of them zoonoses. The poorer populations also tend to be marginalised from the health sector and so are many of the diseases that affect them. The poor in every society, and particularly in developing countries, bear a disproportionately high share of the disease burden. There is a broad range of viral, bacterial, mycotic, chlamydial, rickettsial and parasitic diseases of global and regional importance given their major impact on the health and socio-economic development of many populations. Endemic infectious diseases, including zoonoses, together with emerging and re-emerging diseases, are mostly shouldered by poor and vulnerable populations. Livestock are important in supporting the livelihoods of poor farmers, consumers and traders throughout the developing world. The animals of poor people are particularly vulnerable to disease because of costs, absence or unsuitability of the animal health sector, etc. The impact of endemic animal diseases are mainly felt at the farm level, while a broader economic impact can occur with these diseases through the restriction of trade in livestock and their products. Addressing comprehensive and sustainable solutions to public health problems created by endemic infections cannot be achieved solely by the public health sector alone. Partnerships with other sectors, particularly agriculture, environment, education, local administration, will be necessary to contain and effectively control zoonotic and foodborne diseases that affect mainly the poor. International organisations could support developing countries by coordinating national intersectoral activities, promoting appropriate technology and public health education, community participation and encouraging decision-makers to commit themselves. This is the only perspective for improved quality of life of poor and marginalised populations.	\N	\N
22485050	Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18-55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ≥ 1:32 in initially seronegative; ≥ 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ≥ 98.0% of subjects had rSBA titers ≥ 1:128. Grade 3 solicited AEs were reported in ≤ 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults.   This study is registered at clinicaltrials.gov NCT00453986.	\N	\N
22486286	Patients with chronic kidney disease are exposed to oxidative stress (OS) that contributes to deterioration of health. Decrease in renal excretory capacity contributes to the accumulation of pro-oxidative substances that are detrimental not only to kidney but to the whole organism including the cardiovascular system. Components of antioxidant system play an important role in the elimination of the OS. The monitoring of antioxidant levels and products of oxidative damage in these patients and the correct interpretation of relationship between these markers and the function of kidney and other organs may contribute to the more effective treatment and health improvement of the patients.	\N	\N
22494938	The whipworms Trichuris trichiura and Trichuris suis in humans and pigs, respectively, are believed to be two different species yet closely related. Morphologically, adult worms, eggs and larvae of the two species are indistinguishable. The aim of this study was to examine the genetic variation of Trichuris sp. mainly recovered from natural infected pigs and humans. Worm material isolated from humans and pigs living in the same geographical region in Uganda were analyzed by PCR, cloning and sequencing. Measurements of morphometric characters were also performed. The analysis of the ITS-2 (internal transcribed spacer) region showed a high genetic variation in the human-derived worms with two sequence types, designated type 1 and type 2, differing with up to 45%, the type 2 being identical to the sequence found in pig-derived worms. A single human-derived worm showed exclusively the type 2-genotype (T. suis-type) and three cases of 'heterozygote' worms in humans were identified. However, the analysis showed that sympatric Trichuris primarily assorted with host origin. Sequence analysis of a part of the genetically conserved β-tubulin gene confirmed two separate populations/species but also showed that the 'heterozygote' worms had a T. suis-like β-tubulin gene. A PCR-RFLP on the ITS-2 region was developed, that could distinguish between worms of the pig, human and 'heterozygote' type. The data suggest that Trichuris in pigs and humans belong to two different populations (i.e. are two different species). However, the data presented also suggest that cross-infections of humans with T. suis takes place. Further studies on sympatric Trichuris populations are highly warranted in order to explore transmission dynamics and unravel the zoonotic potential of T. suis.	\N	\N
22498694	Although many of the effects of estrogens on the brain are mediated through estrogen receptors (ERs), there is evidence that neuroprotective activity of estrogens can be mediated by non-ER mechanisms. Herein, we review the substantial evidence that estrogens neuroprotection is in large part non-ER mediated and describe in vitro and in vivo studies that support this conclusion. Also, we described our drug discovery strategy for capitalizing on enhancement in neuroprotection while at the same time, reducing ER binding of a group of synthetic non-feminizing estrogens. Finally, we offer evidence that part of the neuroprotection of these non-feminizing estrogens is due to enhancement in redox potential of the synthesized compounds.	\N	\N
22503230	To investigate whether single nucleotide polymorphisms (SNPs) in interleukin (IL)-1β, IL-6, and IL-12β are associated with the susceptibility and severity of contact lens-related keratitis. Retrospective, case control study. One hundred twelve cases of keratitis and 225 controls were recruited from studies conducted at Moorfields Eye Hospital and in Australia during 2003 through 2005. Buccal swab samples were collected on Whatman FTA cards and were mailed by post for analysis. IL-1β (-31), IL-6 (-174, -572, -597), and IL-12B (3'+1158) genotypes were analyzed with pyrosequencing and analyzed using a regression model for susceptibility (sterile, microbial keratitis, controls) and severity. Statistical significance was set at 0.05. The relative risk of developing contact lens-related keratitis and more severe forms of the disease based on allele, genotype, and haplotype associations. Carriers of IL-6 SNPs were more likely to experience moderate and severe events compared with those with nonmutated genotypes (-174 heterozygous: odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-8.3; homozygous: OR, 6.4; 95% CI, 1.4-28.4; -174/-597: OR, 4.1; 95% CI, 1.6-11.0). More severe keratitis and microbial keratitis were less likely to occur in wearers with the nonmutated IL-6 haplotype (severity OR, 0.4 [95% CI, 0.2-0.7]; microbial OR, 0.6 [95% CI, 0.4-0.9]). Wearers carrying an IL-12B SNP had an increased risk of sterile keratitis (OR, 9.7; 95% CI, 1.2-76.9) compared with controls. The IL-6 SNPs are known to reduce protein expression of this cytokine and thus ocular immune defense, and carriers of these SNPs were more likely to experience more severe and microbial keratitis, suggesting that IL-6 decreases the severity and susceptibility of contact lens-related keratitis. Carriers of a functional SNP of IL-12B that is known to increase IL-12 expression and stability are more likely to experience sterile keratitis, suggesting that this is associated with the intense inflammatory reaction that occurs in this condition.	\N	\N
22505009	To evaluate inhibin-A immunoreactivity and its utility in the differential diagnosis of nervous system neoplasms and non-neoplastic lesions. An immunohistochemical study of 252 central and peripheral nervous system tumors and 40 non-neoplastic lesions was undertaken. Brain lesions included the basic spectrum of astrocytic, oligodendroglial, and ependymal neoplasms, as well as glioneuronal, pineal parenchymal, choroid plexus, and embryonal. Meningeal neoplasms, basic peripheral nerve tumors, and uncommon sellar lesions were also assessed. Non-neoplastic lesions included demyelinating disease, progressive multifocal leukoencephalopathy, organizing infarct, and reactive gliosis. Diffuse cytoplasmic, membranous, and perinuclear cytoplasmic staining patterns were observed. Significant immunoreactivity was noted in glioblastoma (12 of 20), pleomorphic xanthoastrocytoma (6 of 10), ganglioglioma (8 of 10), meningioma (14 of 20), and hemangioblastoma (10 of 10). Peripheral nerve and sellar tumors as well as non-neoplastic lesions were entirely immunonegative. In our study that investigated the inhibin-A immunoreactivity in a broad spectrum of nervous system lesions, inhibin-A positivity was established in various low-grade and high-grade central nervous system tumors. Thus, inhibin-A is not a specific marker of hemangioblastoma and may be of limited utility in the differential diagnosis of astrocytic and meningothelial neoplasms. Its pathophysiologic role in these various tumors remains to be determined. Further evaluation of the possible significance of staining patterns and degrees of reactivity relative to pathobiology and/or prognosis significance is required.	\N	\N
22507833	Osteoporosis, a major health problem among postmenopausal women, is influenced by dietary factors. The purpose of the present study was to evaluate the hypothesis that erythrocyte levels of n-3 polyunsaturated fatty acid (PUFA) and the dietary intake of fish are associated with risk of osteoporosis and correlate with bone mass in postmenopausal Korean women with the disease. Fifty cases and 100 controls were recruited. Osteoporosis was defined according to the International Society for Clinical Densitometry guideline as a score lower than -2.5 SD below the T-score for lumbar vertebrae L₁-L₄, femoral neck or femoral total. The T-score of the femoral neck was positively correlated with erythrocyte levels of n-3 PUFA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the intake of fish, and was negatively correlated with the ratio of n-6/n-3 PUFA after adjusting for age, years after menopause and height. In addition, the risk of osteoporosis was positively associated with erythrocyte levels of saturated fatty acids but negatively associated with EPA + DHA. Erythrocyte levels of n-3 PUFA and the intake of fish were positively correlated with bone mass. In particular, erythrocyte levels of EPA + DHA reduced the risk of osteoporosis in postmenopausal Korean women.	\N	\N
22509749	Mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. Limited attention has been given to the role of mast cells in periodontal diseases, and the effects of mast cell degranulation on the chronic stages of non-allergic inflammation, particularly in periodontitis, are not known. The present study analyzes the relationship between the mast cell degranulation and human periodontal disease progression. A total of 50 clinical specimens including moderate periodontitis (n = 17), advanced periodontitis (n = 18), and healthy control tissues (n = 15) were used in this study. All specimens were fixed in 10% buffered formalin and stained with hematoxylin and eosin for histopathology, with toluidine blue for identifying mast cells, and by immunohistochemistry for the expressions of mast cell tryptase in periodontal tissues. The total and degranulated mast cell densities (per high-power field) were quantified in the specimens. Compared with healthy controls, there were significantly increased both total and degranulated mast cell densities in human moderate (P <0.01) and advanced (P <0.01) periodontitis groups by toluidine blue staining, and there were significantly higher densities of both total and degranulated tryptase-positive mast cell subpopulation in the moderate periodontitis group (P <0.01) and even significantly higher subpopulation densities in the advanced periodontitis group by immunohistochemical staining, in which both total and degranulated mast cell densities were significantly higher in the advanced periodontitis group than those in the moderate periodontitis group (P <0.01) by both toluidine blue staining and immunohistochemical staining. There was significantly more severe periodontal inflammatory pathology in the advanced periodontitis group than in the moderate periodontitis group (P <0.01). These findings indicate a significant correlation among tryptase-positive mast cell density, the degree of their degranulation, and the human periodontitis severity, and the results of this study further indicate that mast cell degranulation appears to be associated with human periodontal disease.	\N	\N
22511575	We sought to examine the contemporary use of thrombectomy during primary percutaneous coronary intervention (PCI) in the United States. Adjunctive thrombectomy during primary PCI for patients with ST-segment elevation myocardial infarction (STEMI) has demonstrated mixed results. While earlier studies showed either unfavorable or neutral effects with rheolytic thrombectomy, recent clinical trials have shown benefits with manual or rheolytic thrombectomy when compared to PCI alone. We analyzed data from 122,449 patients undergoing primary PCI for STEMI from 1,181 centers reported to the CathPCI Registry® between July 2009 and December 2010. We used logistic regression analysis to examine factors associated with the use of manual and rheolytic thrombectomy. Thrombectomy was performed in 23,195 patients (18.9%): 22,404 (18.3%) had manual thrombectomy and 791 (0.6%) had rheolytic thrombectomy. The use of manual thrombectomy increased over time (P < 0.05). The use of rheolytic thrombectomy did not change. There was significant variation in the use of thrombectomy across hospitals. The strongest predictors of manual versus no thrombectomy included TIMI 0/1 flow (odds ratio 1.69), younger age (OR 0.90 per 10 year increase), saphenous vein graft (OR 2.22), glycoprotein IIb/IIIa inhibitor (OR 1.34), single-vessel disease (OR 1.13), and year of admission (OR 1.20 per year; all P < 0.001). The strongest predictor of manual versus rheolytic thrombectomy was year of admission (OR 1.23, P < 0.001). Our data show that thrombectomy is performed infrequently in the US during primary PCI for STEMI. There is significant variation in the use of thrombectomy across US hospitals.	\N	\N
22515999	Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent-onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option.	\N	\N
22523117	Podocyturia, i.e. urinary loss of viable podocytes, may serve as a diagnostic tool for pre-eclampsia and as a marker of active renal disease. The current method to detect podocyturia is technically complex, lengthy and requires a high level of expertise for interpretation. The aim of this study was to develop a new technique for the identification of urinary podocytes, based on the detection of podocyte-specific tryptic peptides by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), which will provide an operator-independent and highly reproducible method. The diagnosis of pre-eclampsia was confirmed in the presence of hypertension (>140/90 mmHg) and proteinuria >0.3 g/24 h urine. The diagnosis of HELLP was confirmed based on the accepted clinical criteria of hemolysis, elevated liver enzymes and low platelet count. Random urine samples within 24 h prior to delivery were collected and centrifuged. One half of the sediment was cultured for 24 h to select for viable cells and then stained with a podocin antibody, followed by a secondary fluorescein isothiocyanate-labeled antibody to identify podocytes. The second half of the pellet was solubilized, digested and analyzed by LC-MS/MS using an internal standard. We have recruited 13 patients with pre-eclampsia and 6 patients with pre-eclampsia/HELLP syndrome. The presence of podocytes was confirmed in all patients by the podocyte culture method. In the respective samples, the presence of a podocin-specific tryptic peptide was confirmed with LC-MS/MS technology. The LC-MS/MS method is a reliable technology for the identification of urinary podocytes, based on the presence of podocyte-specific proteins in the urine.	\N	\N
22525341	Epoxyeicosatrienoic acids (EETs) are natural angiogenic mediators regulated by soluble epoxide hydrolase (sEH). Inhibitors of sEH can stabilize EETs levels and were reported to reduce atherosclerosis and inhibit myocardial infarction in animal models. In this work, we investigated whether increasing EETs with the sEH inhibitor t-AUCB would increase angiogenesis related function in endothelial progenitor cells (EPCs) from patients with acute myocardial infarction (AMI). EPCs were isolated from 50 AMI patients and 50 healthy subjects (control). EPCs were treated with different concentrations of t-AUCB for 24h with or without peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662. Migration of EPCs was assayed in trans-well chambers. Angiogenesis assays were performed using a Matrigel-Matrix in vitro model. The expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) mRNA and protein in EPCs was measured by real-time PCR or Western blot, respectively. Also, the concentration of EETs in the culture supernatant was detected by ELISA. The activity of EPCs in the AMI patient group was reduced compared to healthy controls. Whereas increasing EET levels with t-AUCB promoted a dose dependent angiogenesis and migration in EPCs from AMI patients. Additionally, the t-AUCB dose dependently increased the expression of the angiogenic factors VEGF and HIF-α. Lastly, we provide evidence that these effects were PPARγ dependent. The results demonstrate that the sEH inhibitor positively modulated the functions of EPCs in patients with AMI through the EETs-PPARγ pathway. The present study suggests the potential utility of sEHi in the therapy of ischemic heart disease.	\N	\N
22527997	Early life stress, such as maternal separation, causes adaptive changes in neural mechanisms that have adverse effects on the neuroplasticity of the brain in adulthood. As a consequence, children who are exposed to stress during development may be predisposed to neurodegenerative disorders in adulthood. A possible mechanism for increased vulnerability to neurodegeneration may be dysfunctional mitochondria. Protection from neurotoxins, such as 6-hydroxydopamine (6-OHDA), has been observed following voluntary exercise. The mechanism of this neuroprotection is not understood and mitochondria may play a role. The purpose of this study was to determine the effects of maternal separation and exercise on mitochondrial function in a rat model of Parkinson's disease. Maternally separated (pups separated from the dam for 3 h per day from postnatal day (P) 2-14) and non-separated rats were placed in individual cages with or without attached running wheels for 1 week prior to unilateral infusion of 6-OHDA (5 μg/4 μl, 0.5 μl/min) into the left medial forebrain bundle at P60. After 2 h recovery, rats were returned to their cages and wheel revolutions recorded for a further 2 weeks. On P72, the rats' motor function was assessed using the forelimb akinesia test. On P74, rats were sacrificed for measurement of mitochondrial function. Exercise increased the respiratory control index (RCI) in the non-lesioned hemisphere of 6-OHDA-lesioned rats. This effect was evident in the striatum of non-separated rats and the prefrontal cortex of maternally separated rats. These results suggest that early life stress may reduce the adaptive response to exercise in the striatum, a major target of dopamine neurons, but not the prefrontal cortex in this model of Parkinson's disease.	\N	\N
22531706	To identify the underlying mutation and describe the phenotype in a consanguineous Kurdish family with Leber's congenital amaurosis (LCA)/early onset severe retinal dystrophy (EOSRD). Members of the index family were followed up to 22 years by ophthalmological examinations, including best corrected visual acuity (BCVA), Goldmann visual field (GVF), two-color-threshold perimetry (2CTP) and Ganzfeld electroretinogram (ERG), fundus photographs, fundus autofluorescence (FAF), and optical coherence tomography (OCT). After excluding seven of nine known LCA/EOSRD genes in the index patient, linkage analysis was performed in the family using a microarray followed by microsatellite fine mapping and direct sequencing of candidate genes. RD3 was screened by direct sequencing of 85 independent patients with LCA/EOSRD presenting with a BCVA ≥ 1.0 LogMAR before the age of 2 years to assess the prevalence of RD3 mutations in LCA/EOSRD. Since RD3 and RetGC1 have a functional relation, study authors screened for a modifying effect of RD3 mutations in 17 independent patients with mutations in GUCY2D. BCVA was severely reduced from the earliest examinations (as early as 3 months), never exceeding 1.3 LogMAR. The disease presented as cone-rod dystrophy with dystrophic changes in the macula and bone spicules in the periphery on progression. Linkage analysis narrowed the region of interest towards the LCA12 locus. Direct sequencing of RD3 revealed a homozygous nonsense mutation (c.180C > A) in all affected members tested. Screening of additional unrelated LCA/EOSRD patients revealed only polymorphisms in RD3. This is the second family reported so far with mutations in RD3. Mutations in RD3 are a very rare cause of LCA associated with an extremely severe form of retinal dystrophy.	\N	\N
22533114	Although the number of tuberculosis cases in the US is at an all-time low, with progressive declines seen for the past 17 years, many goals in the tuberculosis elimination process remain unrealized. This report describes a cluster of four tuberculosis cases in a family, including one case of acquired multidrug resistant tuberculosis. It also underscores some important issues in tuberculosis control today, including significant disparities in the foreign-born population with multidrug resistant tuberculosis as a looming problem, as well as utilization of therapeutic drug level monitoring in complicated cases.	\N	\N
22533233	Hen's egg is one of the main causes of food allergy in children. Accidental exposure is common in food-allergic patients. However, the few studies that analyze this problem focus mainly on peanut allergy. We sought to calculate the frequency of accidental exposure reactions in children allergic to hen's egg during a 12-month period, to analyze the clinical characteristics and circumstances surrounding the reactions, and to identify risk factors for the most severe reactions. Ninety-two egg-allergic children (55 boys; median age, 52 months) were included in the study. A systematic questionnaire about accidental exposure was administered. Reactions were classified as mild, moderate, and severe. Egg white-specific immunoglobulin (Ig) E antibody titers were determined. Nineteen (21%) children had 24 reactions in the previous year (42% mild, 50% moderate, and 8% severe). Most reactions took place at home (50%) under routine circumstances (83%). Children with severe or moderate reactions had higher specific IgE levels to egg white (adjusted odds ratio for every 0.1-unit increase in the decimal logarithm, 1.15; 95% CI, 1.03-1.28; P = .008) and lower serum total IgE (adjusted odds ratio for every 1-unit increase in the decimal logarithm, 0.16; 95% CI, 0.05-0.54; P = .001) than those children with mild or no reactions. Reactions to accidental exposure are frequent in children with egg allergy. The proportion of severe or moderate reactions was 58%. The risk factors for such reactions included high titers of specific IgE to egg white and low titers of serum total IgE.	\N	\N
22545160	Successful and sustainable intervention against human helminthiases depends on optimal utilisation of available control measures and development of new tools and strategies, as well as an understanding of the evolutionary implications of prolonged intervention on parasite populations and those of their hosts and vectors. This will depend largely on updated knowledge of relevant and fundamental parasite biology. There is a need, therefore, to exploit and apply new knowledge and techniques in order to make significant and novel gains in combating helminthiases and supporting the sustainability of current and successful mass drug administration (MDA) programmes. Among the fields of basic research that are likely to yield improved control tools, the Disease Reference Group on Helminth Infections (DRG4) has identified four broad areas that stand out as central to the development of the next generation of helminth control measures: 1) parasite genetics, genomics, and functional genomics; 2) parasite immunology; 3) (vertebrate) host-parasite interactions and immunopathology; and 4) (invertebrate) host-parasite interactions and transmission biology. The DRG4 was established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR). The Group was given the mandate to undertake a comprehensive review of recent advances in helminthiases research in order to identify notable gaps and highlight priority areas. This paper summarises recent advances and discusses challenges in the investigation of the fundamental biology of those helminth parasites under the DRG4 Group's remit according to the identified priorities, and presents a research and development agenda for basic parasite research and enabling technologies that will help support control and elimination efforts against human helminthiases.	\N	\N
22547770	Crizotinib (PF02341066, Xalkori; Pfizer) was recently approved by the U.S. Food and Drug Administration for treatment of ALK-positive non-small cell lung cancer (NSCLC) as defined by a jointly approved diagnostic test using a break-apart fluorescence in situ hybridization assay. The approval was based on dramatic response rates in ALK-positive NSCLC patients of 54% to 61% in phase I and II trials. To date, the overall disease control rates in these trials are close to 90%. Progression-free survival approaches 10 months. This review focuses on the ALK-inhibitory activity of crizotinib in preclinical and clinical trials that led to approval, as well as the diagnostic methods to classify patients with ALK-positive NSCLC. Although these patients represent a small subset of all patients with NSCLC, the rapid time course from identification of this unique target to an approved targeted therapy with striking benefit serves as a paradigm for the development of targeted therapeutics in an era of personalized medicine.	\N	\N
22548237	Ochroconis spp. are dematiaceous fungi and have recently become recognized as the cause of human disease. Infections due to members of this genus have primarily occurred in patients with impaired immunity following organ transplantation or chemotherapy for hematologic malignancies. There is no universally agreed upon therapy or duration of treatment, but amphotericin B and/or triazoles are typically employed. We present a case of Ochroconis gallopava infection in a patient with chronic granulomatous disease (CGD). The organism exhibited elevated minimal inhibitory concentrations against itraconazole (0.5 μg/ml) and voriconazole (2 μg/ml) in comparison with results from other studies reported in the literature. This case illustrates the complexities associated with antibiotic susceptibility testing, selection of appropriate drugs, and management in patients with Ochroconis infections. We also review the literature of human infections with Ochroconis to date, and discuss its microbiology to apprise both clinicians and laboratory personnel of this infrequently encountered but potentially aggressive pathogen.	\N	\N
22559253	Polyphenols, a ubiquitous group of secondary plant metabolites sharing at least one aromatic ring structure with one or more hydroxyl groups, represent a large group of natural antioxidants abundant in fruits, vegetables, and beverages, such as grape juice, wine, and tea, and are widely considered to contribute to health benefits in humans. However, little is yet known concerning their bioactive forms in vivo and the mechanisms by which they may alter our metabolome, which ultimately contribute toward disease prevention. Here we report a study to determine the metabolic fate of polyphenolic components in a Chinese tea (Pu-erh) in human subjects using a metabonomic profiling approach coupled with multivariate and univariate statistical analysis. Urine samples were collected at 0 h, 1 h, 3 h, 6 h, 9 h, 12 h, and 24 h within the first 24 h and once a day during a 6 week period including a 2 week baseline phase, a 2 week daily Pu-erh tea ingestion phase, and a 2 week "wash-out" phase, and they were analyzed by gas chromatography mass spectrometry and liquid chromatography mass spectrometry. The dynamic concentration profile of bioavailable plant molecules (due to in vivo absorption and the hepatic and gut bacterial metabolism) and the human metabolic response profile were measured and correlated with each other. This study demonstrates that the metabonomic strategy will enable us to integrate the overwhelming amount of metabolic end points as a systems' response to the absorption, metabolism, and disposition of a multicomponent botanical intervention system, leading to a direct elucidation of their mechanisms of action.	\N	\N
22571342	In carcinogenesis, methylation of DNA promoter regions results in inactivation of tumor-suppressing genes. MG98 was designed to inhibit DNA methyltransferases enzyme 1 production. This multicenter study explored two schedules of MG98 with Interferon-α-2β to identify schedule and dose for patients with metastatic RCC. Doses of IFN 9 MIU/MG98 125 mg/m(2) for a continuous schedule and IFN 9 MIU/MG98 200 mg/m(2) for an intermittent schedule were considered the MTDs. Treatment resulted in one PR and eight SD. MG98 combined with IFN was safe and resulted in clinical activity.	\N	\N
22573749	The increase of severe cases of acute tonsillitis (AT) is presently marked. Severe cases of AT disturb immune and metabolic homoeostasis initiating the development of disease. Therapy optimization is required to select the best treatment. In patients with severe cases of AT of mixed viral/bacterial etiology before the treatment it is revealed the increase of general activity of lactatedehydrigenase (LDH) and increase of the level of cathode "anaerobic" factions LDH4+5 and the decline of concentration ATP in the blood. There was a compensatory rise of level of ADP and АМP. The substantial decline of serum interferon (CIF) activity and diminishing maintenance of α-interferon (α-IFN) and γ-interferon (γ-IFN) in the blood of the patients, that testified to oppressing of interferonogenesis. Treatment of severe cases of AT of mixed viral/bacterial etiology of modern detoxic preparation reamberin and immunoactive preparation cycloferon combination positively influences the studied laboratory indexes. The improvement of power metabolism is marked, that was characterized by normalization of level adenine nucleotides (ATP, АDP, АМP) and general activity of LDH and its izoenzimes spectrum. At the same time the increase of CIF level is set, maintenances α-IFN and γ-IFN in the blood, that testified to the improvement of interferonogenesis. The results demonstrate the therapeutic potential of reamberin and cycloferon combination for treatment of patients with AT of mixed viral/bacterial etiology.	\N	\N
22582962	Infants with viral bronchiolitis are often hospitalised with a proportion requiring respiratory support. The aim of this review was to examine the use of nasal prong continuous positive airway pressure (CPAP) as a management strategy for infants with a diagnosis of bronchiolitis, who required stabilisation and transport to a tertiary centre. A retrospective audit of infants with bronchiolitis requiring CPAP during transport between January 2003 and June 2007. Nasal CPAP was initiated in 54 infants with 51 of these (34 ex-preterm, 17 term) subsequently continuing on CPAP during retrieval. Mean CPAP pressure was 7 cmH(2)O. Oxygenation improved between stabilisation and the end of retrieval (P < 0.01). During retrieval, there was no significant increase in transcutaneous CO(2), no infant required endotracheal ventilation and no adverse events were noted. Five infants were intubated within the first 24 h of admission at the receiving hospital. This review demonstrated that use of nasal prong CPAP to transport infants with bronchiolitis was a safe management strategy in those with moderate to severe disease severity.	\N	\N
22595407	The authors used multidetector computed tomography (MDCT) to study the relation between culprit plaque characteristics and cardiac troponin T (cTnT) elevation after percutaneous coronary intervention (PCI). Percutaneous coronary intervention is often complicated by post-procedural myocardial necrosis manifested by elevated cardiac biomarkers. Stable angina patients (n = 107) with normal pre-PCI cTnT levels underwent 64-slice MDCT before PCI to evaluate plaque characteristics of culprit lesions. Patients were divided into 2 groups according to presence (group I, n = 36) or absence (group II, n = 71) of post-PCI cTnT elevation ≥3 times the upper limit of normal (0.010 ng/ml) at 24 h after PCI. Computed tomography attenuation values were significantly lower in group I than in group II (43.0 [26.5 to 75.7] HU vs. 94.0 [65.0 to 109.0] HU, p < 0.001). Remodeling index was significantly greater in group I than in group II (1.20 ± 0.18 vs. 1.04 ± 0.15, p < 0.001). Spotty calcification was observed significantly more frequently in group I than in group II (50% vs. 11%, p < 0.001). Multivariate analysis showed presence of positive remodeling (remodeling index >1.05; odds ratio: 4.54; 95% confidence interval: 1.36 to 15.9; p = 0.014) and spotty calcification (odds ratio: 4.27; 95% confidence interval: 1.30 to 14.8; p = 0.016) were statistically significant independent predictors for cTnT elevation. For prediction of cTnT elevation, the presence of all 3 variables (CT attenuation value <55 HU; remodeling index >1.05, and spotty calcification) showed a high positive predictive value of 94%, and their absence showed a high negative predictive value of 90%. MDCT may be useful in detecting which lesions are at high risk for myocardial necrosis after PCI.	\N	\N
22610716	A 320-row multidetector CT provides the capability for prospective electrocardiogram (ECG)-gated coronary CT angiography (CTA) and tube current modulated cardiac function assessment (CFA). We assessed and compared the effective radiation dose of these two modes. On a prospective basis, we performed ECG-gated cardiac CT on 119 patients (87 were males). For heart rates (HRs) </=65 beats/min (bpm), we used one-heartbeat acquisition and half-scan reconstruction. HRs from 66 to 79 bpm and >/=80 bpm were scanned with either two or three heartbeats acquisitions, respectively. We used two types of scans. One type was based on a prospective ECG-gated CTA mode and the other using a tube current modulated CFA mode covering an entire R-R interval. The mean BMI of patients was 25.4 (range 18.8-49.3). Fifty-one patients (42.9 %) underwent CFA scanning, while the remaining 68 (57.1 %) had CTA. The majority of patients completed the scan in a single heartbeat (59.7 %). The mean dose of CTA mode at 65-85 % phase window for one and two heartbeats was 3.68 mSv (2.40-7.23) and 8.61 mSv (6.76-10.60), respectively. The mean dose of CFA mode for a single heartbeat measurement with dose modulation (25 % dose for CFA, and 100 % dose during 65-85 % phase window for CTA) was 6.32 mSv (4.69-8.89). CTA with prospective ECG-gating allows for acceptable image quality and radiation dose. HR reduction is mandatory to minimize radiation exposure. Global left ventricle function can be assessed with a single heartbeat within an acceptable radiation dose.	\N	\N
22616529	Global climate warming for the last 10 years actualized the problem of mortality rise in some European countries in anomalous summer heat. Russia faced this problem in July-August 2010 when extreme heat entailed a significant elevation of mortality in 31 regions of the country primarily due to coronary heart disease and cerebrovascular diseases. The analysis of foreign researches has shown that old age and living in cities are leading risk factors of deat in anomalous heat. Experience of the European countries and USA evidences that stay in conditioned apartments and early referral for medical assistance are most effective death preventive measures in heat.	\N	\N
22621617	Graves' disease (GD) is one of the most common autoimmune thyroid disorders and has a striking characteristic of female preponderance. The main objective of this study was to investigate whether IL12B gene polymorphisms were associated with either GD itself or with gender bias in GD. GD patients (151 males, 97 females) and 211 healthy control subjects without antithyroid autoantibodies or a family history of autoimmune disorders were recruited for this study. The G/C polymorphism (rs6887695) of the IL12B gene was analyzed using the polymerase chain reaction-restriction fragment length polymorphism, and the deletion and insertion polymorphism (rs41292470) in the IL12B promoter was detected after polyacrylamide gel electrophoresis-silver staining method. There was no significant difference between GD patients and normal subjects, and no differences in frequencies of genotypes or alleles of either polymorphism between male and female GD subjects. We conclude that these IL12B gene polymorphisms were not associated with sex bias in GD and do not confer susceptibility to Graves' disease (GD) in the Chinese population.	\N	\N
22626277	Inflammation in the ovary, including ovulation and pelvic inflammatory disease, has been proposed to play a role in the pathogenesis of ovarian cancer. Endometriotic lesions trigger a local inflammatory reaction and have been reported to be associated with an increased risk of epithelial ovarian cancer. However, the precise molecular mechanisms of ovarian cancer arising from endometriosis are still to be elucidated. To clarify the involvement of mismatch repair (MMR) abnormalities in the inflammation-associated malignant transformation of endometriosis, the immunohistochemical expression of mismatch repair proteins (human mutL homolog 1 [hMLH1] and human mutS homolog 2 [hMSH2]) was examined in 27 cases of ovarian endometriosis, 25 cases of ovarian carcinoma accompanied by endometriosis, and 39 cases of solitary ovarian carcinoma. In addition, the relationship between mismatch repair abnormalities including the microsatellite instability, PTEN (phosphatase and tensin homolog) mutation, and clinicopathologic parameters was analyzed. The expression of mismatch repair proteins was stepwisely decreased in endometriosis, ovarian carcinoma accompanied by endometriosis, and ovarian carcinoma. Tumors harboring multiple microsatellite instability (high-frequency microsatellite instability [MSI-H]) were detected in 4 (14.8%) of 27 cases of endometriosis and 7 (30.4%) of 23 cases of ovarian carcinomas. The frequency of PTEN mutations was higher in MSI-H cases than in microsatellite instability-stable (MSI-S) cases. In 2 cases of ovarian carcinoma accompanied by endometriosis, the decreased expression of mismatch repair proteins and MSI-H was observed in both the endometriosis and carcinoma lesions. Clinicopathologically, the MSI-H cases were associated with elevated serum levels of C-reactive protein and higher white blood cell counts. These findings suggest that mismatch repair abnormalities might be involved in the malignant transformation of ovarian endometriosis and that inflammation induces mismatch repair abnormalities during ovarian carcinogenesis arising from endometriosis.	\N	\N
22639889	Neuronal protein α-synuclein (α-syn) is an essential player in the development of neurodegenerative diseases called synucleinopathies. A spontaneous autosomal recessive rat model for neurodegeneration was developed in our laboratory. These rats demonstrate progressive increases in α-syn in the brain mesencephalon followed by loss of dopaminergic terminals in the basal ganglia (BG) and motor impairments. The severity of pathology is directly related to the overexpression of α-syn and parallel decrease in dopamine (DA) level in the striatum (ST) of affected rats. The neurodegeneration in this model is characterized by the presence of perikarya and neurites Lewis bodies (LB) and diffuse marked accumulation of perikaryal α-syn in the substantia nigra (SN), brain stem (BS), and striatum (ST) along with neuronal loss. Light and ultrastructural analyses revealed that the process of neuronal degeneration is a 'dying back' type. The disease process is accompanied by gliosis and release of inflammatory cytokines. This neurodegeneration is a multisystemic disease and implicate α-syn as a major factor in the pathogenesis of this inherited autosomal recessive animal model. Decrease dopamine (DA) and overexpression of α-syn in the brain mesencephalon may provide a naturally occurring animal model for Parkinson's disease (PD) and other synucleinopathies that reproduces significant pathological, neurochemical, and behavioral features of the human disease.	\N	\N
22644412	To evaluate retrospectively whether technical factors of hepatic arterial embolization affect the prognosis of patients with hepatocellular carcinoma (HCC). Inclusion criteria of this study were the following: (1) patients received embolization as the initial treatment during 2003-2004, (2) Child A or B liver profile, (3) five or fewer HCCs with maximum diameter of 7 cm or smaller, and (4) no extrahepatic metastasis. Patient data were gathered from 43 centers. Prognostic factors were evaluated using univariate and multivariate analyses. Eight hundred fifteen patients were enrolled. The 1-, 3-, 5-, and 7-year overall survival rates were 92.0 % (95 % CI 90.1-93.9), 62.9 % (95 % CI 59.3-66.6), 39.0 % (95 % CI 35.1-43.0), and 26.7 % (95 % CI 22.6-30.8) in all patients. Univariate analysis showed a Child-Pugh class-A, alpha-fetoprotein level lower than 100 ng/ml, tumor size of 3 cm or smaller, tumor number of 3 or fewer, one-lobe tumor distribution, nodular tumor type, within the Milan criteria, stage I or II, no portal venous invasion, use of iodized oil, and selective embolization were significantly better prognostic factors. In the multivariate Cox model, the benefit to survival of selective embolization remained significant (hazard ratio 0.68; 95 % CI 0.48-0.97; p = 0.033). Selective embolization contributes to survival in patients with HCCs.	\N	\N
22652723	Anemia is a significant cause of morbidity and lowers the quality of life of patients suffering from chronic kidney disease (CKD). Iron deficiency is the most important cause of erythropoietin (EPO) hyporesponsiveness in CKD. EPO administration significantly increases the costs of CKD management. It follows that paramount importance must be given to enhancing responsiveness to EPO thereby ensuring that the patient derives maximum benefit. Intravenous iron (IVI) administration has been used for decades to replenish body iron stores. Multiple preparations of Iron are available in the market. However, IVI administration is fraught with dangers like adverse drug reactions, susceptibility to infection, and, as recently postulated, direct cellular toxicity. Traditional approaches to IVI administration have focused on multiple administrations of lower doses for fear of adverse reactions. However, recent studies have demonstrated that higher doses can be safely administered in a single infusion, thereby reducing hospitalization costs and patient inconvenience. Newer preparations of IVI are relatively safer, easier to administer and efficacious. Preparations like Iron sucrose, ferumoxytol, ferric carboxymaltose and iron isomaltoside do not require test doses and allow higher doses to be administered at a time with cost and effect benefits.	\N	\N
22655515	Recently we reported a cytoplasmic sodium overload to cause a severe osmotic oedema in Duchenne muscular dystrophy (DMD). Our results suggested that this dual overload of sodium ions and water precedes the dystrophic process and persists until fatty muscle degeneration is complete. The present paper addresses the questions as to whether these overloads are important for the pathogenesis of the disease, and if so, whether they can be treated. As a first step, we investigated the effects of various diuretic drugs on a cell model of DMD, i.e. rat diaphragm strips previously exposed to amphotericin B. We found that both carbonic anhydrase inhibitors and aldosterone antagonists were able to repolarise depolarised muscle fibres. Since carbonic anhydrase inhibitors are known to have acidifying effects and this might be detrimental to the ventilation of DMD patients, we mainly concentrated on the modern spironolactone derivative, eplerenone. This drug had a very high repolarizing power, the parameter considered by us as being most relevant for a beneficial effect. In a pilot study we administered this drug to a 22-yr-old female DMD patient who was bound to an electric wheelchair and has had no corticosteroid therapy before. Eplerenone decreased both cytoplasmic sodium and water overload and increased muscle strength and mobility. We conclude that eplerenone has beneficial effects on DMD muscle. In our opinion the cytoplasmic oedema is cytotoxic and should be treated before fatty degeneration takes place.	\N	\N
22658853	Pulmonary complications associated with Sjögren syndrome (SS) have attracted attention in recent years. Sjögren syndrome has been associated with small cyst formation in salivary glands, thymus, and lungs and has been recently brought to the forefront by radiologists due to high-resolution techniques. However, pathologists are less aware of this finding unless clinico-radiologic-pathologic correlation is sought. Formation of large bullae in SS is a rare complication with potential for confusion with other diseases. Here, we present the clinical, radiologic, and pathologic findings in 3 patients with SS associated with multiple pulmonary cystic lesions. All 3 patients had a variable mixed restrictive and obstructive component of the disease. There was good correlation with the pulmonary function tests (PFTs), high-resolution computed tomographic scan, and morphology with regard to the restrictive component. The small cysts appear to correlate with the extent of obstructive changes on the PFTs. However, the large bullae do not, implying noncommunication with the conducting airways. This noncorrelation between the PFTs and extent of bullous disease with predominant involvement of lower lobes in SS enables distinction from bullous emphysema. The mechanism of bulla formation in SS appears to be different from bullous emphysema. A check valve mechanism has been proposed previously in SS, which does not explain cyst formation in the thymus. Alternately, inflammation may play a role with the key suspects being CD4 T-helper cells and perhaps NK cells. This is the first report of a clinico-radiologic-pathologic correlation with analysis of lymphocyte subsets.	\N	\N
22669091	Aim of the study was to analyze outcome in patients who underwent surgery following type A aortic dissections and to evaluate the long-term survival rates in patients 70 years of age and older and those under 70 years of age, and in males as compared to females. Between September 1997 and October 2008, 154 patients were retrospectively enrolled. There were 102 males (66.2%) and 52 females (33.8%) with a mean age of 63.5±12; seven patients (4.5%) were over 80 years of age, 46 (29.8%) were between 70 and 80 years of age and 101 were under 70 years of age at the time of surgery. We compared patients 70 years of age and older with those under 70 years of age, analyzing the early and long-term survival results and postoperative complications. Overall in-hospital mortality was 17.5% and permanent neurological dysfunction occurred in 10 patients (6.5%). Twenty patients (12.9%) died during follow-up. Among the males, the long-term survival rate was 80%, 68% and 51% at 1, 5 and 10 years, respectively. Among the females, survival rate was 84.6%, 72.3% and 47.5% at 1, 5 and 10 years, respectively. Five- and 10-year survival rates were 78.1% and 59.4%, respectively, for patients under 70 years of age, and 50.8% at 5 years and 26.1% at 10 years for those over 70. Patients might not be excluded from surgical intervention for acute type A aortic dissection (ATAAD) only due to age. It is important to consider biological age and the clinical features of the patients at the time of surgery. Age is a relative but not absolute contraindication for surgery in ATAAD. Long-term survival was not statistically different between males and females.	\N	\N
22689018	Ampullary and extensive periampullary lesions can be difficult to treat and often require pancreaticoduodenectomy (PD) for complete removal, even if benign. However, PD may be overtreatment for noninvasive lesions, and pancreas-sparing total duodenectomy (PSTD) is an emerging valid surgical option for selected cases. We reviewed patients undergoing PSTD at our institution over 16 months and a comparison group who had undergone PD for benign duodenal disease over the past 15 years. We also reviewed cases in the English-language literature and performed a meta-analysis of those patients who had undergone PSTD. PSTD had been performed in four patients, who had an average hospital length of stay (LOS) of 13 days; two of them experienced complications. None required conversion to PD, experienced a postoperative fistula or endocrine or exocrine insufficiency, or required intensive care. Two of the PSTDs were performed laparoscopically. Open PD for benign duodenal disease was performed in 22 patients, with overall morbidity and pancreas fistula rates of 82 and 27 %, respectively. The meta-analysis found 128 unique cases of PSTD with morbidity and mortality rates of 46.4 and 2.3 %, respectively. Pancreaticobiliary leak was seen in 20 %, with an average LOS of 17 days. Although PSTD can be used to avoid PD and can be performed laparoscopically, it is technically challenging and still associated with morbidity.	\N	\N
22691438	To describe the small retinal and systemic vessel involvement in Takayasu's arteritis. We described 3 patients with Takayasu's arteritis and small retinal vessel occlusion seen in our department between 2004 and 2011. We performed an extensive literature review and provided a global analysis of small retinal vessel involvement in Takayasu arteritis (i.e., total number of patients analyzed=9). Seven patients had small retinal artery occlusion, and two had venous involvement. Four cases were inaugural of the disease (44.4%). Takayasu's arteritis was extended (Type V) in the majority of patients presenting with small retinal vessel occlusion (5/9, 55.6%), and 8/9 reported cases (88.9%) presented with involvement of the supra-aortic branches. Immunosuppressive regimen allowed an improvement in 5/9 patients and stabilization in 1/9, but the situation worsened in 3/9 patients. The visual outcome was severe, and 3/9 patients (33.3%) experienced irreversible blindness. Occlusion of small retinal vessels is a rare and severe microcirculatory complication in Takayasu's arteritis, as well as necrotizing cutaneous vasculitis or myocarditis. Small retinal vessel involvement can be inaugural of the disease and seriously impact the visual prognosis in TA patients.	\N	\N
22696253	Accumulating evidence demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) may transdifferentiate into cardiomyocytes and replace apoptotic myocardium so as to improve functions of damaged hearts. However, little information is known about molecular mechanisms underlying myogenic conversion of BMSCs. microRNAs as endogenous noncoding small molecules function to inhibit protein translation post-transcriptionally by binding to complementary sequences of targeted mRNAs. Here, we reported that miR-124 was remarkably downregulated during cardiomyocyte differentiation of BMSCs induced by coculture with cardiomyocytes. Forced expression of miR-124 led to a significant downregulation of cardiac-specific markers-ANP, TNT, and α-MHC proteins as well as reduction of cardiac potassium channel currents in cocultured BMSCs. On the contrary, the inhibition of endogenous miR-124 with its antisense oligonucleotide AMO-124 obviously reversed the changes of ANP, TNT, and α-MHC proteins and increased cardiac potassium channel currents. Further study revealed that miR-124 targeted the 3'UTR of STAT3 gene so as to suppress the expression of STAT3 protein but did not affect its mRNA level. STAT3 inhibitors AG490, WP1066, and S3I-201 were shown to attenuate the augmented expression of ANP, TNT, α-MHC, GATA-4 proteins, and mRNAs in cocultured BMSCs with AMO-124 transfection. Moreover, GATA-4 siRNA reduced the expression of ANP, TNT, α-MHC, and GATA-4 proteins but did not impact STAT3 protein in cocultured BMSCs, indicating GATA-4 serves as an effector of STAT3. In summary, we found that miR-124 regulated myogenic differentiation of BMSCs via targeting STAT3 mRNA, which provides new insights into molecular mechanisms of cardiomyogenesis of BMSCs.	\N	\N
22697349	α-1 anti-trypsin (AAT) is the most abundant circulating serine protease inhibitor (serpin) and an acute phase reactant. Systemic deficiency in AAT (AATD) due to genetic mutations can result in liver failure and chronic lung disease such as emphysema. Considered the prototypic serpin, the emphysema observed in patients with AATD, consisting of progressive destruction of the alveoli and small airway structures, formed the basis of the protease/anti-protease imbalance theory of chronic obstructive pulmonary disease (COPD). Over the past decade, however, investigations of AATD have described multiple functions of AAT beyond those generally attributed to its antiprotease activity. Evidence now suggests that AAT plays an important role in modulating immunity, inflammation, proteostasis, apoptosis, and possibly cellular senescence programs. When integrated in vivo, these processes contribute to the lung maintenance program which preserves the lung despite a constant bombardment by damage associated molecular patterns (DAMPs) and/or pathogenassociated molecular patterns (PAMPs) initiated by cigarette smoke, pollutants, or infections. In this review, we discuss the clinical aspects of AATD as they pertain to emphysema; including similarities and differences to cigarette smoke-induced emphysema. Examining the lung maintenance program, we next consider the multiple mechanisms of airspace destruction and explore the role AATD contributes. Finally, we consider the data regarding treatment of AATD, including AAT supplementation and its current limitations, and suggest further avenues of research informed by the multiple functions of AAT.	\N	\N
22697357	We describe two siblings with epiphora, telecanthus, expressionless face, thick facial skin, bulky nose and profound sensorineural hearing loss. Constellation of these features presented a phenotypic overlap with Blepharo-naso-facial syndrome (BNFS) and Nablus mask-like syndrome (NMLS). They in addition had posterior helical pits. The molecular basis of NMLS is known, while BNFS remains an elusive disorder. We report the first Indian family with features having significant overlap between the two but we attempt to summarize the frequency of reported features and bring out the most consistent features for these two syndromes for the treating clinician.	\N	\N
22699458	Innate and adaptive immune responses in neurodegenerative diseases have become recently a focus of research and discussions. Parkinson's disease (PD) is a neurodegenerative disorder without known etiopathogenesis. The past decade has generated evidence for an involvement of the immune system in PD pathogenesis. Both inflammatory and autoimmune mechanisms have been recognized and studies have emphasized the role of activated microglia and T-cell infiltration. In this short review, we focus on dendritic cells, on their role in initiation of autoimmune responses, we discuss aspects of neuroinflammation and autoimmunity in PD, and we report new evidence for the involvement of neuromelanin in these processes.	\N	\N
22699661	Hashimoto's thyroiditis as well as lichen planus has been associated to a number of disorders, generally of auto-immune origin. A novel possible association between oral lichen planus (OLP) and Hashimoto's thyroiditis (HT) is here proposed on the basis of a cross-sectional survey. One hundred and five unrelated OLP patients were considered. Diagnosis of HT was based on positive serum anti-TPO, anti-Tg, TSH levels and the typical ultrasound pattern of the thyroid gland. In the present survey, the prevalence of HT in the OLP group was 14.3 % whereas the prevalence of HT-related hypothyroidism in the general population was reported to be equal to 1 %. By Fisher's exact test, it was revealed that the difference between our data and historical prevalence of HT was found statistically significant. Actually, there is no definitive hypothesis that could explain the coexistence of OLP and HT. However, considering the onset timing of HT followed by OLP in 93.3 % of our series, we suspected a causal or predisposing role for HT. Specifically, we believe that in HT patients, circulating thyroid antibodies could contribute to trigger an organ-specific auto-immune response also in the oral mucosa or skin, leading to the development of LP lesions. Because of the large number of cases of asymptomatic chronic auto-immune thyroiditis, it would be useful that women over 40 years of age affected by OLP were screened for thyroid dysfunction, particularly HT.	\N	\N
22711587	This study investigated associations between chronic inflammation and coagulation and incident locomotor disability using prospective data from the British Women's Heart and Health Study. Locomotor disability was assessed using self-reported questionnaires in 1999/2000, and 3 and 7 years later. Scores for inflammation and coagulation were obtained from summation of quartile categories of all available biomarkers from blood samples taken at baseline. 534 women developed locomotor disability after 3 years, 260 women after 7 years, while 871 women remained free of locomotor disability over the whole study period. After adjustment for demographic characteristics, lifestyle factors and health conditions, we found associations between inflammation and incident locomotor disability after three (OR per unit increase in score = 1.08, 95 % confidence interval (CI): 1.03, 1.13) and 7 years (OR = 1.10, 95 % CI: 1.03, 1.18) and between coagulation and incident locomotor disability after 3 (OR = 1.06, 95 % CI: 0.98, 1.14) and 7 years (OR = 1.09, 95 % CI: 1.00, 1.18). This corresponds to ORs between 1.8 and 2.4 comparing women with highest to lowest inflammation or coagulation scores. These results support the role of inflammation and coagulation in the development of locomotor disability in elderly women irrespective of their lifestyle factors and underlying age-related chronic diseases.	\N	\N
22713729	As science matures, it becomes more mathematical, progressing from enumeration to the use of equations to the formulation of models. Clinical pharmacology has developed to the stage where models play an increasingly important role in predicting and analyzing drug pharmacokinetics and pharmacodynamics, and even in characterizing disease progression and therapeutic response. Useful models have two characteristics that are in ostensible conflict: (i) they must accurately represent the essential features of the underlying system and (ii) the representation must be sufficiently simplified to enable its salient features to be identified and investigated through further experimentation.	\N	\N
22726388	Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis. Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein). A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC.	\N	\N
22739032	Vascular disease and medical factors are associated with cognitive decline and cardiovascular events. We examined the association between vascular risk factors and events in the Alzheimer's Disease Neuroimaging Initiative cohort. The association between vascular risk factors and cardiovascular events in a cohort of 810 participants, including 400 with mild cognitive impairment, 184 with Alzheimer's, and 226 controls was investigated using a longitudinal hazard model. There were 31 events including 11 strokes, 7 myocardial infarctions, 5 revascularizations, and 8 deaths during an average follow-up of 31 months. Longitudinal cardiovascular event rates were low and similar between diagnostic groups. All baseline vascular risk factors that were expected to be associated with longitudinal cardiovascular events were, or were trending toward, associating with cardiovascular events except atrial fibrillation, depression, and apolipoprotein E genotype. Despite differences in baseline vascular risk factors, longitudinal cardiovascular event rates were similar between diagnostic groups.	\N	\N
22740450	Cyclin dependent kinase (CDK) inhibitors, such as flavopiridol, demonstrate significant single-agent activity in chronic lymphocytic leukemia (CLL), but the mechanism of action in these nonproliferating cells is unclear. Here we demonstrate that CLL cells undergo autophagy after treatment with therapeutic agents, including fludarabine, CAL-101, and flavopiridol as well as the endoplasmic reticulum (ER) stress-inducing agent thapsigargin. The addition of chloroquine or siRNA against autophagy components enhanced the cytotoxic effects of flavopiridol and thapsigargin, but not the other agents. Similar to thapsigargin, flavopiridol robustly induces a distinct pattern of ER stress in CLL cells that contributes to cell death through IRE1-mediated activation of ASK1 and possibly downstream caspases. Both autophagy and ER stress were documented in tumor cells from CLL patients receiving flavopiridol. Thus, CLL cells undergo autophagy after multiple stimuli, including therapeutic agents, but only with ER stress mediators and CDK inhibitors is autophagy a mechanism of resistance to cell death. These findings collectively demonstrate, for the first time, a novel mechanism of action (ER stress) and drug resistance (autophagy) for CDK inhibitors, such as flavopiridol in CLL, and provide avenues for new therapeutic combination approaches in this disease.	\N	\N
22744150	To provide information about occurrence and patterns of geriatric morbidity and need for long-term care in patients newly diagnosed with dementia compared to controls without dementia. An analysis of administrative data was conducted to compare the geriatric outpatient diagnoses and the patterns of care dependency of 1,848 incident dementia patients and 7,385 matched non-dementia controls older than 65 years in the incidence year. In most cases the geriatric characteristics show an increased (partly statistically significant) prevalence in the group with dementia as compared to controls. Moreover, dementia patients show a higher number of geriatric comorbidities in contrast to non-dementia controls. Furthermore, the percentage of persons with need for long-term care in the dementia-group is significantly higher than for controls (44.4 vs. 12.9 %). Prevention, early recognition or treatment of attendant symptoms are very important in daily clinical and nursing care in patients with dementia to ameliorate the progression of the disease and to improve the patients' quality of life.	\N	\N
22744504	Screening for idiopathic scoliosis is not very popular in Poland. Some Polish towns and cities have prevention programmes aimed at discovering spine dysfunctions and disorders in children and adolescents. An assessment of the angle of trunk rotation (ATR) is a reliable, effective and non-invasive action that allows use to determine trunk asymmetry. Since then the scoliometer has spread throughout the United States and other countries, where it is a popular device in the clinical practice of diagnosing scoliosis. 9,500 children aged 7-10 were examined as part of a disease prevention programme entitled "Poznan Chooses Health - Bad Posture Prophylaxis in Class I-IV Primary School Children in Poznan". The analysis included results obtained in 2010 during initial posture assessment in 1000 children, Trunk asymmetry was measured by means of the Bunnell scoliometer. The measurement of the angle of trunk rotation was the spontaneous standing position with use the scoliometer during bending (Adams forward test) at three levels: proximal thoracic, main thoracic and lumbar. For the proximal thoracic section the 0° ATR value was found in 6 children, values of 1°-3° were recorded in 883 children, values of 4°-6° in 108 children, 7° or higher in 3 of the examined children. For the main thoracic section the 0° ATR value was found in 101 children, values of 1°-3° were recorded in 735 children, 4°-6° in 155 children, 7° or higher in 9 of the examined children. For the lumbar section ATR values of 0°, 1°-3°, 4°-6°, and 7° or higher were found, respectively, in 147, 883, 108 and 11 of the examined children.	\N	\N
22744756	In newly diagnosed glioblastoma multiforme, surgery, combined radio and chemotherapy, and adjuvant chemotherapy with temozolomide is the standard of care. Therapy for recurrent glioblastoma is less well established and comprises re-operation, re-irradiation, chemotherapy, targeted therapy, inhibition of neoangiogenesis, and others. In this observational study we recorded the efficacy and toxicity of a combination of procarbazine, carmustine, and vincristine (PBV) for 69 patients with recurrent and/or progressive glioblastoma after surgery, concomitant radio and/or chemotherapy, and adjuvant first-line temozolomide therapy. Of 41 patients evaluable for response by MRI, partial response was observed for one, minor response for three, stable disease for at least 6 weeks for ten, and immediate progression for 27. Median PFS was 15 weeks, and PFS-6 was 21 % for 57 patients who could be followed; 12 other patients were lost to follow-up after application of the first PBV cycle. Grade III or IV leucopenia and/or grade III or IV thrombocytopenia were seen in 26 % and 26 % of cycles, respectively. Haematological complications led to interruption of treatment for four (7 %) patients. Non-haematological toxicity was moderate. Salvage PBV therapy in recurrent and/or progressive glioblastoma, pre-treated with temozolomide-based chemotherapy as first-line treatment, is of limited efficacy with a small number of long-term survivors, but is hampered by relevant myelotoxicity.	\N	\N
22753355	Hepatic arterial infusional (HAI) chemotherapy combined with systemic chemotherapy is effective palliative therapy for unresectable colorectal cancer liver metastases (CRLM). Some patients considered for HAI have evidence of minimal extrahepatic disease (EHD), and the role of HAI in these situations is unknown. All patients with unresectable CRLM treated with HAI and systemic chemotherapy from 2000 to 2009 were included. Survival of patients who were ultimately proven to have low-volume EHD was compared to those without EHD. Three hundred seventy-three patients were included in this study. Seventy-nine percent of patients were previously treated with chemotherapy. One hundred forty-five patients (39%) ultimately proved to have EHD. Median overall survival from HAI pump placement in patients without EHD was 32 months compared to 16 months for patients with EHD, P < 0.001. Median overall survival from HAI pump placement in patients with a single site of EHD was 18 months compared to 9 months for those with multiple sites of EHD, P = 0.01. In this study of heavily pre-treated patients, overall survival was favorable in patients who proved to have EHD at one site.	\N	\N
22761515	To explore areas of consensus and disagreement concerning the interhospital transfer of patients with a clinical diagnosis of ruptured abdominal aortic aneurysm. A three-round Delphi questionnaire approach was used among vascular and endovascular surgery and emergency medicine specialists to explore patient characteristics and clinical management issues for emergency interhospital transfer. Analysis is based on 38 responses to rounds 2 and 3 (19 vascular surgeons, 6 interventional radiologists, 13 emergency care specialists) with agreement reported when 70% of respondents were in agreement. Initially there was agreement that transfer patients should be <85 years of age, either alert or with fluctuating consciousness, with moderate or minimal systemic disease, needing no/some help with daily living. Round 3 clarified that patients requiring inotropes and those institutionalised for mental infirmity should be transferred. Those with cardiac arrest in current episode should not be transferred. There was no agreement as to whether those institutionalised with physical infirmities, unconscious/intubated patients or those with severe systemic disease should be transferred. Speed was accepted as important, with agreement for specialty trainees to arrange transfer if consultants were not on site. Consultant-consultant discussion was recommended for patients with severe systemic disease. CT confirmation of diagnosis was considered unnecessary before transfer but ultrasound assessment was desirable, and transfers should not be delayed by waiting for specific tests. There was no agreement about blood tests and ECG before transfer or whether blood should accompany the patient being transferred. There was no agreement as to whether specific staff/facilities needed to be in place at the specialist hospital. A systolic blood pressure ≥70 mm Hg was sufficient for transfer without the need for intravenous fluids unless deterioration occurred. There is broad agreement about the type of patient who should be eligible for transfer but disagreements about patient management before and during transfer remain.	\N	\N
22766701	Cardiovascular disease (CVD) is one of the main causes of mortality in the world representing around 30% of all deaths. It constitutes also an important factor in morbidity and incapacity. There are several related CVD risk factors such as hypertension, metabolic syndrome (MetS) and hypercoagulability. The exact mechanisms that underlie the relation between those factors and CVD are not sufficiently known yet; pathogenic explanations are lacking also for the mechanisms relating metabolic factors to insulin resistance (IR) and the association with the development of atherosclerosis and thrombosis. The possible links between hypertension, hemostasis alterations and MetS are examined in this report.	\N	\N
22766888	Metabolic syndrome (MS) is a cluster of risk factors that predispose to major cardiovascular diseases and its complications, determining liver and kidney impairment. In the last decade, the indications to transplantation are increasing, with a linear incidence of the complications of the procedure. MS represents one of the commonest, being in turn may the consequence of the underlying disease that required the transplantation, or the result of the medical treatment, as well as one of the most important factor influencing the morbidity and mortality of the transplanted patients. Due to the growing incidence of the MS in these patients, it is crucial to focus and clarify the leading causes determining the onset of the metabolic disarrangement, its outcome and the hypothetical mechanism through which the clinicians could reduce the impact of the disease. In fact, prevention, early recognition, and treatment of the factor that could predict the onset or progression of the MS after the transplantation may impact long term survival of patients, that is again the scope of the same transplant. This review will update the different mechanisMS of the pathogenesis of MS in this population, the clinical effects of the presence of the MS, observing the risk factors to be treated before and after the transplantation and suggesting the management of the follow-up.	\N	\N
22767670	This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of the investigational oral drug MLN8237 (alisertib), a small-molecule Aurora A kinase (AAK) inhibitor, in 87 adult patients with advanced solid tumors. Sequential cohorts of patients received MLN8237 5 to 150 mg orally once daily or twice daily for 7, 14, or 21 days, followed by 14 days' rest per cycle. MLN8237 pharmacokinetics was characterized, and the relative bioavailability of an enteric-coated tablet (ECT) formulation was evaluated in reference to the original powder-in-capsule (PIC) formulation. Pharmacodynamic effects of MLN8237 on inhibition of AAK activity were evaluated in skin biopsies. Tolerability and response to treatment were assessed. Common toxicities included fatigue, nausea, and neutropenia. Plasma exposures increased dose proportionally (5-150 mg/d), and were similar for PIC and ECT. The terminal half-life was 23 hours. At the maximum tolerated dose of 50 mg twice daily on the 7-day schedule, the mitotic index of the skin basal epithelium was increased within 24 hours after MLN8237 administration on days 1 and 7, a finding consistent with AAK inhibition. One (1%) patient achieved a partial response lasting for more than 1 year and received MLN8237 for 51 cycles; 20 (23%) patients achieved stable disease for ≥3 months. This first-in-human trial of MLN8237 showed tolerability and favorable pharmacokinetics in this patient population. The recommended phase II dose of MLN8237 is 50 mg twice daily orally for 7 days in 21-day cycles, which is being evaluated further in the treatment of various solid tumors and hematologic malignancies.	\N	\N
22804715	Peripheral arterial disease (PAD) is a chronic, progressive disease with a significant cardiovascular and cerebrovascular risk burden and a considerable impact on functional capacity and quality of life (QoL). Exercise programmes result in significant improvements in walking distances but long-term effects are uncertain. The aim of this study was to assess the one-year effects of participation in a 12-week supervised exercise programme on functional capacity and QoL for PAD patients. Patients were randomly allocated to a control (n = 16) or an exercise (n = 28) group. Data regarding functional capacity (Walking Impairment Questionnaire WIQ), disease-specific QoL (Intermittent Claudication Questionnaire ICQ) and generic QoL (SF-36) were collected at baseline, 12 weeks and 1 year. At 12 weeks, there was a trend towards improved QoL in both groups, with a tendency for greater improvement in the exercise group (p = 0.066) and a trend towards improved functional capacity (WIQ Stair-climbing p = 0.093) in the exercise group. At 1 year, ICQ scores in the exercise group were considerably better than those in the control group (p = 0.058), reflecting improved QoL and maintenance of benefits. Participation in a supervised exercise programme results in improvements in functional capacity and QoL at 1 year post-participation.	\N	\N
22819313	Controversy exists regarding the extent of pelvic lymph node dissection (PLND) in radical prostatectomy (RP) for prostate cancer. Impact of the extent of PLND may be determined by the disease risk. The aim of our study was to find the association between the extent of PLND on biochemical progression and disease risk. The study included 360 consecutive patients treated with RP for clinically localized prostate cancer at our department between 2000 and 2003. Patients were randomized to receive extended PLND (n = 180) and standard PLND (n = 180) at RP. Clinical and pathological data were prospectively collected. The patients did not receive any neoadjuvant or adjuvant therapy. The relation of disease risk and the extent of PLND to biochemical progression-free survival (BPFS) were examined. There were no significant differences in age, prostate-specific antigen, and other preoperative features in patients who underwent standard and extended PLND. Mean patient age was 68 y old and median follow-up was 74 mo. BPFS for the standard PLND group and the extended PLND group was 90.1% and 91.3% in low risk disease (log rank P = 0.807), 73.1% and 85.7% in intermediate risk disease (log rank P = 0.042), and 51.1% and 71.4% in high risk disease (log rank P = 0.036), respectively. In multivariate Cox proportional hazard analysis, extended PLND was an independent prognostic factor of biochemical progression-free survival when adjusting for other clinical and pathologic features. In intermediate and high risk patients, extended PLND positively affects BPFS. In low risk patients, extended PLND may be omitted to reduce operation time and complications.	\N	\N
22822599	Proctocolectomy and ileoanal anastomosis as a treatment of ulcerative colitis Sphincter-saving proctocolectomy, construction of ileal pouch (J pouch) and associated ileoanal anastomosis constitute an established surgical procedure in the treatment of patients having ulcerative colitis. The procedure has been found to improve the condition: the patient is usually relieved of medications and possible associated adverse effects, the cancer risk associated with the disease is minimized and the quality of life will improve. The most common complication is inflammation of the ileal pouch, developing in half of the patients.	\N	\N
22824112	Metabolomics is the systematic study of the unique chemical fingerprints of small molecules or metabolite profiles that are related to a variety of cellular metabolic processes in a cell, organ, or organism. Although messenger RNA gene expression data and proteomic analyses do not tell the whole story of what might be happening in a cell, metabolic profiling provides direct and indirect physiologic insights that can potentially be detectable in a wide range of biospecimens. Although not specific to cardiac conditions, translating metabolomics to cardiovascular biomarkers has followed the traditional path of biomarker discovery from identification and confirmation to clinical validation and bedside testing. With technological advances in metabolomic tools (such as nuclear magnetic resonance spectroscopy and mass spectrometry) and more sophisticated bioinformatics and analytical techniques, the ability to measure low-molecular-weight metabolites in biospecimens provides a unique insight into established and novel metabolic pathways. Systemic metabolomics may provide physiologic understanding of cardiovascular disease states beyond traditional profiling and may involve descriptions of metabolic responses of an individual or population to therapeutic interventions or environmental exposures.	\N	\N
22825384	Asthma is an inflammatory disease of the airways. It is suggested by characteristic history of recurrent episodes of wheezing, breathlessness, chest tightness, and/or cough especially at night or in early morning. In asthmatic patients spirometry or pulmonary function tests demonstrate airflow obstruction that improves significantly, defined as both a 12% and 200 ml improvement in either FEV1 in response to inhaled bronchodilator. Measurement of airways responsiveness to methacholine in specialized pulmonary function laboratories may help to diagnose asthma. The goals for successful management of asthma are to achieve and maintain control of symptoms and to prevent asthma exacerbations.	\N	\N
22825649	This review summarizes and discusses the role and efficacy of moisturizers, particularly the more recently introduced ceramide-based formulations, in the skin care regimen of patients with both active and quiescent atopic dermatitis (AD). It is now well established that a complex interplay of environmental and genetic factors are responsible for disease onset and chronicity. Indeed, several novel genetic mechanisms have been recently discovered to be associated with AD pathogenesis. Moreover, it is increasingly recognized that the epidermal barrier plays a critical role in the initiation, perpetuation, and exacerbation of AD. The skin of patients with AD harbors several defects in epidermal barrier function, including filaggrin and ceramides. An improved understanding of these etiopathogenic factors has led to the development of topical ceramide-dominant moisturizers to replace the deficient molecules and re-establish the integrity of barrier defenses. Some of these products have demonstrated efficacy in the treatment of adult and childhood AD that are similar to mid-potency topical steroids. More importantly, they have been shown to be safe with very few associated side-effects. We recommend the addition of such new agents as both the first step of treatment and in the maintenance of clinically quiescent skin of patients with AD.	\N	\N
22828371	Due to the limited incidence of posttransplant lymphoproliferative disorders (PTLD) in pediatric liver graft recipients, there is a scarcity of data on the characteristics of the disease in this population. We aimed to analyze the special features and behavior of PTLD arising after pediatric liver transplantation. A comprehensive search of the literature was conducted for the available data on PTLD in pediatric liver recipients pediatric PTLD through a search of Pubmed and Google Scholar using appropriate terms. We sought data on liver recipients younger than 18 years of age at the time of transplantation. From 51 reports, 43 fulfilled the inclusion criteria. Overall 250 cases of PTLD (212 pediatric PTLD) were found from 43 reports. Data on pediatric patients was compared to adults. Pediatric PTLD lesions were more likely of the polymorphic type (P=.004) and polyclonal (when age cut-off was defined at 12 years; P=.023). Remission rates, metastasis frequency and organ involvements were not different between the groups (P>.1 for all). Survival analysis showed no disparity between pediatric PTLD and adult patients (P>.1); but when data was reanalyzed for patients surviving at least 4 months post diagnosis, the log rank test showed that pediatric patients have a superior outcome compared to adults (P=.045). Pediatric liver recipients developing PTLD have relatively better disease presentation and behavior than that in adults. Stomach involvement was also more frequently seen in patients younger than 12 years, and should be more intensively evaluated. Future studies with a prospective approach and larger population size are needed for confirming our results.	\N	\N
22828643	Several bacteria cause community-acquired invasive bacterial disease in children; many are vaccine preventable. Knowledge of pathogens causing community-acquired invasive bacterial disease is important when selecting antimicrobial therapy and implementing vaccine prevention strategies. We describe bacteriology of community-acquired invasive disease observed among 31,641 blood and sterile fluid cultures from children aged 28 days to 36 months in 3 Latin American countries over 2 years.	\N	\N
22830284	Features of spread of cowpox in the contemporary conditions are examined. A decrease of population immunity to pox in the population of Russia caused by cancellation of pox immunization, hidden circulation of cowpox virus in various species of rodents, as well as lack of vigilance to pathogenic orthopoxviurses in healthcare workers were noted to create the real preconditions for the emergence of infection of humans caused by cowpox virus. Thereby presence of means of express laboratory diagnostics of cowpox and means of effective medical protection for the prevention of development of this disease in the population of Russia becomes an actual necessity.	\N	\N
22833442	Multiple myeloma is a heterogeneous disease, which is characterized by the occurrence of specific genomic abnormalities that are both of diagnostic and prognostic relevance. Since the detection of these abnormalities through molecular-genetic techniques is hampered by the overall low percentage of plasma cells present in primary bone marrow aspirates, we assessed the efficacy of these techniques in enriched plasma cell fractions from 61 multiple myeloma patients. Using interphase FISH, genomic abnormalities could be detected in 96% of the enriched samples as compared to 61% in the cultured whole bone marrow samples. We also found that microarray-based genomic profiling of enriched plasma samples facilitates the detection of additional, possibly clinically relevant, genomic abnormalities. We conclude that the genomic delineation of enriched plasma cells from multiple myeloma patients results in a significantly increased detection rate of clinically relevant genomic abnormalities. In order to facilitate molecular-genetic data interpretation, we recommend morphological assessment of plasma cell purity after enrichment.	\N	\N
22844693	The restorative integral support (RIS) model is a whole person response that assists people to overcome adversity. The adverse childhood experiences (ACE) Study conducted by Kaiser Permanente and the Centers for Disease Control and Prevention shows the association between stressors in childhood and multiple later-life health and social problems. Older adults experiencing co-occurring disorders are an under-served and vulnerable population where gaps in both practice models and research to inform effective service provision exist. The current empirical case study presents Senior Hope as one social service agency employing RIS to intervene on the linkage between ACEs and co-occurring disorders to assist older adults. RIS usefully articulates the way in which Senior Hope is developing ACE-informed programs that mobilize resilience and recovery to help older adults achieve positive mental health outcomes. Implementation and research on the RIS model is recommended to enhance services for groups with ACE characteristics.	\N	\N
22847755	Putative animal reservoirs and environmental samples were studied to investigate potential routes of transmission for indigenous hepatitis E virus (HEV) infection in Hokkaido, Japan. A total of 468 liver samples and 954 environmental samples were collected from 2003 to 2011 for this study. Four swine livers (1 %) were positive for HEV RNA; two strains belonged to genotype 3 and the other two strains were genotype 4. Genotype 3 HEV was detected in a sewage sample and a seawater sample. HEV strains derived from swine liver, seawater and raw sewage samples shared 93-100 % sequence similarity with human HEV strains.	\N	\N
22849219	This paper examines the State's assumption of medical care for patients with "permanent needs" in 19th century Spain. These patients were the incurably ill, the chronically ill and the elderly. This process is contextualized within the liberal reforms of the Spanish healthcare system in the reign of Isabel 11 (1833-1868). The goal of these reforms was the creation and consolidation of a national health system that would gradually replace the religious health charities. Healthcare reform became necessary due to the increase in migration that started in the 1830's and intensified in the 1850's. Traditional care networks formed by the family, local community and religious charities were no longer available to those who had left their village or town. In addition, many religious charities were bankrupted by the seizure of their properties in a programme of confiscation. Similar healthcare reform processes were taking place in the United Kingdom, France and Germany, among other European countries, and involved significant changes in the lives of patients, who became strictly controlled and medicalised. My aim was to identify changes in the patients' experience of illness through a case study of the living conditions of inmates at the Nuestra Señora del Carmen Hospital for Incurable Men, based in Madrid from 1852 to 1949. This was one of the institutions devoted to caring for patients with "permanent needs" and was under the direct control of the General State Administration.	\N	\N
22851496	Nitrotyrosine is a post-translationally modified amino acid with distinctly different properties than tyrosine or any other of the genetically encoded amino acids. Detecting proteins containing nitrotyrosine is the first step towards a better understanding of the role of nitrotyrosine in health and disease. Moreover, quantifying the extent of nitrotyrosine and determining its location in a protein forms the basis for a better understanding of the effect of tyrosine nitration on biological function. Described in this unit is a method to detect tyrosine-nitrated proteins in tissue sections and on western blots after creating a fluorescent complex between aminotyrosine, salicylaldehyde, and Al(3+). In addition, an approach is detailed for labeling aminotyrosine with biotin to enrich peptides from complex samples. Both methods require reduction of nitrotyrosine to aminotyrosine, which can be achieved with sodium dithionite or hemin plus dithiothreitol.	\N	\N
22869886	Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored. One hundred sixty-nine children diagnosed with stage 4 NB (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 ± GM-CSF ± 13-cis-retinoic acid (CRA) protocols after achieving first remission (complete remission/very good partial remission). Patients enrolled in regimen A (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT); and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT, whereas 28 of 85 required additional induction therapy and were deemed ultra high risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative reverse transcription polymerase chain reaction. Survival probability was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by multivariate Cox regression model. At 5 years from the start of immunotherapy, progression-free survival (PFS) improved from 44% for HR patients receiving regimen A to 56% and 62% for those receiving regimens B and C, respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated sites. Independent adverse prognostic factors included UHR (PFS) and post-cycle two MRD (PFS and OS), whereas the prognostic factors for improved outcome were missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse antibody response (OS), and regimen C (OS). Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.	\N	\N
22870861	Newborn screening for the inborn error of metabolism, classical galactosaemia prevents life-threatening complications in the neonatal period. It does not however influence the development of long-term complications and the complex pathophysiology of this rare disease remains poorly understood. The objective of this study was to report the development of a healthcare database (using Distiller Version 2.1) to review the epidemiology of classical galactosaemia in Ireland since initiation of newborn screening in 1972 and the long-term clinical outcomes of all patients attending the National Centre for Inherited Metabolic Disorders (NCIMD). Since 1982, the average live birth incidence rate of classical galactosaemia in the total Irish population was approximately 1:16,476 births. This reflects a high incidence in the Irish 'Traveller' population, with an estimated birth incidence of 1:33,917 in the non-Traveller Irish population. Despite early initiation of treatment (dietary galactose restriction), the long-term outcomes of classical galactosaemia in the Irish patient population are poor; 30.6 % of patients ≥ 6 yrs have IQs <70, 49.6 % of patients ≥ 2.5 yrs have speech or language impairments and 91.2 % of females ≥ 13 yrs suffer from hypergonadotrophic hypogonadism (HH) possibly leading to decreased fertility. These findings are consistent with the international experience. This emphasizes the requirement for continued clinical research in this complex disorder.	\N	\N
22873223	Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice.	\N	\N
22882216	The use of monoclonal antibodies in the treatment of malignancy and autoimmune diseases has rapidly expanded in the last decade. Rituximab, a monoclonal antibody to the CD20 antigen on B cells, was first approved by the US FDA in 1997 to treat non-Hodgkin's B-cell lymphoma. It is now used, however, for a variety of diseases in both on- and off-label uses. It was approved by the FDA for use in refractory rheumatoid arthritis in 2007, and in April 2011 it was approved for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitides (including granulomatosis with polyangiitis [Wegener's granulomatosis] and microscopic polyangiitis), based on the promising results of the RAVE trial. Within the field of nephrology, in addition to its use in anti-neutrophil cytoplasmic antibody-associated vasculitides, it is has been used in the treatment of membranous nephropathy, membranoproliferative glomerulonephritis and lupus nephritis.	\N	\N
22882559	To test a theoretically and empirically supported model of the relationships among percent truncal fat (truncal obesity); disease severity (carbon monoxide diffusing capacity [DLCO]); symptoms (dyspnea); functional capacity (6-min walk test distance); and functional performance (functional performance index) of elderly people with chronic obstructive pulmonary disease (COPD). A model of functional performance was proposed using a multidimensional framework as expounded by Leidy, and incorporating Wilson and Cleary's model for the relationship between symptoms and functional status. Path analysis was used to examine the relationships among variables. The researchers used a descriptive, cross-sectional design. Subjects were phone screened and completed electrocardiography, physical examination, spirometry testing, and a 4-min walk test as part of initial screening. Enrolled subjects completed a whole-body dual-energy x-ray absorptiometry scan to measure truncal obesity, 6-min walk test, upper body functional performance test, and questionnaires. Subjects were grouped into normal weight, overweight, or obese according to body mass index. The sample consisted of 76 people 55 years of age and older with mild to severe COPD. Percent truncal fat (truncal obesity) did not affect functional performance directly, but did affect it indirectly through dyspnea. The 6-min walk test distance, dyspnea, and DLCO accounted for 29% of the variability in functional performance. We believe that the effectiveness of pulmonary rehabilitation will be enhanced when nurses consider weight loss as a controllable factor for overweight and obese clients. The increasing prevalence of obesity in this population may dictate collaboration between dieticians and pulmonary rehabilitation nurses for effective rehabilitation programs. These findings suggest that percent truncal fat (truncal obesity) may be an indirect factor in the performance of daily activities of people with COPD. We anticipate that clinicians will use knowledge derived from this study to develop interventions to reduce or minimize truncal fat (truncal obesity) and its effects on people with COPD.	\N	\N
22883409	To establish a rat model of ulcerative colitis with syndrome of spleen deficiency and dampness stagnancy. Sixty rats were divided into normal control group, ulcerative colitis group, ulcerative colitis with syndrome of spleen deficiency and dampness stagnancy group (model group) and strengthening spleen for resolving dampness group. Ulcerative colitis in rats was induced by enema containing trinitrobenzene sulfonic acid (TNBS) and ethanol. The rats in the model group were suffered from standing in water, limiting sleeping time and abnormal diet based on administration of TNBS and ethanol. The rats in the spleen strengthening and dampness resolving group were gastrically administered with Shenlin Baizhu Powder, a compound traditional Chinese herbal medicine. Symptoms, signs and pathological changes in colon tissue of rats were observed after modeling. The levels of interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α) in serum of rats were measured by enzyme-linked immunosorbent assay. The rats in the model group showed lethargy, poor appetite, loss of energy, diarrhea and bloody stool. Their body weight decreased significantly compared with the normal control group, and similar changes were found in the comparison of food intake, drinking amount, urine amount, stool wet weight and assay of spontaneous activity (P<0.05). When observed under a light microscope, the colon tissues of rats in the model group showed mucosal edema, congestion, inflammatory cell infiltration and ulceration. The degree of colon injury and IL-6, IL-8 and TNF-α levels were significantly increased (P<0.05) as compared to those in the normal control group. The changes mentioned above were improved by Shenlin Baizhu Powder (P<0.05). The rat model of ulcerative colitis with syndrome of spleen deficiency and dampness stagnancy is successfully induced and has the characteristics of ulcerative colitis of humans both in pathological changes and in syndrome.	\N	\N
22888223	Membranous nanostructures, such as nanovesicles and nanotubules, are an important pool of biological membranes. Recent results indicate that they constitute cell-cell communication systems and that cancer development is influenced by these systems. Nanovesicles that are pinched off from cancer cells can move within the circulation and interact with distant cells. It has been suggested and indicated by experimental evidence that nanovesicles can induce metastases from the primary tumor in this way. Therefore, it is of importance to understand better the mechanisms of membrane budding and vesiculation. Here, a theoretical description is presented concerning consistently related lateral membrane composition, orientational ordering of membrane constituents, and a stable shape of nanovesicles and nanotubules. It is shown that the character of stable nanostructures reflects the composition of the membrane and the intrinsic shape of its constituents. An extension of the fluid mosaic model of biological membranes is suggested by taking into account curvature-mediated orientational ordering of the membrane constituents on strongly anisotropically curved regions. Based on experimental data for artificial membranes, a possible antimetastatic effect of plasma constituents via mediation of attractive interaction between membranous structures is suggested. This mediated attractive interaction hypothetically suppresses nanovesiculation by causing adhesion of buds to the mother membrane and preventing them from being pinched off from the membrane.	\N	\N
22892258	The emergency department (ED) is a common setting for evaluation of patients with urolithiasis based on acute symptoms and a propensity for recurrent disease. We sought to characterize practice patterns in the emergency treatment of stone disease, and to identify potential disparities in care based on non-medical factors. We performed a cross-sectional analysis of ED visits using the National Hospital Ambulatory Medical Care Survey from 2005-2009. Visits with a diagnosis of urolithiasis were identified. The associations between patient, provider and institutional characteristics were analyzed with regard to timing of clinical assessment, use of diagnostic imaging, and use of medical expulsive therapy (MET). The likelihood of a delay in clinical assessment ranged from 30.8%-37.9%. Neither patient nor provider characteristics were associated with a delay in assessment, although urban location (p = 0.004) was more likely, and proprietary ownership was less likely (p = 0.002) to be associated with delay. Factors associated with use of CT included ambulance arrival (p = 0.043), initial ED visit (p = 0.000), and Northeast region (p = 0.030). Patients seen by a resident/intern were more likely to receive MET (p = 0.028). Overall, 10.8% of patients were presenting for follow up treatment, and 7.1% had been seen in the same ED within the last 72 hours. Kidney stones are associated with a high rate of repeated presentations to the ED. Certain non-medical factors did impact details of management. Future efforts should focus on optimizing clinical pathways to improve the efficiency of acute care for kidney stone patients.	\N	\N
22910631	Like many intracellular microbes, the protozoan parasite Toxoplasma gondii injects effector proteins into cells it invades. One group of these effector proteins is injected from specialized organelles called the rhoptries, which have previously been described to discharge their contents only during successful invasion of a host cell. In this report, using several reporter systems, we show that in vitro the parasite injects rhoptry proteins into cells it does not productively invade and that the rhoptry effector proteins can manipulate the uninfected cell in a similar manner to infected cells. In addition, as one of the reporter systems uses a rhoptry:Cre recombinase fusion protein, we show that in Cre-reporter mice infected with an encysting Toxoplasma-Cre strain, uninfected-injected cells, which could be derived from aborted invasion or cell-intrinsic killing after invasion, are actually more common than infected-injected cells, especially in the mouse brain, where Toxoplasma encysts and persists. This phenomenon has important implications for how Toxoplasma globally affects its host and opens a new avenue for how other intracellular microbes may similarly manipulate the host environment at large.	\N	\N
22911240	In this study, the clinical outcome and prognostic factors of adult medulloblastoma patients receiving multimodal treatment were investigated. The clinical manifestations, treatment variables, and outcome of adult patients with medulloblastoma at our institution between 1983 and 2009 were retrospectively reviewed. A total of 20 adult patients were included (median age 22 years). Craniospinal irradiation (CSI) was given postoperatively. The craniospinal axis received a median of 30 Gy (range 23.4-39.6 Gy) in fractions of 1.6-2 Gy/day, and the tumor was boosted to a total median dose of 50 Gy (range 50-55.25 Gy). The 3-year disease-free survival (DFS) and overall survival (OS) rates for all patients were 45% and 50%, respectively. In univariate analysis, Karnofsky Performance Scale (KPS) > 70, neurologic symptoms duration > 30 days, lateral tumor location, standard risk patients, no hydrocephalus, radiotherapy (RT) treatment field (CSI + brain boost), and CSI dose ≥ 30 Gy were associated with better DFS. Standard-risk patients, RT treatment field (CSI + brain boost), and CSI dose ≥ 30 Gy were also significantly associated with better OS. The combined modality treatment results in a favorable outcome for adult medulloblastoma patients. Further investigation of the prognostic factors, radiation-related factors, and systemic chemotherapy is needed.	\N	\N
22917170	Diarrhea is a common clinical feature of inflammatory bowel diseases and may be accompanied by abdominal pain, urgency, and fecal incontinence. The pathophysiology of diarrhea in these diseases is complex, but defective absorption of salt and water by the inflamed bowel is the most important mechanism involved. In addition to inflammation secondary to the disease, diarrhea may arise from a variety of other conditions. It is important to differentiate the pathophysiologic mechanisms involved in the diarrhea in the individual patient to provide the appropriate therapy. This article reviews microscopic colitis, ulcerative colitis, and Crohn's disease, focusing on diarrhea.	\N	\N
22924030	Although many parameters were investigated about weaning and mortality in critical patients in intensive units, no studies have yet investigated predictors in prolonged mechanical ventilation (PMV) patients following successful weaning. A cohort of 142 consecutive PMV patients with successful weaning in our respiratory care center was enrolled in this study. Successful weaning is defined as a patient having smooth respiration for more than 5 days after weaning. The results showed as follows: twenty-seven patients (19%) had the reinstitution within 14 days, and 115 patients (81%) had the reinstitution beyond 14 days. Renal disease RIFLE-LE was associated with the reinstitution within 14 days (P = 0.006). One year mortality rates showed significant difference between the two groups (85.2% in the reinstitution within 14 days group versus 53.1% in the reinstitution beyond 14 days; P < 0.001). Kaplan-Meier analysis showed that age ≥70 years (P = 0.04), ESRD (P = 0.02), and the reinstitution within 14 days (P < 0.001) were associated with one-year mortality. Cox proportional hazards regression model showed that only the reinstitution within 14 days was the independent predictor for mortality (P < 0.001). In conclusion, the reinstitution within 14 days was a poor predictor for PMV patients after successful weaning.	\N	\N
22931913	Prediction of outcome for melanoma patients with surgically resected macroscopic nodal metastases is very imprecise. We performed a comprehensive clinico-pathologic assessment of fresh-frozen macroscopic nodal metastases and the preceding primary melanoma, somatic mutation profiling, and gene expression profiling to identify determinants of outcome in 79 melanoma patients. In addition to disease stage <II at initial presentation, the following clinical and pathologic factors were independent predictors of improved outcome (odds ratios for survival >4 years, 90% confidence interval): the presence of a nodular component in the primary melanoma (6.8, 0.6-76.0), and small cell size (11.1, 0.8-100.0) or low pigmentation (3.0, 0.8-100.0) in the nodal metastases. Absence of BRAF mutation (20.0, 1.0-1000.0) or NRAS mutation (16.7, 0.6-1000.0) were both favorable prognostic factors. A 46-gene expression signature with strong overrepresentation of immune response genes was predictive of better survival (10.9, 0.4-325.6); in the full cohort, median survival was >100 months in those with the signature, but 10 months in those without. This relationship was validated in two previously published independent stage III melanoma data sets. We conclude that the presence of BRAF mutation, NRAS mutation, and the absence of an immune-related expressed gene profile predict poor outcome in melanoma patients with macroscopic stage III disease.	\N	\N
22933250	Renal xenobiotic transporters are important determinants of urinary secretion and reabsorption of chemicals. In addition to glomerular filtration, these processes are key to the overall renal clearance of a diverse array of drugs and toxins. Alterations in kidney transporter levels and function can influence the efficacy and toxicity of chemicals. Studies in experimental animals have revealed distinct patterns of renal transporter expression in response to sex hormones, pregnancy, and growth hormone. Likewise, a number of disease states including diabetes, obesity, and cholestasis alter the expression of kidney transporters. The goal of this review is to provide an overview of the major xenobiotic transporters expressed in the kidneys and an understanding of metabolic conditions and hormonal factors that regulate their expression and function.	\N	\N
22933945	The aim of the study was to evaluate the clinical efficacy of superselective intra-arterial targeted neo-adjuvant chemotherapy in the treatment of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) breast cancer. PATIENTS AND METHODS.: A total of 47 triple-negative breast cancer patients (29 at stage II, 13 at stage III and 5 at stage IV) were randomly assigned to two groups: targeted chemotherapy group (n=24) and control group (n=23). Patients in the targeted chemotherapy group received preoperative superselective intra-arterial chemotherapy with CEF regimen (C: cyclophosphamide [600 mg/m(2)]; E: epirubicin [90 mg/m(2)]; F: 5-fluorouracil [600 mg/m(2)]), and those in the control group received routine neoadjuvant chemotherapy with CEF. The duration of the treatment, changes in lesions and the prognosis were determined. The average course of the treatment was 15 days in the targeted chemotherapy group which was significantly shorter than that in the control group (31 days) (P<0.01). The remission rate of lesions was 91.6% in the targeted chemotherapy group and 60.9% in the control group, respectively. Among these patients, 9 died within two years, including 2 (both at IV stage) in the targeted chemotherapy group and 7 (2 at stage II, 4 at stage III and 1 at stage IV) in the control group. As an neoadjuvant therapy, the superselective intra-arterial chemotherapy is effective for triple-negative breast cancer, with advantages of the short treatment course and favourable remission rates as well as prognoses.	\N	\N
22934539	The existing literature suggests that theories and models can serve as valuable frameworks for the design and evaluation of health interventions. However, evidence on the use of theories and models in social marketing interventions is sparse. The purpose of this systematic review is to identify to what extent papers about social marketing health interventions report using theory, which theories are most commonly used, and how theory was used. A systematic search was conducted for articles that reported social marketing interventions for the prevention or management of cancer, diabetes, heart disease, HIV, STDs, and tobacco use, and behaviors related to reproductive health, physical activity, nutrition, and smoking cessation. Articles were published in English, after 1990, reported an evaluation, and met the 6 social marketing benchmarks criteria (behavior change, consumer research, segmentation and targeting, exchange, competition and marketing mix). Twenty-four articles, describing 17 interventions, met the inclusion criteria. Of these 17 interventions, 8 reported using theory and 7 stated how it was used. The transtheoretical model/stages of change was used more often than other theories. Findings highlight an ongoing lack of use or underreporting of the use of theory in social marketing campaigns and reinforce the call to action for applying and reporting theory to guide and evaluate interventions.	\N	\N
22935019	Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies.	\N	\N
22940074	A 33-year-old woman with Wernicke's encephalopathy (WE) due to poor oral intake after allogeneic stem cell transplantation for acute myeloid leukemia showed a sequential development of bilateral gaze-evoked nystagmus (GEN), rightward gaze palsy, and upbeat nystagmus. Initial MRIs obtained when she had GEN only showed a lesion involving the medullary tegmentum, and follow-up MRIs revealed additional lesions in the pontine and midbrain tegmentum along with development of rightward gaze palsy, and finally bilateral medial thalamus lesions in association with upbeat nystagmus. The evolution of abnormal ocular motor findings and serial MRI changes in our patient with WE provide imaging evidence on relative vulnerability of the neural structures, and on the progression of lesions and ocular motor findings in thiamine deficiency.	\N	\N
22956992	Cerebral palsy (CP) is an upper motor neuron disease that results in a spectrum of movement disorders. Secondary to the neurological lesion, muscles from patients with CP are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in CP is a response to aberrant complex neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response in CP using transcriptional profiling correlated with functional measures to broadly investigate muscle adaptations leading to mechanical deficits.Biopsies were obtained from both the gracilis and semitendinosus muscles from a cohort of patients with CP (n = 10) and typically developing patients (n = 10) undergoing surgery. Biopsies were obtained to define the unique expression profile of the contractures and passive mechanical testing was conducted to determine stiffness values in previously published work. Affymetrix HG-U133A 2.0 chips (n = 40) generated expression data, which was validated for selected transcripts using quantitative real-time PCR. Chips were clustered based on their expression and those from patients with CP clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n = 1,398). Significantly altered genes were analyzed for over-representation among gene ontologies and muscle specific networks.The majority of altered transcripts were related to increased extracellular matrix expression in CP and a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and development of novel therapies.	\N	\N
22958194	Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in haemophilia A. It has been suggested that differences in the distribution of FVIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Data from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and inhibitor risk among individuals of genetically determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and human leucocyte antigen (HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified (N = 49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N = 223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Haplotype 3 was not an independent predictor of inhibitor risk. Furthermore, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual.	\N	\N
22964476	Tocopherol, a member of the vitamin E family, consists of four forms designated as α, β, γ, and δ. Several large cancer prevention studies with α-tocopherol have reported no beneficial results, but recent laboratory studies have suggested that δ- and γ-tocopherol may be more effective. In two different animal models of breast cancer, the chemopreventive activities of individual tocopherols were assessed using diets containing 0.3% of tocopherol (α-, δ-, or γ-) or 0.3% of a γ-tocopherol rich mixture (γ-TmT). Although administration of tocopherols did not prevent human epidermal growth factor receptor 2 (HER2/neu)-driven tumorigenesis, δ- and γ-tocopherols inhibited hormone-dependent mammary tumorigenesis in N-methyl-N-nitrosourea (NMU)-treated female Sprague-Dawley rats. NMU-treated rats showed an average tumor burden of 10.6 ± 0.8 g in the control group at 11 weeks, whereas dietary administration of δ- and γ-tocopherols significantly decreased tumor burden to 7.2 ± 0.8 g (P < 0.01) and 7.1 ± 0.7 g (P < 0.01), respectively. Tumor multiplicity was also reduced in δ- and γ-tocopherol treatment groups by 42% (P < 0.001) and 32% (P < 0.01), respectively. In contrast, α-tocopherol did not decrease tumor burden or multiplicity. In mammary tumors, the protein levels of proapoptotic markers (BAX, cleaved caspase-9, cleaved caspase-3, cleaved PARP) were increased, whereas antiapoptotic markers (Bcl-2, XIAP) were inhibited by δ-tocopherol, γ-tocopherol, and γ-TmT. Furthermore, markers of cell proliferation (PCNA, PKCα), survival (PPAR-γ, PTEN, phospho-Akt), and cell cycle (p53, p21) were affected by δ- and γ-tocopherols. Both δ- and γ-tocopherols, but not α-tocopherol, seem to be promising agents for the prevention of hormone-dependent breast cancer.	\N	\N
22980951	The role of non-complement activating antibodies (ncAbs) to mismatched donor human leukocyte antigen (HLA) in the pathogenesis of chronic lung rejection is not known. We used a murine model of obliterative airway disease (OAD) induced by Abs to major histocompatibility major histocompatibility complex (MHC) class I and serum from donor-specific Abs developed in human lung transplant (LTx) recipients to test the role of ncAbs in the development of OAD and bronchiolitis obliterans syndrome (BOS). Anti-MHC ncAbs were administered intrabronchially in B.10 mice or in C3 knockout (C3KO) mice. Lungs were analyzed by histopathology. Lymphocytes secreting interleukin (IL)-17, interferon-γ, or IL-10 to collagen V and K-α1 tubulin (Kα1T) were enumerated by enzyme-linked immunospot assay. Serum antibodies to collagen V and Kα1T were determined by enzyme-linked immunosorbent assay. Cytokine and growth factor expression in lungs was determined by real-time polymerase chain reaction. Donor-specific Abs from patients with BOS and control BOS-negative LTx recipients were analyzed by C1q assay. Administration of ncAbs in B.10 mice or C3KO resulted in OAD lesions. There were significant increases in IL-17- and interferon-γ-secreting cells to collagen V and Kα1T, along with serum Abs to these antigens. There was also augmented expression of monocyte chemotactic protein-1, IL-6, IL-1β, vascular endothelial growth factor, transforming growth factor-β, and fibroblastic growth factor in mice administered ncAbs by Day 3. Among 5 LTx recipients with BOS, only 1 had C1q binding donor-specific Abs. Complement activation by Abs to MHC class I is not required for development of OAD and human BOS. Therefore, anti-MHC binding to epithelial and endothelial cells can directly activate pro-fibrotic and pro-inflammatory cascades leading to immune response to self-antigens and chronic rejection.	\N	\N
22981307	The "Cohorte Enfant Scanner", a study designed to investigate the risk of radiation-induced cancer after childhood exposure to CT (computed tomography) examinations, used clinical information contained in the "programme de médicalisation des systèmes d'information" (PMSI) database, the French hospital activities national program based upon diagnosis related groups (DRG). However, the quality and adequacy of the data for the specific needs of the study should be verified. The aim of our work was to estimate the percentage of the cohort's children identified in the PMSI database and to develop an algorithm to individualize the children with a cancer or a disease at risk of cancer from medical diagnoses provided by the DRGs database. Of the 1519 children from the "Cohorte Enfant Scanner", who had had a CT scan in the radiology department of a university hospital in 2002, a cross linkage was performed with the DRGs database. All hospitalizations over the period 2002-2009 were taken into account. An algorithm was constructed for the items "cancer" and "disease at risk for cancer" on a sample of 150 children. The algorithm was then tested on the entire population. Overall, 74% of our population was identified in the DRGs database. The algorithm individualized cancer diagnoses with 91% sensitivity (95% confidence interval [95%CI]: 86%; 97%) and 98% specificity (95%CI: 97%; 99%) and 86% positive predictive value (95%CI: 80%; 93%). For the diagnosis of disease at risk for cancer, the sensitivity, specificity and positive predictive value were respectively 91% (95%CI: 84%; 98%), 94% (95%CI: 92%; 95%) and 52% (95%CI: 43%; 61%). The DRG database identified with excellent sensitivity and specificity children with diagnoses of cancer or disease at risk for cancer. Hence, potential confounding factors related to the disease of the child can be taken into account for analyses performed with the cohort.	\N	\N
22990715	Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study. Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models. Among DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA(1c) and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline (~0.7% per month). SEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.	\N	\N
23005903	A tubo-ovarian abscess (TOA) is a common complication of pelvic inflammatory disease in premenopausal women; however, in virginal females, TOAs are an exceedingly rare occurrence. Within this rare subset of patients, there is almost always an underlying condition, such as vaginal voiding, or a concomitant disease process. A virginal adolescent female with no prior medical history presented with a large pelvic mass which proved to be a TOA. An exploratory laparotomy was eventually required to establish the diagnosis. Open drainage and antibiotic therapy successfully treated the patient. With only the organism, Streptococcus viridians, isolated in her cultures, an etiology of direct ascension from the lower genitourinary tract is implicated. We believe this to be the youngest case of a TOA occurring in a virginal adolescent female without a predisposing condition. A TOA should be considered in the differential diagnosis of pelvic masses in previously healthy pediatric patients regardless of their sexual activity.	\N	\N
23008381	Japanese encephalitis (JE) is an epidemic encephalitis characterised by altered sensorium, convulsions, headache, brainstem signs with pyramidal and extrapyramidal features. Immune-mediated manifestation as acute transverse myelitis (ATM) has not been previously reported in JE. We describe a 40-year-old man who presented with an acute onset quadriparesis with urinary retention, which was preceded by fever and headache 3 weeks prior. He had elevated IgM titres against JE virus in serum and cerebrospinal fluid. MRI of cervico-thoracic spine demonstrated signal intensity alterations extending from C1 to D10 spinal segments. The patient was treated with intravenous methyl prednisolone for 5 days. He regained normal power at 6 months follow-up and repeat MRI study demonstrated complete resolution of the lesion. We conclude that in a case of JE, one should be vigilant for early diagnosis of possible complication as ATM, in which an early institution of immunomodulator therapy prevents adverse consequences.	\N	\N
23018067	OBJECTIVES. To evaluate attainment of low-density lipoprotein cholesterol goals among hypercholesterolaemic patients undergoing lipid-lowering drug treatment in Hong Kong and to identify potential determinants of treatment outcomes. DESIGN. Cross-sectional observational study. SETTING. A single site in Hong Kong, as part of the CEPHEUS Pan-Asian survey. PATIENTS. Subjects with hypercholesterolaemia aged 18 years or above, who had been on lipid-lowering drug treatment for at least 3 months with no dose adjustment for at least 6 weeks. RESULTS. A total of 561 such patients (mean age, 65.3; standard deviation, 9.7 years) were evaluated. Most had major cardiovascular risk factors; 534 (95.2%) of 561 patients had coronary heart disease and 534 (95.4%) of 560 patients had low-density lipoprotein cholesterol goals set at lower than 70 mg/dL. In all, 465 (82.9%) patients attained their respective low-density lipoprotein cholesterol goals. Among 75 patients who had coronary heart disease or equivalent risk, and multiple risk factors with a 10-year coronary heart disease risk of over 20%, 62 (82.7%) attained their respective low-density lipoprotein cholesterol goals. Significant predictors of low-density lipoprotein cholesterol goal attainment included the patient's baseline lipid profile (total cholesterol and low-density lipoprotein cholesterol levels), blood pressure, and drugs (statin/non-statin) used for treatment. CONCLUSIONS. Hypercholesterolaemic patients undergoing lipid-lowering drug treatment in the present Hong Kong study were able to achieve a very high attainment rate for the low-density lipoprotein cholesterol goal, despite the fact that most of them had major cardiovascular risk factors.	\N	\N
23020826	A patient with central nervous system involvement of Behçet's disease was refractory to conventional immunosuppressive therapy and showed secondary failure of the anti-TNF agent infliximab. This presented as a progressive weakness of the legs and reduction in walking distance. The cerebrospinal fluid showed signs of inflammation including a vastly elevated IL-6 concentration. Given this result, the anti-IL-6 receptor antibody tocilizumab was administered and a good improvement of inflammatory parameters and a satisfactory increase of the walking distance were achieved.	\N	\N
23028288	The prioritization of candidate disease-causing genes is a fundamental challenge in the post-genomic era. Current state of the art methods exploit a protein-protein interaction (PPI) network for this task. They are based on the observation that genes causing phenotypically-similar diseases tend to lie close to one another in a PPI network. However, to date, these methods have used a static picture of human PPIs, while diseases impact specific tissues in which the PPI networks may be dramatically different. Here, for the first time, we perform a large-scale assessment of the contribution of tissue-specific information to gene prioritization. By integrating tissue-specific gene expression data with PPI information, we construct tissue-specific PPI networks for 60 tissues and investigate their prioritization power. We find that tissue-specific PPI networks considerably improve the prioritization results compared to those obtained using a generic PPI network. Furthermore, they allow predicting novel disease-tissue associations, pointing to sub-clinical tissue effects that may escape early detection.	\N	\N
23028439	Several independent studies have supported the association of DYX1C1 with dyslexia, but its role in general reading development remains unclear. Here, we investigated the contribution of this gene to reading, with a focus on orthographic skills, in a sample of 284 unrelated Chinese children aged 5 to 11 years who were participating in the Chinese Longitudinal Study of Reading Development. We tested this association using a quantitative approach for Chinese character reading, Chinese character dictation, orthographic judgment, and visual skills. Significant or marginally significant associations were observed at the marker rs11629841 with children's orthographic judgments at ages 7 and 8 years (all P values<0.020). Significant associations with Chinese character dictation (all P values<0.013) were also observed for this single-nucleotide polymorphism (SNP) at ages 9, 10, and 11 years. Further analyses revealed that the association with orthographic skills was specific to the processing of specific components of characters (P values<0.046). No association was found at either SNP of rs3743205 or rs57809907. Our findings suggest that DYX1C1 influences reading development in the general Chinese population and supports a universal effect of this gene.	\N	\N
23049998	Although "uremic fetor" has long been felt to be diagnostic of renal failure, the compounds exhaled in uremia remain largely unknown so far. The present work investigates whether breath analysis by ion mobility spectrometry can be used for the identification of volatile organic compounds retained in uremia. Breath analysis was performed in 28 adults with an eGFR ≥ 60 ml/min per 1.73 m(2), 26 adults with chronic renal failure corresponding to an eGFR of 10-59 ml/min per 1.73 m(2), and 28 adults with end-stage renal disease (ESRD) before and after a hemodialysis session. Breath analysis was performed by ion mobility spectrometryafter gas-chromatographic preseparation. Identification of the compounds of interest was performed by thermal desorption gas chromatography/mass spectrometry. Breath analyses revealed significant differences in the spectra of patients with and without renal failure. Thirteen compounds were chosen for further evaluation. Some compounds including hydroxyacetone, 3-hydroxy-2-butanone and ammonia accumulated with decreasing renal function and were eliminated by dialysis. The concentrations of these compounds allowed a significant differentiation between healthy, chronic renal failure with an eGFR of 10-59 ml/min, and ESRD (p<0.05 each). Other compounds including 4-heptanal, 4-heptanone, and 2-heptanone preferentially or exclusively occurred in patients undergoing hemodialysis. Impairment of renal function induces a characteristic fingerprint of volatile compounds in the breath. The technique of ion mobility spectrometry can be used for the identification of lipophilic uremic retention molecules.	\N	\N
23050521	Data from the 2011 Survey of Pathways to Diagnosis and Services The median age when school-aged children with special health care needs (CSHCN) and autism spectrum disorder (ASD) were first identified as having ASD was 5 years. School-aged CSHCN identified as having ASD at a younger age (under age 5 years) were identified most often by generalists and psychologists, while those identified later (aged 5 years and over) were identified primarily by psychologists and psychiatrists. Nine out of 10 school-aged CSHCN with ASD use one or more services to meet their developmental needs. Social skills training and speech or language therapy are the most common, each used by almost three-fifths of these children. More than one-half of school-aged CSHCN with ASD use psychotropic medication.	\N	\N
23058984	Mast cells (MCs) are well known for their detrimental effects in the context of allergic disorders. Strategies that limit MC function can therefore have a therapeutic value. Previous studies have shown that siramesine, a sigma-2 receptor agonist originally developed as an anti-depressant, can induce cell death in transformed cells through a mechanism involving lysosomal destabilization. Since MCs are remarkably rich in lysosome-like secretory granules we reasoned that MCs might be sensitive to siramesine. Here we show that murine and human MCs are highly sensitive to siramesine. Cell death was accompanied by secretory granule permeabilization, as shown by reduced acridine orange staining and leakage of granule proteases into the cytosol. Wild type siramesine-treated MCs underwent cell death with typical signs of apoptosis but MCs lacking serglycin, a proteoglycan crucial for promoting the storage of proteases within MC secretory granules, died predominantly by necrosis. A dissection of the underlying mechanism suggested that the necrotic phenotype of serglycin(-/-) cells was linked to defective Poly(ADP-ribose) polymerase-1 degradation. In vivo, siramesine treatment of mice caused a depletion of the MC populations of the peritoneum and skin. The present study shows for the first time that MCs are highly sensitive to apoptosis induced by siramesine and introduces the possibility of using siramesine as a therapeutic agent for treatment of MC-dependent disease.	\N	\N
23061325	A paradox exists in health disparities research where African-American cigarette smokers consume fewer cigarettes per day, yet experience higher rates of tobacco-related disease compared to White American smokers. In this study we conducted focus group interviews among alternative high school youth (N = 78; age 18-19 years old) in an urban area in Southwest Texas to investigate if African-American youth smoke cigarettes differently than their White-American and Hispanic-American counterparts. The majority of African-American participants reported inhaling deeper and smoking their cigarettes "to the filter" because of their concern over wasting any part of an expensive cigarette. White and Hispanic respondents most often put out their cigarettes closer to the middle, and did not express concern about wasting cigarettes. The implication from this qualitative study is that because African Americans smoke differently they are exposed to a higher level of harmful particulate per cigarette. Further research on smoking topography is warranted.	\N	\N
23063289	A meta-analysis of publicly available gene expression changes in A549 cells upon treatment with anti-cancer drugs is reported. To reduce false positives, both fold-change and significance level cutoffs were used. Simulated datasets and permutation analysis were used to guide choice of ratio cutoff. Of the genes identified, FDXR is the only gene differentially expressed in six of the seven drug treatments. Though FDXR has been reported to be differentially expressed upon treatment with 5-fluorouracil and its expression correlated to long term disease survival, to our knowledge this is a first study implicating a wide effect of anti-cancer drug treatment on FDXR expression. The other genes identified which are differentially expressed in four out of the seven drug treatments are CDKN1A and PARVB which are upregulated and MYC, HBP1, LDLR, SIM2, ALX1 and GPHN which are downregulated.	\N	\N
23063663	Liver cancer is one of most deadly cancers worldwide. Hepatocellular carcinoma (HCC) represents a major histological subtype of liver cancers. As cancer is a genetic disease, genetic lesions play a major role in HCC tumorigenesis and progression. Although significant progress has been made to uncover genetic alterations in HCCs, our understanding of genetics involved in the initiation and progression of HCC is far from complete. Next generation sequencing (NGS) has provided a new paradigm in biomedical research to delineate the genetic basis of human diseases. While identification of cancer somatic mutations has been serendipitous, genome sequencing has provided an unbiased approach to systematically catalog somatic mutations and elucidate the mechanisms of tumourigenesis. A number of recently published NGS studies on HCCs have not only confirmed previously known mutations in CTNNB1 and TP53 in HCC, but also identified novel genetic alterations in HCC including mutations in genes involved in epigenetic regulation. WNT, cell cycle and chromatin remodeling pathways have emerged as key oncogenic drivers in HCCs. The frequently altered genes and pathways in HCC reflect classical cancer hallmarks. These findings have started to depict a genetic landscape in HCC and will facilitate development of novel therapeutics for the treatment of this deadly disease.	\N	\N
23063979	Vascular calcification is a hallmark of cardiovascular disease. Interleukin-24 (IL-24) has been known to suppress tumor progression in a variety of human cancers. However, the role of IL-24 in the pathophysiology of diseases other than cancer is unclear. We investigated the role of IL-24 in vascular calcification. IL-24 was applied to a β-glycerophosphate (β-GP)-induced rat vascular smooth muscle cell (VSMC) calcification model. In this study, IL-24 significantly inhibited β-GP-induced VSMC calcification, as determined by von Kossa staining and calcium content. The inhibitory effect of IL-24 on VSMC calcification was due to the suppression of β-GP-induced apoptosis and expression of calcification and osteoblastic markers. In addition, IL-24 abrogated β-GP-induced activation of the Wnt/β-catenin pathway, which plays a key role in the pathogenesis of vascular calcification. The specificity of IL-24 for the inhibition of VSMC calcification was confirmed by using a neutralizing antibody to IL-24. Our results suggest that IL-24 inhibits β-GP-induced VSMC calcification by inhibiting apoptosis, the expression of calcification and osteoblastic markers, and the Wnt/ β-catenin pathway. Our study may provide a novel mechanism of action of IL-24 in cardiovascular disease and indicates that IL-24 is a potential therapeutic agent in VSMC calcification.	\N	\N
23070622	Multivisceral transplantation includes the simultaneous transplantation of multiple abdominal viscera including the stomach, duodenum, pancreas, and small intestine, with (multivisceral transplant, MVT) or without the liver (modified MVT, MMVT). This study reviews the changing indications and outcomes for this procedure over a 7-year period at a university medical center. This study is a retrospective case review of MVTs performed between 2004 and 2010 at a single center. All cases were either MVT or MMVT and included a simultaneous kidney transplant, if indicated. Graft failure was defined as loss of the graft or complete loss of function. Graft function was monitored by clinical function, laboratory values, and serial endoscopy with biopsy. During the study period, 95 patients received 100 transplants including 84 MVT and 16 MMVT. There were 19 patients who received a simultaneous kidney graft. There were 24 pediatric and 76 adult recipients (range 7 months to 66 years). Indications included intestinal failure alone, intestinal failure with cirrhosis, complete portal mesenteric thrombosis, slow-growing central abdominal tumors, intestinal pseudoobstruction, and frozen abdomen. All patients received antibody-based induction immunosuppression with calcineurin inhibitor-based maintenance immunosuppression. At a median mortality adjusted follow-up of 25 months, 1- and 3-year patient survival is 72 % and 57 %. There was a learning curve with this complex procedure resulting in a 48 % patient survival during the period from 2004 to 2007, followed by a 70 % patient survival during the period from 2008 to 2010. Post-transplant complications included rejection (50 % MMVT and 17 % MVT), infection (>90 % first year), graft versus host disease (13 %), and post-transplant lymphoproliferative disorder (5 %). Indications for MVT and MMVT have broadened to include patients with terminal conditions not amenable to other medical therapies such as slow-growing tumors of the mesenteric root, complete portomesenteric thrombosis, and abdominal catastrophes/frozen abdomen. Outcomes have improved over time with many patients returning to full functional status and enjoying long-term survival.	\N	\N
23079185	Elevated serum levels of the proinflammatory cytokine tumor necrosis factor alpha (TNFα) correlate with an increased risk for atherothrombotic events and TNFα is known to induce prothrombotic molecules in endothelial cells. Based on the preexisting evidence for the impact of TNFα in the pathogenesis of autoimmune disorders and their known association with an acquired hypercoagulability, we investigated the effects of TNFα and the role of the TNF receptor subtypes TNFR1 and TNFR2 for arteriolar thrombosis in vivo. Arteriolar thrombosis and platelet-rolling in vivo were investigated in wildtype, TNFR1-/-, TNFR2-/- and TNFR1-/R2-/- C57BL/6 mice using intravital microscopy in the dorsal skinfold chamber microcirculation model. In vitro, expression of prothrombotic molecules was assessed in human endothelial cells by real-time PCR and flow cytometry. In wildtype mice, stimulation with TNFα significantly accelerated thrombotic vessel occlusion in vivo upon ferric chloride injury. Arteriolar thrombosis was much more pronounced in TNFR1-/- animals, where TNFα additionally led to increased platelet-endothelium-interaction. TNFα dependent prothrombotic effects were not observed in TNFR2-/- and TNFR1-/R2- mice. In vitro, stimulation of human platelet rich plasma with TNFα did not influence aggregation properties. In human endothelial cells, TNFα induced superoxide production, p-selectin, tissue factor and PAI-1, and suppressed thrombomodulin, resulting in an accelerated endothelial dependent blood clotting in vitro. Additionally, TNFα caused the release of soluble mediators by endothelial cells which induced prothrombotic and suppressed anticoagulant genes comparable to direct TNFα effects. TNFα accelerates thrombus formation in an in vivo model of arteriolar thrombosis. Its prothrombotic effects in vivo require TNFR2 and are partly compensated by TNFR1. In vitro studies indicate endothelial mechanisms to be responsible for prothrombotic TNFα effects. Our results support a more selective therapeutic approach in anticytokine therapy favouring TNFR2 specific antagonists.	\N	\N
23083013	Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease affecting > 10% of children and 1-3% of adults, and can cause significant morbidity. The incidence of AD seems to be increasing. Omalizumab, a monoclonal antibody, has recently been suggested as a potential new systemic treatment for patients with recalcitrant AD with elevated IgE levels, based on its efficacy in treating asthma and allergic rhinitis. We report a study of 10 patients with AD (aged 19-35 years) who received anti-IgE treatment for persistent asthma. All patients, regardless of IgE value, were treated with a fixed schedule of eight cycles of omalizumab 300 mg administered subcutaneously at intervals of 2 weeks. Eczema symptoms were scored at baseline and after 2, 4 and 6 months of treatment. There was a steady improvement in the objective SCORAD (SCORing Atopic Dermatitis), with significantly lower scores observed at the 6-month evaluation. At 2 months after the end of treatment, two patients had a very good result (SCORAD reduction of > 50%), five patients had a satisfactory result (reduction of 25-50%), and three patients had no clinically relevant result (reduction of 25-50%). No patient had worsening of the AD (increase of > 25% in SCORAD), and once a clinical improvement occurred, none of the patients experienced worsening of their eczema symptoms while on omalizumab. With the caveats of the financial expense and unknown long-term risks of malignancy associated with omalizumab, this drug should be considered for treatment-resistant patients with AD, particularly patients with high IgE level whose symptoms are not controlled by routine therapies. Omalizumab has proven useful in treating asthma, but it may also prove valuable for other conditions, such as allergic rhinitis, food allergies, chronic urticaria, and AD, as shown by the present study.	\N	\N
23087412	We recently proposed two novel criteria to assess the usefulness of risk prediction models for public health applications. The proportion of cases followed, PCF(p), is the proportion of individuals who will develop disease who are included in the proportion p of individuals in the population at highest risk. The proportion needed to follow-up, PNF(q), is the proportion of the general population at highest risk that one needs to follow in order that a proportion q of those destined to become cases will be followed (Pfeiffer, R.M. and Gail, M.H., 2011. Two criteria for evaluating risk prediction models. Biometrics 67, 1057-1065). Here, we extend these criteria in two ways. First, we introduce two new criteria by integrating PCF and PNF over a range of values of q or p to obtain iPCF, the integrated PCF, and iPNF, the integrated PNF. A key assumption in the previous work was that the risk model is well calibrated. This assumption also underlies novel estimates of iPCF and iPNF based on observed risks in a population alone. The second extension is to propose and study estimates of PCF, PNF, iPCF, and iPNF that are consistent even if the risk models are not well calibrated. These new estimates are obtained from case-control data when the outcome prevalence in the population is known, and from cohort data, with baseline covariates and observed health outcomes. We study the efficiency of the various estimates and propose and compare tests for comparing two risk models, both of which were evaluated in the same validation data.	\N	\N
23089926	Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is associated with obesity, dyslipidemias, hypertension (HTN) and type 2 diabetes mellitus (T2DM). LPL gene polymorphisms can be related with the development of cardiovascular risk factors. The present study was conducted to analyze the relationship of the HindIII and S447X polymorphisms in LPL gene with cardiovascular risk factors in Mexican families. The study population comprised ninety members of 30 Mexican families, in which an index case had obesity, were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical parameters. Screening for both polymorphisms was made by PCR-RFLPs. In the parents, both polymorphisms were in Hardy-Weinberg's equilibrium. We found that the genotype T/T of HindIII was associated with diastolic blood pressure ≥ 85 mmHg (OR=1.1; p=0.011), whereas the genotype C/C of S447X was associated with systolic blood pressure ≥ 130 mmHg (OR=1.2; p<0.001), diastolic blood pressure ≥ 85 mmHg (OR = 1.3; p< 0.001), T2DM (OR=1.3; p< 0.001) and with increase of total cholesterol (β =23.6 mg/mL; p=0.03). These data suggest that the HindIII and S447X LPL gene polymorphisms can confer susceptibility for the development of hypertension and T2DM in Mexican families.	\N	\N
23092312	Many coronary heart disease (CHD) events occur in individuals classified as intermediate risk by commonly used assessment tools. Over half the individuals presenting with a severe cardiac event, such as myocardial infarction (MI), have at most one risk factor as included in the widely used Framingham risk assessment. Individuals classified as intermediate risk, who are actually at high risk, may not receive guideline recommended treatments. A clinically useful method for accurately predicting 5-year CHD risk among intermediate risk patients remains an unmet medical need. This study sought to develop a CHD Risk Assessment (CHDRA) model that improves 5-year risk stratification among intermediate risk individuals. Assay panels for biomarkers associated with atherosclerosis biology (inflammation, angiogenesis, apoptosis, chemotaxis, etc.) were optimized for measuring baseline serum samples from 1084 initially CHD-free Marshfield Clinic Personalized Medicine Research Project (PMRP) individuals. A multivariable Cox regression model was fit using the most powerful risk predictors within the clinical and protein variables identified by repeated cross-validation. The resulting CHDRA algorithm was validated in a Multiple-Ethnic Study of Atherosclerosis (MESA) case-cohort sample. A CHDRA algorithm of age, sex, diabetes, and family history of MI, combined with serum levels of seven biomarkers (CTACK, Eotaxin, Fas Ligand, HGF, IL-16, MCP-3, and sFas) yielded a clinical net reclassification index of 42.7% (p < 0.001) for MESA patients with a recalibrated Framingham 5-year intermediate risk level. Across all patients, the model predicted acute coronary events (hazard ratio = 2.17, p < 0.001), and remained an independent predictor after Framingham risk factor adjustments. These include the slightly different event definition with the MESA samples and inability to include PMRP fatal CHD events. A novel risk score of serum protein levels plus clinical risk factors, developed and validated in independent cohorts, demonstrated clinical utility for assessing the true risk of CHD events in intermediate risk patients. Improved accuracy in cardiovascular risk classification could lead to improved preventive care and fewer deaths.	\N	\N
23097963	This work, partial pressure of the respiratory gases in the capillary blood (pH, PaO2, PaCO2) was studied, following the protective action of the beta2-drenergic stimulator-Hexoprenaline and alpha2-adrenergic blocker-Tolazoline in the bronchoconstriction caused by a beta-blocker-Propranolol. in patients with increased bronchial reactibility. pH, oxygen partial pressure (PaO2), dioxide carbon partial pressure (PaCO2) in the arterial blood, with the assistance of the analyzer IL, following some minutes of sample taking were defined in all patients. As a standard to verify the accuracy of the measurement, ampoule solutions of pH, PaO2 and PaCO2 were utilized (Acidobasel, Berlin). Following the inhalation of the beta-blocker-Propranolol (20 mg/ml-aerosol), there was an evident decrease (p < 0.05) of pO2 and a non-significant increase (p > 0.1) of pCO2. Beta2-adrenergcic stimulator-Hexoprenaline (2 inh x 0.2 mg), shows an protective effect in the decrease of pO2 (p < 0.05) following the bronchoconstriction being provoked by Propranolol. Alpha2-adrenergic blocker-Tolazoline (20 mg/ml-aerosol), has not shown a protective action in the bronchoconstriction caused with propranolol, therefore significant decrease (p < 0.05) of pO2 and a non-significant increase (p > 0.1) of pCO2 appeared. This shows that stimulation of beta2-adrenergic receptor has protective action in changes of the respiratory gases. Meantime, blocker of the alpha2-adrenergic receptor (Tolazoline) has not shown a protective action in changes of the respiratory gases.	\N	\N
23101267	CD200 and its receptor were recognized as having the multiple immunoregulatory functions. Their immunoregulatory, suppressive, and tolerogenic potentials could be very effectively exploited in the treatment of many diseases, e.g. Alzheimer disease, rheumatoid arthritis, and allergy to name only some. Many research projects are aimed to develop clinically valuable methods being based on the structure and function of these paired molecules. In this review, we would like to introduce CD200/CD200R functions in a clinical context.	\N	\N
23114434	Surveillance of nosocomial infections is meanwhile a cornerstone of infection prevention activities in hospitals. The objective of this article is to compare healthcare-associated infection rates in intensive care patients, neonatal intensive care patients and operated patients (ICU-KISS, OP-KISS, NEO-KISS) of the German nosocomial infection surveillance system (KISS) with the corresponding data of the US American National Healthcare Safety Network (NHSN) and the European Centre for Disease Prevention and Control (ECDC). In general, the methodological differences among the three surveillance systems are minor but there are some exceptions. Therefore, differences between countries have to be interpreted very carefully as they may be due to differences in diagnostics, patient mix, types of interventions, length of stay, selection of participating hospitals, post-discharge surveillance activities and interpretation of case definitions. Organizational aspects, such as mandatory participation with public disclosure on infection rates may also have an impact.	\N	\N
23117745	Arterial calcification is the result of the same highly organized processes as seen in bone, which rely on a delicate balance between osteoblasts and osteoclasts. Although previously understood as passive precipitation, evidence has accumulated to suggest that arterial calcification is the result of organized, regulated processes bearing many similarities to osteogenesis in bone, including the presence of subpopulations of arterial wall cells that retain osteoblastic lineage potential. These cells have the potential to form mineralized nodules and express osteoblast markers, including bone morphogenetic protein-2, osteocalcin, osteopontin, and alkaline phosphatase. By contrast, osteoclast-like cells mediate the catabolic process of mineral resorption. Recent data shows that cells positive for tartrate-resistant acid phosphatase, a major marker for osteoclasts, have been histologically identified in atherosclerotic lesions and are referred to as osteoclast-like cells. Evidence has accumulated to suggest that initial arterial calcification through passive precipitation of calcium phosphate initiates balanced mineralization regulated by osteoclast-like and osteoblast-like cells. Subsequently, various pathogenic conditions may trigger an imbalance between osteoblastogenesis and osteoclastogenesis, leading to either calcification in stenotic/occlusive disease or destruction of the extracellular matrix in aneurysmal disease. Further elucidation of these newly emerging concepts could lead to a novel therapeutic approach to arterial stenotic/occlusive disease and/or abdominal aortic aneurysm.	\N	\N
23126056	Amyloidosis is a clinical entity that results from deposition of an extracellular protein material that causes disruption in normal architecture and impairs function of multiple organs and tissues. Secondary amyloidosis (AA) is a rare but serious complication that appears in the context of cancer, chronic inflammation, and chronic infectious disease, including rheumatoid arthritis. Renal failure is the most common clinical presentation of AA, ranging from nephrotic syndrome and impaired renal function to renal failure, with a potential for high morbidity. We present a case of a 52-year-old female patient diagnosed with rheumatoid arthritis at age 27. She was hospitalized due to worsening clinical condition. Physical examination revealed marked peripheral edema in both lower extremities. Laboratory tests showed an increase of inflammatory reactants, anemia, electrolyte disbalance, and severe hypoalbuminemia and hypoproteinemia. She had proteinuria 15.4 g/24 h and renal function estimated by creatinine clearance was 78 mL/min, within the second degree of chronic kidney disease. Renal biopsy was performed for evaluation of renal insufficiency with nephrotic range proteinuria. Congo red staining showed the presence of characteristic amyloid deposits that immunoreacted with the antibody against amyloid A protein, thus confirming the diagnosis of secondary amyloidosis.	\N	\N
23132831	Development of effective therapeutic strategies to eliminate cancer stem cells, which play a major role in drug resistance and disease recurrence, is critical to improve cancer treatment outcomes. Our study showed that glioblastoma stem cells (GSCs) exhibited low mitochondrial respiration and high glycolytic activity. These GSCs were highly resistant to standard drugs such as carmustine and temozolomide (TMZ), but showed high sensitivity to a glycolytic inhibitor 3-bromo-2-oxopropionate-1-propyl ester (3-BrOP), especially under hypoxic conditions. We further showed that combination of 3-BrOP with carmustine but not with TMZ achieved a striking synergistic effect and effectively killed GSCs through a rapid depletion of cellular ATP and inhibition of carmustine-induced DNA repair. This drug combination significantly impaired the sphere-forming ability of GSCs in vitro and tumor formation in vivo, leading to increase in the overall survival of mice bearing orthotopic inoculation of GSCs. Further mechanistic study showed that 3-BrOP and carmustine inhibited glyceraldehyde-3-phosphate dehydrogenase and caused a severe energy crisis in GSCs. Our study suggests that GSCs are highly glycolytic and that certain drug combination strategies can be used to effectively overcome their drug resistance based on their metabolic properties.	\N	\N
23133607	Functional genetic variations play important roles in shaping phenotypic differences among individuals through affecting gene expression, and thus, very likely to influence disease susceptibility, such as cancer susceptibility. One critical question in this era of post-genome wide association studies (GWAS) is how to assess the functional significance of the genetic variations identified from GWAS. In the current study, with lymphoblastoid cell lines (LCLs) from 74 non-related women with familial ovarian cancer and 47 unrelated controls matched on gender and race, we explored the associations between seven ovarian cancer risk variants identified from GWAS (rs3814113 on 9p22.2, rs2072590 on 2q31, rs2665390 on 3q25, rs10088218, rs1516982, rs10098821 on 8q24.21, and rs2363956 on 19p13) and whole genome mRNA expression profiles. We observed 95 significant trans-associations at a permutation level of 0.001. Compared to the other risk variants, rs10088218, rs1516982, and rs10098821 on 8q24.21 had the greatest number of significant associations (25, 16, and 38, respectively). Two possible cis-associations were observed between rs10098821 and c-Myc, and rs2072590 and HS.565379 (Permutated P = 0.0198 and 0.0399, respectively). Pathway enrichment analysis showed that several key biological pathways, such as cell cycle (P = 2.59×10(-06)), etc, were significantly overrepresented. Further characterization of significant associations between mRNAs and risk alleles might facilitate understanding the functions of GWAS discovered risk alleles in the genetic etiology of ovarian cancer.	\N	\N
23136226	A combination of bortezomib (1.3 mg/m(2)), melphalan (5 mg/m(2)), and dexamethasone (40 mg) (BMD), with all three drugs given as a contemporary intravenous administration, was retrospectively evaluated. Fifty previously treated (median 2 previous lines) patients with myeloma (33 relapsed and 17 refractory) were assessed. The first 19 patients were treated with a twice-a-week (days 1, 4, 8, 11, 'base' schedule) administration while, in the remaining 31 patients, the three drugs were administered once a week (days 1, 8, 15, 22, 'weekly' schedule). Side-effects were predictable and manageable, with prominent haematological toxicity, and a better toxic profile in 'weekly' schedule (36% versus 66% in 'base' schedule). The overall response rate was 62%. After median follow-up of 24.5 months (range 2.7-50 months), the median progression-free survival (PFS) was 21.6 with no difference between the two schedules and the median overall survival (OS) was 33.8 months. Independently from the adopted schedule, we found that also in a cohort of relapsed/refractory patients achieving at least partial remission improved PFS (35.2 versus 9 months) and OS (unreached median versus 18 months). Taken together, our observations suggest that BMD is an effective regimen in advanced myeloma patients with acceptable toxicity.	\N	\N
23137772	Molecular cytogenetic evaluation of human osteosarcoma (OS) has revealed the characteristically high degree of genomic reorganization that is the hallmark of this cancer. The extent of genomic disorder in OS has hindered identification of the genomic aberrations driving disease progression. With pathophysiological similarities to its human counterpart, canine OS represents an ideal model for comparison of conserved regions of genomic instability that may be disease-associated rather than genomic passengers. This study used high-resolution oligonucleotide array comparative genomic hybridization and a variety of informatics tools to aid in the identification of disease-associated genome-wide DNA copy number aberrations in canine and human OS. Our findings support and build upon the high level of cytogenetic complexity, through the identification of shared regions of microaberration (<500 kb) and functional analysis of possible orthologous OS-associated genes to pinpoint the cellular processes most commonly affected by aberration in human and canine OS. Aberrant regions contained previously reported genes such as CDC5L, MYC, RUNX2, and CDKN2A/CDKN2B, while expanding the gene of interest list to include ADAM15, CTC1, MEN1, CDK7, and others. Such regions of instability may thus have functional significance in the etiology of OS, the most common primary bone tumor in both species.	\N	\N
23143555	The objective of the study is to investigate the mechanisms of cyclophosphamide sequential therapy for patient with primary Sjögren's syndrome-associated interstitial lung disease (PSS-ILD). This was a retrospective review of 15 patients (2005-2008) with PSS-ILD who underwent cyclophosphamide sequential therapy. Peripheral blood and bronchoalveolar lavage (BALF) were obtained before and 3, 6, 12 and 24 months after the treatment. The TNF-α and TGF-β1 mRNA levels in peripheral blood were measured using reverse transcription polymerase chain reaction. Serum and BALF TNF-α, TGF-β1 and MMP-9 levels were measured using sandwich enzyme-linked immunosorbent assay. The average levels of serum TNF-α (0.39 ± 0.22) and TGF-β1 (0.31 ± 0.18) mRNA in patients with PSS-ILD were higher compared with that in patients with PSS without ILD. TNF-α level (0.23 ± 0.19) was significantly decreased 3 months after cyclophosphamide treatment (t = 2.533, p < 0.05), and TGF-β1 (0.31 ± 0.18) level markedly decreased after 6 months of treatment (t = 2.617, p < 0.05). The levels of serum TNF-α (11.2 ± 2.6) μg/L, TGF-β1 (72 ± 19) μg/L and MMP-9 (38 ± 9) μg/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-β1 (36 ± 12) μg/L level decreased significantly after 3 months of treatment (t = 2.526, p < 0.05), and TNF-α level (7.1 ± 1.3) μg/L markedly decreased after 6 months of therapy (t = 2.578, p < 0.05). MMP-9 level (18 ± 4) μg/L decreased significantly after 12-month treatment (t = 2.329, p < 0.05). The levels of BALF TNF-α (17.1 ± 3.5) μg/L, TGF-β1 (36 ± 17) μg/L and MMP-9 (27 ± 10) μg/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-β1 (21 ± 14) μg/L level decreased significantly after 3-month treatment, and TNF-α level (9.4 ± 1.7) μg/L was decreased after 6 months of cyclophosphamide treatment that may be associated with its inhabitation on production of TNF-α, TGF-β1 and MMP-9.	\N	\N
23144854	The Glutathione S-transferase P1 (GSTP1) polymorphism have been considered a risk modifier for developing head and neck cancer (HNC) in many studies; however, the results of such studies are inconsistent. The aim of this study was to evaluate the possible association between the GSTP1 Ile105Val polymorphism and risk of HNC. We performed a search in the relevant electronic database and a meta-analysis based on 28 published case-control studies that included 6,404 cases and 6,523 controls. To take into account the possibility of heterogeneity across the studies, a Chi-square based I(2)-statistic test was performed. Crude pooled odds ratios (ORs) with 95% confidence intervals (CIs) were assessed using both fixed-effects and random-effects models. The results of this meta-analysis showed that the GSTP1 Ile105Val polymorphism was not significantly associated with risk of HNC in the overall study population (pooled OR 1.00, 95% CI 0.92-1.09) or in subgroup analyses stratified by ethnicity, sample size, tumor site or publication year. Moreover, substantial evidence of heterogeneity among the studies was observed. Publication year was identified as the main cause of heterogeneity. This meta-analysis does not support a significant association between the GSTP1 Ile105Val polymorphism and risk of HNC.	\N	\N
23145068	Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9-15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4).In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation.	\N	\N
23146629	We report a 14-year-old-boy with markedly elevated serum creatine kinase (CK) levels, in whom massive triglyceride storage was found in peripheral blood leukocytes and in muscle biopsy. Sequencing PNPLA2, the gene encoding the adipose triglyceride lipase (ATGL) and responsible for the neutral lipid storage disease with myopathy (NLSDM), we identified two heterozygous mutations, including a previously reported nonsense and a novel missense mutation in the patatin domain of the gene. Lipid storage myopathy can be clinically silent in childhood and presenting only with hyperCKemia.	\N	\N
23154328	Trismus is a common problem among oral cancer patients. This report aimed to study the inciting factors of trismus and to find out the rationale of trismus release. Between 1996 and 2008, 61 oral cancer patients with retrievable records of interincisor distance (IID) were analyzed by retrospective chart review. The IID decreased from 31.4 (12.4) to 24.9 (12.0) mm in 36 patients undergoing cancer ablation only (P = 0.001). Other variables prompting trismus include buccal cancer (P = 0.017), radiotherapy (P = 0.008), and recurrence (P = 0.001). In contrast, the IID improved from 11.7 (7.1) to 22.7 (11.9) mm in 25 patients receiving cancer ablative and trismus releasing surgeries (P = 0.000). The improvement fared better in individuals with IID less than 15 mm than the others (P = 0.037). In conclusion, involvement of buccal region, ablative surgery, radiotherapy, and recurrence are provocative factors of trismus. Patients with IID less than 15 mm will benefit from releasing surgery significantly. Others may better be handled with conservative managements firstly, and enrolled as candidates of surgical release only until the patients entertained a 28-month period of disease-free interval, by which time the risk of recurrence would be markedly reduced.	\N	\N
23159635	Activin, a member of the transforming growth factor-β family, has been known to be a growth and differentiating factor. Despite its pluripotent effects, the roles of activin signaling in prostate cancer pathogenesis are still unclear. In this study, we established several cell lines that express a constitutive active form of activin type IB receptor (ActRIBCA) in human prostate cancer cells, ALVA41 (ALVA-ActRIBCA). There was no apparent change in the proliferation of ALVA-ActRIBCA cells in vitro; however, their migratory ability was significantly enhanced. In a xenograft model, histological analysis revealed that the expression of Snail, a cell-adhesion-suppressing transcription factor, was dramatically increased in ALVA-ActRIBCA tumors, indicating epithelial mesenchymal transition (EMT). Finally, mice bearing ALVA-ActRIBCA cells developed multiple lymph node metastases. In this study, we demonstrated that ActRIBCA signaling can promote cell migration in prostate cancer cells via a network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancers.	\N	\N
23167225	In this study, we hypothesized that subclinical impairment of left ventricular (LV) mechanical function in bicuspid aortic valve (BAV) patients is independent of valvular hemodynamics represented by valvuloarterial impedance and aortic elastic characteristics. Therefore, we aimed to test left ventricular mechanics in cases of isolated non-stenotic BAV with non-dilated aorta. Thirty-three patients with isolated BAV exhibiting non-dilated aorta, and 25 age-and gender-matched healthy subjects were included in the study. Patients with aortic valve velocity > 1.5 m/s and mild-to-moderate aortic regurgitation or ascending aorta diameter > 3.5 cm were excluded from the study. Aortic elasticity parameters and valvulo-arterial impedance were calculated. Strain measurements were reported as the peak longitudinal strain (LS) for four chamber (4C), long axis (LAX) and two chamber (2C) views. Strain rate (Sr) measurements were reported as the peak systolic strain rate (Sr-sm), early diastolic strain rate (Sr-em) and late diastolic strain rate (Sr-am) for 4C, LAX and 2C views. Systolic and diastolic diameters of the ascending aorta, aortic elastic properties (aortic strain, aortic distensibility, aortic stiffness and aortic elastic modulus), and valvulo-arterial impedances were found to be comparable between the BAV and control groups. BAV group was observed to have statistically significantly lower 4C (18.9 +/- 1.7 vs. 17.8 +/- 1.5, p = 0.02), LAX (19.7 +/- 1.7 vs. 17.7 +/- 1.3, p = 0.001) and 2C (20.1 +/- 1.8 vs. 17.7 +/- 1.2, p < 0.001) peak longitudinal strain values compared with the control group. Moreover, LV-GS values were found to be significantly lower in the BAV group than in the control group (19.6 +/- 1.1 vs. 17.7 +/- 0.9, p < 0.001). However, there was no statistically significant difference between the groups in terms of Sr-sm, Sr-em ve Sr-am values in the 4C, LAX, and 2C views. BAV might affect LV systolic functions, assessed by 2D strain imaging, in a fashion independent from the valvular dynamics and aortic elasticity. This might show that BAV is not only a valvular disease, but possibly a ventricular disease as well.	\N	\N
23168153	Allergic rhinitis (AR) is a highly prevalent allergic disease and also counts among the 10 most frequent reasons for medical consultation. Its impact on quality of life (QoL) and work productivity has been established but comparisons with other diseases are rare in the literature. The aim of this study was to evaluate the impact of AR in health-related QoL (HRQoL) and work productivity in primary care patients, compared with other prevalent diseases such as hypertension, diabetes mellitus (DM) type II, and symptomatic depression. Six hundred sixteen patients were included in a multicenter cross-sectional observational study. A generic HRQoL questionnaire, 36-item Short Form, and a specific questionnaire, "Work Productivity and Activity Impairment" were handed out to measure QoL and work productivity impact of the diseases. To assess clinical severity with a comparable scale between diseases Clinical Global Impression (CGI) had been used. Symptomatic depression was found to produce the greatest impairment on work productivity with a decrease of 59.5%, with significant differences compared with AR, hypertension, and DM type II (p < 0.05). Symptomatic depression was found to produce the highest negative impact on daily activities with a statistically significant reduction of 59.4% (p < 0.05) compared with AR (26.6% decrease), hypertension (8.8% decrease), and DM (16.7% decrease) patients. Differences between AR and DM or hypertension were also significant (p < 0.05). Restriction on daily activities for AR was 27.8%, which is significantly higher (p < 0.05) than hypertension (19.8% decrease) but not DM (25.7% decrease). Depression had the highest impairment on daily activities (59.4%), compared with the remaining three groups (p < 0.05). AR impairs work productivity in a greater magnitude than hypertension and DM type II.	\N	\N
23174870	Head and neck cancer is the fifth most common type of cancer worldwide. The objective of this study was to evaluate the clinical and epidemiological parameters in a head and neck surgery service. Cross-sectional study using patients' records, developed in otolaryngology and head and neck department of a university hospital in the northwest of the state of São Paulo. A total of 995 patients in the head and neck surgery service between January 2000 and May 2010 were evaluated. The variables analyzed included: age, gender, skin color, tobacco and alcohol consumption, primary site, staging and histological tumor type, treatment and number of deaths. The disease was more frequent among men (79.70%), smokers (75.15%) and alcohol abusers (58.25%). The most representative sites were oral cavity (29.65%) and larynx (24.12%) for the primary site; squamous cell carcinoma (84.92%) was the most frequent histological type, and surgery (29.04%) and radiotherapy (14.19%) were the most common treatments. The cancer that affects patients assisted by the head and neck surgery service occurs mainly men, smokers and alcohol abusers, and the oral cavity and larynx are the sites with the highest incidence. The high rate of patients with stages III and IV indicates late diagnosis by the treatment centers, which reflects the need for prevention education campaigns for early diagnosis of the disease.	\N	\N
23178050	Antidepressants might increase compliance with cardiovascular disease risk reduction interventions. However, antidepressants have been linked to deleterious metabolic effects. In the present multicenter study, we sought to determine whether patients who take antidepressants derive the expected benefits from cardiac rehabilitation in terms of improvements in multiple atherosclerotic risk factors. A cohort of 26,957 patients who had completed a baseline assessment before participating in an exercise-based cardiac rehabilitation program constituted the study population. The patients were stratified into 3 cohorts (i.e., nondepressed, depressed unmedicated, and depressed medicated) at baseline according to a self-reported history of depression and the current use of antidepressants. Risk factors were assessed at baseline and after ∼12 weeks of program participation. A self-reported history of depression was present at baseline in 5,172 patients (19.2%). Of these patients, 2,147 (41.5%) were taking antidepressants. Patients in the nondepressed cohort (49.4% completion) were more likely (p <0.001) to complete the exit assessment than patients in the depressed unmedicated (44.5% completion) or depressed medicated (43.5% completion) cohorts. Patients in all 3 cohorts who completed the exit assessment showed significant improvement in multiple risk factors. Moreover, the magnitude of improvement in blood pressure, serum lipids and lipoproteins, fasting glucose, weight, and body mass index was similar (p >0.05) in patients taking antidepressants and those who were not. In conclusion, our study is the first to show that antidepressants do not offset the average magnitude of improvement in multiple atherosclerotic risk factors that occurs with completion of a cardiac rehabilitation program.	\N	\N
23179223	Exposomic studies of the rapidly changing environment of the Three Gorges Reservoir (TGR) after its impounding is elaborated as a novel field of human and environmental research. Molecular exposomics is focused on the measure of all exposures to molecules and especially persistent organic pollutants-like compounds are of emerging interest due to their lifetime existence in the environment and humans. Theoretical considerations in general and particular for the TGR are deduced and presented using quantitative approaches for this research field. Since exposomics is strongly time-dependent, a theory is presented to link extension of exposure, time, and related effects. Similarity to the first law of thermodynamics is outlined. On top of this, the integrated use of biomarkers is presented employing chemical analysis for biomarkers of exposure and effects, biomarkers in vivo, in vitro approaches and the link between chemical mixtures, and the onset of disease and lethality. Besides real organisms, also virtual organisms are favored to act as well-defined sub-compartments such as fat of biota and with respect to time of exposure. Exposomics is the perspective of risk evaluation and chronic exposures in the running century. It needs novel theories, approaches, and integrated action between medical and environmental disciplines. The existing knowledge about molecular stressors has to be assembled and put into a context especially with respect not only to time resp. lifetime exposure of humans but also eco-toxicological findings by using highly conserved phylogenetic mechanisms to enable links between human and risks of environmental biota. The TGR is a good example not only to employ biomonitoring of real but also virtual organisms due to the lack of established ecotopes in this changing environment so far. Progress in understanding long-term risks requires a proper theory as well as novel tools such as virtual organisms. On top, multidisciplinary approaches and the utilization of existing knowledge about the exposure of the environment and humans have to be merged and directed into mutual concepts. Effect-oriented and chemical analysis must be designed time-oriented to determine lifetime exposures of mankind and nature. Perspectively, a first attempt about exposomic theory and concepts is proposed and has to be developed experimentally further enclosing virtual besides of real organisms and compartments. Environmental and human exposomics have to be considered as a unified global issue in order to effectively utilize their mutual existing knowledge most effectively. The TGR is a challenging model system aiming this objective.	\N	\N
23179576	In this study of 100,949 new users of oral bisphosphonates age ≥ 35 years, "early quitters" were found to differ from others with poor refill compliance in terms of socioeconomic, demographic, and treatment-related characteristics. New risk factors for poor compliance and persistence were identified. Poor compliance with anti-osteoporotic therapy is an on-going worldwide challenge. In this study, we hypothesized that "early quitters" differ in socioeconomics, demographics, co-medications, and comorbid conditions from other patients with low compliance. The study was a register-based nationwide cohort study of anti-osteoporotic therapy comprising 100,949 men and women. Statistical analysis including backward stepwise logistic regression analysis was used to explain causes of treatment failure and Kaplan-Meier survival analysis to estimate persistence of treatment. It was noted that 56.6 % of the patients were persistent and compliant, 4.7 % of the patients were persistent but "low compliant" while 38.7 % of the patients were "early quitters". "Early quitters" were found to differ in socioeconomics from "low compliant" patients. Differences concerning increased risk of "early quitters" were associated with high household income, subjects' age 71.9-79 years, living in the countryside or village, prior treatment with analgesics and anti-parkinson drugs, and dementia. Differences concerning decreased risk of "early quitters" were associated with male, living in an apartment, children living at home, living close to a university hospital, anti-osteoporotic therapy other than alendronate, number of drugs especially above three, pulmonary disease, collagen disease. The results suggest a need for improved support for patients to facilitate the interpretation of the disease and the perception of the benefits and risks of treatment-to reduce the risk of "early quitters". We were able to identify new risk groups that may be candidates for targeted actions.	\N	\N
23198711	To examine the long-term relationships between costs, utilization, and patient-centered medical home (PCMH) clinical practice systems. Clinical practice systems were evaluated at baseline by the Physician Practice Connections-Research Survey (PPC-RS). Annual costs and utilization of a retrospectively constructed cohort of 58,391 persons receiving primary care at 1 of 22 medical groups over a 5-year period (2005-2009) were compared. Multivariate regressions adjusting for patient demographics, health status, and autoregressive errors compared PPC-RS scores and study outcomes for the entire cohort and 3 subcohorts defined by medical complexity (medication count 0-2 [n = 29,657], 2-6 [n = 19,505], >7 [n = 9229]). Outcomes (adjusted to 2005 dollars) were total costs, outpatient costs, inpatient costs, inpatient days, and emergency department (ED) use. For the entire cohort, a 10% increase in PPC-RS scores was associated with 3.9 (medication count: 0-2), 6 (3-6), and 11.6 (>7) fewer ED visits per 1000 in 2005; and 5.1, 7.6, and 13.6 fewer ED visits in 2009. That 10% increase was not associated with the 0-2 medication subcohort's total (-$22/person in 2005; $184/person in 2009), outpatient (-$11/person in 2005; $42/person in 2009), or inpatient ($26/person in 2005; $29/person in 2009) costs. However, it was associated with significantly decreased total (-$446/person in 2005; -$184/person in 2009) and outpatient (-$241/person in 2005; -$54/person in 2009) costs for the most medically complex subcohort (>7 medications). Association of PCMH clinical practice systems with reduced costs appears limited to the most medically complex patients.	\N	\N
23199744	Due to their unique electric, magnetic, and optical properties, engineered nanostructures have been applied to provide diagnostic, therapeutic, as well as prognostic information about the status of disease. In this study, we report a multifunctional nanoprobe based on PEGylated Gd(2)O(3):Yb(3+), Er(3+) nanorods (denoted as PEG-UCNPs) for in vivo up-conversion luminescence (UCL), T(1)-enhanced magnetic resonance (MR), and X-ray computed tomography (CT) multi-modality imaging. A facile and large-scale hydrothermal system combining the merits of an in situ thermal decomposition method and a surface-modified approach is introduced to construct high-quality PEG-UCNPs. By grafting PEG molecules on the surface of PEG-UCNPs, the nanostructures possess excellent stability against in vivo environment and hold long blood circulation time. Cell-cytotoxicity assay, hemolyticity, as well as post-injection histology, hematology, and inflammation analysis further demonstrate their non-cytotoxic character and indicate further in vivo application. In detail, the capability of PEG-UCNPs as high-performance contrast agents for UCL/MR/CT imaging is evaluated successfully through small-animal experiments. Additionally, pharmacokinetics, biodistribution, and clearance route are studied after intravenous injection in a mouse model, reflecting their overall safety.	\N	\N
23208668	The surgical lesion of different brain structures has been used as a treatment for Parkinson's disease (PD) for several decades. More recently, the favored therapeutic approach has involved the administration of levodopa and the use of DBS. These two major therapeutic advances have greatly modified both the clinical condition of patients and the history of the disease. With the introduction of L-dopa in 1967, patients could regain mobility, because their akinesia, tremor, and rigidity were greatly improved, with consequent significant improvement in quality of life and increased life expectancy. However, after the so-called "honeymoon" period in which the disease seemed to be controlled, motor fluctuations and L-dopa-induced dyskinesias mitigated the initial enthusiasm. In the 1990s, unilateral pallidotomy and DBS of the globus palllidus internus and STN reduced these motor fluctuations and dyskinesias remarkably, thereby inaugurating a new era in the surgical treatment of PD. Short- and medium-term follow-up studies of patients who underwent surgery have documented sustained, significant motor benefits. However, given the progressive nature of PD and the purely symptomatic effects of pallidotomy and DBS, the long-term clinical evolution of these surgical patients currently seems to be associated with a new PD phenotype, mainly characterized by axial motor problems and cognitive impairment. Here, we analyze the long-term clinical outcomes of surgical PD patients with at least 5-year follow-up, focusing on the long-term motor symptoms that were initially responsive to surgery.	\N	\N
23216270	Although associations between autoimmune disorders (AIs) and the development of myeloid neoplasms have been described, the pathologic features and natural history of these malignancies have not been well characterized. We evaluated whether patients with AIs with acute myeloid leukemia (AML) were similar in nature to patients traditionally considered to have therapy-related AML (t-AML). Twenty-three patients with AML with a documented prior AI were included in our analysis. Median age at AML diagnosis was 59 years (range 32-78 years), and four patients were men (17%). Median latency between AI diagnosis and AML was 7.0 years. Ten patients (43%) had normal cytogenetics and six patients (26%) had favorable risk disease. In patients older than 65, all four patients had a normal karyotype. Median follow-up for all patients was 19.8 months (range 1.8-100.4 months), with 12 patients alive at last follow-up and median overall survival for all patients of 68.1 months. The encouraging survival data lend support to the notion that AML in patients with AIs appears to have characteristics and outcome more analogous to de novo than t-AML.	\N	\N
23217354	MicroRNAs are endogenously expressed small noncoding RNAs that regulate gene expression at the post-transcriptional level. MicroRNAs have emerged as key regulators of several physiological and pathophysiological processes in the cardiovascular system. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the development of atherosclerosis and cardiovascular disease, including change in endothelial function, vascular smooth muscle cell proliferation and migration, macrophage function, and foam cell formation. In this review, we summarize the recent data showing the roles of microRNAs in cell studies, studies on atherosclerotic mice, and human studies.	\N	\N
23219418	The appearance of liver metastases during the follow-up of a patient with a skin melanoma has classically been considered a sign of a very poor prognosis. There are limited therapeutic options, since these lesions are non-resectable and form part of a disseminated disease in several organs. In certain cases, in those where the disease is restricted to the liver or accompanied by a resectable extra-hepatic disease, hepatectomy can be useful, obtaining acceptable survivals of about 25% at 5 years, although hepatic or skin recurrence is usually early. The limited number of patient cases published, the absence of randomised studies, and the heterogeneity of the series, makes it difficult to reach conclusions to be able to recommend which patients may benefit from liver resection, with an acceptable level of scientific evidence, and thus define its real usefulness. There are also no action plans defined as to when and what type of adjuvant therapy we should use.	\N	\N
23222568	The rarity of conjunctival melanoma has impeded progress in the management of patients with this cancer; however, much progress has occurred in recent years. Primary acquired melanosis is now differentiated histologically into hypermelanosis and conjunctival melanocytic intra-epithelial neoplasia, for which an objective reproducible scoring system has been developed. Mapping and clinical staging of conjunctival disease has improved. Adjunctive radiotherapy and topical chemotherapy have made tumour control more successful, with reduced morbidity. Genetic analyses have identified BRAF and other mutations, which may predict responsiveness to new chemotherapeutic agents, for example Vemurafenib, should metastatic disease develop. Multicentre studies are under way to enhance survival prediction by integrating clinical stage of disease with histological grade of malignancy and genetic abnormalities. Such improved prognostication would not only be more relevant to individual patients, but would also provide greater opportunities for basic science research.	\N	\N
23222982	The study aimed to assess the efficacy of the adopted principles of the treatment of lung abscess without sequestration on the example of 2397 patients. Treatment led to the complete recovery in 1731 (72,2%) patients. The 614 (25,6%) patients showed the chronization of the process and 52 (2,2%) died. The surgical treatment of lung abscess without sequestration (performed in cases of uneffective conservative treatment) led to the complete recovery on 45.7% more often and the chronization of the process was registered on 26.8% more seldom, whereas the lethality rate was higher than by conservative treatment on 8%.	\N	\N
23226290	MiRNAs are key regulators of tumorigenesis that are aberrantly expressed in the circulation and tissue of patients with cancer. The aim of this study was to determine whether miRNA dysregulation in the circulation reflected similar changes in tumour tissue. Athymic nude mice (n = 20) received either a mammary fat pad (n = 8, MFP), or subcutaneous (n = 7, SC) injection of MDA-MB-231 cells. Controls received no tumour cells (n = 5). Tumour volume was monitored weekly and blood sampling performed at weeks 1, 3 and 6 following tumour induction (total n = 60). Animals were sacrificed at week 6 and tumour tissue (n = 15), lungs (n = 20) and enlarged lymph nodes (n = 3) harvested. MicroRNAs were extracted from all samples (n = 98) and relative expression quantified using RQ-PCR. MiR-221 expression was significantly increased in tumour compared to healthy tissue (p<0.001). MiR-10b expression was significantly higher in MFP compared to SC tumours (p<0.05), with the highest levels detected in diseased lymph nodes (p<0.05). MiR-10b was undetectable in the circulation, with no significant change in circulating miR-221 expression detected during disease progression. MiR-195 and miR-497 were significantly decreased in tumour tissue (p<0.05), and also in the circulation of animals 3 weeks following tumour induction (p<0.05). At both tissue and circulating level, a positive correlation was observed between miR-497 and miR-195 (r = 0.61, p<0.001; r = 0.41, p<0.01 respectively). This study highlights the distinct roles of miRNAs in circulation and tissue. It also implicates miRNAs in disease dissemination and progression, which may be important in systemic therapy and biomarker development.	\N	\N
23227561	We reviewed the tuberculosis (TB) surveillance database to determine the mode of detection, delays in achieving a TB diagnosis, and patients' occupational status upon registration. Of the 23,261 TB patients who were newly notified in 2010, 81.7% were diagnosed at medical institutions. Of these, 12.0% were diagnosed during hospitalisation with a disease other than TB, and 9.9% were diagnosed during outpatient visits with diseases other than TB. The overall proportion of TB cases detected by contact examination was only 2.8%, but this mode of detection was higher (56.1%) among younger TB patients aged 0-14 years. Of the 18,328 pulmonary TB patients, 27.3% had only respiratory symptoms, 31.0% had both respiratory and other symptoms, and 16.4% had only non-respiratory symptoms. Approximately one-quarter of elderly patients aged > or = 80 years with symptomatic pulmonary TB had only non-respiratory symptoms. pulmonary TB tended to have long total delays (the amount of time between the onset of symptoms and diagnosis). Among elderly patients, patient delays tended to be short, whereas doctor delays tended to be long. Of the 2,785 female pulmonary TB patients aged 20-59 years, 14.5% were medical workers and 10.4% of these were nurses.	\N	\N
23251076	NK cells exhibit the highest cytotoxic capacity within the immune system. Alteration of their number or functionality may have a deep impact on overall immunity. This is of particular relevance in aging where the elderly population becomes more susceptible to infection, cancer, autoimmune diseases, and neurodegenerative diseases amongst others. As the fraction of elderly increases worldwide, it becomes urgent to better understand the aging of the immune system to prevent and cure the elderly population. For this, a better understanding of the function and phenotype of the different immune cells and their subsets is necessary. We review here NK cell functions and phenotype in healthy aging as well as in various age-associated diseases.	\N	\N
23254356	Similar to T-helper (Th) cells, CD8(+) T cells also differentiate into distinct subpopulations. However, the existence of IL-9-producing CD8(+) T (Tc9) cells has not been elucidated so far. We show that murine CD8(+) T cells activated in the presence of IL-4 plus TGF-β develop into transient IL-9 producers characterized by specific IFN-γ and IL-10 expression patterns as well as by low cytotoxic function along with diminished expression of the CTL-associated transcription factors T-bet and Eomesodermin. Similarly to the CD4(+) counterpart, Tc9 cells required for their differentiation STAT6 and IRF4. Tc9 cells deficient for these master regulators displayed increased levels of Foxp3 that in turn suppressed IL-9 production. In an allergic airway disease model, Tc9 cells promoted the onset of airway inflammation, mediated by subpathogenic numbers of Th2 cells. This support was specific for Tc9 cells because CTLs failed to exert this function. We detected increased Tc9 frequency in the periphery in mice and humans with atopic dermatitis, a Th2-associated skin disease that often precedes asthma. Thus, our data point to the existence of Tc9 cells and to their supportive function in Th2-dependent airway inflammation, suggesting that these cells might be a therapeutic target in allergic disorders.	\N	\N
23254704	Organ transplantation and other major surgeries are impacted by ischemia-reperfusion injury (IRI). Mesenchymal stromal cells (MSCs) recently became an attractive alternative therapeutic tool to combat IRI. The present review highlights the effects of MSCs in the preclinical animal models of IRI and clinical trials, and explains their potential modes of action based on the pathophysiological IRI cascade. The application of MSCs in animal models of IRI show anti-inflammatory and anti-apoptotic effects, particularly for damage to the kidneys, heart and lungs. The mechanism of MSC action remains unclear, but may involve paracrine factors which could include the transfer of microvesicles, RNA or mitochondria. Although few clinical trials have reached completion, adverse effects appear minimal. MSCs show promise in protecting against IRI-induced damage. They appear to help recovery mainly by affecting the levels of inflammation and apoptosis during the organ repair process. In addition, they may mediate immunomodulatory effects on the innate and adaptive immune processes triggered during reperfusion and reduce fibrosis. Success in preclinical animal models has led to the initiation of ongoing clinical trials.	\N	\N
23265076	Diabetes is an important contributor to the burden of disease in South Africa and prevalence rates as high as 33% have been recorded in Cape Town. Previous studies show that quality of care and health outcomes are poor. The development of an effective education programme should impact on self-care, lifestyle change and adherence to medication; and lead to better control of diabetes, fewer complications and better quality of life. Pragmatic cluster randomized controlled trialParticipants: Type 2 diabetic patients attending 45 public sector community health centres in Cape TownInterventions: The intervention group will receive 4 sessions of group diabetes education delivered by a health promotion officer in a guiding style. The control group will receive usual care which consists of ad hoc advice during consultations and occasional educational talks in the waiting room. To evaluate the effectiveness of the group diabetes education programmeOutcomes: diabetes self-care activities, 5% weight loss, 1% reduction in HbA1c. self-efficacy, locus of control, mean blood pressure, mean weight loss, mean waist circumference, mean HbA1c, mean total cholesterol, quality of lifeRandomisation: Computer generated random numbersBlinding: Patients, health promoters and research assistants could not be blinded to the health centre's allocationNumbers randomized: Seventeen health centres (34 in total) will be randomly assigned to either control or intervention groups. A sample size of 1360 patients in 34 clusters of 40 patients will give a power of 80% to detect the primary outcomes with 5% precision. Altogether 720 patients were recruited in the intervention arm and 850 in the control arm giving a total of 1570. The study will inform policy makers and managers of the district health system, particularly in low to middle income countries, if this programme can be implemented more widely. Pan African Clinical Trial Registry PACTR201205000380384.	\N	\N
23268170	Kawasaki disease is a common paediatric vasculitide. It is usually diagnosed by its classical constellation of mucocutaneous signs. Recurrent Kawasaki disease is a rare phenomenon that occurs in approximately 3% of all patients diagnosed with Kawasaki disease. Its presentation is usually similar to the first episode of Kawasaki disease, and early diagnosis with prompt treatment is key in preventing associated cardiovascular morbidities. Recurrent Kawasaki disease is not well reported, and atypical presentations have not been previously reported in medical literature. Here, we report the case of a young girl with recurrent Kawasaki disease who presented atypically with acute airway obstruction secondary to retropharyngeal phlegmon.	\N	\N
23275389	To determine the longitudinal effects of TNF inhibitors on BMD and radiographic progression in patients with AS and to assess independent factors associated with increased BMD in the lumbar spine. Sixty-three patients with AS were included. Twenty-six patients were treated with TNF inhibitors and 37 were not. BMD in the lumbar spine and right femur was measured by DXA at baseline and 1 and 2 years later. Lumbar spine radiography was performed at baseline and after 2 years. Radiographic progression was scored using the Stoke AS Spinal Score (SASSS) and the modified SASSS. Univariate and multivariate linear regression analyses were performed to identify factors independently associated with spinal BMD increase. BMD in the lumbar spine and total proximal femur of patients receiving TNF inhibitors increased consistently over 2 years compared with that in patients not receiving TNF inhibitors (P < 0.01 and P = 0.02), and treated patients showed increased SASSS scores (P = 0.05); however, syndesmophyte development was no different between the two groups. There was a significant difference in the change of SASSS in patients treated with both TNF inhibitors and bisphosphonates compared with those treated with TNF inhibitors alone (P < 0.01). TNF inhibitor therapy and the increase in SASSS were independently associated with increased lumbar spine BMD (P = 0.009 and P < 0.001). TNF inhibitors appear to be associated with increased SASSS scores and improvements in BMD. Further prospective studies with larger subject numbers are needed to validate this paradoxical role of TNF inhibitors.	\N	\N
23278140	In contrast to adolescent acne, infantile acne (IA) is a rare condition with only a limited body of available literature. In this descriptive, retrospective study, we reviewed six cases from 2002 to 2010 treated with oral isotretinoin. The average age of onset was 6.16 months (range 0-21 mos). Consistent with the previous, limited literature, we found predominantly boys are affected, a predilection for the cheeks, and a polymorphic inflammatory morphology. Two patients had a family history of acne. All cases were successfully and safely treated with oral isotretinoin. The suggested treatment of childhood acne is similar to that of adolescents (graded according to the severity of the skin disease and risk of scarring). Oral isotretinoin appears to be an effective and safe treatment for severe IA.	\N	\N
23280098	Influenza A viruses circulating in pigs in Brazil are still not characterized, and only limited data are available about swine influenza epidemiology in the country. Therefore, we characterized the hemagglutinin (HA) and neuraminidase (NA) genes of influenza viruses isolated from Brazilian pigs. We also evaluated one case of probable swine-to-human transmission. Twenty influenza viruses isolated from pigs during 2009-2010 in five Brazilian states (Minas Gerais, Sao Paulo, Parana, Rio Grande do Sul, and Mato Grosso) were used. One human isolate, from a technician who became ill after visiting a swineherd going through a respiratory disease outbreak, was also used in the study. Phylogenetic analysis for the HA and NA genes and hemagglutinin amino acid sequence alignment were performed. All isolates clustered with pandemic H1N1 2009 (pH1N1) viruses and appeared to have a common ancestor. Genetic diversity was higher in the HA than in the NA gene, and the amino acid substitution S203T in one of HA's antigenic sites was found in most of the samples. The human isolate was more related to swine isolates from the same herd visited by the technician than to other human isolates, suggesting swine-to-human transmission. Our results show that pH1N1 was disseminated and the predominant subtype in Brazilian pigs in 2009-2010.	\N	\N
23284040	Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is one of the two established Hodgkin lymphoma (HL) subtypes. The risk factors of NLPHL are largely unknown. In general, genetic factors are known to have a modest effect on the risk of HL; however, familial risk in NLPHL has not been previously examined. We conducted a population-based study by using the Finnish registries and evaluated the familial risk in NLPHL. We launched a population-based search to identify patients with NLPHL and their relatives by examining the records of the Finnish Cancer Registry, established in 1953, and the official Finnish population registries. We collected a data set of 692 patients with NLPHL, identified their 4,280 first-degree relatives, and calculated the registry-based standardized incidence ratios (SIRs) for different cancers in the first-degree relatives. In addition, the primary tumor biopsies of HL-affected relatives were collected when possible, the HL diagnoses were re-reviewed by a hematopathologist, and the SIR for NLPHL was calculated on the basis of confirmed NLPHL diagnoses. On the basis of confirmed NLPHL diagnoses, the SIR for NLPHL was 19 (95% CI, 8.8 to 36) in the first-degree relatives. The risk was most prominent in female relatives of young patients. The registry-based SIR for classical HL was 5.3 (95% CI, 3.0 to 8.8), and for non-Hodgkin lymphoma, it was 1.9 (95% CI, 1.3 to 2.6). Our results implicate an unexpectedly high familial component in the development of NLPHL. Research is warranted to identify the putative genetic and environmental factors underlying this finding and to develop strategies for better management of patients with NLPHL and their relatives.	\N	\N
23293016	Kawasaki disease (KD) is a systemic inflammatory illness of childhood that particularly affects the coronary arteries. It can lead to coronary artery aneurysms, myocardial infarction, and sudden death. Clinical and epidemiologic data support an infectious cause, and the etiology remains unknown, but recent data support infection with a 'new' virus. Genetic factors influence KD susceptibility; the incidence is 10-fold higher in children of Asian when compared with Caucasian ethnicity. Recent research has identified genes affecting immune response that are associated with KD susceptibility and outcome. A re-examination of the pathologic features of KD has yielded a three process model of KD vasculopathy, providing a framework for understanding the KD arterial immune response and the damage it inflicts and for identifying new therapeutic targets for KD patients with coronary artery abnormalities. The researcher is faced with many challenges in determining the pathogenesis of KD. A systems biology approach incorporating genomics, proteomics, transcriptomics, and microbial bioinformatics analysis of high-throughput sequence data from KD tissues could provide the keys to unlocking the mysteries of this potentially fatal illness of childhood.	\N	\N
23295556	To describe the course and management of a protracted outbreak after intercontinental transfer of 2 patients colonized with multidrug-resistant Acinetobacter baumannii (MDRAB). An 18-month outbreak investigation. An 860-bed university hospital in France. Case patients (ie, carriers) were those colonized or infected with an MDRAB isolate. During the epidemic period, all intensive care unit (ICU) patients and contacts of carriers who were transferred to wards were screened for MDRAB carriage. Contact precautions, environmental screening, and auditing of healthcare worker (HCW) practices were implemented; rooms were cleaned with hydrogen peroxide mist disinfection. One ICU, in which most of the cases occurred, was closed on 4 occasions for thorough cleaning and disinfection. The 2 index case patients were identified as 2 patients who carried the same MDRAB strain and who were admitted to the hospital after repatriation from Tahiti 5 months apart. During an 18-month period, a total of 84 secondary cases occurred. Reintroduction of MDRAB into the ICUs occurred from patients previously colonized or from healthcare personnel. Termination of the outbreak was only achieved when all carriers from wards or the ICU were cohorted to an isolation unit with dedicated healthcare personnel. Intercontinental transfer of carriers of MDRAB can result in extensive outbreaks and serious disruption of the hospital's organization. Transmission from carriers most likely occurred via the hands of HCWs, poor cleaning protocols, airborne spread, and contaminated water from sink traps. This protracted outbreak was controlled only after implementation of an extensive control program and eventual cohorting of all carriers in an isolation unit with dedicated healthcare personnel.	\N	\N
23296696	Previously, most dengue cases in Singapore were hospitalized despite low incidence of dengue hemorrhagic fever (DHF) or death. To minimize hospitalization, the Communicable Disease Centre at Tan Tock Seng Hospital (TTSH) in Singapore implemented new admission criteria which included clinical, laboratory, and DHF predictive parameters in 2007. All laboratory-confirmed dengue patients seen at TTSH during 2006-2008 were retrospectively reviewed for clinical data. Disease outcome and clinical parameters were compared over the 3 years. There was a 33.0% mean decrease in inpatients after the new criteria were implemented compared with the period before (p < 0.001). The proportion of inpatients with DHF increased significantly from 31.7% in 2006 to 34.4% in 2008 (p = 0.008); 68 DHF cases were managed safely on an outpatient basis after compared with none before implementation. DHF inpatients had more serious signs such as clinical fluid accumulation (15.5% vs 2.9% of outpatients), while most DHF outpatients had hypoproteinemia (92.7% vs 81.3% of inpatients). The eight intensive care unit admissions and five deaths during this time period all occurred among inpatients. The new criteria resulted in a median cost saving of US$1.4 million to patients in 2008. The new dengue admission criteria were effective in sustainably reducing length of hospitalization, yielding considerable cost savings. A minority of DHF patients with mild symptoms recovered uneventfully through outpatient management.	\N	\N
23301916	Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia and immune deficiency. WAS gene mutations impair WAS protein function which cause WAS. The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may have similar but less severe symptoms those are also caused by mutations of the same gene. We present two cases of WAS in neonates with WAS gene mutations. Early genetic diagnosis can help to the treatment and prevention this disease.	\N	\N
23313927	Mexican Americans are the fastest aging segment of the U.S. population, yet little scientific literature exists regarding the Alzheimer's disease (AD) among this segment of the population. The extant literature suggests that biomarkers of AD will vary according to race/ethnicity though no prior work has explicitly studied this possibility. The aim of this study was to create a serum-based biomarker profile of AD among Mexican American. Data were analyzed from 363 Mexican American participants (49 AD and 314 normal controls) enrolled in the Texas Alzheimer's Research & Care Consortium (TARCC). Non-fasting serum samples were analyzed using a luminex-based multi-plex platform. A biomarker profile was generated using random forest analyses. The biomarker profile of AD among Mexican Americans was different from prior work from non-Hispanic populations with regards to the variable importance plots. In fact, many of the top markers were related to metabolic factors (e.g., FABP, GLP-1, CD40, pancreatic polypeptide, insulin-like-growth factor, and insulin). The biomarker profile was a significant classifier of AD status yielding an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.77, 0.92, and 0.64, respectively. Combining biomarkers with clinical variables yielded a better balance of sensitivity and specificity. The biomarker profile for AD among Mexican American cases is significantly different from that previously identified among non-Hispanic cases from many large-scale studies. This is the first study to explicitly examine and provide support for blood-based biomarkers of AD among Mexican Americans. Areas for future research are highlighted.	\N	\N
23316660	Polyarteritis nodosa (PAN) is a multi-system disease, characterized by necrotizing vasculitis of medium-sized arteries that may affect any organ system. Cutaneous PAN is the cutaneous limited form of PAN. It affects 10% of all cases of PAN and usually demonstrates a benign and chronic course. We hereby describe a 47-year-old female with diabetes mellitus who presented with painful ulcers on both legs. The clinical and histological findings were consistent with PAN. A thorough investigation ruled out systemic PAN and cutaneous PAN was determined. Despite intensive therapies including corticosteroids and azathioprine, marked progression of the ulcers was noted and large areas of necrosis appeared. The patient underwent above-knee amputation of both legs and eventually died in less than three years. Although cutaneous PAN is known to have a benign and chronic course, we have presented an unusual progressive and severe course that resulted in the death of the patient.	\N	\N
23324593	An under-appreciated clue about pathogenesis in Parkinson disease (PD) is the distribution of pathology in the early and middle stages of the disease. This pathological 'roadmap' shows that in addition to dopaminergic neurons in the substantia nigra pars compacta (SNc), a significant number of other central and peripheral neuronal populations exhibit Lewy pathology, phenotypic dysregulation or frank degeneration in PD patients. This spatially distributed, at-risk population of neurons shares a number of features, including autonomously generated activity, broad action potentials, low intrinsic calcium buffering capacity and long, poorly myelinated, highly branched axons. Many, and perhaps all, of these traits add to the metabolic burden in these neurons, suggesting that mitochondrial deficits could drive pathogenesis in PD-in agreement with a large segment of the literature. What is less clear is how this neuronal phenotype might shape the susceptibility to proteostatic dysfunction or to the spread of α-synuclein fibrils deposited in the extracellular space. The review explores the literature on these issues and their translational implications.	\N	\N
23327371	Over the past few decades a large number of new and emerging infectious diseases have been recognised in humans, partly because of improved diagnostic technologies and increased awareness and also, partly because of dynamic ecological changes between human hosts and their exposure to animals and the environment (Coker et al. 2011). Some 177 new pathogenic organisms have been recognised to be 'emerging', that is, have newly arisen or been newly introduced into human populations; almost three quarters of these, 130 (73%), have come from zoonotic origins (Cascio et al. 2011; Cutler, Fooks &amp; Van Der Poel 2010; Taylor, Latham &amp; Woolhouse 2001; Woolhouse &amp; Gowtage-Sequeria 2005). One of the most prevalent and important human infectious disease is influenza, a disease responsible globally for a quarter million deaths annually. In the USA alone the toll from influenza is estimated at 36 000 deaths and 226 000 hospitalisations, and it ranks as the most important cause of vaccine preventable mortality in that country (CDC 2010). The epidemiological behaviour of human influenza clearly defines it as an emerging infectious disease and the recent understanding of its zoonotic origins has contributed much to the understanding of its behaviour in humans (Fauci 2006).	\N	\N
23330027	Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) constitute important public health problems in developing countries. Children with ARF and RHD seen at Children's Hospital-Sudan from May 2008-2009 were examined clinically and by echocardiography. Blood cytokines (interleukin 10 (IL10), Tumor necrosis factor alpha (TNF- alpha) and interferon gamma (IFN-gamma) were done. Thirty six children were enrolled; 63% had established RHD, and 37% ARF. Mitral regurgitation (MR) was the most common lesion (94%).Ninety five percent of the valve lesions were severe. The serum interleukin IL10 level ranged between 3-6 pg/ml. TNF alpha levels were 9- 100 pg/ml in 12 patients (40%), 101-1000 pg/ml in 10 patients (33%), more than 1000 in 8 patients (26%). The level of IFN gamma ranged between 2-7 pg/m in all patients except 2 (84 and 135 pg/ml). RHD is manifested with severe valvular lesions and a high TNF alpha indicating and ongoing inflammation.	\N	\N
23330952	The authors present 1-year results in 60 patients with cervical radiculopathy due to spondylosis and stenosis that was treated with a bilateral percutaneous facet implant. The implant consists of a screw and washer that distracts and immobilizes the cervical facet for root decompression and fusion. Clinical and radiological results are analyzed. Between 2009 and 2011, 60 patients were treated with the DTRAX Facet System in a multicenter prospective single-arm study. All patients had symptomatic clinical radiculopathy, and conservative management had failed. The majority of patients had multilevel radiographically confirmed disease. Only patients with single-level radiculopathy confirmed by history, physical examination, and in some cases confirmatory nerve blocks were included. Patients were assessed preoperatively with Neck Disability Index, visual analog scale, quality of life questionnaire (Short Form-12 version 2), CT scans, MRI, and dynamic radiographs. Surgery was percutaneous posterior bilateral facet implants consisting of a screw and expandable washer and iliac crest bone aspirate. Patients underwent postoperative assessments at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year with validated outcome questionnaires. Alterations of segmental and overall cervical lordosis, foraminal dimensions, device retention and fusion criteria were assessed for up to 1 year with CT reconstructions and radiographs. Fusion criteria were defined as bridging trabecular bone between the facets, translational motion < 2 mm, and angular motion < 5°. All patients were followed to 1 year postoperatively. Ages in this cohort ranged from 40 to 75 years, with a mean of 53 years. Forty-two patients were treated at C5-6, 8 at C6-7, 7 at C4-5, and 3 at C3-4. Fifty-six had bilateral implants; 4 had unilateral implants due to intraoperative facet fracture (2 patients) and inability to access the facet (2 patients). The Neck Disability Index, Short Form-12 version 2, and visual analog scale scores were significantly improved at 2 weeks and remained significantly improved up to 1 year. At the treated level, 93% had intrafacet bridging trabecular bone on CT scans, translational motion was < 2 mm in 100% and angular movement was < 5° in 83% at the 1-year follow-up. There was no significant change in overall cervical lordosis. There was a 1.6° loss of segmental lordosis at the treated level at 1 year that was significant. Foraminal width, volume, and posterior disc height was significantly increased at 6 months and returned to baseline levels at 1 year. There was no significant decrease in foraminal width and height at adjacent levels. There were no reoperations or surgery- or device-related complications, including implant failure or retained hardware. Results indicate that the DTRAX Facet System is safe and effective for treatment of cervical radiculopathy.	\N	\N
23336917	The use of ventricular assist devices in patients with complex congenital heart disease has not been well described. We present a case of successful ventricular assist device support in a 38-year-old man with congenitally corrected transposition of the great arteries and severe secondary pulmonary hypertension.	\N	\N
23338998	The aim of this study was to verify if genetic factors influence the short- and long-term therapeutic responses to oestroprogestagen (OP) therapy, implemented in girls with functional hypothalamic amenorrhoea (FHA) in order to improve their bone mineral density (BMD). The study included 78 FHA girls who underwent a four-year sequential OP therapy with 17-beta oestradiol and didrogesterone. Changes in the lumbar spine BMD were determined at the end of the therapy and six years after its discontinuation, and analysed in regards to PvuII and XbaI polymorphisms of oestrogen receptor-alpha gene, BsmI polymorphism of vitamin D3 receptor gene, and Sp1 polymorphism of the type-1 collagen gene. After four years of OP therapy, a significant increase in BMD was documented in the studied group. Follow-up densitometry performed six years after completing the therapy revealed a significant decrease in BMD level; nonetheless, the values of this parameter were still significantly higher compared to pretreatment level. Neither the particular polymorphisms nor their combinations influenced the relative change in BMD at the end of the therapy and after a six-year follow-up. Variability of genes involved in oestrogen, vitamin D3 and collagen metabolism does not influence the short- and long-term results of OP therapy in girls with FHA.	\N	\N
23344286	Preeclampsia complicates approximately 3-5% of pregnancies and remains one of the major causes of maternal and neonatal morbidity. It shares pathogenic similarities with adult cardiovascular disease as well as many risk factors. Attempts at prevention of preeclampsia using various supplements and classes of medications have failed or had limited success, and they were not convincing enough to lead to widespread adoption of any particular strategy. Contrary to the experience with preeclampsia, prevention of cardiovascular mortality and other cardiovascular events in nonpregnant patients using 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, or statins, is widely accepted. Pravastatin and other statins have been shown to reverse various pathophysiologic pathways associated with preeclampsia, such as angiogenic imbalance, endothelial injury, inflammation, and oxidative stress. These beneficial effects are likely to contribute substantially to preventing preeclampsia and provide biological plausibility for the use of pravastatin in this setting. Pravastatin has favorable safety and pharmacokinetic profiles. In addition, animal studies and human pregnancy exposure data do not support teratogenicity claims for pravastatin. Therefore, the Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric--Fetal Pharmacology Research Units Network started a pilot trial to collect maternal--fetal safety data and to evaluate pravastatin pharmacokinetics when used as a prophylactic daily treatment in high-risk pregnant women (identifier NCT01717586, clinicaltrials.gov).	\N	\N
23346802	The purpose of this article was to describe the phenomena related to the mechanisms regulating alterations of vascular blood flow in ophthalmic and retrobulbar circulation. In this review, various indirect and direct methods of evaluating retinal blood flow have been discussed. Laser, contrast and ultrasonographic techniques, including color Doppler ultrasonography, electroretinography, electroencephalography, calorimetric investigations, with the radiographic entities and registering changes in tunica vasculosa circulation were described. Additionally, radiographic investigations, isometric measurements and studies with the use of pharmacological agents, evaluation of partial pressure of oxygen or carbon dioxide in both inhaled and exhaled air, and in daylight as well as in darkness were presented. Although there are many control methods of regulating mechanisms of bulbar circulation, none of those techniques used presently and in the past is ideal, hence the only investigations widely applied for this purpose have been both Doppler ultrasonography and laser methods. In the review influence of myogenic and neurogenic mechanisms on blood flow in eyeball was described. Moreover, the part of vessels coarcting and dilating substances in these hemodynamic phenomena has been included. In the course of various ophthalmic disease entities of vascular origin, different substances take part in general and local regulation of ocular and retrobulbar circulation, whose action mechanism might be the cause of hemodynamic disorders. Color Doppler ultrasonography remains one of the more frequently used methods which could indirectly register alterations of vascular blood flow in retrobulbar arteries.	\N	\N
23347399	Methcathinone abuse is a new cause of manganism. The psychostimulant is prepared from pseudoephedrine using potassium permanganate as an oxidant. We describe the clinical, biological, neuroimaging characteristics and follow-up results in a large Estonian cohort of intravenous methcathinone users. During 2006-2012 we studied 38 methcathinone abusers with a mean age of 33 years. Subjects were rated by the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (HY), and Schwab and England (SE) rating scales. Twenty-four cases were reassessed 9-70 (20 ± 15) months after the initial evaluation. Manganese (Mn) in plasma and hair was analysed by inductively coupled plasma-atom emission spectrometry. Magnetic resonance imaging (MRI) was performed in 11, and single-photon emission computed tomography (SPECT) with iodobenzamide (IBZM) in eight subjects. The average total UPDRS score was 43 ± 21. The most severely affected domains in UPDRS Part III were speech and postural stability, the least affected domain was resting tremor. At follow-up there was worsening of HY and SE rating scales. Subjects had a higher mean level of Mn in hair (2.9 ± 3.8 ppm) than controls (0.82 ± 1.02 ppm), P = 0.02. Plasma Mn concentrations were higher (11.5 ± 6.2 ppb) in active than in former users (5.6 ± 1.8 ppb), P = 0.006. Active methcathinone users had increased MRI T1-signal intensity in the globus pallidus, substantia nigra and periaquaductal gray matter. IBZM-SPECT showed normal symmetric tracer uptake in striatum. Methcathinone abusers develop a distinctive hypokinetic syndrome. Though the biomarkers of Mn exposure are characteristic only of recent abuse, the syndrome is not reversible.	\N	\N
23347458	We compared values of baseline serum cystatin C (SCysC), serum creatinine (SCr), and measured glomerular filtration rate (mGFR) for predicting end-stage renal disease (ESRD) in patients with type 2 diabetes and elevated albuminuria. Observational longitudinal study. Pima Indians with type 2 diabetes and elevated albumin-creatinine ratio (ACR ≥30 mg/g). Baseline SCysC, SCr, and mGFR. Individuals were followed up from their first examination with diabetes and ACR ≥30 mg/g until December 2010, onset of ESRD, or death, whichever came first. Incidence rates adjusted for age and sex were computed by Mantel-Haenszel stratification. The abilities of SCysC, SCr, and mGFR values to predict ESRD were compared with receiver operating characteristic curves. Of 234 Pima Indians with a mean age of 42.8 years who were followed up for a median of 10.7 (range, 0.6-21.3) years, 68 (29%) developed ESRD. The incidence of ESRD was significantly higher in patients in the lowest versus highest tertile of 1/SCysC (incidence rate ratio, 2.43; 95% CI, 1.31-4.50). By contrast, mGFR and 1/SCr had J-shaped associations with ESRD. In unadjusted analyses, 1/SCysC had the highest area under the receiver operating characteristic curve (AUROC; 0.719 ± 0.035) and mGFR had the lowest (0.585 ± 0.042; P < 0.001); the AUROC for 1/SCr was intermediate (0.672 ± 0.040; P = 0.1 and P = 0.03 vs 1/SCysC and mGFR, respectively). In analyses adjusted for age, sex, diabetes duration, height, weight, hemoglobin A1c level, and ACR, 1/SCysC had the highest AUROC (0.845 ± 0.026). Models with mGFR or 1/SCr alone had similar AUROCs (P = 0.9) and both were lower than the model with 1/SCysC alone (P = 0.02 and P = 0.03, respectively). The predictive values of the filtration markers are limited to the extent that their precision is based on a single measurement. SCysC level was a better predictor of ESRD than mGFR or SCr level in Pima Indians with type 2 diabetes and elevated albuminuria.	\N	\N
23354259	The surgical treatment of acute colonic diverticulitis is associated with significant morbidity and mortality. However, patient and operative characteristics associated with mortality in this patient population are unclear. We hypothesize that demographic and perioperative variables can be used to predict postoperative mortality.The purpose of this study was to identify perioperative variables predictive of postoperative mortality after emergent surgery for acute diverticulitis. Patients with diverticulitis undergoing colostomy and/or partial colectomy with or without primary anastomosis were retrieved from the American College of Surgeons National Surgical Quality Improvement Program database for years 2005 to 2008 inclusive. Only patients undergoing emergent surgery for acute diverticulitis were included. Univariate analyses were performed to compare demographic characteristics, preoperative laboratory values, comorbidities, and intraoperative variables. Variables with a significant (p < 0.10) difference between survivors and nonsurvivors were included in a stepwise logistic regression model to determine predictors of 30-day mortality. Concordance indices (c indices) for postoperative mortality were calculated using 2005 to 2008 data to determine predictive accuracy and validated on 2009 data. A total of 2,214 patients met inclusion criteria. Mean age was 61 years, and 50% of patients were male. Thirty-day mortality was 5.1%. Nine preoperative variables were significantly associated with postoperative mortality on multivariable analysis. The c index of this nine-variable model was 0.901. Renal dysfunction, hypoalbuminemia, American Society of Anesthesiologists class, and age were chosen to create a simpler model, with a c index of 0.886 for 2005 to 2008 data and 0.893 for 2009 data. Four readily available perioperative variables can be used to predict 30-day mortality after emergent surgery for acute diverticulitis. Prognostic study, level II.	\N	\N
23379818	MicroRNAs (miRNAs) are small noncoding RNAs that not only regulate gene expression during normal development but can also be active players in several diseases. To date, several studies have demonstrated a possible role for specific miRNAs in the regulation of pulmonary vascular homeostasis suggesting that novel therapeutic agents which target these modulators of gene expression could serve to treat pulmonary arterial hypertension (PAH). The characterization of miRNA-mediated gene modulation in the pulmonary circulation is expanding very rapidly. This review summarizes current relevant findings on the role of miRNAs in the pathogenesis of PAH and expands on the potential use of agents that target these molecules as future disease-modifying therapies. Further understanding of miRNA biology and function in the pulmonary circulation will serve to further enhance our understanding of their contribution to the pathogenesis of PAH. The implementation of a systems biology approach will help accelerate the discovery of miRNAs that influence angiogenesis and cellular responses to vascular injury. Experimental characterization of these miRNAs using in vitro and in vivo methods will be required to validate the biological roles of these miRNAs prior to the consideration of their use as therapeutic targets in future clinical trials.	\N	\N
23382786	CXCR4 is a G-protein-coupled receptor involved in a number of physiological processes in the hematopoietic and immune systems. The SDF-1/CXCR4 axis is significantly associated with several diseases, such as HIV, cancer, WHIM syndrome, rheumatoid arthritis, pulmonary fibrosis and lupus. For example, CXCR4 is one of the major co-receptors for HIV entry into target cells, while in cancer it plays an important role in tumor cell metastasis. Several promising CXCR4 antagonists have been developed to block SDF-1/CXCR4 interactions that are currently under different stages of development. The first in class CXCR4 antagonist, plerixafor, was approved by the FDA in 2008 for the mobilization of hematopoietic stem cells and several other drugs are currently in clinical trials for cancer, HIV, and WHIM syndrome. While the long-term safety data for the first generation CXCR4 antagonists are not yet available, several new compounds are under preclinical development in an attempt to provide safer and more efficient treatment options for HIV and cancer patients.	\N	\N
23389330	Childhood tuberculosis (TB) accounts for a significant proportion of the global tuberculosis disease burden. However, current and previous efforts to develop better diagnostic, therapeutic, and preventive interventions have focused on TB in adults, and childhood TB has been relatively neglected. The purpose of this review is to provide an update on the diagnostic and therapeutic recommendations for childhood TB with an emphasis on intrathoracic disease. The literature from a range of sources was reviewed and synthesized to provide an overview of the contemporary approaches for the diagnosis and treatment of childhood TB. This review summarizes the clinical, radiological, bacteriological, and immunological approaches to diagnose TB infection and disease in children. In addition, we summarize the updated guidelines for the treatment of TB in children. The development of better diagnostic and therapeutic methods for childhood TB remains a significant challenge. As the strategies for diagnosis and treatment of childhood TB continue to improve and the knowledge base increases, the implementation of these strategies will be crucial.	\N	\N
23393912	The most common autosomal form of Chronic Granulomatous Disease, p47-phox deficient CGD, generally features a GT (deltaGT) deletion in the GTGT sequence at the start of exon 2 on the NCF-1 gene. This consistency is due to the coexistence of and the recombination between 2 homologous pseudogenes (psi s) and NCF-1. The GTGT: deltaGT ratio mirrors the NCF-I: NCF-1 psi ratio and is 2:4 in normal individuals. To determine the molecular basis of the Autosomal-CGD in a family with 2 children, a male and female, affected by the disease. The female patient suffered recurrent infection, retinitis pigmentosa and discoid lupus. Chemiluminescence (CL) was used to study the respiratory burst, while genetic analysis was done by RT-PCR, PCR, deltaGT and the 20bp gene scans. The CL response of the patient was profoundly low. The patient's p47-phox band was absent in the RT-PCR for NADPH-oxidase component mRNAs. The deltaGT scan showed that the patient's GTGT: deltaGT ratio was 0:6, the parents' and the younger brother's was 1:5 and the younger sister's was 2:4. Examination of other NCF-1/ NCF-1 psi s differences showed that the father had a compound deltaGT allele ie. deltaGT-20bp, inherited by the patient, and that both parents had compound GTGT alleles with a single 30bp segment in intron 1. The patient was a classic, homozygous deltaGT p47-phox deficient CGD with one allele harbouring a compound deltaGT-20bp gene. The deltaGT and 20bp gene scans offer a relatively simple and efficient means of defining a p47-phox deficient CGD patient.	\N	\N
23394360	Acute kidney injury (AKI) is common in hospitalized human immunodeficiency virus (HIV)-infected patients and is associated with hospital mortality. We aimed to evaluate the impact of AKI on long-term mortality of hospitalized HIV-infected patients. Retrospective analysis of a cohort of 433 hospitalized HIV-infected patients who were discharged alive from the hospital. AKI was defined according to 'Risk Injury Failure Loss of kidney function End-stage kidney disease' creatinine criteria, as an increase of baseline serum creatinine (SCr) X 1.5 or in patients with baseline SCr > 4 mg/dL if there was an acute rise in SCr of at least 0.5 mg/dL. Cumulative mortality curves were determined by the Kaplan-Meier method, and log-rank test was employed to analyze statistically significant differences between curves. Cox regression method was used to determine independent predictors of mortality. Risk factors were assessed with univariate analysis, and variables that were statistically significant (P < 0.05) in the univariate analysis were included in the multivariate analysis. Sixty-four patients (14.8%) had AKI. Median follow-up was 37 months. At follow-up 81 patients (18.7%) died. At 1, 2 and 5 years of follow-up, the cumulative probability of death of patients with AKI was 21.2, 25 and 31.3%, respectively, as compared with 10, 13.3 and 16.5% in patients without AKI (log-rank, P = 0.011). In multivariate analysis AKI was associated with increased mortality (adjusted HR 1.7, 95% CI 1.1-3; P = 0.049). AKI was independently associated with long-term mortality of hospitalized HIV-infected patients.	\N	\N
23394995	Maintenance of an adequate and properly regulated immune system is essential for health and well-being. Components in food may modulate immune responses in a positive way (immunonutrition), and some of these components are present in kiwifruit. Kiwifruit contains vitamin C, carotenoids, polyphenols, and dietary fiber, and these are all potentially beneficial to the immune system. Research that has contributed to our understanding of the beneficial effects that kiwifruit may have on immune responses spans from in vitro studies using cell lines and human blood cells, to using animal models targeting both mucosal and systemic immunity. Some limited human intervention trials have been undertaken and are described, in which kiwifruit has been shown to influence a number of biomarkers of oxidative stress and beneficial immune responses, to reduce the incidence and severity of symptoms of upper respiratory tract infections and potentially be more beneficial than supplementation with vitamin C alone.	\N	\N
23395237	To investigate the expression and possible roles of Twist1 and Y-box-binding protein-1 (YB-1) in bladder cancer tissue. Twist1 belongs to the family of basic helix-loop-helix transcription factors. A functional link between Twist1 and YB-1 has recently been determined to play an important role in bladder cancer cell lines. Frozen samples from 75 patients with bladder cancer were analyzed by quantitative real-time polymerase chain reaction (PCR). Formalin-fixed and paraffin-embedded tissues from 53 patients with bladder cancer were examined by immunohistochemistry. Twist1 transcript levels were positively correlated with YB-1 transcript levels (coefficient of correlation = 0.42, P<0.001), tumor grade (low grade vs. high grade; P<0.001), invasiveness (non-muscle-invasive bladder cancer vs. muscle invasive bladder cancer; P = 0.0018), and metastasis (meta- vs. meta+; P<0.001). YB-1 transcript level was also correlated with grade (P = 0.029) and invasiveness (P = 0.006). By immunohistochemistry, Twist1 expression was also correlated with YB-1 expression (P<0.001). Further, both Twist1 and YB-1 expression were positively correlated with invasiveness (P = 0.007 and P = 0.002, respectively). Patients with high Twist1 expression and high YB-1 expression had lower overall survival rates, compared with patients with low expression (log-rank test, P = 0.040 and P<0.001, respectively). These results suggest a functional link between Twist1 and YB-1, and they indicate that Twist1 and YB-1 promote bladder cancer progression.	\N	\N
23396208	Regulatory T (Treg) cells suppress autoimmune disease, and impaired Treg cell function is associated with rheumatoid arthritis. Here we demonstrate that forkhead box P3 (FOXP3) transcriptional activity and, consequently, Treg cell suppressive function are regulated by phosphorylation at Ser418 in the C-terminal DNA-binding domain. In rheumatoid arthritis-derived Treg cells, the Ser418 site was specifically dephosphorylated by protein phosphatase 1 (PP1), whose expression and enzymatic activity were induced in the inflamed synovium by tumor necrosis factor α (TNF-α), leading to impaired Treg cell function. Moreover, TNF-α-induced Treg cell dysfunction correlated with increased numbers of interleukin-17 (IL-17)(+) and interferon-γ (IFN-γ)(+)CD4(+) T cells within the inflamed synovium in rheumatoid arthritis. Treatment with a TNF-α-specific antibody restored Treg cell function in subjects with rheumatoid arthritis, which was associated with decreased PP1 expression and increased FOXP3 phosphorylation in Treg cells. Thus, TNF-α controls the balance between Treg cells and pathogenic TH17 and TH1 cells in the synovium of individuals with rheumatoid arthritis through FOXP3 dephosphorylation.	\N	\N
23399616	Tyrosine kinase inhibitors (TKIs) are increasingly common treatments for cancer; however, their effective use is hampered by unwanted side effects. One of the most common of these is TKI-induced diarrhea, although so far very little is known about its mechanisms and the best management approaches. As such, this review will briefly cover the extent of the problem, models for researching the problem and touch on future directions for management approaches to the problem. As there is a paucity of knowledge regarding the mechanisms of TKI-induced diarrhea in humans, this review will discuss the rodent models that have been used in the investigation of TKI-induced gut injury. This will be put into context with the pharmacological targets of TKIs and how this new information might help to better tailor treatment and management of patients on these drugs. The recognition of TKI-induced diarrhea as a significant treatment side effect has prompted efforts into uncovering the pathogenesis of this complication. This will enable future patients to be better managed throughout their treatment with these highly effective cancer drugs.	\N	\N
23399972	Blood pressure (BP) is characterized by marked short-term fluctuations occurring within a 24 h period (beat-to-beat, minute-to-minute, hour-to-hour, and day-to-night changes) and also by long-term fluctuations occurring over more-prolonged periods of time (days, weeks, months, seasons, and even years). Rather than representing 'background noise' or a randomly occurring phenomenon, these variations have been shown to be the result of complex interactions between extrinsic environmental and behavioural factors and intrinsic cardiovascular regulatory mechanisms. Although the adverse cardiovascular consequences of hypertension largely depend on absolute BP values, evidence from observational studies and post-hoc analyses of data from clinical trials have indicated that these outcomes might also depend on increased BP variability (BPV). Increased short-term and long-term BPV are associated with the development, progression, and severity of cardiac, vascular, and renal damage and with an increased risk of cardiovascular events and mortality. Of particular interest are the findings from post-hoc analyses of large intervention trials in hypertension, showing that within-patient visit-to-visit BPV is strongly prognostic for cardiovascular morbidity and mortality. This result has prompted discussion on whether antihypertensive treatment should be targeted not only towards reducing mean BP levels but also to stabilizing BPV with the aim of achieving consistent BP control over time, which might favour cardiovascular protection.	\N	\N
23404743	In 2010, guidelines published by the National Institute for Clinical Excellence (NICE) suggested a change in the way patients with stable chest pain of suspected cardiac origin were investigated. These guidelines removed exercise treadmill testing from routine use and introduced cardiac CT to regular use. To investigate whether these guidelines had improved our service provision by reducing the number of further investigations required to make a diagnosis, and to see if our costs had increased now that the less expensive exercise treadmill tests were not recommended. Clinic letters were used to assess patients pretest likelihood of coronary artery disease for two six-month cohorts of consecutive patients seen in the rapid access chest pain clinic (January-June 2010 and July-December 2011) using NICE published methodology, and to ascertain which investigations patients had. Using NICE modelled costs, we generated comparative hypothetical costs for each cohort and an average cost per patient. In the January-June 2010 cohort, 435 patients with chest pain were seen, and in July-December 2011, 334 patients were seen. In the pre-NICE guidelines cohort, 23% of patients required two investigations as compared with 11.4% in the post-NICE guidelines cohort, with no patient requiring three investigations as compared with 3% in the original cohort. There was no significant increase in costs per patient in the post-NICE guidance group. Implementing NICE guidance reduced the number of investigations needed per patient, and did not prove more expensive for our department in the short term.	\N	\N
23406712	The Centers for Medicare and Medicaid Services (CMS) require high-risk (HR) criteria for carotid artery stenting (CAS) reimbursement. The impact of these criteria on outcomes after carotid endarterectomy (CEA) and CAS remains uncertain. Additionally, if these HR criteria are associated with more adverse events after CAS, then existing comparative effectiveness analysis of CEA vs CAS may be biased. We sought to elucidate this using data from the SVS Vascular Registry. We analyzed 10,107 patients undergoing CEA (6370) and CAS (3737), stratified by CMS HR criteria. The primary endpoint was composite death, stroke, and myocardial infarction (MI) (major adverse cardiovascular event [MACE]) at 30 days. We compared baseline characteristics and outcomes using univariate and multivariable analyses. CAS patients were more likely to have preoperative stroke (26% vs 21%) or transient ischemic attack (23% vs 19%) than CEA. Although age ≥ 80 years was similar, CAS patients were more likely to have all other HR criteria. For CEA, HR patients had higher MACEs than normal risk in both symptomatic (7.3% vs 4.6%; P < .01) and asymptomatic patients (5% vs 2.2%; P < .0001). For CAS, HR status was not associated with a significant increase in MACE for symptomatic (9.1% vs 6.2%; P = .24) or asymptomatic patients (5.4% vs 4.2%; P = .61). All CAS patients had MACE rates similar to HR CEA. After multivariable risk adjustment, CAS had higher rates than CEA for MACE (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0-1.5), death (OR, 1.5; 95% CI, 1.0-2.2), and stroke (OR, 1.3; 95% CI,1.0-1.7), whereas there was no difference in MI (OR, 0.8; 95% CI, 0.6-1.3). Among CEA patients, age ≥ 80 (OR, 1.4; 95% CI, 1.02-1.8), congestive heart failure (OR, 1.7; 95% CI, 1.03-2.8), EF <30% (OR, 3.5; 95% CI, 1.6-7.7), angina (OR, 3.9; 95% CI, 1.6-9.9), contralateral occlusion (OR, 3.2; 95% CI, 2.1-4.7), and high anatomic lesion (OR, 2.7; 95% CI, 1.33-5.6) predicted MACE. Among CAS patients, recent MI (OR, 3.2; 95% CI, 1.5-7.0) was predictive, and radiation (OR, 0.6; 95% CI, 0.4-0.8) and restenosis (OR, 0.5; 95% CI, 0.3-0.96) were protective for MACE. Although CMS HR criteria can successfully discriminate a group of patients at HR for adverse events after CEA, certain CMS HR criteria are more important than others. However, CEA appears safer for the majority of patients with carotid disease. Among patients undergoing CAS, non-HR status may be limited to restenosis and radiation.	\N	\N
23408511	Intellectual disability is a condition characterized by significant limitations in cognitive abilities and social/behavioral adaptive skills and is an important reason for pediatric, neurologic, and genetic referrals. Approximately 10% of protein-encoding genes on the X chromosome are implicated in intellectual disability, and the corresponding intellectual disability is termed X-linked ID (XLID). Although few mutations and a small number of families have been identified and XLID is rare, collectively the impact of XLID is significant because patients usually are unable to fully participate in society. To reveal the molecular mechanisms of various intellectual disabilities and to suggest small molecules which by binding to the malfunctioning protein can reduce unwanted effects. Using various in silico methods we reveal the molecular mechanism of XLID in cases involving proteins with known 3D structure. The 3D structures were used to predict the effect of disease-causing missense mutations on the folding free energy, conformational dynamics, hydrogen bond network and, if appropriate, protein-protein binding free energy. It is shown that the vast majority of XLID mutation sites are outside the active pocket and are accessible from the water phase, thus providing the opportunity to alter their effect by binding appropriate small molecules in the vicinity of the mutation site. This observation is used to demonstrate, computationally and experimentally, that a particular condition, Snyder-Robinson syndrome caused by the G56S spermine synthase mutation, might be ameliorated by small molecule binding.	\N	\N
23409482	Although cutaneous amebiasis (CA) is a rare disease, it is a public health concern worldwide, particularly in developing nations. It gains importance because of its severe clinical course, which can be confused with other disorders. Therefore, knowledge of its clinical features, histopathology, and pathogenesis is essential. We present a retrospective analysis over 50 years of 26 patients with CA who were diagnosed and treated at 2 Mexican institutions. Our main focus was to draw clinical information to identify mechanisms by which amebae reach the skin, occurring in a relatively small percentage of infected individuals. The recorded data included age and sex of the patients, form of presentation, any associated illnesses and/or factors, and methods for diagnosis. Histologic slides were reviewed in all cases; cytologic preparations also were available for 6 cases. Most patients were male (overall male to female ratio, 1.9 to 1). The disease always presented as painful ulcers containing varying amounts of amebae microscopically; the amebae were fairly easy to identify with routine stains, particularly when examination of tissue or smears was prepared from the edges of the ulcer instead of the necrotic centers. Erythrophagocytosis by the trophozoites was found and represented an unequivocal sign of its pathogenicity. We review the 2 mechanisms by which the organisms reach the skin. Most cases resolve with the use of specific antiamebic drugs; however, if left untreated, progression is rapid and unrelenting, sometimes with massive destruction of skin and subcutaneous tissues. Therefore, CA is a particularly virulent form of amebiasis.	\N	\N
23412808	The use of natural remedies and pharmacological mineral supplements for liver disease treatment has a long history. In present study, the levels of selenium (Se) and zinc (Zn) were determined in biological samples (serum and whole blood) of female hepatitis C patients (n = 132), age ranged 30-45 years, before and after 30 days treatment with herbal/pharmaceutical supplements. For comparative study, 128 age-matched female subjects, residing in the same residential areas and have socioeconomic status, were selected as referents. The Se and Zn in supplements, blood, and sera were determined by atomic absorption spectrometry. It was observed that Zn and Se in blood and serum samples of viral hepatitis C (HCV) patients were reduced in the range of 28.6-39 % and 24-36 %, respectively, as compared to those of referents. After herbal/pharmaceutical supplementations, 20.6-25.0 and 9.15-13.2 % of Zn and 10.6-12.1 and 19.6-21.4 % of Se were enhanced in sera and blood samples of HCV patients, respectively. The resulted data indicated that the levels of Se and Zn in addition to some biochemical parameters were improved in HCV patients after herbal/pharmaceutical supplementation. The effects of both supplements were not significantly different (p > 0.05).	\N	\N
23412860	We report 20 infants aged between 1 month and 6 months found to have subdural bleeding and also multiple unexplained fractures in a pattern similar to that described earlier as temporary brittle bone disease. Child abuse seemed unlikely as a cause of the fractures as in no case was there clinical evidence of injury commensurate with the fracturing, as some patients had fractures while in hospital and as metaphyseal lesions, when present, were often symmetrical in distribution. Abuse seemed unlikely to have been the cause of the subdural bleeding in several patients; three had clear histories of accidental injury and five had evidence that the initial bleeding was likely to have taken place at birth. Abuse also seemed unlikely as the cause of the syndrome; the nine patients who were returned to their parents had no subsequent allegations of abuse with a mean follow-up period of 15.8 years. The finding of hypermobile joints in the parents of eight of the children is an additional pointer to a natural cause for this condition. The cause of this combination of fractures and subdural bleeding is not yet clear but it is important to be aware that it can result from natural disease.	\N	\N
23423257	Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitides characterized by small-to-medium-sized blood vessel vasculitis and the presence of ANCA. Although our understanding of the causes of AAV remains limited, new information supporting an autoimmune basis is emerging. This review highlights recent progresses in etiology, pathogenesis, classification, and treatment. A genome-wide association study has confirmed a role for genetic susceptibility in AAV, and links between environmental factors and AAV induction through abnormal neutrophil extracellular traps has been demonstrated. Ongoing international consensus initiatives have revised approaches to the classification of vasculitis that has been enhanced by the analysis of large-scale prospective clinical data sets. New autoantibodies to human lysosome-associated membrane protein-2 antibody, moesin, and plasminogen have been detected in AAV sera and a prognostic classification of renal biopsies developed. Clinical trial networks have extended the evidence base for the treatment of AAV, and rituximab has emerged as an alternative to cyclophosphamide for remission induction. Long-term outcomes following current treatment strategies have been determined and increased risks for cardiovascular and malignant disease reported.	\N	\N
23425809	Liver diseases are responsible for metabolic disturbances and the loss of muscle mass and function. This study aims to correlate maximal oxygen uptake (VO2max) with the Model for End Stage Liver Disease (MELD) severity score and associate VO2max with mortality in patients with alcoholic cirrhosis. This prospective study included 27 patients who had a diagnosis of alcoholic liver cirrhosis. All subjects were followed for 3 years and performed an exercise test to determine VO2max. The study included 18 men and 9 women. We observed a strong inverse correlation between VO2max and MELD (r=-0.91, p<0.001). In a survival analysis, individuals who had a VO2max less than 14mL/kg showed 60% mortality when compared with those who had a VO2max greater than 14mL/kg (p<0.0001; OR: 3.29; 95% CI: 1.44-5.25). The VO2max is directly associated with the survival of patients with alcoholic cirrhosis and demonstrates a strong inverse correlation with the MELD severity score.	\N	\N
23440103	We hereby report two patients with parathyroid carcinoma presenting extremely high calcium and PTH levels, severe bone disease, and palpable neck mass at diagnosis. They both underwent parathyroidectomy, and one of them evolved to lung metastasis. Important hypocalcemia was observed after surgery in both: after parathyroidectomy in one patient, and only after surgical removal of the metastasis in the other. Both required intravenous calcium replacement, thus revealing hungry bone syndrome (HBS). HBS usually reflects rapid mineralization after correction of hyperparathyroidism. The more severe the bone disease before surgery, the more prone the patient is to HBS after surgery. Despite being an unfavorable outcome, HBS state suggests that surgical removal of hypersecretory parathyroid tissue was accomplished. In this study, HBS was observed in both patients, who presented severe bone disease prior to surgery. HBS would be expected post-operatively in successful parathyroid carcinoma removal.	\N	\N
23442763	The relationship between cytomegalovirus (CMV) infection and mortality among immunocompetent individuals is uncertain. We aimed to examine whether seropositivity for CMV and the level of CMV immunoglobulin G (IgG) antibody are associated with all-cause and cause-specific mortality. We used data from a random sample of 13 090 participants aged 40-79 years at recruitment in 1993-1997 to the European Prospective Investigation of Cancer-Norfolk population-based cohort study. We measured baseline IgG antibody levels against CMV. Death certificates were obtained for all participants who died before 31 March 2011. Codes for the underlying cause of death were used to investigate cause-specific mortality. A total of 2514 deaths occurred during a mean follow-up of 14.3 years (SD, 3.3 years). Compared to seronegative participants (age- and sex-adjusted mortality rate, 12.4 [95% confidence interval {CI}, 11.3-13.2] per 1000 person-years at risk), rates increased across thirds of IgG antibody levels (score test of trend P < .0001). CMV seropositivity (prevalence 59%) was associated with increased all-cause mortality (age- and sex-adjusted hazard ratio [HR], 1.16 [95% CI, 1.07-1.26]), similarly in men and women (P for interaction = .52). The association persisted after additionally adjusting for measures of socioeconomic status and possible confounders. Cause-specific analyses suggested that increased mortality from cardiovascular disease (HR, 1.06 [95% CI, .91-1.24]), cancer (HR, 1.13 [95% CI, .98-1.31]), and other causes (HR, 1.23 [95% CI, 1.04-1.47) all appeared to contribute to the overall associations. Seropositivity and higher IgG antibody levels against CMV are associated with increased mortality and after adjustment for a range of potential confounders in the general population.	\N	\N
23443955	Radioiodine (RAI) is used in the treatment of hyperthyroidism and differentiated thyroid cancer. Radioiodine therapy is associated with dry eyes and some side effects are seen especially due to beta rays. In this study, the functional and cytological status of lacrimal glands after RAI therapy was evaluated. Twenty-five patients with a mean age of 55.16 years with planned low-dose RAI therapy were evaluated. Just before and 6 months after the treatment, the lacrimal glands were evaluated with tear break-up time (BUT), Schirmer's test, impression cytology and "Ocular Surface Disease Index (OSDI)" questionnaire. The mean value of Schirmer's test was 16.20 ± 3.61 pre-treatment and 11.28 ± 4.39 post-treatment for the right eye, and 15.76 ± 3.27 and 10.60 ± 4.42 for the left eye, respectively. The mean value of Schirmer's test decreased significantly post-treatment in both eyes (p = 0.0001). The BUT score also decreased significantly post-treatment (p = 0.001). The mean value of OSDI score was 27.5 ± 8.02 pre-treatment and 46.36 ± 10.27 post-treatment. The mean value of OSDI score increased post-treatment (p = 0.0001). The impression scores also increased post-treatment in both eyes (p = 0.0001). Even low-dose (≤30 mci) RAI treatment affects lacrimal gland functions. Low-dose RAI causes a decrease in the value of Schirmer's test and the BUT test, and an increase in the value of OSDI score and impression scores.	\N	\N
23444587	In this paper, we explore the benefits of storytelling in health communication and, in particular, immunization education. During the mid-20th century polio epidemic, both personal stories and scientific information abounded in the media. However, as rates of vaccine-preventable diseases declined, narratives about the dangers of such diseases faded as did the public fear of them. Meanwhile, anti-vaccine advocates flooded the media and Internet with stories of injured children and tied those injuries, such as autism, to vaccines. Medical experts often counter anti-vaccine concerns with scientific information which can fail to persuade parents. Furthermore, evidence suggests that many people misunderstand quantitative information resulting in a misinterpretation of risk. Compared to scientific information, stories relate life lessons and values. They are effective because they are memorable and relatable. Evidence also suggests that storytelling can effectively improve health knowledge and behaviors. Inspired by In Harm's Way--True Stories of Uninsured Texas Children by the Children's Defense Fund and Faces of Influenza by the American Lung Association, we published Vaccine-Preventable Disease: The Forgotten Story, a collection of photographs and personal stories of families affected by vaccine-preventable diseases. We have found that the stories included in our booklet capture all the benefits of storytelling. Given the many benefits of storytelling, providers should strive to include stories along with medical facts in their daily practice.	\N	\N
23446227	Neuroendocrine tumors (NET) are malignant solid tumors that arise in hormone-secreting tissue of the diffuse neuroendocrine system or endocrine glands. Although traditionally understood to be a rare disease, the incidence and prevalence of NET have increased greatly in the past 3 decades. However, during this time, progress in diagnosis and outcome of NET has generally been modest. In order to achieve improved outcome in NET, a better understanding of NET biology combined with more reliable serum markers and better techniques to identify tumor localization and small lesions are needed. Although some NET biomarkers exist, sensitive and specific markers that predict tumor growth and behavior are generally lacking. In addition, the integration of new molecular imaging technologies in patient diagnosis and follow-up has the potential to enhance care. To discuss developments and issues required to improve diagnostics and management of NET patients, with specific focus on the latest advances in molecular imaging and biomarker science, 17 global leaders in the fields of NET, molecular imaging and biomarker technology gathered to participate in a 2-day meeting hosted by Prof. Kjell Öberg at the University of Uppsala in Sweden. During this time, findings were presented regarding methods with potential prognostic and treatment applications in NET or other types of cancers. This paper describes the symposium presentations and resulting discussions.	\N	\N
23447119	Erdheim-Chester disease (ECD) is a rare, non-Langerhans form of histiocytosis of unknown origin with distinct clinicopathologic and radiographic features. Reports detailing the cytology of ECD are rare. We describe a case of ECD with pericardial effusion. Cytologic examination revealed a hypercellular specimen composed of clusters and singly dispersed foamy macrophages with round nuclei and inconspicuous nucleoli, admixed with lymphocytes, eosinophils, and Touton-type multinucleated giant cells. Immunostains for CD68 were strongly positive in the foamy macrophages while S100 and CD1a were negative. The presence of foamy histiocytes, multinucleated giant cells, lymphocytes and eosinophils are also features of other systemic histiocytic disorders, including Langerhans cell histiocytosis (LCH), Rosai-Dorfman disease (RDD) and sarcoidosis. To the best of out knowledge, this is the first report describing the cytological features of ECD in a pericardial effusion.	\N	\N
23449087	Single cell genomics has made increasingly significant contributions to our understanding of the role that somatic genome variations play in human neuronal diversity and brain diseases. Studying intercellular genome and epigenome variations has provided new clues to the delineation of molecular mechanisms that regulate development, function and plasticity of the human central nervous system (CNS). It has been shown that changes of genomic content and epigenetic profiling at single cell level are involved in the pathogenesis of neuropsychiatric diseases (schizophrenia, mental retardation (intellectual/leaning disability), autism, Alzheimer's disease etc.). Additionally, several brain diseases were found to be associated with genome and chromosome instability (copy number variations, aneuploidy) variably affecting cell populations of the human CNS. The present review focuses on the latest advances of single cell genomics, which have led to a better understanding of molecular mechanisms of neuronal diversity and neuropsychiatric diseases, in the light of dynamically developing fields of systems biology and "omics".	\N	\N
23451796	Lowering blood glucose with insulin therapy towards beneficial target levels while also avoiding hypoglycaemia is a challenging task. An important confounding factor, which might be under-appreciated in this scenario, is that of variable glucose readings causing difficulties with dose adjustment. Furthermore, this glucose variability is, to some extent, a reflection of variability in the glucose-lowering action of the insulin therapy itself. Not only is glucose variability a major confounding factor in disease management but it is possibly also of direct prognostic consequence and is increasingly recognized as an informative measurement in diabetes management. The scope for insulin-induced glucose variability is particularly great with basal insulins because of their prolonged absorption from high-dose depots. Pharmacodynamic (PD) variability manifests as both fluctuations in the level of glucose-lowering effect over time, and as inconsistencies in the response from one injection to another. Well-controlled pharmacokinetic (PK)/PD studies using repeated isoglycaemic clamp methodology clearly how that many injected basal insulin products have high variable absorption with correspondingly variable action. Incomplete resuspension and precipitation appear to be important issues with regard to unpredictability in this action, while an inadequate duration of action relative to the dosing interval results in a fluctuating action profile. There are some ultra-long-acting basal insulins with novel protraction mechanisms currently in clinical development for which clamp studies show markedly improved PK/PD profiles.	\N	\N
23456185	The temporal lobe is of importance for visuospatial orientation. Intracranial arachnoid cysts have a predilection for the temporal fossa, and might therefore affect visuospatial orientation. The aim was to find out whether temporal cysts affect maze learning and if surgical cyst decompression improves maze performance. Forty-five patients with a temporal arachnoid cyst and 17 control patients with cervical disc disease were tested in a labyrinth route in the hospital corridors the day before surgery and at least 3 months postoperatively. Thirty-five cyst patients (78 %) experienced postoperative improvement of their preoperative complaints. The cyst patients spent significantly longer time than the controls navigating through the maze in the preoperative test, 161 s and 127 s, respectively, but there was no difference in number of errors between the two groups. However, the cyst patients improved significantly in the postoperative test, both with regards to number of errors they made and time spent, contrary to the control patients, whose postoperative performance equalled that of the preoperative test. For the cyst patients, postoperative improvement in the labyrinth test correlated with the clinical outcome-but not the neuroradiological outcome-after the operation. Thus, temporal arachnoid cysts may affect visuospatial orientation and learning in a reversible manner.	\N	\N
23459906	this paper reports the results of a nursing-administered theory-based intervention, the "Moving Heart Program", based on the implementation intention theory and pointed at improving physical activity adherence among coronary heart disease outpatients in Brazil. this experimental study applied assessments at baseline, 1 and 2 months after baseline. The Consolidated Standards of Reporting Trials statement was followed. Participants were randomly assigned to intervention, comprising action and coping plans on how to deal with anticipated barriers (n=69), or a standard-care control group (n=67). participants submitted to the intervention showed significant higher levels of physical activity 2 months after baseline and were significantly more active than the control group. the results indicate that the intervention is feasible for patients with coronary heart disease and can be a useful tool to facilitate intended lifestyle changes. This study brings relevant contributions to the Nursing field and other health-related areas, once the intervention presents low cost to health services and can be applied in cardiac rehabilitation programs, showing significant benefits to participants.	\N	\N
23462063	To assess the effectiveness of flow reversal as an alternative means of cerebral protection by using transcranial Doppler recordings and diffusion-weighted imaging (DWI) as surrogate markers of brain injury. Eighteen patients with symptomatic carotid artery disease were recruited. Magnetic resonance imaging was performed before the intervention and at 3 and 24 hours and 30 days after the intervention to detect new ischemic lesions with DWI. Transcranial Doppler recordings were made during the procedure to assess for microembolic signals (MESs). Data were compared against data from a historical control cohort of patients who underwent CAS placement with or without filter protection (n = 15 each) under the same protocol in a different study. There were fewer periprocedural new lesions on DWI in the reverse-flow cohort compared with the historical control cohort with filter protection (P = .084). Reverse flow revealed significantly fewer MESs during the whole procedure compared with the filter-protected group (P = .01) but not the unprotected group (P = .55). There was a marked decrease in MES counts for reverse flow protection during the embologenic stages of the procedure (P = .004). Use of the reverse flow device was associated with fewer overall lesions on DWI and proportionately fewer positive scans compared with the use of filter-type devices (P = .08, not significant). Transcranial Doppler recordings demonstrated a significant reduction in embolization to the brain during carotid artery stent placement with the use of reverse-flow cerebral protection.	\N	\N
23462484	Patients suffering from Parkinson's disease (PD) frequently experience painful sensations that may be due to central modification of nociception in PD. We compared pain thresholds and cerebral activity in nociceptive areas using Positron Emission Tomography (PET) during nociceptive stimulation before (OFF condition) and after (ON condition) levodopa challenge between nine PD patients with and nine PD patients without neuropathic pain. Pain thresholds were determined using a cold pressor test in the two conditions. We used H2(15)O PET to study the regional cerebral blood flow changes in subjects while they received alternate randomized noxious and innocuous cold stimuli during OFF and ON periods. Pain thresholds were not significantly different between PD patients with and without pain in either condition (OFF and ON). In both groups of PD patients, levodopa significantly raised pain threshold (F1,16 = 26.71; p < 0.0001) with a mean variation of -2.7 (±2.3 °C). In the OFF condition, PD patients with pain had a lower pain activation in the right prefrontal cortex and posterior insula and a higher pain activation in the right anterior cingulate cortex (BA32/8) than pain-free patients. Levodopa significantly reduced pain-induced-activation in the right insula and in the anterior cingulate cortex in both groups. Levodopa decreased nociceptive perception in both PD patients with and without pain. In PD patients with neuropathic pain the medial affective pathway was preferentially recruited whereas pain-free PD patients exhibited a greater activation in lateral discriminative nociceptive areas.	\N	\N
23462618	The objective of this study was to compare the toxicological effects of different source-related ambient PM10 samples in regard to their chemical composition. In this context we investigated airborne PM from different sites in Aachen, Germany. For the toxicological investigation human alveolar epithelial cells (A549) and murine macrophages (RAW264.7) were exposed from 0 to 96 h to increasing PM concentrations (0-100 μg/ml) followed by analyses of cell viability, pro-inflammatory and oxidative stress responses. The chemical analysis of these particles indicated the presence of 21 elements, water-soluble ions and PAHs. The toxicological investigations of the PM10 samples demonstrated a concentration- and time-dependent decrease in cell viability and an increase in pro-inflammatory and oxidative stress markers.	\N	\N
23470563	The IGF-I receptor (IGF-IR) has an important role in malignant disease and is the target of several drugs presently in clinical trials. Gene therapy has been explored as cancer treatment, mainly for delivery of genes that induce cell death or enhance the immunological response to cancer. Previously, we have shown that the implantation of autologous bone-marrow stromal cells producing a soluble form of IGF-IR (sIGFIR) inhibited experimental liver metastasis of several tumor types in mice. Here, we evaluated the utility of adenovirus-based gene delivery for generating therapeutically effective plasma levels of this decoy. We constructed a third generation gutless adenovirus expressing sIGFIR and found that HEK-293 cells transduced by this, but not control adenoviruses, secreted soluble receptor protein that blocked IGF-I-induced tumor cell migration, proliferation and survival in vitro. Following virus injection in vivo, viral DNA was detectable by PCR in several host organs, particularly the liver, and this resulted in the production of measurable sIGFIR plasma levels for up to 21 days post injection. In mice producing virus-encoded sIGFIR, experimental liver metastasis was inhibited, indicating that sIGFIR levels were therapeutically effective. The results show that adenovirus-based delivery of inhibitory soluble proteins can provide an effective anticancer strategy.	\N	\N
23475581	Tissue oxidative stress is a common hallmark of atherosclerosis and non-alcoholic steatohepatitis (NASH), 2 conditions linked epidemiologically and pathophysiologically. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of inducible antioxidant responses, that can attenuate cellular injury from oxidative stress induced by obesity and other redox insults. Nrf2 expression and activation is reduced in mouse and human vessels that harbor accelerated atherosclerosis and in livers with histologic criteria of NASH. Systemic antioxidants have thus been attractive therapeutic targets, but clinical trials have been largely unsuccessful in improving cardiovascular health. Macrophage-selective Nrf2 activation may, however, provide an approach to reduce vascular and hepatocyte injury without the complications of systemic antioxidants, since macrophages play key roles in the development and progression of both atherosclerosis and NASH. In this article, we review the common mechanisms of oxidative stress and inflammation in atherosclerosis and NASH, and discuss the role of Nrf2 in vascular and hepatocyte protection.	\N	\N
23478151	Primary carcinoid tumors of the kidney are very rare, malignant tumors consisting of neuroendocrine cells. The pathogenesis of renal carcinoid is unclear because neuroendocrine cells are not normally found in adult renal parenchyma. Electron microscopy, immunohistochemistry, octreotide scan, positron emission tomography along with conventional radiographic imaging techniques are used in diagnosis and follow-up. Presenting symptoms usually include flank pain and haematuria. Early stage disease is treated with surgery only. However, randomized trials are lacking because of the very low number of reported cases. Thus, the role of debulking surgery, chemotherapy, radiotherapy, octreotide and targeted therapy in the management of advanced disease remains an open question. In this article the clinicopathologic features and prognosis of this very rare disease along with treatment outcomes of the reported cases are reviewed. In addition, we report a new case of a metastatic primary renal atypical carcinoid tumor treated with octreotide therapy.	\N	\N
23479135	Platinum-based chemotherapy is the most common treatment for patients with advanced non-small cell lung cancer (NSCLC). Genetic polymorphisms in the base excision repair (BER) pathway are suspected to influence the response of patients to this type of therapy. In this study, we investigated whether nonsynonymous single nucleotide polymorphisms (SNPs) in the BER pathway were associated with the response, progression-free survival (PFS) and overall survival (OS) of NSCLC patients following platinum-based chemotherapy. We used TaqMan to genotype four SNPs (APE1 Asp148Glu, PARP1 Va1762Ala, XRCC1 Arg194Trp and XRCC1 Arg399Gln) in 147 patients with advanced NSCLC who had undergone routine platinum-based chemotherapy. Logistic regression analysis showed that subjects with the XRCC1-399 A allele had a significantly better response to platinum-based chemotherapy than those with the XRCC1-399 GG genotype (AA/AG vs. GG: adjusted OR = 2.35, 95 % CI = 1.11-5.00). Furthermore, multivariate Cox proportional hazard regression analysis showed that the PARP1-762 CC genotype was a significantly unfavorable prognostic factor for PFS (CC vs. CT/TT: adjusted HR = 1.90, 95 % CI = 1.02-3.52). In contrast, the APE1-148 GG genotype was a significantly protective prognostic factor for OS (GG vs. TT: adjusted HR = 0.33, 95 % CI = 0.12-0.92). We found that XRCC1 Arg399Gln, PARP1 Va1762Ala and APE1 Asp148Glu SNPs in the BER pathway may influence the prognosis of advanced NSCLC patients following platinum-based chemotherapy.	\N	\N
23484318	To increase the death rate of fatal anaphylaxis in guinea pigs and the detectahie level of the tryptase of mast cell in hlood serum. Seventy-four guinea pigs were randomly divided into five groups: original model group, original model control group, improved model group, improved model control group, improved model with non-anaphylaxis group. Using mixed human serum as the allergen, the way of injection, sensitization and induction were improved. ELISA was used to detect the serum mast cell tryptase and total IgE in guinea pigs of each group. The death rate of fatal anaphylaxis in original model group was 54.2% with the different degree of hemopericardium. The severe pericardial tamponade appeared in 9 guinea pigs in original model group and original model control group. The death rate of fatal anaphylaxis in improved model group was 75% without pericardial tamponade. The concentration of the serum total IgE showed no statistically difference hetween original model group and original model control group (P > 0.05), hut the serum mast cell tryptase level was higher in the original model group than that in the original model control group (P > 0.05). The concentration of the serum total IgE and the serum mast cell tryptase level were significantly higher in improved model group than that in the improved model control group (P < 0.05). The death rate of the improved model significantly increases, which can provide effective animal model for the study of serum total IgE and mast cell tryptase.	\N	\N
23484512	An increasing number of people with mild cognitive impairment (MCI) visits a memory clinic to find out whether their symptoms indicate Alzheimer's disease (AD). Markers in cerebrospinal fluid are increasingly used for the diagnosis of Alzheimer's disease. In the short term, CSF biomarkers are more accurate in ruling out progression to AD-type dementia than demonstrating progression. The predictive value of the CSF biomarkers increases with longer-duration follow-up and declines with age. The added value of CSF biomarkers is not yet clear in MCI patients in whom extensive clinical, neuropsychological examination or imaging have already been performed.	\N	\N
23485507	An optimal prostate biopsy in clinical practice is based on a balance among adequate detection of clinically significant prostate cancers (sensitivity), assuredness regarding the accuracy of negative sampling (negative predictive value), limited detection of clinically insignificant cancers and good concordance with whole gland surgical pathology results to allow accurate risk stratification and disease localization for treatment selection. Inherent within this optimization is variation of the core number, location, labeling and processing for pathological evaluation. To date, there is no consensus in this regard. The purpose of this review is to 1) define the optimal number and location of biopsy cores during primary prostate biopsy among men with suspected prostate cancer, 2) define the optimal method of labeling prostate biopsy cores for pathological processing which will provide relevant and necessary clinical information for all potential clinical scenarios, and 3) determine the maximal number of prostate biopsy cores allowable within a specimen jar which would not preclude accurate histological evaluation of the tissue. A bibliographic search using PubMed® covering the period up to July 2012 yielded approximately 550 articles. Articles were reviewed and categorized based on which of the 3 objectives of this review was addressed. Data were extracted, analyzed and summarized. Recommendations are provided based on this literature review and our clinical experience. The use of 10 to 12-core extended sampling protocols increases cancer detection rates compared to traditional sextant sampling methods and reduces the likelihood of repeat biopsy by increasing negative predictive value, ultimately allowing more accurate risk stratification without increasing the likelihood of detecting insignificant cancers. As the number of cores increases above 12, the increase in diagnostic yield becomes marginal. Only limited evidence supports the use of initial biopsy schemes involving more than 12 cores or saturation. Apical and laterally directed sampling of the peripheral zone increases cancer detection rate, reduces the need for repeat biopsies and predicts pathological features on prostatectomy while transition zone biopsies do not. There are little data to suggest that knowing the exact site of an individual positive biopsy core provides meaningful clinical information. However, determining laterality of cancer on biopsy may be helpful for predicting sites of extracapsular extension and therapeutic planning. Placement of multiple biopsy cores in a single container (greater than 2) appears to compromise pathological evaluation, which can reduce cancer detection rate and increase the likelihood of equivocal diagnoses. A 12-core systematic biopsy that incorporates apical and far-lateral cores in the template distribution allows maximal cancer detection, avoids repeat biopsy, and provides information adequate for identifying men who need therapy and planning that therapy while minimizing the detection of occult, indolent prostate cancers. This literature review does not provide compelling evidence that individual site specific labeling of cores benefits clinical decision making regarding the management of prostate cancer. Based on the available literature, we recommend packaging no more than 2 cores in each jar to avoid reduction of the cancer detection rate through inadequate tissue sampling.	\N	\N
23494361	Disseminated intravascular coagulation (DIC) is a life-threatening complication, and its control is essential for therapeutic success. Recombinant human soluble thrombomodulin alfa (rTM) is a novel therapeutic agent for DIC. The efficacy of rTM in the treatment of DIC is reportedly superior to that of conventional anti-DIC treatments, such as unfractionated heparin or low molecular weight heparin, but hemorrhagic events occasionally interfere with the therapeutic benefits of rTM. We assessed the clinical features of 20 consecutive patients who were given rTM for DIC associated with various hematologic disorders. Eight patients achieved remission of both primary disease and DIC, eight died due to progression of the primary disease, and four died of various hemorrhagic complications. Assessment of 16 biomarkers for coagulation showed that the four patients who died of hemorrhagic complications despite remission of their primary disease showed lower ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin Type 1 motif, member 13) plasma activity than other patients (P = 0.016). The optimal cut-off level of ADAMTS-13 for predicting risk of hemorrhagic complications was 42 % (P = 0.007). Plasma ADAMTS-13 activity determined at diagnosis of DIC may help predict the risk of hemorrhagic events during and/or following DIC treatment with hematologic disorders.	\N	\N
23494513	The use of self-expandable metal stents (SEMS) for the treatment of malignant colorectal obstruction is increasing. However, results of risk factors for its complications are inconsistent. This study aimed to examine the clinical effectiveness of the procedure as well as the complications and risk factors associated with the complications. Medical records of patients with malignant colorectal obstruction who underwent endoscopic placement of covered or uncovered SEMS were reviewed retrospectively. The procedure was performed by two endoscopists with experience in pancreatobiliary endoscopy. A total of 152 patients were included (102 men; mean age, 70 ± 12.5 years). The procedure was performed for palliative management in 83 patients and performed as a bridge to surgery in 69 patients. There were 111 uncovered stents and 41 covered stents. The technical success rate was 100% and the clinical success rate 94.1%. Overall complications were observed in 49 patients (32.2%) during the follow-up period (median, 98 days; interquartile range, 19-302 days). Obstruction (17.1%), migration (7.9%), perforation (5.2%), bleeding (1.3%), and tenesmus (0.7%) were the causes of the complications. Stage IV disease, carcinomatosis peritonei, complete obstruction of the colon, palliative intention, and covered stents increased the complications based on the univariate analysis. Multivariate analysis revealed that complete obstruction of the colon and covered stents were significantly independent risk factors for complications. In the palliative group, Kaplan-Meier analysis showed significantly shorter median duration to the onset of complications in the covered stent group than in the uncovered stent group. Although SEMS in patients with malignant colorectal obstruction is effective both as palliative therapy and as a bridge to surgery, one-third of patients experienced complications. Severity of obstruction and stent type can influence outcomes.	\N	\N
23510013	Children with disabilities are two to three times more likely to become overweight or obese than typically developing children. Children with spina bifida (SB) are at particular risk, yet obesity prevalence and weight management with this population are under-researched. This retrospective chart review explored how weight is assessed and discussed in a children's SB outpatient clinic. Height/weight data were extracted from records of children aged 2-18 with a diagnosis of SB attending an outpatient clinic at least once between June 2009-2011. Body mass index was calculated and classified using Centers for Disease Control and Prevention cut-offs. Notes around weight, diet and physical/sedentary activities were transcribed verbatim and analysed using descriptive thematic analysis. Of 180 eligible patients identified, only 63 records had sufficient data to calculate BMI; 15 patients were overweight (23.81%) and 11 obese (17.46%). Weight and physical activity discussions were typically related to function (e.g. mobility, pain). Diet discussions focused on bowel and bladder function and dietary challenges. Anthropometrics were infrequently recorded, leaving an incomplete picture of weight status in children with SB and suggesting that weight is not prioritised. Bowel/bladder function was highlighted over other benefits of a healthy body weight, indicating that health promotion opportunities are being missed. Implications for Rehabilitation It is important to assess, categorise and record anthropometric data for children and youth with spina bifida as they may be at particular risk of excess weight. Information around weight categorisation should be discussed openly and non-judgmentally with children and their families. Health promotion opportunities may be missed by focusing solely on symptom management or function. Healthcare professionals should emphasise the broad benefits of healthy eating and physical activity, offering strategies to enable the child to incorporate healthy lifestyle behaviours appropriate to their level of ability.	\N	\N
23511908	Corticostriatal projections are essential components of forebrain circuits and are widely involved in motivated behaviour. These axonal projections are formed by two distinct classes of cortical neurons, intratelencephalic (IT) and pyramidal tract (PT) neurons. Convergent evidence points to IT versus PT differentiation of the corticostriatal system at all levels of functional organization, from cellular signalling mechanisms to circuit topology. There is also growing evidence for IT/PT imbalance as an aetiological factor in neurodevelopmental, neuropsychiatric and movement disorders - autism, amyotrophic lateral sclerosis, obsessive-compulsive disorder, schizophrenia, Huntington's and Parkinson's diseases and major depression are highlighted here.	\N	\N
23515578	Disturbances in proteostasis are observed in many neurodegenerative diseases. This leads to activation of protein quality control to restore proteostasis, with a key role for the removal of aberrant proteins by proteolysis. The unfolded protein response (UPR) is a protein quality control mechanism of the endoplasmic reticulum (ER) that is activated in several neurodegenerative diseases. Recently we showed that the major proteolytic pathway during UPR activation is via the autophagy/lysosomal system. Here we investigate UPR induction if the other major proteolytic pathway of the ER -ER associated degradation (ERAD)-is inhibited. Surprisingly, impairment of ERAD results in decreased UPR activation and protects against ER stress toxicity. Autophagy induction is not affected under these conditions, however, a striking relocalization of the lysosomes is observed. Our data suggest that a protective UPR-modulating mechanism is activated if ERAD is inhibited, which involves lysosomes. Our data provide insight in the cross-talk between proteolytic pathways involved in ER proteostasis. This has implications for neurodegenerative diseases like Alzheimer's disease where disturbed ER proteostasis and proteolytic impairment are early phenomena in the pathology.	\N	\N
23523498	Unicompartmental knee arthroplasty (UKA) is a less invasive treatment for medial gonarthrosis. However, registry data have demonstrated higher revision and early failure rates. The purpose of this study is to report the early survivorship and failure modes in a series of 1000 consecutive medial mobile bearing UKA. UKA patients with a minimum of 2 year follow-up or those meeting the study endpoint (UKA failure or death) were included. Demographic variables, pre and post-operative clinical variables, and mode of failure were analyzed. Eight hundred and thirty-nine knees were included in the analysis. Forty revisions were performed at an average of 23.1 months (range, 2.3-74.2) following UKA for a survivorship of 95.2%. Indications for revision were aseptic loosening (15), tibial collapse (7), mobile bearing dislocation (2), persistent pain (12), progression of disease (2), infection (1), and tibiofemoral instability (1). These results are from a single center and may not be comparable to those of larger reports such as national registries.	\N	\N
23526950	Transformation is a complex process, involving many changes in the cell. In this work, we investigated the transcriptional changes that arose during the development of squamous cell carcinoma (SCC) in mice. Using microarray analysis, we looked at gene expression during different stages in cancer progression in 31 mice. By analyzing tumor progression in each mouse separately, we were able to define the global changes that were common to all 31 mice, as well as significant changes that occurred in fewer individuals. We found that different genes can contribute to the tumorigenic process in different mice, and that there are many ways to acquire the malignant properties defined by Hanahan and Weinberg as "hallmarks of cancer". Eventually, however, all these changes lead to a very similar cancerous phenotype. The finding that gene expression is strongly heterogeneous in tumors that were induced by a standardized protocol in closely related mice underscores the need for molecular characterization of human tumors and personalized therapy.	\N	\N
23528171	Surgical resection of lung metastases of epithelial and mesenchymal tumors has an irreplaceable position in the complex treatment of advanced stages of these malignancies. Among the most significant prognostic factors affecting longterm survival of these patients are: parameter of complete resection, number and size of metastases, histological type of primary tumor, lymph node involvement, DFI (Disease Free Interval) and biological aggressiveness of the tumor or TDT (Tumor Doubling Time). retrospective analysis of patients with lung metastases of epithelial and mesenchymal tumors operated on at the I. Department of Surgery from 2005 to 2011. The authors present a set of 50 patients and evaluation of their age, gender, type of primary tumor, number of metastases, occurrence of bilateral metastases, repeat metastasectomies, duration of DFI, type of operation and selected approach and performance of mediastinal lymphadenectomy. The probability of five-year survival, relationship between survival on DFI, difference in survival between metastases of colorectal cancer versus renal cancer and the influence of repeated metastasectomies and number of metastases on survival were statistically analyzed. Sixty operations were performed on a set of 50 patients (average age 61.2 years). Forty-two procedures were performed by thoracotomic approach. A solitary metastasis was discovered in 43 patients; in 8 patients, more than 3 metastases were resected. Repeated metastasectomies were performed 10 times. Mediastinal lymphadenectomy was performed in 21 cases. The most frequent procedure was extraanatomic resection (28×). Fourteen patients had DFI < 12 months, 19 patients had DFI 12-36 months and 17 patients had DFI > 36 months. Average survival was 66.9 months; the probability of five-year survival was 0.549 (54.9%). A relationship between DFI and survival was not discovered. There was no statistically significant difference in survival after metastasectomy for colorectal cancer and renal cancer. A relationship between survival interval and number of metastases and repeated metastasectomies was not discovered. Surgical resection of lung metastases plays an important role in multidisciplinary care, assuming a precise selection of patients indicated for this treatment. When properly adhering to the indication criteria, very positive results of long-term survival may be expected.	\N	\N
23537409	Nitric oxide (NO) is involved in the regulation of several physiological processes such as vascular homeostasis. Exogenous NO supply offers major therapeutic interest, especially in the treatment of coronary artery disease, ischemic syndromes and other cardiovascular pathologies. Nevertheless, the administration of NO itself is limited by its short half-life. NO prodrugs have been marketed for decades, e.g. organic nitrates for angina pectoris. These prodrugs display undeniable advantages such as angina crisis relief and preconditioning effect. Nevertheless, they suffer from several drawbacks: toxicity, tolerance, endothelial dysfunction exacerbation. These negative effects are related to massive production of reactive species derived from oxygen or nitrogen, which trigger oxidative and nitrosative stress. New NO donors are under development to overcome those disadvantages, among which the S-nitrosothiols family seems especially promising.	\N	\N
23539255	Laparoscopy-assisted total gastrectomy (LATG) has been used more frequently despite the associated technical difficulty and concerns over oncological safety. This study was undertaken to compare the short- and long-term surgical outcomes following either LATG or open total gastrectomy (OTG) for gastric cancer. A total of 120 LATG and 228 OTG were retrospectively matched with respect to sex, age (±5 years), and pathological tumor-node-metastasis stage for comparison of the clinical outcomes. The total complication rate among 120 LATG and 228 OTG was 18.3 % (22/120) and 16.2 % (37/228), respectively. The most common complication after LATG was anastomotic-related complication (6.7 %); five anastomotic leakages (4.2 %) and three anastomotic strictures were reported (2.5 %). That after OTG was wound complication (3.5 %), including seroma or infection. Matched patients analysis: Time to first gas passing and time to the resumption of a soft diet were significantly shorter in the LATG group than in the OTG group. The postoperative hospital stay of LATG was shorter in the LATG group (9.3 ± 4.2 days) than in the OTG group (11.7 ± 7.3 days; p = 0.057). Among matched patients, there was no significant difference between complication rate (24 vs. 32 %; p = 0.504) or leakage rate (6 vs. 4 %). During median follow-up of 50 (range, 10-92) months, there was no significant difference in the disease-free survival rate between the matched groups, respectively (94.5 vs. 87.1 %: p = 0.148). As for patients with TNM stage I gastric cancer, the disease-free survival rate (100 vs. 90.9 %; p = 0.5) and the cumulative survival rate (91.5 vs. 95.2 %; p = 0.618) did not differ significantly between the LATG and OTG groups. LATG for gastric cancer has the advantage over an OTG in terms of better short-term outcomes and similar long-term outcome. LATG is an acceptable alternative to OTG for the treatment of gastric cancer.	\N	\N
23541879	This consensus document was prepared by an expert panel of the Grupo de Estudio de Sida (GESIDA [Spanish AIDS Study Group]) and the Plan Nacional sobre el Sida (PNS [Spanish National AIDS Plan]). The document updates current guidelines on the treatment of tuberculosis (TB) in HIV-infected individuals contained in the guidelines on the treatment of opportunistic infections published by GESIDA and PNS in 2008. The document aims to facilitate the management and treatment of HIV-infected patients with TB in Spain, and includes specific sections and recommendations on the treatment of drug-sensitive TB, multidrug-resistant TB, and extensively drug-resistant TB, in this population. The consensus guidelines also make recommendations on the treatment of HIV-infected patients with TB in special situations, such as chronic liver disease, pregnancy, kidney failure, and transplantation. Recommendations are made on the timing and initial regimens of antiretroviral therapy in patients with TB, and on immune reconstitution syndrome in HIV-infected patients with TB who are receiving antiretroviral therapy. The document does not cover the diagnosis of TB, diagnosis/treatment of latent TB, or treatment of TB in children. The quality of the evidence was evaluated and the recommendations graded using the approach of the Grading of Recommendations Assessment, Development and Evaluation Working Group.	\N	\N
23542225	BM failure (BMF) is a major and frequent complication of dyskeratosis congenita (DKC). Allogeneic hematopoietic SCT (allo-HSCT) represents the only curative treatment for BMF associated with this condition. Transplant-related morbidity/mortality is common especially after myeloablative conditioning regimens. Herein, we report nine cases of patients with DKC who received an allo-SCT at five different member centers within the Eastern Mediterranean Blood and Marrow Transplantation Registry. Between October 1992 and February 2011, nine DKC patients (male, 7 and female, 2), with a median age at transplantation of 19.1 (4.9-31.1) years, underwent an allo-HSCT from HLA-matched, morphologically normal-related donors (100%). Preparative regimens varied according to different centers, but was reduced intensity conditioning (RIC) in eight patients. Graft source was unstimulated BM in five cases (56%) and G-CSF-mobilized PBSCs in four (44%) cases. The median stem cell dose was 6.79 (2.06-12.4) × 10(6) cells/kg body weight. GVHD prophylaxis consisted of CsA in all nine cases; MTX or mycophenolate mofetil were added in five (56%) and two (22%) cases, respectively. Anti-thymocyte globulin was administered at various doses and scheduled in four (44%) cases. Median time-to-neutrophil engraftment was 21 (17-27) days. In one case, late graft failure was noted at 10.4 months post allo-HSCT. Only one patient developed grade II acute GVHD (11%). Extensive chronic GVHD was reported in one case, whereas limited chronic GVHD occurred in another four cases. At a median follow-up of 61 (0.8-212) months, seven (78%) patients were still alive and transfusion independent. One patient died of metastatic gastric adenocarcinoma and graft failure was the cause of death in another patient. This study suggests that RIC preparative regimens are successful in inducing hematopoietic cell engraftment in patients with BMF from DKC. Owing to the limited sample size, the use of registry data and heterogeneity of preparative as well as GVHD prophylaxis regimens reported in this series, we are unable to recommend a particular regimen to be considered as the standard for patients with this disease.	\N	\N
23544766	To evaluate chemotherapy regimen utilization in patients with non-small cell lung cancer (NSCLC) treated in US community oncology practices, to examine the relationship between evidence-based guideline adherence and the follow-up monitoring period (FUMP) over 1.5 years, and to understand the relative costs of commonly administered chemotherapy regimens. Retrospective data analysis. Using a large US medical oncology clinical database derived from a proprietary web-based drug dispensing technology, we identified adult patients with NSCLC who started adjuvant therapy for early-stage disease or first-line therapy for advanced and metastatic disease from July 1, 2009, through June 30, 2010. Adjuvant or first-line regimen utilization and the FUMP within 1.5 years were analyzed with respect to national evidence-based guideline adherence. Costs for commonly administered regimens based on 2010 Medicare reimbursement were compared. A total of 3505 patient treatment regimens were included in this study. Rates of guideline adherence were 75.0% and 61.3% for the first-line and the adjuvant treatment groups, respectively (P < .0001). Treatment with guidelinebased regimens correlated with a significantly longer FUMP in the first-line treatment groupcompared with non-guideline-based regimens (P = .005). Regimen costs for the top 11 regimens in the adjuvant and first-line treatment settings varied greatly. Low-cost regimens were prescribed more commonly. Rates of guideline adherence were significantly higher in the first-line than in the adjuvant NSCLC treatment group. First-line treatment with guideline-based regimens correlated with an extended FUMP for advanced NSCLC patients.	\N	\N
23544828	Osteoporosis is a systemic disease that affects millions of people worldwide. It is estimated that 50% of women and approximately 20% of men more than 50 years of age will sustain a fragility fracture. The cause of nonunion in patients with osteoporosis is likely multifactorial, and includes age-related changes in fracture repair as well as challenges in achieving stable internal fixation. This article discusses fracture healing in patients with osteoporosis and the principles of fixation. Pharmacotherapy for the patient with osteoporosis is also discussed.	\N	\N
23547660	Tiotropium bromide is an effective therapy for COPD patients. Comparing across programs tiotropium Respimat Soft Mist inhaler was at least as efficacious as tiotropium HandiHaler, however, concerns have been raised about tiotropium's safety when given via Respimat. The TIOSPIR trial (NCT01126437) compares the safety and efficacy of tiotropium Respimat 5 μg once daily (marketed) and 2.5 μg once daily (investigational) with tiotropium HandiHaler 18 μ once daily (marketed). The hypotheses to be tested are 1). that tiotropium Respimat 5 μg once daily and Respimat 2.5 μg once daily are non-inferior to HandiHaler in terms of all-cause mortality, and 2). that tiotropium Respimat 5 μg once daily is superior to HandiHaler in terms of time to first exacerbation. A spirometry substudy evaluates the bronchodilator efficacy. The trial is a randomized, double-blind, double dummy, event-driven, parallel group study. Participants can use any background treatment for COPD except inhaled anticholinergic agents. The study encompasses a wide range of COPD patients, e.g. patients with stable cardiac diseases including arrhythmia can be included. Clinical sites are international and include both primary care as well as specialists. To date, over 17,000 participants have been randomized from over 1200 sites in 50 countries with an anticipated treatment duration of 2-3 years. TIOSPIR will provide precise estimates of the relative safety and efficacy of the Respimat and HandiHaler formulations of tiotropium, assess potential dose-dependence of important outcomes and provide information on the clinical epidemiology of COPD in a large international patient cohort.	\N	\N
23549020	Metastatic prostate carcinoma commonly involves bones and extrapelvic lymph nodes, with occasional visceral deposits. Central nervous system involvement is unusual and particularly the occurrence of leptomeningeal metastasis (LM) is extremely rare, with few cases described in the medical literature. The clinical presentation is characterized by multifocal neurological deficit and the prognosis is generally dismal, with survival ranging between 3 and 6 months. We report on a patient affected by LM due to prostate cancer who was treated with a combined-modality approach consisting of sequential chemotherapy and radiotherapy. A 70-year-old man was referred to our group for cognitive mental disorder, left-sided frontal headache and nausea; the patient had a previous history of metastatic prostate cancer. LM was diagnosed neuroradiologically with brain MRI and evidence of a detectable level of PSA in the cerebrospinal fluid. He was treated with docetaxel and prednisone for 3 cycles followed by external beam radiotherapy (EBRT) to the whole brain to a total dose of 30 Gy in 10 fractions with a simultaneous integrated boost to the macroscopic disease (total dose of 35 Gy in 10 fractions). No acute toxicity was observed. A substantial clinical response was obtained after EBRT with neurological improvement and radiologically stable disease at post-treatment imaging until 10 weeks after radiation. The patient died of sudden general condition deterioration 3 months after EBRT. Since LM derived from prostate cancer is likely to become a more common clinical event, such patients would need to be included in clinical trials evaluating new therapeutic approaches, considering that the current treatment strategies have been shown to be rather ineffective.	\N	\N
23549631	The prognosis of thrombotic thrombocytopenic purpura (TTP) has considerably improved since the introduction of plasma exchange (PEX) therapy. However, unresponsive thrombotic thrombocytopenic purpura (Un-TTP) still carries high morbidity and mortality rates, indicating a need for early specific treatments. In a retrospective study including consecutive adults with TTP admitted between January 1997 and January 2011 in a teaching hospital intensive care unit (ICU), our objective here is to identify early clinical and laboratory features predicting Un-TTP. Patients who responded to plasma exchange and steroids (N = 49) were compared with patients with unresponsive TTP defined as requirement for other treatments, protracted course, or death (N = 37, 43 %). Hospital mortality was 24.3 % in the Un-TTP group. Variables associated with Un-TTP on univariate logistic regression were older age, cardiac involvement, neurological involvement, higher anti-a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS13) immunoglobulin G (IgG) titer, lower platelet counts starting on day 2, higher Sequential Organ Failure Assessment (SOFA) scores starting on day 3, need for higher plasma volumes to obtain remission, and greater use of adjuvant treatments and life-sustaining interventions. Multivariate logistic regression identified four factors independently associated with Un-TTP: age over 60 years [odds ratio (OR) 7.90; 95 % confidence interval (95 % CI) 1.06-78.34], cardiac (OR 5.17; 95 % CI 1.63-16.39) or neurological (OR 8.04; 95 % CI 1.27-51.03) manifestations at diagnosis, and day 2 platelet count less than 15 G/l (OR 3.88; 95 % CI 1.30-11.62). Therapeutic intensification starting on day 3 or even earlier in patients with the independent risk factors for unresponsive TTP identified in our study deserves evaluation in a multicenter prospective study.	\N	\N
23554958	Intracranial Artery Stenosis (ICAS) is one of the most common causes of ischemic stroke in Asia. Previous studies have shown the number of ideal cardiovascular health (CVH) metrics was associated with lower risk of stroke. This study aimed to investigate the relationship between ideal CVH metrics and prevalence of ICAS. A random sample of 5,412 participants (selected from Kailuan Study as a reference population) aged 40 years or older (40.10% women), free of stroke, transient ischemic attack, and coronary disease, were enrolled in the Asymptomatic Polyvascular Abnormalities Community study from 2010 to 2011. We collected information on the seven CVH metrics (including smoking, body mass index, dietary intake, physical activity, blood pressure, total cholesterol and fasting blood glucose); and assessed ICAS by transcranial Doppler. The relationship between the ideal CVH metrics and prevalence of ICAS was analyzed using the multivariate logistic regression. After adjusting for age, sex, and other potential confounders, the adjusted odds ratios(95% confidence interval) for ICAS were 0.76(0.58-0.99), 0.55(0.43-0.72), 0.49(0.37-0.65), 0.43(0.31-0.61), and 0.36(0.22-0.62), respectively, for those having 2, 3, 4, 5, and 6-7 ideal CVH metrics compared with those having 0-1 ideal metric(p-trend<0.0001). Similar inverse associations were observed in different age and gender groups (all p-trends<0.05). We found a clear gradient relationship between the number of ideal CVH metrics and lower prevalence of ICAS in a Chinese population, which supports the importance of ideal health behaviors and factors in the prevention of ICAS.	\N	\N
23557197	Human leukocyte antigen matching at allelic resolution is proven clinically significant in hematopoietic stem cell transplantation, lowering the risk of graft-versus-host disease and mortality. However, due to the ever growing HLA allele database, tissue typing laboratories face substantial challenges. In light of the complexity and the high degree of allelic diversity, it has become increasingly difficult to define the classical transplantation antigens at high-resolution by using well-tried methods. Thus, next-generation sequencing is entering into diagnostic laboratories at the perfect time and serving as a promising tool to overcome intrinsic HLA typing problems. Therefore, we have developed and validated a scalable automated HLA class I and class II typing approach suitable for diagnostic use. A validation panel of 173 clinical and proficiency testing samples was analysed, demonstrating 100% concordance to the reference method. From a total of 1,273 loci we were able to generate 1,241 (97.3%) initial successful typings. The mean ambiguity reduction for the analysed loci was 93.5%. Allele assignment including intronic sequences showed an improved resolution (99.2%) of non-expressed HLA alleles. We provide a powerful HLA typing protocol offering a short turnaround time of only two days, a fully integrated workflow and most importantly a high degree of typing reliability. The presented automated assay is flexible and can be scaled by specific primer compilations and the use of different 454 sequencing systems. The workflow was successfully validated according to the policies of the European Federation for Immunogenetics. Next-generation sequencing seems to become one of the new methods in the field of Histocompatibility.	\N	\N
23557266	Adhesion molecules play a key role in the pathogenetic mechanisms of inflammatory bowel disease (IBD), both in Crohn's disease (CD) and ulcerative colitis (UC). In the last decade, some progress has been made in understanding their key role in leukocyte trafficking control in terms of basic research, but evidence of clinical efficacy is lacking. In the last 2 years, new molecules directed against integrins and integrin receptors have been developed and investigated in clinical trials, showing that anti-α4β7 integrin agents can be effective and safe for the induction and maintenance of remission in active CD and UC. Preliminary data show that anti-MAdCAM, anti-β7 and anti-integrin receptor agents are not all effective in IBD. Such results open new perspectives on clinical management of IBD, and new directions in understanding the role of adhesion molecules and leukocyte recruitment both in CD and UC.	\N	\N
23578358	Angiogenic stimulation is a promising new strategy for treating patients with arteriosclerotic coronary artery disease. This strategy aims to ameliorate cardiac function by improving myocardial perfusion and lowering the risk of myocardial infarction. However, angiogenesis may contribute to the growth of atherosclerotic lesions. Atherogenesis is also a potential side effect of angiogenic therapy. Early clinical trials were performed using fibroblast growth factor 2 (FGF2) protein, which enhances the formation of new collateral vessels to reduce ischaemic symptoms. Conversely, angiogenic stimulation by FGF2 is a dilemma because it could cause negative angiogenic effects, such as atherosclerosis. Thus far, clinical trials in patients with recombinant FGF2 protein therapy have not yet yielded undisputable beneficial effects. Future trials should determine whether an improvement can be obtained in patients with coronary artery disease using a combination of FGF2 and other growth factors or a combination of the FGF2 gene and stem cell therapy. This review summarises the multiple roles of FGF2 in the progression of atherosclerosis, its effect on pro-angiogenesis and improvement of cardiac function in coronary artery disease, and the potentially unfavourable effect of angiogenesis on the prevention and treatment of atherogenesis.	\N	\N
23581956	To review cases of nosocomial influenza and compare the epidemiology, clinical characteristics and outcomes with community-acquired cases. Prospective case series of adults hospitalised with influenza during April - November of 2010 and 2011 using a hospital-based sentinel surveillance system. A nosocomial case was defined as polymerase chain reaction-confirmed influenza where symptom onset was more than 2 15s after admission or, if this was not known, where the date of the positive test was more than 7 15s after admission. Demographic, clinical and outcome measures for patients with nosocomial influenza compared with patients admitted with community-acquired influenza. In 2010-2011, 598 cases of influenza were detected, of which 26 (4.3%) were nosocomial. All patients with nosocomial influenza had chronic comorbidities, compared with 71.7% of patients (410/572) with community-acquired influenza (P = 0.001). Similar proportions of community-acquired (32.5%) and nosocomial (36.4%) cases occurred in patients vaccinated in the current season. Clinical findings at time of enrollment did not differ between the two groups, with similar rates of fever, cough, chest pain and dyspnoea. Compared with community-acquired cases, a higher proportion of patients with nosocomial influenza received neuraminidase inhibitors within 2 15s of symptom onset (38.5% v 15.9%; P = 0.003). Admission to intensive care took place in 21.3% and 23.1% of community-acquired and nosocomial cases, respectively. One death from nosocomial influenza occurred in a patient with end-stage respiratory disease. Nosocomial influenza is uncommon but may be associated with severe disease. It may be partially preventable as patients frequently have comorbidities for which influenza vaccination is recommended. Patients, particularly those at high risk of complications, and their contacts (including health care workers) should be vaccinated to prevent severe disease.	\N	\N
23591331	Self-expandable metal stents (SEMSs) are used to relieve malignant biliary obstruction. To compare outcomes between covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (USEMSs) in malignant biliary obstruction. Retrospective cohort study. Tertiary cancer center. Patients with malignant biliary obstruction. Placement of CSEMS or USEMS. Time to recurrent biliary obstruction (TRO), overall survival (OS), and adverse events. From January 2000 to June 2011, 749 patients received SEMSs: 171 CSEMSs and 578 USEMSs. At 1 year, there was no significant difference in the percentage of patients with recurrent obstruction (CSEMSs, 35% vs USEMSs, 38%) and survival (CSEMSs, 45% vs USEMSs, 49%). There was no significant difference in the median OS (CSEMSs, 10.4 months vs USEMSs, 11.8 months; P = .84) and the median TRO (CSEMSs, 15.4 months vs USEMSs, 26.3 months; P = .61). The adverse event rate was 27.5% for the CSEMS group and 27.7% for the USEMS group. Although tumor ingrowth with recurrent obstruction was more common in the USEMS group (76% vs 9%, P < .001), stent migration (36% vs 2%, P < .001) and acute pancreatitis (6% vs 1%, P < .001) were more common in the CSEMS group. Retrospective study. There was no significant difference in the patency rate or overall survival between CSEMSs and USEMSs for malignant distal biliary strictures. The CSEMS group had a significantly higher rate of migration and pancreatitis than the USEMS group. No significant SEMS-related adverse events were observed in patients undergoing neoadjuvant chemoradiation or surgical resection.	\N	\N
23594492	To detect fully penetrant rare recessive variants that could constitute Mendelian subentities of complex diseases, we propose a novel strategy, the HBD-GWAS strategy, which can be applied to genome-wide association study (GWAS) data. This strategy first involves the identification of inbred individuals among cases using the genome-wide SNP data and then focuses on these inbred affected individuals and searches for genomic regions of shared homozygosity by descent that could harbor rare recessive disease-causing variants. In this second step, analogous to homozygosity mapping, a heterogeneity lod-score, HFLOD, is computed to quantify the evidence of linkage provided by the data. In this paper, we evaluate this strategy theoretically under different scenarios and compare its performances with those of linkage analysis using affected sib-pair (ASP) data. If cases affected by these Mendelian subentities are not enriched in the sample of cases, the HBD-GWAS strategy has almost no power to detect them, unless they explain an important part of the disease prevalence. The HBD-GWAS strategy outperforms the ASP linkage strategy only in a very limited number of situations where there exists a strong allelic heterogeneity. When several rare recessive variants within the same gene are involved, the ASP design indeed often fails to detect the gene, whereas, by focusing on inbred individuals using the HBD-GWAS strategy, the gene might be detected provided very large samples of cases are available.	\N	\N
23594728	The presence of baseline proteinuria predicts the outcome in patients with chronic kidney disease and in the general population, independent of renal function. However, the predictive value of proteinuria during an episode of acute illness has not been reported yet. Therefore, we investigated the incidence and predictive value of proteinuria in patients with community-acquired pneumonia. An analysis of prospectively collected data, obtained from patients >18 years of age, was performed. Patients were hospitalized with community-acquired pneumonia in two hospitals in the Netherlands and participated in two consecutive clinical trials. A total protein/creatinine (P/C) ratio was measured in a urine sample from the day of admission. Patients were categorized in quartiles of P/C ratio. Primary outcome was length of hospital stay. 198/319 patients (62%) had a P/C ratio >23 mg/mmol creatinine. In multivariate analysis, proteinuria turned out to be an independent predictor for length of stay and admission to the intensive care unit. The incidence of proteinuria during pneumonia is high and proteinuria is an independent predictor for length of hospital stay and admission to the intensive care unit. Proteinuria is a cheap and easily accessible marker for outcome and might be used to assess the severity of pneumonia.	\N	\N
23602249	Obesity is associated with elevated risk of heart disease. A solid understanding of the safety and potential adverse effects of high-fat, low-carbohydrate diet (HFLCD) similar to that used by humans for weight loss on the heart is crucial. High fat intake is known to promote increases in reactive oxygen species and mitochondrial damage. We hypothesized that there would be adverse effects of HFLCD on myocardial ischemia/reperfusion injury through enhancing oxidative stress injury and impairing mitochondrial biogenesis in a nongenetic, diet-induced rat model of obesity. To test the hypothesis, 250-g male Sprague-Dawley rats were fed an obesity-promoting diet for 7 weeks to induce obesity, then switched to HFLCD or a low-fat control diet for 2 weeks. Isolated hearts underwent global low flow ischemia for 60 minutes and reperfusion for 60 minutes. High-fat, low-carbohydrate diet resulted in greater weight gain and lower myocardial glycogen, plasma adiponectin, and insulin. Myocardial antioxidant gene transcript and protein expression of superoxide dismutase and catalase were reduced in HFLCD, along with increased oxidative gene NADPH oxidase-4 transcript and xanthine oxidase activity, and a 37% increase in nitrated protein (nitrotyrosine) in HFLCD hearts. The cardiac expression of key mitochondrial regulatory factors such as nuclear respiratory factor-1 and transcription factor A-mitochondrial were inhibited and myocardial mitochondrial DNA copy number decreased. The cardiac expression of adiponectin and its receptors was down-regulated in HFLCD. High-fat, low-carbohydrate diet impaired recovery of left ventricular rate-pressure product after ischemia/reperfusion and led to 3.5-fold increased injury as measured by lactate dehydrogenase release. In conclusion, HFLCD leads to increased ischemic myocardial injury and impaired recovery of function after reperfusion and was associated with attenuation of mitochondrial biogenesis and enhanced oxidative stress in obese rats. These findings may have important implications for diet selection in obese patients with ischemic heart disease.	\N	\N
23607333	Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of -308 G < A tumour necrosis factor (TNF)-α, -174 G > C interleukin (IL)-6 and -1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case-control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-α/IL-10 combinations, it was observed that low TNF-α plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-α producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16-4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19-12·23; P = 0·02). In this study, the combination of low TNF-α plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients.	\N	\N
23613224	High-intensity interval training (HIT) as exercise therapy is gradually implemented in cardiac rehabilitation as the cardiovascular benefits from exercise is intensity dependent. However, in previous studies, HIT has been performed with strict supervision. The aim of the study was to assess the feasibility and effectiveness of different modes of HIT in cardiac rehabilitation. a randomized clinical study. Ninety participants with coronary artery disease (80 men/10 women, mean age 57 ± 8 years) were randomly assigned to one of three exercise modes: group exercise (GE), treadmill exercise (TE), or home-based exercise (HE). HIT was performed twice a week for 12 weeks with an exercise intensity of 85-95% of peak heart rate. The primary outcome measure was change in peak oxygen uptake (peak VO2). Eighty-three participants (92%) completed the intervention without any severe adverse events. Peak VO2 increased from 34.7 ± 7.3 to 39.0 ± 8.0 ml/kg/min, 32.7 ± 6.5 to 36.0 ± 6.2 ml/kg/min, and 34.4 ± 4.8 to 37.2 ± 5.2 ml/kg/min in TE, GE, and HE, respectively. Mean group difference for TE vs. HE was 1.6 ml/kg/min (95% confidence interval, CI, 0.7 to 3.1, p = 0.02), TE vs. GE 1.1 ml/kg/min (95% CI-0.5 to 2.5, p = 0.27), and GE vs. HE 0.6 ml/kg/min (95% CI -1.0 to 2.1, p = 1). However, on-treatment analysis showed no significant difference between groups. HIT was efficiently performed in three settings of cardiac rehabilitation, with respect to target exercise intensity, exercise attendance, and increase in peak VO2. Exercise mode was not essential for exercise capacity.	\N	\N
23613636	To investigate the significance of Twist2 for colorectal cancer (CRC). In this study, 93 CRC patients were included who received curative surgery in Eastern Hepatobiliary Surgery Hospital from January 1999 to December 2010. Records of patients' clinicopathological characteristics and follow up data were reviewed. Formalin-fixed, paraffin-embedded tissue blocks were used to observe the protein expression of Twist2 and E-cadherin by immunohistochemistry. Two independent pathologists who were blinded to the clinical information performed semiquantitative scoring of immunostaining. A total score of 3-6 (sum of extent + intensity) was considered as Twist2-positive expression. The expression of E-cadherin was divided into two levels (preserved and reduced). An exploratory statistical analysis was conducted to determine the association between Twist2 expression and clinicopathological parameters, as well as E-cadherin expression. Furthermore, the variables associated with prognosis were analyzed by Cox's proportional hazards model. Kaplan-Meier analysis was used to plot survival curves according to different expression levels of Twist2. Twist2-positive expression was observed in 66 (71.0%) samples and mainly located in the cytoplasm. Forty-three (46.2%) samples showed reduced expression of E-cadherin. There were no significant correlations between Twist2 expression and any of the clinicopathological parameters. However, Twist2-positive expression was significantly associated with reduced expression of E-cadherin (P = 0.040). Multivariate analysis revealed that bad M-stage [hazard ratio (HR) = 7.694, 95%CI: 2.927-20.224, P < 0.001] and Twist2-positive (HR = 5.744, 95%CI: 1.347-24.298, P = 0.018) were the independent risk factors for poor overall survival (OS), while Twist2-positive (HR = 3.264, 95%CI: 1.455-7.375, P = 0.004), bad N-stage (HR = 2.149, 95%CI: 1.226-3.767, P = 0.008) and bad M-stage (HR = 10.907, 95%CI: 4.937-24.096, P < 0.001) were independently associated with poor disease-free survival (DFS). Survival curves showed a definite trend for Twist2-negative patients to have longer OS and DFS than Twist2-negative patients, not only overall, but also for patients in different stages, especially for DFS of patients in stage III (P = 0.033) and IV (P = 0.026). Our data suggests, for the first time, that Twist2 is a valuable prognostic biomarker for CRC, particularly for patients in stage III and IV.	\N	\N
23617953	By definition, a generic product is considered interchangeable with the innovator brand product. Controversy exists about interchangeability, and attention is predominantly directed to contaminants. In particular for chronic, degenerative conditions such as in Parkinson's disease (PD) generic substitution remains debated among physicians, patients and pharmacists. The objective of this study was to compare the pharmaceutical quality of seven generic levodopa/benserazide hydrochloride combination products marketed in Germany with the original product (Madopar® / Prolopa® 125, Roche, Switzerland) in order to evaluate the potential impact of Madopar® generics versus branded products for PD patients and clinicians. Madopar® / Prolopa® 125 tablets and capsules were used as reference material. The generic products tested (all 100 mg/25 mg formulations) included four tablet and three capsule formulations. Colour, appearance of powder (capsules), disintegration and dissolution, mass of tablets and fill mass of capsules, content, identity and amounts of impurities were assessed along with standard physical and chemical laboratory tests developed and routinely practiced at Roche facilities. Results were compared to the original "shelf-life" specifications in use by Roche. Each of the seven generic products had one or two parameters outside the specifications. Deviations for the active ingredients ranged from +8.4% (benserazide) to -7.6% (levodopa) in two tablet formulations. Degradation products were measured in marked excess (+26.5%) in one capsule formulation. Disintegration time and dissolution for levodopa and benserazide hydrochloride at 30 min were within specifications for all seven generic samples analysed, however with some outliers. Deviations for the active ingredients may go unnoticed by a new user of the generic product, but may entail clinical consequences when switching from original to generic during a long-term therapy. Degradation products may pose a safety concern. Our results should prompt caution when prescribing a generic of Madopar®/Prolopa®, and also invite to further investigations in view of a more comprehensive approach, both pharmaceutical and clinical.	\N	\N
23620363	The number of missense mutations being identified in cancer genomes has greatly increased as a consequence of technological advances and the reduced cost of whole-genome/whole-exome sequencing methods. However, a high proportion of the amino acid substitutions detected in cancer genomes have little or no effect on tumour progression (passenger mutations). Therefore, accurate automated methods capable of discriminating between driver (cancer-promoting) and passenger mutations are becoming increasingly important. In our previous work, we developed the Functional Analysis through Hidden Markov Models (FATHMM) software and, using a model weighted for inherited disease mutations, observed improved performances over alternative computational prediction algorithms. Here, we describe an adaptation of our original algorithm that incorporates a cancer-specific model to potentiate the functional analysis of driver mutations. The performance of our algorithm was evaluated using two separate benchmarks. In our analysis, we observed improved performances when distinguishing between driver mutations and other germ line variants (both disease-causing and putatively neutral mutations). In addition, when discriminating between somatic driver and passenger mutations, we observed performances comparable with the leading computational prediction algorithms: SPF-Cancer and TransFIC. A web-based implementation of our cancer-specific model, including a downloadable stand-alone package, is available at http://fathmm.biocompute.org.uk.	\N	\N
23620431	To report the findings of en face adaptive optics (AO) near infrared (NIR) reflectance fundus flood imaging in eyes with geographic atrophy (GA). Observational clinical study of AO NIR fundus imaging was performed in 12 eyes of nine patients with GA, and in seven controls using a flood illumination camera operating at 840 nm, in addition to routine clinical examination. To document short term and midterm changes, AO imaging sessions were repeated in four patients (mean interval between sessions 21 days; median follow up 6 months). As compared with scanning laser ophthalmoscope imaging, AO NIR imaging improved the resolution of the changes affecting the RPE. Multiple hyporeflective clumps were seen within and around GA areas. Time-lapse imaging revealed micrometric-scale details of the emergence and progression of areas of atrophy as well as the complex kinetics of some hyporeflective clumps. Such dynamic changes were observed within as well as outside atrophic areas. in eyes affected by GA, AO nir imaging allows high resolution documentation of the extent of RPE damage. this also revealed that a complex, dynamic process of redistribution of hyporeflective clumps throughout the posterior pole precedes and accompanies the emergence and progression of atrophy. therefore, these clumps are probably also a biomarker of rpe damage. AO NIR imaging may, therefore, be of interest to detect the earliest stages, to document the retinal pathology and to monitor the progression oF GA. (ClinicalTrials.gov number, NCT01546181.).	\N	\N
23625177	Expression and function of the immunoregulatory molecule HLA-E was investigated in patients with relapsing-remitting (RR) multiple sclerosis (MS). Serum and cerebrospinal fluid (CSF) soluble (s)HLA-E and -G levels were measured by ELISA in 80 RRMS patients. Controls were patients with other inflammatory neurological disorders (OIND, n = 81) and noninflammatory neurological disorders (NIND, n = 86). Serum sHLA-E concentrations were higher in RRMS than in NIND patients only. CSF sHLA-E concentrations were higher in RRMS than controls. Increased CSF sHLA-E levels were detected in MRI inactive and clinically stable RRMS patients. sHLA-E intrathecal synthesis (ITS) was higher in RRMS than controls, and the number of patients with sHLA-E ITS above cut-off was higher i) in MS than controls, and ii) in clinically stable than clinically active MS patients. sHLA-E CSF levels and ITS correlated with i) the same sHLA-G parameters, and ii) disease duration. HLA-E expression and co-expression with CD markers were investigated in MS plaques from three different cases by immunohistochemistry and confocal microscopy, respectively. Infiltrating T lymphocytes and macrophages, as well as resident microglial cells and astrocytes expressed HLA-E. CSF samples from MS patients were finally tested for inhibitory activity of in vitro CTL and NK cell mediated cytotoxicity. sHLA-E⁺ were more effective than sHLA-E⁻ CSF samples in such inhibition. Maximum inhibition was achieved with sHLA-E⁺/sHLA-G⁺ CSF samples In conclusion, increased sHLA-E CSF levels may play an immunomodulatory role in MS, contributing to the inhibition of intrathecal inflammatory response. The potential of sHLA-E as biomarker of MS activity warrants further investigation.	\N	\N
23628099	The apex is a particular region of the prostate in its surgical dissection and pathological analysis. We sought to evaluate the prognostic value of the apical localization of prostate tumors. From 1988 to 2010, data pre- (age, clinical stage, preoperative PSA, biopsy Gleason score) and postoperative (prostate weight, pathologic stage TNM 2010, Gleason score, margin status) of 2765 total prostatectomies were collected prospectively. These data were compared according to existence or absence of tumor at the apex. The prognostic impact of tumor at the apex on biochemical recurrence-free survival (PSA>0.2 ng/mL) has been studied in univariate and multivariate models. One thousand eight hundred seventeen tumors had a location at the apex (65.7%). In univariate analysis, there was a significant difference in the clinical stage, the biopsy and pathological Gleason score, the result of curage, the pathological stage and the margin status between apical tumors and others. With a mean decline of 34.6 months, 502 patients had a biochemical recurrence (18.1%). Disease-free survival at 10 years was 60.7% for tumor at the apex versus 65.9% in other cases. The location at the apex was significantly associated with biochemical recurrence on univariate analysis (P=0.01). After adjustment for clinical and pathological stage, PSA level, Gleason score and surgical margins, the apex was not anymore a pejorative independent predictor (P=0.0087). The existence of tumor in the prostatic apex was associated with more aggressive tumoral criteria and was an independent and pejorative predictor of biochemical recurrence-free survival at 10 years in univariate analysis. The apical localization could be an additional argument in the decision of adjuvant therapy after prostatectomy.	\N	\N
23638302	Immune cells called mast cells can hinder rather than help the body's response to dengue virus, which suggests that mast cell products could be used as biomarkers to identify severe forms of the disease.	\N	\N
23644526	Vertebral metastases affect 20 to 50% of cancer patients and represent a major turning point in the disease from the functional impact they generate. Early treatment is mandatory to prevent or treat any neurological compression. Due to the high variability of clinical and radiological presentations, best care requires a multidisciplinary team, involving oncologists, radiation oncologists, interventional radiologists and spine surgeons. Recent advances in radiotherapy and interventional radiology have offered various efficient therapeutic solutions with relatively low morbidity rate in the management of symptomatic spine metastases. However, surgery remains the standard treatment for patients with rapidly progressive spinal cord compression or significant osteolytic lesion leading to a high risk of fracture. However, conventional surgical strategies are associated with significant morbidity and contraindicated in patients in poor general condition. In addition, postoperative complications are likely to affect patient's quality of life and delay the initiation of anticancer therapies. In order to reduce iatrogenic lesions, new "minimally invasive" techniques were developed to achieve immediate stabilisation and decompression while reducing the morbidity of the approach. We aim to inform the reader of the existence of these techniques so that each patient can benefit from treatment best suited to their situation.	\N	\N
23645623	Weight gain increases the prevalence of obesity, a risk factor for cardiovascular disease. Nevertheless, unintentional weight loss can be a harbinger of health problems. The Atherosclerosis Risk in Communities Study (1987-2009) included 15,792 US adults aged 45-64 years at baseline and was used to compare associations of long-term (30 years) and short-term (3 years) weight change with the risks of coronary heart disease (CHD) and ischemic stroke. Age-, gender-, and race-standardized incidence rates were 4.9 (95% confidence interval (CI): 4.6, 5.2) per 1,000 person-years for CHD and 2.5 (95% CI: 2.3, 2.8) per 1,000 person-years for stroke. After controlling for baseline body mass index and other covariates, long-term weight gain (since age 25 years) of more than 2.7% was associated with elevated CHD risk, and any long-term weight gain was associated with increased stroke risk. Among middle-aged adults, short-term (3-year) weight loss of more than 3% was associated with elevated immediate CHD risk (hazard ratio = 1.46, 95% CI: 1.18, 1.81) and stroke risk (hazard ratio = 1.45, 95% CI: 1.10, 1.92). Risk tended to be larger in adults whose weight loss did not occur through dieting. Avoidance of weight gain between early and middle adulthood can reduce risks of CHD and stroke, but short-term, unintentional weight loss in middle adulthood may be an indicator of immediate elevated risk that has not previously been well recognized.	\N	\N
23649916	CD146 is an adhesion molecule localized at endothelial cell junctions and facilitates cell-cell interactions. The circulating soluble form (sCD146) lacks both the intracellular and the transmembrane domains. In this study we show that CD146 expression was significantly decreased in the lung tissue of smokers with chronic obstructive pulmonary disease (COPD) and also in rats exposed to second-hand smoke (SHS). Concurrently, levels of sCD146 were increased in both the plasma and bronchoalveolar lavage fluid (BALF) of COPD patients as well as in BALF from rats exposed to SHS. Decreased or abolished CD146 protein expression in rat pulmonary micro- and macrovascular endothelial cells was found after treatment with cigarette smoke extract (CSE), proinflammatory cytokine interleukin 18 (IL-18) or after silencing CD146 expression with siRNA. The decrease in CD146 protein was accompanied by increased endothelial monolayer permeability and enhanced macrophage infiltration in vitro. In CD146 knockout (KO) mice, distinct perivascular oedema was seen and increased numbers of inflammatory cells, along with increased protein levels in BALF. Increased sCD146 was found in BALF and plasma from patients with COPD. The circulating plasma levels of sCD146 correlated positively with the presence of anti-endothelial cell antibodies (AECAs). sCD146 in combination with AECAs may be useful markers for early detection of COPD. Our study indicates that loss of CD146 function damages pulmonary endothelial integrity. This damage may represent part of the pathophysiological processes that are involved in the basic aetiology of COPD/emphysema.	\N	\N
23653428	Colistin is increasingly used as the last-resort treatment option against infections caused by multidrug-resistant (MDR) Gram-negative pathogens, but its nephrotoxicity is of concern, especially in severely ill patients. The aim of this study was to analyze the toxicity of colistin therapy in adults and children with hematological malignancies (HM) and hematopoietic stem cell transplantation (HSCT) recipients. Data on HSCT recipients and HM patients, treated with intravenous colistin (2.5-5 mg/kg/day in children and 3-6 million international units (IU) in adults, adjusted to renal function) during the period 2008-2011 in our center, were retrospectively collected and analyzed. Nephrotoxicity was defined according to the RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease). Twenty-nine children and adults received 38 courses of intravenous colistin (2.5-5 mg/kg/day in children and 3-6 × 10(6) IU in adults, adjusted to renal function) [allogeneic HSCT (22 courses) and HM (16 courses)] for 3-28 days (median 10 days) for empirical therapy for nosocomial clinical sepsis (28) or local infection (6), and bacteremia with MDR Gram-negative rods (4). Nephrotoxicity was observed at the end of 4 (10.5%) courses. In 32 (84%) courses, nephrotoxic medications were concomitantly administered. Two patients had convulsions, probably unrelated to colistin. Seven patients (18%) died while on colistin therapy. No death was attributed to an adverse effect of colistin. Treatment with intravenous colistin, with dosage adjusted to renal function, was relatively safe for HM/HSCT patients, even with concomitantly administered nephrotoxic medications. Concern about nephrotoxicity should not justify a delay in initiating empirical colistin treatment in situations where infection with MDR Gram-negative rods is likely.	\N	\N
23658247	The implementation of national estimated glomerular filatration rate reporting and the inclusion of renal-specific indicators in a primary care pay for performance (P4P) system since April 2006 has promoted identification and better management of risk factors related to chronic kidney disease (CKD). In the UK, the P4P framework is known as the Quality and Outcomes Framework (QOF). One of the key targets for intervention in primary care was hypertension. It is clear that hypertension is a major predictor of development and progression of CKD; thus, targeting better blood pressure control is likely to have a positive impact on outcomes in CKD. The aim of this study was to evaluate the effectiveness of renal indicators outlined in P4P on the management of hypertension in primary care. To estimate the cost implications of the resulting changes in prescribing patterns of antihypertensive medication following introduction of such indicators. We performed a prospective cohort study using a large primary care database. This cohort was taken from a database collated as part of a clinical decision support system used to assist the management of CKD in primary care. We investigated a total population of 90 250 individuals on general practitioner (GP) registers with a valid serum creatinine estimation in the 6-year study period. A total of 10 040 patients had confirmed stage 3-5 CKD in the 2 years pre-QOF and formed the study cohort. Patients were studied over three time periods, pre-QOF (1 April 2004 to 31 March 2006), 2 years post-QOF (1 April 2006 to 31 March 2008) and finally the two subsequent years (1 April 2008 to 31 March 2010). The mean systolic and diastolic blood pressures (BP) together with antihypertensive medication were analysed over the three time periods. Cost calculation was based on 2009 British National Formulary list prices for antihypertensives. The mean age of the cohort at the start of the study period was 64.8 years, 55% were female. In those patients with stage 3-5 CKD 83.9% were hypertensive, defined by a pre-P4P BP of >140/85 or currently taking antihypertensive medication. The proportion of patients with CKD 3-5 attaining the BP target of 145/80 increased from 41.5% in the pre-QOF period to 50.0% in the post-QOF period. This increase was even more marked for those with hypertension in the pre-QOF period (28.8-45.1%). In the hypertensive patients, mean BP fell from 146/79 mmHg to 140/76 in the first 2 years post-P4P [P < 0.01, analysis of variance (ANOVA)]. This BP reduction was sustained in the last 2 years of the study, 139/75 (P < 0.01, ANOVA). The proportion of hypertensive patients taking angiotensin-converting enzyme inhibitors or angiotensin blockers increased, this was also sustained in the third time period. An increase in the prescribing of diuretics, calcium channel blockers and β-blockers was also observed. The additional cost of increased prescribing was calculated to be €25.00 per hypertensive patient based on GP prescription data. Population BP control has improved since the introduction of P4P renal indicators, and this improvement has been sustained. This was associated with a significant increase in the use of antihypertensive medication, resulting in increased prescription cost. Longer-term follow-up will establish whether or not this translates to improved outcomes in terms of progression of CKD, cardiovascular disease and patient mortality.	\N	\N
23662931	An intradural somatic-to-autonomic anastomosis, or Xiao procedure, has been described to create a "skin-CNS-bladder" reflex that improves bladder and bowel function in patients with neurogenic bladder and bowel dysfunction. The authors present their experience with a 10-year-old boy with chronic neurogenic bladder and bowel dysfunction related to spinal cord injury who underwent the Xiao procedure. After undergoing a left L-5 ventral root to left S2-3 intradural anastomosis, the patient reported that his bladder and bowel dysfunction improved between 6 and 12 months. Two years after the procedure, however, he reported that there was no change in his bladder or bowel dysfunction as compared with his condition prior to the procedure. Frequent, systematic multidisciplinary evaluations produced conflicting data. Electrophysiological and histological evaluation of the previously performed anastomosis during surgical reexploration 3 years after the Xiao procedure revealed that the anastomosis was in anatomical continuity but neuroma formation had prevented reinnervation. Nerve action potentials were not demonstrable across the anastomosis, and stimulation of the nerve above and below the anastomosis created no bladder or perineal contractions. This is the first clinical report on the outcome of the Xiao procedure in a child with spinal cord injury outside of China. It is impossible to draw broad conclusions about the efficacy of the procedure based on a single patient with no demonstrable benefit. However, future studies should carefully interpret transient improvements in bladder function, urodynamic findings, and the patient's ability to void in response to scratching after the Xiao procedure. The authors' experience with the featured patient, in whom reinnervation could not be demonstrated, suggests that such changes could be related to factors other than the establishment of a skin-CNS-bladder reflex as a result of a somatic-to-autonomic anastomosis.	\N	\N
23664519	In the field of emerging innovative therapies, such as thrombopoietin mimetics, the question of who needs splenectomy remains highly relevant. Removal of the spleen is an accepted and potentially curative treatment of immune thrombocytopenia (ITP) after decades with a favorable economical-effect ratio but with relevant morbidity particularly in the young patients. ITP is rare and splenectomy is performed in a minority of children, which makes its research almost impossible, resulting in a poor standardization of the procedure. Hence, in children, recommendation and decision for splenectomy is individually based and rests on expert opinions. Furthermore, local practice and availability of health products affect the frequency of splenectomy. Current guidelines agree on one point: splenectomy should be postponed for at least 12 months after the initial diagnosis of ITP, due to the high probability of improvement or even spontaneous remission. However, evidence-based data are lacking and splenectomy remains controversial. This article reviews the current literature and delineates controversies and complexities of splenectomy in children with ITP. There is an urgent need for consensus of this procedure in pediatric patients.	\N	\N
23668671	Recent genome-wide association studies have identified multiple loci associated with BMI or the waist:hip ratio (WHR). However, evidence on gene-lifestyle interactions is still scarce, and investigation of the effects of well-documented dietary and other lifestyle data is warranted to assess whether genetic risk can be modified by lifestyle. We assessed whether previously established BMI and WHR genetic variants associate with obesity and weight change in the Finnish Diabetes Prevention Study, and whether the associations are modified by dietary factors or physical activity. Individuals (n 459) completed a 3 d food record and were genotyped for twenty-six BMI- and fourteen WHR-related variants. The effects of the variants individually and in combination were investigated in relation to obesity and to 1- and 3-year weight change by calculating genetic risk scores (GRS). The GRS were separately calculated for BMI and the WHR by summing the increasing alleles weighted by their published effect sizes. At baseline, the GRS were not associated with total intakes of energy, macronutrients or fibre. The mean 1- and 3-year weight changes were not affected by the BMI or WHR GRS. During the 3-year follow-up, a trend for higher BMI by the GRS was detected especially in those who reported a diet low in fibre (P for interaction=0·065). Based on the present findings, it appears unlikely that obesity-predisposing variants substantially modify the effect of lifestyle modification on the success of weight reduction in the long term. In addition, these findings suggest that the association between the BMI-related genetic variants and obesity could be modulated by the diet.	\N	\N
23669496	We evaluated the prevalence of chronotropic incompetence (CI), a marker of autonomic dysfunction, and its prognostic value in patients with chronic obstructive pulmonary disease (COPD). We performed a retrospective analysis of 449 patients with severe COPD who underwent a cardiopulmonary exercise test, after excluding patients with lung volume reduction surgery, left ventricular dysfunction and those not in sinus rhythm. CI was defined as percent predicted heart rate reserve (%HRR). Events were defined as death or lung transplant during a median follow-up of 68 months. Median age was 61 years; median percent predicted forced expiratory volume in one second (%FEV1) of 25% and median %HRR of 33%. The hazard ratio for an event in the lowest quartile of %HRR, taking the highest quartile as reference, was of 3.2 (95% confidence interval: 2.1-4.8; p<0.001). In a multivariate regression model, %HRR was an independent predictor of events. In conclusion, CI was an independent and powerful outcome predictor in patients with severe COPD.	\N	\N
23669598	Although human papillomavirus (HPV) infections have been causally linked to oral cavity squamous cell carcinoma (OSCC), the potential role of low-risk HPV (LR-HPV) types in the pathogenesis of this malignancy remains unclear. We sought to investigate the distribution of HPV genotypes and their prognostic significance in OSCC patients treated by radical surgery, either with or without adjuvant therapy. We studied two non-overlapping OSCC cohorts for the periods 2005-2006 (2005 cohort, n = 204) and 2010-2011 (2010 cohort, n = 206). Paraffin-embedded tissue blocks were collected, and the HPV genotype was determined using PCR plus HPV blot tests. The primary study endpoint was the prevalence of HPV genotypes. The secondary endpoints were the 2-year therapeutic outcomes. The overall prevalence of HPV infections did not differ significantly in the two study cohorts. However, the prevalence of LR-HPV was significantly higher in the 2010 cohort than in the 2005 cohort (p = 0.002). The overall prevalence of HPV infections was not significantly associated with the 2-year outcomes. However, multivariate analysis demonstrated that LR-HPV infection was a predictor of poor 2-year disease-free survival (p = 0.036, hazard ratio [HR] = 3.1), disease-specific survival (p = 0.014, HR = 3.8), and overall survival (p = 0.016, HR = 3.2) in the subgroups of OSCC patients with poor differentiation, pN2 lymph node metastases, or extracapsular spread (n = 150). LR-HPV infections may have an important role in determining the clinical outcomes of certain OSCC patients bearing specific risk factors.	\N	\N
23670309	It is a matter of debate whether increased brain iron levels are the cause or only the consequence of neurodegenerative process in degenerative parkinsonism. The aim of this study is to characterize disease-related changes in volumes and iron-related R2 values of basal ganglia and thalamus. 13 patients with progressive supranuclear palsy (PSP), 15 with a parkinsonian variant of multiple system atrophy (MSA-p), 29 with Parkinson's disease (PD), and 21 age-matched controls underwent 3-Tesla MRI. The R2 values and volumes were calculated for the selected subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) using an automated region-based analysis. Voxel-based analysis was also performed to visualize a topographical correlation of R2 value and volume. The PSP group had significantly higher R2 values in globus pallidus and caudate nucleus (p < 0.05), whereas the MSA-p group had higher R2 values in putamen (p < 0.001) than PD and controls. The globus pallidus in PSP and the putamen in MSA-p were the most significant areas of atrophy to differentiate PSP, MSA-p and PD (AUC = 0.856, 0.832, respectively, p < 0.001). The R2 values in both structures increased in parallel with the extent of atrophy. They were negatively correlated with volumes in putamen (r = -0.777, p < 0.001) and globus pallidus (r = -0.409, p = 0.025) of MSA-p, and globus pallidus (r = -0.4, p = 0.043) of PSP. Voxel-based analysis identified higher R2 values in more severely atrophic sub-regions in these structures. We observed topographical differences of iron deposition as well as atrophy between MSA-p and PSP. Increased iron levels were related to the structural atrophy in basal ganglia. Our results imply that iron accumulation is likely an epiphenomenon of the degenerative process.	\N	\N
23682773	Some studies have shown differences in specific cognitive ability domains between the sexes at 60 years-of-age. However is important to analyze whether the rate of cognitive decline is also similar between the sexes after this age. The present study examined previously published literature to investigate whether cognitive decline is distinct between men and women after the age of 60 years. A systematic review was carried out with the PubMed, LILACS and PsycINFO databases (2001-2011) using the following search terms: aging, aged, cognitive function, mild cognitive impairment, mental health and cognition. We analyzed longitudinal research that used neuropsychological tests for evaluating cognitive function, showed results separated by sex and that excluded participants with dementia. Elderly women showed better performance in tests of episodic memory, whereas elderly men had a better visuospatial ability. Only one study detected distinct rates of cognitive decline in specific tests between the sexes. Despite differences observed in some domains, most of the studies showed that this rate is similar between the sexes until the age of 80 years. It is unclear whether sex influences the rate of cognitive decline after the age of 80 years. The present review observed that sex does not determine the rate of cognitive decline between 60 and 80 years-of-age. The contextual and cultural factors that involve men and women might determine a distinct decline between them, rather than sex alone.	\N	\N
23683938	The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than LDL cholesterol (LDLC), total LDL particles and usual measurement of oxidized LDL. The association between LAB and intima-media thickness (IMT) of carotid artery was investigated by ultrasound in US and Japan men. Participants were 297 US Caucasian and 310 Japanese men, aged 40-49 years without past history of cardiovascular disease. Serum LAB levels were measured by ELISAs with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody. Serum LAB levels [median (interquartile range), μg/L] were 1321 (936, 1730) in US Caucasians and 940 (688, 1259) in Japanese. For Caucasian men, average IMT was higher in higher LAB quartile, which was 0.653, 0.667, 0.688, and 0.702 mm, respectively (p for trend = 0.02). Linear regression analysis showed serum LAB was significantly associated with IMT after adjustment for LDLC or total LDL particles in addition to other traditional or novel risk factors for atherosclerosis such as C-reactive protein. However, there was no significant relationship between LAB and IMT in Japanese men. Serum LAB, a new candidate biomarker for residual risk, was associated with an increased carotid IMT in US Caucasian men independently of various risk factors; however, ethnic difference should be clarified in the future.	\N	\N
23685553	Current guidelines do not support the use of genetic profiles in risk assessment of coronary heart disease (CHD). However, new single nucleotide polymorphisms associated with CHD and intermediate cardiovascular traits have recently been discovered. We aimed to compare several multilocus genetic risk score (MGRS) in terms of association with CHD and to evaluate clinical use. We investigated 6 Swedish prospective cohort studies with 10 612 participants free of CHD at baseline. We developed 1 overall MGRS based on 395 single nucleotide polymorphisms reported as being associated with cardiovascular traits, 1 CHD-specific MGRS, including 46 single nucleotide polymorphisms, and 6 trait-specific MGRS for each established CHD risk factors. Both the overall and the CHD-specific MGRS were significantly associated with CHD risk (781 incident events; hazard ratios for fourth versus first quartile, 1.54 and 1.52; P<0.001) and improved risk classification beyond established risk factors (net reclassification improvement, 4.2% and 4.9%; P=0.006 and 0.017). Discrimination improvement was modest (C-index improvement, 0.004). A polygene MGRS performed worse than the CHD-specific MGRS. We estimate that 1 additional CHD event for every 318 people screened at intermediate risk could be saved by measuring the CHD-specific genetic score in addition to the established risk factors. Our results indicate that genetic information could be of some clinical value for prediction of CHD, although further studies are needed to address aspects, such as feasibility, ethics, and cost efficiency of genetic profiling in the primary prevention setting.	\N	\N
23685743	We evaluate sex-based differences in the effectiveness of early cardiac computed tomographic angiography (CCTA) and standard emergency department (ED) evaluation in patients with acute chest pain. In the Rule-Out Myocardial Infarction With Computer-Assisted Tomography (ROMICAT)-II multicenter, controlled trial, we randomized 1000 patients (47% women) 40 to 74 years of age with symptoms suggestive of acute coronary syndrome to an early CCTA or standard ED evaluation. In this prespecified analysis, women in the CCTA arm had a greater reduction in length of stay, lower hospital admission rates, and lesser increased cumulative radiation dose than men in a comparison of ED strategies (P for interaction ≤0.02). Although women had lower acute coronary syndrome rates than men (3% versus 12%; P<0.0001), sex differences in length of stay persisted after adjustment for baseline differences, including acute coronary syndrome rate (P for interaction <0.03). Length of stay was similar between sexes with normal CCTA findings (P=0.11). There was no missed acute coronary syndrome for either sex. No difference was observed in major adverse cardiac events between sexes and ED strategies (P for interaction =0.39). Women had more normal CCTA examinations than men (58% versus 37%; P<0.0001), less obstructive coronary disease by CCTA (5% versus 17%; P=0.0001), but similar normalcy rates for functional testing (P=0.65). Men in the CCTA arm had the highest rate of invasive coronary angiography (18%), whereas women had comparable low 5% rates regardless of ED strategy. This trial provides data supporting an early CCTA strategy as an attractive option in women presenting to the ED with symptoms suggestive of acute coronary syndrome. The findings may be explained by lower CAD prevalence and severity in women than men. http://www.clinicaltrials.gov. Unique identifier: NCT01084239.	\N	\N
23689410	Coronary heart disease and ischemic stroke are frequent coexistent conditions that share risk factors and pose major burdens to global health. Even though a clear relation has been established between extracranial internal carotid artery atherosclerosis and symptomatic or asymptomatic coronary heart disease, there is a gap in knowledge about the association between intracranial atherosclerosis and coronary heart disease. Intracranial atherosclerosis is associated with high risks of stroke recurrence and vascular death. More research and clinical trials are needed to answer whether early diagnosis of asymptomatic coronary heart disease and aggressive treatment can decrease the risk of vascular death in patients with ischemic stroke caused by intracranial atherosclerosis.	\N	\N
23698559	Animal models will be critical for preclinical evaluations of novel HIV eradication and/or functional cure strategies in the setting of suppressive combination antiretroviral therapy (cART). Here, the strengths, limitations, and challenges of recent efforts to develop nonhuman primate (NHP) models of cART-mediated suppression for use in studies of persistent virus and curative approaches are discussed. Several combinations of NHP species and viruses that recapitulate key aspects of human HIV infection have been adapted for cART-mediated suppression studies. Different cART regimens incorporating drugs targeting multiple different steps of the viral replication cycle have provided varying levels of virologic suppression, dependent in part upon the host species, virus, drug regimen and timing, and virologic monitoring assay sensitivity. New, increasingly sensitive virologic monitoring approaches for measurements of plasma viral RNA, cell-associated and tissue-associated viral RNA and DNA, and the replication-competent residual viral pool in the setting of cART in NHP models are being developed to allow for the assessment of persistent virus on cART and to evaluate the impact of viral induction/eradication strategies in vivo. Given the vagaries of each specific virus and host species, and cART regimen, each model will require further development and analysis to determine their appropriate application for addressing specific experimental questions.	\N	\N
23700280	Lymphoma-associated hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal disease. Differences between B cell and T cell lymphoma-associated HLH remain unclear, specifically clinical characteristics and survival. We retrospectively analyzed 30 lymphoma-associated HLH patients from July 2004 to October 2012. Patients were divided into B cell (n = 13) and T cell (n = 17) lymphoma groups. Patients' age, performance status, presence of Epstein-Barr virus infection, international prognostic index, presence of disseminated intravascular coagulopathy, serum triglyceride, fibrinogen, and lactate dehydrogenase levels were not significantly different between B cell and T cell lymphoma groups. HLH was an indicator for treatment resistance in patients with B cell (p = 0.048), but not T cell (p = 0.217), lymphoma. Patients in the T cell lymphoma group, however, had higher serum ferritin levels than patients in the B cell lymphoma group (11,525.6 versus 3,790.6 ng/mL; p = 0.043). The median survival time for patients in the B cell and T cell lymphoma groups was 330 and 96 days, respectively. Although the difference was not statistically significant (p = 0.273), our results suggested a trend toward a better overall survival time in patients with B cell lymphoma. This survival advantage could be at least partially due to use of rituximab (p = 0.045) for the treatment of patients with B cell lymphoma. Our results also suggested that allogeneic hematopoietic stem cell transplantation could possibly provide survival benefits to T cell lymphoma-associated HLH by graft-versus-lymphoma effect.	\N	\N
23701659	Reduced endogenous pain inhibition, as part of the degenerative process, is presumed to be the mechanism underlying the common presence of pain in patients with Parkinson's disease (PD). The present study aimed to assess an endogenous pain inhibitory system in PD using the conditioned pain modulation paradigm. Twenty-six predominantly unilateral PD patients and 19 controls underwent psychophysical pain assessment before and after patients' morning dopaminergic medication. An unexpected increase in several parameters of pain perception for PD patients was found after dopaminergic medication (e.g. for 49°C noxious heat stimulation an increase from 70.6 ± 4.0 to 77.6 ± 4.0 on the numerical pain scale, P < 0.001). This increase was seen in patients with predominantly left-sided PD, regardless of the stimulated side (for 49°C noxious heat stimulation, predominantly left-sided PD patients, pain perception increased from 73.5 ± 6.8 to 85.0 ± 6.8, P < 0.001, whereas predominantly right-sided PD patients did not show a significant increase, 68.3 ± 6.8 to 70.4 ± 6.5, P = 0.777). Baseline efficiency of conditioned pain modulation inversely correlated with age at disease onset (r = -0.522; P = 0.009) and disease severity (Unified PD Rating Scale, r = 0.447; P = 0.032) but did not differ between patients and controls. Increased sensory response causing hyperalgesia occurs after dopaminergic medication in patients with predominantly left-sided PD.	\N	\N
23704428	Human monocytic ehrlichiosis (HME) is a tick-born disease that presents predominantly as a mild to moderate acute illness. Severe life-threatening disease has been reported with a case death rate of approximately 3%, often in immunosuppressed persons. A delay in therapy initiation has been proven to increase the morbidity of the disease. We report a case of an elderly immunocompetent man with severe HME disease and multiorgan failure to emphasise on the severity of this disease in the elderly, as well as the importance of early therapy for overall favourable prognosis.	\N	\N
23706729	The health of the tens of millions of street children globally is understudied. We undertook a systematic review of the existing quantitative literature regarding the health status of street children and youth in low- and middle-income countries to summarize available knowledge, identify underexplored areas of research, and inform the future research agenda regarding the health of this population. A total of 108 articles met our inclusion criteria. Demographic data and structural factors associated with street life are summarized. Although data in specific regions or diseases are sparse, the literature review illustrates that youth's survival behaviors and the exposures associated with poor shelter have resulted in disproportionate morbidity in the areas of infectious illness, psychiatric disease, reproductive health, and perhaps to a lesser extent, growth. Vast areas of health that may disproportionately affect street children in childhood or later on as adults have not been investigated, including chronic diseases and cognitive deficits. Studies of specific diseases or conditions vary considerably by region. Strengths and limitations of the literature are discussed and principles for future research in this area are proposed.	\N	\N
23709100	This multicenter analysis evaluated patient outcome and clinical pathologic features of thymic epithelial tumors after complete surgical resection and adjuvant treatment. Histologic classification and clinical staging were performed according to WHO classification and Masaoka staging system, respectively. We analyzed 62 patients, 20 (32%) of whom had myasthenia at diagnosis. Clinical and pathologic staging was as follows: 31 (50%) and 30 (48%) patients had stage I disease, 19 (30%) and 22 (35%) stage II, 5 (8%) and 3 (6%) stage III, 2 (4%) and 2 (3%) stage IVa, and 5 (8%) and 5 (8%) stage IVb, respectively. Histologic examination revealed 11 (19%) type A tumors, 19 (30%) type AB tumors, 7 (12%) type B1 tumors, 11 (17%) type B2 tumors, 11 (17%) type B3 tumors, and 3 (5%) type C tumors. Adjuvant therapies comprised chemotherapy in 3 (5%) patients and radiotherapy in 16 (26%) patients. Median follow-up was 71 months (range 1-145). DFS and OS at 48, 60, and 72 months were 89 and 89%, 86 and 97%, and 95% and 92%, respectively. Myasthenia at the onset of disease (P=0.18 for DFS; P=0.97) and tumor size>5 cm (P=0.94 for DFS; P=0.56) were not prognostic factors. TETs are rare and indolent tumors. Complete surgical resection followed by adjuvant therapies, such as chemotherapy and/or radiotherapy, in patients at risk of recurrence show very good DFS and OS results, even in cases with radically resected pleural-pulmonary metastases.	\N	\N
23712633	Ticagrelor, a recently approved platelet antagonist indicated for the reduction of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS), has been reported to cause dyspnea in more than 13% of patients. Dyspnea is not a clinically relevant adverse event with other medications indicated for ACS. One suggested mechanism of ticagrelor-induced dyspnea involves an increase in systemic adenosine concentrations through adenosine deaminase inhibition. Dyspnea, a subjective finding resulting from physiologic and sensory mechanisms, may be a consequence of increased systemic adenosine concentrations, leading to amplified and prolonged receptor activity. Current literature suggests, however, that pulmonary status is not compromised, with no reduction of efficacy seen in patients with ticagrelor-induced dyspnea, thus allowing clinicians to continue therapy without reservation. Still, patients with a history of asthma and chronic obstructive pulmonary disease may be more susceptible to ticagrelor-induced dyspnea, potentially leading to nonadherence and exacerbations of morbidity. Therefore, it is paramount that health care providers continually monitor these patients with the aims of maintaining medication therapy adherence and providing relevant options if dyspnea becomes intolerable.	\N	\N
23723040	We previously identified a four-generation family with medullary thyroid cancer (MTC) and a germline p.Y791F RET mutation whose cancer lacked a strong genotype-phenotype correlation. The entire gene coding region of the RET gene should be sequenced when genotype-phenotype discrepancies are observed in patients with multiple endocrine neoplasia type 2 (MEN 2), even if a RET hotspot mutation has been identified. A new genetic test was performed in the index case of this family with the p.Y791F RET germline mutation. The entire coding region of the RET gene was investigated by direct sequencing of PCR products. Once a mutation was identified, the target exon was sequenced in all at-risk relatives. An additional p.C634Y germline mutation in the RET gene was identified in the reported family. The double mutation occurred in cis and segregated with the phenotype. Through the Brazilian Genetic Screening Program developed at our institution, we additionally report the combination of these two mutations (p.C634Y/p.Y791F) in the RET gene in four other unrelated families. The overall penetrance of MTC and pheochromocytoma in patients with the p.C634Y/p.Y791F mutations was 79% and 13%, respectively. Our data emphasises that a comprehensive analysis of the RET gene may reveal multiple germline mutations in MEN 2 patients who exhibit an atypical clinical course of the disease.	\N	\N
23725082	To examine the effect of hypertensive disease of pregnancy (HDP) on the development of respiratory distress syndrome (RDS) in preterm neonates. A retrospective cohort study. All neonatal intensive care units in New South Wales and the Australian Capital Territory. A total of 18,845 preterm neonates aged between 24 and 36 weeks gestation admitted to the units from 1998 to 2006 were included for study purpose. Exclusion criteria were multiple pregnancies, chorioamnionitis, antepartum hemorrhage and neonates who developed respiratory diagnoses other than RDS. Effect of HDP on the development of RDS was measured. A total of 1093 neonates from hypertensive and 2274 from normotensive pregnancies with complete datasets were included. The association between HDP and the development of RDS was modified by gestational age (HDP-by-gestational age interaction p value <0.0001). Therefore the cohort was divided into extreme (24-28 weeks gestation, n = 752), severe (29-32 weeks gestation, n = 1448) and moderate (33-36 weeks gestation, n = 1167) preterm groups. HDP was associated with a decreased risk of RDS in the moderate preterm group (OR: 0.68; 95% CI: 0.48-0.98, p = 0.04) and a non-significant change in risk for the severe preterm group. Almost all neonates in the extreme preterm group experienced RDS. HDP is associated with a lower risk of developing RDS in moderate preterm neonates. This could have clinical implications in terms of risk stratification for this group of neonates.	\N	\N
23726393	The balance of risk and benefit from early neurosurgical intervention for conscious patients with superficial lobar intracerebral haemorrhage of 10-100 mL and no intraventricular haemorrhage admitted within 48 h of ictus is unclear. We therefore tested the hypothesis that early surgery compared with initial conservative treatment could improve outcome in these patients. In this international, parallel-group trial undertaken in 78 centres in 27 countries, we compared early surgical haematoma evacuation within 12 h of randomisation plus medical treatment with initial medical treatment alone (later evacuation was allowed if judged necessary). An automatic telephone and internet-based randomisation service was used to assign patients to surgery and initial conservative treatment in a 1:1 ratio. The trial was not masked. The primary outcome was a prognosis-based dichotomised (favourable or unfavourable) outcome of the 8 point Extended Glasgow Outcome Scale (GOSE) obtained by questionnaires posted to patients at 6 months. Analysis was by intention to treat. This trial is registered, number ISRCTN22153967. 307 of 601 patients were randomly assigned to early surgery and 294 to initial conservative treatment; 298 and 291 were followed up at 6 months, respectively; and 297 and 286 were included in the analysis, respectively. 174 (59%) of 297 patients in the early surgery group had an unfavourable outcome versus 178 (62%) of 286 patients in the initial conservative treatment group (absolute difference 3·7% [95% CI -4·3 to 11·6], odds ratio 0·86 [0·62 to 1·20]; p=0·367). The STICH II results confirm that early surgery does not increase the rate of death or disability at 6 months and might have a small but clinically relevant survival advantage for patients with spontaneous superficial intracerebral haemorrhage without intraventricular haemorrhage. UK Medical Research Council.	\N	\N
23731266	Existing nutritional guidelines suggest that protein requirements of adults with stage five chronic kidney disease undergoing haemodialysis (HD) or peritoneal dialysis (PD) are increased as a result of protein losses during dialysis. The present review aimed to update previous guidance and develop evidence-based practice guidelines on the protein requirements of adults undergoing maintenance dialysis. Following a PICO approach (Participants or Population, Intervention or Exposure, Comparison and Outcome), four research questions were formulated to investigate the total protein requirement and protein quality required by adults undergoing HD and PD. A comprehensive, systematic review was undertaken using the databases Medline, EMBASE and the Cochrane Library from 2005 to September 2009 for HD studies and from 1997 to September 2009 for PD studies. The literature search yielded 2931 studies, which were assessed for inclusion. Following appraisal, 19 studies in HD and 18 studies in PD met the inclusion criteria and were systematically reviewed. Limited good quality evidence supports the recommendations that: (i) adults undergoing maintenance HD require a minimum protein intake of 1.1 g kg(-1) ideal body weight (IBW) per day; and (ii) adults undergoing maintenance PD require a minimum protein intake of 1.0-1.2 kg(-1) IBW per day, in conjunction with an adequate energy intake. There were no studies that addressed the quality of protein for either HD or PD. Evidence suggests that nutritional status may be maintained with lower protein intakes than previously recommended. However, the evidence base is limited and further randomised controlled trials are required to establish the optimal protein intake for dialysis patients.	\N	\N
23742957	To determine the prevalence and persistence of new-onset clinical remission in rheumatoid arthritis (RA) patients. The Consortium of Rheumatology Researchers of North America (CORRONA) cohort was used to examine the prevalence of remission and associated comorbidities and RA therapies according to the 2011 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) remission criteria. Factors influencing the likelihood of remaining in remission were identified by logistic regression with generalized estimating equations. Analysis of variance and Tukey's test were used to determine differences in disability according to whether RA patients had been in remission or only low disease activity (LDA). A total of 2105 individuals met ACR/EULAR remission criteria at the most recent visit within CORRONA, yielding an 8% point prevalence of remission. Patients with certain comorbidities (e.g., heart failure) were significantly less likely to achieve or remain in remission compared to those without these conditions (p < 0.001 for each). Among prednisone users, the prevalence of remission was 1-6% (depending on dose) higher compared to those not on prednisone (10%). More than 50% of patients who had consistently been in remission for ≥1 year were able to remain in remission over the next year. Patients consistently in remission had less disability than patients who achieved LDA or who fluctuated between remission and LDA. Patients consistently in remission for at least 1 year had a high likelihood to remain in remission. These individuals might be considered the most likely candidates for de-escalation or withdrawal of RA treatments.	\N	\N
23745323	The GOLD 2011 recommendations for chronic obstructive pulmonary disease (COPD) introduce a new classification system to optimize treatment in individual patients. Except for FEV,, this classification incorporates breathlessness measurement using modified medical research council questionnaire (mMRC) or the COPD assessment Test (CAT) and the number of exacerbations. The aim of our study was to compare the GOLD 2010 and GOLD 2011 COPD. The study group consisted of 143 patients. Based on the post-bronchodilator FEV, only, as recommended in the GOLD 2010 report, there were 24 patients in stage I, 57patients in II, 43 in Ill and 19 in IV, respectively. In all patients, the number of exacerbations per year was noted and dyspnea was assessed with the modified MRC scale. The patients were subsequently graded to group A,B,C,D as proposed in the combined COPD assessment in GOLD 2011. Grading of 51 (35,7%) patients according to the GOLD 2011 criteria was difficult; there were 22 patients in GOLD stage I/II with > or =2 exacerbations per year and 29 patients in GOLD stage Ill/IV with < 2 exacerbations per year. They were grading to more risk group. The new classification according to GOLD 2011 lets on optimizations of the treatment, in most cases of COPD patients but in clinical practice, there may be problems with the classification of the patients with severe airway obstruction without frequent exacerbations and especially those with mild/moderate airflow limitation and frequent exacerbations.	\N	\N
23750230	All non-human great apes are endangered in the wild, and it is therefore important to gain an understanding of their demography and genetic diversity. Whole genome assembly projects have provided an invaluable foundation for understanding genetics in all four genera, but to date genetic studies of multiple individuals within great ape species have largely been confined to mitochondrial DNA and a small number of other loci. Here, we present a genome-wide survey of genetic variation in gorillas using a reduced representation sequencing approach, focusing on the two lowland subspecies. We identify 3,006,670 polymorphic sites in 14 individuals: 12 western lowland gorillas (Gorilla gorilla gorilla) and 2 eastern lowland gorillas (Gorilla beringei graueri). We find that the two species are genetically distinct, based on levels of heterozygosity and patterns of allele sharing. Focusing on the western lowland population, we observe evidence for population substructure, and a deficit of rare genetic variants suggesting a recent episode of population contraction. In western lowland gorillas, there is an elevation of variation towards telomeres and centromeres on the chromosomal scale. On a finer scale, we find substantial variation in genetic diversity, including a marked reduction close to the major histocompatibility locus, perhaps indicative of recent strong selection there. These findings suggest that despite their maintaining an overall level of genetic diversity equal to or greater than that of humans, population decline, perhaps associated with disease, has been a significant factor in recent and long-term pressures on wild gorilla populations.	\N	\N
23752073	Several studies have indicated that plasma citrulline levels reflect the extent of mucosal injury of the small intestine. This study was performed to determine whether plasma citrulline levels correlate with the disease activity in pediatric patients with Crohn disease (CD). A total of 63 CD and 23 ulcerative colitis (UC) patients were included in this study. Disease severity was assessed by pediatric CD activity index (PCDAI), pediatric UC activity index, simplified endoscopic activity score for CD, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The correlations among these variables and plasma citrulline levels were evaluated. We performed subgroup analysis whether correlations between plasma citrulline levels and disease activity depend on small bowel involvement in patients with CD. The plasma citrulline levels correlated negatively with CRP (r = -0.332, P = 0.008), ESR (r = -0.290, P = 0.022), and PCDAI (r = -0.424, P = 0.001) in patients with CD. The plasma citrulline levels were significantly lower in patients with jejunal involvement than in those without (P = 0.027). In subgroup analysis, patients with CD with jejunal involvement showed significantly negative correlations of plasma citrulline levels with CRP (r = -0.628, P = 0.016) and PCDAI (r = -0.632, P = 0.015); however, patients with CD without jejunal involvement revealed no correlations of plasma citrulline levels with CRP and PCDAI. There were no significant correlations between plasma citrulline levels and simplified endoscopic activity score for CD. There were no significant correlations of plasma citrulline levels with CRP, ESR, and pediatric UC activity index in patients with UC. Plasma citrulline levels correlated with disease severity as measured by PCDAI, CRP, and ESR in pediatric patients with CD with jejunal involvement.	\N	\N
23756272	To assess the effectiveness of a multidisciplinary team approach to reduce severe maternal morbidity in women with invasive placenta previa. We conducted a prospective study of 33 women with placenta previa and increta-percreta (diagnosed by ultrasound and/or magnetic resonance imaging) delivering at Mount Sinai Hospital, Toronto, following the introduction in January 2008 of a team-based approach to women with this condition. We included women who delivered by June 2012. We reviewed antenatal outpatient and inpatient records for use of six pre-defined team components by the attending staff obstetrician: (1) antenatal maternal-fetal medicine consultation, (2) surgical gynaecology consultation, (3) antenatal MRI, (4) interventional radiology consultation and preoperative placement of balloon catheters in the anterior divisions of the internal iliac arteries, (5) pre-planned surgical date, and (6) surgery performed by members of the invasive placenta surgical team. Antenatal course, delivery, and postpartum details were recorded to derive a five-point composite severe maternal morbidity score based on the presence or absence of: (1) ICU admission following delivery, (2) transfusion > 2 units of blood, (3) general anaesthesia start or conversion, (4) operating time in highest quartile (> 125 minutes), and (5) significant postoperative complications (readmission, prolonged postpartum stay, and/or pulmonary embolism). All 33 women survived during this time period. Two thirds (22/33) had either five or six of the six components of multidisciplinary care. Increasing use of multidisciplinary team components was associated with a significant reduction in composite morbidity (R2 = 0.228, P = 0.005). Team-based assessment and management of women with invasive placenta previa is likely to improve maternal outcomes and should be encouraged on a regional basis.	\N	\N
23774792	Both genetic inactivation and pharmacological inhibition of the cholesteryl ester synthetic enzyme acyl-CoA:cholesterol acyltransferase 1 (ACAT1) have shown benefit in mouse models of Alzheimer's disease (AD). In this study, we aimed to test the potential therapeutic applications of adeno-associated virus (AAV)-mediated Acat1 gene knockdown in AD mice. We constructed recombinant AAVs expressing artificial microRNA (miRNA) sequences, which targeted Acat1 for knockdown. We demonstrated that our AAVs could infect cultured mouse neurons and glia and effectively knockdown ACAT activity in vitro. We next delivered the AAVs to mouse brains neurosurgically, and demonstrated that Acat1-targeting AAVs could express viral proteins and effectively diminish ACAT activity in vivo, without inducing appreciable inflammation. We delivered the AAVs to the brains of 10-month-old AD mice and analyzed the effects on the AD phenotype at 12 months of age. Acat1-targeting AAV delivered to the brains of AD mice decreased the levels of brain amyloid-β and full-length human amyloid precursor protein (hAPP), to levels similar to complete genetic ablation of Acat1. This study provides support for the potential therapeutic use of Acat1 knockdown gene therapy in AD.	\N	\N
23782739	Shewanella spp. is infrequently recovered from clinical specimens. Following two outbreaks of food poisoning, eight Shewanella spp. strains were obtained from the fecal specimens of patients, food and food processing-related materials. Tetrodotoxin (TTX) was identified in the culture supernatants of these strains, and the toxin's biological activity was detected using a mouse bioassay. This study suggested that Shewanella strains can colonize and survive in human intestines. The study also raises the issues of the accumulation of TTX produced by Shewanella in food and the possible role of TTX-producing Shewanella in food poisoning.	\N	\N
23793899	Middle East Respiratory Syndrome coronavirus (MERS CoV) came to attention as an emerging pathogen causing severe respiratory illness in patients from the Middle East in September 2012. As of 14 June 2013, 58 human cases of MERS CoV infection have been confirmed, including 33 deaths (case fatality rate of 57%). MERS CoV is a beta-coronavirus, in the same family as SARS-CoV, and shares a probable origin from bats. No animal reservoir or intermediates have been definitely implicated in transmission. Limited human-to-human transmission has occurred within several clusters, as individuals without a recent travel history have become infected after exposure to an ill returned traveler.	\N	\N
23811578	Acute thallium poisoning rarely occurs but is a serious and even fatal medical condition. Currently, patients with acute thallium poisoning are usually treated with Prussian blue and blood purification therapy. However, there are few studies about these treatments for acute thallium poisoning. Nine patients with acute thallium poisoning from 1 family were treated successfully with Prussian blue and different types of blood purification therapies and analyzed. Prussian blue combined with sequential hemodialysis, hemoperfusion and/or continuous veno-venous hemofiltration were effective for the treatment of patients with acute thallium poisoning, even after delayed diagnosis. Blood purification therapies help in the clearance of thallium in those with acute thallium poisoning. Prussian blue treatment may do the benefit during this process.	\N	\N
23815257	A hallmark of acute inflammation involves the recruitment of polymorphonuclear leukocytes (neutrophils) to infected or injured tissues. The processes underlying this recruitment are complex, and include multiple mechanisms of intercellular communication between neutrophils and the inflamed tissue. In recent studies of the systemic and pulmonary vasculature, interest has increased in novel forms of intercellular communication, such as microparticle exchange and gap junctional intercellular communication. To understand the roles of these novel forms of communication in the onset, progression, and resolution of inflammatory lung injury (such as acute respiratory distress syndrome), we review the literature concerning the contributions of microparticle exchange and gap junctional intercellular communication to neutrophil-alveolar crosstalk during pulmonary inflammation. By focusing on these cell-cell communications, we aim to demonstrate significant gaps of knowledge and identify areas of considerable need for further investigations of the processes of acute lung inflammation.	\N	\N
23817139	Animal models of chronic kidney disease (CKD) approximate the human condition and are keys to understanding its pathogenesis and to developing rational treatment strategies. The ethical use of animals requires a detailed understanding of the strengths and limitations of each species and the disease model, and the way in which findings can be translated from animals to humans. While not perfect, the careful use of animal experiments offers the opportunity to examine individual mechanisms in an accelerated time frame.	\N	\N
23830210	Postoperative chylothorax is a frequently encountered pathology occurring in up to 4% of patients undergoing surgery for repair of congenital heart disease. Symptomatic thrombosis is associated with chylothorax and may contribute to its severity and duration. Furthermore, vessel thrombosis resulting in persistent vessel occlusion may impede future treatments, diagnostic studies and cardio-surgical interventions. The objective of this study was to determine the incidence of upper system thrombosis in pediatric congenital heart patients with confirmed chylothorax with ultrasound screening of all patients diagnosed with chylothorax. All pediatric patients with confirmed with chylothorax underwent doppler ultrasound of the upper venous system as per hospital standard. This retrospective cohort study enrolled all children between February 1, 2010-August 2012, post cardiac surgery with confirmed chylothorax to determine the incidence of all thrombosis. There were 1396 children who underwent 1396 cardiac surgical procedures during the study time with 760 undergoing cardiopulmonary bypass. Development of chylothorax occurred in 54 of 1396, 3.9% (95%CI 3.0;5.0) procedures in all children. In those children with chylothorax, 28 of 54 episodes, 51.8% (95%CI 38.9;64.6) had confirmed VTE. The 51.8% incidence in this study demonstrates a 2.6 fold increase in risk of thrombosis compared to 20% in children with heart disease and central venous lines and may result in serious clinical consequences. The contribution of upper venous system thrombosis to chylothorax is unknown. Often, clinical suspicion of chylothorax exists, however the lack of a standardized approach to objective diagnosis results in delayed confirmation. Approaches to therapy either treatment of confirmed thrombosis or prevention of thrombosis in patients with chylothorax require formal evaluation. Future studies are urgently needed.	\N	\N
23832758	Kallikrein 6 (KLK6) is a secreted serine protease preferentially expressed by oligodendroglia in CNS white matter. Elevated levels of KLK6 occur in actively demyelinating multiple sclerosis (MS) lesions and in cases of spinal cord injury (SCI), stroke, and glioblastoma. Taken with recent evidence establishing KLK6 as a CNS-endogenous activator of protease-activated receptors (PARs), we hypothesized that KLK6 activates a subset of PARs to regulate oligodendrocyte physiology and potentially pathophysiology. Here, primary oligodendrocyte cultures derived from wild type or PAR1-deficient mice and the murine oligodendrocyte cell line, Oli-neu, were used to demonstrate that Klk6 (rodent form) mediates loss of oligodendrocyte processes and impedes morphological differentiation of oligodendrocyte progenitor cells (OPCs) in a PAR1-dependent fashion. Comparable gliopathy was also elicited by the canonical PAR1 agonist, thrombin, as well as PAR1-activating peptides (PAR1-APs). Klk6 also exacerbated ATP-mediated oligodendrogliopathy in vitro, pointing to a potential role in augmenting excitotoxicity. In addition, Klk6 suppressed the expression of proteolipid protein (PLP) RNA in cultured oligodendrocytes by a mechanism involving PAR1-mediated Erk1/2 signaling. Microinjection of PAR1 agonists, including Klk6 or PAR1-APs, into the dorsal column white matter of PAR1(+/+) but not PAR1(-/-) mice promoted vacuolating myelopathy and a loss of immunoreactivity for myelin basic protein (MBP) and CC-1(+) oligodendrocytes. These results demonstrate a functional role for Klk6-PAR1 signaling in oligodendroglial pathophysiology and suggest that antagonists of PAR1 or its protease agonists may represent new modalities to moderate demyelination and to promote myelin regeneration in cases of CNS white matter injury or disease.	\N	\N
23838529	Classical multiple sclerosis (CMS) and neuromyelitis optica spectrum disorders (NMOSD) are distinct central nervous system inflammatory demyelinating disorders (CNS IDD). Early diagnosis of CNS IDD is important as appropriate immunotherapies to optimize prognosis. We studied the diagnoses of CNS IDD among Hong Kong Chinese in a hospital-based setting. Consecutive Chinese patients who presented to our hospital with clinically isolated syndrome and subsequently diagnosed to have CNS IDD from 1980 to 2010 were reviewed. Patients with known diagnosis of CNS IDD referred for further care were excluded. Serial sera were assayed for aquaporin-4 autoantibodies (AQP4 Ab), at least 3 assays within 2-5years. A total of 210 patients diagnosed to have CNS IDD with disease duration of at least 2years were studied. Among 198 patients with serial sera available, 40 (20.2%, 20 had NMO and 20 other NMOSD) were AQP4 Ab-positive. Four patients who were AQP4 Ab-negative on the initial assay converted to AQP4 Ab-positive on repeated assays. The diagnoses of 210 patients were CMS in 88 (41.9%), NMOSD 47 (22.4%, 27 NMO, 20 other NMOSD), single attack of myelitis 23 (11.0%), single attack of optic neuritis 21 (10.0%), relapsing myelitis 10 (4.8%), acute disseminated encephalomyelitis (ADEM) 9 (4.3%), relapsing optic neuritis in 6 (2.9%), opticospinal multiple sclerosis 3 (1.4%) and single attack of brainstem encephalitis 3 (1.4%). Compared to CMS, NMOSD patients had older onset age, lower frequencies of brain MRI abnormalities and CSF OCB, higher frequency of LETM, higher CNS inflammation attack frequency in the first 2years, worse clinical outcome with higher EDSS score and mortality rate. This hospital-based study suggests that CMS (41.9%) and NMOSD (22.4%) are the most common CNS IDD among Hong Kong Chinese. NMOSD has worse clinical outcome than CMS. Detection of AQP4 Ab facilitates early diagnosis and prompts immunotherapies of NMOSD.	\N	\N
23846297	Decoy receptor 3 (DcR3) is abundantly expressed in human tumors and protects cells from a wide range of apoptotic stimuli. In this study, we demonstrate that DcR3 is overexpressed in pancreatic carcinoma cells, and that the pancreatic carcinoma cell lines, Panc-1 and SW1990, are resistant to Fas ligand (FasL)-mediated apoptosis. To further define the function of DcR3 in cell growth and apoptosis, we used small interfering RNA (siRNA) to knockdown the expression of the DcR3 gene in Panc-1 and SW1990 cells. Our results revealed that the silencing of DcR3 expression enhanced the inhibitory effects of FasL and reduced the capabiltiy of the cells for proliferation and colony formation in vitro. In addition, the downregulation of DcR3 modulated the cell apoptotic regulators, Fas-associated death domain (FADD), caspase‑3 and caspase‑8, thus triggering cell apoptosis. Furthermore, the knockdown of DcR3 inhibited the growth of Panc-1 tumor xenografts. Taken together, our findings indicate that DcR3 is important in cancer progression and may be a used as a potential therapeutic target for the gene therapy of pancreatic carcinoma.	\N	\N
23849416	Abiraterone, an androgen synthesis inhibitor, has been successfully used in the treatment of castration-resistant prostate cancer (CRPC) for 2 yr. Enzalutamide is a second-generation nonsteroidal antiandrogen that has recently been approved for the same indication. This is the first study to evaluate the effectiveness of enzalutamide after failure of abiraterone. Thirty-five patients were identified as having received sequential therapy with abiraterone followed by enzalutamide. All patients had undergone prior docetaxel chemotherapy, and no patient had received ketoconazole. Posttreatment changes in prostate-specific antigen (PSA) were used to determine the activity of enzalutamide in patients who had received prior abiraterone. The median duration of abiraterone treatment was 9.0 mo (range: 2.0-19.0 mo). Of the 35 patients, 16 (45.7%) achieved a >50% decline in PSA, and 14 (40%) had a rising PSA as the best response. The median duration of subsequent enzalutamide treatment was 4.9 mo (Kaplan-Meier estimate; 95% confidence interval [CI], 2.4-7.4). Seven of 16 CRPC patients who were initially abiraterone-sensitive (43.8%) and 3 of 19 CRPC patients who were initially abiraterone-insensitive (15.8%) showed a >50% PSA decline while taking enzalutamide. Of the 35 patients, 17 (48.6%) were primarily enzalutamide-resistant and showed a rising PSA as the best response. Median time to progression was 4.0 mo (95% CI, 2.0-6.0) for 18 of 35 patients with at least one declining PSA value while taking enzalutamide (51.4%). Of the 17 patients who were assessable radiologically, only 1 (2.9%) attained a confirmed partial response. Small sample size was the major limitation. Enzalutamide treatment achieved only a modest response rate in patients progressing after abiraterone. Although cross-resistance between abiraterone and enzalutamide was a common phenomenon, it was not inevitable, and a small but significant number of patients showed significant benefit from sequential treatment.	\N	\N
23850538	A few years ago, Anisakis infection was almost unknown. Since the first observation in the Netherlands in 1960, several cases of gastrointestinal infections due to a zoonosis sustained by this nematode have been described in countries in which the consumption of raw or uncooked fish (e.g., marinated or salted) is common. Japan alone accounts for 90% of all cases of anisakiasis described in the literature because of the widespread use of raw fish in traditional Japanese cuisine, with sushi and sashimi. Nonetheless, other cases have been reported in Europe, North and South America, and Asia. In Italy, this zoonosis is rare and mostly transmitted by the ingestion of marinated anchovies in coastal areas, or fashion foods (sushi, sashimi, etc.) in inland areas. Once eaten, this parasite can cause an acute form of disease characterized by severe abdominal pain, and for this reason many patients receive the final diagnosis only on obtaining the surgical specimen. Since conservative medical treatment for acute anisakiasis relies on endoscopic removal of the nematode from the gastrointestinal wall if performed within 12h from the ingestion of contaminated fish, it should be compulsory to consider this parasitosis in the accident and emergency department. Here we describe two cases of infection by Anisakis simplex due to ingestion of marinated anchovies in a coastal area of the Tyrrhenian Sea and discuss the types and varieties of Anisakis infection in humans.	\N	\N
23861956	Severe stress experienced in early life may have long-term effects on adult physiological and psychological health and well-being. We studied physical and psychosocial functioning in late adulthood in subjects separated temporarily from their parents in childhood during World War II. The 1803 participants belong to the Helsinki Birth Cohort Study, born 1934-44. Of them, 267 (14.8%) had been evacuated abroad in childhood during WWII and the remaining subjects served as controls. Physical and psychosocial functioning was assessed with the Short Form 36 scale (SF-36) between 2001 and 2004. A test for trends was based on linear regression. All analyses were adjusted for age at clinical examination, social class in childhood and adulthood, smoking, alcohol intake, physical activity, body mass index, cardiovascular disease and diabetes. Physical functioning in late adulthood was lower among the separated men compared to non-separated men (b = -0.40, 95% confidence interval [95% CI]: -0.71 to -0.08). Those men separated in school age (>7 years) and who were separated for a duration over 2 years had the highest risk for lower physical functioning (b = -0.89, 95% CI: -1.58 to -0.20) and (b = -0.65, 95% CI: -1.25 to -0.05), respectively). Men separated for a duration over 2 years also had lower psychosocial functioning (b = -0.70, 95% CI: -1.35 to -0.06). These differences in physical and psychosocial functioning were not observed among women. Early life stress may increase the risk for impaired physical functioning in late adulthood among men. Timing and duration of the separation influenced the physical and psychosocial functioning in late adulthood.	\N	\N
23866601	The lecture considers a number of molecular and cellular mechanisms underlying the structural and functional rearrangement and development of renal and cardiac fibrosis in chronic kidney disease (CKD). It details the key component of disadaptative organ remodeling (the formation of myofibroblasts via epithelial-mesenchymal and endothelial-mesenchymal transdifferentiation) and the role of leading angiofibrogenic mediators (angiotensin II, transforming growth factor-beta type 1, a plasminogen activator inhibitor type 1, etc.) in the regulation of these processes. Investigation of the molecular and cellular bases of organ fibrosis, including the factors of dysregulated activation, differentiation and survival of microfibroblasts, makes it possible to specify the mechanisms of action of traditional nephro- and cardioprotective agents, to offer a possibility for a goal-oriented (target) effect on individual fibrogenic components, and to expand the arsenal of medications suppressing renal and cardiac remodeling.	\N	\N
23868901	Dabigatran is an oral direct thrombin inhibitor widely used to prevent and treat various thromboembolic complications. An advantage of this agent over other anticoagulants is that routine laboratory monitoring and related dose adjustments are considered unnecessary. A major disadvantage is the absence of a reliable means of reversing its anticoagulant effect. After U.S. Food and Drug Administration approval, recently emerged data suggest a higher bleeding risk with dabigatran, especially in the elderly. Clinicians are thus faced with caring for patients with serious bleeding events without readily available tests to measure drug levels or the anticoagulant effects of dabigatran and without effective antidotes to rapidly reverse the anticoagulant effect. On the basis of dabigatran's pharmacokinetic profile, hemodialysis and continuous renal replacement therapy have been used to remove dabigatran with the hope, still unproven, that this would rapidly reverse the anticoagulant effect and reduce bleeding in patients with normal and those with reduced kidney function. However, the best clinical approach to the patient with serious bleeding is not known, and the risks of placing a hemodialysis catheter in an anticoagulated patient can be substantial. This article reviews this issue, addressing clinical indications, drug pharmacokinetics, clinical and laboratory monitoring tests, and dialytic and nondialytic approaches to reduce bleeding in dabigatran-treated patients.	\N	\N
23871729	Acute ischemic stroke is a major cerebrovascular disease with potential morbidity and mortality. Despite the availability of thrombolytic therapy in some centers, risk factor modification and rehabilitation therapy are the mainstays of stroke management. There is supporting evidence that Ginkgo biloba may afford neuroprotection and improve the outcomes of patients with acute ischemic stroke. In a double-blind, placebo-controlled, randomized controlled trial, we assessed the efficacy of G biloba on functional outcome in patients with acute stroke. The National Institutes of Heath Stroke Scale (NIHSS) was used to measure functional outcome. A total of 102 patients with acute ischemic stroke were studied. All patients received either G biloba or placebo tablets for 4 months. This trial was registered to the Iranian Registry of Clinical Trials (www.irct.ir; trial IRCT138804212150N1). There were 52 patients who received G biloba and 50 patients who were in the placebo group. Age, sex distribution, previous medical condition, and laboratory data did not have any significant difference between the 2 groups (P>.05). The mean difference of 4-month follow-up NIHSS scores and NIHSS scores at admission was 4.7±2.7 and 4.1±3.0 in the G biloba and placebo groups, respectively (P>.05). The primary outcome-a 50% reduction in the 4-month follow-up NIHSS score compared to the baseline NIHSS score-was reached in 17 patients (58.6%) and 5 patients (18.5%) in the G biloba and placebo groups, respectively (P<.05). The risk ratio and number needed to treat were 3.16 (confidence interval 1.35-7.39) and 2.50 (confidence interval 1.58-5.90), respectively. In addition, multivariate regression adjusted for age and sex revealed a significant NIHSS decline in the G biloba group compared to the placebo group (P<.05). Our data suggest that G biloba may have protective effects in ischemic stroke. Therefore, the administration of G biloba is recommended after acute ischemic stroke.	\N	\N
23872666	Sequences of human endogenous retroviruses (HERVs) are members of the long terminal repeat (LTR) retrotransposon family. Although the expression of HERV has long been a topic of investigation, HERV-insertion polymorphisms are not well known, and a genetic association between HERV-insertion polymorphisms and cancer has never been reported. To identify novel HERV loci in the genome from cancer tissues, we carried out the inverse PCR method targeting a conserved LTR region of HML-2, which is the most recently acquired HERV group. Novel two insertions, HML-2_sLTR(1p13.2) and HML-2_sLTR(19q12), were identified as insertionally polymorphic solo LTRs. Furthermore, a significant prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in female never-smoking patients aged 60 years and over who had lung adenocarcinoma [versus the other genotyping; odds ratio (OR): 1.97; 95% confidence interval (CI): 1.01-3.81]. In another cohort consisting of female never-smoking patients with lung adenocarcinoma, a prevalence of HML-2_sLTR(1p13.2) homozygosity tended to be high in patients aged 60 years and over (versus the other genotyping; OR: 2.03; 95% CI: 0.96-4.29), whereas a low prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in patients <60 years old (versus the other genotyping; OR: 0.31; 95% CI: 0.11-0.94). Our results suggest that HML-2_sLTR(1p13.2) is involved with the susceptibility to lung adenocarcinoma in female never-smokers in an age-dependent manner and that other HERV polymorphisms related to human diseases might remain to be identified in the human genome.	\N	\N
23874931	The HIV-1 characteristics associated with mother to child transmission (MTCT) are still poorly understood and if known would indicate where intervention strategies should be targeted. In contrast to horizontally infected individuals, exposed infants possess inherited antibodies (Abs) from their mother with the potential to protect against infection. We investigated the HIV-1 gp160 envelope proteins from seven transmitting mothers (TM) whose children were infected either during gestation or soon after delivery and from four non-transmitting mothers (NTM) with similar viral loads and CD4 counts. Using pseudo-typed viruses we tested gp160 envelope glycoproteins for TZM-bl infectivity, CD4 and CCR5 interactions, DC-SIGN capture and transfer and neutralization with an array of common neutralizing Abs (NAbs) (2F5, 2G12, 4E10 and b12) as well as mother and infant plasma. We found no viral correlates associated with HIV-1 MTCT nor did we find differences in neutralization with the panel of NAbs. We did, however, find that TM possessed significantly higher plasma neutralization capacities than NTM (P = 0.002). Furthermore, we found that in utero (IU) TM had a higher neutralization capacity than mothers transmitting either peri - partum (PP) or via breastfeeding (BF) (P = 0.002). Plasma from children infected IU neutralized viruses carrying autologous gp160 viral envelopes as well as those from their corresponding mothers whilst plasma from children infected PP and/or BF demonstrated poor neutralizing capacity. Our results demonstrate heightened autologous NAb responses against gp120/gp41 can associate with a greater risk of HIV-1 MTCT and more specifically in those infants infected IU. Although the number of HIV-1 transmitting pairs is low our results indicate that autologous NAb responses in mothers and infants do not protect against MTCT and may in fact be detrimental when considering IU HIV-1 transmissions.	\N	\N
23876833	Tyrosine kinase inhibitors treatment in responding chronic myeloid leukaemia (CML) patients is generally continued indefinitely. In this randomised phase II trial, we investigated whether CML patients in molecular response(4.5) (MR(4.5), quantitative reverse-transcription polymerase chain reaction (RQ-PCR)) after previous combination therapy with imatinib and cytarabine may discontinue imatinib treatment safely. Thirty-three patients from the HOVON 51 study with an MR(4.5) for at least 2 years who were still on imatinib treatment were randomised between continuation of imatinib (arm A, n=18) or discontinuation of imatinib (arm B, n=15). After a median follow up of 36 months since randomisation, 3 patients (17%) in arm A and 10 patients (67%) in arm B had a molecular relapse. All 3 relapsing patients in arm A had also stopped imatinib after randomisation. All but one relapsing patient relapsed within 7 months after discontinuation of imatinib. The molecular relapse rate at 12 and 24 months after randomisation was 0% and 6% (arm A) and 53% and 67% (arm B) respectively. As-treated analysis revealed 56% and 61% relapses at 1 and 2 years since cessation in patients who discontinued imatinib, in contrast to 0% of patients who continued imatinib. All evaluable patients remained sensitive to imatinib after reinitiation and regained a molecular response. Our data suggest that discontinuation of imatinib is safe in patients with durable MR(4.5).	\N	\N
23877014	This study aimed to evaluate the efficacy of radiation therapy for pelvic lymph node metastasis from uterine cervical cancer and identify an optimal radiation regimen. A total of 111 metastatic pelvic lymph nodes, ranging from 11 to 56 mm (median, 25 mm) on CT/MRI, in 62 patients with uterine cervical cancer were treated initially with curative radiation therapy, with 46 patients receiving concurrent chemotherapy. Total radiation doses ranged from 45 to 61.2 Gy (median, 50.4 Gy) in 1.8-2 Gy (median, 1.8 Gy) fractions. At a median follow-up of 33 months, 46 of the 62 patients survived. Only 2 irradiated lymph nodes, 24 and 28 mm in diameter, in 1 patient progressed after irradiation alone with 50.4 Gy in 1.8 Gy fractions. All 33 metastatic lymph nodes ≥ 30 mm in diameter were controlled by irradiation at a median dose of 55.8 Gy. The 3-year lymph node-progression free rates were 98.2% in all 62 patients and 98.0% in all 111 metastatic lymph nodes. Except for transient hematologic reactions, 2 patients developed grade ≥ 3 therapy-related toxicities, 1 with an ulcer and the other with perforation of the sigmoid colon. In addition, 2 patients experienced ileus after irradiation. Radiation therapy effectively controlled pelvic lymph node metastases in patients with uterine cervical cancer, with most nodes <24 mm in diameter controlled by total doses of 50.4 Gy in 1.8 Gy fractions and larger nodes controlled by 55.8 Gy, particularly with concurrent chemotherapy. Higher doses to metastatic lymph nodes may increase intestinal toxicities.	\N	\N
23880785	The most abundant urinary protein, Tamm-Horsfall protein, later renamed uromodulin, is expressed exclusively by the thick ascending limb cells of the kidney and released into urine from the apical cell membrane. Uromodulin is believed to protect against urinary tract infections and stones, but its other physiologic functions have remained obscure until recently. Renewed interest in uromodulin has been brought about by the identification of uromodulin mutations as causes of a discrete group of diseases that are distinct from nephronophthisis. The three overlapping clinical uromodulin-associated kidney diseases (UAKD) are medullary cystic disease type 2, familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Previously thought of as "adult diseases", it is now recognized that they may also present in childhood and even in infancy. Common characteristics of all three diseases are autosomal dominant inheritance, unremarkable urine sediment and slow progression to end-stage renal disease (ESRD). They are frequently associated with hyperuricemia and gout. These diseases appear to result from failure of the mutant uromodulin to be incorporated into the apical cilium, thereby placing UAKD in the category of "ciliopathies". In addition to causing specific UAKD, certain uromodulin gene polymorphisms have been linked to ESRD in general, suggesting that uromodulin plays a modulatory role in kidney disease progression.	\N	\N
23886073	Influenza A and B viruses form different genera, which were originally distinguished by antigenic differences in their nucleoproteins and matrix 1 proteins. Cross-protection between these two genera has not been observed in animal experiments, which is consistent with the low homology in viral proteins common to both viruses except for one of three polymerase proteins, polymerase basic 1 (PB1). Recently, however, antibody and CD4+ T cell epitopes conserved between the two genera were identified in humans. A protective antibody epitope was located in the stalk region of the surface glycoprotein, hemagglutinin, and a CD4+ T cell epitope was located in the fusion peptide of the hemagglutinin. The fusion peptide was also found to contain antibody epitopes in humans and animals. A short stretch of well-conserved peptide was also identified in the other surface glycoprotein, neuraminidase, and antibodies binding to this peptide were generated by peptide immunization in rabbits. Although PB1, the only protein which has relatively high overall sequence homology between influenza A and B viruses, is not considered an immunodominant protein in the T cell responses to influenza A virus infection, amino acid sequence comparisons show that a considerable number of previously identified T cell epitopes in the PB1 of influenza A viruses are conserved in the PB1 of influenza B viruses. These data indicate that B and T cell cross-reactivity exists between influenza A and B viruses, which may have modulatory effects on the disease process and recovery. Although the antibody titers and the specific T cell frequencies induced by natural infection or standard vaccination may not be high enough to provide cross protection in humans, it might be possible to develop immunization strategies to induce these cross-reactive responses more efficiently.	\N	\N
23894446	A prostacyclin analogue, ONO-1301, is reported to upregulate beneficial proteins, including stromal cell derived factor-1 (SDF-1). We hypothesized that the sustained-release delivery of ONO-1301 would enhance SDF-1 expression in the acute myocardial infarction (MI) heart and induce bone marrow cells (BMCs) to home to the myocardium, leading to improved cardiac function in mice. ONO-1301 significantly upregulated SDF-1 secretion by fibroblasts. BMC migration was greater to ONO-1301-stimulated than unstimulated conditioned medium. This increase was diminished by treating the BMCs with a CXCR4-neutralizing antibody or CXCR4 antagonist (AMD3100). Atelocollagen sheets containing a sustained-release form of ONO-1301 (n = 33) or ONO-1301-free vehicle (n = 48) were implanted on the left ventricular (LV) anterior wall immediately after permanent left-anterior descending artery occlusion in C57BL6/N mice (male, 8-weeks-old). The SDF-1 expression in the infarct border zone was significantly elevated for 1 month in the ONO-1301-treated group. BMC accumulation in the infarcted hearts, detected by in vivo imaging after intravenous injection of labeled BMCs, was enhanced in the ONO-1301-treated hearts. This increase was inhibited by AMD3100. The accumulated BMCs differentiated into capillary structures. The survival rates and cardiac function were significantly improved in the ONO-1301-treated group (fractional area change 23±1%; n = 22) compared to the vehicle group (19±1%; n = 20; P = 0.004). LV anterior wall thinning, expansion of infarction, and fibrosis were lower in the ONO-1301-treated group. Sustained-release delivery of ONO-1301 promoted BMC recruitment to the acute MI heart via SDF-1/CXCR4 signaling and restored cardiac performance, suggesting a novel mechanism for ONO-1301-mediated acute-MI heart repair.	\N	\N
23899604	In the mammalian nervous system, axons are commonly surrounded by myelin, a lipid-rich sheath that is essential for precise and rapid conduction of nerve impulses. In the peripheral nervous system (PNS), myelin sheaths are formed by Schwann cells which wrap around individual axons. While the tyrosine kinase receptors ERBB2 and ERBB3 are established mediators of peripheral myelination, less is known about the functions of the related epidermal growth factor receptor (EGFR) in the regulation of PNS myelination. Here, we report a peripheral neurodegenerative disease caused by increased EGFR activation. Specifically, we characterize a symmetric and distally pronounced, late-onset muscular atrophy in transgenic mice overexpressing the EGFR ligand epigen. Histological examination revealed a demyelinating neuropathy and axon degeneration, and molecular analysis of signaling pathways showed reduced protein kinase B (PKB, AKT) activation in the nerves of Epigen-tg mice, indicating that the muscular phenotype is secondary to PNS demyelination and axon degeneration. Crossing of Epigen-tg mice into an EGFR-deficient background revealed the pathology to be completely EGFR-dependent. This mouse line provides a new model for studying molecular events associated with early stages of peripheral neuropathies, an essential prerequisite for the development of successful therapeutic interventions.	\N	\N
23902839	To explore the value of sentinel lymph nodes (SLN) metastasis status in predicting the presence of residual disease in non-sentinel lymph nodes (nSLN) and the feasibility of avoiding or reducing the scope of axillary lymph node dissection (ALND) for patients with single positive SLN. A retrospective study was conducted for 2265 patients with invasive breast carcinomas undergoing sentinel lymph nodes biopsy (SLNB) at Shandong Cancer Hospital between November 1999 and December 2011. And 1228 patients with axillary dissection were screened and divided into 5 groups of (-), (1/n), (1/1), (n/N), (n/n) (n ≥ 2, N ≥ 3, N > n) according to the status of SLN metastasis. The nSLN metastasis rate of SLN(-), (1/n), (1/1), (n/N) and (n/n) groups was 11.8%(73/618), 25.2%(65/258), 49.6%(67/135), 48.4%(60/124)and 65.6%(61/93)respectively. A comparison of SLN(-), (1/n), (1/1), (n/N), and (n/n) groups of nSLN metastasis showed a significant difference (P = 0.000). The differences of nSLN metastasis between SLN(-) and other groups (including 1/n, 1/1, n/N, n/n group) were significant (P = 0.000). This difference was also significant between SLN (1/n) and other positive groups (include 1/1, n/N, n/n group) (P = 0.000), but not significant between SLN(1/1), (n/N) and (n/n) groups (P = 0.842, 0.017, 0.042 respectively, Chi-square segmentation). No significant difference existed between axillary lymph node metastasis on Level II and III of SLN 1/n group and SLN(-) group (P = 0.012, 0.570,χ(2) segmentation). The status of SLN metastasis is one of influencing factors for the nSLN metastasis of patients with invasive breast cancer. The possibility of non-sentinel lymph node involvement for patients with single SLN metastasis was smaller than that of other SLN-positive patients. It is safe for some SLN 1/n patients to undergo low lymph node dissection. But ALND is not avoided for patients with single positive SLN (SLN 1/n n ≥ 2). Their clinicopathological variables should be also considered.	\N	\N
23905909	Peripheral arterial diseases associated with an increased risk of death in kidney transplant patients. Natriuretic peptide has anti-atherosclerotic effects. We sought to evaluate the relation between ankle-brachial index and fasting serum long-acting natriuretic peptide concentrations in kidney transplant patients. Fasting blood samples were obtained from 69 kidney transplant patients. Serum long-acting natriuretic peptide concentrations were measured using a commercially available enzyme immunoassay kit. Left or right ankle-brachial index values that were < 0.9 were included in the low ankle-brachial index group. Fifteen patients (21.7%) were enrolled in the low ankle-brachial index group. Increased waist circumference (P = .013), higher serum total cholesterol levels (P = .019), higher triglyceride levels (P = .002), and decreased serum long-acting natriuretic peptide concentrations (P = .006) were noted in the low ankle-brachial index group. Univariate linear regression analysis indicated that the left/right ankle-brachial index values of the subjects were negatively correlated with serum triglycerides (P = .008 or P < .001) and fasting glucose levels (P = .034 or P = .012), but were positively correlated with long-acting natriuretic peptide concentrations (P = .011 or P = .011). Multivariate forward stepwise linear regression analyses of the significant variables revealed that serum triglycerides and long-acting natriuretic peptide levels were independent predictors of the left/right ankle-brachial index values of kidney transplant patients. Serum long-acting natriuretic peptide concentrations correlate positively with ankle-brachial index values among the kidney transplant patients.	\N	\N
23908572	To evaluate the clinical usefulness of binocular multifocal electroretinography (mfERG) by comparing results with conventional monocular mfERG in patients with monocular macular disease. mfERG testing was conducted on 32 patients with monocular macular disease and 30 normal subjects. An initial mfERG was simultaneously recorded from both eyes with two recording electrodes under binocular stimulation. A second mfERG was subsequently recorded with conventional monocular stimulation. Amplitudes and implicit times of each ring response of the binocular and monocular recordings were compared. Ring ratios of the binocular and monocular recording were also compared. In the macular disease group, there were no statistical differences in amplitude or implicit time for each of the five concentric rings between the monocular and binocular recordings. However, with binocular simulation, the ring ratios (ring 1 / ring 4, ring 1 / ring 5) were significantly reduced in the affected eye. In the normal control group, there were no statistical differences in any parameters between the monocular and binocular recordings. Binocular mfERG could be a good alternative to the conventional monocular test. In addition, given that the test needs stable fixation of the affected eye during the binocular test, the reliability of the test results could be improved, especially for patients with monocular macular disease.	\N	\N
23934213	Human Nijmegen breakage syndrome, caused by the hypomorphic mutation of Nbn gene, is a hereditary instability disease, characterized by chromosomal instability, immunodeficiency, radiosensitivity, cancer predisposition and microcephaly. To study the roles of Nbn protein in microcephaly, Nbn gene was specifically deleted in the central nervous system of mice by nestin-Cre targeting gene system (Frappart et al. in Nat Med 11:538-544, 2005). Strikingly, newborn Nbn-deficient mice exhibit the evident microcephalic cerebellum, which contributes to severe ataxia and balance deficiency. In this study, we first report that PI3K/AKT/mTOR signaling pathway that performs neurotrophic-protecting role in neuronal growth is significantly inhibited in newborn Nbn-deficient cortex and cerebellum. In addition, JNK signaling and ATR signaling are likely to converge to regulate the cerebellar apoptosis of newborn Nbn-deficient mice.	\N	\N
23935207	This Phase II trial was designed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy in patients with poor-risk rectal cancer. Patients with magnetic resonance imaging-defined poor-risk rectal cancer received neoadjuvant oxaliplatin and capecitabine and bevacizumab followed by total mesorectal excision or more extensive surgery. Between February 2010 and December 2011, 32 patients were enrolled in this study. The completion rate of the scheduled chemotherapy was 91%. Reasons for withdrawal were refusal to continue therapy in two patients and disease progression in one, with two of these three patients not undergoing surgery. Among the 29 patients who completed the scheduled chemotherapy, one refused surgery within 8 weeks after the completion of chemotherapy, which was the period stipulated by the protocol, and another had rectal perforation, requiring urgent laparotomy. As a result, the completion rate of this experimental treatment was 84%. Of the 30 patients who underwent surgery, the R0 resection rate was 90% and a postoperative complication occurred in 43%. A pathological complete response was observed in 13% and good tumor regression was exhibited in 37%. Neoadjuvant oxaliplatin and capecitabine plus bevacizumab for poor-risk rectal cancer caused a high rate of anastomotic leakage and experienced a case with perforation during chemotherapy, both of which were bevacizumab-related toxicity. Although the short-term results with the completion rate of 84.4% and the pathological complete response rate of 13.3% were satisfactory, we have to reconsider the necessity of bevacizumab in neoadjuvant chemotherapy (UMIN number, 000003507).	\N	\N
23955530	Type 1 diabetes (T1D) is one of the most common chronic diseases with childhood onset, and the disease incidence has increased two to fivefold over the past half century by as yet unknown means. T1D occurs when the body's immune system turns against itself, destroying in a very specific and targeted way-the pancreatic β-cells. T1D results from poorly defined interactions between susceptibility genes and environmental determinants. In contrast to the rapid progress in finding T1D genes, identification and confirmation of environmental determinants remain a formidable challenge. This review article will give an overview of ongoing prospective cohort studies aiming to identify the environmental trigger(s) causing T1D.	\N	\N
23956301	Human papillomavirus 16 (HPV16) infection causes 50 % or more of cervical cancers in women. The HPV16 E7 oncogene is continuously expressed in infected epithelium with its oncogenicity linked to cervical cancer. The E7 protein is an ideal target in control of HPV infection through T-cell-mediated immunity. Using HPV16 E7-transgenic mouse keratinocytes (KCs-E7) to investigate T-cell-mediated immune responses, we have shown previously that HPV16-encoded E7 protein inhibits IFN-γ-mediated enhancement of MHC class I antigen processing and T-cell-induced target cell lysis. In this study, we found that HPV16 E7 suppresses IFN-γ-induced phosphorylation of STAT1((Tyr701)), leading to the blockade of interferon regulatory factor-1 (IRF-1) and transporter associated antigen processing subunit 1 (TAP-1) expression in KCs-E7. The results of a (51)Cr release assay demonstrated that IFN-γ-treated KCs-E7 escaped from CTL recognition because HPV16 E7 downregulated MHC class I antigen presentation on KCs. Restoration of IRF-1 expression in KCs-E7 overcame the inhibitory effect of E7 protein on IFN-γ-mediated CTL lysis and MHC class I antigen presentation on KCs. Our results suggest that HPV16 E7 interferes with the IFN-γ-mediated JAK1/JAK2/STAT1/IRF-1 signal transduction pathway and reduces the efficiency of peptide loading and MHC class I antigen presentation on KCs-E7. These results may reveal a new mechanism whereby HPV16 escapes from immune surveillance in vivo.	\N	\N
23962064	Understanding how alveoli and the underlying capillary network develop and how these mechanisms are disrupted in disease states is critical for developing effective therapies for lung regeneration. Recent evidence suggests that lung angiogenesis promotes lung development and repair. Vascular endothelial growth factor (VEGF) preserves lung angiogenesis and alveolarization in experimental O2-induced arrested alveolar growth in newborn rats, but combined VEGF+angiopoietin 1 treatment is necessary to correct VEGF-induced vessel leakiness. Hypoxia-inducible factors (HIFs) are transcription factors that activate multiple O2-sensitive genes, including those encoding for angiogenic growth factors, but their role during postnatal lung growth is incompletely understood. By inducing the expression of a range of angiogenic factors in a coordinated fashion, HIF may orchestrate efficient and safe angiogenesis superior to VEGF. We hypothesized that HIF inhibition impairs alveolarization and that HIF activation regenerates irreversible O2-induced arrested alveolar growth. HIF inhibition by intratracheal dominant-negative adenovirus (dnHIF-1α)-mediated gene transfer or chetomin decreased lung HIF-1α, HIF-2α, and VEGF expression and led to air space enlargement and arrested lung vascular growth. In experimental O2-induced arrested alveolar growth in newborn rats, the characteristic features of air space enlargement and loss of lung capillaries were associated with decreased lung HIF-1α and HIF-2α expression. Intratracheal administration of Ad.HIF-1α restored HIF-1α, endothelial nitric oxide synthase, VEGF, VEGFR2, and Tie2 expression and preserved and rescued alveolar growth and lung capillary formation in this model. HIFs promote normal alveolar development and may be useful targets for alveolar regeneration.	\N	\N
23962825	G protein-mediated signal transduction is essential for the regulation of cardiovascular function, including heart rate, growth, contraction, and vascular tone. Regulators of G protein Signaling (RGS proteins) fine-tune G protein-coupled receptor-induced signaling by regulating its magnitude and duration through direct interaction with the α subunits of heterotrimeric G proteins. Changes in the RGS protein expression and/or function in the heart often lead to pathophysiological changes and are associated with cardiac disease in animals and humans, including hypertrophy, fibrosis development, heart failure, and arrhythmias. This article focuses on Regulator of G protein Signaling 2 (RGS2), which is widely expressed in many tissues and is highly regulated in its expression and function. Most information to date has been obtained in biochemical, cellular, and animal studies, but data from humans is emerging. We review recent advances on the functional role of cardiovascular RGS2 and the mechanisms that determine its signaling selectivity, expression, and functionality. We highlight key unanswered questions and discuss the potential of RGS2 as a therapeutic target.	\N	\N
23968196	Actinic prurigo (AP) is an idiopathic photodermatosis that usually onsets during childhood and predominates in women. It is characterized by the symmetrical involvement of sun-exposed areas of the skin, lips, and conjunctiva. This study aimed to analyze the risk factors associated with AP using a case-control design. All patients diagnosed with AP during 1990-2006 at Dr. Manuel Gea González General Hospital in Mexico City were included. Respective controls were recruited. Race, demographic, geographic, socioeconomic, environmental, clinical, and nutritional risk factors were assessed. A total of 132 persons were enrolled. These included 44 cases and two control groups comprising, respectively, dermatology and non-dermatology outpatients without AP or any autoimmune disease. Distribution by gender, age, place of birth, place of residence, and economic status did not differ significantly among the three groups. A total of 256 variables were analyzed. Only 19 variables were found to be statistically significant (P < 0.05). These were: use of a boiler; use of firewood; car ownership; use of earthenware; mixed material housing; socioeconomic level 1; sun exposure; use of soap; lemon consumption; use of moisturizing hair cream; living with pets in the house; living with farm animals; age; having a family member with AP; having had surgery; having had trauma; having been hospitalized; use of oral medication; and use of herbal medication. Of 40 macro- and micronutrients analyzed, 11 were found to have statistically significant effects (P < 0.05). Multiple epidemiologic, geographic, clinical, and immunologic factors are involved in the etiology of AP. This study proposes a clear line for research directed at specific risk factors that refer to an individual's clinical, allergic, health, and socioeconomic status. Further study should also investigate the etiologic role of diet in AP and the molecular mechanisms behind the development of AP to establish whether AP is caused by exposure to polycyclic aromatic hydrocarbons.	\N	\N
23982030	To determine the rate of unplanned PICU readmissions, examine the characteristics of index admissions associated with readmission, and compare outcomes of readmissions versus index admissions. Retrospective cohort analysis. Ninety North American PICUs that participated in the Virtual Pediatric Intensive Care Unit Systems. One hundred five thousand four hundred thirty-seven admissions between July 2009 and March 2011. None. Unplanned PICU readmission within 48 hours of index discharge was the primary outcome. Summary statistics, bivariate analyses, and mixed-effects logistic regression model with random effects for each hospital were performed.There were 1,161 readmissions (1.2%). The readmission rate varied among PICUs (0-3.3%), and acute respiratory (56%), infectious (35%), neurological (28%), and cardiovascular (20%) diagnoses were often present on readmission. Readmission risk increased in patients with two or more complex chronic conditions (adjusted odds ratio, 1.72; p < 0.001), unscheduled index admission (adjusted odds ratio, 1.37; p < 0.001), and transfer to an intermediate unit (adjusted odds ratio, 1.29; p = 0.004, compared with ward). Trauma patients had a decreased risk of readmission (adjusted odds ratio, 0.67; p = 0.003). Gender, race, insurance, age more than 6 months, perioperative status, and nighttime transfer were not associated with readmission. Compared with index admissions, readmissions had longer median PICU length of stay (3.1 vs 1.7 d, p < 0.001) and higher mortality (4% vs 2.5%, p = 0.002). Unplanned PICU readmissions were relatively uncommon, but were associated with worse outcomes. Several patient and admission characteristics were associated with readmission. These data help identify high-risk patient groups and inform risk-adjustment for standardized readmission rates.	\N	\N
23983044	To determine the differences in carotid intima-media thickness (CIMT) between patients with psoriatic diseases with and without metabolic syndrome. Eligible patients from the Cardiometabolic Outcome Measures in Psoriatic Arthritis Study database, which is comprised of both psoriasis and psoriatic arthritis (PsA) patients enrolled at 2 academic medical centers, were included. Detailed cardiovascular (CV) risk factors, including metabolic syndrome profiles, medication use, disease activity, and CIMT, were examined. A total of 343 patients with psoriatic disease were evaluated (42.28% with psoriasis and 57.72% with PsA). PsA patients were significantly older, with longer disease duration and higher blood pressure, body mass index, and C-reactive protein (CRP) level. PsA patients took more disease-modifying antirheumatic drugs (DMARDs) and corticosteroids and underwent more CV procedures. There were no differences in prior CV events, family history of CV risk, and Framingham/Adult Treatment Panel III Risk Score. PsA patients had a higher risk of metabolic syndrome (univariate odds ratio [OR] 1.78 [95% confidence interval (95% CI) 1.08-2.95], P = 0.025). Even after adjusting for age, CRP level, and diastolic blood pressure, PsA patients not taking DMARDs were twice as likely to have metabolic syndrome compared to psoriasis patients (adjusted OR 2.09 [95% CI 0.78-5.59], P = 0.049). PsA patients with metabolic syndrome had the thickest CIMT compared to any other group (P < 0.001). PsA patients had an increased prevalence of metabolic syndrome with significantly greater CIMT measurements compared to patients with psoriasis. Furthermore, PsA patients with metabolic syndrome had the greatest CIMT measurements compared to PsA patients without metabolic syndrome and psoriasis patients with or without metabolic syndrome. Incremental increases in inflammatory pathways in PsA may contribute to a higher CV risk as compared to psoriasis patients.	\N	\N
23987905	This study evaluated effectiveness of three different surgical strategies for treating ascending aorta aneurysm, with or without involvement of the aortic root, associated with bicuspid aortic valve (BAV). Between 2005 and 2011, 150 consecutive patients underwent a Bentall operation in the presence of ascending aorta and aortic root dilation exceeding 45 mm in diameter and malfunctioning BAV (n = 46, group 1); separate aortic valve and ascending aorta replacement in presence of ascending aorta dilation exceeding 45 mm, aortic root of less than 45 mm, and malfunctioning BAV (n = 77, group 2); or ascending aorta replacement, with or without BAV repair, in the presence of ascending aorta dilation exceeding 45 mm, aortic root of less than 45 mm, and normally functioning or mildly insufficient BAV (n = 27, group 3). Compared with groups 2 and 3, group 1 patients were younger and affected by more severe BAV insufficiency and worse left ventricular function. In groups 1, 2, and 3, respectively, operative mortality was 2.1%, 1.3%, and 0%, and 5-year survival was 94% ± 4%, 92% ± 3.4%, and 100%. At 5 years, no patient in any group required reoperation on the ascending aorta or experienced aortic complications. In groups 2 and 3, root dimensions did not increase and were also significantly smaller compared with preoperative measurements (p < 0.05). Aortic regurgitation grade in group 3 (0.5 ± 0.8/4+) did not increase compared with the preoperative grade (0.8 ± 0.9/4+). At midterm follow-up, the Bentall operation remains associated with optimal results for the treatment of BAV, despite a worse preoperative presentation. In presence of a mildly diseased or normal aortic root and normal BAV function at the time of operation, less invasive surgical procedures, BAV-sparing, or repair procedures, appear to offer gratifying results.	\N	\N
23993863	Despite extensive study, few therapeutic targets have been identified for glioblastoma (GBM). Here we show that patient-derived glioma sphere cultures (GSCs) that resemble either the proneural (PN) or mesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics. Moreover, we found that a subset of the PN GSCs undergoes differentiation to a MES state in a TNF-α/NF-κB-dependent manner with an associated enrichment of CD44 subpopulations and radioresistant phenotypes. We present data to suggest that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process. We further show that the MES signature, CD44 expression, and NF-κB activation correlate with poor radiation response and shorter survival in patients with GBM.	\N	\N
24010694	Lenalidomide is an immunomodulatory drug approved by the AEMPS and the EMA, in combination with dexamethasone, for the treatment of multiple myeloma in adult patients who have received at least one prior therapy. Moreover, it has recently been approved for the treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate. It has also shown to be active in other hematologic and no hematologic diseases. Growing evidence of its use entails a challenge when situating the drug in a cost-effective way to treat these diseases. On this article we review the available evidence on the use of lenalidomide in the second line treatment of patients with chronic lymphocytic leukemia, primary amyloidosis and primary myelofibrosis, and in the first line treatment of patients with myelodysplastic syndrome, and also the evidence of other immunomodulators. Different clinical practice guidelines and scientific evidence portals consider lenalidomide a valid alternative in the first-line treatment of patients with myelodysplastic syndromes, specially those with the deletion of 5q, and in second line for patients with chronic lymphocytic leukemia. However, the available evidence of lenalidomide in the treatment of patients with primary amyloidosis and primary myelofibrosis is limited, ant thus is not considered as the first choice treatment. In any case, the treatment of choice should consider the safety profile in each patient, the previous treatments that has received and the own therapeutic protocols of each center.	\N	\N
24016609	Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. This retrospective study investigated ROP, including incidence, demographic information,risk factors, treatments, and refractive outcomes, in southern Taiwan over a 10-year period. The authors retrieved the National Cheng Kung University Hospital database between the years 2000 and 2009 for newborns with a gestational age less than 32 weeks and/or with a birth weight less than 1500 g who had been screened for ROP. We recorded sex, birth weight, gestational age, in-hospital versus out-of-hospital birth, paternal and maternal ages, whether there were multiple gestations, parity, Apgar scores, length of hospital stay, risk factors, presence and severity of ROP and whether it was treated, and refraction at the last visit. Regression analyses were performed to identify risk factors for ROP. A total of 503 live births were included. ROP was identified in 190 (37.8%) and met criteria for treatment in 59 (11.7%).ROP was diagnosed as stage 1, 2, 3, 4, and 5 in 61 (12.1%), 36 (7.2%), 81 (16.1%), 11 (2.2%), and 1 (0.2%) infant, respectively. Lower birth weight and younger gestational age were risk factors for greater severity of ROP (p < 0.001). Of the 167 with extremely low birth weight (<1000 g), 118 (70.7%) had ROP and 49 (29.3%) required treatment. On univariate analysis, low birth weight, younger gestational age, and risk factors such as respiratory distress syndrome, chronic lung disease, patent ductus arteriosus, surfactant usage, indomethacin usage, sepsis, upper gastrointestinal bleeding, blood transfusion, and necrotizing enterocolitis were associated with ROP. Multivariate logistic regression analysis showed that only lower birth weight was a significant and independent risk factor for ROP. Myopia (76%)and anisometropia (28%)were common in advanced ROP. Low birth weight is a major risk factor for ROP. Infants with extremely low birth weight had a higher risk of severe ROP. Common ocular sequelae of advanced ROP were myopia and anisometropia.	\N	\N
24021446	We present two young patients with morphea or localized scleroderma undergoing systemic treatment, who developed papular lesions on pre-existing sclerotic plaques. Histology was compatible with a papular presentation of morphea and other entities in the differential diagnosis were ruled out. We believe this is a very uncommon presentation of activity in lesions of morphea and should be made known to clinicians so that activity and progression of the disease can be recognized and treated to avoid complications.	\N	\N
24032423	Spinocerebellar ataxia type 1 (SCA1) is a hereditary, progressive and fatal movement disorder that primarily affects the cerebellum. Non-invasive imaging markers to detect early disease in SCA1 will facilitate testing and implementation of potential therapies. We have previously demonstrated the sensitivity of neurochemical levels measured by (1) H magnetic resonance spectroscopy (MRS) to progressive neurodegeneration using a transgenic mouse model of SCA1. In order to investigate very early neurochemical changes related to neurodegeneration, here we utilized a knock-in mouse model, the Sca1(154Q/2Q) line, which displays milder cerebellar pathology than the transgenic model. We measured cerebellar neurochemical profiles of Sca1(154Q/2Q) mice and wild-type littermates using 9.4T MRS at ages 6, 12, 24, and 39 weeks and assessed the cerebellar pathology of a subset of the mice at each time point. The Sca1(154Q/2Q) mice displayed very mild cerebellar pathology even at 39 weeks, however, were distinguished from wild types by MRS starting at 6 weeks. Taurine and total choline levels were significantly lower at all ages and glutamine and total creatine levels were higher starting at 12 weeks in Sca1(154Q/2Q) mice than controls, demonstrating the sensitivity of neurochemical levels to neurodegeneration related changes in the absence of overt pathology. We measured cerebellar neurochemical alterations in a knock-in mouse model of spinocerebellar ataxia type 1, a hereditary movement disorder, using ultra-high field magnetic resonance spectroscopy (MRS). Very early neurochemical alterations were detectable prior to overt pathology in the volume-of-interest for MRS. Alterations were indicative of osmolytic changes and of disturbances in membrane phospholipid and energy metabolism.	\N	\N
24039761	Pig is an important agricultural animal for meat production and provides a valuable model for many human diseases. Functional studies have demonstrated that microRNAs (miRNAs) play critical roles in almost all aspects of skeletal muscle development and disease pathogenesis. To investigate the miRNAs involved in regulating different periods of skeletal muscle development, we herein performed a comprehensive research for porcine microRNAome (miRNAome) during 10 skeletal muscle developmental stages including 35, 49, 63, 77, 91 dpc (days post coitum) and 2, 28, 90, 120, 180 dpn (days postnatal) using Solexa sequencing technology. Our results extend the repertoire of pig miRNAome to 247 known miRNAs processed from 210 pre-miRNAs and 297 candidate novel miRNAs through comparison with known miRNAs in the miRBase. Expression analysis of the 15 most abundant miRNAs in every library indicated that functional miRNAome may be smaller and tend to be highly expressed. A series of muscle-related miRNAs summarized in our study present different patterns between myofibers formation phase and muscle maturation phase, providing valuable reference for investigation of functional miRNAs during skeletal muscle development. Analysis of temporal profiles of miRNA expression identifies 18 novel candidate myogenic miRNAs in pig, which might provide new insight into regulation mechanism mediated by miRNAs underlying muscle development.	\N	\N
24050030	To evaluate serum and peritoneal concentrations of amyloid protein A in women with endometriosis and to compare them with those of women without endometriosis. A prospective study evaluated 76 women suspected of having pelvic endometriosis. Fifty-seven women (group A) were confirmed by videolaparoscopy and had their serum and peritoneal amyloid A concentrations measured by ELISA. The average levels from group A were compared to those obtained in group B. Group B was composed of 13 women without endometriosis, submitted to elective laparoscopy for tubal ligation. Peritoneal amyloid A concentrations in group A (310.3 +/- 97.8 ng/mL) were higher than those of group B (53.4 +/- 58.2 ng/mL); p = 0.0. However, serum concentrations in groups A (14.01 +/- 32.3 ng/mL) and B (9.5 +/- 15.9 ng/mL) did not differ significantly; p = 0.35. The peritoneal amyloid A protein concentration in pelvic endometriosis was higher when compared to normal controls, corroborating the inflammatory nature of the disease. This finding suggests that the procedure of evaluating the peritoneal amyloid A concentration in endometriosis merits further investigation.	\N	\N
24052521	Resistin, which is derived from the gene of RSTN, belongs to a family of cysteine-rich secretory proteins called resistin-like molecules (RELMs). Increased serum resistin levels are associated with coronary artery disease (CAD) and the risk of cardiovascular death. Patients (n = 214) with an initial diagnosis of stable angina pectoris, unstable angina pectoris, and myocardial infarction without ST-segment elevation and referred to catheter laboratory for coronary angiography were enrolled in the study. We aimed to investigate the relationship between increased serum resistin level and CAD. The severity of CAD was calculated by the Gensini scoring system. In conclusion, we established a significant correlation between serum resistin levels and CAD (P = .010). Also, serum resistin levels correlated with the Gensini score that represents the severity of CAD angiographically (P = .010).	\N	\N
24063011	Aspergillus fumigatus is a ubiquitously present respiratory pathogen. The outcome of a pulmonary disease may vary significantly with fungal viability and host immune status. Our objective in this study was (1) to assess the ability of inhaled irradiation-killed or live A. fumigatus spores to induce allergic pulmonary disease and (2) to assess the extent to which inhaled dead or live A. fumigatus spores influence pulmonary symptoms in a previously established allergic state. Our newly developed fungal delivery apparatus allowed us to recapitulate human exposure through repeated inhalation of dry fungal spores in an animal model. We found that live A. fumigatus spore inhalation led to a significantly increased humoral response, pulmonary inflammation, and airway remodeling in naïve mice and is more likely to induce allergic asthma symptoms than the dead spores. In contrast, in allergic mice, inhalation of dead and live conidia recruited neutrophils and induced goblet cell metaplasia. This data suggests that asthma symptoms might be exacerbated by the inhalation of live or dead spores in individuals with established allergy to fungal antigens, although the extent of symptoms was less with dead spores. These results are likely to be important while considering fungal exposure assessment methods and for making informed therapeutic decisions for mold-associated diseases.	\N	\N
24064013	Since the publication of the first reports on the efficiency of colchicine in familial Mediterranean fever (FMF), very few randomised studies have investigated issues related to its long-term use. Thus, different approaches taken by physicians involved in FMF care, are exclusively empiric, emulative, and based on case-reports or case-series. Problems such as colchicine intolerance and colchicine resistance have not been solved yet. This paper aims to evaluate trends in colchicine therapy among physicians taking care of FMF patients around the world. We conducted a survey by sending questionnaires to FMF research and treatment centres in Europe and Asia. Many issues (such as dosages, schedules, side effects, interactions, efficacy and toxicity monitoring, definition of colchicine intolerance, colchicine resistance and responsiveness, etc) have been investigated. When more than 70% of physicians responded giving similar answers to an item, the response was considered as a 'trend'. A comparison between answers of physicians from FMF-prevalent and non-prevalent countries was also made. Thirty-five physicians from 11 countries filled the questionnaires, taking care of a total of more than 15000 FMF patients (pts). Different approaches were evident among the various physicians. Statistically significant different approaches between physicians from FMF-prevalent countries with respect to those from non-prevalent countries were found in items like colchicine during pregnancy, severity score and blood tests for disease monitoring. No consensus was found regarding the definition of colchicine resistance. The current study demonstrated significant variations in the strategy of colchicine therapy for FMF around the world and re-emphasised the need for standardised definitions of colchicine resistance and colchicine intolerance.	\N	\N
24072601	Increasing evidence suggests low disease activity or remission is achievable in rheumatoid arthritis (RA). Using a treat to target strategy (T2T) has been shown to achieve these targets of remission or low disease activity in RA. In order to successfully treat to target, rheumatologists need reliable measures of disease activity to switch and/or escalate therapy to achieve or maintain therapeutic targets. Multiple disease-activity measures have been developed for both research and clinical practice. For clinical practice, the American College of Rheumatology (ACR) has recommended the PAS, PAS II, RAPID 3, CDAI, DAS 28, and SDAI for measuring disease activity in rheumatoid arthritis. Each of these measures has strengths and limitations, but they all accurately reflect disease activity, discriminate well between disease states, and are feasible to perform in the clinical setting. Implementation in the clinical setting can be optimized through leveraging technology and systems redesign. Tools such as web-based and smartphone applications have been developed to increase the ease with which these measures can be deployed. Disease-activity measurement in rheumatoid arthritis is included in the rheumatoid arthritis quality measures group in the Centers for Medicare and Medicaid Services' incentive-based Physician Quality Reporting System.	\N	\N
24098438	Seminoma is one of the most common Testicular Germ Cell Tumours that originates during embryonic development due to an alteration of the local niche that in turn results in a delayed or blocked differentiation of Primordial Germ Cells. The block of differentiation is actually a common way to develop cancer disease as postulated by the "embryonic rest theory of cancer". In agreement with this theory different studies have demonstrated that embryonic cues display the capacity of reprogramming aggressive cancer cells towards a less aggressive phenotype. Herein we investigate the ability of a culture medium added with 10% egg albumen (EW, Egg White) to modulate seminoma cell phenotype and behaviour, by ensuring a proper set of morphogenetic signals. We chose to use the TCam-2 seminoma cell line that has been established as the only available cell line, obtained from a primary testicular seminoma. EW is able to: 1) modify TCam-2 cell spreading rate and cell-substrate adhesion without affecting proliferation and survival indexes; 2) modulate TCam-2 actin distribution pattern increasing cortical localization of actin filaments; 3) increase TCam-2 cell-cell junction capability; 4) decrease both chemo-sensitive and collective TCam-2 migratory behaviour. According to these observations morphometric fractal analysis revealed the ability of EW to increase Circularity and Solidity parameters and, consequently, to decrease Fractal dimension. Prompted by these observations we hypothesize that EW treatment could rescue, at least in part, the neoplastic-metastatic behaviour of seminoma cells.	\N	\N
24102319	Transient receptor potential (TRP) channels are important mediators of sensory signals with marked effects on cellular functions and signalling pathways. Indeed, mutations in genes encoding TRP channels are the cause of several inherited diseases in humans (the so-called 'TRP channelopathies') that affect the cardiovascular, renal, skeletal and nervous systems. TRP channels are also promising targets for drug discovery. The initial focus of research was on TRP channels that are expressed on nociceptive neurons. Indeed, a number of potent, small-molecule TRPV1, TRPV3 and TRPA1 antagonists have already entered clinical trials as novel analgesic agents. There has been a recent upsurge in the amount of work that expands TRP channel drug discovery efforts into new disease areas such as asthma, cancer, anxiety, cardiac hypertrophy, as well as obesity and metabolic disorders. A better understanding of TRP channel functions in health and disease should lead to the discovery of first-in-class drugs for these intractable diseases. With this review, we hope to capture the current state of this rapidly expanding and changing field.	\N	\N
24107731	The metabolic dysfunction accompanying the polycystic ovary syndrome (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD). Although menopause per se may be an additional risk factor of CVD, the association between PCOS in postmenopausal women and cardiovascular risk has not been adequately investigated. We aimed to evaluate the effect of PCOS on markers of subclinical atherosclerosis in nondiabetic postmenopausal women. This cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS phenotype was defined if three of the following were present: insulin resistance, current hyperandrogenism or history of clinical androgen excess, history of infertility, central obesity and history of irregular menses. Traditional CVD risk factors, as well as indices of arterial structure (intima-media thickness, atheromatous plaques presence) and function [flow-mediated dilation, pulse wave velocity (PWV), augmentation index] were compared between women with a PCOS phenotype and the rest of the sample, who served as controls. Women with the PCOS phenotype (N=43) had higher SBP and triglycerides and lower high-density lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed significantly between PCOS cases and controls (9.46±1.74 vs. 8.60±1.51 m/s, P=0.001, univariate). Multivariate regression analysis showed that the PCOS phenotype, age and SBP were the only independent predictors of PWV. Arterial stiffness is increased in asymptomatic, nondiabetic women with a putative PCOS phenotype, independently of age, BMI or blood pressure. This might present one mechanism through which PCOS increases the risk of CVD and hypertension later in life.	\N	\N
24108471	Brain vasculature is uniquely programmed to protect central nervous system tissues and respond to their metabolic demands. These functions are subverted during the development of primary and metastatic brain tumors, resulting in vascular perturbations that are thought to contribute to progression and comorbidities of the underlying disease, including thrombosis and hemorrhage. Chronic activation of the coagulation system is particularly obvious in glioblastoma multiforme (GBM), where intratumoral vasoocclusive thrombosis may contribute to hypoxia, pseudopalisading necrosis, and angiogenesis. GBM is also associated with spontaneous or iatrogenic bleeding, and the emission of circulating procoagulants implicated in the unusually high risk of peripheral venous thromboembolism. Tissue factor (TF) expression is elevated in several types of brain tumors, including adult and pediatric GBM, as is the production of TF-containing microparticles (TF-MPs). Both TF expression and its vesicular emission are regulated by tumor microenvironment (e.g., hypoxia), in concert with activated oncogenic and growth factor pathways (RAS, EGFR, MET), as well as the loss of tumor suppressor gene activity (PTEN). Discovery of distinct oncogenic networks led to recognition of unique molecular subtypes within brain tumors, of which GBM (proneural, neural, classical, and mesenchymal), and medulloblastoma (SHH, WNT, group 3, and group 4) exhibit subtype-specific composition of the tumor coagulome. It remains to be established whether mechanisms of thrombosis and biological effects of coagulation in brain tumors are also subtype specific. In this regard, TF pathway represents a paradigm, and its impact on tumor dormancy, inflammation, angiogenesis, formation of cancer stem cell niches, and dissemination is a subject of considerable interest. However, establishing the extent to which TF and TF-MPs contribute to pathogenesis and thromboembolic disease in the context of primary and secondary brain tumors may require molecular stratification of patient populations. We suggest that a better understanding of these molecular linkages may pave the way to a more effective (targeted) therapy, prophylaxis, adjunctive use of anticoagulants, and other agents able to modulate interactions between brain tumors and the coagulation system.	\N	\N
24124671	To explore the exercise characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH). From November 2010 to September 2012 , 76 consecutive IPAH patients and 24 healthy controls from Fuwai Cardiovascular Hospital were enrolled to undergo cardiopulmonary exercise testing. The exercise parameters were compared. Correlations among peak oxygen consumption, anaerobic threshold, peak oxygen pulse, New York Heart Association (NYHA) class, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6 MWD) and cardiac index are analyzed in IPAH. There were 21 males and 55 females in IPAH and 8 males and 16 females in controls. Their mean ages were (31.5 ± 10.6) and (35.5 ± 6.4) years respectively. Significant differences (P = 0.000) existed between two groups in peak oxygen consumption ((12.7 ± 3.3) vs (25.6 ± 5.8) ml·min(-1)·kg(-1)), anaerobic threshold ((9.8 ± 2.5) vs (16.7 ± 3.9) ml·min(-1)·kg(-1)), peak oxygen pulse ((5.3 ± 1.6) vs (9.9 ± 2.5) ml/bpm) and ventilator efficiency (slope of minute ventilation in relation to CO2 produced) ((42.6 ± 2.0) vs (25.5 ± 3.5)). In IPAH, peak oxygen consumption was significantly correlated with NYHA class (r = -0.509, P = 0.000), 6 MWD (r = 0.443, P = 0.002) and NT-proBNP levels (r = -0.423, P = 0.011). And anaerobic threshold was significantly correlated with NYHA class (r = -0.362, P = 0.002), 6MWD (r = 0.343, P = 0.004) and NT-proBNP levels (r = -0.275, P = 0.017). Peak oxygen pulse and ventilator efficiency were both correlated well with total pulmonary vascular resistance. Partial correlation analysis demonstrated that there were significant correlations among peak oxygen consumption, anaerobic threshold, NYHA class, NT-proBNP levels and 6MWD after adjusting for age, gender and weight. Peak oxygen consumption and anaerobic threshold decrease ventilator efficiency in IPAH patients. Cardiopulmonary exercise testing is an invasive tool of assessing safely the function of IPAH patients.	\N	\N
24127735	Knee osteoarthritis (OA) is a major cause of pain, functional limitation, and reduced quality-of-life, particularly in older adults. This study evaluated the 'real world' NSAID-sparing effect of glucosamine (specifically Structoflex®) in patients with knee OA compared with a control population of patients who did not receive a slow-acting symptomatic anti-osteoarthritis agent. This analysis was conducted over a 1-year follow-up period. Data were sourced from the French Disease Analyzer (IMS Lifelink EMR™) database. The primary measure was the NSAID-sparing effect produced by Structoflex® compared with a matched control group. Secondary measures included an evaluation of the change in the number of general practitioner visits and use of other medicinal products related to knee OA. A total of 11,772 patients (67.66% female) were included in the analysis (436 and 11,336 patients in the Structoflex® and control groups, respectively). Most patients were aged 50-65 years (58.72%); 19.5% of patients were aged >76 years. At study inclusion, 51.61% of patients had experienced OA for <1 year. Prior to starting Structoflex®, 51.61% of patients had received an NSAID prescription. Significantly more patients who were receiving an NSAID at the time of starting Structoflex® discontinued their NSAID treatment during the follow-up period compared with patients in the control group (32% vs 23%; p = 0.0452). During the 1-year follow-up period, the total mean duration of NSAID prescription (30.39 ± 38.64 days vs 37.82 ± 54.62 days; p = 0.0109) and the mean number of days (calculated using Defined Daily Dose) on NSAID (45.12 ± 49.03 days vs 53.00 ± 71.14 days; p = 0.0333) was significantly lower in Structoflex®-treated patients compared with control group patients. This large 'real world' analysis demonstrated a significant NSAID-sparing effect of glucosamine in patients with knee OA.	\N	\N
24138892	I shall discuss the work of researchers at Harvard Medical School who came together in the early 1990s. Scattered across various Harvard-affiliated hospitals and research centers, these individuals were unified by their interest in ocular neovascularization. Together and separately, they investigated models of ocular neovascularization, exploring tumor angiogenesis in eye development and disease.	\N	\N
24141443	To validate the Clinical Gait and Balance Scale (GABS) for a Brazilian population of patients with Parkinson's disease (PD) and to compare it to the Berg Balance Scale (BBS). One hundred and seven PD patients were evaluated by shortened UPDRS motor scale (sUPDRSm), Hoehn and Yahr (HY), Schwab and England scale (SE), Falls Efficacy Scale International (FES-I), Freezing of Gait Questionnaire (FOG-Q), BBS and GABS. The internal consistency of the GABS was 0.94, the intra-rater and inter-rater reliability were 0.94 and 0.98 respectively. The area under the receiver operating characteristic (ROC) curve was 0.72, with a sensitivity of 0.75 and specificity of 0.6, to discriminate patients with a history of falls in the last twelve months, for a cut-off score of 13 points. Our study shows that the Brazilian version of the GABS is a reliable and valid instrument to assess gait and balance in PD.	\N	\N
24144148	Pompe disease is a rare, progressive and often fatal neuromuscular disorder. It is caused by a deficiency of the lysosomal alpha-glucosidase. Among glycogen storage disorders, it is one of the most common. Its clinical manifestations can start at any moment of life, with a very variable symptomatology. In this article, we show an extended revision of the literature in regards to the main medical aspects of Pompe disease: etiology, psychopathology, epidemiology, clinical variants, pathological diagnosis, and enzyme replacement therapy. With this information, we created a diagnostic and therapeutic guide, which is addressed to specialists and to first-level physicians, in order to let them identify both the classic and the late forms of this disease. We describe as well the best, timely, multidisciplinary treatment in use. Also, we show some suggestions to the proper functioning of health institutions, and routes to diagnosis. We conclude that Pompe disease may be properly diagnosed and treated if health care professionals follow the internationally approved recommendations.	\N	\N
24151631	Cystic echinococcosis (CE) is a chronic, clinically complex, and neglected disease. Its prevalence in Italy, a country of medium to high endemicity, remains poorly defined, as notification has long ceased to be mandatory. We set up a retrospective cohort study involving all CE patients followed at our institute between January 2005 and December 2012. Demographical and clinical features were recorded and analyzed. CE was found in 28 patients (64.3%), mostly Italians from the central regions (50%), followed by subjects from the islands (33.3%) and Southern Italy (16.7%). Their median age was 45 years (IQR: 38.5-66.5), with Eastern Europeans being significantly younger (28 years, IQR: 19-39) than other patients (P ≤ 0.0001). A total of 149 cysts, mostly with hepatic localization (96%), were described. Based on the WHO classification, the cysts were mainly small (80.5%) and active (CE1 (73.8%); CE2 (7.4%)). Active cysts were more common in Eastern Europeans (85.7%) than Italians (66.7%). Our data confirm CE occurrence in Italy. We emphasize the importance to have a national CE registry, opportunely recently introduced. This is essential to assess CE prevalence in this country, implement appropriate control measures, and improve patient management.	\N	\N
24152546	Pre-diagnosis oophorectomy and estrogen therapy could impact mortality due to breast cancer and cardiovascular disease (CVD) among breast cancer survivors. Elective bilateral oophorectomy at the time of hysterectomy for benign conditions is not uncommon among US women. We examined the association between pre-diagnosis total abdominal hysterectomy with bilateral salpingooophorectomy (TAHBSO) and both overall and cause-specific mortality in the Collaborative Breast Cancer Studies cohort. Medical history and prior estrogen use were collected during standardized telephone interviews. Vital status, including date and cause of death, was obtained by linkage with the National Death Index. Multivariate hazard ratios (HR) and 95% confidence intervals (CI) for cause-specific mortality were calculated using Cox proportional hazards regression. Seventeen percent (N = 1,778) of breast cancer survivors (mean age at diagnosis = 63.5) reported pre-diagnosis TAHBSO. During follow-up (mean = 9.5 years), 2,856 deaths occurred, including 1,060 breast cancer deaths and 459 CVD deaths. Breast cancer deaths occurred a median of 5.1 years after diagnosis; CVD deaths occurred further from diagnosis (median = 9.7 years). Women who reported pre-diagnosis TAHBSO had a 16% decrease in all-cause mortality (HR = 0.84; 95% CI: 0.76, 0.92) compared to those with an intact uterus and ovaries. This overall decrease reflected a 27% lower breast cancer mortality among women who never used postmenopausal hormones (HR = 0.73; CI: 0.55, 0.96) and 43% lower CVD risk among women who reported using estrogen (HR = 0.57; CI: 0.39, 0.83) after TAHBSO. Information on prior TAHBSO and estrogen use can inform risk of death fromboth breast cancer and cardiovascular disease among breast cancer survivors.	\N	\N
24152582	The Ca(2+) channel-binding domain 3 (CBD3) peptide, derived from the collapsin response mediator protein 2 (CRMP-2), is a recently discovered voltage-gated Ca(2+) channel (VGCC) blocker with a preference for CaV2.2. Rodent administration of CBD3 conjugated to cell penetrating motif TAT (TAT-CBD3) has been shown to reduce pain behavior in inflammatory and neuropathic pain models. However, TAT-CBD3 analgesia has limitations, including short half-life, lack of cellular specificity and undesired potential off-site effects. We hypothesized that these issues could be addressed by expressing CBD3 encoded by high-expression vectors in primary sensory neurons. We constructed an adeno-associated viral (AAV) vector expressing recombinant fluorescent CBD3 peptide and injected it into lumbar dorsal root ganglia (DRGs) of rats before spared nerve injury (SNI). We show that selective expression of enhanced green fluorescent protein (EGFP)-CBD3 in lumbar 4 (L4) and L5 DRG neurons and their axonal projections results in effective attenuation of nerve injury-induced neuropathic pain in the SNI model. We conclude that AAV-encoded CBD3 delivered to peripheral sensory neurons through DRG injection may be a valuable approach for exploring the role of presynaptic VGCCs and long-term modulation of neurotransmission, and may also be considered for development as a gene therapy strategy to treat chronic neuropathic pain.	\N	\N
24157515	While undernutrition and infectious diseases are still persistent in developing countries, overweight, obesity, and associated comorbidities have become more prevalent. Uganda, a developing sub-Saharan African country, is currently experiencing the public health paradox of undernutrition and overnutrition. We utilized the 2011 Uganda Demographic and Health Survey (DHS) to examine risk factors and hot spots for underweight, overweight, and obesity among adult females (N = 2,420) and their children (N = 1,099) using ordinary least squares and multinomial logit regression and the ArcGIS Getis-Ord Gi* statistic. Overweight and obese women were significantly more likely to have overweight children, and overweight was correlated with being in the highest wealth class (OR = 2.94, 95% CI = 1.99-4.35), and residing in an urban (OR = 1.76, 95% CI = 1.34-2.29) but not a conflict prone (OR = 0.48, 95% CI = 0.29-0.78) area. Underweight clustered significantly in the Northern and Northeastern regions, while overweight females and children clustered in the Southeast. We demonstrate that the DHS can be used to assess geographic clustering and burden of disease, thereby allowing for targeted programs and policies. Further, we pinpoint specific regions and population groups in Uganda for targeted preventive measures and treatment to reduce the burden of overweight and chronic diseases in Uganda.	\N	\N
24169298	Morbidity and mortality from preventable, noncommunicable chronic disease (NCD) threatens the health of our populations and our economies. The accumulation of vast amounts of scientific knowledge has done little to change this. New and innovative thinking is essential to foster new creative approaches that leverage and integrate evidence through the support of big data, technology, and design thinking. The purpose of this paper is to summarize the results of a consensus meeting on NCD prevention sponsored by the International Olympic Committee (IOC) in April 2013. Within the context of advocacy for multifaceted systems change, the IOC's focus is to create solutions that gain traction within health care systems. The group of participants attending the meeting achieved consensus on a strategy for the prevention and management of chronic disease that includes the following: 1. Focus on behavioral change as the core component of all clinical programs for the prevention and management of chronic disease. 2. Establish actual centers to design, implement, study, and improve preventive programs for chronic disease. 3. Use human-centered design (HCD) in the creation of prevention programs with an inclination to action, rapid prototyping and multiple iterations. 4. Extend the knowledge and skills of Sports and Exercise Medicine (SEM) professionals to build new programs for the prevention and treatment of chronic disease focused on physical activity, diet, and lifestyle. 5. Mobilize resources and leverage networks to scale and distribute programs of prevention. True innovation lies in the ability to align thinking around these core strategies to ensure successful implementation of NCD prevention and management programs within health care. The IOC and SEM community are in an ideal position to lead this disruptive change. The outcome of the consensus meeting was the creation of the IOC Non-Communicable Diseases ad hoc Working Group charged with the responsibility of moving this agenda forward.	\N	\N
24171516	The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era. We treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus rituximab. Patients with a response were randomly assigned to receive three additional cycles of induction chemotherapy (control group) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation (transplantation group). The primary efficacy end points were 2-year progression-free survival and overall survival. Of 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression-free survival rates of 69 and 55%, respectively (hazard ratio in the control group vs. the transplantation group, 1.72; 95% confidence interval [CI], 1.18 to 2.51; P=0.005). Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71%, respectively (hazard ratio, 1.26; 95% CI, 0.82 to 1.94; P=0.30). Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P=0.04 for interaction) and overall survival (P=0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82% in the transplantation group and 64% in the control group. Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy. Overall survival after transplantation was not improved, probably because of the effectiveness of salvage transplantation. (Funded by the National Cancer Institute, Department of Health and Human Services, and others; SWOG-9704 ClinicalTrials.gov number, NCT00004031.).	\N	\N
24172078	Many symptomatic patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) are denied surgery and have a grim prognosis with medical management. Between 2003 and 2012, among 550 patients with severe isolated AS and preserved LVEF on transthoracic echocardiography, 241 did not undergo aortic valve replacement (mean age, 83.2±7.6 years; 54% female; aortic valve area index, 0.40±0.13cm(2)/m(2); mean LVEF, 64.8±7.6%) and 67% presented with cardiac symptoms. At a mean follow-up of 25.5±25.1 months, 134 patients (56%) had died. Survival at 1, 5 and 9.5 years was 71%, 28% at 12%, respectively. Median survival was 36.3 months (95% confidence interval [CI]: 27.2-42.4 months). In unadjusted analyses, age, heart failure, hypertension, renal insufficiency, left atrial size, pulmonary artery systolic pressure (PASP), relative wall thickness and LV mass/LV end diastolic volume ratio were associated with mortality. On multivariate analysis adjusted for all significant univariate predictors, age ≥78 years, history of hypertension, left atrial diameter ≥40mm and PASP ≥42mmHg gave a joint area under the curve of 0.80 (95% CI: 0.73-0.86) for mortality. In medically treated patients with severe isolated AS and preserved LVEF, older age, history of hypertension, and echo-Doppler variables reflecting LV diastolic dysfunction are independent predictors of death.	\N	\N
24203705	Microbial genome sequencing is one of the longest-standing areas of biological database development, but high-throughput, low-cost technologies have increased its throughput to an unprecedented number of new genomes per year. Several thousand microbial genomes are now available, necessitating new approaches to organizing information on gene function, phylogeny and microbial taxonomy to facilitate downstream biological interpretation. MetaRef, available at http://metaref.org, is a novel online resource systematically cataloguing a comprehensive pan-genome of all microbial clades with sequenced isolates. It organizes currently available draft and finished bacterial and archaeal genomes into quality-controlled clades, reports all core and pan gene families at multiple levels in the resulting taxonomy, and it annotates families' conservation, phylogeny and consensus functional information. MetaRef also provides a comprehensive non-redundant reference gene catalogue for metagenomic studies, including the abundance and prevalence of all gene families in the >700 shotgun metagenomic samples of the Human Microbiome Project. This constitutes a systematic mapping of clade-specific microbial functions within the healthy human microbiome across multiple body sites and can be used as reference for identifying potential functional biomarkers in disease-associate microbiomes. MetaRef provides all information both as an online browsable resource and as downloadable sequences and tabular data files that can be used for subsequent offline studies.	\N	\N
24206993	Ulnar impaction syndrome generally occurs with positive ulnar variance. The solution to the problem is to unload the ulnocarpal joint. Effective surgical options include diaphyseal ulnar shortening osteotomy, open wafer osteotomy, and arthroscopic wafer osteotomy. Recently, Slade and Gillon described an open procedure of ulnar shortening in the osteochondral region of the ulnar head. The procedure minimizes the risk of hemarthrosis and does not require hardware removal, which are problems with other surgical options. This article introduces a new arthroscopic technique of distal metaphyseal ulnar shortening osteotomy for ulnar impaction syndrome. This technique offers the advantages of minimizing surgical injury to the dorsal capsule of the distal radoulnar joint and so protects its stability.	\N	\N
24211848	Crimean-Congo hemorrhagic fever virus (CCHFV) etiology was detected in a family cluster (nine cases, including two deaths) in the village of Karyana, Amreli District, and also a fatal case in the village of Undra, Patan District, in Gujarat State, India. Anti-CCHFV IgG antibodies were detected in domestic animals from Karyana and adjoining villages. Hyalomma ticks from households were found to be positive for CCHF viral RNA. This confirms the emergence of CCHFV in new areas and the wide spread of this disease in Gujarat State.	\N	\N
24218343	Regional body-fat distribution is one of the key variables that explains the metabolic heterogeneity of obesity and its related cardiovascular risks. According to the ectopy concept, the inability of subcutaneous adipose tissue to store surplus triglycerides may lead to the development of fat in ectopic sites, such as the heart. Epicardial adipose tissue is a metabolically active endocrine organ that produces numerous factors that can modulate cardiac structure and function. The development of in vivo noninvasive imaging has made it possible to quantify its thickness and volume with increasing accuracy. In this review, we discuss the local interaction and cross-talk between epicardial fat and neighboring structures, such as coronary arteries and myocardium, and its relevance to cardiac diseases, such as coronary-artery disease or atrial fibrillation. Beneficial and harmful effects of epicardial adipose tissue are described and analyzed. What leads to an imbalance between protective and deleterious actions has to be further explored. We believe that epicardial fat, which has been neglected for years, plays a key role in cardiovascular disease pathophysiology and represents a "new world" exploration for therapeutic targets, which will be addressed in future clinical and research studies. Elucidating the mechanisms that drive the deposition or mobilization of cardiac adiposity between other ectopic-fat stores needs to be accomplished within the next few years.	\N	\N
24223459	We evaluated whether the methylenetetrahydrofolate reductase (MTHFR) 677C>T marker influences the risk and severity of Alzheimer's disease (AD) and whether AD is associated with homocysteine, vitamin B12, and cholesterol levels in Egypt. Forty-three Alzheimer's cases and 32 non-AD controls were genotyped for the 677C>T polymorphism. Clinical characteristics and levels of homocysteine, vitamin B12, and cholesterol were assessed. No significant differences in the frequencies of the MTHFR alleles or genotypes between AD cases and controls (P = 0.14) were identified. The 677T mutant allele was significantly overrepresented in AD cases compared to controls (OR = 2.22; P = 0.03). The 677T/T frequency was three times higher in AD patients than in controls, which could increase plasma homocysteine levels. Severe cases of AD were the most frequent in patients with the T/T genotype (11.6%). The effect of the MTHFR polymorphism on the risk of AD may be independent of homocysteine, vitamin B12, or even cholesterol levels. The MTHFR 677C>T polymorphism--especially the presence of one copy of the T allele--appears to confer a potential risk for the development of AD. The T/T genotype may contribute to hypercysteinemia as a sensitive marker.	\N	\N
24226095	Sterol 12α-hydroxylase (CYP8B1) is required for cholic acid synthesis and plays a critical role in intestinal cholesterol absorption and pathogenesis of cholesterol gallstone, dyslipidemia, and diabetes. In this study we investigated the underlying mechanism of fasting induction and circadian rhythm of CYP8B1 by a cholesterol-activated nuclear receptor and core clock gene retinoic acid-related orphan receptor α (RORα). Fasting stimulated, whereas restricted-feeding reduced expression of CYP8B1 mRNA and protein. However, fasting and feeding had little effect on the diurnal rhythm of RORα mRNA expression, but fasting increased RORα protein levels by cAMP-activated protein kinase A-mediated phosphorylation and stabilization of the protein. Adenovirus-mediated gene transduction of RORα to mice strongly induced CYP8B1 expression, and increased liver cholesterol and 12α-hydroxylated bile acids in the bile acid pool and serum. A reporter assay identified a functional RORα response element in the CYP8B1 promoter. RORα recruited cAMP response element-binding protein-binding protein (CBP) to stimulate histone acetylation on the CYP8B1 gene promoter. In conclusion, RORα is a key regulator of diurnal rhythm and fasting induction of CYP8B1, which regulates bile acid composition and serum and liver cholesterol levels. Antagonizing RORα activity may be a therapeutic strategy for treating inflammatory diseases such as non-alcoholic fatty liver disease and type 2 diabetes.	\N	\N
24226419	IL-32 is a pro-inflammatory cytokine expressed by activated natural killer cells, T cells, keratinocytes, and fibroblasts. In this study, we examined the role of IL-32 in cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF) and Sézary syndrome (SS). IL-32 mRNA expression levels in lesional skin of MF patch, plaque, and tumor were increased compared with those of normal skin, which positively correlated with CCL17 and CCL18 mRNA expression levels. Serum IL-32 levels positively correlated with disease activity within each patient. Immunostaining showed that keratinocytes expressed IL-32 in the lesional skin of MF patch and plaque, whereas in MF tumor, atypical T cells in the dermis strongly expressed IL-32. We also showed that IL-32 dose-dependently accelerated the proliferation of MF and SS cell lines in vitro, which was inhibited by blocking mitogen-activated protein kinase and NF-κB-mediated signaling. The addition of anti-IL-32 antibodies in culture decreased the proliferation of SS cells and the viability of MF cells, suggesting that IL-32 serves as an autocrine growth factor. In conclusion, our results suggest that IL-32 has a role in the formation and maintenance of CTCL lesions, providing a possible therapeutic target for patients with this disease.	\N	\N
24240787	To assess the efficacy of pirfenidone in patients with advanced-stage idiopathic pulmonary fibrosis (IPF), we conducted a retrospective study of patients who received pirfenidone therapy. In addition, the combined effects of inhaled N-acetylcysteine (NAC) and pirfenidone were evaluated. Eligible patients had a clinical and radiologic diagnosis of advanced-stage IPF (stages of severity III&IV). Patients who exhibited a relative decline in forced vital capacity (FVC) of 10% or more within the preceding six (±2) months were enrolled. The outcome was evaluated from the date of the 6-month follow-up PFT. Relative declines in FVC of more than 10% were defined as progressive disease (ineffective group), while those less than 10% were defined as stable disease (effective group). The clinical features were compared between the two groups. We also compared the efficacy of the combined therapy with inhaled NAC and pirfenidone (n=11) with that of pirfenidone alone (n=7). Eighteen patients 59-82 years of age with IPF who received pirfenidone therapy were reviewed. Pirfenidone stabilized declines in FVC by 10% at six months in eight of the 18 cases (44%). The median changes in FVC at six months were +120 mL in the effective group and -590 mL in the ineffective group. The number of NAC users was significantly higher in the effective group (7/8=87.5%) than in the ineffective group (3/10=30%) (p=0.02). Furthermore, the use of combined NAC therapy was correlated with a favorable outcome. The median change in FVC at six months was 0 mL in the NAC group and -290 mL in the non-NAC group. The median survival period was 557 ± 66 days in the NAC group and 196 ± 57 days in the non-NAC group (p=0.03). Among the advanced-stage IPF patients with a more progressive status, pirfenidone decreased the rate of decline in FVC. In addition, patients treated with pirfenidone combined with NAC therapy exhibited favorable outcomes. Additional studies are needed to confirm the efficacy of this combined therapy for IPF.	\N	\N
24246538	The use of "chimney" stents to augment the proximal landing zone for endovascular aneurysm repair has been increasingly reported. Despite mounting enthusiasm for this technique, the durability of this type of repair and capability to preserve perfusion to target branches remains a paramount concern. Here, we report management of a patient presenting with acute bilateral renal chimney stent thrombosis and a type Ia endoleak.	\N	\N
24252129	Favre-Racouchot syndrome (FRS) is both disfiguring and difficult to treat. Available medical and surgical therapies are of variable efficacy. Most treatments do not achieve complete resolution and do not show maintenance of therapeutic response. To assess the response to a novel two-step treatment using the CO2 laser in patients with FRS. Seven patients with FRS were treated with the CO2 laser in resurfacing mode with manual expression of comedones under infiltrative local anaesthesia. The procedure was completed in one treatment session lasting 30 min and the wound was left to heal by secondary intention. A topical antibiotic was applied to treated areas, which were covered with a nonadherent dressing. All patients were assessed 3 months postoperatively by the operating laser surgeon and a visual assessment of clinical response to treatment in comparison with pretreatment photographs was made. Patient satisfaction was also recorded. All patients achieved complete resolution of FRS. The follow-up duration for our cohort ranged from 8 months to 3 years. Two patients required further treatment within a 2-3-year period from initial treatment. Disease relapse was noted over 1 year after the primary treatment; both these cases were smokers and repeat treatment with similar laser parameters maintained reproducible results. Our longest disease-free follow-up duration was 3 years postprimary treatment. The laser surgeons and patients reported high levels of therapeutic benefit and satisfaction with the results. This two-step treatment of FRS (CO2 laser resurfacing and manual pressure-induced expression of comedones) is an effective and durable treatment for FRS with an excellent cosmetic outcome. Long-term follow-up beyond 3 years is planned to determine whether later recurrence occurs with this technique.	\N	\N
24263779	Over recent decades, the prevalence of high blood pressure (BP) has increased among children. Several risk factors are involved in the genesis of high BP during childhood, and their early identification can prevent the development of that disease. To assess the prevalence of high BP and associated factors in children. Cross-sectional, population-based study, carried out at the household. This study included 276 two- to five-year-old children in the city of Goiânia, state of Goiás, and assessed their BP, sociodemographic characteristics, birth weight, high BP family history, passive smoking, maternal breastfeeding, dietary habits, sedentary lifestyle and nutritional status. Poisson regression was used to assess the association between risk factors and high BP. Their mean age was 3.1 ± 0.79 years, and high BP and overweight were observed in 19.9% and 11.2% of the children, respectively. Direct association of high BP was identified with age [prevalence ratio (PR) = 2.3; 95%CI: 1.2 - 4.8; p = 0.017] and overweight (PR = 2.0; 95%CI: 1.2 - 3.6; p = 0.014). No other variable associated with high BP. The prevalence of high BP in children was high. Overweight and younger children had greater prevalence of high BP.	\N	\N
24264509	According to 1981-2009 data, homicide accounts for 16,000-26,000 deaths annually in the United States and ranks within the top four leading causes of death among U.S. residents aged 1-40 years. Homicide can have profound long-term emotional consequences on families and friends of victims and on witnesses to the violence, as well as cause excessive economic costs to residents of affected communities. For years, homicide rates have been substantially higher among certain populations. Previous reports have found that homicides are higher among males, adolescents and young adults, and certain racial/ethnic groups, such as non-Hispanic blacks, non-Hispanic American Indian/Alaska Natives (AI/ANs), and Hispanics. The 2011 CDC Health Disparities and Inequalities Report (CHDIR) described similar findings for the year 2007. For example, the 2011 report showed that the 2007 homicide rate was highest among non-Hispanic blacks (23.1 deaths per 100,000), followed by AI/ANs (7.8 deaths per 100,000), Hispanics (7.6 deaths per 100,000), non-Hispanic whites (2.7 deaths per 100,000), and Asian/Pacific Islanders (A/PIs) (2.4 deaths per 100,000). In addition, non-Hispanic black men aged 20-24 years were at greatest risk for homicide in 2007, with a rate that exceeded 100 deaths per 100,000 population. Other studies have reported that community factors such as poverty and economic inequality and individual factors such as unemployment and involvement in criminal activities can play a substantial role in these persistent disparities in homicide rates. Public health strategies are needed in communities at high risk for homicide to prevent violence and save lives.	\N	\N
24269993	To report on unexpected findings in 4 patients with chronic paraplegia who underwent the laparoscopic implantation of neuroprosthesis procedure in the pelvic lumbosacral nerves. Observational case series. Tertiary referral unit specialized in advanced gynecological surgery and neuropelveology. Three patients with incomplete American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade B (n=2) and AIS grade C (n=1) spinal cord injury (SCI) and 1 patient with flaccid complete chronic SCI (AIS grade A) (n=1). Functional electrical stimulation (FES)-assisted locomotor training and continuous low-frequency pelvic-lumbosacral neuromodulation. Change in ASIA Lower Extremity Motor Scores, ASIA sensory scores for light touch and pinprick sensation, and Walking Index for Spinal Cord Injury scores. All 4 patients developed progressive recovery of some sensory and voluntary motor functions below the lesions. Three are currently capable of voluntary weight-bearing standing and walking a few meters with a walker without FES. The first patient with the longest follow-up is even capable of electrically assisted standing/walking with 2 crutches without braces or assistance for a distance of about 900 meters, and of weight-bearing standing and walking for 30 meters with a walker without stimulation. We report unexpected sensory and locomotor recovery in 4 people with paraplegia with SCI. Our findings suggest that FES-assisted locomotor training with continuous low-frequency pelvic nerve stimulation in patients with SCI may induce changes that affect the central pattern generator and allow supra- and infraspinal inputs to engage residual spinal pathways.	\N	\N
24274981	DMD gene which is composed of 79 exons is the largest known gene located on X chromosome (Xp21). Point mutations in the dystrophin gene are responsible for 30-35% of cases with DMD/BMD. Mutation analysis of all the exons of the DMD gene is costly in developing countries, therefore, a few of the exons are selected to be analyzed routinely in clinical laboratories. In this study, direct sequencing was used for detection of point mutations in 10 exons of dystrophin gene in patients affected with DMD without detectable large rearrangements. Freely available programs were used to predict the damaging effects of the mutations. Point mutations were successfully detected in three patients. Three novel mutations, two missense mutations located on nonconservative domains and a single nucleotide deletion, were detected. Missense mutations were predicted to change splicing efficiency. Detection of point mutations by DNA analysis followed by prediction of the pathogenecity by using bioinformatic tool might be an asset to provide proper diagnosis or genetic counseling to patients and their family.	\N	\N
24276026	Early detection and improved (neo)-adjuvant treatment has extended survival of breast cancer over the last decades. It remains controversial whether a survival benefit is achieved once metastases have occurred. This study investigates survival trends in metastatic breast cancer (MBC) looking at the distribution of prognostic factors and the time period of the diagnosis of the primary and metastatic disease. In this retrospective study, 1635 patients, diagnosed with MBC and treated at three German cancer centers, were included. For the survival analysis, patients were grouped into three time periods [1980-1994 (a), 1995-1999 (b) and 2000-2009 (c)], which were chosen according to the availability of new antineoplastic drugs for the treatment of MBC. Additionally, patients were divided into three risk groups using the simultaneously published prognostic score. The analysis of overall survival according to the date of primary diagnosis demonstrated a significant decline compared with the reference (a): (a versus b) hazard ratio (HR) = 1.37; P < 0.001; (a versus c) HR = 2.45; P < 0.001. Considering the time of first occurrence of metastasis, survival remains unchanged over the three periods (a versus b): HR = 0.94 P = 0.436; (a versus c): HR = 0.95; P = 0.435. However, a significant shift towards more unfavorable risk factors was seen. Although survival in MBC remains unchanged over time, patients developing metastatic disease have a more aggressive disease that is presumably compensated by more effective treatment. This alteration of tumor biology in MBC may be explained by a negative selection of patients with adverse risk profiles due to the advantages of the adjuvant therapy.	\N	\N
24280762	Helicobacter pylori infections can induce pathologies ranging from chronic gastritis, peptic ulceration to gastric cancer. Bacterial isolates harbor numerous well-known adhesins, vacuolating cytotoxin VacA, protease HtrA, urease, peptidoglycan, and type IV secretion systems (T4SS). It appears that H. pylori targets more than 40 known host protein receptors on epithelial or immune cells. A series of T4SS components such as CagL, CagI, CagY, and CagA can bind to the integrin α 5β 1 receptor. Other targeted membrane-based receptors include the integrins αvβ 3, αvβ 5, and β 2 (CD18), RPTP-α/β, GP130, E-cadherin, fibronectin, laminin, CD46, CD74, ICAM1/LFA1, T-cell receptor, Toll-like receptors, and receptor tyrosine kinases EGFR, ErbB2, ErbB3, and c-Met. In addition, H. pylori is able to activate the intracellular receptors NOD1, NOD2, and NLRP3 with important roles in innate immunity. Here we review the interplay of various bacterial factors with host protein receptors. The contribution of these interactions to signal transduction and pathogenesis is discussed.	\N	\N
24281461	Pediatric-onset Crohn disease is more aggressive than adult-onset disease, has high rates of resistance to existing drugs, and can lead to permanent impairments. Few trials have evaluated new drugs for refractory Crohn disease in children. To determine whether thalidomide is effective in inducing remission in refractory pediatric Crohn disease. Multicenter, double-blind, placebo-controlled, randomized clinical trial of 56 children with active Crohn disease despite immunosuppressive treatment, conducted August 2008-September 2012 in 6 pediatric tertiary care centers in Italy. Thalidomide, 1.5 to 2.5 mg/kg per day, or placebo once daily for 8 weeks. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks. Primary outcomes were clinical remission at week 8, measured by Pediatric Crohn Disease Activity Index (PCDAI) score and reduction in PCDAI by ≥25% or ≥75% at weeks 4 and 8. Primary outcomes during the open-label follow-up were clinical remission and 75% response. Twenty-eight children were randomized to thalidomide and 26 to placebo. Clinical remission was achieved by significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26 [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2-12.5]; P = .01; number needed to treat [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs 3/26 [11.5%]; RR, 4.0 [95% CI, 1.2-12.5]; NNT = 2.86; P = .01; and 25% response, 18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI, 1.1-3.9]; NNT = 2.99; P = .01). Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%) subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4-14.1]; NNT = 2.45; P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved clinical remission, and 32 of 49 (65.3%) achieved 75% response. Mean duration of clinical remission in the thalidomide group was 181.1 weeks (95% CI, 144.53-217.76) vs 6.3 weeks (95% CI, 3.51-9.15) in the placebo group (P < .001). Cumulative incidence of severe adverse events was 2.1 per 1000 patient-weeks, with peripheral neuropathy the most frequent severe adverse event. In children and adolescents with refractory Crohn disease, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and longer-term maintenance of remission in an open-label follow-up. These findings require replication to definitively determine clinical utility of this treatment. clinicaltrials.gov Identifier: NCT00720538.	\N	\N
24284613	The aim of this review was to identify, evaluate and summarize all relevant studies reporting on the clinical response to gluten challenge by adult or pediatric patients with suspected or diagnosed coeliac disease (CD) on a gluten-free diet. We evaluated the effect of gluten challenge on changes in symptoms, intestinal mucosa histology, and serum antibodies. A systematic electronic search was performed for studies published as of 1966 using PubMed and Scopus databases. In the reviewed studies, doses ranged from 0.2 to 30 g/day of wheat gluten or comprised a gluten-containing diet. The onset of symptoms upon gluten intake varied largely from days to months and did not parallel serum antibody or histological changes. Within 3 months of gluten challenge, 70%-100% of pediatric CD patients became positive for AGA-IgA and EMA-IgA antibodies and 50%-70% for AGA-IgG. A limited number of trials suggest that no more than half of adult patients developed positive AGA-IgA, EMA-IgA, tTG-IgA or DGP-IgA/IgG titers. Approximately 50%-100% of pediatric and adult patients experienced mucosal relapse of gluten provocation within 3 months, which was preceded by increased mucosal intra-epithelial lymphocytes within several days of challenge. A 3-month high-dose gluten challenge should be suitable to diagnose the majority of CD patients. In some cases prolonged challenge may be needed to verify diagnosis. Combination testing for antibodies and mucosal histology may fasten the diagnosis.	\N	\N
24286024	Brain changes reminiscent of Alzheimer disease (AD) have been previously reported in a substantial portion of elderly cognitive healthy (HC) subjects. The major aim was to evaluate the accuracy of MRI assessed regional gray matter (GM) volume, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and neuropsychological test scores to identify those HC subjects who subsequently convert to mild cognitive impairment (MCI) or AD dementia. We obtained in 54 healthy control (HC) subjects a priori defined region of interest (ROI) values of medial temporal and parietal FDG-PET and medial temporal GM volume. In logistic regression analyses, these ROI values were tested together with neuropsychological test scores (free recall, trail making test B (TMT-B)) as predictors of HC conversion during a clinical follow-up between 3 and 4 years. In voxel-based analyses, FDG-PET and MRI GM maps were compared between HC converters and HC non-converters. Out of the 54 HC subjects, 11 subjects converted to MCI or AD dementia. Lower FDG-PET ROI values were associated with higher likelihood of conversion (p = 0.004), with the area under the curve (AUC) yielding 82.0% (95% CI = (95.5%, 68.5%)). The GM volume ROI was not a significant predictor (p = 0.07). TMT-B but not the free recall tests were a significant predictor (AUC = 71% (95% CI = 50.4%, 91.7%)). For the combination of FDG-PET and TMT-B, the AUC was 93.4% (sensitivity = 82%, specificity = 93%). Voxel-based group comparison showed reduced FDG-PET metabolism within the temporo-parietal and prefrontal cortex in HC converters. In conclusion, medial temporal and-parietal FDG-PET and executive function show a clinically acceptable accuracy for predicting clinical progression in elderly HC subjects.	\N	\N
24286594	Optimal management of colon cancer (CC) requires detailed assessment of extent of disease. This study prospectively investigates the diagnostic accuracy of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) for staging and detection of recurrence in primary CC. PET/CT for preoperative staging was performed in 66 prospectively included patients with primary CC. Diagnostic accuracy for PET/CT and CT was analyzed. In addition to routine follow up, 42 stages I-III CC patients had postoperative PET/CT examinations every 6 months for 2 years. Serological levels of tissue inhibitor of metalloproteinase-1 (TIMP-1), carcinoembryonic antigen, and liberated domain I of urokinase plasminogen activator receptor were analyzed. Accuracy for tumor, nodal, and metastases staging by PET/CT were 82% (95% confidence interval [CI]: 70; 91), 66% (CI: 51; 78), and 89% (CI: 79; 96); for CT the accuracy was 77% (CI: 64; 87), 60% (CI: 46; 73), and 69% (CI: 57; 80). Cumulative relapse incidences for stages I-III CC at 6, 12, 18, and 24 months were 7.1% (CI: 0; 15); 14.3% (CI: 4; 25); 19% (CI: 7; 31), and 21.4% (CI: 9; 34). PET/CT diagnosed all relapses detected during the first 2 years. High preoperative TIMP-1 levels were associated with significant hazards toward risk of recurrence and shorter overall survival. This study indicates PET/CT as a valuable tool for staging and follow up in CC. TIMP-1 provided prognostic information potentially useful in selection of patients for intensive follow up.	\N	\N
24292183	Pulmonary arterial hypertension (PAH) is a rare, progressive, and fetal disease. The five-year survival rate after diagnosis is ～50%. In Japan, PAH is listed in the Specified Rare and Intractable Diseases. Pulmonary vascular remodeling and sustained pulmonary vasoconstriction are the major causes for the elevated pulmonary vascular resistance (PVR) in PAH. The pathogenic mechanisms involved in the pulmonary vascular abnormalities in PAH remain unclear. Sustained vasoconstriction and vascular remodeling owing to proliferation of pulmonary arterial smooth muscle cells (PASMCs) are key pathogenic events that lead to early morbidity and mortality. These events have been closely linked to Ca(2+) mobilization and signaling in PASMCs. An increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) in PASMCs is an important stimulus for pulmonary vasoconstriction and cell proliferation which subsequently cause pulmonary vascular wall thickening followed by the increase in PVR. Increased resting [Ca(2+)]cyt and enhanced Ca(2+) influx have been implicated in PASMCs from PAH patients, but precise therapeutic targets to interrupt these signal pathways have not been identified. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), a G protein-coupled receptor (GPCR), is upregulated in PASMCs from patients with idiopathic pulmonary arterial hypertension (IPAH). In addition, blockage of the CaSR with an antagonist (NPS2143) prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The functionally upregulated CaSR in PASMCs is a novel pathogenic mechanism contributing to the augmented Ca(2+) signaling and excessive cell proliferation in IPAH. Targeting CaSR in PASMCs may help develop novel therapeutic approach for PAH.	\N	\N
24298283	In January 2012, Boström and colleagues identified a new muscle tissue secreted peptide, which they named irisin, to highlight its role as a messenger that comes from skeletal muscle to other parts of the body. Irisin is a cleaved and secreted fragment of FNDC5 (also known as FRCP2 and PeP), a member of fibronectin type III repeat containing gene family. Major interest in this protein arose because of its great therapeutic potential in diabetes and perhaps also therapy for obesity. Here we review the most important aspects of irisin's action and discuss its involvement in energy and metabolic homeostasis and whether the beneficial effects of exercise in these disease states could be mediated by this protein. In addition the effects of irisin at the central nervous system (CNS) are highlighted. It is concluded that although current and upcoming research on irisin is very promising it is still necessary to deepen in several aspects in order to clarify its full potential as a meaningful drug target in human disease states.	\N	\N
24299152	Patients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE. Fibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38) previous VD and from matched healthy controls (n = 68) were analyzed for the presence of complexes formed between contact system enzymes and antithrombin (AT) or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory parameters. Fibrin clots elicited FXII activation and acted as co-factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa-C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa-AT was elevated in the SLE patients with a history of VD, while the corresponding levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated strongly with platelet parameters. The odds ratio for VD among the SLE patients was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa-C1INH and increased levels of FXIIa-AT. Activation of FXII is elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered levels of FXIIa-serpin complexes, supporting that the contact system is involved in this disease. FXIIa-serpin complexes are strongly associated with previous VD in SLE patients, suggesting that these complexes are potential biomarkers for monitoring and assessing the risk of thrombotic events in SLE.	\N	\N
24305931	Intense postoperative monitoring has resulted in increasing detection of patients with recurrent papillary thyroid cancer (PTC). Our goals included quantifying successful reoperation, and analyzing surgical complications and reasons for relapse. From 1999 to 2008, a total of 410 patients underwent reoperation for PTC relapse. We analyzed post-reoperative disease outcomes, reasons for relapse, and complications. Bilateral reoperative thyroidectomy was performed in 13 (3 %) patients; lobectomy, 34 (8 %); central neck (VI) soft tissue local recurrence excision, 47 (11.5 %); bilateral VI node dissection, 107 (26 %); unilateral VI dissection, 112 (27 %); levels II-V dissection, 93 (23 %); levels III-V, 86 (21 %); lateral single- or two-compartment dissection, 51 (12 %); and node picking, 20 (5 %) of level VI and 53 (13 %) lateral neck. Complications occurred in 6 %; including hypoparathyroidism, 3 %; unintentional recurrent laryngeal nerve (RLN) paralysis, 3 %; phrenic nerve injury, 0.5 %; spinal accessory nerve injury, 0.5 %; and chyle leak in 1.6 %. Of 380 (93 %) patients with follow-up (mean 5.2 years); 274 (72 %) patients are alive with no structural evidence of disease, 38 % developed disease relapse (mean 2.1 years), 42 (11 %) died from PTC, and 55 (14 %) are alive with disease. The reason for relapse was a false negative pre-reoperative ultrasound (US) in 18 (5 %), nodal recurrence in the operative field in 37 (10 %), a combination of these two reasons in 10 (3 %), and disease virulence (local or systemic recurrence) in 81 (21 %). Although 72 % of patients were rendered structurally disease free after reoperation, nearly 40 % suffered additional relapse. Improved surgical technique or preoperative localization might positively affect 15-20 %; at least 20 % reflect the biologic aggressiveness of the disease.	\N	\N
24319959	To study the clinical characteristics of pediatric Kawasaki disease complicating mycoplasma pneumoniae pneumonia. Retrospective analysis was conducted on 11 children who had been diagnosed with Kawasaki disease with Mycoplasma pneumoniae pneumonia. The 11 cases presented with varying degrees of fever, conjunctival congestion, skin rashes, lymphadenectasis, distal extremities lesions, heart and lung lesions. 8 of them were standartly treated with azithromycin, while 3 of them were treatad with azithromycin and erythromycin. 2 patients with pleural effusion complicated by lobar pneumonia consolidation were treated with gamma globulin combined aspirin. All of the 11 patients were healed. Infections are common at the diagonosis of KD. Reasonable examination and antibiotics is useful to cure KD with MPP.	\N	\N
24321203	Data from surveillance networks help epidemiologists and public health officials detect emerging diseases, conduct outbreak investigations, manage epidemics, and better understand the mechanics of a particular disease. Surveillance networks are used to determine outbreak intensity (i.e., disease burden) and outbreak timing (i.e., the start, peak, and end of the epidemic), as well as outbreak location. Networks can be tuned to preferentially perform these tasks. Given that resources are limited, careful site selection can save costs while minimizing performance loss. We study three different site placement algorithms: two algorithms based on the maximal coverage model and one based on the K-median model. The maximal coverage model chooses sites that maximize the total number of people within a specified distance of a site. The K-median model minimizes the sum of the distances from each individual to the individual's nearest site. Using a ground truth dataset consisting of two million de-identified Medicaid billing records representing eight complete influenza seasons and an evaluation function based on the Huff spatial interaction model, we empirically compare networks against the existing Iowa Department of Public Health influenza-like illness network by simulating the spread of influenza across the state of Iowa. We show that it is possible to design a network that achieves outbreak intensity performance identical to the status quo network using two fewer sites. We also show that if outbreak timing detection is of primary interest, it is actually possible to create a network that matches the existing network's performance using 59% fewer sites. By simulating the spread of influenza across the state of Iowa, we show that our methods are capable of designing networks that perform better than the status quo in terms of both outbreak intensity and timing. Additionally, our results suggest that network size may only play a minimal role in outbreak timing detection. Finally, we show that it may be possible to reduce the size of a surveillance system without affecting the quality of surveillance information produced.	\N	\N
24326825	Lymph node metastasis (LNm), local recurrence (LR), and second primary tumor (SPT) after primary surgery for oral squamous cell carcinoma (OSCC) have been considered poor prognostic entities in terms of survival rate. The purpose of this study was to identify the clinicopathologic parameters significantly related to LNm, LR, and SPT. Records from 180 patients who underwent radical surgery for OSCC were retrospectively reviewed. Perineural invasion was significantly related to LNm (18% vs 8%) and LR (15% vs 5%), while the status of the surgical margin (10% in case of clear margins, 18% close margins, and 24% involved margins), namely epithelial precursor lesions (43%) was an independent factor influencing SPT. Perineural invasion proved a good prognostic factor for early events, either LNm or LR, while a surgical margin width less than 5 mm or with epithelial precursor lesions may be considered a risk factor for late events such as SPT.	\N	\N
24342581	To evaluate the efficacy of plasma-rich growth factor (PRGF) in improving socket healing after tooth extraction in diabetic patients. This was a split-mouth study in which each patient also served as the control: the study socket was treated with PRGF, whereas the control socket underwent natural healing. The outcome variables were the Healing Index, residual socket volume, visual analog scale score, postsurgical complications, and outcome of a patient questionnaire. The investigation considered the impact of hyperglycemia, glycated hemoglobin, End Organ Disease Score, and smoking habits. Follow-up included 4 postextraction checkups over a 21-day period. Pairs of correlated continuous variables were analyzed with the Wilcoxon test, independent continuous variables with the Mann-Whitney test, and categorical variables with the χ(2) test or Fisher test. From January 2012 to December 2012, 34 patients affected by insulin-dependent diabetes mellitus underwent contemporary bilateral extractions of homologous teeth. The treatment-versus-control postoperative comparison showed that PRGF resulted in significantly smaller residual socket volumes and better Healing Indices from days 3 to 14. The patients' questionnaire outcomes were unanimously in favor of PRGF treatment. The small sample of patients with glycemia values of at least 240 mg/dL showed worse Healing Index and minor socket decreases. PRGF application after extraction improved the healing process in diabetic patients by accelerating socket closure (epithelialization) and tissue maturation, proving the association between PRGF use and improved wound healing in diabetic patients.	\N	\N
24349495	Panton-Valentine leukocidin (PVL; gene designation lukF/S-PV) is likely an important virulence factor for Staphylococcus aureus (S. aureus), as qualitative expression of the protein correlates with severity for specific clinical presentations, including skin and soft tissue infections (SSTIs). Development of genetic approaches for risk-assessment of patients with S. aureus infections may prove clinically useful, and whether lukF/S-PV gene expression correlates with specific clinical presentations for S. aureus has been largely unexplored. In the present study, we quantified lukS-PV mRNA among 96 S. aureus isolates to determine whether expression levels correlated with specific clinical presentations in adults and children. Expression level of lukS-PV mRNA among isolates from skin and soft tissue infections (SSTIs) was significantly greater than among isolates from blood stream infection (BSIs), and expression level of lukS-PV mRNA among BSI isolates from children was significantly greater than for BSI isolates among adults. Moreover, expression level of lukS-PV mRNA among community-acquired (CA) isolates was significantly greater than for hospital-acquired (HA) isolates. These data justify additional studies to determine the potential clinical utility for lukS-PV mRNA quantification as a predictive tool for severity of S. aureus infection.	\N	\N
24352112	This report contains CDC guidance that augments the 2011 recommendations of the Advisory Committee on Immunization Practices (ACIP) for evaluating hepatitis B protection among health-care personnel (HCP) and administering post-exposure prophylaxis. Explicit guidance is provided for persons working, training, or volunteering in health-care settings who have documented hepatitis B (HepB) vaccination years before hire or matriculation (e.g., when HepB vaccination was received as part of routine infant [recommended since 1991] or catch-up adolescent [recommended since 1995] vaccination). In the United States, 2,890 cases of acute hepatitis B were reported to CDC in 2011, and an estimated 18,800 new cases of hepatitis B occurred after accounting for underreporting of cases and asymptomatic infection. Although the rate of acute hepatitis B virus (HBV) infections have declined approximately 89% during 1990-2011, from 8.5 to 0.9 cases per 100,000 population in the United States, the risk for occupationally acquired HBV among HCP persists, largely from exposures to patients with chronic HBV infection. ACIP recommends HepB vaccination for unvaccinated or incompletely vaccinated HCP with reasonably anticipated risk for blood or body fluid exposure. ACIP also recommends that vaccinated HCP receive postvaccination serologic testing (antibody to hepatitis B surface antigen [anti-HBs]) 1-2 months after the final dose of vaccine is administered (CDC. Immunization of health-care personnel: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2011;60 [No. RR-7]). Increasing numbers of HCP have received routine HepB vaccination either as infants (recommended since 1991) or as catch-up vaccination (recommended since 1995) in adolescence. HepB vaccination results in protective anti-HBs responses among approximately 95% of healthy-term infants. Certain institutions test vaccinated HCP by measuring anti-HBs upon hire or matriculation, even when anti-HBs testing occurs greater than 2 months after vaccination. This guidance can assist clinicians, occupational health and student health providers, infection-control specialists, hospital and health-care training program administrators, and others in selection of an approach for assessing HBV protection for vaccinated HCP. This report emphasizes the importance of administering HepB vaccination for all HCP, provides explicit guidance for evaluating hepatitis B protection among previously vaccinated HCP (particularly those who were vaccinated in infancy or adolescence), and clarifies recommendations for postexposure management of HCP exposed to blood or body fluids.	\N	\N
24355565	The pancreas consists of two major divisions, the exocrine and the endocrine pancreas. Recent data from our laboratory have shown that the functions of the two divisions are under modulatory regulation by separate neurocircuits that originate in the dorsal motor nucleus of the vagus (DMV). Metabotropic glutamate receptors (mGluRs) are expressed throughout the central nervous system and have been implicated in the modulation of synaptic transmission. mGluRs consist of three groups of receptors, which can be distinguished based on their pharmacological properties and second messenger systems. Group I mGluRs predominantly increase, whereas group II and III mGluRs decrease synaptic transmission. Group II and group III mGluRs are present on excitatory and inhibitory synaptic terminals impinging on pancreas-projecting DMV neurons. We have shown that group II mGluRs regulate both exocrine pancreatic secretions and insulin release, whereas group III mGluRs only regulate insulin release. Several mGluR agonists and antagonists have been shown to have clinical uses for disorders accompanied by abnormal synaptic transmission, including anxiety and Parkinson's disease. Moreover, a negative allosteric modulator of Group I mGluRs is effective in alleviating symptoms of gastro-esophageal reflux disease (GERD). Since the role of the three mGluR groups in mediating different gastrointestinal (GI) functions appears to be highly specific, the use of agonists or antagonists directed at a single receptor group could potentially provide highly selective targets for the treatment of GI disorders including GERD, functional dyspepsia and acute pancreatitis.	\N	\N
24361034	The integration of body, mind, and spirit has become a key dimension of health education and disease prevention and treatment; however, our health care system remains primarily disease centered. Finding simple steps to help each of us find our own balance can improve our lives, our work, and our relationships. On the basis of interviews with health care experts at the leading edge of the new model of medicine, this article identifies simple tools to improve the health of patients and caregivers.	\N	\N
24362818	Follicular lymphoma is an incurable malignancy, with transformation to an aggressive subtype representing a critical event during disease progression. Here we performed whole-genome or whole-exome sequencing on 10 follicular lymphoma-transformed follicular lymphoma pairs followed by deep sequencing of 28 genes in an extension cohort, and we report the key events and evolutionary processes governing tumor initiation and transformation. Tumor evolution occurred through either a 'rich' or 'sparse' ancestral common progenitor clone (CPC). We identified recurrent mutations in linker histone, JAK-STAT signaling, NF-κB signaling and B cell developmental genes. Longitudinal analyses identified early driver mutations in chromatin regulator genes (CREBBP, EZH2 and KMT2D (MLL2)), whereas mutations in EBF1 and regulators of NF-κB signaling (MYD88 and TNFAIP3) were gained at transformation. Collectively, this study provides new insights into the genetic basis of follicular lymphoma and the clonal dynamics of transformation and suggests that personalizing therapies to target key genetic alterations in the CPC represents an attractive therapeutic strategy.	\N	\N
24368549	Hugh Henry Bentall, the inventor of the surgical procedure that enabled concomitant replacement of the aortic valve and ascending aorta, died on September 2012 at the age of 92. He was the first Professor of Cardiothoracic Surgery in the United Kingdom, at the Hammersmith Hospital, and carried out the first open-heart operations with a heart-lung machine in London in 1953. Besides cardiac surgery, he paid particular attention to cardiac anatomy and embryology, which he enriched even following retirement. He leaves three sons and a daughter.	\N	\N
24369205	Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en-bloc removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation, and re-implantation back in the body. We report our preliminary experience of using ECI for management of MBT. From year 2009 to 2010, 14 patients with primary MBT were enrolled into this study. The eligibility criteria included histopathological proof of malignancy, no evidence of distant metastases, and suitability for limb preservation therapy. Surgery was performed about 4 weeks after completion of neoadjuvant chemotherapy. The affected bone segment was resected, irradiated extracorporeally with a dose of 50 Gy and reimplanted. Local control, complications and short-term survival were studied. Functional outcome was assessed by Musculoskeletal Tumor Society (MSTS) scoring system. There were 10 males and four females with median age of 14 years. Histopthologically, nine patients had osteosarcoma (OS) and five had Ewing's sarcoma family of tumors (ESFT). Distribution of primary site was as follows: Femur eight patients, tibia five patients and humerus one patient. At a median follow-up was 22 months, three patients (two OS, one ESFT) had local recurrence. Two patients (14%) developed wound infection in the perioperative period. The 2 year local recurrence free survival was 73% and mean MSTS score was 88. Results of our study suggest that ECI is technically feasible in the management of MBT and provides decent local control and short-term survival rates.	\N	\N
24377187	Optimal nutrition, immunological state and psychological condition play an important role in the process of chronic wound healing. Infections caused by pathogens resistant to commonly used antibiotics additionally complicate and disturb regeneration of wounds. As part of the treatment, modern wound dressings are used, for example designed on the basis of alginates, dextranomers, hydrogels, hydrofiber, polyurethanes foams, hydrocolloids and liquids for wound debridement such us 0.9% NaCl, the PWE liquid, Ringer's liquid, octenidine. Owing to their features, treatment in accordance with TIME concept could be realized, because they provide moisture wound bed, protection against contamination, gas exchange, protection of wound edges and infection control. Repairing process in chronic wounds is dependent on blood flow in tissues, which may be insufficient. The result is a permanent hypoxia. Natural occurring antioxidants are becoming more crucial in chronic wound treatment. They decrease oxygen radical concentration, increase angiogenesis, reduce inflammatory response, stimulate fibroblasts and keratinocytes proliferation, possess antibacterial properties against chemotherapeutic resistant strains. There are a lot of antioxidants in honey, papaya fruit (Carrica papaia L.), transgenic flax (Linum usitatissimum), and in orange oil (Citrus sinensis), stem of acanthus (Acanthus ebracteatus), leafs of tea (Camellia sinensis). Application of biologically active, natural derived compounds is nowadays a direction of intense in vitro and in vivo research focused on the chronic wound treatment. Results suggest beneficial influence of antioxidant on wound repairing process. Clinical research are needed to state effective influence of natural compound in the chronic wound treatment.	\N	\N
24382893	Pathological inflammation and autoimmune disease frequently involve elevated neutrophil activity in the absence of infectious agents. Tumor necrosis factor-α (TNF-α) contributes to many of the problems associated with autoimmune diseases. We investigated the ability of serum α-1 antitrypsin (AAT) to control TNF-α biosynthesis and signaling in neutrophils and assessed whether AAT deficiency (AATD) is a TNF-α-related disease. In vitro studies demonstrate that serum AAT coordinates TNF-α intracellular signaling and neutrophil degranulation of tertiary and secondary granules via modulation of ligand-receptor interactions. AATD patients homozygous for the Z allele were characterized by increased activation of the TNF-α system, as demonstrated by increased membrane TNF-α levels and increased plasma concentrations of TNF receptor 1 and neutrophil-released secondary and tertiary granule proteins. The incidence of autoantibodies directed against degranulated lactoferrin and surface protein accessible to these antibodies was increased in ZZ-AATD, leading to an enhanced rate of neutrophil reactive oxygen species production. Treatment of ZZ-AATD individuals with AAT augmentation therapy resulted in decreased membrane TNF-α expression and plasma levels of granule antigenic proteins and immunoglobulin G class autoantibodies. These results provide a mechanism by which AAT augmentation therapy affects TNF-α signaling in the circulating neutrophil, indicating promising potential of this therapy for other TNF-α-related diseases.	\N	\N
24390521	Patients with atrial fibrillation (AF) have an increased risk of congestive heart failure (CHF) as well as ischemic stroke. The aim of this study was to investigate the clinical predictors of CHF in patients with non-valvular AF (NVAF). Three hundred and forty-seven patients (derivation cohort) with NVAF were retrospectively evaluated between 2004 and 2005. The associations between potential risk factors and CHF were tested using a Cox proportional hazards analysis, and a risk score for predicting CHF was created. The model was then validated in 161 patients (validation cohort) enrolled between 2008 and 2010. During the follow-up period, 41 patients in the derivation cohort developed CHF requiring hospitalization due to New York Heart Association (NYHA) class III or IV disease. Four independent risk factors were identified, each of which was assigned a number of points as follows: Age ≥72 years (1 point), heart rate ≥80 bpm (1 point), hypertension (1 point), and a previous history of congestive heart failure (2 points). The patients were grouped into one of three risk categories according to the calculated risk score (ARC2H score): low risk (0 points), intermediate risk (1-3 points) and high risk (4-5 points). In the derivation cohort, the annual rates of CHF in these risk categories were 0%, 2.5% and 18% per year respectively. In the validation cohort, the corresponding rates were 0.8%, 8% and 35% per year respectively. A simple clinical risk score, the ARC2H score, was developed to predict CHF in patients with NVAF and validated in an independent cohort.	\N	\N
24395633	Although Hodgkin's lymphoma (HL) was one of the first human cancers to be cured by chemotherapy, no new agents other than brentuximab vedotin (Adcetris®, CD 30 directed antibody drug conjugate) have received US Food and Drug Administration (FDA) approval for HL since 1977. Subsets of young adult patients with HL continue to relapse, even after stem cell transplantation, warranting new approaches. Against this background, we report a dramatic response in a young patient with advanced HL refractory to the standard treatment who responded to the combination of a pan-histone deacetylase inhibitor (vorinostat, suberoylanilide hydroxamic acid, SAHA) and mammalian target of rapamycin (mTOR) inhibitor therapy (sirolimus,rapamume). In-depth immunohistochemical and morphoproteomic analyses of this exceptional responder to targeted therapy have yielded potential insights into the biology of advanced HL. The PI3K/AKT/mTOR pathway is a commonly activated pathway in multiple tumor types including HL. The patient was treated using therapy based on mechanistic in vitro data demonstrating that combined histone deacetylase (HDAC) and mTOR inhibition act together on this pathway, resulting in inhibition of reciprocal feedback networks, leading to better anti-proliferative activity. The in vivo response signature from this patient's tissue sample sheds light on immune dysregulation in HL. We describe the response signature achieved from targeting immune dysregulation in addition to targeting the key oncogenic PI3K/AKT/mTOR pathway. We also expand on the role of rapamycin analogs in oncology. This study supports a role for an immune-type pathogenesis that is amenable to immune modulating targeted therapy in refractory HL. We report an exceptional responder to molecularly targeted and immune modulator therapy in advanced Hodgkin's lymphoma. The morphoproteomic/morphometric findings in this "unusual responder" patient's relapsed HL that correlate best, as a response signature with the subsequent clinical remission following rapamycin (sirolimus) and vorinostat (SAHA) therapies, center on an immune dysregulation involving an imbalance between effector and functional T regulatory cells in addition to targeting the mTOR pathway. This underscores the need for an approach illustrated in our study--namely of focusing on pathogenetic mechanisms and combinatorial therapies that target both the pathogenesis and adaptive responses to contemplated therapies.	\N	\N
24395648	Information on the chimpanzee nasopharygeal colonization in captive sanctuaries and in the wild is rare. This study was undertaken to establish the nasopharygeal colonization and potential bacterial pathogens in sanctuary chimpanzees as a basis for improving chimpanzee and employee health. Nasopharygeal colonization of 39 healthy chimpanzees were analyzed by microbiological cultivation method and polymerase chain reaction (PCR) targeting the bacterial 16S rRNA gene. We report four major phyla dominated by Proteobacteria (50%), Fermicutes (35.7%), Bacteriodes (7.1%), and Cynobacteria (7.1%) in healthy semi-captive chimpanzees. Further classification based on 7-base oligomers revealed the following genera: Streptococcus, Veillonella, Neisseria, Prevotella, Kingella and unclassified Cynobacteria, Actinobacillus, Bacteriodes and Pasteurellaceae. On microbiological cultivation we were able to identify and characterize some of the bacteria to species level as Klebsiella pneumonie and Pseudomonas aeruginosa being dominant bacteria with 54.7% and 50% colonization, respectively. Of these, Streptococcus, Neisseria, Klebsiella, and Haemophillus have representatives known to potentially cause severe respiratory disease. Our data present important information on chimpanzee nasopharygeal colonization as a guide to understanding disease processes and pharmaceutical therapies required for improving the health of chimpanzees. The results from this study will guide the processes to improve procedures for routine management of sanctuary chimpanzees and use it as a basis for evaluation of future reintroduction possibilities.	\N	\N
24418861	Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma and is mostly represented by the embryonal (ERMS) and alveolar (ARMS) histotypes. Whereas ERMS shows variable genetic alterations including TP53, RB1, and RAS mutations, ARMS carries a gene fusion between PAX3 or PAX7 and FOXO1. Epithelioid RMS is a morphologic variant of RMS recently described in adults. Five cases of epithelioid RMS were identified after histologic review of 85 cases of ARMS enrolled in Italian therapeutic protocols. Immunostaining analyses (muscle-specific actin, desmin, myogenin, AP-2β, EMA, cytokeratins, INI-1) and reverse transcription polymerase chain reaction assays to detect MyoD1, myogenin, and PAX3/7-FOXO1 transcripts were performed. In 4 cases DNA sequencing of TP53 was performed; and RB1 allelic imbalance and homozygous deletion were analyzed by quantitative real-time polymerase chain reaction. Histologically, epithelioid RMS displayed sheets of large cells without rhabdomyoblastic differentiation or anaplasia in 3 and prominent rhabdoid cells in 2; necrosis was evident in 4, often with a geographic pattern. Immunostainings for INI, desmin, myogenin (scattered cells in 4, diffuse in 1) were positive in all; EMA and MNF116 were positive in 2; AP-2β was negative. PAX3/7-FOXO1 transcripts were absent. In all cases RB1 was wild type, and a TP53 mutation at R273H codon was found in 1. All patients are in complete remission, with a median follow-up of 6 years. Epithelioid RMS may occur in children and is probably related to ERMS, as suggested by lack of fusion transcripts, weak staining for myogenin, negative AP-2β, evidence of TP53 mutation (although only in 1 case), and a favorable clinical course.	\N	\N
24424075	Hyperphosphataemia, a common biochemical abnormality in chronic kidney disease, poses significant management challenges. This study aims to determine whether the reasons for this are multifactorial; including poor dietary knowledge, poor adherence to a low phosphate diet and phosphate-binding medications and the impact of age on these parameters. In order to compare serum phosphate and other associated parameters to the UK Renal Association Clinical Practice Guidelines 2010 an audit and service evaluation questionnaire was carried out in May 2011 on 130 haemodialysis outpatients attending the Plymouth Dialysis Unit. Fifty-three percent of patients had serum phosphate within the target range of 1.1-1.7 mmol/l, 77% and 85% had serum calcium and parathyroid hormone within target ranges, respectively. Younger patients (18-45 years) were significantly less likely to have serum phosphate within range χ(2) (2, n=124)=18.77, P<0.001. Despite better knowledge of their own phosphate levels (P=0.005), phosphorus-rich foods (P<0.001), symptoms of hyperphosphataemia (P<0.001) and increased use of Renal Patient View (P=0.002), <65 years old had significantly higher phosphate levels than those >65 years (P<0.001). No significant associations were found between phosphate control and the following factors: gender, timing of dialysis shift, years on dialysis or dialysis adequacy. In this population, despite better knowledge, younger patients have worse phosphate control than older patients. Using the same dietary education techniques may not be suitable for all ages, more innovative approaches supported by skilled health professionals are needed to motivate and engage with younger patients to promote self-management and adherence.	\N	\N
24424629	To evaluate the long-term efficacy of pain reduction by two dose fractionation schedules used for low-dose radiotherapy of painful elbow syndrome. Between February 2006 and February 2010, 199 evaluable patients were recruited for this prospective trial. All patients received low-dose orthovoltage radiotherapy. One course consisted of 6 fractions in 3 weeks. In the case of insufficient pain remission after 6 weeks, a second course was administered. Patients were randomly assigned to one of two groups to receive single doses of either 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before radiotherapy, as well as immediately after (early response), 6 weeks after (delayed response) and approximately 3 years after (long-term response) completion of radiotherapy using a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS). Median follow-up was 35 months (range 9-57 months). The overall early, delayed and long-term response rates for all patients were 80, 90 and 94 %, respectively. The mean VAS scores before treatment and those for early, delayed and long-term response in the 0.5- and 1.0-Gy groups were 59.6 ± 20.2 and 55.7 ± 18.0 (p = 0.46); 32.1 ± 24.5 and 34.4 ± 22.5 (p = 0.26); 27.0 ± 27.7 and 23.5 ± 21.6 (p = 0.82) and 10.7 ± 15.0 and 21.5 ± 26.9 (p = 0.12), respectively. The mean CPS values before treatment and those for early, delayed and long-term response were 8.7 ± 2.9 and 8.1 ± 3.1 (p = 0.21); 4.5 ± 3.2 and 5.0 ± 3.4 (p = 0.51); 3.9 ± 3.6 and 2.8 ± 2.8 (p = 0.19) and 1.5 ± 2.3 and 2.4 ± 3.5 (p = 0.27), respectively. No significant differences in the quality of the long-term response were found between the 0.5- and 1.0-Gy arms (p = 0.28). Low-dose radiotherapy is an effective treatment for the management of benign painful elbow syndrome. For radiation protection reasons, the dose for a radiotherapy series should not exceed 3.0 Gy.	\N	\N
24436152	L-Asparaginase is an integral component of standard chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL). Clinical hypersensitivity, a common reason for treatment discontinuation, has been reported in 10-30% of patients receiving Escherichia coli-derived asparaginase. After hypersensitivity, E. coli-derived asparaginase should be discontinued and an alternative asparaginase preparation, such as asparaginase Erwinia chrysanthemi, may be initiated. We conducted a compassionate-use study to collect additional safety information on asparaginase Erwinia chrysanthemi and to support FDA approval of the product. Patients with ALL or lymphoblastic lymphoma (LBL; N = 1368) who developed a hypersensitivity reaction (grade ≥2) to an E. coli-derived asparaginase participated in this trial. The recommended asparaginase Erwinia chrysanthemi dose was 25,000 IU/m(2) three days per week (Monday/Wednesday/Friday) for two consecutive weeks for each missed pegylated E. coli-derived asparaginase dose and 25,000 IU/m(2) for each missed nonpegylated asparaginase dose for the completion of their planned asparaginase treatment. Adverse event reports and/or case report forms were completed for 940 patients. The most common adverse event (AE) was hypersensitivity (13.6%). Eighteen patients (1.9%) died during the study. Most patients (77.6%) completed their planned asparaginase treatment with asparaginase Erwinia chrysanthemi. There was no apparent difference in the incidence of the most commonly reported AEs with asparaginase treatment by age, administration, or disease state. This study further established the safety profile of asparaginase Erwinia chrysanthemi in patients with ALL or LBL who had a hypersensitivity reaction to an E. coli-derived asparaginase.	\N	\N
24437400	The development of culture-independent techniques has revolutionized our understanding of how our human cells interact with the even greater number of microbial inhabitants of our bodies. As part of this revolution, data are increasingly challenging the old dogma that in health, the lung mucosa is sterile. To understand how the lung microbiome may play a role in human health, we identified five major questions for lung microbiome research: (1) Is the lung sterile? (2) Is there a unique core microbiome in the lung? (3) How dynamic are the microbial populations? (4) How do pulmonary immune responses affect microbiome composition? and (5) Are the lungs influenced by the intestinal immune responses to the gut microbiome? From birth, we are exposed to continuous microbial challenges that shape our microbiome. In our changing environment, perturbation of the gut microbiome affects both human health and disease. With widespread antibiotic use, the ancient microbes that formerly resided within us are being lost, for example, Helicobacter pylori in the stomach. Animal models show that antibiotic exposure in early life has developmental consequences. Considering the potential effects of this altered microbiome on pulmonary responses will be critical for future investigations.	\N	\N
24446993	With an estimated 12.1% of children aged 2-5 years already obese, prevention efforts must target our youngest children. One of the best places to reach young children for such efforts is the early care and education setting (ECE). More than 11 million U.S. children spend an average of 30 hours per week in ECE facilities. Increased attention at the national, state, and community level on the ECE setting for early obesity prevention efforts has sparked a range of innovative efforts. To assist these efforts, CDC developed a technical assistance and training framework - the Spectrum of Opportunities for Obesity Prevention in the ECE setting - which also served as the organizing framework for the Weight of the Nation ECE track. Participants highlighted their efforts at national, state, and local levels pursuing opportunities on the Spectrum, the standards and best practices that had been the emphasis of their efforts, and common steps for developing, implementing, and evaluating initiatives. Strong leadership and collaboration among a broad group of stakeholders; systematic assessment of needs, opportunities and resources; funding sources; and training and professional development were reported to be integral for successful implementation of standards and best practices, and sustainability.	\N	\N
24447640	Fungal endophthalmitis is a rare but serious infection. In March 2012, several cases of probable and laboratory-confirmed fungal endophthalmitis occurring after invasive ocular procedures were reported nationwide. We identified 47 cases in 9 states: 21 patients had been exposed to the intraocular dye Brilliant Blue G (BBG) during retinal surgery, and the other 26 had received an intravitreal injection containing triamcinolone acetonide. Both drugs were produced by Franck's Compounding Lab (Ocala, FL, USA). Fusarium incarnatum-equiseti species complex mold was identified in specimens from BBG-exposed case-patients and an unopened BBG vial. Bipolaris hawaiiensis mold was identified in specimens from triamcinolone-exposed case-patients. Exposure to either product was the only factor associated with case status. Of 40 case-patients for whom data were available, 39 (98%) lost vision. These concurrent outbreaks, associated with 1 compounding pharmacy, resulted in a product recall. Ensuring safety and integrity of compounded medications is critical for preventing further outbreaks associated with compounded products.	\N	\N
24449063	Psychotic symptoms have previously been reported following right hemisphere brain injury. We sought to identify the specific neuroanatomical basis of delusions following stroke by studying a series of patients with post-stroke psychosis. Lesion overlap analysis was conducted on three individuals with delusions following right hemisphere stroke. These cases were compared with a control group of patients with similar anatomical damage. The main outcome measures were presence of delusions and presence of behavioural susceptibility. The right inferior frontal gyrus and underlying white matter, including the superior longitudinal fasciculus and anterior corona radiata, were involved in all three cases. All three had a preexisting untreated psychiatric disorder. In contrast, only one of nine control cases with equivalent lesions had evidence of previous psychiatric disorder (p = 0.0182, Fisher's exact test), and this was being treated at the time of stroke. We provide clinical evidence from patients with structural brain lesions implicating damage to the right inferior frontal lobe in the generation of persistent psychosis following stroke. We suggest that preexisting psychiatric disease provided a behavioural susceptibility to develop delusions in these individuals.	\N	\N
24449064	The logopenic variant of primary progressive aphasia (lvPPA) strongly associates with Alzheimer's disease, but can also associate with frontotemporal lobar degeneration. We aimed to assess the frequency of lvPPA in patients with speech and language disorders without β-amyloid deposition, and to perform detailed neuroimaging and genetic testing in such lvPPA patients. Seventy-six patients with a neurodegenerative speech and language disorder and Pittsburgh compound B (PiB) PET imaging demonstrating no β-amyloid deposition were analyzed. Six lvPPA patients (8 %) were identified. All six underwent progranulin (GRN) gene testing. Structural abnormality index maps and Cortex ID analysis were utilized to assess individual patterns of grey matter atrophy on MRI and hypometabolism on 18-F fluorodeoxyglucose (FDG) PET. Statistical parametric mapping was used to perform MRI and FDG-PET group comparisons between those with (GRN-positive) and without (GRN-negative) progranulin mutations. All six lvPPA patients showed left temporoparietal atrophy and hypometabolism. Three patients (50 %) were GRN-positive. Speech, language, and neurological and neuropsychological profiles did not differ between GRN-positive and negative patients, although GRN-positive patients had family histories, were on average 8 years younger, and had lower PiB-PET ratios. All six patients showed similar patterns of atrophy and hypometabolism, although, as a group, GRN-positive patients had more severe abnormalities, particularly in anteromedial temporal lobes. Logopenic PPA accounts for a small minority of neurodegenerative speech and language disorders not associated with β-amyloid deposition. Identification of such patients, however, should prompt testing for GRN mutations, since GRN-positive patients do not have distinctive features, yet account for 50 % of this patient population.	\N	\N
24449169	Low-frequency, bilateral stimulation of the subthalamic nucleus can improve axial symptoms of advanced Parkinson's disease (PD), but it is not particularly effective for segmental symptoms. The optimal contacts for low-frequency (60 Hz) and high-frequency (130 Hz) single monopolar stimulation were determined. Then, in a randomized, double-blind, prospective crossover manner, 60-Hz and 130-Hz stimulations via the respective optimal contacts were compared for immediate efficacy in improving the motor function of patients with PD. The optimal contacts for 60-Hz stimulation were situated more ventrally than those for 130-Hz stimulation (P = 0.038). Under the respective optimal, single monopolar stimulation, 60 Hz provided superior efficacy over 130 Hz in improving the total Unified Parkinson's Disease Rating Scale motor score (P < 0.001) and the akinesia (P = 0.011) and axial motor signs (P = 0.012) subscores without compromising the therapeutic effect on tremor and rigidity. Low-frequency stimulation via the optimal contacts is effective in improving overall motor function of patients with PD.	\N	\N
24450996	Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. Our results demonstrate that vaccinating children 2-17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany.	\N	\N
24459296	Huntington disease (HD) is a debilitating neurodegenerative disease characterized by the loss of motor control and cognitive ability that ultimately leads to death. It is caused by the expansion of a polyglutamine tract in the huntingtin (HTT) protein, which leads to aggregation of the protein and eventually cellular death. Both the wild-type and mutant form of the protein are highly regulated by post-translational modifications including proteolysis, palmitoylation and phosphorylation. We now demonstrate the existence of a new post-translational modification of HTT: the addition of the 14 carbon fatty acid myristate to a glycine residue exposed on a caspase-3-cleaved fragment (post-translational myristoylation) and that myristoylation of this fragment is altered in a physiologically relevant model of mutant HTT. Myristoylated HTT553-585-EGFP, but not its non-myristoylated variant, initially localized to the ER, induced the formation of autophagosomes and accumulated in abnormally large autophagolysosomal/lysosomal structures in a variety of cell types, including neuronal cell lines under nutrient-rich conditions. Our results suggest that accumulation of myristoylated HTT553-586 in cells may alter the rate of production of autophagosomes and/or their clearance through the heterotypic autophagosomal/lysosomal fusion process. Overall, our novel observations establish a role for the post-translational myristoylation of a caspase-3-cleaved fragment of HTT, highly similar to the Barkor/ATG14L autophagosome-targeting sequence domain thought to sense, maintain and/or promote membrane curvature in the regulation of autophagy. Abnormal processing or production of this myristoylated HTT fragment might be involved in the pathophysiology of HD.	\N	\N
24460750	In patients with essential thrombocythemia (ET), vascular complications contribute to both morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score of thrombosis for ET (IPSET-thrombosis) was recently developed. We hereby presented an external validation and analysis of this model in a large Cohort of Chinese Patients. We retrospectively evaluated the characteristics and risk factors for thrombosis in 970 Chinese patients with ET and estimated the clinical implications of the IPSET-thrombosis model. The median follow-up was 49 months (range, 0-360). Chinese ET patients had similar clinical characteristics as Caucasian patients. Similar to the IPSET-thrombosis study, our multivariate analysis revealed age >60 (HR = 1.949), previous thrombosis (HR = 2.484), JAK2V617F mutation (HR = 1.719), and cardiovascular risk factors (HR = 1.877) as independent risk factors for thrombosis. We confirmed that the above risk factors in IPSET-thrombosis, when compared with traditional risk factors (e.g., age ≥60 and previous thrombotic events), were more predictive of thrombotic events (C-index 0.714 vs. 0.647). Classification by IPSET-thrombosis risk groups revealed different cumulative thrombosis-free survival (P < 0.001). For treatment, patients in the intermediate- and high-risk group derived clinical benefit from cytoreductive agents (P < 0.05), but those in the low-risk group did not (P = 0.446). The lower risk of thrombosis on cytoreductive therapy was related to decrease in leukocyte count during the disease course. We validate the reproducibility of IPSET-thrombosis in Chinese ET patients and provide key clinical implications.	\N	\N
24467498	alcohol use disorders are associated with a greater incidence of certain comorbidities in patients with celiac disease. Currently there is no available information about the impact that these disorders may have on length of hospital stays, overexpenditures during hospital stays, and excess mortality in these patients. a case-control study was conducted with a selection of patients 18 years and older hospitalized during 2008-2010 in 87 hospitals in Spain. Estimations of excess length of stays, costs, and attributable mortality were calculated using a multivariate analysis of covariance, which included age, gender, hospital group, alcohol use disorders, tobacco related disease and 30 other comorbidities. patients who had both celiac disease and alcohol use disorders had an increased length of hospital stay, an average of 3.1 days longer in women, and 1.7 days longer in men. Excess costs per stay ranged from 838.7 euros in female patients, to 389.1 euros in male patients. Excess attributable mortality was 15.1 % in women, 12.2 % in men. apart from a gluten-free diet and other medical measures, the prevention of alcohol abuse is indicated in these patients. Patients hospitalized who present these disorders should receive specialized attention after leaving the hospital. Early detection and treatment should be used to prevent the appearance of organic lesions and should not be solely focused on male patients.	\N	\N
24469423	The molecular epidemiology of group B Streptococcus (GBS) in Ireland was investigated. Invasive (n = 132) and non-invasive (n = 45) isolates, collected in 2007-2011, were analysed by multilocus locus sequence typing, capsular polysaccharide (CPS) serotyping, profiling of surface proteins, pilus islands (PI), and antimicrobial susceptibility. Isolates grouped into 45 sequence types and five main clonal complexes (CC). CC1, CC17 and CC23 represented 67.2 % of isolates and the most prevalent serotypes Ia, III and V. Serotype and surface protein genes were largely predictive of CC. Accordingly, CPS V/alp3, CPS Ib/CPS II/bca + bac, and CPS Ia/eps predominated in CC1, CC12 and CC23, respectively, and CPS III/rib in CC17 and CC19. Supporting their vaccine potential, all isolates harboured at least one PI, of which the PI-1 + PI-2a combination was most prevalent. Macrolide resistance was found in 18.6 % of isolates. erm(B) and the globally disseminated CC1/CPS V were the most common resistance mechanism and CC/CPS type, respectively. CC17, significantly associated with neonatal disease, was also prevalent in pregnant adults, but was underrepresented among non-pregnant adults. Two of 46 CC17 isolates (typically CPS III) were CPS IV. Sequence analysis confirmed capsular switching and their relatedness to CC17/CPS IV strains recently characterized in France. CPS IV, detected only in invasive isolates (6.8 %), was most prevalent in adults (12 %) and showed an increase in prevalence to that reported (1.4 %) for invasive isolates in Ireland 1997-1999. Increases in serotype IV and evidence of capsular switching in CC17 highlights the importance of ongoing surveillance of GBS and may have implications for vaccine development strategies.	\N	\N
24478094	Evidence from clinical trials of malaria vaccine candidates suggests that both cell-mediated and humoral immunity to pre-erythrocytic parasite stages can provide protection against infection. Novel pre-erythrocytic antibody (Ab) targets could be key to improving vaccine formulations, which are currently based on targeting antigens such as the circumsporozoite protein (CSP). However, methods to assess the effects of sporozoite-specific Abs on pre-erythrocytic infection in vivo remain underdeveloped. Here, we combined passive transfer of monoclonal Abs (MAbs) or immune serum with a luciferase-expressing Plasmodium yoelii sporozoite challenge to assess Ab-mediated inhibition of liver infection in mice. Passive transfer of a P. yoelii CSP MAb showed inhibition of liver infection when mice were challenged with sporozoites either intravenously or by infectious mosquito bite. However, inhibition was most potent for the mosquito bite challenge, leading to a more significant reduction of liver-stage burden and even a lack of progression to blood-stage parasitemia. This suggests that Abs provide effective protection against a natural infection. Inhibition of liver infection was also achieved by passive transfer of immune serum from whole-parasite-immunized mice. Furthermore, we demonstrated that passive transfer of a MAb against P. falciparum CSP inhibited liver-stage infection in a humanized mouse/P. falciparum challenge model. Together, these models constitute unique and sensitive in vivo methods to assess serum-transferable protection against Plasmodium sporozoite challenge.	\N	\N
24501382	It has been established that bimanual coordination with augmented feedback (FB) versus no augmented feedback (NFB) is associated with activity in different brain regions. It is unclear however, whether this distinction remains after practice comprising both these conditions. Functional magnetic resonance imaging was used in humans to compare visual FB versus NFB conditions for a bimanual tracking task, and their differential evolution across learning. Scanning occurred before (Pre) and after 2 weeks (Post) of mixed FB and NFB training using an event-related design, allowing differentiation between the planning and execution phase of the task. Activations at the whole-brain level initially differed for FB versus NFB movements but this differentiation diminished with training for the movement execution phase. Specifically, in right dorsal premotor cortex and right dorsolateral prefrontal cortex activation increased for NFB and decreased for FB trials to converge toward the end of practice. This suggests that learning led to a decreased need to adjust the ongoing movement on the basis of FB, whereas online monitoring became more pronounced in NFB trials as discrepancies between the required and the produced motor output were detected more accurately after training, due to a generic internal reference of correctness supporting movement control under varying conditions.	\N	\N
24505382	Public health surveillance systems provide valuable data for reliable predication of future epidemic events. This paper describes a study that used nine types of infectious disease data collected through a national public health surveillance system in mainland China to evaluate and compare the performances of four time series methods, namely, two decomposition methods (regression and exponential smoothing), autoregressive integrated moving average (ARIMA) and support vector machine (SVM). The data obtained from 2005 to 2011 and in 2012 were used as modeling and forecasting samples, respectively. The performances were evaluated based on three metrics: mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE). The accuracy of the statistical models in forecasting future epidemic disease proved their effectiveness in epidemiological surveillance. Although the comparisons found that no single method is completely superior to the others, the present study indeed highlighted that the SVMs outperforms the ARIMA model and decomposition methods in most cases.	\N	\N
24507376	Human infections with different avian influenza viruses--eg, H5N1, H9N2, and H7N9--have raised concerns about pandemic potential worldwide. We report the first human infection with a novel reassortant avian influenza A H10N8 virus. We obtained and analysed clinical, epidemiological, and virological data from a patient from Nanchang City, China. Tracheal aspirate specimens were tested for influenza virus and other possible pathogens by RT-PCR, viral culture, and sequence analyses. A maximum likelihood phylogenetic tree was constructed. A woman aged 73 years presented with fever and was admitted to hospital on Nov 30, 2013. She developed multiple organ failure and died 9 days after illness onset. A novel reassortant avian influenza A H10N8 virus was isolated from the tracheal aspirate specimen obtained from the patient 7 days after onset of illness. Sequence analyses revealed that all the genes of the virus were of avian origin, with six internal genes from avian influenza A H9N2 viruses. The aminoacid motif GlnSerGly at residues 226-228 of the haemagglutinin protein indicated avian-like receptor binding preference. A mixture of glutamic acid and lysine at residue 627 in PB2 protein--which is associated with mammalian adaptation--was detected in the original tracheal aspirate samples. The virus was sensitive to neuraminidase inhibitors. Sputum and blood cultures and deep sequencing analysis indicated no co-infection with bacteria or fungi. Epidemiological investigation established that the patient had visited a live poultry market 4 days before illness onset. The novel reassortant H10N8 virus obtained is distinct from previously reported H10N8 viruses. The virus caused human infection and could have been associated with the death of a patient. Emergency Research Project on human infection with avian influenza H7N9 virus, the National Basic Research Program of China, and the National Mega-projects for Infectious Diseases.	\N	\N
24508287	Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue receptor and is closely associated with chronic heart failure (CHF). We undertook this study to investigate the relevance of ghrelin in CHF prognosis. A total of 145 in-patients with CHF in NYHA class II, III or IV despite optimized therapy were prospectively included in the study, grouped according to NYHA class and compared with 55 healthy control subjects. Ghrelin and N-terminal pro-B-type natriuretic peptide (Nt pro-BNP) were measured in plasma by ELISA. Echocardiographic information was also measured, including left atrial dimension, left ventricular end-diastolic diameter, LV volume and left ventricular ejection fraction (LVEF). Patients were followed for 2 years or until major adverse cardiac events. Plasma ghrelin levels were significantly lower in patients with CHF than in control subjects (p = 0.014). In addition, plasma ghrelin levels differed significantly with the severity of CHF. Notably, survival analysis showed that high ghrelin levels were an indicator of a favorable prognosis for CHF. Our results also showed that ghrelin correlated inversely with plasma Nt pro-BNP levels (r = -0.562, p <0.001) and positively with LVEF (r = 0.620, p <0.001) in patients with CHF. Furthermore, multivariate analysis showed that ghrelin levels were independently associated with adverse cardiac events (hazard ratio: 0.72; 95% CI: 0.64-0.81, p = 0.03). Ghrelin is a new biomarker of CHF severity as well as a new prognostic predictor for patients with CHF. Future experimental and clinical studies are warranted to evaluate ghrelin as a novel prognostic tool and for its therapeutic potential in patients with CHF.	\N	\N
24512284	To perform psychometric testing an owner self-administered questionnaire, the Canine Orthopedic Index (COI), designed to assess outcome in dogs with orthopedic disease. Original study. Owners (n = 20) of dogs with osteoarthritis (OA) for item (question) pretesting, and 80 owners of dogs with OA for reliability and validity testing. Standard methodology for the stepwise development and testing of instruments designed to assess subjective states was followed. Items generated in previous studies were pretested for readability, ambiguity, and inter-item correlations; poorly performing items were removed; and the reduced set of items subjected to factor analysis, reliability, and validity testing. Four factors were identified and named on the basis of the items contained in them: "Stiffness," "Gait," "Function," and "Quality of Life." Cronbach's α ranged from 0.76 to 0.86, suggesting the items in each factor could be assessed as a group to compute factor scores (i.e., stiffness, gait, function, and quality of life scores). The test-retest analysis revealed κ values from 0.68 to 0.80. Overall, the scores amongst the 4 factors correlated moderately well (r = 0.52-0.58), with a mild correlation (r = 0.35) between gait and function scores. The COI is a psychometrically sound owner completed instrument that can assess 4 domains in dogs with OA: Stiffness, Gait, Function, and Quality of Life.	\N	\N
24513795	Blood sample and placenta were taken from a 37-week pregnant woman; serologic results indicated acute toxoplasmosis. Placenta was inoculated into mice. Seropositive mice were sacrificed and tissue cysts from brain were inoculated into new mice. Specific DNA was detected by PCR, and the isolate was characterized as Type II by nPCR-RFLP for nSAG2, SAG3, BTUB, GRA6, c29-2, c22-8, L358, PK1 and Apico markers. This is the first isolation and molecular characterization of Toxoplasma gondii from humans in Argentina.	\N	\N
24517642	Salvage liver transplantation (SLT) is an attractive sequential strategy which combines liver resection (LR) for hepatocellular carcinoma (HCC), followed by liver transplant (LT) in the event of HCC recurrence or progressive liver deterioration. To compare the long-term results of SLT with primary liver transplant (PLT). Between 2000 and 2011, 125 patients (72 transplantable) underwent LR and 226 underwent LT in our unit. The outcome of SLT was analysed in a two-step fashion: firstly, SLT (n = 28) was compared with PLT (n = 198), secondly an intention-to-treat analysis was performed on all transplantable HCC patients who underwent LR (LRT group = 72) compared to PLT (n = 198). The five-year overall survival (OS) was 65.4% vs. 49.2% (P = 0.63), and disease-free survival (DFS) was 89.7% vs. 80.6% (P = 0.31) for PLT and SLT respectively. Predictive factors for DFS after LT included HCC total diameter [hazard ratio (HR) 1.29 P = 0.003], alpha-foetoprotein (HR 1.002 P < 0.001) and number of HCC nodules (HR 1.317 P = 0.035), whereas viral hepatitis C positivity (HR 1.911 P = 0.03) and outside Up-to-seven criteria (HR 2.652 P < 0.001) were negative independent prediction factors of OS. Intention-to-treat analysis showed that OS at 5 years was improved in PLT vs. LRT (LRT n = 72 including SLT plus LR group) and was 69.4% vs. 42.2% (P < 0.004), with an additional increase in DFS (89.2% vs. 54.5% respectively P < 0.001). Salvage liver transplantation is a safe treatment strategy, as it does not impair long-term survival. At intention-to-treat analysis, PLT showed improved survival compared with LRT.	\N	\N
24519340	Mental health is a human right and fundamental to good personal health. Developing, planning, and implementing mental health programs is a key part of health policies worldwide. This paper uses the perspective of "mental health mainstreaming" to define mental health and explore its relationship with mental illness and psychiatric disease. Further, we apply this perspective to Taiwan's three-tiered community mental illness prevention strategy as a reference for mental health promotion and rehabilitation programs in hopes that all healthcare providers help facilitate holistic community health.	\N	\N
24524071	Heat shock protein 72 (Hsp72) exhibits a protective role during times of increased risk of pathogenic challenge and/or tissue damage. The aim of the study was to ascertain Hsp72 protective effect differences between animal and human studies in sepsis using a hypothetical "comparative study" model. Forty-one in vivo (56.1%), in vitro (17.1%), or combined (26.8%) animal and 14 in vivo (2) or in vitro (12) human Hsp72 studies (P < 0.0001) were enrolled in the analysis. Of the 14 human studies, 50% showed a protective Hsp72 effect compared to 95.8% protection shown in septic animal studies (P < 0.0001). Only human studies reported Hsp72-associated mortality (21.4%) or infection (7.1%) or reported results (14.3%) to be nonprotective (P < 0.001). In animal models, any Hsp72 induction method tried increased intracellular Hsp72 (100%), compared to 57.1% of human studies (P < 0.02), reduced proinflammatory cytokines (28/29), and enhanced survival (18/18). Animal studies show a clear Hsp72 protective effect in sepsis. Human studies are inconclusive, showing either protection or a possible relation to mortality and infections. This might be due to the fact that using evermore purified target cell populations in animal models, a lot of clinical information regarding the net response that occurs in sepsis is missing.	\N	\N
24529770	When tried in court, mothers accused of neonaticide may claim that the umbilical cord just broke during birth and the newborn child bled to death accordingly. To evaluate the possibility of a breakage of the umbilical cord is the goal of this work. Therefore 25 umbilical cords from neonates of both sexes born at term were stretched using an electrically operated material testing machine and the energy necessary to break them was measured. This experimental set-up equals a static strain, not a dynamic one. The maximum force endured (F max) ranged from 37.24 N to 150.04 N. The average force endured was 79.87 N with a standard deviation of 27.39. The elongation at break varied from 13.24% to a maximum of 119.93%. We found no relationship between the force endured and any of the following parameters: birth weight, pH of the venous umbilical blood, diameter of cord, free length under testing, duration of pregnancy or the mother's age. We performed a literature research and tried to define the circumstances in which a break is more likely to occur, these being malformations, entanglement or disease, e.g. inflammation.	\N	\N
24550581	Levosimendan is a calcium sensitizer drug which has been used in cardiac surgery for the prevention of postoperative low cardiac output syndrome (LCOS) and in difficult weaning from cardiopulmonary bypass (CPB). This study aims to evaluate perioperative hemodynamic effects of levosimendan pretreatment in patients for off-pump coronary artery bypass graft (OPCABG) surgery with low left ventricular ejection fractions (LVEF < 30%). Fifty patients undergoing OPCABG surgery with low LVEF (<30%) were enrolled in the study. Patients were randomly divided in two groups: Levosimendan pretreatment (Group L) and placebo pretreatment (Group C) of 25 each. Group L, patients received levosimendan infusion 200 μg/kg over 24 h and in Group C Patients received placebo. The clinical parameters measured before and after the drug administration up to 48 h were heart rate (HR; for the hour after drug infusion), cardiac index (CI), and pulmonary capillary wedge pressure (PCWP). The requirement of inotropes, intraaortic balloon pump (IABP), CPB, intensive care unit (ICU) stay, and hospital stay were also measured. The patients in group L exhibited higher CI and PCWP during operative in early postoperative period as compared to control group C. Group L also had a less requirement for inotropes, CPB support and IABP with shorter ICU stay as well as hospital stay. Levosimendan pretreatment (24 h infusion) in patient for OPCABG with poor LVEF shows better outcomes and hemodynamics in terms of inotropes, CPB and IABP requirements. It also reduces ICU stay.	\N	\N
24554437	The ER is the largest cellular compartment and a major storage site for lipids and ions. In recent years, much attention has focused on contacts between the ER and other organelles, and one particularly intimate relationship is that between the ER and the endosomal system. ER-endosome contacts intensify when endosomes mature, and the ER participates in endosomal processes, such as the termination of surface receptor signaling, multi-vesicular body formation, and transport and fusion events. Cholesterol and Ca(2+) are transferred between the ER and endosomes, possibly acting as messengers for ER-endosome crosstalk. Here, we summarize different types of ER-endosomal communication and discuss membrane contact sites that might facilitate this crosstalk. We review the protein pairs that interact at the ER-endosome interface and find that many of these have a role in cholesterol exchange. We also summarize Ca(2+) exchange between the ER and endosomes, and hypothesize that ER-endosome contacts integrate several cellular functions to guide endosomal maturation. We post the hypothesis that failure in ER-endosome contacts is an unrecognized but important contributor to diseases, such as Niemann-Pick type C disease, Alzheimer's disease and amyotrophic lateral sclerosis.	\N	\N
24555602	This article will describe the elements of performing a thorough venous ultrasound evaluation of the lower extremity in patients with manifestations of chronic venous disorder. The emphasis will be on the evaluation of superficial venous reflux. Only the specific aspects of the evaluation of the deep system pertaining to chronic venous disease will be discussed. Duplex ultrasound requires the examiner to solve a puzzle to explain the patient's clinical manifestations. Patients who have been treated with surgery, thermal ablation, or ultrasound-guided sclerotherapy will require duplex ultrasound after treatment to identify complications, gauge the extent of treatment success, and evaluate the cause for any recurrence.	\N	\N
24557586	The survival of patients with axial skeletal or pelvic osteosarcoma (OS) remains poor, and the management of these patients is challenging. The object of this study is a cohort of unselected patients aged < 19 years with primary high-grade pelvic/axial OS. Patients were treated with high-dose methotrexate, doxorubicin, cisplatin, ifosfamide followed or preceded by local treatment (surgery and/or radiotherapy). Twenty patients aged 3-19 years were treated. Eight patients had pelvic OS, 8 axial OS and 4 mandible/maxilla OS. All patients received chemotherapy, after which necrosis was evaluable in 9 patients (≥ 90% in 3). Sixteen patients underwent surgery. Radiotherapy was administered to 8 patients (total dose 34-60 Gy). The median follow-up was 35 months (8-276), and the 5-year disease-free survival and overall survival rates were 37 and 40%, respectively. Six patients were alive at the time of this report: 2 with pelvic OS (both responded well to chemotherapy, one underwent hemipelvectomy and the other had non-radical surgery plus radiotherapy); 1 with axial and multicentric OS (with a good histological response and radical surgery); 3 with mandible/maxilla OS. Two patients died of secondary tumors (one bone and one breast cancer). It is worth noting that 4 patients had a p53 mutation: 1 is alive, 2 died of their OS, 1 of breast cancer. Adequacy of local treatment and pathological response influenced the prognosis for axial OS, which remained dismal. A high incidence of p53 mutation emerged in our series of patients.	\N	\N
24560191	In this issue of Immunity, Funabiki et al. (2014) have identified in mice a mutation of the IFIH1 gene, encoding the viral receptor MDA5 that causes constitutive IFN production and fatal autoimmune disease. The authors show that the autoimmune disease-associated variant of human MDA5 is permanently switched on.	\N	\N
24566636	In the current open society and with the growth of human rights, people are more and more concerned about the privacy of their information and other important data. This study makes use of electrocardiography (ECG) data in order to protect individual information. An ECG signal can not only be used to analyze disease, but also to provide crucial biometric information for identification and authentication. In this study, we propose a new idea of integrating electrocardiogram watermarking and compression approach, which has never been researched before. ECG watermarking can ensure the confidentiality and reliability of a user's data while reducing the amount of data. In the evaluation, we apply the embedding capacity, bit error rate (BER), signal-to-noise ratio (SNR), compression ratio (CR), and compressed-signal to noise ratio (CNR) methods to assess the proposed algorithm. After comprehensive evaluation the final results show that our algorithm is robust and feasible.	\N	\N
24568610	The generation of induced pluripotent stem cells (iPSCs) from somatic cells by expressing ectopic reprogramming transcriptional factors such as Oct3/4, Sox2, Klf4, c-Myc, and Nanog is one of the cutting-edge discoveries in stem cell and cancer research. This discovery has raised several safety issues regarding the use of iPSC technology for human disease research. Tumorigenesis is the major obstacle observed for iPSC-mediated transplantation therapy. Recently, a new method to generate human iPSCs either by a chemical method or by direct delivery of reprogramming factors has become a promising approach for future customized cell therapy of human disorders. These reprogramming transcriptional factors play critical roles in diverse cellular functions such as transactivation, cellular proliferation, differentiation, apoptosis, and tumorigenesis. Posttranslational modifications (PTMs) (phosphorylation, ubiquitination, acetylation, sumoylation, and so on) of these proteins act as a regulatory signal to control protein activity, expression, and stability in a wide variety of cellular processes. We attempt to summarize the accumulated evidence to address the role of PTMs of Oct3/4, Sox2, Klf4, c-Myc, and Nanog in regulating their biological functions. This review allows us to understand the importance of PTMs and their application in developing an efficient and safe reprogramming method without cancer development for cell therapy. Finally, we discuss the importance of PTMs of reprogramming factors in tumor pathogenesis.	\N	\N
24574413	Interferons (IFNs) are cytokines produced by host cells in response to the infection with pathogens. By binding to the corresponding receptors, IFNs trigger different pathways to block intracellular replication and growth of pathogens and to impede the infection of surrounding cells. Due to their key role in host defense against viral infections, as well as for clinical therapies, the IFN responses and regulation mechanisms are well studied. However, studies of type I IFNs have mainly focused on alpha interferon (IFN-α) and IFN-β subtypes. Knowledge of IFN-κ and IFN-ω is limited. Moreover, most studies are performed in humans or mouse models but not in the original host of zoonotic pathogens. Bats are important reservoirs and transmitters of zoonotic viruses such as lyssaviruses. A few studies have shown an antiviral activity of IFNs in fruit bats. However, the function of type I IFNs against lyssaviruses in bats has not been studied yet. Here, IFN-κ and IFN-ω genes from the European serotine bat, Eptesicus serotinus, were cloned and functionally characterized. E. serotinus IFN-κ and IFN-ω genes are intronless and well conserved between microchiropteran species. The promoter regions of both genes contain essential regulatory elements for transcription factors. In vitro studies indicated a strong activation of IFN signaling by recombinant IFN-ω, whereas IFN-κ displayed weaker activation. Noticeably, both IFNs inhibit to different extents the replication of different lyssaviruses in susceptible bat cell lines. The present study provides functional data on the innate host defense against lyssaviruses in endangered European bats. We describe here for the first time the molecular and functional characterization of two type I interferons (IFN-κ and -ω) from European serotine bat (Eptesicus serotinus). The importance of this study is mainly based on the fact that very limited information about the early innate immune response against bat lyssaviruses in their natural host serotine bats is yet available. Generally, whereas the antiviral activity of other type I interferons is well studied, the functional involvement of IFN-κ and -ω has not yet been investigated.	\N	\N
24579399	Patients with chronic kidney disease (CKD) who are treated with dialysis have impaired physical functioning that is associated with poor outcomes. Gait speed is an important measure of mobility that predicts adverse events and mortality in older people. Gait speed is low in patients with CKD, and those treated with hemodialysis average below cut-points known to indicate increased risk of reduced survival and adverse health events. Measurement of gait speed in patients with CKD may be valuable in identifying those at risk for adverse events, including disability and mortality.	\N	\N
24583421	Magnetic resonance imaging has been shown to be a powerful tool for diagnosing multiple sclerosis (MS) and evaluating surrogate markers of the disease activity. However, biomarkers may provide more accurate information regarding ongoing immune responses leading to demyelination and treatment effects in MS patients. Although serum biomarkers are easily accessible, they do not provide clear-cut results, whereas cerebrospinal fluid (CSF) biomarkers provide unequivocal information, although samples cannot be repeatedly obtained. For diagnosis, the presence of oligoclonal IgG bands remains important. In addition, measuring the levels of adhesion molecules, matrix metalloproteinase-9 and complement regulator factor H in the serum and evaluating the proportion of Th1/Th2 cells in the blood may be clinically feasible for monitoring the disease activity. In CSF samples, increased IL-8, IL-12, IL-17, CCL3, CCL5 and CXCL10 levels indicate active disease, and the flow cytometry findings of CSF cells can be used to detect increases in Th1 and CD4(+)CD25(+) cells during relapse. Biomarkers closely linked to the disease activity may be informative of the pathogenesis of MS, while those associated with tissue damage or repair may be targets of new treatment strategies. Establishing the latter will be a primary point of research in the near future.	\N	\N
24583589	A 76-year-old woman was admitted to our hospital because of convulsions that developed after a 1-month history of progressive right-leg palsy. MRI showed thickening of the meninges with gadolinium enhancement in the left parietal lobe and it revealed pia-subarachnoid space pattern. A lumbar puncture was performed, and cerebrospinal fluid analysis revealed no abnormality. Her serum adenosine deaminase level was elevated (28.7 IU/l). The results of serum cultures were normal. To differentially diagnose collagen disease, infection, malignancy, and inflammation of uncommon causes, we conducted brain and meningeal biopsies on the 15th hospital day. Histopathological examination of the brain tissue showed mainly necrosis and inflammation. There was severe pachymeningeal thickening without necrosis. Although it was difficult to reach a definitive diagnosis, a tissue sample taken from under the leptomeninges tested positive for mycobacterium on Ziehl-Neelsen staining. The results of polymerase chain reaction for mycobacterium were negative in the meningeal tissue. The patient received anti-tuberculous drugs, anti-nontuberculous mycobacteriosis drugs, and corticosteroids to treat Mycobacterium tuberculosis and nontuberculous mycobacterium. After starting treatment, the findings on magnetic resonance imaging improved dramatically, and no convulsions occurred during hospitalization. She was discharged on the 153rd hospital day without any neurological deficit. Because previous studies have reported that isolated mycobacterium meningitis is a diagnostically challenging condition, brain and meningeal biopsies should be considered in patients with gadolinium enhancement in the meninges.	\N	\N
24585436	The development of fully automated and high-throughput systems for proteomics is now in demand because of the need to generate new protein-based disease biomarkers. Unfortunately, it is difficult to identify protein biomarkers that are low abundant when in the presence of highly abundant proteins, especially in complex biological samples such as serum, cell lysates, and other biological fluids. Membrane proteins, which are in many cases of low abundance compared to the cytosolic proteins, have various functions and can provide insight into the state of a disease and serve as targets for new drugs making them attractive biomarker candidates. Traditionally, proteins are identified through the use of gel electrophoretic techniques, which are not always suitable for particular protein samples such as membrane proteins. Microfluidics offers the potential as a fully automated platform for the efficient and high-throughput analysis of complex samples, such as membrane proteins, and do so with performance metrics that exceed their bench-top counterparts. In recent years, there have been various improvements to microfluidics and their use for proteomic analysis as reported in the literature. Consequently, this review presents an overview of the traditional proteomic-processing pipelines for membrane proteins and insights into new technological developments with a focus on the applicability of microfluidics for the analysis of membrane proteins. Sample preparation techniques will be discussed in detail and novel interfacing strategies as it relates to MS will be highlighted. Lastly, some general conclusions and future perspectives are presented.	\N	\N
24588669	Tumour hypoxia is increasingly recognized as a major deleterious factor in cancer therapies, as it compromises treatment and drives malignant progression. This review seeks to clarify the oxygen levels that are pertinent to this issue. It is argued that normoxia (20% oxygen) is an extremely poor comparator for "physoxia", i.e. the much lower levels of oxygen universally found in normal tissues, which averages about 5% oxygen, and ranges from about 3% to 7.4%. Importantly, it should be recognized that the median oxygenation in untreated tumours is significantly much lower, falling between approximately 0.3% and 4.2% oxygen, with most tumours exhibiting median oxygen levels <2%. This is partially dependent on the tissue of origin, and it is notable that many prostate and pancreatic tumours are profoundly hypoxic. In addition, therapy can induce even further, often unrecognized, changes in tumour oxygenation that may vary longitudinally, increasing or decreasing during treatment in ways that are not always predictable. Studies that fail to take cognizance of the actual physiological levels of oxygen in tissues (approximately 5%) and tumours (approximately 1%) may fail to identify the real circumstances driving tumour response to treatment and/or malignant progression. This can be of particular importance in genetic studies in vitro when comparison to human tumours is required.	\N	\N
24590608	Iron is an essential mineral in many proteins and enzymes in human physiology, with limited means of iron elimination to maintain iron balance. Iron accrual incurs various pathological mechanisms linked to cardiovascular disease. In atherosclerosis, iron catalyzes the creation of reactive oxygen free radicals that contribute to lipid modification, which is essential to atheroma formation. Inflammation further fuels iron-related pathologic processes associated with plaque progression. Given iron's role in atherosclerosis development, in vivo detection techniques sensitive iron are needed for translational studies targeting iron for earlier diagnosis and treatment. Magnetic resonance imaging is uniquely able to quantify iron in human tissues noninvasively and without ionizing radiation, offering appealing for longitudinal and interventional studies. Particularly intriguing is iron's complementary biology vs. calcium, which is readily detectable by computed tomography. This review summarizes the role of iron in atherosclerosis with considerable implications for novel diagnostic and therapeutic approaches.	\N	\N
24603533	Telomere biology is frequently associated with disease evolution in human cancer and dysfunctional telomeres have been demonstrated to contribute to genetic instability. In BCR-ABL(+) chronic myeloid leukemia (CML), accelerated telomere shortening has been shown to correlate with leukemia progression, risk score and response to treatment. Here, we demonstrate that proliferation of murine CML-like bone marrow cells strongly depends on telomere maintenance. CML-like cells of telomerase knockout mice with critically short telomeres (CML-iG4) are growth retarded and proliferation is terminally stalled by a robust senescent cell cycle arrest. In sharp contrast, CML-like cells with pre-shortened, but not critically short telomere lengths (CML-G2) grew most rapidly and were found to express a specific 'telomere-associated secretory phenotype', comprising secretion of chemokines, interleukins and other growth factors, thereby potentiating oncogene-driven growth. Moreover, conditioned supernatant of CML-G2 cells markedly enhanced proliferation of CML-WT and pre-senescent CML-iG4 cells. Strikingly, a similar inflammatory mRNA expression pattern was found with disease progression from chronic phase to accelerated phase in CML patients. These findings demonstrate that telomere-induced senescence needs to be bypassed by leukemic cells in order to progress to blast crisis and provide a novel mechanism by which telomere shortening may contribute to disease evolution in CML.	\N	\N
24610167	The aim of this study was to evaluate the diagnostic accuracy of postnatal multidetector computed tomography (MDCT) compared with prenatal ultrasound (US), surgical findings, and histology, in 33 patients with congenital cystic lung disease. Thirty-three patients, 17 males and 16 females, were evaluated by MDCT. Twenty-seven of these patients underwent prenatal US between week 18 and 22, and between week 32 and 35 of gestation. Lung lobectomy, segmentectomy, atypical resection, lesion resection were performed in 31 patients and surgical specimens were analysed. Prenatal US and MDCT correctly diagnosed 76.9 and 94 % of the lesions, respectively. Disagreement occurred in six lesions with prenatal US and in two lesions with MDCT. No statistically significant differences were observed between the two techniques (P = 0.122). As most surgeons consider the surgical resection of these lesions mandatory, our study underscores the essential role of imaging, in particular CT, in providing invaluable preoperative information on congenital cystic lung diseases recognised in uterus.	\N	\N
24611185	To investigate factors associated with 30-day perioperative complications (POC) after aorto-iliac (AI) stenting, and to compare follow-up cardiovascular prognosis between patients with and without POC. This was a retrospective multicenter study. We used a multicenter database of 2012 consecutive patients who successfully underwent AI stenting for peripheral arterial disease in 18 centers in Japan from January 2005 to December 2009 to analyze independent predictors of POC and impact of POC on prognosis by logistic regression and a Cox proportional hazard regression model, respectively. Mean age was 71 ± 9 years (median: 72 years; range: 37-98 years), and 1,636 patients (81%) were men. POC occurred in 126 patients (6.3%). In multivariate logistic regression analysis, old age (≥80 years), critical limb ischemia (CLI), and Trans Atlantic Inter-Societal Consensus (TASC) II class C/D were independently associated with POC with adjusted odds ratios and 95% confidence intervals (CI) of 1.9 (1.3-2.9), 2.3 (1.5-3.4), and 2.4 (1.6-3.4), respectively. Out of 2012 patients, 1995 were followed up for more than 30 days (mean: 2.6 ± 1.5 years; range: 2-2,393 days). In a Cox hazard regression model adjusted for baseline clinical characteristics, POC was positively and independently associated with follow-up major adverse cardiac events (adjusted hazard ratio [HR]: 1.9; 95% CI: 1.3-2.8; p = .002), but not with major adverse limb events and target lesion revascularization (adjusted HR: 1.4; 95% CI: 0.7-2.7; p = .25; and adjusted HR: 1.2; 95% CI 0.6-2.6; p = .568), respectively. Age >80 years, CLI, and TASC C/D lesion were positively associated with POC after AI stenting. Occurrence of POC appears to adversely affect follow-up cardiovascular, but not limb and vessel prognosis.	\N	\N
24614649	The microsatellite instability (MSI) pathway is one of the important mutational pathways that play a critical role in colorectal carcinogenesis. About 15% of colorectal cancers (CRCs) are characterized by MSI. MSI tumors usually arise because of a genetic defect in mismatch repair (MMR) genes, one of the main DNA-repairing systems. MMR is a highly conserved biological pathway that plays a key role in maintaining genomic stability by correcting the base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Mutations in at least five pivotal genes of MMR, namely, in those encoding mutS homolog 2 (MSH2), mutL homolog 1 (MLH1), mutS homolog 6 (MSH6), postmeiotic segregation increased 1 (PMS1), and postmeiotic segregation, increased 2 (PMS2) have been found in CRC, highlighting the importance of understanding the basic structure and functions of the essential molecules that make up the MMR system. In this review, we have attempted to focus on this aspect, that is, the role that MMR molecules play in CRC carcinogenesis.	\N	\N
24617559	Exaggerated postprandial lipemia has been reported after spinal cord injury (SCI). We examined metabolite and accompanying pro-inflammatory biomarker responses to repeat feeding of typical high-fat meals in individuals with chronic paraplegia. Descriptive trial. Metabolites (triglycerides, glucose, and insulin) and inflammatory biomarkers (interleukin-6 and high-sensitivity C-reactive protein (hsCRP)) were measured under fasting conditions in 11 recreationally active individuals with chronic (>1 year) paraplegia. Subjects received high-fat meals at time point 0 and again at minute 240. Antecubital venous blood was obtained at time points -30 (fasting), 0 (first meal), 30, 60, 90, 120, 240 (second meal), 360, and 480 minutes. Correlations were examined among the study variables. Exploratory subgroup analysis was performed for subjects with levels of postprandial glucose greater than >200 mg/dl. Triglycerides showed a significant rise 4 hours after eating. Basal inflammatory markers were elevated, and did not undergo additional change during the testing. Additionally, subjects with excessive postprandial glucose responses showed higher hsCRP levels than those having typical glucose responses both for fasting (11.8 ± 6.5 vs. 2.9 ± 2.7 mg/l, P = 0.064) and postprandial (11.1 ± 4.9 vs. 3.7 ± 3.8 mg/l, P = 0.018) values. Despite elevations in metabolic response markers, inflammatory markers did not change significantly after consumption of population-representative (i.e. hypercaloric) mixed-nutrient meals. Levels of fasting CRP in the high-risk range are consistent with other reports in persons with SCI and continue to pose concern for their cardiovascular disease risk. The possible association between postprandial metabolic responses and inflammatory states warrants further investigation to identify individual component risks for this secondary health hazard.	\N	\N
24619118	The northward spread of leishmaniasis from Mediterranean to Continental Europe affects our area where it is typically associated with Leishmania infantum infection. In this study a 22-year survey was performed in patients (including both patients with and without history of travel through endemic areas other than Italy) attending the University Hospital of Parma, Northern Italy, in order to make a contribution to describe the cases of the visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) diagnosed in this area. One hundred fifty-six samples from 134 patients with clinical suspicion of leishmaniasis (96 suspected of having VL, 37 CL and one both VL and CL) were analyzed in our laboratory during 1992-2013 by microscopy, culture and, from 2005, also by real-time PCR. Leishmania spp. were detected in 23 samples of 15 patients (seven with VL and eight with CL), representing an infection rate of 11.2%. The figure of the cases of leishmaniasis herein reported, even if not comparable to that described for Italian areas other than Parma, underlines that suitable tools are mandatory for correct diagnosis. Moreover, the severity of this disease, particularly VL with its documented northward spread, requires physicians of continental Europe to increase their attention about the possibility of suspecting leishmaniasis in patients reporting related signs and symptoms and/or risk factors.	\N	\N
24626438	Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited. Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome. In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.	\N	\N
24628295	Imatinib (Glivec(®)/Gleevec(®)) has shown long-term efficacy and safety in randomized trials. No large-scale studies have prospectively assessed the benefit-risk profile of an imatinib copy drug. We prospectively evaluated the response of patients with chronic myeloid leukemia in chronic phase in one institution. Patients with a complete hematologic response (n = 126) switched from branded imatinib to an imatinib copy drug. Subsequently, all patients switched back to the branded imatinib. Many patients in this study had a loss of hematologic response and tolerability issues with the imatinib copy drug. Hematologic response and tolerability improved upon retreatment with branded Glivec.	\N	\N
24628740	Pentraxin 3 (PTX3) is probably a specific marker of vascular inflammation. However, associations of PTX3 with cardiovascular disease (CVD) risk have not been well studied in healthy adults or multi-ethnic populations. We examined associations of PTX3 with CVD risk factors, measures of subclinical CVD, coronary artery calcification (CAC) and CVD events in the Multi-Ethnic Study of Atherosclerosis. Two thousand eight hundred and thirty-eight participants free of prevalent CVD with measurements of PTX3 were included in the present study. After adjustment for age, sex, and ethnicity, PTX3 was positively associated with age, obesity, insulin, systolic blood pressure, C-reactive protein (CRP), and carotid intima-media thickness (all P < 0.045). A one standard deviation increase in PTX3 level (1.62 ng mL(-1) ) was associated with the presence of CAC in fully adjusted models including multiple CVD risk factors (relative risk of 1.05; 95% confidence interval [CI] 1.01-1.08). In fully adjusted models, a standard deviation higher level of PTX3 was associated with an increased risk of myocardial infarction (hazard ratio [HR] 1.51; 95% [CI] 1.16-1.97), combined CVD events (HR 1.23; 95% [CI] 1.05-1.45), and combined CHD events (HR 1.33; 95% [CI] 1.10-1.60), but not stroke, CVD-related mortality, or all-cause death. In these apparently healthy adults, PTX3 was associated with CVD risk factors, subclinical CVD, CAC and incident coronary heart disease events independently of CRP and CVD risk factors. These results support the hypothesis that PTX3 reflects different aspects of inflammation than CRP, and may provide additional insights into the development and progression of atherosclerosis.	\N	\N
24631511	The aim of this study was to report the frequency, patient and lesion-related characteristics, and outcomes of subclinical, nonculprit plaque ruptures in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Plaque rupture and subsequent thrombosis is the most common cause of acute coronary syndrome (ACS). Secondary, subclinical, nonculprit plaque ruptures have been seen in both stable patients and patients with ACS; however, reports of the natural history of these secondary plaque ruptures are limited. After successful stenting in 697 patients with ACS, 3-vessel grayscale and intravascular ultrasound virtual histology (IVUS-VH) was performed in the proximal-mid segments of all 3 coronary arteries as part of a prospective multicenter study. Among 660 patients with complete IVUS data, 128 plaque ruptures were identified in 105 nonculprit lesions in 100 arteries from 93 patients (14.1%). Although the minimum lumen area (MLA) was similar, the plaque burden was significantly greater in nonculprit lesions with a plaque rupture compared with nonculprit lesions without a plaque rupture (66.0% [95% confidence interval: 64.5% to 67.4%] vs. 56.0% [95% confidence interval: 55.6% to 56.4%]; p < 0.0001). IVUS-VH analysis revealed that a nonculprit lesion with a plaque rupture was more often classified as a fibroatheroma than a nonculprit lesion without a plaque rupture (77.1% vs. 51.4%; p < 0.0001). Independent predictors of a plaque rupture were lesion length (per 10 mm; odds ratio: 1.30; p < 0.0001), plaque burden at the MLA site (per 10%; odds ratio: 2.56; p < 0.0001), vessel area at the MLA site (per 1 mm(2); odds ratio: 1.13; p < 0.0001), and VH-thin-cap fibroatheroma (odds ratio: 1.80; p = 0.016). During 3 years of follow-up, the incidence of overall major adverse cardiac events did not differ significantly between the patients with and patients without subclinical, nonculprit plaque ruptures. Secondary, nonculprit plaque ruptures were seen in 14% of patients with ACS and were associated with a fibroatheroma phenotype with a residual necrotic core but not with adverse outcomes if patients were treated with optimal medical therapy as part of a multicenter study. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree [PROSPECT]; NCT00180466).	\N	\N
24634197	The redox-active transition metal copper is an essential trace element for growth and development and serves as a structural or catalytic cofactor for many enzymes in a range of physiological processes. Mammalian copper homeostasis is tightly regulated, and an imbalance in copper metabolism is implicated in various pathological disorders. Radioactive copper isotopes, in particular (64) Cu (t1/2  = 12.7 h) and (67) Cu (t1/2  = 62.01 h), have made important contributions to the understanding of copper metabolism in health and disease. This review gives a brief account of how radiolabelled copper(II) salts and bioreductive copper complexes have been used to trace copper uptake, transport and efflux in vitro and in vivo. Recently, positron emission tomography (PET) has emerged as a noninvasive tool to image copper metabolism in living subjects and (64) Cu-PET is investigated for the study of copper-related neurological disorders, genetic diseases and cancer.	\N	\N
24642005	Every year about 2500 patients in Sweden undergo surgery due to heart valve disease. A mechanical heart valve prosthesis causes risk of thromboembolic stroke or thrombus formation in the valve while anticoagulant treatment increases the risk of bleeding. Treatment quality with warfarin is crucial for patients with mechanical valve prostheses. It has previously been shown that poorly controlled warfarin treatment increases mortality in this patient group. TTR (Time in Therapeutic Range) on warfarin has been shown to affect the risk of complications in atrial fibrillation, but has not been studied in patients with mechanical heart valves. Our aim is to evaluate the impact of TTR on the risk of complications in this patient group. A non-randomized, prospective study of 534 adults with mechanical heart valve prostheses from Malmö and Sundsvall registered in the Swedish National Quality Registry Auricula between 01.01.2008 and 31.12.2011. Quartiles regarding individual TTR levels were compared regarding risk of complications. The risk of complications was significantly higher at lower TTR levels for all complications (p=0.005), bleeding (p=0.01) and death (p=0.018) but not for thromboembolism. In multivariate analysis the risk was significantly increased at lower TTR levels for bleeding and all complications but not for death or thromboembolism. Patients with a lower warfarin treatment quality measured by TTR have a higher risk of complications such as severe bleeding or death. A TTR of 83% or higher at the individual level should be obtained for best outcome.	\N	\N
24653575	There are various models of health care, such as the epidemiological, psychosocial, sociological, economic, systemic of Neuman, cognitive medicine or ecological, ayurvedic, supraparadigmatic among others. All of them are seeking to combine one or more elements to integrate a model of health care. The article presents a systemic approach to health care with complementary medicines such as rehabilitative acupuncture, homeopathy and chiropractic through the application of a method of holistic care and integrated approach. There was a participatory action research in January 2012 to January 2013, with a comprehensive approach in 64 patients using the clinical method. We included the environmental aspects, biological, emotional, and behavioral to identify, recognize and integrate the form of manifestation of the disease. Later, it was ordered in a coherent way the etiologic factors, precipitating factors and identified the vulnerability of the patients as well as the structural alterations, classifying them in immediate, mediate and late. Referred to the three disciplines: rehabilitative acupuncture, homeopathy and chiropractic to be seen doing references and against-references between them, evaluating the current state of health and each meeting by noting the clinical and behavioral changes submitted and thus the area of attention to which would be forwarded to continue their treatment. 64 patients rotated by the 3 areas taking an average of 30 meetings with rehabilitative acupuncture, 12 with homeopathy and 10 with chiropractic. The changes were submitted clinical attitudinal, behavioral, clinical and organic. The model of care was multifaceted and interdisciplinary with a therapeutic approach of individualization and a holistic view to carry out a comprehensive diagnosis and provide quality health care to the population.	\N	\N
24654676	To identify the frequency of disc hyperfluorescence, and to use optical coherence tomography to look for vitreopapillary traction as a possible underlying cause. Eight patients with presumed Fuchs uveitis syndrome were included. A complete ocular examination, fundus fluorescein angiography, and spectral-domain optical coherence tomography for optic nerve head were performed. There were 4 males and 4 female patients, and the mean age at diagnosis was 41.7 years. The most common ocular symptom was floaters (5/9). The range of initial visual acuity was 6/5-6/12. The most frequent clinical sign was inflammatory cells in the anterior chamber (9/9). Fundus fluorescein angiography showed disc hyperfluorescence in all but 1 patient. Optical coherence tomography did not show evidence of vitreopapillary traction in all eyes but one eye. We think that the high frequency of disc hyperfluorescence on fundus fluorescein angiography is an indication of an inflammatory process rather than a mechanical one.	\N	\N
24655021	Gliomas are highly vascular and rich in VEGF, which promotes angiogenesis. Bevacizumab is a monoclonal antibody against VEGF, inhibiting angiogenesis by preventing receptor activation. Early Phase II clinical trials using bevacizumab in both newly diagnosed and recurrent high-grade gliomas (HGG) showed promising results, but these have not been confirmed in recent Phase III trials. This review is an update including recently reported Phase II and III study results. This is a review of clinical trials investigating bevacizumab in newly diagnosed and recurrent HGG with a focus on outcome results. A future perspective about the expected future role of bevacizumab is given. Bevacizumab efficacy, safety and tolerability, the combination of radiation and bevacizumab, as well as the use of bevacizumab to treat pseudoprogression are discussed. Further criteria of response evaluation needed to be adjusted in the age of antiangiogenic therapy are also discussed. Bevacizumab has been shown to be safe and tolerable in HGG. In the recurrent disease setting, bevacizumab might offer clinical benefits and is currently approved as a single agent for this indication. Although clinical trials demonstrate a prolonged progression-free survival (PFS) in bevacizumab-treated HGG, a benefit on overall survival has not been demonstrated. Research so far shows that bevacizumab appears to prolong PFS in newly diagnosed glioblastoma. Available data do not demonstrate a survival benefit in newly diagnosed patients. In the recurrent setting, there is no adequately powered randomized clinical trial to address whether there is a PFS or survival benefit with bevacizumab. Bevacizumab has also been introduced into other settings in neuro-oncology, including concurrent administration with re-irradiation for recurrent HGG.	\N	\N
24659875	Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide, and alterations of glucose metabolism have reached pandemic proportions in western countries. However, the frequent coexistence between these two conditions is more than simply coincidental, since HCV can induce insulin resistance through several mechanisms. Indeed, the virus interferes with insulin signaling both directly and indirectly, inducing the production of pro-inflammatory cytokines. Furthermore, the entire viral life cycle has strict interconnections with lipid metabolism, and HCV is responsible for a "viral" steatosis which is frequently superimposed to a "metabolic" one. Several evidences suggest that HCV-induced metabolic disorders contribute both to the evolution of liver fibrosis and, likely, to the progression of the other disorders which are typically associated with altered metabolism, in particular atherosclerosis. In the present review, we will examine in depth the links between HCV infection and insulin resistance, liver steatosis and diabetes, and analyze the impact of these interactions on the progression of liver fibrosis and atherosclerosis. Special attention will be focused on the highly debated topic of the relationship between HCV infection and cardiovascular disease. The available clinical literature on this item will be broadly reviewed and all the mechanisms possibly implied will be discussed.	\N	\N
24669569	Nasopharyngeal carcinoma (NPC) has the propensity to develop distant metastases at a high rate and with poor prognosis. The metastatic sites are usually multifocal and involve the bones, lungs, liver and distant lymph nodes. The management of metastatic disease is essenti- ally palliative and is based on radiochemotherapy. A 50-year old man with a huge hematoma in the liver derived from a diagnosed NPC was treated with intermittent drainage of the hepatic hematoma for abdominal decompression, and the cavity was packed with omentum. In addition, 2 suspected metastatic lesions were excised. Neoadjuvant radiochemotherapy followed by concurrent chemotherapy was administered. After surgical treatment of the huge hematoma, the suspect sites in the liver were diagnosed as metastatic carcinoma, similar to the primary tumor. Several months later, bone metastatic lesions in the vertebra and oss iliaca dextra were detected due to distant metastasis. Treatment of metastatic NPC is essentially palliative and survival is usually poor.	\N	\N
24670466	To evaluate the feasibility of monitoring clopidogrel resistance with flow cytometric analysis of platelet vasodilator stimulated phosphoprotein (VASP) phosphorylation. Twenty patients with coronary heart disease (CHD) and 17 healthy volunteers were examined for platelet aggregation rate and phosphorylation of VASP (calculated as platelet reactivity index, PRI) using traditional optical nephelometry and flow cytometry before and after concurrent therapy of clopidogrel and aspirin. No significant differences were found in PRI between CHD group and healthy control group [(89.45∓5.22)% vs (86.58∓4.35)%] before treatment. The PRI in CHD group was significantly lowered after treatment to (67.66∓19.77)% (P<0.05). Clopidogrel resistance was found in 6 (30%) cases in CHD group by flow cytometric analysis, which showed a higher sensitivity than optical nephelometry (10%). Flow cytometric analysis of VASP phosphorylation is a more reliable test to specifically evaluate clopidogrel resistance.	\N	\N
24670932	The second leading cause of cancer-related deaths (both genders combined) in the United States is colorectal cancer (CRC). This emphasizes the need to develop both effective therapies for CRC patients and pre-clinical models mimicking human disease that carry translational potential in drug-development. Notably, at present there are no in situ models of CRC metastasis to lung. In our azoxymethane-induced colon tumorigenesis study in A/J mice assessing grape seed extract (GSE) efficacy, during necropsy we also found multiple lung nodules suggestive of colon tumor metastasis to lung that were significantly inhibited in GSE fed group. Both histopathological and molecular studies were performed to characterize and establish the origin of these lesions in lung. Histologically these nodules were determined as adenocarcinoma of mucin origin. Molecular analyses by immunohistochemistry (IHC) and RT-PCR revealed strong protein and transcript levels of colon specific markers CDX2 and CK20 in these lung nodules compared to uninvolved control lung tissue. Vis-à-vis, these nodules also showed minimally expressed lung specific biomarkers, specifically surfactant D and TTF-1, in IHC analysis. Additionally, 0.25% GSE supplementation in diet (w/w) decreased the incidence of these lung nodules by 53% and their total number by 66%. Together, the characterization of this unique in situ mouse model of CRC metastasis to lung provides translational opportunities in developing effective therapies to clinically manage and treat CRC at the advanced stage. Moreover, GSE efficacy in inhibiting CRC metastasis to lung in this model further supports its translational potential in controlling CRC growth, progression and metastasis in patients.	\N	\N
24671083	Determining the composition and function of subgingival dental plaque is crucial to understanding human periodontal health and disease, but it is challenging because of the complexity of the interactions between human microbiomes and human body. Here, we examined the phylogenetic and functional gene differences between periodontal and healthy individuals using MiSeq sequencing of 16S rRNA gene amplicons and a specific functional gene array (a combination of GeoChip 4.0 for biogeochemical processes and HuMiChip 1.0 for human microbiomes). Our analyses indicated that the phylogenetic and functional gene structure of the oral microbiomes were distinctly different between periodontal and healthy groups. Also, 16S rRNA gene sequencing analysis indicated that 39 genera were significantly different between healthy and periodontitis groups, and Fusobacterium, Porphyromonas, Treponema, Filifactor, Eubacterium, Tannerella, Hallella, Parvimonas, Peptostreptococcus and Catonella showed higher relative abundances in the periodontitis group. In addition, functional gene array data showed that a lower gene number but higher signal intensity of major genes existed in periodontitis, and a variety of genes involved in virulence factors, amino acid metabolism and glycosaminoglycan and pyrimidine degradation were enriched in periodontitis, suggesting their potential importance in periodontal pathogenesis. However, the genes involved in amino acid synthesis and pyrimidine synthesis exhibited a significantly lower relative abundance compared with healthy group. Overall, this study provides new insights into our understanding of phylogenetic and functional gene structure of subgingival microbial communities of periodontal patients and their importance in pathogenesis of periodontitis.	\N	\N
24674299	Erdheim-Chester disease is a rare systemic disease. The diagnosis is difficult due to significant clinical and morphological polymorphism. Orbital involvement is rare, but constitutes a classic means of detection. We report the case of a 60-year-old man, who consulted for evaluation of bilateral retro-orbital tumors. These tumors had been discovered on head CT two years previously during work-up of proptosis. Two biopsies were performed. The first one revealed polymorphous inflammatory tissue. The second one revealed intense granulomatous reaction, rich in non-specific foamy histiocytes. Thoracic-abdominal-pelvic CT scan detected peri-aortic and retroperitoneal infiltration. The association of these signs pointed to a diagnosis of Erdheim-Chester disease, confirmed by the re-examination of the histological samples. Erdheim-Chester disease is a rare non-Langerhans histiocytosis with a specific tropism for perivascular and fatty connective tissue. The cause is not known. The diagnosis of this systemic disease is histological. In the case of bilateral intra-orbital tumors, the diagnosis of Erdheim-Chester disease must be considered.	\N	\N
24674770	Excessive daytime sleepiness (EDS) is common in Parkinson's Disease (PD). Actigraphy uses periods of immobility as surrogate markers of nighttime sleep but there are no examples of its use in assessing EDS of PD. A commercial wrist worn system for measuring bradykinesia and dyskinesia also detects 2 min periods of immobility, which have a 85.2% concordance with the detection of sleep by ambulatory daytime polysomnography, (p < 0.0001 Chi Squared). High Epworth Sleepiness Scores (ESS) were associated with a proportion of time immobile (PTI) (p = 0.01 Mann-Whitney U). The median PTI between 0900 and 1800 h w in 30 age matched control subjects was 2%, representing 10 min and PTI at or above the 75th percentile (5% or 27 min) was taken as a high level. PD patients had higher PTI (median 4.8%) than controls (p < 0.0001, Mann-Whitney U). PD subjects with a high PTI had more bradykinesia, less dyskinesia and higher PDQ39 scores than those with low PTI. There was no relationship between PTI and dose or type of PD medications. However, in 53% of subjects, PTI increased in the 30-60 min after levodopa confirming that in some subjects levodopa results in increased sleepiness. In summary, immobility is a surrogate marker of daytime sleep in PD, confirmed by correlation with PSG and ESS. PD subjects measured this way are more likely to be sleepy and sleepy PD subjects are more likely to be bradykinetic and have a higher PDQ39. Levodopa leads to an increase in sleepiness in more than half of subjects post dosing.	\N	\N
24677192	Donor factors influence hepatitis C virus (HCV) disease severity in liver transplant (LT) recipients. Living donors, because they are typically young and have short cold ischemic times, may be advantageous for HCV-infected patients. Among HCV-infected patients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) surviving >90 days and followed for a median 4.7 years, advanced fibrosis (Ishak stage ≥3) and graft loss were determined. The 5-year cumulative risk of advanced fibrosis was 44% and 37% in living donor LT (LDLT) and deceased donor LT (DDLT) patients (P = 0.16), respectively. Aspartate aminotransferase (AST) activity at LT (hazard ratio [HR] = 1.38 for doubling of AST, P = 0.005) and biliary strictures (HR = 2.68, P = 0.0001) were associated with advanced fibrosis, but LDLT was not (HR = 1.11, 95% confidence interval [CI] 0.73-1.69, P = 0.63). The 5-year unadjusted patient and graft survival probabilities were 79% and 78% in LDLT, and 77% and 75% in DDLT (P = 0.43 and 0.32), with 27% and 20% of LDLT and DDLT graft losses due to HCV (P = 0.45). Biliary strictures (HR = 2.25, P = 0.0006), creatinine at LT (HR = 1.74 for doubling of creatinine, P = 0.0004), and AST at LT (HR = 1.36 for doubling of AST, P = 0.004) were associated with graft loss, but LDLT was not (HR = 0.76, 95% CI: 0.49-1.18, P = 0.23). Donor type does not affect the probability of advanced fibrosis or patient and graft survival in HCV-infected recipients. Thus, while LDLT offers the advantage of shorter wait times, there is no apparent benefit for HCV disease progression. Biliary strictures have a negative effect on HCV fibrosis severity and graft survival, and a high AST at LT may be an important predictor of fibrosis risk post-LT.	\N	\N
24684672	Rheumatoid arthritis (RA) is an autoimmune disease of unknown cause and a chronic and progressive inflammatory disorder ensuing in genetically predisposed subjects, characterized by synovitis causing joint destruction, as well as inflammation in body organ systems, leading to anatomical alteration and functional disability. Immune competent cells, deregulated synoviocytes and cytokines play a key role in the pathophysiological mechanisms. The immune system function shows time-related variations related to the influence of the neuroendocrine system and driven by the circadian clock circuitry. Immune processes and symptom intensity in RA are characterized by oscillations during the day following a pattern of circadian rhythmicity. A cross-talk between inflammatory and circadian pathways is involved in RA pathogenesis and underlies the mutual actions of disruption of the circadian clock circuitry on immune system function as well as of inflammation on the function of the biological clock. Modulation of molecular processes and humoral factors mediating in RA the interplay between the biological clock and the immune response and underlying the rhythmic fluctuations of pathogenic processes and symptomatology could represent a promising therapeutic strategy in the future.	\N	\N
24685603	The effects of thymidylate synthase (TS) polymorphisms on susceptibility to colorectal cancer (CRC) have been investigated in many studies, but the results remain conflicting rather than conclusive. To resolve these conflicts, we performed a quantitative synthesis of the evidence on the association between these two polymorphisms and CRC risk. All eligible case-control studies published up to September 2013 were identified by searching PubMed, Web of Science and CNKI. Effect sizes of odds ratio (OR) and 95% confidence interval (95% CI) were calculated by using a fixed- or random-effect model. A total of 11 case-control studies were included, including 10 studies (3324 cases and 4622 controls) for TSER polymorphism and 9 studies (3223 cases and 3886 controls) for TS1494del6 polymorphism. Overall, no significant association between the TS polymorphisms and CRC risk was found. In the subgroup analysis by ethnicity, a significantly association were found among Caucasian populations for TSER polymorphism; but for TS1494del6 polymorphism, no significantly association was observed in both Asian and Caucasian populations. When stratifying by source of controls, we found there was a statistically significant association between TSER polymorphism and risk of CRC in the population-based population; however, we detected no association in both population-based and hospital-based populations for TS1494del6 polymorphism. This meta-analysis suggests that the TSER polymorphism in TS gene but not TS1494del6 polymorphism might be a protective factor for CRC among Caucasian populations.	\N	\N
24713244	To study the expression and clinicopathologic significance of cancer stem cell markers CD44v6 and CD24 in ovarian serous carcinoma tissues. One hundred and two cases of ovarian carcinoma diagnosed during the period from June, 2001 to December, 2010 were retrieved from archival files. The histology slides were reviewed and a two-tier system for grading of ovarian serous carcinoma was applied. The expression of CD44v6 and CD24 was detected by immunohistochemistry using EnVision method. The relationship between CD44v6/CD24 expression and various clinicopathologic parameters was analyzed. There were 46.1% (47/102) and 59.8% (61/102) cases expressing CD44v6 and CD24, respectively. Both CD44v6 and CD24 expression showed positive correlation with higher histopathologic grade (P = 0.003 and P < 0.05, respectively). CD24 expression also correlated with the presence of lymph node metastasis (P < 0.05). There was no statistically significant relationship between the expression of these two markers (χ(2) = 0.394, P = 0.530). The age of the patients, histopathologic grade, clinical stage and nodal status correlated with progression-free survival time (P < 0.05). CD44v6 expression and histopathologic grade correlated with the overall survival time (P < 0.05). Patient age was an independent poor prognostic factor by multivariate analysis. CD44v6 expression, age older than 50 years, high clinical stage and presence of lymph node metastasis are associated with poor prognosis in patients with ovarian serous carcinoma. The two-tier system for grading of ovarian serous carcinoma is useful in predicting survival; and high tumor grade represents an important poor prognostic indicator for ovarian serous carcinoma.	\N	\N
24713591	High-density-lipoprotein cholesterol (HDL-C) has been identified in population studies as an independent inverse predictor of cardiovascular events. Although the causal nature of this association has been questioned, HDL and its major protein, apolipoprotein (apo)A1, have been shown to prevent and reverse atherosclerosis in animal models. In addition, HDL and apoA1 have several putatively atheroprotective functions, such as the ability to promote efflux of cholesterol from macrophages in the artery wall, inhibit vascular inflammation, and enhance endothelial function. Therefore, HDL-C and apoA1 have been investigated as therapeutic targets for coronary heart disease. However, recent clinical trials with drugs that raise HDL-C, such as niacin and inhibitors of cholesteryl ester transfer protein, have been disappointing. Here, we review the current state of the science regarding HDL as a therapeutic target.	\N	\N
24715127	The objective of this study was to evaluate the 25-year outcome of patients with primary Sjögren's syndrome (pSS). One hundred and fifty-two patients diagnosed with pSS (American-European classification criteria) were retrospectively and descriptively analysed (1986-2011). Of all 152 patients, 55.9% were alive, 18.4% had died and 25.7% discontinued follow-up (mostly due to old age). Malignancy affected 28.3% and non-Hodgkin's lymphoma (NHL) affected 10.5%. The adjusted risk for development of NHL was an odds ratio (OR) of 10.5 (95% confidence interval [CI]: 3.05-36.42) in patients with vasculitis (p<0.001), and OR 3.4 (95% CI 1.05-11.2) in the presence of glandular complications (parotid swelling, lymphadenopathy) (p < 0.041). Seventy-five patients (49.3%) developed other autoimmune diseases (autoimmune thyroid disease [15.8%], pulmonary fibrosis [7.2%] and vasculitis [10.5%]). Although the course of pSS is relatively benign, over 25 years patients experience more clinical complications than previously described. In addition, vasculitis and glandular manifestations were significant predictors for NHL.	\N	\N
24720286	There is currently no cure for metastatic castration-resistant prostate cancer (CRPC). Chemoresistance and metastatic disease remain the main causes of treatment failure and mortality in CaP patients. Although several advances have been made in the control of CRPC with some newly developed drugs, there is still an urgent need to investigate the mechanisms and pathways of prostate cancer (CaP) metastasis and chemoresistance, identify useful therapeutic targets, develop novel treatment approaches, improve current therapeutic modalities and increase patients' survival. Cancer stem cells (CSCs), a minority population of cancer cells characterised by self-renewal and tumor initiation, have gained intense attention as they not only play a crucial role in cancer recurrence but also contribute substantially to chemoresistance. As such, a number of mechanisms in chemoresistance have been identified to be associated with CSCs. Therefore, a thorough and integral understanding of these mechanisms can identify novel biomarkers and develop innovative therapeutic strategies for CaP treatment. Our recent data have demonstrated CSCs are associated with CaP chemosensitivity. In this review, we discuss the roles of putative CSC markers in CaP chemoresistance and elucidate several CSC-associated signaling pathways such as PI3K/Akt/mTOR, Wnt/β-catenin and Notch pathways in the regulation of CaP chemoresistance. Moreover, we will summarize emerging and innovative approaches for the treatment of CRPC and address the challenging CRPC that is driven by CSCs. Understanding the link between CSCs and metastatic CRPC will facilitate the development of novel therapeutic approaches to overcome chemoresistance and improve the clinical outcomes of CaP patients.	\N	\N
24723322	The mitochondrial toxin 3-nitropropionic acid (3-NP) is an irreversible inhibitor of respiratory chain complex II. Chronic systemic administration of 3-NP to mice, rats, and non-human primates leads to preferential degeneration of the striatum, and produces motor and cognitive symptoms that are highly reminiscent of Huntington's disease (HD). HD is caused by a dominant inherited expansion of CAG repeats in the Huntington gene. Thus, many aspects of HD cannot be mimicked by 3-NP. However, recent research shows that mitochondrial defects and oxidative stress may play a key role in HD pathogenesis, further supporting the potential utility of the 3-NP model of striatal degeneration. First, a basic protocol to produce acute striatal lesions in rats using repeated intraperitoneal injection of 3-NP is described. Second, a more complex protocol that takes advantage of the use of osmotic minipumps to steadily release 3-NP leading to consistent lesions and motor symptoms in Lewis rats is presented. Curr. Protoc. Neurosci. 67:9.48.1-9.48.14. © 2014 by John Wiley & Sons, Inc.	\N	\N
24725410	Maintenance of a constant cell volume in response to extracellular or intracellular osmotic changes is critical for cellular homeostasis. Activation of a ubiquitous volume-regulated anion channel (VRAC) plays a key role in this process; however, its molecular identity in vertebrates remains unknown. Here, we used a cell-based fluorescence assay and performed a genome-wide RNAi screen to find components of VRAC. We identified SWELL1 (LRRC8A), a member of a four-transmembrane protein family with unknown function, as essential for hypotonicity-induced iodide influx. SWELL1 is localized to the plasma membrane, and its knockdown dramatically reduces endogenous VRAC currents and regulatory cell volume decrease in various cell types. Furthermore, point mutations in SWELL1 cause a significant change in VRAC anion selectivity, demonstrating that SWELL1 is an essential VRAC component. These findings enable further molecular characterization of the VRAC channel complex and genetic studies for understanding the function of VRAC in normal physiology and disease.	\N	\N
24726273	Central obesity represents the major factor responsible for NAFLD, but several immunological and endocrinological mechanisms are involved in fatty infiltration in the liver, inflammation and fibrosis. Gut microbiota and genetic factors were recently indicated as major players in liver injury. Loss of weight and physical activity represent till now the cornerstone of treatment, but they are very difficult to obtain and to maintain. Several pharamocotherapeutic approaches including insulin sensitizers, omega-3 fatty acids and vitamin E have been extensively studied in randomized trials, but final conclusions still could not be formulated. Therefore, new treatments based on pathogenetic mechanisms leading to NAFLD are under evaluation to establish the effective pharmacological therapy of this disorder.	\N	\N
24734429	In 2013 the main efforts of the Medical Service were aimed at the following tasks: optimization of management system of military medical service, improvement of medical evacuation system, medical service security for military contingents, assigned according to territory principle to military-medical facilities of the Ministry of Defence of the Russian Federation, implementation of innovations at all stages of medical evacuation in peace- and wartime, security of combat and mobilization readiness of regulatory bodies of the Medical Service, medical military units and military medical facilities, medical service of troops battle training, improvement of material and technical resources, security of regular pharmacy and equipment supply, activation of research work in the Medical Service interests. Lines of military medicine development in 2014 are: transfer of treatment facilities that are not used by the Ministry of Defence into the Federal Biomedical Agency till the end of 2014, prevention of pneumonia and meningitis in military personnel, improvement of early diagnosis system, medical service for military contingents according to territory principle, improvement of diagnostic and treatment work in military-medical units and subunits and military-medical facilities by means of development of material and technical resources, monitor the implementation of innovative diagnostic and treatment technologies, completion of construction projects of central military hospitals and etc.	\N	\N
24744504	Consumption of tomato fruits, like those of many other plant species that are part of the human diet, is considered to be associated with several positive effects on health. Indeed, tomato fruits are an important source of bioactive compounds with known beneficial effects including vitamins, antioxidants, and anticancer substances. In particular, antioxidant metabolites are a group of vitamins, carotenoids, phenolic compounds, and phenolic acid that can provide effective protection by neutralizing free radicals, which are unstable molecules linked to the development of a number of degenerative diseases and conditions. In this review, we will summarize the recent progress on tomatoes nutritional importance and mechanisms of action of different phytochemicals against inflammation processes and prevention of chronic noncommunicable diseases (e.g., obesity, diabetes, coronary heart disease, and hypertension). In addition, we will summarize the significant progress recently made to improve the nutritional quality of tomato fruits through metabolic engineering and/or breeding.	\N	\N
24748016	Food allergy is a common condition that plays an important role in the pathogenicity and maintenance of atopic dermatitis (AD), however, must be carefully investigated before imposing a restrictive diet. The aim of this study was to evaluate the sensitivity to foods in patients with AD, correlating it with the severity of the disease and other possible associated factors. One hundred and eleven children (6-180 months of age) with AD were evaluated and later followed up at the Allergy and Clinical Immunology Division, Department of Pediatrics at FMABC. The serum concentrations of specific IgE to cow's milk (CM), egg, soy, wheat, corn, peanut and fish were measured using an enzymatic fluorescence method (ImmunoCAP™). In order to identify the clinical reactivity, the open oral provocation test was performed when specific IgE was positive to CM, egg and wheat and in all those who related symptoms after the intake of such foods regardless of the presence or absence of sensitization. In total, 40.5 % of the studied population was sensitized to at least one food allergen, especially those between 73 and 180 months of age. There was a higher prevalence of sensitization in children with more severe AD, and foods like CM, egg and wheat were the most involved, but with low clinical reactivity. We observed increased severity of AD in cases that initiated symptoms earlier and who had shorter duration of exclusive breastfeeding as well as a linear increase in sensitization in the most serious cases. Serum-specific immunoglobulin E was the only factor associated with the relationship that showed sensitization. The occurrence of sensitization to foods was frequent, mainly in the age group of 6-9 years and in patients with severe AD; however, the validation of the clinical reactivity was negative in most of the provocations performed, which agrees with the need to prove the same before the imposition of restrictive diets, often unnecessary and complex.	\N	\N
24748137	This report describes the case of a 44-year-old Caucasian woman of Northern European descent with a medical history of pyoderma gangrenosum, chronic abdominal pain and erythema nodosum which required intermittent use of high-dose steroids that failed to improve her symptoms. The patient was initially diagnosed with Crohn's disease and most recently with sclerosing mesenteritis. She presented to the hospital with worsening abdominal pain. She was found to have recurrent painful aphthous oral, genital and perianal ulcers and a clinical diagnosis of Behçet's disease was made. Her hospitalisation was complicated by haemoptysis, and bronchoscopy revealed alveolar haemorrhage. Treatment was initiated with three days of pulse intravenous solumedrol 1 g/day and cyclophosphamide at 700 mg/m(2). The case had a favourable outcome despite the initial diagnostic challenges. This report emphasises that systemic diseases, including Behçet's disease, can have variable presentations and can be frequently misdiagnosed.	\N	\N
24751894	Both the diagnosis and treatment of Mycoplasma pneumoniae infections in children are currently facing two main challenges: a relatively high carriage in asymptomatic children, and a worldwide increase in macrolide-resistant M. pneumoniae (MRMP). This review focuses on the scientific and clinical implications of these crucial issues. Recent studies have indicated that the prevalence of M. pneumoniae in the upper respiratory tract is similar among asymptomatic, healthy children and children with a symptomatic respiratory tract infection, and that current diagnostic procedures for M. pneumoniae are unable to differentiate between bacterial carriage and infection. It is therefore possible that the burden of M. pneumoniae-associated disease is overestimated. Another phenomenon that has an important impact on the treatment of M. pneumoniae infections is the rapid worldwide emergence of MRMP isolates. The current diagnostic procedures for M. pneumoniae cannot discern between bacterial carriage and infection in a clinically relevant time frame. It is therefore imperative that these procedures be modified such as to unambiguously detect symptomatic M. pneumoniae infections. Moreover, the emergence of MRMP necessitates the application of methods to detect macrolide resistance as well as the implementation of restrictive policies regarding the use of macrolides.	\N	\N
24763465	Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity. As the population ages and the prevalence of AF continues to rise, the socioeconomic consequences of AF will become increasingly burdensome. Although there are well-defined clinical risk factors for AF, a significant heritable component is also recognized. To identify the molecular basis for the heritability of AF, investigators have used a combination of classical Mendelian genetics, candidate gene screening, and genome-wide association studies. However, these avenues have, as yet, failed to define the majority of the heritability of AF. The goal of this review is to describe the results from both candidate gene and genome-wide studies, as well as to outline potential future avenues for creating a more complete understanding of AF genetics. Ultimately, a more comprehensive view of the genetic underpinnings for AF will lead to the identification of novel molecular pathways and improved risk prediction of this complex arrhythmia.	\N	\N
24782446	We aimed to evaluate whether a recent knee injury was associated with accelerated knee osteoarthritis (OA) progression. In the Osteoarthritis Initiative, we studied participants free of knee OA on their baseline radiographs (Kellgren/Lawrence [K/L] <2). We compared 3 groups as follows: 1) individuals with accelerated progression of knee OA: defined as having at least 1 knee that progressed to end-stage knee OA (K/L grade 3 or 4) within 48 months, 2) common knee OA progression: at least 1 knee increased in radiographic scoring within 48 months (excluding those defined as accelerated knee OA), and 3) no knee OA: no change in K/L grade in either knee. At baseline, participants were asked if their knees had ever been injured, and at each annual visit they were asked about injuries during the prior 12 months. We used multinomial logistic regressions to determine whether a new knee injury was associated with the outcome of accelerated knee OA or common knee OA progression, after adjusting for age, sex, body mass index, static knee malalignment, and systolic blood pressure. A knee injury during the total observation period was associated with accelerated knee OA progression (n = 54; odds ratio [OR] 3.14) but not common knee OA progression (n = 187; OR 1.08). Furthermore, a more recent knee injury (within a year of the outcome) was associated with accelerated (OR 8.46) and common knee OA progression (OR 3.12). Recent knee injuries are associated with accelerated knee OA. Most concerning is that certain injuries may be associated with a rapid cascade toward joint failure in less than 1 year.	\N	\N
24783461	Patients with established rheumatoid arthritis (RA) have a higher cardiovascular morbidity and mortality in comparison with the general population. It is considered to be an independent risk factor for cardiovascular disease. The purpose of this article is to describe the mechanisms responsible for accelerated atherogenesis in RA patients and to give an overview of the effects of different RA therapies (methotrexate, TNF antagonists and other biologicals).	\N	\N
24800540	To analyze the clinical features and treatment of tuberculous otitis media and mastoiditis. Thirteen patients with tuberculous otitis media and mastoiditis were retrospectively analyzed and the related literatures were reviewed. One case was treated by surgery only, and anti-tuberculosis treatment was given to another one patient, and surgical removal of disease lesions in combination with anti-tuberculosis treatment were given to 12 patients. One patient received surgery only was found to recur after follow-up for seven months. The patient did not recur after seven months' follow-up after antituberculosis therapy,and other patients did not recur. Although the regular anti-tuberculosis chemotherapy treatment was the main treatment for tuberculous otitis and mastoiditis, surgical treatment was helpful to achieved more rapid healing of the ear.	\N	\N
24804836	Non-melanoma skin cancers (NMSCs) are among the most common human malignancies. Current methods for their prevention include avoidance of natural and artificial sources of UV radiation and using photoprotective clothing and sunscreens. However, these methods have proven to be inadequate in stemming the rise in skin cancer incidence over the past several years. There is accumulating evidence that cyclooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis, may be involved in the pathogenesis of NMSC. In preclinical studies, animals genetically deficient in the COX-2 enzyme or that have been treated with pharmacological inhibitors of COX-2 develop significantly fewer tumors when subjected to a UV-induced skin carcinogenesis protocol compared with control mice. Several epidemiological studies in humans support the concept that this enzyme is intimately involved in UV-induced skin cancer development, and UV radiation is known to augment COX-2 expression in human skin. Recent studies suggest that drugs that block COX-2 expression may prevent the development of NMSCs. Thus, pharmacologic agents that inhibit the enzyme COX-2 may be effective chemopreventive agents for NMSCs.	\N	\N
24806099	The use of liver retransplantation (ReLT) for hepatitis C virus (HCV) recurrence is controversial because of subsequent viral recurrence after ReLT. Case-control analysis between patients undergoing ReLT for HCV reinfection between 1993 and 2012 (ReLT group: 26 patients) and patients undergoing liver transplantation (LT) for HCV infection immediately before and after each ReLT (LT group: 52 patients). ReLT group had worse hepatocellular function, higher preoperative viral load, higher transfusion requirements, and increased number of postoperative complications than LT group. ReLT patients showed a trend toward worse graft survival compared with LT (five-yr graft survival: 42.3% vs. 64.3%, p = 0.145), but the rate of severe HCV recurrence and infection-free survival (IFS) was similar. The use of donors older than 60 yr led to a lower IFS and graft survival in both groups. Early severe HCV infection rate was similar in both groups, but it affected prognosis in ReLT more markedly than in LT (three-yr graft survival: 0% vs. 66.7%, p = 0.003). ReLT for HCV reinfection has acceptable results when strict selection policies of donor and recipient are applied. However, early severe recurrence more markedly impairs prognosis in ReLT patients than in LT.	\N	\N
24820120	Regardless of whether alone or in combination, cecal ligation and puncture (CLP) is the most commonly used model to emulate human polymicrobial sepsis. Numerous CLP studies have shown that female mice survive better than males. In adult mice, this effect may be partly due to the unequal cecum mass (larger in males), as cecum ligation is frequently not size standardized. Comparing two ligation approaches, we investigated whether cecum size influences gender-specific outcome differences. 15-month-old (middle-aged) female and male CD-1 mice underwent sublethal trauma/hemorrhage followed by CLP 48 h later. The evaluation of cecum size (in centimeters) and filling (score) was immediately followed by two ligation protocols: (1) ileocecal ligation (IC-L; n = 28/each gender) below the ileocecal valve, and (2) apex ligation (AP-L; n = 31 males, n = 24 females) 2 cm from the apex ceci - all followed by an identical double puncture and 10-day monitoring. Cecum length (3.4 cm in males vs. 2.65 cm in females) and filling (2.5 score points in males vs. 1.7 in females; both p < 0.05) were always greater in male than female mice (27 vs. 44%, respectively). Compared to AP-L, the 10-day CLP mortality was higher with IC-L (86% in males and 61% in females), and this exacerbation was similar in both genders (by 21% in male and 23% in female mice). Finally, the intergender comparison demonstrated that female mice displayed a significant and similar survival advantage regardless of the ligation approach: the difference reached 25% with IC-L and 24% with AP-L. Standardization by AP-L did not eliminate the gender-specific difference in mortality due to posttraumatic sepsis. The greater cecum length/filling in middle-aged male mice was not responsible for their inferior survival compared to females.	\N	\N
24821164	Nephronophthisis is an autosomal recessive disease that leads to end-stage renal disease. These days, molecular genetic analysis is used pre-emptively for making a definitive diagnosis in patients who have clinical and radiological data suggestive of the disease. Herein, we are reporting a 12-year-old girl who was genetically diagnosed to have juvenile nephronophthisis, which explained the mystery of the chronic kidney disease in her four affected siblings.	\N	\N
24821649	Hepatocellular carcinoma (HCC) is associated with a poor prognosis because of a lack of effective treatment options. The objective of this study was to examine a new strategy for HCC treatment, namely the use of poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor (ABT-888) together with Temozolomide (TMZ) incorporated onto magnetic nanoparticles. Magnetic Fe3 O4 /Fe cores were encapsulated within a silica shell to facilitate the simultaneous incorporation of ABT-888 and TMZ. In vitro tests were performed with HepG2, Hep3B and PLC-PRF-5 liver tumoural cell lines and with WRL-68 liver non-tumoural cells. The magnetic nanocarriers were loaded simultaneously with ABT-888 and TMZ. High stability and extended release were achieved in culture medium. Confocal microscopy images showed that drug-loaded particles were uptaken and accumulated into the cytoplasm of liver tumoural cells, inducing the following effects: G2/M cell cycle arrest (P < 0.05), accumulation of DNA damage (P < 0.05), mitochondrial depolarization (P < 0.01), reduction in BCL-xL, FOS, JUND gene expression (P < 0.05), PARP-1 fragmentation, Caspase-3 activation and apoptotic cell death (P < 0.05). Interestingly, drugs loaded onto nanoparticles exhibited better efficiency than free drugs (cell death triggered by drug delivery nanosystem: 53.5% vs. 34.5% by free drugs, P = 0.01). These magnetic nanocompounds are able to incorporate both drugs simultaneously, enter the tumour cells and release them. ABT-888/TMZ/NPs decrease the transcription of key genes involved in tumour survival and induce apoptotic cell death in a more effective manner than is achieved by free drugs.	\N	\N
24821915	Only a small fraction of individuals exposed to Mycobacterium tuberculosis develop clinical tuberculosis (TB). Over the past century, epidemiological studies have shown that human genetic factors contribute significantly to this interindividual variability, and molecular progress has been made over the past decade for at least two of the three key TB-related phenotypes: (i) a major locus controlling resistance to infection with M. tuberculosis has been identified, and (ii) proof of principle that severe TB of childhood can result from single-gene inborn errors of interferon-γ immunity has been provided; genetic association studies with pulmonary TB in adulthood have met with more limited success. Future genetic studies of these three phenotypes could consider subgroups of subjects defined on the basis of individual (e.g. age at TB onset) or environmental (e.g. pathogen strain) factors. Progress may also be facilitated by further methodological advances in human genetics. Identification of the human genetic variants controlling the various stages and forms of TB is critical for understanding TB pathogenesis. These findings should have major implications for TB control, in the definition of improved prevention strategies, the optimization of vaccines and clinical trials and the development of novel treatments aiming to restore deficient immune responses.	\N	\N
24843888	The adaptive function of melanin located in the integument is well known. Although pigments are also deposited in various internal organs, their function is unclear. A review of the literature revealed that 'internal melanin' protects against parasites, pollutants, low temperature, oxidative stress, hypoxemia and UV light, and is involved in the development and function of organs. Importantly, several studies have shown that the amount of melanin deposited on the external body surface is correlated with the amount located inside the body. This finding raises the possibility that internal melanin plays more important physiological roles in dark than light-colored individuals. Internal melanin and coloration may therefore not evolve independently. This further emphasizes the major role played by indirect selection in evolutionary processes.	\N	\N
24845215	Over 5100 colorectal cancers (CRCs) are diagnosed in the United Kingdom in 85 years and older age group per year but little is known of cancer progression in this group. We assessed clinical, pathological and molecular features of CRC with early and late mortality in such patients. Data were analysed in relation to early mortality and long-term survival in 90 consecutive patients with CRC aged 85 years or older in a single hospital. Patients not undergoing operation, those with an ASA score of III or greater and those with advanced tumour stage were more likely to die within 30 days. Regression analysis showed that 30 day mortality was independently related to failure to undergo resection (odds ratio (O.R.), 10.0; 95% confidence interval [C.I.], 1.7-58.2; p=0.01) and an ASA score of III or greater (O.R. 13.0; 95% C.I., 1.4-12.6; p=0.03). All cause three and five year survival were 47% and 23% respectively for patients who are alive 30 days after diagnosis. Three and five year relative survivals were 64% and 54%, respectively. Long-term outcome was independently related to tumour stage (relative risk [R.R.], 2; 95% C.I., 1.3-3.1; p=0.001), presence of co-morbid diseases (R.R., 2.8; 95% C.I., 1.3-6.0; p=0.007) and lipid peroxidation status (R.R., 2.9; 95% C.I., 1.1-7.5; p=0.025). An active multidisciplinary approach to the care of patients with CRC at the upper extreme of life is reasonable. It also seems sensible to individualise care based upon the extent of disease at diagnosis and the presence of co-morbid conditions. Further studies to examine the role of lipid peroxidation are warranted.	\N	\N
24850149	Inflammasomes are specialized signaling platforms critical for the regulation of innate immune and inflammatory responses. Various NLR family members (i.e., NLRP1, NLRP3, and IPAF) as well as the PYHIN family member AIM2 can form inflammasome complexes. These multi-protein complexes activate inflammatory caspases (i.e., caspase-1) which in turn catalyze the maturation of select pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. Activation of the NLRP3 inflammasome typically requires two initiating signals. Toll-like receptor (TLR) and NOD-like receptor (NLR) agonists activate the transcription of pro-inflammatory cytokine genes through an NF-κB-dependent priming signal. Following exposure to extracellular ATP, stimulation of the P2X purinoreceptor-7 (P2X7R), which results in K(+) efflux, is required as a second signal for NLRP3 inflammasome formation. Alternative models for NLRP3 activation involve lysosomal destabilization and phagocytic NADPH oxidase and/or mitochondria-dependent reactive oxygen species (ROS) production. In this review we examine regulatory mechanisms that activate the NLRP3 inflammasome pathway. Furthermore, we discuss the potential roles of NLRP3 in metabolic and cognitive diseases, including obesity, type 2 diabetes mellitus, Alzheimer's disease, and major depressive disorder. Novel therapeutics involving inflammasome activation may result in possible clinical applications in the near future.	\N	\N
24851665	Self-efficacy, a central construct in health interventions, has been measured in various contexts. The absence of any published meta-review of self-efficacy instrumentation led to the current meta-synthesis that reports and evaluates the instrumentation processes. A systematic search resulted in 39 self-efficacy instrumentation studies, which were evaluated for the aspects of conceptual bases, health contexts, operational definition, instrumentation procedures, reliability and scale length, and item content. Primarily based in Bandura's social cognitive theory, these studies reported self-efficacy instrumentation for developing new scales and modifying/validating measures for illness management, healthy behavior adoption/maintenance, disease/risk prevention, and aging management. Trait-like, specific-domain, and situation approaches were used for generating item content. Problems in some studies include non-efficacy items, a lack of systematic instrumentation procedures, item content too general for specific-domain self-efficacy, and measurement inefficiency. The piecemeal fashion of self-efficacy instrumentation has resulted in incomparable self-efficacy measures of similar domains of health functioning. A trans-domain framework, thus, is warranted. Suggestions are provided for solving other problems in self-efficacy instrumentation.	\N	\N
24852869	The ABC-02 trial has defined the standard therapy for patients with advanced biliary tract cancer (ABC); however, outcome in an unselected patient population in the UK has not been described. We aimed to investigate the outcome of a series of patients with ABC from two large UK cancer networks. We retrospectively reviewed all cases of ABC presenting to two UK cancer networks over a nine-year period. Overall survival (OS) and factors influencing OS were assessed. Four hundred and two patients were available for analysis. The median OS was 6.2 months. On univariate analysis, age ≥70 years (P = 0.047), advanced disease stage (P <0.001), gall bladder primary (P = 0.033), poor performance status (P <0.001) and lack of chemotherapy (P <0.001) were associated with worse outcome. Survival was superior in the 36.4% of patients who received palliative chemotherapy (12.5 vs 4.3 months; P <0.001). On multivariate analysis of patients who had chemotherapy, those who did not receive fluoropyrimidine-based regimens (HR = 5.12; P = 0.022) or gemcitabine-based regimens (HR = 5.01; P = 0.021) had a higher mortality, whereas the effect of platinum-containing regimens was of borderline significance (HR = 2.23; P = 0.086). Sites, age, and multi-agent regimens were not significant. This is one of the largest retrospective studies reporting outcome of palliative chemotherapy for ABC. It confirms the benefit of palliative chemotherapy in an unselected group of patients. Fluoropyrimidine-based regimens appear to be as effective as gemcitabine-based treatments.	\N	\N
24853219	Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of many cancers, and the cutaneous toxicity profile associated with these agents has become prominent. In fact, dermatologic side effects have also been reported with other targeted agents, including both BRAF and mTOR inhibitors. During her presentation at the NCCN 19th Annual Conference, Dr. Barbara Burtness reviewed the array of skin complications caused by many targeted therapies, focusing on the more common culprits, the role of prophylactic versus reactive management strategies, the need to be attentive to potential infections, the importance of mastering local measures to improve quality of life and cosmetic issues, the therapeutic mainstays (oral and topical antibiotics and topical steroids), and the preference of improving these cutaneous complications over suspending anticancer treatment.	\N	\N
24861877	Vitamin D deficiency has been associated with hypertension, diabetes mellitus, and incident stroke. Little is known about the association between vitamin D and subclinical cerebrovascular disease. To examine the relationship of 25-hydroxyvitamin D (25[OH]D) levels with cerebrovascular abnormalities as assessed on brain magnetic resonance imaging (MRI) among participants of the Atherosclerosis Risk in Communities (ARIC) Brain MRI study. Participants were white and black adults aged 55 to 72 years with no history of clinical stroke who underwent a cerebral MRI at ARIC visit 3 (n = 1622) and a second cerebral MRI approximately 10 years later (n = 888). The 25(OH)D level was measured by mass spectrometry at visit 3, with levels adjusted for calendar month and categorized using race-specific quartiles. The cross-sectional and prospective associations of 25(OH)D levels with white matter hyperintensities (WMHs) and MRI-defined infarcts were investigated using multivariable regression models. The mean age of the participants was 62 years, 59.6% were women, and 48.6% were black. Lower 25(OH)D levels were not significantly associated with WMH score of severity, prevalent high-grade WMH score (≥3), or prevalent infarcts in cross-sectional, multivariable-adjusted models (all P > .05). Similarly, no significant prospective associations were found for lower 25(OH)D levels with change in WMH volume, incident high WMH score (≥3), or incident infarcts on the follow-up MRI, which occurred approximately 10 years later. A single measure of 25(OH)D was not cross-sectionally associated with WMH grade or prevalent subclinical infarcts and was not prospectively associated with WMH progression or subclinical brain infarcts seen on serial cerebral MRIs obtained approximately 10 years apart. These findings do not support optimizing vitamin D levels for brain health.	\N	\N
24871260	A major symptom of hand-arm vibration syndrome is a secondary Raynaud's phenomenon-vibration white finger (VWF)-which results from a vasospasm of the digital arteries caused by work with vibration devices leading to occupational disease. Pharmacotherapy of VWF is often ineffective or has adverse effects. The aim of this work was to verify the influence of inhalation of partially ionized oxygen (O2•-) on peripheral blood vessels in the hands of patients with VWF. Ninety one (91)patients with VWF underwent four-finger adsorption plethysmography, and the pulse wave amplitude was recorded expressed in numeric parameters-called the native record. Next, a cold water test was conducted following with second plethysmography. The patients were divided in to the three groups. First and second inhaled 20-min of ionized oxygen O2•- or oxygen O2 respectively. Thirth group was control without treatment. All three groups a follow-up third plethysmography-the post-therapy record. Changes in the pulse wave amplitudes were evaluated. Inpatients group inhaling O2•- a modest increase of pulse wave amplitude was observed compared to the native record; patients inhaling medical oxygen O2 and the control showed a undesirable decline of pulse wave amplitude in VWF fingers. Strong vasodilatation were more frequent in the group inhaling O2•- compare to O2 (p < 0.05). Peripheral vasodilatation achieved by inhalation of O2•- could be used for VWF treatment without undesirable side effect in hospital as well as at home environment.	\N	\N
24872268	Excessive postoperative hemorrhage in cardiac surgery is a serious complication associated with adverse postoperative events. Also, its associated risk of re-exploration, places a high demand on hospital resources in terms of transfusion needs, ventilatory support requirements, intensive care support, and manpower requirements. To determine predictors of 24-hour drain volume (pleural and mediastinal) after coronary artery bypass graft (CABG), in order to focus on preventive measures for patients with identified risk factors. Fifty-four consecutive adult patients who had CABG at the Madras Medical Mission, Chennai, India in July 2008 were retrospectively studied. In order to determine risk factors for excessive post-operative bleeding, 11 pre-operative, and 13 operative and 2 post-operative variables were analyzed using univariate analysis and multiple linear regression. Cardiopulmonary bypass was used for all the patients and anti-fibrinolytic in 13 (22.8%). No mortality was recorded. Mean 24-hour post-operative drain volume was 458 ± 270 ml (range 90-1230). Re-exploration for bleeding was required in 2 (3.5%) patients. Predictors of 24-hour drain volume were heparin therapy before commencement of CPB (p=0.024), intra-operative transfusion of fresh frozen plasma (p=0.010), and pre-operative serum ALT value (p=0.047). The strongest predictor was intra-operative transfusion of platelets (p=0.005). To guard against excessive post-operative haemorrhage after CABG, pre-operative stabilisation and correction of coagulation should be achieved. Also the administration of heparin intra-operatively should be individualized and not only based on dose per body weight.	\N	\N
24875660	Peritoneal dialysis (PD) continues to be underutilized in the United States, even though it is less expensive, provides better quality of life and has better outcomes compared with hemodialysis. The reasons for low utilization of PD are influenced by complex psychosocial and economic factors, lack of physician training, physician bias and inadequate pre-end-stage renal disease care and education to the patients. Providing quality pre-end-stage renal disease education to patients and families and improving education and training of physician in PD, so that they become comfortable with the therapy, are of paramount importance to increase PD growth. Minimizing episodes of PD-related infections and noninfectious complications, preserving peritoneal membrane using more biocompatible solutions and drugs, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and careful management of volume status can reduce the loss of PD patients to hemodialysis. Timely surgical interventions can prevent the malfunction and loss of PD catheters. Consolidating smaller PD facilities in a given geographical area into a single large PD center can further improve PD outcomes and PD growth. Finally, with the introduction of bundled payment for dialysis services, PD may emerge as a cost-effective therapy and rekindle interest in the dialysis community to consider PD as a better renal replacement therapy option.	\N	\N
24877851	This was a systematic review of the literature to determine which compression method is superior in promoting ulcer healing and reducing recurrence in patients with lower extremity venous ulcer disease. We conducted a comprehensive search of multiple databases for randomized and nonrandomized comparative studies from 1990 to December 2013. We identified 36 studies and two Cochrane systematic reviews. Many studies had moderate risk of bias. We found no overall difference between compression stockings vs compression bandages with respect to ulcer healing, time to ulcer healing, or ulcer recurrence outcomes. When we compared stockings vs short stretch bandages, stockings were superior with respect to ulcer healing. However, stockings compared with four-layer systems showed no difference in ulcer healing outcomes. When four-layer systems were compared with compression with less than four layers, there was also no significant difference in ulcer healing outcomes. Similarly, short stretch bandages were not superior to long stretch bandages with respect to ulcer healing, time to ulcer healing, or ulcer recurrence. One Cochrane review presented many additional comparisons and reported increased wound healing with compression compared with no compression, with multicomponent systems over single component systems, and compression systems with an elastic component over no elastic component. Another Cochrane review demonstrated a reduction in recurrence with compression in patients with healed ulcers. At least moderate-quality evidence supports compression over no compression, multicomponent systems over single component systems, and systems with an elastic component over those without. We did not find significant differences with respect to ulcer healing outcomes for other comparisons. Low-quality evidence supports the effect of compression on ulcer recurrence.	\N	\N
24878150	To explore barriers and facilitators to implementing and sustaining Healthy Choices, a 3-year multicomponent obesity prevention intervention implemented in middle schools in Massachusetts. Using purposive sampling, 56 in-depth interviews were conducted with middle school employees representing different positions (administrators, teachers, food service personnel, and employees serving as intervention coordinators). Interviews were recorded and transcribed. Emergent themes were identified using thematic analyses. State-mandated testing, budget limitations, and time constraints were viewed as implementation barriers, whereas staff buy-in, external support, and technical assistance were seen as facilitating implementation. Respondents thought that intervention sustainability depended on external funding and expert assistance. Results confirm the importance of gaining faculty and staff support. Schools implementing large-scale interventions should consider developing sustainable partnerships with organizations that can provide resources and ongoing training. Sustainability of complex interventions may depend on state-level strategies that provide resources for implementation and technical assistance.	\N	\N
24882305	Loeys-Dietz syndrome (LDS) is a recently recognized connective tissue disorder caused by mutations of the transforming growth factor (TGF)-β receptors. It is an autosomal dominant syndrome characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. We treated an 18-year-old woman with a 100-mm-diameter aortic root aneurysm and severe aortic valve regurgitation. She underwent urgent aortic root replacement and bioprosthetic valve implantation. LDS was diagnosed by postoperative genetic screening results. Histopathologic examination of the aortic wall showed diffuse degeneration and elastin fragmentation in the media.	\N	\N
24895051	Haploidentical stem cell transplantation (haploSCT) offers an alternative treatment option for advanced leukemia patients lacking a HLA-compatible donor. Transfer of NK cells represents a promising therapeutic option in combination with SCT, as NK cells can promote graft versus leukemia with low risk of GVH disease. In this study, we show results from a phase I/II trial in which 24 acute myeloid leukemia patients underwent haploSCT in combination with early transfer of unmodified NK cells and observed a promising 2-year overall survival rate of 37%. By performing immunomonitoring and subsequent principal component analysis, we tracked donor NK-cell dynamics in the patients and distinguished between NK cells reconstituting from CD34(+) precursors, giving rise over time to a continuum of multiple differentiation stages, and adoptively transferred NK cells. Transferred NK cells displayed a mature phenotype and proliferated in vivo during the early days after haploSCT even in the absence of exogenous IL-2 administration. Moreover, we identified the NK-cell phenotype associated with in vivo expansion. Thus, our study indicates a promising path for adoptive transfer of unmodified NK cells in the treatment of high-risk acute myeloid leukemia.	\N	\N
24896322	The design of antioxidant pharmaceuticals is a major challenge for the treatment of many clinical conditions and in aging. Free radical damage (FRD) is primarily catalysed by iron catalytic centers. Most of the natural and synthetic antioxidants are ineffective in inhibiting FRD because of the achievement of low concentrations at the affected tissues. Despite that many chelators inhibit FRD in vitro and in vivo, only Deferiprone (L1) has been shown to be effective and safe in the reversal of oxidative stress related tissue damage in iron overload and other conditions such as cardiomyopathy, acute kidney disease, Friedreich ataxia etc. Deferiprone, other chelators and their combinations could be used as main, adjuvant and alternative therapies in untreated conditions eg forms of cancer, Alzheimer's and Parkinson's diseases. Therapeutic targeting in each case requires specific chelator selection based on structure/activity correlation and consideration of other parameters eg ADMET. The ability of L1 to reach extracellular and intracellular compartments of almost all tissues including the brain is a major advantage for further development and use in many clinical conditions.	\N	\N
24896980	Abnormally aggregated tau is the hallmark pathology of tauopathy neurodegenerative disorders and is a target for development of both diagnostic tools and therapeutic strategies across the tauopathy disease spectrum. Development of carbon-11- or fluorine-18-labeled radiotracers with appropriate affinity and specificity for tau would allow noninvasive quantification of tau burden using positron emission tomography (PET) imaging. We have synthesized [(18)F]lansoprazole, [(11)C]N-methyl lansoprazole, and [(18)F]N-methyl lansoprazole and identified them as high affinity radiotracers for tau with low to subnanomolar binding affinities. Herein, we report radiosyntheses and extensive preclinical evaluation with the aim of selecting a lead radiotracer for translation into human PET imaging trials. We demonstrate that [(18)F]N-methyl lansoprazole, on account of the favorable half-life of fluorine-18 and its rapid brain entry in nonhuman primates, favorable kinetics, low white matter binding, and selectivity for binding to tau over amyloid, is the lead compound for progression into clinical trials.	\N	\N
24902046	Infection, graft-versus-host disease (GVHD), and to a lesser extent sinusoidal obstructive syndrome (SOS) represent the major causes of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). During the last decade, progress in prevention and treatment of these complications led to improvement in the outcome of these patients. Despite the fact that nonmyeloablative regimens have been increasingly used in elderly patients and in patients with co-morbidities, the nonrelapse related mortality remains a challenge and long-term follow-up is required. The objective of this manuscript is to provide an updated concise review of the complications of AHSCT and of the available treatment interventions.	\N	\N
24910429	Acute myeloid leukemia (AML) therapy involves compounds that are cytotoxic to both normal and cancer cells, and relapsed AML is resistant to subsequent chemotherapy. Thus, agents are needed that selectively kill AML cells with minimal toxicity. Here, we report that AML is dependent on DDX5 and that inhibiting DDX5 expression slows AML cell proliferation in vitro and AML progression in vivo but is not toxic to cells from normal bone marrow. Inhibition of DDX5 expression in AML cells induces apoptosis via induction of reactive oxygen species (ROS). This apoptotic response can be blocked either by BCL2 overexpression or treatment with the ROS scavenger N-acetyl-L-cysteine. Combining DDX5 knockdown with a BCL2 family inhibitor cooperates to induce cell death in AML cells. By inhibiting DDX5 expression in vivo, we show that DDX5 is dispensable for normal hematopoiesis and tissue homeostasis. These results validate DDX5 as a potential target for blocking AML.	\N	\N
24924164	Drug resistance mutations (DRMs) can serve as distinct, nonpolymorphic markers for evaluating diversity of expressed HIV-1. We screened for DRMs during early-acute viremia and examined the diversity in reverse transcriptase (RT) relative to envelope (env) in cases of transmitted drug resistance. We evaluated 111 longitudinal plasma samples collected every 2-7 days from 15 individuals who seroconverted for HIV-1 infection in 1994-2000. The samples were screened with sensitive polymerase chain reaction assays for the commonly transmitted M41L and K70R mutations and for K65R, which was undetected by bulk sequencing. Mutation-positive samples were further characterized by clonal sequencing of RT and env V1-V3. Drug resistance mutations were detected in 4 of 15 seroconverters at 5-50 days of viral nucleic acid expression; most mutations disappeared about the time of seroconversion. Clonal sequencing verified low-level K65R at frequencies of 0.4%-4.9%. In each case, K65R coexisted unlinked with variants carrying 2-5 thymidine analog mutations at frequencies of 1.6%-23.0%. In one seroconverter, variants with M184V and nonnucleoside RT inhibitor mutations were also identified at first RNA expression. Each seroconverter displayed a homogeneous V1-V3 env population. Reverse-transcriptase DRMs demonstrate that the breadth of variants in transmission may be greater than what is reflected in envelope sequences.	\N	\N
24935472	In the context of cancer, transforming growth factor β (TGF-β) is a cell growth suppressor; however, it is also a critical inducer of invasion and metastasis. SMAD is the important mediator of TGF-β signaling pathway, which includes receptor-regulated SMADs (R-SMADs), common-mediator SMADs (co-SMADs), and inhibitory SMADs (I-SMADs). I-SMADs block the activation of R-SMADs and co-SMADs and thus play important roles especially in the SMAD-dependent signaling. SMAD7 belongs to the I-SMADs. As an inhibitor of TGF-β signaling, SMAD7 is overexpressed in numerous cancer types and its abundance is positively correlated to the malignancy. Emerging evidence has revealed the switch-in-role of SMAD7 in cancer, from a TGF-β inhibiting protein at the early stages that facilitates proliferation to an enhancer of invasion at the late stages. This role change may be accompanied or elicited by the tumor microenvironment and/or somatic mutation. Hence, current knowledge suggests a tumor-favorable timer nature of SMAD7 in cancer progression. In this review, we summarized the advances and recent findings of SMAD7 and TGF-β signaling in cancer, followed by specific discussion on the possible factors that account for the functional changes of SMAD7.	\N	\N
24940479	Although the pathophysiology of facioscapulohumeral dystrophy (FSHD) has been controversial over the last decades, progress in recent years has led to a model that incorporates these decades of findings and is gaining general acceptance in the FSHD research community. Here we review how the contributions from many labs over many years led to an understanding of a fundamentally new mechanism of human disease. FSHD is caused by inefficient repeat-mediated epigenetic repression of the D4Z4 macrosatellite repeat array on chromosome 4, resulting in the variegated expression of the DUX4 retrogene, encoding a double-homeobox transcription factor, in skeletal muscle. Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD. Although some disagreements regarding the details of mechanisms remain in the field, the coalescing agreement on a central model of pathophysiology represents a pivot-point in FSHD research, transitioning the field from discovery-oriented studies to translational studies aimed at developing therapies based on a sound model of disease pathophysiology.	\N	\N
24944260	To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH). Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100-600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities. From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in "dizziness/lightheadedness." Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for "standing a long time." Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥ 3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events. In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated. This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days.	\N	\N
24948193	Acute inflammation is the result of a complex signal transduction pathway that protects and heals our body and is necessary for our good health and normal wellbeing. Whereas, chronic inflammation can be correlated well with the onset of a plethora of autoimmune disorders; rheumatoid arthritis, systemic lupus and polymyalgia, rheumatic and other diseases like asthma, inflammatory bowel diseases, cardiovascular disorders, ulcerative colitis and Crohn's disease. Also, it has been reported to be associated with the onset of various cancers. An effective anti-inflammatory drug should be able to inhibit the development of chronic inflammation without interfering in normal homeostasis. A number of herbal drugs have been identified in the past that can target inflammatory cytokines. Among these, Ganoderma lucidum: a powerful medicinal mushroom has been found to possess immune-modulating and immune-potentiating capabilities and has been characterized as a wonder herb. This review mainly focuses on the molecular mechanism of anti-inflammatory and antiallergic action of this mushroom and also sheds light on various patent studies related to its pharmacological action.	\N	\N
24952923	Extraosseous Gaucher cell deposits are a rare complication of Gaucher disease that can mimic malignancy. We describe a case of Gaucher cell deposition in the subcutaneous soft tissues overlying the lower thoracic spine in an 18-year-old woman with known type III Gaucher disease. This case is unique in the literature because this subcutaneous Gaucher mass was not associated with extension from underlying bone involvement or clear lymph node origin. It demonstrated no discernible continuity with the adjacent thoracic spinous processes, the cortices of which appeared intact. Although patients with Gaucher disease are at increased risk of malignancy, Gaucher cell deposition should remain a differential consideration for soft tissue masses with or without adjacent bone involvement in patients with known Gaucher disease.	\N	\N
24953225	The association between the C3435T polymorphism in the MDR1 gene and refractory epilepsy remains controversial. The association appears to be influenced by ethnicity and region. We have performed a systematic review and meta-analysis to assess the link between the MDR1 C3435T polymorphism and refractory epilepsy in the Chinese population. We searched the Cochrane Library, MIDLINE, EMBASE, CBM disc, CNKI, VIP, and WANFANG databases for literature published through August 2013 for case-control studies that evaluated the association between the MDR1 C3435T polymorphism and refractory epilepsy. Twenty-one case-control studies involving 4269 patients (1863 cases in the group with drug-resistant epilepsy and 2406 in the group with drug-responsive epilepsy) were included in the systematic review and meta-analysis. The analysis showed that there were significantly more cases with the MDR1 3435 CC genotype in the group with drug-resistant epilepsy than in the group with drug-responsive epilepsy [odds ratio (OR)=1.50, 95% confidence interval (CI)=1.09-2.06, P=0.01]. In a subanalysis of patients from the southern regions of China, the correlation was not significant [odds ratio (OR)=1.2, 95% confidence interval (CI)=0.89-1.64, P=0.24]. The relationship established in a subset of the Chinese population between the MDR1 C3435T polymorphism and refractory epilepsy will guide epilepsy treatment and development of new AEDs.	\N	\N
24955837	Pulmonary arterial hypertension (PAH) is a life-threatening disorder that is associated with elevated pulmonary pressures and right heart failure resulting from progressive loss and thickening of small pulmonary arteries. Despite their ability to improve symptoms, current therapies fail to prevent disease progression, leaving lung transplantation as the only therapy in end-stage PAH. To overcome the limitations of current therapies, there is an active search for disease-modifying agents capable of altering the natural history of, and improving clinical outcomes in, PAH. The Wnt signaling pathways have emerged as attractive treatment targets in PAH given their role in the preservation of pulmonary vascular homeostasis and the recent development of Wnt-specific compounds and biological therapies capable of modulating pathway activity. In this review, we summarize the literature describing the role of Wnt signaling in the pulmonary circulation and discuss promising advances in the field of Wnt therapeutics that could lead to novel clinical therapies capable of preventing and/or reversing pulmonary vascular pathology in patients with this devastating disease.	\N	\N
24962034	The HIV Modes of Transmission (MOT) model estimates the annual fraction of new HIV infections (FNI) acquired by different risk groups. It was designed to guide country-specific HIV prevention policies. To determine if the MOT produced context-specific recommendations, we analyzed MOT results by region and epidemic type, and explored the factors (e.g. data used to estimate parameter inputs, adherence to guidelines) influencing the differences. We systematically searched MEDLINE, EMBASE and UNAIDS reports, and contacted UNAIDS country directors for published MOT results from MOT inception (2003) to 25 September 2012. We retrieved four journal articles and 20 UNAIDS reports covering 29 countries. In 13 countries, the largest FNI (range 26 to 63%) was acquired by the low-risk group and increased with low-risk population size. The FNI among female sex workers (FSWs) remained low (median 1.3%, range 0.04 to 14.4%), with little variability by region and epidemic type despite variability in sexual behaviour. In India and Thailand, where FSWs play an important role in transmission, the FNI among FSWs was 2 and 4%, respectively. In contrast, the FNI among men who have sex with men (MSM) varied across regions (range 0.1 to 89%) and increased with MSM population size. The FNI among people who inject drugs (PWID, range 0 to 82%) was largest in early-phase epidemics with low overall HIV prevalence. Most MOT studies were conducted and reported as per guidelines but data quality remains an issue. Although countries are generally performing the MOT as per guidelines, there is little variation in the FNI (except among MSM and PWID) by region and epidemic type. Homogeneity in MOT FNI for FSWs, clients and low-risk groups may limit the utility of MOT for guiding country-specific interventions in heterosexual HIV epidemics.	\N	\N
24965397	Several studies indicated that the expression level of MLL3 gene in gastric cancer tissue was associated with prognosis, and previous studies also suggested that genetic polymorphisms of MLL3 were related to the risk for gastric cancer. The present study aimed to investigate the association of a missense mutation (S3660L) in the MLL3 gene with gastric cancer risk in a Chinese population. In the present study, we identified a novel missense mutation in MLL3 gene (S3660L) by directly sequencing method in 48 gastric cancer patients. To further explore the relation between gastric cancer and this mutation, we selected 354 gastric cancer patients and 377 healthy control subjects and designed a case-control study. We found that the AG genotype (14.9 vs 6.40%, odds ratio/OR=2.58, 95% CI: 1.33-4.54, p<0.001) and A allele (7.5 vs 3.2%, OR=2.46, 95% CI: 1.55~5.34, p<0.001) were common in the gastric cancer patients than in the control subjects. We concluded that this novel missense (S3660L) mutation in MLL3 gene is likely to increase the gastric cancer risk.	\N	\N
24970372	During the 2009 A(H1N1) influenza pandemic, a suite of studies conducted in Canada showed an unexpected finding, that patients with medically attended laboratory-confirmed pandemic influenza were more likely to have received seasonal influenza vaccination than test-negative control patients. Different bodies, including scientific journals and government scientific advisory committees, reviewed the evidence simultaneously to determine its scientific validity and implications. Decision-making was complicated when the findings made their way into the media. The normal trajectory of non-urgent research includes peer-review publication after which decision-makers can process the information taking into account other evidence and logistic considerations. In the situation that arose, however, the congruence of an unexpected finding and the simultaneous review of the evidence both within and outside the traditional peer-review sphere raised several interesting issues about how to deal with emerging evidence during a public health emergency. These events are used in this article to aid discussion of the complex interrelationship between researchers, public health decision-makers and scientific journals, the trade-offs between sharing information early and maintaining the peer-review quality assurance process, and to emphasise the need for critical reflection on the practical and ethical norms that govern the way in which research is evaluated, published and communicated in public health emergencies.	\N	\N
24973485	This study explored the care challenges experienced by older patients with multimorbidity, their informal caregivers and family physicians. Semi-structured interviews were conducted with 27 patients, their informal caregivers and family physicians. Qualitative description was used to identify key themes in the interview transcripts. Participants experienced many common challenges when managing multimorbidity, including a lack of decision-making support, poor communication and uncoordinated health services. Within these themes, unique perspectives specific to the role of being a patient, caregiver or family physician emerged. The study adds to a limited evidence base on the experience of patients with multimorbidity. By including the perspectives of their family caregivers and physicians, we provide important insight into the management of multimorbidity and recommend the uptake of specific strategies to address them.	\N	\N
24986275	Cyclical outbreaks of mumps have been noticed across Chandigarh city during winter months. Chandigarh does not provide measles, mumps and rubella (MMR) vaccination in the State immunization schedule. Epidemiological shift in age at diagnosis of mumps was noticed with higher incidence in older children and adults. Increased occurrence of complications can be predicted with this age shift. Silent burden of rubella with serious outcomes in newborns further strengthen the case for MMR vaccine inclusion in routine immunization program of Chandigarh.	\N	\N
24988612	Autophagy, the process of degradation of unwanted or damaged cell elements, is extremely important for a variety of human diseases, especially cancers. This process influences various stages of initiation and progression of cancer, which is caused by overlapping signaling pathways of autophagy and carcinogenesis. However, due to the complexity of cancer as a systemic disease, the fate of tumor cells is not determined by one signal pathway. Chronic autophagy inhibition leads to tumor promotion, due to instability of the genome, defective cell growth, also as a result of cellular stress. However, increased induction of autophagy may be a mechanism for tumor cell survival in the state of hypoxia, acidosis, as well as under the influence of chemotherapy. Therefore, in the context of cancer development, the process of autophagy should be considered in two directions. Determination of the molecular mechanisms underlying the process of autophagy and its role in the carcinogenesis is a key element of the anticancer strategy. The main objective of modern oncology, which should eventually lead to personalized therapy, is the possibility to predict the response of a particular type of cancer to the used drug. Results of in vitro and in vivo studies show the magnitude of the relationship between changes in the genome, and response to the therapy. This information indicates the mechanism and thereby the target point of the drugs. In this review we focus on the mechanism of autophagy and its role in cancer therapy, which can help to understand the autophagy-cancer relationship and indicate the direction for the design of new drugs with anticancer activity.	\N	\N
24989056	Flow volume loops (FVLs) are considered part of the workup of patients with thyroid enlargement presenting to the endocrinology clinic. They are used to detect upper airway obstruction (UAO) secondary to tracheal compression (TC) from a goitre. Surgical assessment in contrast tends to focus on clinical evaluation supplemented when required by imaging. The aim of this study was to investigate whether FVLs influence the decision to operate in patients with a goitre. We identified patients with a goitre referred by the department of endocrinology for FVLs between 2006 and 2011. The results of the FVL were collated, and their impact on patient management was assessed. Ninety-six patients were referred for FVL. In 38 patients, the indication was specifically to evaluate the effects of a goitre. Of these, 33 were reported as normal. Five FVLs were reported as abnormal (3 suggesting lung pathology and 2 TC). Both patients with TC on FVL presented no CT evidence of TC and underwent surgery due to abnormal cytology. Of the 33 normal FVLs, 7 underwent surgery: 2 for local compression, 4 for abnormal cytology and 1 for Graves' disease. None of the FVLs influenced the decision to operate. FVLs may detect subradiological TC, but rarely influence management in patients with a goitre. In view of this and the cost of £235 per investigation, FVL should be reserved for goitre patients with suspected primary lung pathology, where the distinction between large and small airway compression is likely to influence management.	\N	\N
24994677	Uveal melanoma (UM) is the most common primary tumor of the eye in adults. There is no standard adjuvant treatment to prevent metastasis and no effective therapy in the metastatic setting. We have established a unique panel of 7 UM cell lines from either patient's tumors or patient-derived tumor xenografts (PDXs). This panel recapitulates the molecular landscape of the disease in terms of genetic alterations and mutations. All the cell lines display GNAQ or GNA11 activating mutations, and importantly four of them display BAP1 (BRCA1 associated protein-1) deficiency, a hallmark of aggressive disease. The mTOR pathway was shown to be activated in most of the cell lines independent of AKT signaling. mTOR inhibitor Everolimus reduced the viability of UM cell lines and significantly delayed tumor growth in 4 PDXs. Our data suggest that mTOR inhibition with Everolimus, possibly in combination with other agents, may be considered as a therapeutic option for the management of uveal melanoma.	\N	\N
25003989	Understanding how the immune system facilitates or controls HIV-1 disease progression has important implications for the design of effective interventions. We report that although B-cell dysregulations associated with HIV-1 disease progression are accompanied by an overall decrease in the percentage of total blood B-cells, we observe an increase in relative frequencies of cells presenting characteristics of both transitional immature and first-line marginal zone (MZ) B-cell populations, we designated as precursor MZ-like B-cells. B-cells with similar attributes have been associated with IL-10 expression and "regulatory" potential. As such, the relative frequencies of precursor MZ-like B-cells expressing IL-10 are increased in the blood of viremic HIV-1-infected individuals when compared to HIV-negative subjects. Importantly, in aviremic HIV-1 Elite-Controllers (EC), we found unaltered relative percentages of precursor MZ-like B-cells which presented normal IL-10 expression patterns. Furthermore, EC had increased relative frequencies of blood MZ-like B-cells expressing LT-α. Thus in contrast to viremic HIV-1-infected individuals, EC present MZ-like B-cell populations which IL-10 and LT-α expression profiles may favour homeostasis of immune responses and lymphoid microenvironments.	\N	\N
25011952	We recently demonstrated a beneficial effect of metformin compared with glipizide in type 2 diabetic patients regarding cardiovascular outcomes for 3-year treatment in the SPREAD-DIMCAD study. However, the potential mechanism for the clinical effects remains unclear. Here, we performed a comprehensive lipidomics study to evaluate the different lipid metabolites in serum samples obtained from participants in this study. Liquid chromatography-quadrupole time of flight-mass spectrometry was used to evaluate the different lipid metabolites in serum samples obtained from the participants (21 patients in glipizide group and 23 patients in metformin group) before and after each year of treatment (at 0 [baseline], 1, 2, and 3 years of study drug administration). A total of 118 serum lipid molecular species was identified and quantified. During treatment, metformin induced a substantially greater change in serum lipid species compared with glipizide, especially at the 2- and 3-year time points (with 2, 11, and 12 lipid species being significantly different between the groups after each year of treatment [1, 2, or 3 years], P < 0.05). Among the significantly changed lipid species, three lipid metabolites were linked to long-term composite cardiovascular events (adjusted P < 0.05). After treatment, triacylglycerols (TAGs) of a relatively higher carbon number showed a clearly increased trend in metformin group compared with the glipizide group, whereas the changes in TAGs with different double bonds were minimal. Our findings revealed the differential therapeutic effects of metformin and glipizide on comprehensive lipidomics, which were comparable with their different long-term effects on cardiovascular outcomes.	\N	\N
25014130	To conduct the first population size estimation and biological and behavioral surveillance survey among men who have sex with men (MSM) in Angola. Population size estimation with multiplier method and a cross-sectional study using respondent-driven sampling. Luanda Province, Angola. Study was conducted in a large hospital. Seven hundred ninety-two self-identified MSM accepted a unique object for population size estimation. Three hundred fifty-one MSM were recruited with respondent-driven sampling for biological and behavioral surveillance survey. Interviews and testing for HIV and syphilis were conducted on-site. Analysis used Respondent-Driven Sampling Analysis Tool and STATA 11.0. Univariate, bivariate, and multivariate analyses examined factors associated with HIV and unprotected sex. Six imputation strategies were used for missing data for those refusing to test for HIV. A population size of 6236 MSM was estimated. Twenty-seven of 351 individuals were tested positive. Adjusted HIV prevalence was 3.7% (8.7% crude). With imputation, HIV seroprevalence was estimated between 3.8% [95% confidence interval (CI): 1.6 to 6.5] and 10.5% (95% CI: 5.6 to 15.3). Being older than 25 (odds ratio = 10.8, 95% CI: 3.5 to 32.8) and having suffered episodes of homophobia (odds ratio = 12.7, 95% CI: 3.2 to 49.6) significantly increased the chance of HIV seropositivity. Risk behaviors are widely reported, but HIV seroprevalence is lower than expected. The difference between crude and adjusted values was mostly due to treatment of missing values in Respondent-Driven Sampling Analysis Tool. Solutions are proposed in this article. Although concerns were raised about feasibility and adverse outcomes for MSM, the study was successfully and rapidly completed with no adverse effects.	\N	\N
25015744	Endoscopic ultrasound (EUS)-guided drainage is an effective treatment for many abscesses in the abdomen. We review our experience with EUS-guided drainage of pelvic abscesses. Thirty consecutive patients who underwent EUS-guided pelvic abscess drainage were evaluated after excluding three patients with distance to transducer >2 cm or organized abscess. Thirty patients (25 male) aged 60 ± 4.5 years (mean ± SD) had 4 prostatic abscesses, 7 perisigmoid abscesses, and 19 perirectal abscesses with mean ± SD sizes of 2.5 ± 0.3, 4.7 ± 0.6, and 5.4 ± 0.4 cm, respectively. Surgery was the most common predisposing factor (n = 14, 46.6 %) followed by diverticulitis (n = 5, 16.6 %). Interventions included aspiration only (2 prostatic and 3 perisigmoid), aspiration and dilatation (2 patients in each group), and dilatation and stenting (2 perisigmoid and 17 perirectal). Five (16.6 %) patients needed re-intervention, and two (6.6 %) needed surgery. There were no recurrences. Technical success of EUS-guided pelvic abscess drainage overall was 90.9 % (30/33) and was 93.3 % (27/30) in patients in whom EUS-guided drainage was attempted, with 16.5 % (n = 5) re-intervention rate. EUS-guided drainage has an excellent success rate in drainage of pelvic abscesses.	\N	\N
25022060	The measurement of antinuclear antibodies (ANA) is used for screening of connective tissue diseases (CTD) in the laboratory. ANA detection is performed by indirect immunofluorescence (IF) assay on HEp-2 cells from human larynx carcinoma. However, it lacks specificity for the identification of specific diseases and antigen reactivity. The aim of the present study was to evaluate the EliA CTD Screen (EliA), a new enzyme fluoroimmunoassay (Phadia AB, Uppsala, Sweden) for detection of ANA in human serum. The study involved a total of 732 serum samples, 200 from healthy donors, 297 from patients with CTD and 235 from patients with rheumatoid arthritis, vasculitis syndrome and relative disease of CTD. For all sera, ANA was measured by IF, commercial assay (MESACUP) and EliA. The sensitivity and specificity of EliA were 73.7% and 78.7%, respectively, whereas those of MESACUP were 80.8% and 64.7%, respectively. Area under the receiver operating curves for EliA, MESACUP and IF were 0.821, 0.786 and 0.730, respectively. The concordance rate between EliA and MESACUP was 84.2%. These discrepancies between those 2 assays were found in 84 sera. Further investigation were done by each ANA antigen tests for the discrepant results of EliA in 83 sera. The discrepancies might be occurred by antigen difference or non-specific response. AUC results showed that the diagnostic performance of EliA was superior to MESACUP and IF. EliA had a good performance as method for screening of CTD.	\N	\N
25027632	This longitudinal, exploratory study was designed to better understand the lived experience of spousal caregivers age 60 and older providing care to partners with Alzheimer's disease and related dementias resident in a care facility. Twenty eight spousal caregivers were interviewed up to three times over a period of 2 years, and long-term care facility staff from four locations across British Columbia (BC), Canada participated in four focus groups. Thematic analysis of interview and focus group transcripts revealed a central, unifying theme 'together but apart'. The results identify key targets for policy makers and service providers to support positive health and well-being outcomes for spousal caregivers providing care to their partners diagnosed with Alzheimer's disease and related dementia and living in care facilities.	\N	\N
25034390	Patients with multiple myeloma (MM) manifesting acute kidney injury (AKI) and who later recover renal function and independence from renal replacement therapy (RRT) are considered to have a better outcome. The aim of this work was to study the factors associated with renal function recovery (independence of hemodialysis) and longer survival in these patients. A retrospective single center study including patients with a diagnosis of MM and severe AKI, defined as stage 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) criteria: 3.0 times baseline increase in serum creatinine (sCr) or increase in sCr to ≥4.0mg/dL or initiation of RRT, was conducted. Data was registry-based and collected between January 2000 and December 2011. We examined demographic and laboratorial data, presenting clinical features, precipitating factors, need for RRT and chemotherapy. Death was considered the primary endpoint. Lower serum β2-microglobulin was the only independent factor associated with recovery of renal function and independence of RRT (OR 0.95, 95% CI: 0.91-0.99, P=0.02). The median survival after AKI was 10.7±12.1months. The factors associated with longer survival were independence of RRT (HR 2.21; 95% CI: 1.08-4.49; P=0.02), lower CRP (HR 1.07; 95% CI: 1.03-1.12; P=0.001) and younger age (HR 1.03; 95% CI: 1.01-1.06; P=0.005). Our study suggests that MM patients with lower serum β2-microglobulin have a higher likelihood of recovering renal function after severe AKI. Independence of RRT, lower CRP and younger age are associated with longer survival.	\N	\N
25038555	The rapidly increasing availability of electronic health records (EHRs) from multiple heterogeneous sources has spearheaded the adoption of data-driven approaches for improved clinical research, decision making, prognosis, and patient management. Unfortunately, EHR data do not always directly and reliably map to medical concepts that clinical researchers need or use. Some recent studies have focused on EHR-derived phenotyping, which aims at mapping the EHR data to specific medical concepts; however, most of these approaches require labor intensive supervision from experienced clinical professionals. Furthermore, existing approaches are often disease-centric and specialized to the idiosyncrasies of the information technology and/or business practices of a single healthcare organization. In this paper, we propose Limestone, a nonnegative tensor factorization method to derive phenotype candidates with virtually no human supervision. Limestone represents the data source interactions naturally using tensors (a generalization of matrices). In particular, we investigate the interaction of diagnoses and medications among patients. The resulting tensor factors are reported as phenotype candidates that automatically reveal patient clusters on specific diagnoses and medications. Using the proposed method, multiple phenotypes can be identified simultaneously from data. We demonstrate the capability of Limestone on a cohort of 31,815 patient records from the Geisinger Health System. The dataset spans 7years of longitudinal patient records and was initially constructed for a heart failure onset prediction study. Our experiments demonstrate the robustness, stability, and the conciseness of Limestone-derived phenotypes. Our results show that using only 40 phenotypes, we can outperform the original 640 features (169 diagnosis categories and 471 medication types) to achieve an area under the receiver operator characteristic curve (AUC) of 0.720 (95% CI 0.715 to 0.725). Moreover, in consultation with a medical expert, we confirmed 82% of the top 50 candidates automatically extracted by Limestone are clinically meaningful.	\N	\N
25044634	The potential benefit of vitamin K as a therapeutic in osteoporosis is controversial and the vitamin K regimen being used clinically (45 mg/day) employs doses that are many times higher than required to ensure maximal gamma-carboxylation of the vitamin K-dependent bone proteins. We therefore tested the hypothesis that vitamin K catabolites, 5-carbon (CAN5C) and 7-carbon carboxylic acid (CAN7C) aliphatic side-chain derivatives of the naphthoquinone moiety exert an osteotrophic role consistent with the treatment of osteoporosis. Osteoblast-like MG63 cell cultures were challenged with lipopolysaccharide and the levels of interleukin-6, an osteoclastogenic cytokine, measured with and without catabolites; low concentrations of CAN7C significantly inhibited interleukin-6 release, but CAN5C did not. In models of bone loss induced by ovariectomy or sciatic neurectomy in C57BL/6 mice, we found that the rarer CAN7C catabolite markedly restricted ovariectomy-induced bone loss and possibly limited sciatic neurectomy-induced bone loss. CAN7C activity depends on a free carboxylic acid and its particular side-chain structure. These in vivo data indicate for the first time that the clinical utility of vitamin K for osteoporosis may reside in an unusual catabolite.	\N	\N
25046696	Cystic and alveolar hydatid disease of humans caused by infection with Echinococcus granulosus or Echinococcus multilocularis are significant zoonoses in developing countries. For human infections, the main definitive host is the dog, and reduction in the population of unwanted dogs, together with anthelmintic treatment of wanted dogs, are recommended control procedures for these zoonoses. Both owned and unowned dogs have been shown to be a major source of Echinococcus spp. infection in developing countries. Unowned dogs are the most challenging category in dog population management for the control of major zoonotic diseases. Unowned dogs are those dogs that do not have an owner, and those dogs whose owner cannot readily be identified. Control of numbers of unowned dogs can be done in various ways if funds are available. Fertility control and humane euthanasia are likely to be the most effective procedures in developing countries. Fertility control requires significant funding, and where resources are scarce humane euthanasia may be the most effective option. Both procedures are ongoing events, with no predictable end point. This paper examines the sociology and technology for the population management of owned and unowned dogs, specifically for the reduction of human hydatid disease. Examples are given for developing and developed countries. Although a "One Health" approach is desirable, the technology for hydatid control is different from that for rabies, and FAO Animal Welfare recommendations for dog population management should be adjusted accordingly.	\N	\N
25051669	The paper presents data on the frequency of polymorphisms of candidate genes involved in the formation of endothelial dysfunction--endothelin-1 (EDN1 Lys198Asn) and endothelial nitric oxide synthase (NOS3 T786C) together with the concentrations of their active products (nitric oxide, endothelin-1) in individuals with chronic mercury intoxication. The concentration change of nitric oxide and endothelin-1 indicates the presence of endothelial dysfunction in the individuals examined. The studied polymorphisms appeared to play a minor role in the pathogenesis of endothelial dysfunction in patients with chronic mercury intoxication.	\N	\N
25055486	Postoperative intracranial infectious complications are one of the most topical problems of neurosurgical intensive care due to theirs significant capability to impair outcomes of the main disease. To define the risk factors of postoperative meningitis in patients with chiasm-sellar tumors. 1. to define the effect of somatic and intracranial risk factors on occurrence of postoperative meningitis in patients after transsphenoidal and transcranial approaches to the tumor. 2. To define the effect of postoperative meningitis on outcomes of treatment in patients after transsphenoidal and transcranial approaches to the tumor. Somatic and intracranial risk factors of occurrence of postoperative meningitis (pneumonia, urinary tract infection, sepsis, intra-abdominal hypertension, the presence of external ventricular and lumbar drainage, monitoring of intracranial pressure, cerebrospinal fluid, and reoperation) were fixed every day. The study was conducted in the ICU of the Burdenko from October, 2010 to July, 2012. The 34 patients (19 males, 15 females) were included in the study (average age 47.5 years). The patients were divided into two groups; 17 patients each group. The group-1 included patients after transcranial approach to the tumor and the group-2 included patients after transsphenoidal approach. In the group-1 a meningitis occurred in 3 patients (17.6% +/- 9.2%, DI [-0.4 - 35.6]). In the group-2 a meningitis occurred in 7 patients (41.2% +/- 11.9) DI 95% [17.8 - 64.4]. Accumulation of cerebrospinal fluid under the skin flap authentically increased a risk of a meningitis occurrence in patients after transcranial approach to the tumor (p = 0.031). There was no defined statistical significance of other risk factors. But there was defined a trend of the increasing of meningitis occurrence in patients after transsphenoidal approach in case of lumbar drainage or reoperation. Duration of mechanical ventilation and ICU stay in patients with meningitis was authentically longer than in patients without meningitis in both groups. In the group-2 the duration of mechanical ventilation and ICU stay was significantly shorter than in the group-1. Meningitis is not a typical complication of postoperative period in patients with transcranial approach to the tumor. After transsphenoidal approach a meningitis occurrence is likely in case of postoperative liquorrhea, lumbar drainage or reoperation. Subcutaneous accumulation of cerebrospinal fluid is a single defined statistically significant risk factor of meningitis. Postoperative meningitis impairs a condition of patients with chiasm-sellar tumors, increases the duration of mechanical ventilation and impairs treatment outcomes.	\N	\N
25056937	Cancer is responsible for many deaths and is a major source of healthcare expenditures. The identification of new, non-invasive biomarkers might allow improvement of the direct diagnostic or prognostic ability of already available tools. Here, we took the innovative approach of interrogating the activity of exopeptidases in the serum of cancer patients with the aim of establishing a distinction based on enzymatic function, instead of simple protein levels, as a means to biomarker discovery. We first analyzed two well-characterized mouse models of prostate cancer, each with a distinct genetic lesion, and established that broad exopeptidase and targeted aminopeptidase activity tests reveal proteolytic changes associated with tumor development. We also describe new peptide-based freeze-frame reagents uniquely suited to probe the altered balance of selected aminopeptidases, as opposed to the full array of exopeptidases, and/or their modulators in patient serum or plasma. One particular proteolytic activity was impaired in animals with aggressive disease relative to cancer-free littermates. We identified the protease in question as dipeptidyl peptidase 4 (DPP4) by analyzing selected knockout mice and evaluating the effect of specific inhibitors. DPP4 activity was also reduced in the sera of patients with metastatic prostate cancer relative to patients with localized disease or healthy controls. However, no significant differences in DPP4 serum levels were observed, which established the loss of activity as the result of impaired enzymatic function. Biochemical analysis indicated that reduced activity was the result not of post-translational modifications or allosteric changes, but instead of a low-molecular-weight inhibitor. After we adjusted for age and total prostate-specific antigen, reduced DPP4 activity remained a significant predictor of cancer status. The results of this proof-of-principle study suggest that DPP4 activity might be a potential blood-based indicator of the presence of metastatic cancer of prostatic origin, either by itself or, more likely, as a means to improve the sensitivity and specificity of existing markers.	\N	\N
25063009	When microinvasion cannot be ruled out on core needle biopsy (CNB) in the setting of ductal carcinoma in situ (DCIS), the surgeon must decide whether to perform a sentinel lymph node biopsy (SLNB) at the time of surgery. Up to 10 % of patients with T1mi have nodal disease, but the utility of SLNB in DCIS suspicious for microinvasion (Smic) is unclear. The University of Chicago pathology database was queried for a diagnosis of Smic or definite microinvasion (Mic) on CNB from 2000 to 2014. We analyzed histology, imaging, core needle size, and the use of myoepithelial immunohistochemistry (IHC) markers. We identified 103 women, 72 with Smic and 31 with Mic on CNB. After surgery, 32 % of Smic patients had infiltrating ductal carcinoma (IDC). Seventy-two percent of Smic patients underwent SLNB, with 67 % performed at the initial surgery. SLNB was positive in 6 % and 10 % of Smic and Mic patients, respectively (p = 0.66). Excluding N1mic, the incidence of macrometastatic nodal disease was 1.9 % for Smic patients and 3.3 % for Mic patients (p = 1.00). For Smic patients, IDC was associated with a larger lesion size and smaller CNB needle. In the setting of Smic, grade, necrosis, or presence of a mass did not increase the risk of IDC. In patients with Smic on CNB, the incidence of macrometastatic nodal disease after SLNB is rare. Surgeons may consider omitting SLNB until IDC is definitively confirmed, especially in patients with Smic apart from other high-risk features.	\N	\N
25065742	Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive oxygen species (ROS) are generated during aerobic respiration in mitochondria, mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease. Hence, the correlation between mt tRNA activity and mitochondrial dysfunction has been assessed. Then, cybrid cells, which are constructed by the fusion of an enucleated cell harboring altered mtDNA with a ρ(0) cell, have long been used for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease. The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was successfully translocated to the mitochondrial matrix. Additionally, mt tRNA cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity, was observed.	\N	\N
25076776	Schizophrenia and bipolar disorder are severe neuropsychiatric disorders, affecting about 1% of the population. Identifying endophenotypes in the brains of neuropsychiatric patients is now considered the way to understand the underlying mechanisms and to improve therapeutic outcomes. However, the endophenotypes and brain mechanisms of the disorders remain unknown. We have previously reported that alpha-CaMKII heterozygous knockout mice show abnormal behaviors related to neuropsychiatric disorders. In these mutant mice, almost all neurons in the hippocampal dentate gyrus stay at a pseudo-immature state, which we refer to as "immature dentate gyrus (iDG)." So far, the iDG phenotype and similar behavioral abnormalities have been found in Schnurri-2 knockout, SNAP-25 mutant, and forebrain-specific calcineurin knockout mice. In addition, we found that both chronic fluoxetine treatment and pilocarpine-induced seizures can reverse the maturation state of the mature neurons, resulting in the iDG phenotype in wild-type mice. Such an iDG-like phenomenon was observed in the post-mortem brains from patients with schizophrenia/bipolar disorder. Recent studies suggest that cortex and amygdala of schizophrenia patients are also at a pseudo-immature state. Based on the findings, we proposed that immaturity of certain types of cells in the brain is a potential endophenotype of neuropsychiatric disorders.	\N	\N
25081727	To retrospectively review the safety and clinical efficacy of bevacizumab concomitant with chemotherapy in Chinese patients with advanced non-squamous non-small cell lung cancer (NSNSCLC). Clinical data for 79 patients with NSNSCLC who received bevacizumab concomitant with chemotherapy in Chinese PLA General Hospital from April 28th 2009 to May 5th 2013 were retrospectively reviewed to analyze the clinical efficacy including disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), the Eastern Cooperative Oncology Group (ECOG) score and the safety. The Eastern Cooperative Oncology Group (ECOG) score was 0-2. By the final cutoff date (June 9, 2013), 54 (68.4%) patients had disease progression and 37 (46.8%) died. The ORR was 32.9% and the DCR was 83.5%. The ORR of the first-, second-, and third- or later-line treatments were 51.4%, 25.0% and 12.5%, while the DCR were 94.3%, 80.0% and 70.8%, respectively. The median OS (mOS) and PFS (mPFS) were 13.5 and 5.83 months, respectively. The mOS of patients with the first-, second-, and third- or later-line treatments were 16.2, 10.9 and 8.30 months, while the mPFS were 7.27, 5.90 and 5.17 months, respectively. Chemotherapy-related adverse events included myelosuppression, vomiting, hepatic dysfunction and renal dysfunction, while the common serious bevacizumab-related adverse events were thromboembolic problems, gastrointestinal perforation and reversible posterior leukoencephalopathy syndrome, which could be well managed. Bevacizumab concomitant with chemotherapy is effective and the related toxicity can be well tolerated in Chinese patients with NSNSCLC.	\N	\N
25083284	Diagnosing coeliac disease (CD) can be challenging, despite highly specific autoantibodies and typical mucosal changes in the small intestine. The T-cell response to gluten is a hallmark of the disease that has been hitherto unexploited in clinical work-up. We aimed to develop a new method that directly visualizes and characterizes gluten-reactive CD4+ T cells in blood, independently of gluten challenge, and to explore its diagnostic potential. We performed bead-enrichment of DQ2.5-glia-α1a and DQ2.5-glia-α2 tetramer+ cells in the blood of control individuals, treated (TCD) and untreated patients (UCD). We visualized these cells by flow cytometry, sorted them and cloned them. We assessed their specificity by antigen stimulation and re-staining with tetramers. We detected significantly more gliadin-tetramer+ CD4+ effector memory T cells (TEM) in UCD and TCD patients, compared to controls. Significantly more gliadin-tetramer+ TEM in the CD patients than in controls expressed the gut-homing marker integrin-β7. Quantification of gut-homing, gluten-specific TEM in peripheral blood, visualized with human leukocyte antigen (HLA) -tetramers, may be used to distinguish CD patients from healthy individuals. Easy access to gluten-reactive blood T cells from diseased and healthy individuals may lead to new insights on the disease-driving CD4+ T cells in CD.	\N	\N
25095816	Falls in people with Parkinson's disease (PD) are frequent and recurrent events with devastating and widespread consequences. Despite this, understanding of the predictive and explanatory value of fall risk factors, as well as the development and testing of interventions aimed at reducing falls, are in their infancy. This review focuses on fall prediction and risk factors that are potentially remediable with physical interventions. We show that falls can be predicted with high accuracy using a simple three-step clinical tool. Evidence from recently published randomized controlled trials supports the implementation of balance-challenging exercises in reducing falls. Larger scale trials utilizing technologically advanced monitoring methods will further elucidate those interventions most likely to be cost effective according to individual risk factor profiles.	\N	\N
25097994	Results of surgical treatment of 1220 patients, suffering inguinal hernia, were analyzed. Among the patients there were 810 ageing more than 60 yrs old (main group), from 40 to 59 yrs--410 (control group). There was established, that in patients older than 60 yrs, due to presence of age-related atrophic-dystrophic changes in the inguinal channel muscles, the disease recurrence rate is more than in younger patients. That is why in the inguinal channel hernioplasty the priority must be on the side of alloplastic methods with application of miniinvasive and endoscopic procedures. There was not trustworthy difference between the groups of patients for the rate of intraoperative and early postoperative complications.	\N	\N
25115192	Good prognostic tools for predicting disease progression in early stage prostate cancer (PCa) are still missing. Detection of molecular subtypes, for instance by using microarray gene technology, can give new prognostic information which can assist personalized treatment planning. The detection of new subtypes with validation across additional and larger patient cohorts is important for bringing a potential prognostic tool into the clinic. We used fresh frozen prostatectomy tissue of high molecular quality to further explore four molecular subtype signatures of PCa based on Gene Set Enrichment Analysis (GSEA) of 15 selected gene sets published in a previous study. For this analysis we used a statistical test of dependent correlations to compare reference signatures to signatures in new normal and PCa samples, and also explore signatures within and between sample subgroups in the new samples. An important finding was the consistent signatures observed for samples from the same patient independent of Gleason score. This proves that the signatures are robust and can surpass a normally high tumor heterogeneity within each patient. Our data did not distinguish between four different subtypes of PCa as previously published, but rather highlighted two groups of samples which could be related to good and poor prognosis based on survival data from the previous study.The poor prognosis group highlighted a set of samples characterized by enrichment of ESC, ERG-fusion and MYC + rich signatures in patients diagnosed with low Gleason score,. The other group consisted of PCa samples showing good prognosis as well as normal samples. Accounting for sample composition (the amount of benign structures such as stroma and epithelial cells in addition to the cancer component) was important to improve subtype assignments and should also be considered in future studies. Our study validates a previous molecular subtyping of PCa in a new patient cohort, and identifies a subgroup of PCa samples highly interesting for detecting high risk PCa at an early stage. The importance of taking sample tissue composition into account when assigning subtype is emphasized.	\N	\N
25120773	Hirschsprung's disease (HSCR) is characterized by the absence of enteric ganglion cells along variable regions of the colon. Established theory demonstrates that HSCR is the consequence caused by the abnormal arrest of the migration and differentiation of neural crest-derived stem cells (NCSCs). And retinoid signaling was considered to be involved. We speculated that, HA117, a retinoid-related transcript of a long noncoding RNA (LncRNA), may be involved in the genesis of HSCR. In current research, colon specimens were collected from 25 HSCR patients and grouped into 3 segments: proximal anastomosis, dilated segment and stenotic segment. Real-Time PCR was used to analyze the expression profiles of HA117 and its neighboring gene DPF3 in different colon segments. Fluorescence in situ hybridization (FISH) was employed to detect the distribution of HA117 in the gut wall. Immunohistochemistry was performed to analyze the protein expression of DPF3 in different colon segments. HA117 expression in stenotic segment was higher compared to proximal anastomosis and dilated segment (p < 0.05). Whereas DPF3b mRNA was lower in stenotic segment than that in two other segments (p < 0.05). FISH detected HA117 was distributed in mucosa and muscle layer, mainly present in stenotic segment. Immunohistochemical staining showed that intensive DPF3 staining occurred in proximal anastomosis and the positive staining was hardly observed in stenotic segment. The results suggested that HA117 may be a factor exerting an anti-differentiation or or anti-maturation role in the genesis of HSCR. This gave us a novel cue for better understanding the etiology of HSCR.	\N	\N
25132753	More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori eradication and H. pylori induced related gastric disease prevention.	\N	\N
25142630	To describe metastatic pattern of uterine leiomyosarcomas (ULMS) and correlate it with clinical and histopathologic parameters. We included 113 women (mean age, 53 years; range, 29 to 72 years) with histopathology-confirmed ULMS from 2000 to 2012. Distribution of metastases was noted from imaging by two radiologists in consensus. Predictors of development of metastases were analyzed with univariate and multivariate analysis. Impact of various clinical and histopathologic parameters on survival was compared using Log-rank test and Cox proportional hazard regression model. Distant metastases were seen in 81.4% (92/113) of the patients after median interval of 7 months (interquartile range, 1 to 21). Lung was most common site of metastases (74%) followed by peritoneum (41%), bones (33%), and liver (27%). Local tumor recurrence was noted in 57 patients (50%), 51 of whom had distant metastases. Statistically significant correlation was noted between local recurrence and peritoneal metastases (p<0.001) and between lung and other common sites of hematogeneous metastases (p<0.05). Age, serosal involvement, local recurrence, and the International Federation of Gynecology and Obstetrics (FIGO) stage were predictive factors for metastases. At the time of reporting, 65% (74/113) of the patients have died; median survival was 45 months. Stage, local recurrence, and age were poor prognostic factors. ULMS metastasizes most frequently to lung, peritoneum, bone, and liver. Local recurrence was associated with peritoneal spread and lung metastases with other sites of hematogeneous metastases. Age, FIGO stage and local recurrence predicted metastatic disease and advanced stage, older age and local recurrence predicted poor outcome.	\N	\N
25148165	The purpose of this study is to compare CT urography (CTU) with unenhanced CT in the evaluation of upper urinary tracts in adults younger than 50 years with asymptomatic microscopic hematuria. In this study, 1516 CTU examinations were reviewed in adults younger than 50 years. Inclusion criteria were no significant prior urologic disease and asymptomatic microscopic hematuria with at least one urinalysis with greater than or equal to 3 RBCs/high-power field and less than or equal to 50 RBCs/high-power field. Upper urinary tract findings on CTU were classified as malignancy-related or non-malignancy-related hematuria and incidental non-hematuria-related findings. A blinded radiologist reviewed the unenhanced images, recording upper urinary tract findings and recommendations for further contrast-enhanced imaging. The modified Wald equation at a 95% CI, the "Rule of Threes" equation, and binomial distribution were used for malignancy-related findings. Four hundred forty-five examinations in 442 patients met inclusion criteria. CTU reports showed zero malignancy-related hematuria findings, 64 non-malignancy-related hematuria findings (62 renal calculi and two others), and 138 incidental non-hematuria-related findings. Unenhanced CT interpretation had a sensitivity of 100% (64/64) and a specificity of 89.2% (337/378). The theoretic risk of an upper urinary tract malignancy is 0-1.1%. CTU added no additional diagnostic benefit versus unenhanced CT in evaluating the upper urinary tracts of adults younger than 50 years with asymptomatic microscopic hematuria. Using only unenhanced CT can reduce radiation and minimize contrast agent-associated risk, with a less than 1.0% risk of missing upper urinary tract hematuria-related malignancy.	\N	\N
25151899	To assess the effects of neoadjuvant chemoradiotherapy on survival outcomes of low rectal cancer after sphincter-preserving or removing surgery. A total of 135 patients with rectal cancer within 10 cm from anal verge after neoadjuvant chemoradiotherapy were enrolled into this retrospective study from 2005 to 2012 at a single institute. There were 79 males and 56 females with a mean age of (58 ± 12) years and an average distance of (5.2 ± 2.1) cm from anal verge. The effects of gender, age, distance of tumor from anal verge, surgical procedure, T-stage downstaging, lateral resection margin and post-treatment lymphatic node status on 3-year disease-free survival (DFS) were examined. The overall 3-year DFS was 85.2% (115/135). Among 95 sphincter-preserving operations, there were anterior resection (n = 79), anterior perineal plane for ultra low anterior resection (APPEAR) technique (n = 12), Hartmann procedure (n = 3) and Parks procedure (n = 1). Among 40 sphincter-removing operations, there were abdominoperineal resection (APR) procedure (n = 39) and intersphincteric resection(ISR) (n = 1). The survival of patients undergoing sphincter-preserving or removing procedures did not differ in 3-year DFS (85.3% (81/95) vs 85.0% (34/40) , χ(2) = 0.000, P = 0.985) . Lateral resection margin and post-treatment lymphatic node status significantly affected DFS. The differential level from anal verge showed a trend of close relationship to 3-year DFS (81.5% (22/27) for 2-3 cm, 82.5% (47/57) for 4-5 cm vs 95.1% (39/41) for 6-7 cm), but without statistic significance (χ(2) = 3.111, 3.522; P = 0.078, 0.061). The survival rate for patients with sphincter-preserving at 6-7 cm from anal verge was significantly higher than that at 4-5 cm (95.0% (38/40) vs 79.5% (31/39) ,χ(2) = 4.227, P = 0.039) , but showed no differences to that with sphincter-removing at 2-3 cm from anal verge (81.0% (17/21),χ(2) = 2.864, P = 0.091) . The multivariate analysis showed that post-treatment lymphatic node status was the only prognostic factor to 3-year DFS (Wald = 4.454, P = 0.035) . Lateral resection margin and post-treatment lymphatic node status play an important role on DFS for patients with low rectal cancer after neoadjuvant chemoradiotherapy. The distance from anal verge is correlated with 3-year disease-free survival. Patients with tumor at 4-5 cm from annal verge can not benefit for survival when they get sphincter-preserving operations.	\N	\N
25155018	Frontotemporal dementia (FTD) is the most common cause of dementia in people under 60 yr of age and is pathologically associated with mislocalization of TAR DNA/RNA binding protein 43 (TDP-43) in approximately half of cases (FLTD-TDP). Mutations in the gene encoding progranulin (GRN), which lead to reduced progranulin levels, are a significant cause of familial FTLD-TDP. Grn-KO mice were developed as an FTLD model, but lack cortical TDP-43 mislocalization and neurodegeneration. Here, we report retinal thinning as an early disease phenotype in humans with GRN mutations that precedes dementia onset and an age-dependent retinal neurodegenerative phenotype in Grn-KO mice. Retinal neuron loss in Grn-KO mice is preceded by nuclear depletion of TDP-43 and accompanied by reduced expression of the small GTPase Ran, which is a master regulator of nuclear import required for nuclear localization of TDP-43. In addition, TDP-43 regulates Ran expression, likely via binding to its 3'-UTR. Augmented expression of Ran in progranulin-deficient neurons restores nuclear TDP-43 levels and improves their survival. Our findings establish retinal neurodegeneration as a new phenotype in progranulin-deficient FTLD, and suggest a pathological loop involving reciprocal loss of Ran and nuclear TDP-43 as an underlying mechanism.	\N	\N
25159901	Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic acid (ALA, 18 : 3n-3), a plant-derived long-chain essential n-3 fatty acid, is associated with a lower risk of these outcomes is unclear. The aim of the present study was to examine the associations of plasma phospholipid and dietary ALA with the risk of mortality, CHD and stroke among older adults who participated in the Cardiovascular Health Study, a cohort study of adults aged ≥ 65 years. A total of 2709 participants were included in the plasma phospholipid ALA analysis and 2583 participants were included in the dietary ALA analysis. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with the risk of mortality, incident CHD and stroke. In minimally and multivariable-adjusted models, plasma phospholipid ALA was found to be not associated with the risk of mortality, incident CHD or stroke. After adjustment for age, sex, race, enrolment site, education, smoking status, diabetes, BMI, alcohol consumption, treated hypertension and total energy intake, higher dietary ALA intake was found to be associated with a lower risk of total and non-cardiovascular mortality; on comparing the highest quintiles of dietary ALA with the lowest quintiles, the HR for total mortality and non-cardiovascular mortality were found to be 0·73 (95 % CI 0·61, 0·88) and 0·64 (95 % CI 0·52, 0·80), respectively. Dietary ALA was found to be not associated with the risk of cardiovascular mortality, incident CHD or stroke. In conclusion, the results of the present suggest study that dietary ALA, but not plasma phospholipid ALA, is associated with a lower risk of total and non-cardiovascular mortality in older adults.	\N	\N
25176287	Oxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests. COPD patients (n=40), mean FEV1 58% predicted normal, received single-dose inhaled formoterol 9μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler(®) 320/9μg or formoterol Turbuhaler(®). OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function. OE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p<0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p<0.05) and increased oxygen extraction from the lung by 58% (p<0.01). Single-dose formoterol increased both lung wash-out time (+47%, p<0.05) and lung oxygenation time (+47%, p<0.05). FEV1 was improved by single-dose formoterol (+12%, p<0.001) and 8 weeks of budesonide/formoterol (+ 18%, p<0.001), consistent with published studies. In COPD, OE-MRI parameters showed response to both single-dose bronchodilatory effects of a β2-agonist, formoterol, and 8-week treatment with an inhaled corticosteroid, budesonide, and the measurements are feasible in a small-scale multi-center trial setting.	\N	\N
25178342	In the last decade, the clinical picture of primary hyperparathyroidism has changed, with the majority of patients being diagnosed while asymptomatic and the "classical" clinical pattern characterized by bone disease, recurrent nephrolithiasis, peptic ulcer disease, neurological or psychiatric disorders being rarely encountered. In this context, most patients have minimal hypercalcemia and small parathyroid adenomas. Not surprisingly, giant parathyroid adenomas have seldom been described in the literature. We herein report three cases of giant parathyroid adenomas weighing more than 30 g and discuss their clinicopathological and therapeutic particularities. We also review the relevant literature, with the principal aim of outlining the rarity of these giant parathyroid adenomas and the issues concerning their diagnosis and treatment.	\N	\N
25179307	To explore if inhibition of vitronectin can be used for the treatment of hepatocellular carcinoma. RNAi technology was used to silence the expression of VTN in HepG2 and SMMC 7721 cells. Change of growth characteristics in these cells was evaluated. VTN silencing does not affect growth characteristics of cancer cells in monolayer cell culture, but could suppress the colonized growth of cells in soft agar. VTN-siRNA suppresses colony formation more than 80% compared with that of control in SMMC7721cells and leads to the inhibition of colony formation of over 70% in HepG2 cells. In addition, VTN silencing decreases the size of tumor xenografts in nude mice, particularly in male mice, with an inhibition rate of 46.6%. VTN plays a significant role in the malignant growth of tumor. Inhibition of VTN could potentially be applied for the treatment of hepatocellular carcinoma.	\N	\N
25182131	The difficulties arising from association analysis with rare variants underline the importance of suitable reference population cohorts, which integrate detailed spatial information. We analyzed a sample of 1684 individuals from Western France, who were genotyped at genome-wide level, from two cohorts D.E.S.I.R and CavsGen. We found that fine-scale population structure occurs at the scale of Western France, with distinct admixture proportions for individuals originating from the Brittany Region and the Vendée Department. Genetic differentiation increases with distance at a high rate in these two parts of Northwestern France and linkage disequilibrium is higher in Brittany suggesting a lower effective population size. When looking for genomic regions informative about Breton origin, we found two prominent associated regions that include the lactase region and the HLA complex. For both the lactase and the HLA regions, there is a low differentiation between Bretons and Irish, and this is also found at the genome-wide level. At a more refined scale, and within the Pays de la Loire Region, we also found evidence of fine-scale population structure, although principal component analysis showed that individuals from different departments cannot be confidently discriminated. Because of the evidence for fine-scale genetic structure in Western France, we anticipate that rare and geographically localized variants will be identified in future full-sequence analyses.	\N	\N
25185440	To estimate the prevalence and risk factors of dry eye disease (DED) in a female cohort in the UK. Population-based cross-sectional association study of 3824 women from the TwinsUK cohort aged 20-87 years. A questionnaire was used to evaluate DED and several risk factors. Binary logistic regression, corrected for age, was used to examine the association between DED and risk factors. 9.6% of women had a DED diagnosis and concomitant use of artificial tears, and 20.8% experienced DED symptoms in the past 3 months. Risk factors that were significantly associated with DED were age, asthma, eczema, the presence of any allergy, cataract surgery, rheumatoid arthritis, osteoarthritis, migraine and stroke. The highest effect sizes were found with depression, pelvic pain, irritable bowel syndrome and chronic widespread pain syndrome (all p<0.0005). Subjects with DED symptoms scored significantly lower on self-perceived health, compared with controls (p=0.001). DED is common and increases with age within this cohort of female twins. We confirmed established risk factors for the first time in a British population, and found important risk factors that might relate to an underlying aetiology involving chronic pain predisposition or somatisation.	\N	\N
25187623	The phenomenon that adverse environmental exposures in early life are associated with increased susceptibilities for many adult, particularly metabolic diseases, is now referred to as 'developmental origins of health and disease (DOHAD)' or 'Barker' hypothesis. Fetal overnutrition and undernutrition have similar long-lasting effects on the setting of the neuroendocrine control systems, energy homeostasis, and metabolism, leading to life-long increased morbidity. There are sensitive time windows during early development, where environmental cues can program persistent epigenetic modifications which are generally assumed to mediate these gene-environment interactions. Most of our current knowledge on fetal programing comes from animal models and epidemiological studies in humans, in particular the Dutch famine birth cohort. In industrialized countries, there is more concern about adverse long-term consequences of fetal overnutrition, i.e. by exposure to gestational diabetes mellitus and/or maternal obesity which affect 10-20% of pregnancies. Epigenetic changes due to maternal diabetes/obesity may predispose the offspring to develop metabolic disease later in life and, thus, transmit the adverse environmental exposure to the next generation. This vicious cycle could contribute significantly to the worldwide metabolic disease epidemics. In this review article, we focus on the epigenetics of an adverse intrauterine environment, in particular gestational diabetes, and its implications for the prevention of complex disease.	\N	\N
25197402	After 3 months of combination treatment using interferon α-2a and Ribavirin, a case of 59-year-old female patient with chronic viral hepatitis C demonstrated symptoms such as headache, dizziness accompanied by nausea, vomiting, dry cough, breathing difficulty, and shortness of breath. Dynamic electrocardiogram showed occasional atrial premature beats, paroxysmal tachycardia, and abnormal ST-T (T wave inversion and prolongation of the QT interval). Ambulatory blood pressure indicated that mean blood pressure was elevated than before. Myocardial radionuclide scan showed focal myocardial ischemia in left ventricular inferior wall. Pulmonary function tests showed that pulmonary diffusion function was decreased, indicating the possibility of interstitial pneumonia. The patient had no history of coronary heart disease or chest X-ray abnormalities before medication, but had hypertensive medical history for 8 years with good blood pressure control. After withdrawal of antiviral drugs, symptoms such as dry cough, breathing difficulty and T wave inversion were gradually relieved. This case indicated that myocardial ischemia and pulmonary lesions were associated with the application of pegylated interferon α-2a.	\N	\N
25204216	Acquired immunodeficiency syndrome (AIDS) is a major health problem worldwide. The number of infected people is increasing daily. Knowledge and awareness toward prevention and control of the disease is necessary among both educated and illiterate people. This study is aimed at assessing the knowledge and awareness about human immunodeficiency virus (HIV)/AIDS among undergraduate students studying in a technical institute in Gorakhpur, Uttar Pradesh, India. A community-based cross-sectional study was conducted among youths aged 15-30 years studying in a technical institution in Gorakhpur. Data were collected using a semistructured questionnaire developed with the help of existing literature, from 250 participants (students). The main source of information was the television; knowledge about the difference between HIV/AIDS was satisfactory. The findings showed that the knowledge about modes of prevention (blood checkup, needle/syringe sterilization) was satisfactory. There were several misconceptions about the modes of transmission of the disease, such as through mosquito bites, eating/drinking, and kissing. The knowledge of the study population was satisfactory, and there is a need for innovation and comprehensive education to impart better knowledge and understanding about HIV/AIDS.	\N	\N
25204587	Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder involving both upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Vascular endothelial growth factor (VEGF) was originally described as a factor with a regulatory role in vascular growth and development, and now it also functions as a neurotrophic factor protecting motoneurons from insults such as oxidative stress, hypoxia and glutamate-excitotoxicity, but the role of VEGF in ALS is still unclear. The aim of this study is to measure cerebrospinal fluid (CSF) and serum VEGF levels in patients with ALS, and to investigate whether there are correlations between CSF and serum VEGF levels and clinical parameters of the disease and whether VEGF has a prognostic and evaluating potential for ALS. Results showed that VEGF levels were found to increase significantly in CSF and serum in ALS patients studied; they were positively and significantly correlated with the disease duration in ALS patients and inversely and significantly correlated with disease progression rate (DPR) of ALS patients. Moreover, CSF and serum from ALS patients with long duration and slow disease progression rate revealed higher VEGF levels as compared to ALS patients with short duration and rapid disease progression rate. In conclusion, VEGF upregulation may indicate an activation of compensatory responses in ALS which may reflect or in fact account for increased duration and slow disease progression rate. We propose that VEGF may be a useful biomarker having the prognostic and evaluating potential for ALS.	\N	\N
25216396	Whether carotid artery stenosis predicts stroke after noncardiac surgery remains unknown. We therefore tested the primary hypothesis that degree of carotid artery stenosis is associated with in-hospital stroke or 30-day all-cause mortality after noncardiac surgery. As carotid artery stenosis is also a marker for cardiovascular disease, our secondary hypothesis was that degree of carotid artery stenosis is associated with postoperative myocardial injury. We included adults who had noncardiac, noncarotid surgery at Cleveland Clinic from 2007 to 2011 and had carotid duplex ultrasound performed either within 6 months before or 1 month after surgery. Internal carotid artery peak systolic velocity (ICA PSV) was used as a measure of carotid artery stenosis severity. A multivariate (i.e., multiple outcomes per patient) generalized estimating equation model was used to assess the association between highest ICA PSV and the composite of stroke and 30-day mortality after adjusting for predefined potentially confounding variables. Of 2,110 patients included, 112 (5.3%) died within 30 days and 54 (2.6%) suffered postoperative in-hospital stroke. ICA PSV was not associated with this composite outcome (odds ratio of 1.0 [95% confidence interval: 0.99, 1.02] for a 10-unit increase, P = 0.55). ICA PSV was also not associated with postoperative myocardial injury (odds ratio 1.00 [0.99, 1.02], P = 0.49). This cohort represents a high-risk population, as carotid duplex examinations were likely prompted by neurological symptoms. There was nonetheless no association between carotid artery stenosis and perioperative stroke or 30-day mortality after noncardiac surgery.	\N	\N
25222481	Thrombocytopenia (defined as a platelet count <150×10(9)) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×10(9) to 75×10(9)) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease.	\N	\N
25225437	Cabozantinib (XL184), an oral inhibitor of multiple receptor tyrosine kinases such as MET and VEGFR2, was evaluated in a phase II nonrandomized expansion study in castration-resistant prostate cancer (CRPC). Patients received open-label cabozantinib at daily starting doses of 100 mg or 40 mg until disease progression or unacceptable toxicity. The primary end point was bone scan response, defined as ≥ 30% reduction in bone scan lesion area. Other efficacy end points included overall survival, pain, analgesic use, and biomarkers. One hundred forty-four patients sequentially enrolled in either a 100-mg (n = 93) or 40-mg (n = 51) study cohort. Ninety-one patients (63%) had a bone scan response, often by week 6. Treatment resulted in clinically meaningful pain relief (57% of patients) and reduction or discontinuation of narcotic analgesics (55% of patients), as well as improvements in measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Improvements in each of these outcomes were observed in both cohorts: bone scan response in 73% and 45%, respectively; reductions in measurable soft tissue disease in 80% and 79%, respectively. Median overall survival was 10.8 months for the entire population. Most common grade 3 or 4 adverse events were fatigue (22%) and hypertension (14%). Fewer dose reductions because of toxicity were required in the 40-mg group. The evidence suggests that cabozantinib has clinically meaningful activity in CRPC. Cabozantinib resulted in improvements in bone scans, pain, analgesic use, measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Taken together, these phase II observations warrant further development of cabozantinib in prostate cancer.	\N	\N
25230241	Chagas disease (CD) has been associated with an elevated risk of stroke, but current data are conflicting and prospective controlled studies are lacking. We performed a systematic review and meta-analysis examining the association between stroke and CD. Pubmed, Embase, Cochrane Central, Latin American database, and unpublished data were searched with the use of the following terms: ("Chagas" OR "American trypanosomiasis") AND ("dilated" OR "ischemic" OR "idiopathic" OR "nonChagasic" OR "stroke" OR "cerebrovascular"). We included studies that reported prevalence or incidence of stroke in a CD group compared with a non-CD control group. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed with the use of a random-effects model. A total of 8 studies and 4,158 patients were included, of whom 1,528 (36.7%) had CD. Risk of stroke was elevated in the group of patients with CD (OR 2.10, 95% CI 1.17-3.78). Similar results were observed in a subanalysis of cardiomyopathy patients (OR 1.74, 95% CI 1.02-3.00) and in sensitivity analysis with removal of each individual study. Furthermore, exclusion of studies at higher risk for bias also yielded consistent results (OR 1.70, 95% CI 1.06-2.71). Subanalysis restricted to studies that included patients with the indeterminate form found no significant difference in the stroke prevalence between CD and non-CD patients (OR 3.10, 95% CI 0.89-10.77). CD is significantly associated with cerebrovascular events, particularly among patients with cardiomyopathy. These findings underline the need for prospective controlled studies in patients with Chagas cardiomyopathy to ascertain the prognostic significance of cerebrovascular events and to evaluate the role of therapeutic anticoagulation in primary prevention.	\N	\N
25231249	Drug-induced liver injury (DILI) is a major safety concern during drug development and remains one of the main reasons for withdrawal of drugs from the market. Although it is crucial to develop methods that will detect potential hepatotoxicity of drug candidates as early and as quickly as possible, there is still a lack of sensitive and specific biomarkers for DILI that consequently leads to a scarcity of reliable hepatotoxic data. Hence, in this study, we assessed characteristic molecular signatures in rat liver treated with drugs (pyrazinamide, ranitidine, enalapril, carbamazepine and chlorpromazine) that are known to cause DILI in humans. Unsupervised hierarchical clustering analysis of transcriptome changes induced by DILI-causing drugs resulted in three different subclusters on dendrogram, i.e., hepatocellular, cholestatic and mixed type of DILI at early time points (2 days), and multiclassification analysis suggested 31 genes as discernible markers for each DILI pattern. Further analysis for characteristic molecular signature of each DILI pattern provided a molecular basis for different modes of DILI action. A proteomics study of the same rat livers was used to confirm the results, and the two sets of data showed 60 matching classifiers. In conclusion, the data of different DILI-causing drug treatments from genomic analysis in a rat model suggest that DILI-specific molecular signatures can discriminate different patterns of DILI at an early exposure time point, and that they provide useful information for mechanistic studies that may lead to a better understanding of the molecular basis of DILI.	\N	\N
25297522	Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered.	\N	\N
25302175	Cervical cancer is a worldwide disease that constitutes a significant public health problem, especially in developing countries, not only due to its high incidence but also because the most affected population comprises women who belong to marginalized socio-economic classes. Clinical and molecular research has identified immunological impairment in squamous intraepithelial cervical lesions and cervical cancer patients. Human Papillomavirus (HPV) has several mechanisms for avoiding the immune system: it down-regulates the expression of interferon and upregulates interleukin (IL)-10 and transforming growth factor (TGF)-β1 to produce a local immunosuppressive environment, which, along with altered tumor surface antigens, forms an immunosuppressive network that inhibits the antitumor immune response. In this review we analyzed the available data on several deregulated cellular immune functions in patients with NIC I, NIC II and NIC III and cervical cancer. The effects of immunosuppressive cytokines on innate immune response, T-cell activation and cellular factors that promote tumor cell proliferation in cervical cancer patients are summarized. We discuss the functional consequences of HPV E2, E6, and E7 protein interactions with IL-10 and TGF-β1 promoters in the induction of these cytokines and postulate its effect on the cellular immune response in squamous intraepithelial cervical lesions and cervical cancer patients. This review provides a comprehensive picture of the immunological functions of IL-10 and TGF-β1 in response to HPV in humans.	\N	\N
25305425	Vascular blowout syndrome is a well-known, life-threatening condition complicating advanced-stage head and neck malignancies but has rarely been reported in the gynecologic oncology realm in association with the femoral circulation. A 50-year-old woman with metastatic vulvar squamous cell carcinoma presented with left threatened femoral arterial blowout, secondary to an exophytic neoplastic mass originating from the left inguinal lymph nodes. Bland embolization of the tumor as well as 3 vessel covered stent revascularization was successfully performed with excellent tumor devascularization and reinstitution of arterial integrity. Successful devascularization of the tumor, with no non-target embolization was achieved, with excellent apposition and deployment of 3 covered stents in the femoral artery bifurcation. We present a unique case of threatened femoral artery blowout syndrome in the setting of metastatic vulvar carcinoma requiring various endovascular techniques for palliation. These endovascular techniques can be invaluable in minimally invasive palliation of advanced stage neoplasms abutting the iliofemoral circulation.	\N	\N
25312087	Despite the pressing need for novel cancer treatments, our improved understanding of tumor biology is not being successfully translated into better therapies. Here we present a lentiviral vector that enables in vivo validation of cancer therapeutic targets when combined with existing cancer animal models that faithfully reproduce the natural history of human disease. Unlike the conventional genetic approaches with targeted alleles, the outlined experimental strategy could be used to assess the preclinical efficacy of a growing number of putative therapeutic hits in a rapid and cost-effective manner.	\N	\N
25313751	There is a rising trend in the incidence of (colorectal carcinoma) colorectal cancer (CRC) in India. Nuclear factor kappa B (NFkB) is a transcription factor which belongs to the Rel family. It has an impact on phenomena such as apoptosis, tumor progression and differentiation. (1) To evaluate the grade and stage in 50 cases of colorectal carcinoma. (2) To evaluate the NFkB translocation into the nucleus of the cells. (3) To compare the benign and malignant areas with the degree of NFkB translocation and compare the translocation with the grade and pathological stage. The grade and stage of the tumors was evaluated. NFkB staining was performed on the tissues. The results of the immunostaining were analyzed semi quantitatively as a percentage of positive cells. Statistical Package for Social Sciences 13.0 statistical package program (SPSS, Lead Technologies Inc, USA) for windows was used. Correlation was carried out using the Pearson's correlation co-efficient and the Chi-square test. There were 29 males (58%) and 21 females (42%). Most of the cases were well-differentiated adenocarcinomas (58%). There was a significant difference between NFkB translocation in the epithelial cells and lymphocytes in the benign and malignant areas (P - 0.04 and P - 0.001 respectively). There was a significant correlation between the grade of NFkB staining in the malignant epithelial cells with the tumor and nodal status (P - 0.001 and P - 0.001). It is likely that NFkB is an important factor in the pathogenesis of CRC. Further studies including therapeutic intervention using strategies which prevent activation of NFkB in colorectal carcinoma patients will tell if we could alter the course of the disease favorably.	\N	\N
25320726	Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.	\N	\N
25323223	Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored. Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children. The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality. PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.	\N	\N
25326379	Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is highly expressed in neurons. A possible role for UCH-L1 in neurodegeneration has been highlighted because of its presence in Lewy bodies associated with Parkinson disease and neurofibrillary tangles observed in Alzheimer disease. UCH-L1 exists in two forms in neurons, a soluble cytoplasmic form (UCH-L1(C)) and a membrane-associated form (UCH-L1(M)). Alzheimer brains show reduced levels of soluble UCH-L1(C) correlating with the formation of UCH-L1-immunoreactive tau tangles, whereas UCH-L1(M) has been implicated in α-synuclein dysfunction. Given these reports of divergent roles, we investigated the properties of UCH-L1 membrane association. Surprisingly, our results indicate that UCH-L1 does not partition to the membrane in the cultured cell lines we tested. Furthermore, in primary cultured neurons, a proportion of UCH-L1(M) does partition to the membrane, but, contrary to a previous report, this does not require farnesylation. Deletion of the four C-terminal residues caused the loss of protein solubility, abrogation of substrate binding, increased cell death, and an abnormal intracellular distribution, consistent with protein dysfunction and aggregation. These data indicate that UCH-L1 is differently processed in neurons compared with clonal cell lines and that farnesylation does not account for the membrane association in neurons.	\N	\N
25332150	We conducted this pilot randomized clinical trial to determine the feasibility of a large clinical trial aimed at testing whether early use of catheter ablation of ventricular tachycardia (VT) is superior to antiarrhythmic medications at reducing mortality. Patients were enrolled at 4 sites if they had ischemic heart disease, an implantable cardioverter defibrillator (ICD), and received ≥1 ICD shock or ≥3 antitachycardia pacing therapies for VT. Patients were randomized to 2 arms: (1) antiarrhythmic medication (n = 14) and (2) catheter ablation (n = 13); patients were followed at 3 and 6 months. Endpoints included recurrent VT, time to first ICD therapy for VT, and death. Of 243 screened patients, 27 were enrolled. Main reasons for screen failures were: (1) patient was already on an antiarrhythmic medication (88 [41%]), (2) VT due to a reversible cause (23 [11%]), and (3) incessant VT (20 [9%]). Fourteen patients had recurrent VT, 8 (62%) in the ablation arm and 6 (43%) in the antiarrhythmic medication arm. Median time to recurrent VT was 75 days (25th, 75th: 51, 89) in the ablation arm and 57 days (30, 145) in the antiarrhythmic arm. Four patients died, 2 in each arm. This clinical trial shows that most patients in clinical practice have already failed antiarrhythmic drug therapy before catheter ablation is considered, and the VT recurrence rates and death in these patients are high. For a large clinical trial to be feasible, factors limiting early consideration of catheter ablation need to be identified and addressed.	\N	\N
25336691	To evaluate the relevance between lumican expression patterns and the clinical course of patients with pancreatic ductal adenocarcinoma (PDAC), and to investigate the role of lumican in PDAC progression. One hundred thirty-one patient tumors were chosen for tissue microarray staining, and Cox regression analysis was used to test the associations between lumican expression and clinical, pathologic, and oncologic outcomes in all patients. Primary PDAC cells and recombinant human lumican protein were used to establish a working model to mimic the in vivo interactions between stromal lumican and PDAC cells. Using this model, we tested the effects of lumican on EGFR signaling via Akt and hypoxia-inducible factor-1α (HIF1α) and its subsequent influence on glucose consumption, lactate production, intracellular ATP, and apoptotic cell death. Lumican was present in the stroma surrounding PDAC cells in roughly one-half of primary tumors and the direct xenografts. Patients with stromal lumican were associated with a profound reduction in metastatic recurrence after surgery and 3-fold longer survival than patients without stromal lumican. In PDAC cells, extracellular lumican reduced EGFR expression and phosphorylation through enhanced dimerization and internalization of EGFR and the resultant inhibition of Akt kinase activity. Lumican also reduced HIF1α expression and activity via Akt. PDAC cells with enhanced HIF1α activity were resistant to lumican-induced inhibition of glucose consumption, lactate production, intracellular ATP, and apoptosis. There is a positive association between stromal lumican in primary PDAC tumors and prolonged survival after tumor resection. Lumican plays a restrictive role in EGFR-expressing pancreatic cancer progression.	\N	\N
25348595	Bioorthogonal cleavable linkers are attractive building blocks for compounds that can be manipulated to study biological and cellular processes. Sodium dithionite sensitive azobenzene-containing (Abc) peptides were applied for the temporary stabilization of recombinant MHC complexes, which can then be employed to generate libraries of MHC tetramers after exchange with a novel epitope. This technology represents an important tool for high-throughput studies of disease-specific T cell responses.	\N	\N
25348708	Papillary squamous cell carcinoma (PSCC) of the uterine cervix is difficult to diagnose due to its rarity and limited data regarding its clinical behavior. We attempted to assess the degree of stromal invasion using magnetic resonance imaging (MRI) and evaluate possible treatments for this lesion in view of its clinical behavior. We analyzed 28 cases of PSCC diagnosed on the colposcopic selective biopsies. We studied the rate of accuracy of diagnoses of the colposcopic selective biopsies compared with the final diagnoses, and compared the rate of stromal invasion between the MRI and pathological findings while focusing on surgical methods and the clinical prognosis. Of the 28 patients, only 12 exhibited true PSCC. The other 16 patients were ultimately diagnosed with SCC or adenosquamous carcinoma based on the finding of the surgical specimens and exhibited relatively poor prognoses. Among the 12 true PSCC cases, the rate of diagnostic accuracy of stromal invasion (with or without) was only 58% (7/12) on the colposcopic selective biopsies. However, we were able to predict the presence of stromal invasion (microscopic borderline: approximately 3 mm) before surgery using MRI. None of the 10 patients treated with radical surgery displayed lymph node metastases. In addition, all 12 study patients exhibited no recurrence (mean: 49 months) and survived. MRI can be used to detect preinvasive and microinvasive disease before surgery. It is possible to select a less invasive surgical method than radical surgery in cases of preinvasive and microinvasive PSCC in view of the indolent clinical behavior of this disease.	\N	\N
25348855	This perspective discusses the report by Pinsky and colleagues, which addresses whether noncalcified pulmonary nodules identified on CT screening carry short- and long-term risk for lung cancer. We are facing challenges related to distinguishing a large majority of benign nodules from malignant ones and among those a majority of aggressive from indolent cancers. Key questions in determining individual probabilities of disease, given their history, findings on CT, and upcoming biomarkers of risk, remain most challenging. Reducing the false positives associated with current low-dose computed tomography practices and identification of individuals who need therapy and at what time during tumor surveillance could reduce costs and morbidities associated with unnecessary interventions.	\N	\N
25359996	To determine whether the prescription of co-trimoxazole with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker is associated with sudden death. Population based nested case-control study. Ontario, Canada, from 1 April 1994 to 1 January 2012. Ontario residents aged 66 years or older treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. Each case was matched with up to four controls on age, sex, chronic kidney disease, and diabetes. Odds ratio for the association between sudden death and exposure to each antibiotic relative to amoxicillin, after adjustment for predictors of sudden death according to a disease risk index. Of 39,879 sudden deaths, 1027 occurred within seven days of exposure to an antibiotic and were matched to 3733 controls. Relative to amoxicillin, co-trimoxazole was associated with an increased risk of sudden death (adjusted odds ratio 1.38, 95% confidence interval 1.09 to 1.76). The risk was marginally higher at 14 days (adjusted odds ratio 1.54, 1.29 to 1.84). This corresponds to approximately three sudden deaths within 14 days per 1000 co-trimoxazole prescriptions. Ciprofloxacin (a known cause of QT interval prolongation) was also associated with an increased risk of sudden death (adjusted odds ratio 1.29, 1.03 to 1.62), but no such risk was observed with nitrofurantoin or norfloxacin. In older patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers, co-trimoxazole is associated with an increased risk of sudden death. Unrecognized severe hyperkalemia may underlie this finding. When appropriate, alternative antibiotics should be considered in such patients.	\N	\N
25372658	In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date. From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors. Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, >93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007). Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%.	\N	\N
25375073	As of October 29, 2014, a total of 6,454 Ebola virus disease (Ebola) cases had been reported in Liberia by the Liberian Ministry of Health and Social Welfare, with 2,609 deaths. Although the national strategy for combating the ongoing Ebola epidemic calls for construction of Ebola treatment units (ETUs) in all 15 counties of Liberia, only a limited number are operational, and most of these are within Montserrado County. ETUs are intended to improve medical care delivery to persons whose illnesses meet Ebola case definitions, while also allowing for the safe isolation of patients to break chains of transmission in the community. Until additional ETUs are constructed, the Ministry of Health and Social Welfare is supporting development of community care centers (CCCs) for isolation of patients who are awaiting Ebola diagnostic test results and for provision of basic care (e.g., oral rehydration salts solutions) to patients confirmed to have Ebola who are awaiting transfer to ETUs. CCCs often have less bed capacity than ETUs and are frequently placed in areas not served by ETUs; if built rapidly enough and in sufficient quantity, CCCs will allow Ebola-related health measures to reach a larger proportion of the population. Staffing requirements for CCCs are frequently lower than for ETUs because CCCs are often designed such that basic patient needs such as food are provided for by friends and family of patients rather than by CCC staff. (It is customary in Liberia for friends and family to provide food for hospitalized patients.) Creation of CCCs in Liberia has been led by county health officials and nongovernmental organizations, and this local, community-based approach is intended to destigmatize Ebola, to encourage persons with illness to seek care rather than remain at home, and to facilitate contact tracing of exposed family members. This report describes one Liberian county's approach to establishing a CCC.	\N	\N
25378846	The world-wide use of fireworks with their consequent detrimental effect on the air quality is widely recognized with elevated ambient air levels of particulate matter and its several metallic components and gases identified in several studies carried out during such events. Exposed individuals may be at risk following inhalation of such produced pollutants. This review focuses on the impact of fireworks on air quality and the potential effect of fireworks on the respiratory system of healthy individuals as well as those suffering from underlying respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). This applies not only to spectators including children but also to pyrotechnicians themselves. An extensive Medline search revealed that a strong evidence of the impact of fireworks on respiratory health is lacking in susceptible as well as healthy individuals with no formal studies on COPD or asthma, other than a few case reports in the latter. The implementation of global strategies to control the use of fireworks and hence improve air quality could possibly reduce their likely detrimental effect on human respiratory health in exposed individuals, but clearly a more targeted research is needed.	\N	\N
25380207	In this paper a review of the researches on the role of Escherichia coli strain Nissle 1917 (EcN) in gastrointestinal diseases was presented. EcN is a non-pathogenic strain of the Enterobacteriaceae family, which has probiotic properties. In a number of studies conducted among humans and  experimental animals the application of EcN in treatment of gastrointestinal diseases was observed. Most studies about EcN has been devoted to this organism efficacy in ulcerative colitis treatment. Comparable results were obtained, by citied authors, in the treatment (sustaining remission) of EcN and mesalazine in ulcerative colitis. Moreover, this probiotic therapy, compared to placebo, contributes to obtaining a faster remission and improvement of intestinal histopathology. The use of EcN in Crohn's disease has not been the subject of as many studies as in the case of ulcerative colitis. Assessing the importance of EcN in treatment of other gastrointestinal disorders, authors of the studies observed, that in patients with irritable bowel syndrome, who receiving this probiotic there was a pain, nausea and bloating reduction. In studies conducted among children a positive impact of EcN in prevention and treatment of diarrhea was demonstrated. Similar results were obtained in studies conducted in experimental animals. Based on the presented review it can be concluded that the strain of Escherichia coli Nissle 1917 is useful in treatment of gastrointestinal diseases, especially in treatment of ulcerative colitis. This probiotic may constitute a part of treatment of irritable bowel syndrome and diarrhea. The effectiveness of this strain in treatment of Crohn's disease is not clearly established and further research are require.	\N	\N
25385258	The objective of this meta-analysis was to determine the association of the apolipoprotein E (ApoE) gene with exceptional longevity (EL) (i.e., reaching 100+ years) by identifying possible unequal distribution of alleles/genotypes in the common variants ε2, ε3, and ε4 among centenarians and younger population. The association of ApoE with EL was analyzed in a total of 2776 centenarians (cases) and 11,941 younger controls (from 13 case-control studies) using the chi-squared test with the Yates correction. We conducted combined and separate analyses for all ethnic groups studied in the literature (Caucasian and Asian). The main result for all ethnic groups combined was that the likelihood of reaching EL was negatively associated with ε4 allele carriage [pooled odds ratio (OR)=0.43; 95% confidence interval (CI) 0.36, 0.50; p<0.001] and with ε4/ε4 (OR=0.18; 95% CI 0.08, 0.39; p<0.001), ε3/ε4 (OR=0.44; 95% CI 0.37, 0.53; p<0.001) and ε2/ε4 genotypes (OR=0.48; 95% CI 0.31, 0.74; p<0.001). In contrast, the ε2/ε3 genotype was positively associated with EL (OR=1.35; 95% CI 1.06, 1.72; p=0.017). When compared with the ε3 allele, the ε2 allele was not associated with increased odds of EL (OR=1.08; 95% CI 0.77, 1.50, p=0.660). The present meta-analysis confirms that, besides its previously documented influence on Alzheimer's and cardiovascular disease risk, the ApoE gene is associated with the likelihood of reaching EL.	\N	\N
25386825	Hypertension is the most common cardiovascular disease and remains the most prevalent risk factor for cardiovascular diseases and a major cause of death worldwide. Despite the large number of antihypertensive drugs available, in the majority of patients blood pressure still remains not optimally controlled and persists at high risk of cardiovascular complications. The limitations of current therapies have stimulated the research and development of new classes of antihypertensive agents, with different mechanisms of action, that provide a better blood pressure control, greater protection against organ damage, better tolerability and more effective prevention of cardiovascular diseases. However, essential hypertension is a multifactorial and multigenic disorder, which means that various mechanisms contribute to a greater or lesser extent to increase BP. Recent advances in the understanding of the multiple and complex cellular signalling pathways that modulate vascular smooth muscle cell contraction and growth involved in the regulation of vascular tone and in hypertension-induced end-organ damage have provided valuable insight in identifying new therapeutic targets. This article reviews new antihypertensive drugs under development, focusing on their mechanisms of action and possible advantages compared with traditional drugs.	\N	\N
25391248	We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution within the mineralized matrix. We show that calcium gluconate supplementation can increase bone mineral density in gastrectomized individuals and performs superior to calcium carbonate in restoring calcium/skeletal homoeostasis in a mouse model of achlorhydria.	\N	\N
25391854	Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons. Therefore, the expression level of glutamate transporters could be important in essential tremor pathogenesis. Using Western blotting, we compared the expression levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched controls. We also studied the localization of EAAT1 and EAAT2 using immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein levels were similar in cases and controls (1.12 ± 0.83 vs. 1.01 ± 0.69, p =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of that in controls (0.35 ± 0.23 vs. 1.00 ± 0.62, p < 0.01). Interestingly, EAAT2, but not EAAT1, was expressed in astrocytic processes surrounding the Purkinje cell axon initial segment, a region of previously observed pathological changes in essential tremor. Our main finding, a significant reduction in cerebellar cortical EAAT2 protein levels in essential tremor, suggests that Purkinje cells in essential tremor might be more vulnerable to excitotoxic damage than those of controls.	\N	\N
25400038	Schistosomiasis, one of the most important neglected tropical diseases worldwide, is caused by flatworms (blood flukes or schistosomes) that live in the bloodstream of humans. The hepatointestinal form of this debilitating disease results from a chronic infection with Schistosoma mansoni or Schistosoma japonicum. No vaccine is available to prevent schistosomiasis, and treatment relies predominantly on the use of a single drug, praziquantel. In spite of considerable research effort over the years, very little is known about the complex in vivo events that lead to granuloma formation and other pathological changes during infection. Here we use, for the first time, a lentivirus-based transduction system to deliver microRNA-adapted short hairpin RNAs (shRNAmirs) into the parasite to silence and explore selected protein-encoding genes of S. mansoni implicated in the disease process. This gene-silencing system has potential to be used for functional genomic-phenomic studies of a range of socioeconomically important pathogens.	\N	\N
25400122	We report a 10-year-old male with relapsing Ph-like acute lymphoblastic leukemia (ALL) bearing ATF7IP/PDGFRB translocation. He was refractory to conventional therapy, and was finally treated with single-agent second-generation TKI dasatinib. The therapeutic response was prompt, with the disappearance of minimum residual disease (MRD) based on genomic PCR analysis within 3 months, and he has maintained complete molecular remission for 12 months. This case report describes an early-phase response to TKI monotherapy on Ph-like ALL, and technical tips for MRD monitoring on long-term follow-up.	\N	\N
25404522	Untreated human immunodeficiency virus type 1 (HIV) infection is associated with persistent immune activation, which is an independent driver of disease progression in European and United States cohorts. In Uganda, HIV-1 subtypes A and D and recombinant AD viruses predominate and exhibit differential rates of disease progression. HIV-1 seroconverters (n = 156) from rural Uganda were evaluated to assess the effects of T-cell activation, viral load, and viral subtype on disease progression during clinical follow-up. The frequency of activated T cells was increased in HIV-1-infected Ugandans, compared with community matched uninfected individuals, but did not differ significantly between viral subtypes. Higher HIV-1 load, subtype D, older age, and high T-cell activation levels were associated with faster disease progression to AIDS or death. In a multivariate Cox regression analysis, HIV-1 load was the strongest predictor of progression, with subtype also contributing. T-cell activation did not emerge an independent predictor of disease progression from this particular cohort. These findings suggest that the independent contribution of T-cell activation on morbidity and mortality observed in European and North American cohorts may not be directly translated to the HIV epidemic in East Africa. In this setting, HIV-1 load appears to be the primary determinant of disease progression.	\N	\N
25406883	Periorbital burns are an infrequent but potentially devastating injury. This study aimed to elucidate the spectrum of such injuries presenting to a UK burns centre and the outcome achieved in the cases requiring periorbital reconstruction for the restoration of function and form. Patients admitted to a UK regional burns centre between January 2005 and January 2011 with periorbital burns were identified from the Patient Administration System (PAS), theatre logs and the International Burns Injury database (IBID). Multiple parameters were assessed using patient notes, ITU and hospital image databases. Over 6 years, 167 patients with facial burns requiring surgery were treated, including 103 patients with eyelid burns. The mean burn size was 33% total body surface area. The eyelid burn depth varied; 67% superficial partial thickness, 17% deep dermal and 16% full thickness. Two patients lost complete vision in one eye, one patient underwent amniotic membrane grafting. In total 16 patients required periorbital reconstruction to maintain eye closure, with 1.8 operations on average per patient. Acute surgery was required in 11 patients, whilst late intervention (>3 months) was needed in 5, 2 patients had both acute and delayed surgery. Of the 5 late intervention patients 4 were treated with full thickness skin grafts and 1 with a Z plasty. Average time for final reconstruction with delayed surgery was 4.5 months. The goal in management of periorbital burns is preservation of vision, prevention of future complications and restoration of an acceptable aesthetic outcome. Total visual loss is thankfully rare, but early ophthalmology intervention is vital given the evidence of corneal damage as a brief therapeutic window exists.	\N	\N
25410176	The goal of this cross-sectional observational study was to quantify the pattern-shift visual evoked potentials (VEP) and the thickness as well as the volume of retinal layers using optical coherence tomography (OCT) across a cohort of Parkinson's disease (PD) patients and age-matched controls. Forty-three PD patients and 38 controls were enrolled. All participants underwent a detailed neurological and ophthalmologic evaluation. Idiopathic PD cases were included. Cases with glaucoma or increased intra-ocular pressure were excluded. Patients were assessed by VEP and high-resolution Fourier-domain OCT, which quantified the inner and outer thicknesses of the retinal layers. VEP latencies and the thicknesses of the retinal layers were the main outcome measures. The mean age, with standard deviation (SD), of the PD patients and controls were 63.1 (7.5) and 62.4 (7.2) years, respectively. The patients were predominantly in the initial Hoehn-Yahr (HY) disease stages (34.8% in stage 1 or 1.5, and 55.8 % in stage 2). The VEP latencies and the thicknesses as well as the volumes of the retinal inner and outer layers of the groups were similar. A negative correlation between the retinal thickness and the age was noted in both groups. The thickness of the retinal nerve fibre layer (RNFL) was 102.7 μm in PD patients vs. 104.2 μm in controls. The thicknesses of retinal layers, VEP, and RNFL of PD patients were similar to those of the controls. Despite the use of a representative cohort of PD patients and high-resolution OCT in this study, further studies are required to establish the validity of using OCT and VEP measurements as the anatomic and functional biomarkers for the evaluation of retinal and visual pathways in PD patients.	\N	\N
25412555	Ovary cancer is a disease charged of paradigms and a serious health problem. It's important to know its natural history, because has a multifactor origins, and understanding its behavior since risk factors until patient's death because metastatic disease is a challenger for oncology group. In this work we made a bibliographic, analytic review that brings up concepts related to its origin, evolution, risk factors, preclinical horizon, and clinical symptoms until the death of patient.	\N	\N
25424781	While a PhD candidate, doing my thesis at the Oak Ridge National Laboratory, Biology Division under Dr. Charles Congdon, my introduction to the immune response was studying graft vs. host (GVH) disease as a consequence of bone marrow transplantation in mice. The sequalae of GVH was impressive, and demonstrated the potential of negative clinical consequences of the immune system. The idea of harnessing this immunological phenomena in cancer therapy was appealing even in the late 1960s. The problem was that at the time T-cells as a component of the immune system were identified but not defined. We moved to soluble antigen stimulation in mice and recognized and described the post antigen stimulation changes in lymphatic tissue germinal centers during the first 48 h after the induction of the humoral immune response. We described the extracellular localization of soluble antigens on the surface of dendritic reticular cells of the stroma, directing a response of B-cells to produce antibody against non-self. The ensuing reaction was the rapid proliferation of B-cells toward antibody secreting plasma cells.	\N	\N
25428209	The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) is a multicenter randomized trial of stenting versus endarterectomy in patients with symptomatic and asymptomatic carotid disease. This study assesses management of vascular risk factors. Management was provided by the patient's physician, with biannual monitoring results collected by the local site. Therapeutic targets were low-density lipoprotein, cholesterol <100 mg/dL, systolic blood pressure <140 mm Hg, fasting blood glucose <126 mg/dL, and nonsmoking status. Optimal control was defined as achieving all 4 goals concurrently. Generalized estimating equations were used to compare risk factors at baseline with those observed in scheduled follow-up visits for up to 48 months. In the analysis cohort of 2210, significant improvements in risk-factor control were observed across risk factors for all follow-up visits compared with baseline. At 48 months, achievement of the low-density lipoprotein cholesterol goal improved from 59.1% to 73.6% (P<0.001), achievement of the systolic blood pressure goal improved from 51.6% to 65.1% (P<0.001), achievement of the glucose goal improved from 74.9% to 80.7% (P=0.0101), and nonsmoking improved from 74.4% to 80.9% (P<0.0001). The percentage with optimal risk-factor control also improved significantly, from 16.7% to 36.2% (P<0.001), but nearly 2 of 3 study participants did not achieve optimal control during the study. Site-based risk-factor control improved significantly in the first 6 months and over the long term in CREST but was often suboptimal. Intensive medical management should be considered for future trials of carotid revascularization. ClinicalTrials.gov. Unique identifier: NCT00004732.	\N	\N
25439075	Gastric cancer is the third cause of cancer death worldwide, and Helicobacter pylori infection causes almost 90% of non-cardia cancers, the predominant type. H. pylori infection is treatable, and in clinical trials there is evidence of a 30-40% reduction in incidence of gastric cancer among treated subjects. However, with a few exceptions, there are no public health programmes for gastric cancer prevention. In December 2013, the International Agency for Research on Cancer (IARC), organized a Working Group of international experts to discuss and make recommendations for gastric cancer control. The Working Group considered that the enormous burden of disease, which is not expected to decline in the coming decades, requires decisive public health action to include gastric cancer in cancer control programmes. Interventions should be tailored to the local conditions and consider population-based screening and eradication of H. pylori, in the context of evaluation of feasibility, efficacy and adverse consequences.	\N	\N
25439990	We report a case of KSHV/EBV associated germinotropic lymphoproliferative disorder (LPG) in a 49-year-old African patient, without immunosuppression. LPG is a rare entity arising in immunocompetent patients in opposition to other lymphoproliferative disorders associated to Kaposi sarcoma-associated herpes virus (KSHV). The disease presents itself as localized lymphadenopathy with an infiltration of germinal centers by plasmablastic cells coinfected by KSHV and EBV (Epstein-Barr Virus). After treatment, the outcome is favorable. Differential diagnosis in our case, due to the presence of clusters of Hodgkin-like cells in the mantle zone, included lymphocyte rich classic Hodgkin lymphoma (LHCRL) and nodular lymphocyte predominant Hodgkin lymphoma (LHNPL). Finally, we highlight the differential diagnostic criteria of KSHV lymphoproliferative diseases.	\N	\N
25440885	While important efforts were made in the development of positron emission tomography (PET) tracers for the in vivo molecular diagnosis of Alzheimer's disease, very few investigations to develop magnetic resonance imaging (MRI) probes were performed. Here, a new generation of Gd(III)-based contrast agents (CAs) is proposed to detect the amyloid β-protein (Aβ) aggregates by MRI, one of the earliest biological hallmarks of the pathology. A building block strategy was used to synthesize a library of 16 CAs to investigate structure-activity relationships (SARs) on physicochemical properties and binding affinity for the Aβ aggregates. Three types of blocks were used to modulate the CA structures: (i) the Gd(III) chelates (Gd(III)-DOTA and Gd(III)-PCTA), (ii) the biovectors (2-arylbenzothiazole, 2-arylbenzoxazole and stilbene derivatives) and (iii) the linkers (neutrals, positives and negatives with several lengths). These investigations revealed unexpected SARs and a difficulty of these probes to cross the blood-brain barrier (BBB). General insights for the development of Gd(III)-based CAs to detect the Aβ aggregates are described.	\N	\N
25445322	Aleutian disease virus (ADV, Amdovirus, Parvoviridae) primarily infects farmed mustelids (mink and ferrets) but also other fur-bearing animals and humans. Three Aleutian disease (AD) cases have been described in captive striped skunks; however, little is known about the relevance of AD in free-ranging carnivores. This work describes the pathological findings and temporospatial distribution in 7 cases of AD in free-ranging striped skunks. All cases showed neurologic disease and were found in a 46-month period (2010-2013) within a localized geographical region in California. Lesions included multisystemic plasmacytic and lymphocytic inflammation (ie, interstitial nephritis, myocarditis, hepatitis, meningoencephalitis, pneumonia, and splenitis), glomerulonephritis, arteritis with or without fibrinoid necrosis in several organs (ie, kidney, heart, brain, and spleen), splenomegaly, ascites/hydrothorax, and/or encephalomalacia with cerebral microangiopathy. ADV infection was confirmed in all cases by specific polymerase chain reaction and/or in situ hybridization. The results suggest that AD is an emerging disease in free-ranging striped skunks in California.	\N	\N
25445432	The relationship between pre-hospital care and the prognosis of out-of-hospital cardiac arrest (OHCA) caused by respiratory disease is unclear. This study aimed to assess the impact of pre-hospital care on the prognosis of OHCA caused by respiratory disease. In a nationwide, population-based, observational study, we enrolled 121,081 adults aged ≥18 years who experienced OHCA from January 1, 2010, to December 31, 2010. The primary endpoint was favourable neurological outcomes. Of the 120,256 eligible adult OHCA patients, 7,071 (5.9%) experienced OHCA caused by respiratory disease. Of these 7,071 patients, 3,911 (55.3%) received no cardiopulmonary resuscitation (CPR), 2,403 (34.0%) received chest-compression-only CPR, and 757 (10.7%) received conventional CPR by a bystander. There was no significant difference between the three types of bystander CPR with regard to the neurological outcome (no CPR: OR 0.68, 95%CI 0.39-1.24, p=0.1951; chest-compression-only CPR: OR 0.68, 95%CI 0.37-1.29, p=0.2295; and conventional CPR: as a reference). Pre-hospital administration of epinephrine (OR 0.37, 95%CI 0.13-0.85, p=0.0170) and the implementation of advanced airway management (OR 0.32, 95%CI 0.19-0.52, p<0.0001) were associated with poor neurological outcomes. Even in OHCA caused by respiratory disease, not only pre-hospital epinephrine administration but also pre-hospital advanced airway management and rescue breathing in bystander CPR may not be critical.	\N	\N
25456683	Group A streptococcal (GAS) infections are frequent in developing countries but the epidemiology is incompletely known. In 2005, 90 % of symptomatic pharyngitis, 96 % of invasive diseases and 97 % of deaths due to GAS were observed in these countries. Clinical features of GAS invasive infections are identical to those reported in developed countries, but frequency and mortality are higher, as is the number of the different emm types involved. In the world, from 15.6 to 19.6 millions of persons are affected by rheumatic heart disease (282,000 new cases and 233,000-468,000 deaths per year). Incidence of acute post-streptococcal glomerulonephritis varies with time and location: in 2005, 472,000 new cases have been reported in the world (83 % in a developing country). World Heart Federation recently aimed at reducing the burden of rheumatic heart diseases by 25 % among < 25 years persons in 2025.	\N	\N
25467562	Patients are increasingly being admitted with chronic atrial fibrillation, and disease-specific management might reduce recurrent admissions and prolong survival. However, evidence is scant to support the application of this therapeutic approach. We aimed to assess SAFETY--a management strategy that is specific to atrial fibrillation. We did a pragmatic, multicentre, randomised controlled trial in patients admitted with chronic, non-valvular atrial fibrillation (but not heart failure). Patients were recruited from three tertiary referral hospitals in Australia. 335 participants were randomly assigned by computer-generated schedule (stratified for rhythm or rate control) to either standard management (n=167) or the SAFETY intervention (n=168). Standard management consisted of routine primary care and hospital outpatient follow-up. The SAFETY intervention comprised a home visit and Holter monitoring 7-14 days after discharge by a cardiac nurse with prolonged follow-up and multidisciplinary support as needed. Clinical reviews were undertaken at 12 and 24 months (minimum follow-up). Coprimary outcomes were death or unplanned readmission (both all-cause), measured as event-free survival and the proportion of actual versus maximum days alive and out of hospital. Analyses were done on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTRN 12610000221055). During median follow-up of 905 days (IQR 773-1050), 49 people died and 987 unplanned admissions were recorded (totalling 5530 days in hospital). 127 (76%) patients assigned to the SAFETY intervention died or had an unplanned readmission (median event-free survival 183 days [IQR 116-409]) and 137 (82%) people allocated standard management achieved a coprimary outcome (199 days [116-249]; hazard ratio 0·97, 95% CI 0·76-1·23; p=0·851). Patients assigned to the SAFETY intervention had 99·5% maximum event-free days (95% CI 99·3-99·7), equating to a median of 900 (IQR 767-1025) of 937 maximum days alive and out of hospital. By comparison, those allocated to standard management had 99·2% (95% CI 98·8-99·4) maximum event-free days, equating to a median of 860 (IQR 752-1047) of 937 maximum days alive and out of hospital (effect size 0·22, 95% CI 0·21-0·23; p=0·039). A post-discharge management programme specific to atrial fibrillation was associated with proportionately more days alive and out of hospital (but not prolonged event-free survival) relative to standard management. Disease-specific management is a possible strategy to improve poor health outcomes in patients admitted with chronic atrial fibrillation. National Health and Medical Research Council of Australia.	\N	\N
25470167	This article provides a practical clinical approach for the role of exercise in the treatment and management of neurologic disorders. A number of clinical studies have reported positive benefits from exercise in various neurologic disease states, suggesting that this mode of intervention should be considered as another option in clinical management. Significant evidence-based data exists confirming the positive effects of exercise in otherwise healthy populations. Good evidence also exists that physical activity may benefit people with long-term neurologic conditions. Despite this evidence, exercise is often neglected in patients with normal aging or neurologic disease progression. Neurologists should counsel patients on this therapeutic adjunct and provide specific recommendations when possible.	\N	\N
25476560	Cardiovascular risk remains uncertain in patients with cardiovascular disease despite achieving target lipid levels. Serum levels of lipoprotein(a) [Lp(a)] can be risk factors for adverse events. The aim of this study was to determine the role of Lp(a) as a residual risk factor in patients who achieve target lipid levels by the time of treatment by percutaneous coronary intervention (PCI). A total of 3,508 patients were treated by PCI from 1997 to 2011 at our institution. Among them, we analyzed consecutive 569 patients who achieved target lipid levels of low-density lipoprotein cholesterol <100 mg/dl, high-density lipoprotein cholesterol ≥40 mg/dl, and triglycerides <150 mg/dl at PCI. A total of 411 eligible patients were assigned to groups according to Lp(a) levels of ≥30 mg/dl (high Lp(a); n = 119) or <30 mg/dl (low Lp(a); n = 292). The primary outcome was a composite of all-cause death and acute coronary syndrome. The median follow-up period was 4.7 years. Cumulative event-free survival was significantly worse for the group with high Lp(a) than with low Lp(a) group (p = 0.04). Multivariate analysis selected a high Lp(a) level as an independent predictor of primary outcomes (hazard ratio 1.68, 95% confidence interval 1.03 to 2.70, p = 0.04). In conclusion, a high Lp(a) value (≥30 mg/dl) could be associated with a poor prognosis after PCI even for patients who achieved target lipid levels.	\N	\N
25481243	The presence of somatic mutations in splicing factor 3b subunit 1 (SF3B1) in patients with Myelodysplastic syndromes with ring sideroblasts (MDS-RS) highlights the importance of the RNA-splicing machinery in MDS. We previously reported the presence of bone marrow (BM) RS in Sf3b1 heterozygous (Sf3b1 (+/-)) mice which are rarely found in mouse models of MDS. Sf3b1 (+/-) mice were originally engineered to study the interaction between polycomb genes and other proteins. We used routine blood tests and histopathologic analysis of BM, spleen, and liver to evaluate the hematologic and morphologic characteristics of Sf3b1 (+/-) mice in the context of MDS by comparing the long term follow-up (15 months) of Sf3b1 (+/-) and Sf3b1 (+/+) mice. We then performed a comprehensive RNA-sequencing analysis to evaluate the transcriptome of BM cells from Sf3b1 (+/-) and Sf3b1 (+/+) mice. Sf3b1 (+/-) exhibited macrocytic anemia (MCV: 49.5 ± 1.6 vs 47.2 ± 1.4; Hgb: 5.5 ± 1.7 vs 7.2 ± 1.0) and thrombocytosis (PLTs: 911.4 ± 212.1 vs 878.4 ± 240.9) compared to Sf3b1 (+/+) mice. BM analysis showed dyserythropoiesis and occasional RS in Sf3b1 (+/-) mice. The splenic architecture showed increased megakaryocytes with hyperchromatic nuclei, and evidence of extramedullary hematopoiesis. RNA-sequencing showed higher expression of a gene set containing Jak2 in Sf3b1 (+/-) compared to Sf3b1 (+/+). Our study indicates that Sf3b1 (+/-) mice manifest features of low risk MDS-RS and may be relevant for preclinical therapeutic studies.	\N	\N
25482988	Cancer cell metabolism is deregulated, and signalling pathways can be involved. For instance, PI3K/Akt/mTOR is associated with normal proliferation and differentiation, and its alteration is detectable in cancer cells, that exploit the normal mechanisms to overcome apoptosis. On the other hand, also the family of Phospholipase C (PLC) enzymes play a critical role in cell growth, and any change concerning these enzymes or their downstream targets can be associated with neoplastic transformation. Here, we review the role of PLC and PI3K/Akt/mTOR signal transduction pathways in pathophysiology.	\N	\N
25486686	The current economic difficulties and the changed epidemiological picture, characterized by an increase in life expectancy, which shows in the elderly, chronically ill and disabled the main, both health and social, care needs,r equires a remark on the hospital network and organization. Today, most of the application assistance is usually at low intensity of care, whereas the acute event is shrinking. The prevalence of hospital admissions concern the elderly, who get into acute events but on a substrate of chronicity and co-morbidity conditions. There must be a new model of hospital network, with the possibility of converting some hospital centres for medium intensity care and selecting few centres for high intensity care, where concentrating the more expensive technology and the skill and expertise of the professional. The -suggestion is a renewed health planning that detects:- hospitals for widespread disease, equipped with emergency war for minor codes-hospital at high intensity of care for emergency-urgency- hospital for particular fields of medical speciality and research.	\N	\N
25497401	We present a Dutch family with a novel disease-causing mutation in the mitochondrial tRNA(Ser(UCN)) gene, m.7507A>G. The index patient died during the neonatal period due to cardio-respiratory failure and fatal lactic acidosis. A second patient, his cousin, has severe hearing loss necessitating cochlear implants and progressive exercise intolerance. Laboratory investigations of both patients revealed combined deficiencies of the enzyme complexes of the mitochondrial respiratory chain in several tissues. Reduced levels of fully assembled complexes I and IV in fibroblasts by BN-PAGE associated with (near) homoplasmic levels of the m.7507A>G mutation in several tissues and a severe reduction in the steady-state level of mt-tRNA(Ser(UCN)) in fibroblasts were observed. The novel mitochondrial DNA mutation was shown to segregate with disease; several healthy maternal family members showed high heteroplasmy levels (up to 76 ± 4% in blood and 68 ± 4% in fibroblasts) which did not lead to any alterations in the activities of the enzyme complexes of the respiratory chain in fibroblasts or clinical signs and symptoms. We hereby conclude that the m.7507A>G mutation causes a heterogeneous clinical phenotype and is only pathogenic at very high levels of mtDNA heteroplasmy.	\N	\N
25500436	The abnormal formation and insufficient clearance of neutrophil extracellular traps (NETs) has been reported to be involved in the pathogenesis of lupus nephritis (LN). The abnormal regulation of NETs may contribute to increases in the levels of circulating cell-free DNA (cfDNA). The present study tested the hypothesis that elevated plasma cfDNA levels are related to LN. Fifty-four systemic lupus erythematosus (SLE) patients and 43 control subjects were included in this study. The cfDNA concentrations were measured using the Picogreen Kit, the low-density granulocyte (LDG) percentage in peripheral blood mononuclear cells (PBMCs) was tested using a flow cytometer and the DNase I activity was measured according to the radial enzyme-diffusion method. The mean cfDNA concentration in the SLE group was 236.66±40.09 ng/mL, which was significantly higher than that observed in the healthy control group (187.96±40.55 ng/mL, p<0.0001). Meanwhile, the mean cfDNA concentration in the patients with LN was significantly higher than that observed in the patients without LN (247.27±46.79 ng/mL vs. 213.56±31.34 ng/mL, p=0.0094), and the mean cfDNA concentration in the patients with active LN was significantly higher than that observed in the patients with inactive LN (254.22±50.16 ng/mL vs. 215.93±29.10 ng/mL, p=0.0349). In the SLE group, the cfDNA concentration was to positively correlate with the quantitative 24-hour urinary protein (r=0.350, p=0.013), LDG (r=0.6361, p=0.0019) and neutrophil (r=0.5990, p<0.0001) levels and inversely correlate with the albumin level (r=-0.500, p<0.0001) and endogenous creatinine clearance rate (r=-0.354, p=0.044). Compared to that observed in the control group, the SLE group exhibited a significantly increased percentage of LDGs in PBMCs and a significantly decreased DNase I activity. Our data indicate that elevated plasma cfDNA concentrations may be associated with active LN and partially attributed to the abnormal regulation of NETs in SLE patients, thus suggesting that NETs constitute an intrinsic link between cfDNA and active LN.	\N	\N
25524212	The cause of type 1 diabetes remains unknown. To dissect the link between hyperexpression of human leukocyte antigen (HLA) class I on the islet cells, we examined its expression in subjects with recent-onset type 1 diabetes. IHC showed seemingly pronounced hyperexpression in subjects with recent-onset type 1 diabetes, as well as in some nondiabetic subjects. In all subjects, HLA class I expression on exocrine tissue was low. However, no difference in the level of HLA class I expression was found between islet and exocrine tissue using Western blot, flow cytometry, real-time quantitative PCR, or RNA sequencing analyses. Also, the level of HLA class I expression on the messenger level was not increased in islets from subjects with recent-onset type 1 diabetes compared with that in nondiabetic subjects. Consistently, the HLA class I specific enhanceosome (NLRC5) and related transcription factors, as well as interferons, were not enhanced in islets from recent-onset type 1 diabetic subjects. In conclusion, a discrepancy in HLA class I expression in islets assessed by IHC was observed compared with that using quantitative techniques showing similar expression of HLA class I in islets and exocrine tissue in subjects with recent-onset type 1 diabetes, nor could any differences be found between type 1 diabetic and nondiabetic subjects. Results presented provide important clues for a better understanding on how this complex disease develops.	\N	\N
25536728	Brucellosis is an important disease in developing countries. We aimed to determine the epidemiologic, clinical, and laboratory characteristics of brucellosis, which still has a high morbidity in Turkey. Seventy-two patients with brucellosis, monitored at our clinic from January 2004 to July 2010, were reviewed retrospectively. The average age was determined to be 44.8 ± 18 years, and 40 of the patients were female (55.6%). The most frequent transmission route was the use of raw milk and dairy products, in 45 of the patients (62.5%). The most frequent complaints were joint pain, high fever, weakness, low back pain, and gastrointestinal symptoms, whereas the most frequent physical examination findings were fever, osteoarticular involvement, splenomegaly, hepatomegaly, and lymphadenopathy. All of the patients were positive for Rose Bengal testing. The standard tube agglutination titer was 1/160 or higher in 64 (88.9%) patients. Brucella melitensis was isolated from blood cultures of 13 (18.1%) patients and bone marrow cultures of 7 (9.7%) patients. Complications of sacroiliitis in 6 (8.3%), spondylodiscitis in 4 (5.6%), endocarditis in 2 (2.8%), neurobrucellosis in 1 (1.4%), and epididymo-orchitis in 1 (1.4%) of the patients were observed. Brucellosis has various clinical presentations. It should be included in the differential diagnosis of high fever and joint pains in endemic countries.	\N	\N
25539271	Pancreatic adenocarcinoma is a rapidly progressive malignancy characterized by its tendency for early metastatic spread. MDCT is the primary diagnostic modality for the preoperative staging of patients with pancreatic cancer, with an accuracy established in multiple studies. However, for a variety of reasons, there is often a prolonged interval between staging MDCT and the surgical intervention. This study examines the relationship between the interval between imaging and surgery and the accuracy of MDCT in determining the presence or absence of metastatic disease at surgery in patients with pancreatic cancer. Patients were identified who had undergone surgery for pancreatic cancer at our institution with a dedicated preoperative pancreas-protocol MDCT performed in our department. Findings from the preoperative MDCT report were correlated with the operative findings, as well as the time between imaging and surgery. Two hundred ninety-two MDCT scans were performed on 256 patients who underwent exploration for pancreatic adenocarcinoma. The patients had a median age of 67 years (range, 30-95 years), and 51.6% (132/256) were male. The median time between MDCT and surgical exploration was 15.5 days (range, 1-198 days). MDCT correctly predicted the absence of metastatic disease at surgery in 233 of 274 (85.0%) studies. MDCT was more accurate in predicting the absence of metastatic disease if the study was performed within 25 days of surgery than it was if the study was performed within more than 25 days of surgery (89.3% vs 77.0%; p = 0.0097). Furthermore, regression models showed that the negative predictive value of a given MDCT significantly decreased after approximately 4 weeks. MDCT is an accurate method to stage patients with pancreatic cancer, but its accuracy in excluding distant metastatic disease depreciates over time. Patients should undergo a repeat MDCT within 25 days of any planned definitive operative intervention for pancreatic cancer to avoid unexpectedly finding metastatic disease at surgery.	\N	\N
25545990	Dependence on invasive procedures for classification of patients with Sjögren's syndrome (SS) hampers timely diagnosis and suitable patient followup. The aim of this study was to recapitulate the diagnosis of SS through noninvasive means and to define the biologic state of SS patients' salivary glands. Using a 187-plex capture antibody-based assay, salivary proteomic biomarker profiles were generated from patients with primary SS, patients with rheumatoid arthritis, and asymptomatic controls. Discriminant function analyses and Gene Ontology-based network analyses allowed data analyses with a reductionist approach and with a focus on systems biology. Characterized by significant changes in 61 and 55 proteins, respectively, the salivary proteome of SS patients appeared profoundly altered compared to that of individuals without SS. On this basis, 4-plex and 6-plex biomarker signatures, both including interleukin-4 (IL-4), IL-5, and clusterin, achieved accurate prediction of an individual's group membership for at least 94% of cases. Of note, all misclassified SS patients presented with ectopic germinal center-like structures. Systematic inference of biologic meaning identified SS-related protein patterns delineating B cell-dominated immune responses, macrophage differentiation, and signs of T cell chemotaxis. In addition, proteomic Multi-Analyte Profiles provided insight about proteins related to collagen, cytokine, and growth factor synthesis as well as lipid transport. The SS-related molecular landscape conveyed by saliva showed great congruence with histopathologic features found in SS and advances understanding of this disease at a molecular level. Such salivary biomarker signatures harbor great potential for improving timeliness of SS diagnosis and enabling suitable patient followup.	\N	\N
25546563	Sjögren's Syndrome (SS) is an autoimmune disease that causes sicca (dryness) symptoms by affecting secretions most notably of the lacrimal and salivary glands. Voice disorders have been documented in patients with SS, but the true prevalence and relationships among possible contributing factors remain unknown. This preliminary epidemiological investigation examined prevalence and risk factors for voice disorders in SS. Self-report epidemiological questionnaire. One hundred and one (101) patients with SS (94 females, 7 males; M age = 59.4 years; standard deviation [SD] = 14.1 years) completed an extensive interview using a previously validated questionnaire involving the patient's medical, family, occupational, psychosocial, social/lifestyle, voice use, and general health histories. Summary statistics, chi-squares, risk ratios, and multiple logistic regression were used to determine the frequency and severity of voice disorders in individuals with SS, as well as associations with demographic, lifestyle, health, disease severity, and voice use factors. The prevalence of a current voice disorder in individuals with SS was 59.4%. In general, voice disorders began gradually; were chronic; and correlated with SS disease severity independent of age, sex, duration of the disease, comorbid autoimmune conditions, and use of SS-related medication. Specific voice symptoms including chronic throat dryness and soreness were significantly associated with SS disease severity. Voice disorders are relatively common in SS and are more frequent as disease severity worsens. These findings have important implications for evaluation and treatment of patients with SS. 4.	\N	\N
25549186	After injection into muscle and peripheral nerves, a variety of viral vectors undergo retrograde transport to lower motor neurons. However, because of its attractive safety profile and durable gene expression, adeno-associated virus (AAV) remains the only vector to have been applied to the human nervous system for the treatment of neurodegenerative disease. Nonetheless, only a very small fraction of intramuscularly injected AAV vector arrives at the spinal cord. To engineer a novel AAV vector by inserting a neuronal targeting peptide (Tet1), with binding properties similar to those of tetanus toxin, into the AAV1 capsid. Integral to this approach was the use of structure-based design to increase the effectiveness of functional capsid engineering. This approach allowed the optimization of scaffolding regions for effective display of the foreign epitope while minimizing disruption of the native capsid structure. We also validated an approach by which low-titer tropism-modified AAV vectors can be rescued by particle mosaicism with unmodified capsid proteins. Importantly, our rationally engineered AAV1-based vectors exhibited markedly enhanced transduction of cultured motor neurons, diminished transduction of nontarget cells, and markedly superior retrograde delivery compared with unmodified AAV1 vector. This approach promises a significant advancement in the rational engineering of AAV vectors for diseases of the nervous system and other organs.	\N	\N
25549677	To explore the clinical features of neuromyelitis optica (NMO) spectrum disease (NMOSD) with connective tissue disease (CTD). The clinical features of 184 NMO/NMOSD patients (NMO/NMOSD: 119/184, 64.7%; NMO/NMOSD-CTD: 65/184, 35.3%) from May 2013 to May 2014 were analyzed retrospectively. And the effectiveness of long-term treatment of immunosuppressive drugs in NMOSD was evaluated. NMO/NMOSD-CTD patients had significantly higher female percentage (93.8% vs 83.2%, P < 0.05) and significantly higher percentage of patients with cerebral spinal fluid (CSF)-restricted oligoclonal band (OB)(41.5% vs 21.9%, P < 0.05). As compared with NMO/NMOSD-CTD counterparts, NMO/NMOSD patients had significantly higher percentage of non-specific lesions on brain MRI (62.5% vs 35.9%, P < 0.01). After >6 months consecutive long-term treatment of immunosuppressive drugs, the relapse rate post-treatment (0.36 ± 0.85) was significantly lower than that pre-treatment (2.91 ± 4.10, P < 0.01). And no significant difference existed in expanded disability status scale (EDSS) score between pre-and post-treatment. When using azathioprine (AZA), the percentage of relapse was significantly higher in NMO/NMOSD-CTD patients (50.0%) versus NMO/NMOSD ones (18.5%, P = 0.064); When using cyclophosphamide (CTX), there was no such significant difference. Female patients are more susceptible to have NMO/NMOSD with CTD. NMO/NMOSD-CTD patients tend to have higher percentage of CSF-restricted OB and fewer non-specific lesions on brain MRI. AZA and CTX may effectively reduce relapses in both NMO/NMOSD and NMO/NMOSD-CTD patients. However CTX is superior to AZA for reducing relapses in NMO/NMOSD-CTD patients.	\N	\N
25551964	The aim of this study was to investigate if vaginal preparation procedure affects the occurrence of oocyte pickup-associated pelvic inflammation (OPU-PI) and the reproductive outcome in an in vitro fertilization (IVF) program. The occurrence of OPU-PI and the reproductive outcome were compared between 956 infertile patients undergoing vaginal preparation with saline douching alone versus 1,216 infertile patients undergoing a combination ofpovidone iodine disinfection and subsequent saline douching in an IVF program. OPU-PI occurred in four patients (0.042%) in the saline douching alone group, whereas there were no cases in the combination group (p = 0.016). There were no significant differences in the rate of fertilization, morphologically good embryo acquisition, clinical and ongoing pregnancy between the two groups (p > 0.23). This large cohort study demonstrated that a combination of vaginal povidone iodine disinfection and subsequent saline douching is more effective procedure than saline douching alone to prevent OPU-PI, without spoiling the oocyte quality.	\N	\N
25553466	Hemophilia is an X-linked inherited bleeding disorder consisting of two classifications, hemophilia A and hemophilia B, depending on the underlying mutation. Although the disease is currently treatable with intravenous delivery of replacement recombinant clotting factor, this approach represents a significant cost both monetarily and in terms of quality of life. Gene therapy is an attractive alternative approach to the treatment of hemophilia that would ideally provide life-long correction of clotting activity with a single injection. In this review, we will discuss the multitude of approaches that have been explored for the treatment of both hemophilia A and B, including both in vivo and ex vivo approaches with viral and nonviral delivery vectors.	\N	\N
25553772	Farnesoid x receptor (FXR) belongs to the group of nuclear receptors (NRs), which regulate the expression of various genes by binding to DNA either as a monomer or a heterodimer with retinoid x receptor. FXR affects several metabolic pathways through its specific target genes, regulating bile acid (BA) synthesis and homeostasis, glucose and lipid metabolism, also exhibiting a crucial role in intestinal bacterial growth and liver regeneration. Additionally, FXR is involved in the pathogenesis of different cholestatic diseases, as well as non-alcoholic fatty liver disease, inflammatory bowel disease (IBD) and primary idiopathic BA malabsorption. Analyses of certain FXR polymorphisms revealed associations with clinical phenotypes and susceptibility to various human diseases. FXR single-nucleotide polymorphisms seem to be correlated with differences in glucose homeostasis, gallstone formation, intrahepatic cholestasis of pregnancy, IBD and therapeutic response to hypolipidemic therapy, among studied populations. Unfortunately, little data are still available and more studies remain to be done to determine the contribution of FXR polymorphisms in estimating risk factors and clinical outcomes for several diseases.	\N	\N
25575898	The Hundred Person Wellness Project is an ambitious pilot undertaking, which aims to intensely monitor 100 individuals over 10 months. Patients with abnormal findings will be treated, in hopes that this early intervention will avoid, or delay, symptomatic disease. Google's "Baseline Study" is of similar scope and will enroll 10,000 people over 2 to 3 years. I here speculate that these approaches will likely not be effective in preventing disease, but instead, lead to unnecessary and potentially harmful interventions. Examples from the cancer screening experience over the last 30 years are provided, which show that intensive testing may uncover indolent disease or incidental findings which, when treated, may cause more harm than good. Additional examples show that aggressive treatments for cancer and other diseases do not always lead to better patient outcomes. I conclude that the recent advances in omics provide us with unprecedented opportunities for high content clinical testing, but such testing should be used with caution to avoid the harmful consequences of over-diagnosis and over-treatment. Despite the detailed rebuttals by Hood and colleagues in another commentary in BMC Medicine, time will show the actual benefits and harms of these ambitious initiatives.	\N	\N
25585384	In 2014, a major epidemic of human Ebola virus disease emerged in West Africa, where human-to-human transmission has now been sustained for greater than 12 months. In the summer of 2014, there was great uncertainty about the answers to several key policy questions concerning the path to containment. What is the relative importance of nosocomial transmission compared with community-acquired infection? How much must hospital capacity increase to provide care for the anticipated patient burden? To which interventions will Ebola transmission be most responsive? What must be done to achieve containment? In recent years, epidemic models have been used to guide public health interventions. But, model-based policy relies on high quality causal understanding of transmission, including the availability of appropriate dynamic transmission models and reliable reporting about the sequence of case incidence for model fitting, which were lacking for this epidemic. To investigate the range of potential transmission scenarios, we developed a multi-type branching process model that incorporates key heterogeneities and time-varying parameters to reflect changing human behavior and deliberate interventions in Liberia. Ensembles of this model were evaluated at a set of parameters that were both epidemiologically plausible and capable of reproducing the observed trajectory. Results of this model suggested that epidemic outcome would depend on both hospital capacity and individual behavior. Simulations suggested that if hospital capacity was not increased, then transmission might outpace the rate of isolation and the ability to provide care for the ill, infectious, and dying. Similarly, the model suggested that containment would require individuals to adopt behaviors that increase the rates of case identification and isolation and secure burial of the deceased. As of mid-October, it was unclear that this epidemic would be contained even by 99% hospitalization at the planned hospital capacity. A new version of the model, updated to reflect information collected during October and November 2014, predicts a significantly more constrained set of possible futures. This model suggests that epidemic outcome still depends very heavily on individual behavior. Particularly, if future patient hospitalization rates return to background levels (estimated to be around 70%), then transmission is predicted to remain just below the critical point around Reff = 1. At the higher hospitalization rate of 85%, this model predicts near complete elimination in March to June, 2015.	\N	\N
25590983	Pseudomonas aeruginosa, the predominant cause of chronic airway infections of patients with cystic fibrosis, exhibits extensive phenotypic diversity among isolates within and between sputum samples, but little is known about the underlying genetic diversity. To characterize the population genetic structure of transmissible P. aeruginosa Liverpool Epidemic Strain in chronic infections of nine patients with cystic fibrosis, and infer evolutionary processes associated with adaptation to the cystic fibrosis lung. We performed whole-genome sequencing of P. aeruginosa isolates and pooled populations and used comparative analyses of genome sequences including phylogenetic reconstructions and resolution of population structure from genome-wide allele frequencies. Genome sequences were obtained for 360 isolates from nine patients. Phylogenetic reconstruction of the ancestry of 40 individually sequenced isolates from one patient sputum sample revealed the coexistence of two genetically diverged, recombining lineages exchanging potentially adaptive mutations. Analysis of population samples for eight additional patients indicated coexisting lineages in six cases. Reconstruction of the ancestry of individually sequenced isolates from all patients indicated smaller genetic distances between than within patients in most cases. Our population-level analysis demonstrates that coexistence of distinct lineages of P. aeruginosa Liverpool Epidemic Strain within individuals is common. In several cases, coexisting lineages may have been present in the infecting inoculum or assembled through multiple transmissions. Divergent lineages can share mutations via homologous recombination, potentially aiding adaptation to the airway during chronic infection. The genetic diversity of this transmissible strain within infections, revealed by high-resolution genomics, has implications for patient segregation and therapeutic strategies.	\N	\N
25595571	Noonan Syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Autoimmune Hepatitis (AIH) is a cryptogenic, chronic and progressive necroinflammatory liver disease. Common features of AIH are hypergammaglobulinemia (IgG), presence of circulating autoantibodies, histological picture of interface hepatitis and response to immunosuppressant drugs. Conventional treatment with Prednisone and Azathioprine is effective in most patients. We describe the case of a 6 years-old girl with Noonan Syndrome and Autoimmune Hepatitis type 1. Molecular analysis of PTPN11 gene showed heterozygous mutation c.923A>G (Asn308Ser) in exon 8. Though association between NS and autoimmune disorders is known, this is the second case of association between Noonan Syndrome and Autoimmune Hepatitis type 1 described in literature. In the management of NS, an accurate clinical evaluation would be recommended. When there is a clinical suspicion of autoimmune phenomena, appropriate laboratory tests should be performed with the aim of clarifying whether the immune system is involved in NS. We think that autoimmunity represents a characteristic of NS, even if the etiopathogenesis is still unknown.	\N	\N
25600917	Hepatitis B virus surface antigen (HBsAg) levels reflect disease status and can predict the clinical response to antiviral treatment; however, the emergence of HBsAg mutant strains has become a challenge. The Abbott HBsAg quantification assay provides enhanced detection of HBsAg and HBsAg mutants. We aimed to evaluate the performance of the Abbott HBsAg quantification assay with automatic sample dilutions (shortened as automatic Architect assay), compared with the Abbott HBsAg quantification assay with manual sample dilutions (shortened as manual Architect assay) and the Roche HBsAg quantification assay with automatic sample dilutions (shortened as Elecsys). A total of 130 sera samples obtained from 87 hepatitis B virus (HBV)-infected patients were collected to assess the correlation between the automatic and manual Architect assays. Among the 87 patients, 41 provided 42 sera samples to confirm the linearity and reproducibility of the automatic Architect assay, and find out the correlation among the Elecsys and two Architect assays. The coefficients of variation (0.44-9.53%) and R(2) = 0.996-1, which were both determined using values obtained from the automatic Architect assay, showed good reproducibility and linearity. Results of the two Architect assays demonstrated a feasible correlation (n = 130 samples; R = 0.898, p < 0.01). With regard to subgroups, correlations between the two Architect assays were better in the hepatitis B e antigen (HBeAg)-negative group (HBeAg-negative group vs. HBeAg-positive group: R = 0.885 vs. R = 0.865, both p < 0.01) and low HBV DNA group (low DNA group vs. high DNA group: R = 0.886 vs. R = 0.844, both p < 0.01). Significant correlations were also found between the results of the Elecsys and Architect assays (R > 0.93 in all cases). In conclusion, the correlation between the automatic and manual dilution Architect assays was feasible, particularly in the HBeAg-negative and low DNA groups. With lower labor costs and less human error than the manual version, the Abbott automatic dilution Architect assay provided a good clinical performance with regard to the HBsAg levels.	\N	\N
25601965	Many cancer patients receive supplemental ascorbate (vitamin C) in the belief that it synergizes the anticancer effects of chemotherapy and reduces its toxicity. A systematic review was performed to evaluate the antitumor effects and toxicity of ascorbate treatment. Medline (1946 to March 2014), EMBASE (1947 to March 2014), and the Cochrane central register (1993 to March 2014) were searched for randomized and observational studies. Of 696 identified records, 61 full-text articles were screened and 34 were included. In total, 5 randomized controlled trials (RCTs) (n = 322), 12 phase I/II trials (n = 287), 6 observational studies (n = 7,599), and 11 case reports (n = 267) were identified. Because of study heterogeneity, no meta-analyses were performed. No RCTs reported any statistically significant improvements in overall or progression-free survival or reduced toxicity with ascorbate relative to control arm. Evidence for ascorbate's antitumor effects was limited to case reports and observational and uncontrolled studies. There is no high-quality evidence to suggest that ascorbate supplementation in cancer patients either enhances the antitumor effects of chemotherapy or reduces its toxicity. Given the high financial and time costs to patients of this treatment, high-quality placebo-controlled trials are needed.	\N	\N
25602998	No current therapy for relapsing-remitting multiple sclerosis (MS) results in significant reversal of disability. To determine the association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability and other clinical outcomes in patients with MS. Case series of patients with relapsing-remitting MS (n = 123) or secondary-progressive MS (n = 28) (mean age, 36 years; range, 18-60 years; 85 women) treated at a single US institution between 2003 and 2014 and followed up for 5 years. Final follow-up was completed in June 2014. Treatment with cyclophosphamide and alemtuzumab (22 patients) or cyclophosphamide and thymoglobulin (129 patients) followed by infusion of unmanipulated peripheral blood stem cells. Primary end point was reversal or progression of disability measured by change in the Expanded Disability Status Scale (EDSS) score of 1.0 or greater (score range, 0-10). Secondary outcomes included changes in the Neurologic Rating Scale (NRS) score of 10 or greater (score range, 0-100), Multiple Sclerosis Functional Composite (MSFC) score, quality-of-life Short Form 36 questionnaire scores, and T2 lesion volume on brain magnetic resonance imaging scan. Outcome analysis was available for 145 patients with a median follow-up of 2 years and a mean of 2.5 years. Scores from the EDSS improved significantly from a pretransplant median of 4.0 to 3.0 (interquartile range [IQR], 1.5 to 4.0; n = 82) at 2 years and to 2.5 (IQR, 1.9 to 4.5; n = 36) at 4 years (P < .001 at each assessment). There was significant improvement in disability (decrease in EDSS score of ≥1.0) in 41 patients (50%; 95% CI, 39% to 61%) at 2 years and in 23 patients (64%; 95% CI, 46% to 79%) at 4 years. Four-year relapse-free survival was 80% and progression-free survival was 87%. The NRS scores improved significantly from a pretransplant median of 74 to 88.0 (IQR, 77.3 to 93.0; n = 78) at 2 years and to 87.5 (IQR, 75.0 to 93.8; n = 34) at 4 years (P < .001 at each assessment). The median MSFC scores were 0.38 (IQR, -0.01 to 0.64) at 2 years (P < .001) and 0.45 (0.04 to 0.60) at 4 years (P = .02). Total quality-of-life scores improved from a mean of 46 (95% CI, 43 to 49) pretransplant to 64 (95% CI, 61 to 68) at a median follow-up of 2 years posttransplant (n = 132) (P < .001). There was a decrease in T2 lesion volume from a pretransplant median of 8.57 cm3 (IQR, 2.78 to 22.08 cm3) to 5.74 cm3 (IQR, 1.88 to 14.45 cm3) (P < .001) at the last posttransplant assessment (mean follow-up, 27 months; n = 128). Among patients with relapsing-remitting MS, nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes. These preliminary findings from this uncontrolled study require confirmation in randomized trials.	\N	\N
25622254	The accumulation and aggregation of misfolded proteins in the brain, such as amyloid-β (Aβ) and hyperphosphorylated tau, is a neuropathological hallmark of Alzheimer's disease (AD). Previously, we developed and validated a novel non-human primate model for sporadic AD (sAD) research using intracerebroventricular administration of streptozotocin (icv STZ). To date, no characterization of AD-related genes in different brain regions has been performed. Therefore, in the current study, the expression of seven amyloid precursor protein (APP) pathway-related and five tau phosphorylation-related genes was investigated by quantitative real-time PCR experiments, using two matched-pair brain samples from control and icv STZ-treated cynomolgus monkeys. The genes showed similar expression patterns within the control and icv STZ-treated groups; however, marked differences in gene expression patterns were observed between the control and icv STZ-treated groups. Remarkably, other than β-secretase (BACE1) and cyclin-dependent kinase 5 (CDK5), all the genes tested showed similar expression patterns in AD models compared to controls, with increased levels in the precuneus and occipital cortex. However, significant changes in gene expression patterns were not detected in the frontal cortex, hippocampus, or posterior cingulate. Based on these results, we conclude that APP may be cleaved via the general metabolic mechanisms of increased α- and γ-secretase levels, and that hyperphosphorylation of tau could be mediated by elevated levels of tau protein kinase, specifically in the precuneus and occipital cortex.	\N	\N
25631478	The dihydropteroate sulfate (DHPS) gene is associated with resistance to sulfa/sulfone drugs in Pneumocystis jirovecii. We investigated the DHPS mutation rate in three groups of Iranian HIV-positive and HIV-negative patients by polymerase chain reaction-restricted fragment length polymorphism analysis. Furthermore, an association between P. jirovecii DHPS mutations and strain typing was investigated based on direct sequencing of internal transcribed spacer region 1 (ITS1) and ITS2. The overall P. jirovecii DHPS mutation rate was (5/34; 14.7%), the lowest rate identified was in HIV-positive patients (1/16; 6.25%) and the highest rate was in malignancies patients (3/11; 27.3%). A moderate rate of mutation was detected in chronic obstructive pulmonary disease (COPD) patients (1/7; 14.3%). Most of the isolates were wild type (29/34; 85.3%). Double mutations in DHPS were detected in patients with malignancies, whereas single mutations at codons 55 and 57 were identified in the HIV-positive and COPD patients, respectively. In this study, two new and rare haplotypes were identified with DHPS mutations. Additionally, a positive relationship between P. jirovecii strain genotypes and DHPS mutations was identified. In contrast, no DHPS mutations were detected in the predominant (Eg) haplotype. This should be regarded as a warning of an increasing incidence of drug-resistant P. jirovecii strains.	\N	\N
25636578	Psoriasis is a T cell-dependent immune-mediated disease of the skin and joints. It is clear that co-stimulatory and co-inhibitory molecules (currently named co-signaling molecules collectively) synergize with TCR signaling to promote or inhibit T cell activation and function. In recent years, enthusiasm in the field of co-signaling research has been fueled by the success of co-stimulatory and co-inhibitory immunotherapy for the treatment of human diseases. This review outlines the involvement of several sets of co-signaling molecules in the immunopathogenesis of psoriasis. We then describe the relevant preclinical studies and summarize recent clinical findings on targeting these molecules for the treatment of psoriasis.	\N	\N
25648029	Western blot is the gold standard method to determine individual protein expression levels. However, western blot is technically difficult to perform in large sample sizes because it is a time consuming and labor intensive process. Dot blot is often used instead when dealing with large sample sizes, but the main disadvantage of the existing dot blot techniques, is the absence of signal normalization to a housekeeping protein. In this study we established a one dot two development signals (ODTDS) dot blot method employing two different signal development systems. The first signal from the protein of interest was detected by horseradish peroxidase (HRP). The second signal, detecting the housekeeping protein, was obtained by using alkaline phosphatase (AP). Inter-assay results variations within ODTDS dot blot and western blot and intra-assay variations between both methods were low (1.04-5.71%) as assessed by coefficient of variation. ODTDS dot blot technique can be used instead of western blot when dealing with large sample sizes without a reduction in results accuracy.	\N	\N
25656590	The purpose of this study was to examine the practice patterns of intraoperative completion imaging (CI) for lower extremity bypass (LEB) in the Vascular Quality Initiative (VQI). A retrospective review of all LEB procedures in the VQI database from January 2003 to October 2013 was performed. Regions with fewer than 200 LEB procedures were excluded from the regional analysis. The modality of CI was defined as duplex ultrasound, angiography, or both. A total of 14,140 LEBs were captured, with the rate of CI being 43%. After exclusion of three regions for insufficient volume (<200 LEBs), 13,945 LEB operations across 13 regions were available for regional analysis. Use of any type of intraoperative CI varied across regions from a low of 8% to a high of 70%, with angiography being performed most frequently. When CI was performed, the type of imaging modality varied between regions from a high of 99% for angiography to a high of 75% for duplex ultrasound. CI was more common in male patients (44% of male patients vs 42% of female patients; P = .032), diabetics (44% of diabetic patients vs 42% of nondiabetic patients; P = .026), and patients with coronary artery disease (45% of patients with coronary artery disease vs 42% of patients with no coronary artery disease; P = .0015). CI was performed less frequently in LEB using single-segment great saphenous vein vs LEB using lesser saphenous, arm, or composite vein (48% vs 57%; P < .0001). CI was used in 51% of LEBs with a tibial or pedal target vessel vs 38% of LEBs with a more proximal target vessel (P < .0001). Patients with an indication of critical limb ischemia underwent CI in 45% of LEBs vs 39% with an indication other than critical limb ischemia (P < .0001). Within the VQI database, considerable practice pattern variation exists in the use of CI. Currently, CI is most commonly employed for patients with critical limb ischemia, infrageniculate target vessel, and disadvantaged venous conduit. Further study is required to standardize and to define the appropriate use of CI for LEBs.	\N	\N
25659158	Dengue virus infection is a leading cause of morbidity among children in the Philippines in recent years. In order to investigate the association of HLA Class I and II alleles and dengue disease severity in a cohort of Filipino children, we performed a case control study in 2 hospitals in Metro Manila from June 2008 to December 2009. A total of 250 laboratory confirmed dengue patients and 300 healthy individuals aged 5 to 15 years old were typed for HLA-A, B and DRB1 alleles. The frequency of HLA-A*33:01 was significantly decreased in severe dengue (DHF/ DSS; Pc = 0.0016)) and DSS (Pc = 0.0032) compared to the background population. These findings support a previous study that this allele may confer protection against the severe form of dengue and provide the first evidence of HLA association with dengue in the Philippines. Future studies should be directed in investigating the possible mechanisms of protection.	\N	\N
25659380	The 18th WHO Global Tuberculosis Annual Report indicates that there were an estimated 8.6 million incident cases of tuberculosis (TB) in 2012, which included 2.9 million women and 530,000 children. TB caused 1.3 million deaths including 320,000 human immunodeficiency virus (HIV)-infected people; three-quarters of deaths occurred in Africa and Southeast Asia. With one-third of the world's population latently infected with Mycobacterium tuberculosis (Mtb), active TB disease is primarily associated with a break down in immune surveillance. This explains the strong link between active TB disease and other communicable diseases (CDs) or noncommunicable diseases (NCDs) that exert a toll on the immune system. Comorbid NCD risk factors include diabetes, smoking, malnutrition, and chronic lung disease, all of which have increased relentlessly over the past decade in developing countries. The huge overlap between killer infections such as TB, HIV, malaria, and severe viral infections with NCDs, results in a "double burden of disease" in developing countries. The current focus on vertical disease programs fails to recognize comorbidities or to encourage joint management approaches. This review highlights major disease overlaps and discusses the rationale for better integration of tuberculosis care with services for NCDs and other infectious diseases to enhance the overall efficiency of the public health responses.	\N	\N
25662376	To determine the number, distribution and cost of hospital admissions for chronic obstructive pulmonary disease (COPD) in New Zealand. National patient-level routine data on admissions with a principal diagnosis of COPD (mostly ICD-10- AN J440 and J441) were obtained for the period July 1st 2008 to June 30th 2013. Admissions with length of stay (LOS) = 90 days were excluded. There were 61,516 admissions in 5 years. Admission rates and budget impact (in 2012/13 dollar values) were stable but the average length of stay (ALOS) declined from 5.09 to 4.37 days. In FY2012/13 the admission rate was 2.82 per 1000 population, with age standardised rate (ASR) 4.4- and 3.6-fold higher for Maori and Pacific peoples respectively than for European/others. For age = 15 years the ASR was 2.55 per 1000. Admission rates were higher for men than women and increased steeply with age and socioeconomic deprivation (NZDep06). The mean age at discharge was lower for Maori and Pacific peoples than for European/Others (63.4, 67.1 and 72.3 years). The mean 30-day readmission rate was 6.7%. The average LOS increased with age and was shorter for Maori (3.6 days) and Pacific peoples (3.5 days) than for European/Others (4.7 days). Admission rates varied widely across District Health Boards, and were higher in rural than urban regions. The estimated cost of admissions in FY2012/13 was $NZ59.6m. Hospital admissions for COPD are costly and are over-represented in high risk groups including rural, elderly, socioeconomically deprived and Maori and Pacific peoples. Effective interventions that are targeted to high risk groups are required to improve equity and reduce the burden of COPD.	\N	\N
25664604	A novel oral octreotide formulation was tested for efficacy and safety in a phase III, multicenter, open-label, dose-titration, baseline-controlled study in patients with acromegaly. We enrolled 155 complete or partially controlled patients (IGF-1 <1.3 × upper limit of normal [ULN], and 2-h integrated GH <2.5 ng/mL) receiving injectable somatostatin receptor ligand (SRL) for ≥ 3 months. Subjects were switched to 40 mg/d oral octreotide capsules (OOCs), and the dose escalated to 60 and then up to 80 mg/d to control IGF-1. Subsequent fixed doses were maintained for a 7-month core treatment, followed by a voluntary 6-month extension. Of 151 evaluable subjects initiating OOCs, 65% maintained response and achieved the primary endpoint of IGF-1 <1.3 × ULN and mean integrated GH <2.5 ng/mL at the end of the core treatment period and 62% at the end of treatment (up to 13 mo). The effect was durable, and 85 % of subjects initially controlled on OOCs maintained this response up to 13 months. When controlled on OOCs, GH levels were reduced compared to baseline, and acromegaly-related symptoms improved. Of 102 subjects completing the core treatment, 86% elected to enroll in the 6-month extension. Twenty-six subjects who were considered treatment failures (IGF-1 ≥ 1.3 × ULN) terminated early, and 23 withdrew for adverse events, consistent with those known for octreotide or disease related. OOC, an oral therapeutic peptide, achieves efficacy in controlling IGF-1 and GH after switching from injectable SRLs for up to 13 months, with a safety profile consistent with approved SRLs. OOC appears to be effective and safe as an acromegaly monotherapy.	\N	\N
25675517	Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by joint destruction and severe morbidity. Methotrexate (MTX) is the standard first-line therapy of RA. However, about 40% of RA patients are unresponsive to MTX treatment. Regulatory T cells (Tregs, CD4(+)CD25(+)FoxP3(+)) are thought to play an important role in attenuating RA. To investigate the role of Tregs in MTX resistance, we recruited 122 RA patients (53 responsive, R-MTX; 69 unresponsive, UR-MTX) and 33 healthy controls. Three months after MTX treatment, R-MTX but not UR-MTX showed higher frequency of peripheral blood CD39(+)CD4(+)CD25(+)FoxP3(+) Tregs than the healthy controls. Tregs produce adenosine (ADO) through ATP degradation by sequential actions of two cell surface ectonucleotidases: CD39 and CD73. Tregs from UR-MTX expressed a lower density of CD39, produced less ADO, and had reduced suppressive activity than Tregs from R-MTX. In a prospective study, before MTX treatment, UR-MTX expressed a lower density of CD39 on Tregs than those of R-MTX or control (P < 0.01). In a murine model of arthritis, CD39 blockade reversed the antiarthritic effects of MTX treatment. Our results demonstrate that MTX unresponsiveness in RA is associated with low expression of CD39 on Tregs and the decreased suppressive activity of these cells through reduced ADO production. Our findings thus provide hitherto unrecognized mechanism of immune regulation in RA and on mode of action of MTX. Furthermore, our data suggest that low expression of CD39 on Tregs could be a noninvasive biomarker for identifying MTX-resistant RA patients.	\N	\N
25675716	Cardiorehabilitation of patients with multivessel coronary lesions is an obligatory component of ambulatory stage of care. With the aim of potentiating cardioprotective and antiischemic impact of rehabilitative preventive measures in 36 patients with ischemic heart disease (IHD) and multivessel coronary artery involvement who had undergone percutaneous coronary intervention we studied cardioprotective and antiischemic effect of long-term (24 weeks) administration of 70 mg/day trimetazidine in combination with moderate intensity physical training with the use of distance surveillance by a physician. The chosen therapeutic approach in patients with residual ischemia after incomplete anatomical revascularization provided early persistent formation of cardioprotective and antiischemic effect proven by increase of tolerance to physical exercise, improvement of diastolic function, and positive dynamics of both ECG parameters and biochemical markers of myocardial ischemia.	\N	\N
25678847	5-Fluorouracil (5Fu) chemotherapy is the first treatment of choice for advanced gastric cancer (GC), but its effectiveness is limited by drug resistance. Emerging evidence suggests that the existence of cancer stem cells (CSCs) contributes to chemoresistance. The aim of the present study was to determine whether 5Fu chemotherapy generates residual cells with CSC-like properties in GC. Human GC cell lines, SGC7901 and AGS, were exposed to increasing 5Fu concentrations. The residual cells were assessed for both chemosensitivity and CSC-like properties. B lymphoma Mo-MLV insertion region 1 (BMI1), a putative CSC protein, was analyzed by immunohistochemical staining and subjected to pairwise comparison in GC tissues treated with or without neoadjuvant 5Fu-based chemotherapy. The correlation between BMI1 expression and recurrence-free survival in GC patients who received 5Fu-based neoadjuvant chemotherapy was then examined. The residual cells exhibited 5Fu chemoresistance. These 5Fu-resistant cells displayed some CSC features, such as a high percentage of quiescent cells, increased self-renewal ability and tumorigenicity. The 5Fu-resistant cells were also enriched with cells expressing cluster of differentiation (CD)133+, CD326+ and CD44+CD24-. Moreover, the BMI1 gene was overexpressed in 5Fu-resistant cells, and BMI1 knockdown effectively reversed chemoresistance. The BMI1 protein was highly expressed consistently in the remaining GC tissues after 5Fu-based neoadjuvant chemotherapy, and BMI1 levels were correlated positively with recurrence-free survival in GC patients who received 5Fu-based neoadjuvant chemotherapy. Our data provided molecular evidence illustrating that 5Fu chemotherapy in GC resulted in acquisition of CSC-like properties. Moreover, enhanced BMI1 expression contributed to 5Fu resistance and may serve as a potential therapeutic target to reverse chemoresistance in GC patients.	\N	\N
25679282	There is inconsistency among the perioperative management strategies currently used for chronic subdural hematoma (cSDH). Moreover, postoperative complications such as acute intracranial bleeding and cSDH recurrence affect clinical outcome of cSDH surgery. This study evaluated the risk factors associated with acute intracranial bleeding and cSDH recurrence and identified an effective perioperative strategy for cSDH patients. A retrospective study of patients who underwent bur hole craniostomy for cSDH between 2008 and 2012 was performed. A consecutive series of 303 cSDH patients (234 males and 69 females; mean age 67.17 years) was analyzed. Postoperative acute intracranial bleeding developed in 14 patients (4.57%) within a mean of 3.07 days and recurrence was observed in 37 patients (12.21%) within a mean of 31.69 days (range 10-104 days) after initial bur hole craniostomy. The comorbidities of hematological disease and prior shunt surgery were clinical factors associated with acute bleeding. There was a significant risk of recurrence in patients with diabetes mellitus, but recurrence did not affect the final neurological outcome (p = 0.776). Surgical details, including the number of operative bur holes, saline irrigation of the hematoma cavity, use of a drain, and type of postoperative ambulation, were not significantly associated with outcome. However, a large amount of drainage was associated with postoperative acute bleeding. Bur hole craniostomy is an effective surgical procedure for initial and recurrent cSDH. Patients with hematological disease or a history of prior shunt surgery are at risk for postoperative acute bleeding; therefore, these patients should be carefully monitored to avoid overdrainage. Surgeons should consider informing patients with diabetes mellitus that this comorbidity is associated with an increased likelihood of recurrence.	\N	\N
25680251	The orbital manifestations of acquired immunodeficiency syndrome(AIDS) are uncommon. To provide a review of orbital manifestations of AIDS, the predisposing factors, investigations, treatment and outcome. Meticulous and systematic literature search of Pubmed to identify manuscripts describing orbital manifestations of AIDS was done and the articles were reviewed.The keywords used in the search were “orbit and AIDS”, “HIV positive and orbit”,“orbit manifestations in AIDS”, “orbital disease and AIDS” and “orbital infections and AIDS”. The orbital involvement in AIDS may present with opportunistic infections from organisms like fungi, viruses, bacteria and protozoa or with malignancies like Kaposi’s sarcoma, squamous cell carcinoma, smooth muscle cell tumors and lymphoma.The predisposing factors for orbital involvement in AIDS are low CD4+ cell count and the immunosuppressive states like diabetes, diabetic ketoacidosis, intravenous drug abuse and neutropenia. A patient may present with fever, headache, nausea, vomiting,decreased vision, ocular pain, and, in cases of mass formation, there is periorbital swelling, axial proptosis, globe displacement and swollen optic disc. Radiologically,mass formation, orbital bony destruction, and spread of disease to contiguous structures including the central nervous system may be seen. The medical management includes therapy for infection and HIV-1 protease inhibitors (highly active antiretroviral therapy)to suppress HIV-1 replication. For tumors, radical surgery including debulking followed by postoperative radiotherapy is generally needed. Orbital involvements with AIDS in any form, infective or malignancy, causes significant morbidity and mortality and should be diagnosed and managed as early as possible.	\N	\N
25682204	The goal of this study is to validate a new, continuous, noninvasive stroke volume (SV) method, known as transbrachial electrical bioimpedance velocimetry (TBEV). TBEV SV was compared to SV obtained by cardiac magnetic resonance imaging (cMRI) in normal humans devoid of clinically apparent heart disease. Thirty-two (32) volunteers were enrolled in the study. Each subject was evaluated by echocardiography to assure that no aortic or mitral valve disease was present. Subsequently, each subject underwent electrical interrogation of the brachial artery by means of a high frequency, low amplitude alternating current. A first TBEV SV estimate was obtained. Immediately after the initial TBEV study, subjects underwent cMRI, using steady-state precession imaging to obtain a volumetric estimate of SV. Following cMRI, the TBEV SV study was repeated. Comparing the cMRI-derived SV to that of TBEV, the two TBEV estimates were averaged and compared to the cMRI standard. CO was computed as the product of SV and heart rate. Statistical methods consisted of Bland-Altman and linear regression analysis. TBEV SV and CO estimates were obtained in 30 of the 32 subjects enrolled. Bland-Altman analysis of pre- and post-cMRI TBEV SV showed a mean bias of 2.87 % (2.05 mL), precision of 13.59% (11.99 mL) and 95% limits of agreement (LOA) of +29.51% (25.55 mL) and -23.77% (-21.45 mL). Regression analysis for pre- and post-cMRI TBEV SV values yielded y = 0.76x + 25.1 and r(2) = 0.71 (r = 0.84). Bland-Altman analysis comparing cMRI SV with averaged TBEV SV showed a mean bias of -1.56% (-1.53 mL), precision of 13.47% (12.84 mL), 95% LOA of +24.85% (+23.64 mL) and -27.97% (-26.7 mL) and percent error = 26.2 %. For correlation analysis, the regression equation was y = 0.82x + 19.1 and correlation coefficient r(2) = 0.61 (r = 0.78). Bland-Altman analysis of averaged pre- and post-cMRI TBEV CO versus cMRI CO yielded a mean bias of 5.01% (0.32 L min(-1)), precision of 12.85% (0.77 L min(-1)), 95% LOA of +30.20 % (+0.1.83 L min(-1)) and -20.7% (-1.19 L min(-1)) and percent error = 24.8%. Regression analysis yielded y = 0.92x + 0.78, correlation coefficient r(2) = 0.74 (r = 0.86). TBEV is a novel, noninvasive method, which provides satisfactory estimates of SV and CO in normal humans.	\N	\N
25713121	Lyme disease is the most important vector-borne disease in the Northern hemisphere and represents a major public health challenge with insufficient means of reliable diagnosis. Skin is rarely investigated in proteomics but constitutes in the case of Lyme disease the key interface where the pathogens can enter, persist, and multiply. Therefore, we investigated proteomics on skin samples to detect Borrelia proteins directly in cutaneous biopsies in a robust and specific way. We first set up a discovery gel prefractionation-LC-MS/MS approach on a murine model infected by Borrelia burgdorferi sensu stricto that allowed the identification of 25 Borrelia proteins among more than 1300 mouse proteins. Then we developed a targeted gel prefractionation-LC-selected reaction monitoring (SRM) assay to detect 9/33 Borrelia proteins/peptides in mouse skin tissue samples using heavy labeled synthetic peptides. We successfully transferred this assay from the mouse model to human skin biopsies (naturally infected by Borrelia), and we were able to detect two Borrelia proteins: OspC and flagellin. Considering the extreme variability of OspC, we developed an extended SRM assay to target a large set of variants. This assay afforded the detection of nine peptides belonging to either OspC or flagellin in human skin biopsies. We further shortened the sample preparation and showed that Borrelia is detectable in mouse and human skin biopsies by directly using a liquid digestion followed by LC-SRM analysis without any prefractionation. This study thus shows that a targeted SRM approach is a promising tool for the early direct diagnosis of Lyme disease with high sensitivity (<10 fmol of OspC/mg of human skin biopsy).	\N	\N
25716730	Allogeneic bone marrow transplantation (allo-BMT) is currently the only way to cure many hematoproliferative disorders. However, allo-BMT use is limited by severe complications, the foremost being graft-versus-host disease (GVHD). Due to the lack of efficiency of the existing methods of GVHD prophylaxis, new methods are being actively explored, including the use of donors' multipotent mesenchymal stromal cells (MMSC). In this work, we analyzed the results of acute GVHD (aGVHD) prophylaxis by means of MMSC injections after allo-BMT in patients with hematological malignancies. The study included 77 patients. They were randomized into two groups - those receiving standard prophylaxis of aGVHD and those who were additionally infused with MMSC derived from the bone marrow of hematopoietic stem cell donors. We found that the infusion of MMSC halves the incidence of aGVHD and increases the overall survival of patients. Four of 39 MMSC samples were ineffective for preventing aGVHD. Analysis of individual donor characteristics (gender, age, body mass index) and the MMSC properties of these donors (growth parameters, level of expression of 30 genes involved in proliferation, differentiation, and immunomodulation) revealed no significant difference between the MMSC that were effective or ineffective for preventing aGVHD. We used multiple logistic regression to establish a combination of features that characterize the most suitable MMSC samples for the prevention of aGVHD. A model predicting MMSC sample success for aGVHD prophylaxis was constructed. Significant model parameters were increased relative expression of the FGFR1 gene in combination with reduced expression levels of the PPARG and IGF1 genes. Depending on the chosen margin for probability of successful application of MMSC, this model correctly predicts the outcome of the use of MMSC in 82-94% of cases. The proposed model of prospective evaluation of the effectiveness of MMSC samples will enable prevention of the development of aGVHD in the maximal number of patients.	\N	\N
25721731	Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR-TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45-15.33] and nonsteroidal anti-inflammatory drugs (OR: 6.54; 95% CI: 3.19-12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33-0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63-2.34), smoking (OR: 1.93; 95% CI: 1.54-2.61), family history of GC (OR: 2.83; 95% CI: 2.01-3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07-1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12-1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16-1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse-type GC (hazard ratio: 1.85; 95% CI: 1.12-3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians.	\N	\N
25727171	In this study, we investigated the vasorelaxant and antihypertensive effects of gallic acid (GA), a polyphenol isolated from the green alga Spirogyra sp., to assess its suitability as a therapeutic for cardiovascular diseases (CVDs). We examined the effect of GA on endothelium-dependent vasorelaxation in human umbilical vein endothelial cells (HUVECs). GA increased nitric oxide (NO) levels by increasing phosphorylation of endothelial nitric oxide synthase (eNOS), and its effect on NO production was attenuated by pretreatment with the eNOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). We also investigated its antihypertensive effect by examining GA-mediated inhibition of angiotensin-I converting enzyme (ACE). GA inhibited ACE with a half-maximal inhibitory concentration (IC50) value of 37.38 ± 0.39 μg/ml. In silico simulations revealed that GA binds to the active site of ACE (PDB: 1O86) with a binding energy of -270.487 kcal/mol. Furthermore, GA clearly reduced blood pressure in spontaneously hypertensive rats (SHR) to an extent comparable to captopril. These results suggest that GA isolated from Spirogyra sp. exerts multiple therapeutic effects and has potential as a CVD treatment.	\N	\N
25728727	The American Heart Association (AHA) established recommendations based on 7 ideal health behaviors and factors with the goal of improving cardiovascular health (CVH) and reducing both morbidity and mortality from cardiovascular disease by 20% by 2020. Few studies have investigated their association with subclinical coronary heart disease. We sought to examine whether the 7 AHA CVH metrics were associated with calcified atherosclerotic plaque in the coronary arteries. In a cross-sectional design, we studied 1,731 predominantly white men and women from the National Heart, Lung, and Blood Institute Family Heart Study without prevalent coronary heart disease. Diet was assessed by a semiquantitative food frequency questionnaire. Coronary artery calcium (CAC) was measured by cardiac computed tomography. We defined prevalent CAC using an Agatston score of 100+ and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age was 56.8 years, and 41% were male. The median number of ideal CVH metrics was 3, and no participant met all 7. There was a strong inverse relationship between number of ideal CVH metrics and prevalent CAC. Odds ratios (95% CI) for CAC of 100+ were 1.0 (reference), 0.37 (0.29-0.45), 0.35 (0.26-0.44), and 0.27 (0.20-0.36) among subjects with 0 to 1, 2, 3, and 4+ ideal CVH metrics, respectively (P = .0001), adjusting for sex, age, field center, alcohol, income, education, and energy consumption. These data demonstrate a strong and graded inverse relationship between AHA ideal CVH metrics and prevalent CAC in adult men and women.	\N	\N
25738293	Celiac disease (CD) is an autoimmune disease induced by an autoimmune reaction to indigested gluten, which occurs in genetically predisposed population. The etiology of CD is linked to innate and adaptive immunity, mostly mediated by lymphocytes, especially T cells, infiltrating into the small intestinal wall. The subpopulations of T cells that infiltrate inflamed intestinal tissues comprise various CD4+ T cells and CD8+ T cells. The plethora of T cell subtypes activated in CD leads to simultaneous activation of different signaling cascades including GATA1, NF-kB, JAK or STAT5 the activity of which may be modified by diet or drugs. It was recently showed that food allergens may accelerate CD by altering the interaction between IL-15 and CD4+ T cells in the activation of CD8+ T cells. Increased levels of cytokines like IL-15 are considered to play a role in CD development. Furthermore it was showed that some drugs like tofacitinib or ruxolitinib may influence CD by blocking IL-15 signaling and CD8+ T cell activity. This mini-review will summarize the current knowledge on the role of CD4+ T cell and CD8+ T cell in clinical and experimental CD and will describe how T cell-activated signaling pathways and locally released proteins may be influenced by dietary factors and drugs used in CD treatment.	\N	\N
25750286	Herpesvirus entry mediator (HVEM) has been recently suggested to play certain roles in cancer biology. We examined HVEM expression in human colorectal cancer (CRC) to reveal its clinical importance. Immunohistochemical staining was carried-out in normal epithelium, benign and malignant lesions. While intense HVEM expression was not observed in normal epithelium and hyperplastic polyps, 24% of adenoma and more than half of CRCs had high HVEM expression. In 234 CRCs, HVEM expression was significantly associated with tumor status and pathological stage. Patients with high HVEM expression had a significantly poorer prognosis than those with low expression. Importantly, HVEM status had an independent prognostic value in CRC. Furthermore, HVEM status was inversely corrected with the presence of tumor-infiltrating T-cells. HVEM may play a critical role in tumor progression and immune evasion, and may also be a novel prognostic marker and potential therapeutic target in human CRC.	\N	\N
25770253	Although obesity has been viewed traditionally as a disease of excess nutrition, evidence suggests that it may also be a disease of malnutrition. Specifically, thiamin deficiency was found in 15.5-29% of obese patients seeking bariatric surgery. It can present with vague signs and symptoms and is often overlooked in patients without alcohol use disorders. This review explores the relatively new discovery of high rates of thiamin deficiency in certain populations of people with obesity, including the effects of thiamin deficiency and potential underlying mechanisms of deficiency in people with obesity. The 2 observational studies that examined the prevalence in preoperative bariatric surgery patients and gaps in our current knowledge (including the prevalence of thiamin deficiency in the general obese population and whether the current RDA for thiamin meets the metabolic needs of overweight or obese adults) are reviewed. Suggestions for future areas of research are included.	\N	\N
25774918	We sought to determine whether genomic polymorphism in collagen IX genes (COL9A) was associated with Kashin-Beck disease (KBD). Twenty seven single nucleotide polymorphisms (SNPs) in COL9AI, COL9A2 and COL9A3 were genotyped in 274 KBD cases and 248 healthy controls using the Sequenom MassARRAY system. Associations between the COL9A polymorphism and KBD risk were detected using an unconditional logistic regression model. Linkage disequilibrium (LD) and haplotypes analysis were performed with the Haploview software. After Bonferroni correction, the frequency distribution of genotypes in rs6910140 in COL9A1 was significantly different between the KBD and the control groups (X2 = 16.74, df = 2, P = 0.0002). Regression analysis showed that the allele "C" in SNP rs6910140 had a significant protective effect on KBD [odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.34-0.70, P = 0.0001]. The frequencies of alleles and genotypes in rs6910140 were significantly different among subjects of different KBD stages (allele: X2 = 7.82, df = 2, P = 0.02, genotype: X2 = 14.81, df = 4, P = 0.005). However, haplotype analysis did not detect any significant association between KBD and COL9A1, COL9A2 and COL9A3. We observed a significant association between rs6910140 of COL9A1 and KBD, suggesting a role of COL9A1 in the development of KBD.	\N	\N
25795200	The study aims to compare the efficacy and safety of capecitabine plus oxaliplatin (XELOX) with 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOXs) in patients with advanced gastric cancer. Five databases were searched up to June 2014, without language restrictions. The outcomes included overall response rate (ORR), clinical benefit rate (CBR), and toxicity. Twenty-six eligible trials were selected from 178 studies that initially were identified. All trials were published in Chinese journals between 2005 and 2014 and included 1585 patients (787 in XELOX group and 798 in FOLFOXs group). The pooled results failed to show statistical significance of XELOX regimen on ORR (OR 1.18, 95% CIs 1.00-1.41, P = 0.057) and CBR (OR 1.10, 95% CIs 0.95-1.28, P = 0.191) as compared with FOLFOXs regimen. None of the 26 clinical trials reported progression-free survival, and only one reported overall survival rate. The meta-analysis demonstrated that XELOX regimen was associated with a significant lower risk with nausea, stomatitis, diarrhea and alopecia, and a significant higher risk of hand-foot syndrome. The evidence is limited to suggest that XELOX may share similar efficacy as FOLFOXs and reduce toxicities of chemotherapy in advanced gastric cancer therapy. However, owing to limited data and potential bias of the included studies, further rigorously controlled trials are required.	\N	\N
25801012	Eccentric distribution of atheroma has been associated with plaques likely to rupture and cause an acute coronary syndrome, but the factors responsible for the development of eccentricity remain unknown. Endothelial shear stress (ESS) drives plaque formation. We aimed to investigate the role of the local ESS characteristics in the de novo development and progressive worsening of plaque eccentricity in humans. Vascular profiling (3-vessel 3D coronary reconstruction by angiography/intravascular ultrasound, and blood flow simulation for ESS computation) was performed in 374 patients at baseline & 6-10 months follow-up. At baseline, we identified (i) disease-free segments (n=2157), and (ii) diseased regions of luminal obstructions (n=408). In disease-free regions, baseline low ESS magnitude (p<0.001), marked ESS circumferential heterogeneity (p=0.001), and their interaction (p=0.026) were associated with an increased probability of de novo eccentric plaque formation at follow-up. In diseased regions, baseline low ESS (odds ratio [OR]: 2.33, p=0.003) and large plaque burden (OR: 2.46, p=0.002) were independent predictors of substantially increasing plaque eccentricity index with worsening lumen encroachment. This combined outcome was more frequent in obstructions with both features vs. all others (33 vs. 12%; p<0.001). The incidence of percutaneous coronary intervention in worsening obstructions with increasing plaque eccentricity was higher (13.3 vs. 4.3%, p=0.011). The local hemodynamic environment has a critical effect on the development of eccentric coronary plaques at both an early and advanced stage of atherosclerosis. Local ESS assessment could help in predicting sites prone to plaque disruption and acute coronary syndromes in humans.	\N	\N
25811383	Nephropathic cystinosis is a lysosomal storage disorder caused by mutations in the CTNS gene encoding cystine transporter cystinosin that results in accumulation of amino acid cystine in the lysosomes throughout the body and especially affects kidneys. Early manifestations of the disease include renal Fanconi syndrome, a generalized proximal tubular dysfunction. Current therapy of cystinosis is based on cystine-lowering drug cysteamine that postpones the disease progression but offers no cure for the Fanconi syndrome. We studied the mechanisms of impaired reabsorption in human proximal tubular epithelial cells (PTEC) deficient for cystinosin and investigated the endo-lysosomal compartments of cystinosin-deficient PTEC by means of light and electron microscopy. We demonstrate that cystinosin-deficient cells had abnormal shape and distribution of the endo-lysosomal compartments and impaired endocytosis, with decreased surface expression of multiligand receptors and delayed lysosomal cargo processing. Treatment with cysteamine improved surface expression and lysosomal cargo processing but did not lead to a complete restoration and had no effect on the abnormal morphology of endo-lysosomal compartments. The obtained results improve our understanding of the mechanism of proximal tubular dysfunction in cystinosis and indicate that impaired protein reabsorption can, at least partially, be explained by abnormal trafficking of endosomal vesicles.	\N	\N
25813338	Poor data regarding skin involvement in Myotonic Dystrophy, also named Dystrophia Myotonica type 1, have been reported. This study aimed to investigate the prevalence and types of skin disorders in adult patients with Myotonic Dystrophy type 1. Fifty-five patients and one hundred age- and sex-matched healthy subjects were referred to a trained dermatologist for a complete skin examination to check for potential cutaneous hallmarks of disease. No difference in prevalence of preneoplastic, neoplastic, and cutaneous lesions was detected between the two groups. Among morphofunctional, proliferative and inflammatory lesions, focal hyperhidrosis (p < 0.0001), follicular hyperkeratosis (p = 0.0003), early androgenic alopecia (p = 0.01), nail pitting (p = 0.003), pedunculus fibromas (p = 0. 01), twisted hair (p = 0.01), seborrheic dermatitis (p = 0.02), macules of hyperpigmentation (p = 0.03) were significantly more frequent in patients compared with controls. In patients with Myotonic Dystrophy type 1 significant differences according to sex were found for: early androgenic alopecia, twisted hair and seborrheic dermatitis, whose prevalence was higher in males (p < 0.0001). Our preliminary results seem to rule out an increased prevalence of pre-neoplastic, and neoplastic skin lesions in Myotonic Dystrophy type 1. On the other hand, an increased prevalence of morphofunctional, inflammatory, and proliferative diseases involving adnexal structures seems to characterize adult patients with Myotonic Dystrophy type 1.	\N	\N
25834326	To investigate whether transarterial chemoembolization (TACE) before liver transplantation (LT) improves long-term survival in hepatocellular carcinoma (HCC) patients. A retrospective study was conducted among 204 patients with HCC who received LT from January 2002 to December 2010 in PLA General Hospital. Among them, 88 patients received TACE before LT. Prognostic factors of serum α-fetoprotein (AFP), intraoperative blood loss, intraoperative blood transfusion, disease-free survival time, survival time with tumor, number of tumor nodules, tumor size, tumor number, presence of blood vessels and bile duct invasion, lymph node metastasis, degree of tumor differentiation, and preoperative liver function were determined in accordance with the Child-Turcotte-Pugh (Child) classification and model for end-stage liver disease. We also determined time of TACE before transplant surgery and tumor recurrence and metastasis according to different organs. Cumulative survival rate and disease-free survival rate curves were prepared using the Kaplan-Meier method, and the log-rank and χ(2) tests were used for comparisons. In patients with and without TACE before LT, the 1, 3 and 5-year cumulative survival rate was 70.5% ± 4.9% vs 91.4% ± 2.6%, 53.3% ± 6.0% vs 83.1% ± 3.9%, and 46.2% ± 7.0% vs 80.8% ± 4.5%, respectively. The median survival time of patients with and without TACE was 51.857 ± 5.042 mo vs 80.930 ± 3.308 mo (χ(2) = 22.547, P < 0.001, P < 0.05). The 1, 3 and 5-year disease-free survival rates for patients with and without TACE before LT were 62.3% ± 5.2% vs 98.9% ± 3.0%, 48.7% ± 6.7% vs 82.1% ± 4.1%, and 48.7% ± 6.7% vs 82.1% ± 4.1%, respectively. The median survival time of patients with and without TACE before LT was 50.386 ± 4.901 mo vs 80.281 ± 3.216 mo (χ(2) = 22.063, P < 0.001, P < 0.05). TACE before LT can easily lead to pulmonary or distant metastasis of the primary tumor. Although there was no significant difference between the two groups, the chance of metastasis of the primary tumor in the group with TACE was significantly higher than that of the group without TACE. TACE pre-LT for HCC patients increased the chances of pulmonary or distant metastasis of the primary tumor, thus reducing the long-term survival rate.	\N	\N
25836637	The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD.	\N	\N
25857492	Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment.	\N	\N
25861414	Chronic kidney disease (CKD) is characterized by increased levels of oxidative stress and inflammation. Oxidative stress and inflammation promote renal injury via damage to molecular components of the kidney. Unfortunately, relationships between inflammation and oxidative stress are cyclical in that the inflammatory processes that exist to repair radical-mediated damage may be a source of additional free radicals, resulting in further damage to renal tissue. Oxidative stress and inflammation also have the ability to become systemic, serving to injure tissues distal to the site of original insult. This review describes select mediators in the exacerbatory relationship between oxidative stress, inflammation, and CKD. This review also discusses oxidative stress, inflammation, and CKD as they pertain to the development and progression of common CKD-associated comorbidities. Lastly, the utility of several widely accessible and cost-effective lifestyle interventions and their ability to reduce oxidative stress and inflammation are discussed and recommendations for future research are provided.	\N	\N
25897458	As of late 2014, interferon beta injection was the standard "disease-modifying" treatment for patients with relapsing-remitting multiple sclerosis, in the absence of a better alternative. Alemtuzumab (Lemtrada degree, Genzyme Therapeutics), an antilymphocyte monoclonal antibody first used in some types of leukaemia, is authorised in the European Union, at a different dosage, for patients with multiple sclerosis. Clinical evaluation in multiple sclerosis is based on three unblinded trials comparing alemtuzumab with interferon beta-1a. These trials were all biased in favour of alemtuzumab and thus fail to establish the potential value of this immunosuppressant. Overall, adverse effects, including the most severe, were more frequent with alemtuzumab than with interferon beta-1a. The adverse effects of alemtuzumab reported in these trials had already been observed in cancer patients. They included potentially severe reactions to the infusion, as well as a risk of infections and cancer due to profound and prolonged immunosuppression. At the dosage authorised in multiple sclerosis, autoimmune disorders such as thyroid disorders and immune thrombocytopenic purpura are particularly frequent and serious. In practice, patients with multiple sclerosis already have difficulty coping with the troublesome consequences of their underlying disease. They should not be subjected to the serious adverse effects of alemtuzumab, especially given the absence of any proven benefit.	\N	\N
25924288	The paper describes the development of alopecia with a patient with echinocccosis alveolaris during treatment with Nemozole (albandazole). To decide to continue or to discontinue Nemozole treatment in the development of alopecia, the patient should be given full information on the risk of alopecia to his life and quality of life as compared to the sequels of recurrent hydatid disease when Nemozole is discontinued.	\N	\N
25924757	Hypercalcaemia is a common biochemical abnormality in the blood that can be caused by malignancy, hyperparathyroidism, medications or underlying medical conditions. Initial signs and symptoms are often vague, however, if someone has severe hypercalcaemia it is treated as an emergency, requiring prompt management to prevent life-threatening complications such as dehydration, cardiac arrhythmias or coma. Understanding the pathophysiology, signs and symptoms of hypercalcaemia enables effective diagnosis and holistic management of the patient with complex health needs.	\N	\N
25925920	Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically susceptible individuals. CD-related enteropathy leads to multiple nutritional deficiencies involving macro- and micronutrients. Currently, medical nutrition therapy consisting of the gluten-free diet (GFD) is the only accepted treatment for CD. The GFD is the cornerstone of treatment for CD. Prior published studies have concluded that maintenance of the GFD results in improvement of the majority of nutritional deficiencies. In the past, counseling for CD focused mainly on the elimination of gluten in the diet. However, the GFD is not without its inadequacies; compliance to the GFD may result in certain deficiencies such as fiber, B vitamins, iron, and trace minerals. Paucity of fortified gluten-free foods may be responsible for certain deficiencies which develop on the GFD. Weight gain and obesity have been added to the list of nutritional consequences while on the GFD and have been partially attributed to hypercaloric content of commercially available gluten-free foods. Follow-up of patients diagnosed with CD after starting the GFD has been reported to be irregular and, hence, less than ideal. Monitoring of the nutritional status using blood tests and use of appropriate gluten-free supplementation are integral components in the management of CD. The ideal GFD should be nutrient-dense with naturally gluten-free foods, balanced with macro- and micronutrients, reasonably priced, and easily accessible. Rotation of the pseudo-cereals provides a good source of complex carbohydrates, protein, fiber, fatty acids, vitamins and minerals. Fortification/enrichment of commonly consumed gluten-free commercial grain products should be encouraged. Dietitians specializing in CD play a critical role in the education and maintenance of the GFD for patients with CD.	\N	\N
25934387	C5a plays a central role in antineutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. A previous study showed that C5a played a crucial role in the regulation of high mobility group box 1 (HMGB1) release from human neutrophils. The current study further investigated the interaction between C5a and HMGB1 in ANCA-induced neutrophil activation. The effects of HMGB1 inhibitors on the translocation of ANCA antigens, ANCA-induced respiratory burst and degranulation of C5a-primed neutrophils were tested. We found that blocking HMGB1 decreased C5a-mediated translocation of ANCA antigens, as well as ANCA-induced respiratory burst and degranulation of C5a-primed neutrophils. Further study showed that supernatant of C5a-primed neutrophils, which contained HMGB1, also caused translocation of ANCA antigens of primary neutrophils, whereas blocking HMGB1 decreased the translocation. In conclusion, blocking HMGB1 may attenuate ANCA-induced activation of C5a-primed neutrophils. The interaction between HMGB1 and C5a might play an important role in ANCA-induced neutrophil activation.	\N	\N
25945002	To compare ultrasound-based acoustic structure quantification (ASQ) with established non-invasive techniques for grading and staging fatty liver disease. Type 2 diabetic patients at risk of non-alcoholic fatty liver disease (n = 50) and healthy volunteers (n = 20) were evaluated using laboratory analysis and anthropometric measurements, transient elastography (TE), controlled attenuation parameter (CAP), proton magnetic resonance spectroscopy ((1)H-MRS; only available for the diabetic cohort), and ASQ. ASQ parameters mode, average and focal disturbance (FD) ratio were compared with: (1) the extent of liver fibrosis estimated from TE and non-alcoholic fatty liver disease (NAFLD) fibrosis scores; and (2) the amount of steatosis, which was classified according to CAP values. Forty-seven diabetic patients (age 67.0 ± 8.6 years; body mass index 29.4 ± 4.5 kg/m²) with reliable CAP measurements and all controls (age 26.5 ± 3.2 years; body mass index 22.0 ± 2.7 kg/m²) were included in the analysis. All ASQ parameters showed differences between healthy controls and diabetic patients (P < 0.001, respectively). The ASQ FD ratio (logarithmic) correlated with the CAP (r = -0.81, P < 0.001) and (1)H-MRS (r = -0.43, P = 0.004) results. The FD ratio [CAP < 250 dB/m: 107 (102-109), CAP between 250 and 300 dB/m: 106 (102-114); CAP between 300 and 350 dB/m: 105 (100-112), CAP ≥ 350 dB/m: 102 (99-108)] as well as mode and average parameters, were reduced in cases with advanced steatosis (ANOVA P < 0.05). However, none of the ASQ parameters showed a significant difference in patients with advanced fibrosis, as determined by TE and the NAFLD fibrosis score (P > 0.08, respectively). ASQ parameters correlate with steatosis, but not with fibrosis in fatty liver disease. Steatosis estimation with ASQ should be further evaluated in biopsy-controlled studies.	\N	\N
25971299	Cancer recurrence and disease-free survival are key outcomes for measuring the burden of illness, assessing the quality of cancer care, and informing decisions about increasingly costly cancer therapies. Yet information about recurrence is not collected in cancer registries or other population-based data sources. To address the lack of population-based recurrence information, researchers are increasingly using algorithms applied to health claims to infer recurrence. However, the validity of these approaches has not been comprehensively evaluated. In this commentary, we review existing studies and discuss options for improving the availability of recurrence data. We found that the validity of claims-based approaches appears promising in small, single institution studies, but larger population-based studies have identified substantial limitations with using claims to identify recurrence. With the increasing availability of health data, there are potential options that can be implemented to enhance information about recurrence. These options include design of software for the electronic medical record that enables rapid and standardized reporting of recurrence, use of electronic pathology reports to facilitate streamlined collection of recurrence by cancer registries, and mandates by insurers to require reporting of recurrence on health claims submitted by physicians. All of these options will require that governmental agencies, health insurers, professional societies, and other groups recognize the importance of population-based recurrence data and determine that this information is a priority for assessing cancer outcomes and costs.	\N	\N
25972525	Relations of the 25 mammalian selenoprotein genes with obesity and the associated inflammation remain unclear. This study explored impacts of high-fat diet-induced obesity on inflammation and expressions of selenoprotein and obesity-related genes in 10 tissues of pigs. Plasma and 10 tissues were collected from pigs (n = 10) fed a corn-soy-based control diet or that diet containing 3-7% lard from weanling to finishing (180 d). Plasma concentrations (n = 8) of cytokines and thyroid hormones and tissue mRNA abundance (n = 4) of 25 selenoprotein genes and 16 obesity-related genes were compared between the pigs fed the control and high-fat diets. Stepwise regression was applied to analyze correlations among all these measures, including the previously reported body physical and plasma biochemical variables. The high-fat diet elevated (P < 0.05) plasma concentrations of tumor necrosis factor α, interleukin-6, leptin, and leptin receptor by 29-42% and affected (P < 0.05-0.1) tissue mRNA levels of the selenoprotein and obesity-related genes in 3 patterns. Specifically, the high-fat diet up-regulated 12 selenoprotein genes in 6 tissues, down-regulated 13 selenoprotein genes in 7 tissues, and exerted no effect on 5 genes in any tissue. Body weights and plasma triglyceride concentrations of pigs showed the strongest regressions to tissue mRNA abundances of selenoprotein and obesity-related genes. Among the selenoprotein genes, selenoprotein V and I were ranked as the strongest independent variables for the regression of phenotypic and plasma measures. Meanwhile, agouti signaling protein, adiponectin, and resistin genes represented the strongest independent variables of the obesity-related genes for the regression of tissue selenoprotein mRNA. The high-fat diet induced inflammation in pigs and affected their gene expression of selenoproteins associated with thioredoxin and oxidoreductase systems, local tissue thyroid hormone activity, endoplasmic reticulum protein degradation, and phosphorylation of lipids. This porcine model may be used to study interactive mechanisms between excess fat intake and selenoprotein function.	\N	\N
25998164	In atopic dermatitis (AD), the inflammatory response between skin-infiltrating T cells and keratinocytes is fundamental to the development of chronic lesional eczema. The aim of this study was to investigate whether skin-derived T cells from AD patients could induce an inflammatory response in mice through keratinocyte activation and consequently cause the development of eczematous lesions. Punch biopsies of the lesional skin from AD patients were used to establish skin-derived T cell cultures, which were transferred to NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that the subcutaneous injection of the human AD skin-derived T cells resulted in the migration of the human T cells from subcutis to the papillary dermis followed by the development of erythema and oedema in the mouse skin. Furthermore, the human T cells induced a transient proliferative response in the mouse keratinocytes shown as increased numbers of Ki-67(+) keratinocytes and increased epidermal thickness. Out of six established AD skin-derived T cell cultures, two were superior at inducing a skin reaction in the mice, and these cultures were found to contain >10% CCR10(+) T cells compared to <2% for the other cultures. In comparison, blood-derived in vitro-differentiated Th2 cells only induced a weak response in a few of the mice. Thus, we conclude that human AD skin-derived T cells can induce a reaction in the mouse skin through the induction of a proliferative response in the mouse keratinocytes.	\N	\N
26026650	The aim of the Activating Schoolyards Study is to develop, implement, document and assess a comprehensive schoolyard intervention to promote physical activity (PA) during school recess for primary school children (grade 4-8). The intervention is designed to implement organizational and structural changes in the physical environment. The study builds on a quasi-experimental study design using a mixed method approach including: 1) an exploratory study aimed at providing input for the developing process; 2) an evaluation of the effect of the interventions using a combination of accelerometer, GPS and GIS; 3) a process evaluation facilitating the intervention development process and identifying barriers and facilitators in the implementation process; 4) a post-intervention end-user evaluation aimed at exploring who uses the schoolyards and how the schoolyards are used. The seven project schools (cases) were selected by means of an open competition and the interventions were developed using a participatory bottom-up approach. The participatory approach and case selection strategy make the study design novel. The use of a mixed methods design including qualitative as well as quantitative methods can be seen as a strength, as the different types of data complement each other and results of one part of the study informed the following parts. A unique aspect of our study is the use of accelerometers in combination with GPS and GIS in the effect evaluation to objectively determine where and how active the students are in the schoolyard, before and after the intervention. This provides a type of data that, to our knowledge, has not been used before in schoolyard interventions. Exploring the change in behavior in relation to specific intervention elements in the schoolyard will lead to recommendations for schools undergoing schoolyard renovations at some point in the future.	\N	\N
26029704	Many common diseases have a complex genetic basis in which large numbers of genetic variations combine with environmental factors to determine risk. However, quantifying such polygenic effects has been challenging. In order to address these difficulties we developed a global measure of the information content of an individual's genome relative to a reference population, which may be used to assess differences in global genome structure between cases and appropriate controls. Informally this measure, which we call relative genome information (RGI), quantifies the relative "disorder" of an individual's genome. In order to test its ability to predict disease risk we used RGI to compare single-nucleotide polymorphism genotypes from two independent samples of women with early-onset breast cancer with three independent sets of controls. We found that RGI was significantly elevated in both sets of breast cancer cases in comparison with all three sets of controls, with disease risk rising sharply with RGI. Furthermore, these differences are not due to associations with common variants at a small number of disease-associated loci, but rather are due to the combined associations of thousands of markers distributed throughout the genome. Our results indicate that the information content of an individual's genome may be used to measure the risk of a complex disease, and suggest that early-onset breast cancer has a strongly polygenic component.	\N	\N
26037125	Vaginal inflammation (vaginitis) is the most common disease caused by the human-pathogenic fungus Candida albicans. Secretory aspartyl proteinases (Sap) are major virulence traits of C. albicans that have been suggested to play a role in vaginitis. To dissect the mechanisms by which Sap play this role, Sap2, a dominantly expressed member of the Sap family and a putative constituent of an anti-Candida vaccine, was used. Injection of full-length Sap2 into the mouse vagina caused local neutrophil influx and accumulation of the inflammasome-dependent interleukin-1β (IL-1β) but not of inflammasome-independent tumor necrosis factor alpha. Sap2 could be replaced by other Sap, while no inflammation was induced by the vaccine antigen, the N-terminal-truncated, enzymatically inactive tSap2. Anti-Sap2 antibodies, in particular Fab from a human combinatorial antibody library, inhibited or abolished the inflammatory response, provided the antibodies were able, like the Sap inhibitor Pepstatin A, to inhibit Sap enzyme activity. The same antibodies and Pepstatin A also inhibited neutrophil influx and cytokine production stimulated by C. albicans intravaginal injection, and a mutant strain lacking SAP1, SAP2, and SAP3 was unable to cause vaginal inflammation. Sap2 induced expression of activated caspase-1 in murine and human vaginal epithelial cells. Caspase-1 inhibition downregulated IL-1β and IL-18 production by vaginal epithelial cells, and blockade of the IL-1β receptor strongly reduced neutrophil influx. Overall, the data suggest that some Sap, particularly Sap2, are proinflammatory proteins in vivo and can mediate the inflammasome-dependent, acute inflammatory response of vaginal epithelial cells to C. albicans. These findings support the notion that vaccine-induced or passively administered anti-Sap antibodies could contribute to control vaginitis. Candidal vaginitis is an acute inflammatory disease that affects many women of fertile age, with no definitive cure and, in its recurrent forms, causing true devastation of quality of life. Unraveling the fungal factors causing inflammation is important to be able to devise novel tools to fight the disease. In an experimental murine model, we have discovered that aspartyl proteinases, particularly Sap2, may cause the same inflammatory signs of vaginitis caused by the fungus and that anti-Sap antibodies and the protease inhibitor Pepstatin A almost equally inhibit Sap- and C. albicans-induced inflammation. Sap-induced vaginitis is an early event during vaginal infection, is uncoupled from fungal growth, and requires Sap and caspase-1 enzymatic activities to occur, suggesting that Sap or products of Sap activity activate an inflammasome sensor of epithelial cells. Our data support the notion that anti-Sap antibodies could help control the essence of candidal vaginitis, i.e., the inflammatory response.	\N	\N
26041263	Several mutations in nuclear genes encoding for mitochondrial components have been associated with an increased cancer risk or are even causative, e.g. succinate dehydrogenase (SDHB, SDHC and SDHD genes) and iso-citrate dehydrogenase (IDH1 and IDH2 genes). Recently, studies have suggested an eminent role for mitochondrial DNA (mtDNA) mutations in the development of a wide variety of cancers. Various studies associated mtDNA abnormalities, including mutations, deletions, inversions and copy number alterations, with mitochondrial dysfunction. This might, explain the hampered cellular bioenergetics in many cancer cell types. Germline (e.g. m.10398A>G; m.6253T>C) and somatic mtDNA mutations as well as differences in mtDNA copy number seem to be associated with cancer risk. It seems that mtDNA can contribute as driver or as complementary gene mutation according to the multiple-hit model. This can enhance the mutagenic/clonogenic potential of the cell as observed for m.8993T>G or influences the metastatic potential in later stages of cancer progression. Alternatively, other mtDNA variations will be innocent passenger mutations in a tumor and therefore do not contribute to the tumorigenic or metastatic potential. In this review, we discuss how reported mtDNA variations interfere with cancer treatment and what implications this has on current successful pharmaceutical interventions. Mutations in MT-ND4 and mtDNA depletion have been reported to be involved in cisplatin resistance. Pharmaceutical impairment of OXPHOS by metformin can increase the efficiency of radiotherapy. To study mitochondrial dysfunction in cancer, different cellular models (like ρ(0) cells or cybrids), in vivo murine models (xenografts and specific mtDNA mouse models in combination with a spontaneous cancer mouse model) and small animal models (e.g. Danio rerio) could be potentially interesting to use. For future research, we foresee that unraveling mtDNA variations can contribute to personalized therapy for specific cancer types and improve the outcome of the disease.	\N	\N
26083239	Dual-isotope simultaneous-acquisition (DISA) rest-stress myocardial perfusion SPECT (MPS) protocols offer a number of advantages over separate acquisition. However, crosstalk contamination due to scatter in the patient and interactions in the collimator degrade image quality. Compensation can reduce the effects of crosstalk, but does not entirely eliminate image degradations. Optimizing acquisition parameters could further reduce the impact of crosstalk. In this paper we investigate the optimization of the rest Tl-201 energy window width and relative injected activities using the ideal observer (IO), a realistic digital phantom population and Monte Carlo (MC) simulated Tc-99m and Tl-201 projections as a means to improve image quality. We compared performance on a perfusion defect detection task for Tl-201 acquisition energy window widths varying from 4 to 40 keV centered at 72 keV for a camera with a 9% energy resolution. We also investigated 7 different relative injected activities, defined as the ratio of Tc-99m and Tl-201 activities, while keeping the total effective dose constant at 13.5 mSv. For each energy window and relative injected activity, we computed the IO test statistics using a Markov chain Monte Carlo (MCMC) method for an ensemble of 1,620 triplets of fixed and reversible defect-present, and defect-absent noisy images modeling realistic background variations. The volume under the 3-class receiver operating characteristic (ROC) surface (VUS) was estimated and served as the figure of merit. For simultaneous acquisition, the IO suggested that relative Tc-to-Tl injected activity ratios of 2.6-5 and acquisition energy window widths of 16-22% were optimal. For separate acquisition, we observed a broad range of optimal relative injected activities from 2.6 to 12.1 and acquisition energy window of widths 16-22%. A negative correlation between Tl-201 injected activity and the width of the Tl-201 energy window was observed in these ranges. The results also suggested that DISA methods could potentially provide image quality as good as that obtained with separate acquisition protocols. We compared observer performance for the optimized protocols and the current clinical protocol using separate acquisition. The current clinical protocols provided better performance at a cost of injecting the patient with approximately double the injected activity of Tc-99m and Tl-201, resulting in substantially increased radiation dose.	\N	\N
26086077	Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the 'human blood metabolome-transcriptome interface' (BMTI). Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease.	\N	\N
26109487	The aim of this study was to evaluate the long-term outcomes of patients with colorectal cancer liver metastasis (CRCLM) exhibiting disease progression after portal vein embolization (PVE). Patients with CRCLM requiring PVE before hepatectomy between 2003 and 2014 were included. Clinical variables, and liver and tumour volumes determined by three-dimensional CT volumetry were assessed before and after PVE. Overall and disease-free survival data were obtained. Univariable and multivariable logistic regression analyses were performed to identify predictors of tumour progression after PVE. Of 141 patients who underwent PVE, 93 (66.0 per cent) had tumour progression and 17 (12.1 per cent) developed new contralateral lesions. Significantly fewer patients had resectable disease in the group with disease progression than among those with stable disease: 43 (46 per cent) of 93 versus 36 (75 per cent) of 48 respectively (P = 0.001). Median survival was similar in patients with and without tumour growth after PVE: 22.5 versus 26.0 months for patients with unresectable tumours (P = 0.706) and 46.2 versus 52.2 months for those with resectable disease (P = 0.953). However, disease-free survival for patients with tumour progression after PVE was shorter than that for patients with stable disease (6.0 versus 20.2 months; P = 0.045). Response to neoadjuvant chemotherapy was the only significant factor associated with tumour progression in multivariable analysis. Tumour progression after PVE did not affect overall survival, but patients with resected tumours who had tumour growth after embolization experienced earlier recurrence. A borderline response to neoadjuvant chemotherapy seemed to be associated with tumour progression after PVE.	\N	\N
26118068	There has been a significant increase in diabetes morbidity in the past years. Prolonged asymptomatic progression of disease presents a problem and leads to late diagnosis and development of complications. Present study shows efficiency of screening measures to determine actual spread of carbohydrate metabolism disorders among residents of Odessa, frequency of type 2 diabetes mellitus risk factors determination and prevention of complications.	\N	\N
26141335	In the past few years, new biological insights into the myelodysplastic syndromes (MDS) resulting from molecular genetic analysis have improved pathologic understanding, but treatment advances have not kept pace. More than 40 genes are now known to be recurrently mutated in MDS. However, because most of these genes encode spliceosome components, chromatic remodeling factors, epigenetic pattern modulators, or transcription factors rather than more easily inhibited activated tyrosine kinases, there are as of yet few narrowly targeted therapies available for MDS. Three drugs--azacitidine, decitabine, and lenalidomide--were approved by the US Food and Drug Administration for MDS indications a decade ago, and these agents can improve hematopoiesis, delay disease progression, and improve survival and quality of life for a subset of patients. However, only a few patients with MDS respond to these agents, and their benefit is temporary. The only potentially curative therapy for MDS is allogeneic hematopoietic stem cell transplant, but owing to the advanced age of many patients with MDS and the frequency of serious comorbid conditions, less than 10% of patients currently undergo stem cell transplant. This narrative review summarizes the current understanding of MDS and treatment options for these challenging disorders.	\N	\N
26143070	Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95 % CI 2.5-14.5, p = 0.004) with high resolution CT. In the multivariate analysis ethnicity (p = 0.02) and disease state (p < 0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95 % CI 2.5-14.5, p = 0.004) and in HAM/TSP patients compared with all other categories 8.4 (95 % CI 2.7-26.1, p = 0.0002). Subjects not of African/Afro-Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95 % 1.2-9.7, p = 0.02). Bronchiectasis was common in the cohort (3.4 %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis.	\N	\N
26148061	In humans, neurodegenerative disorders such as Huntington's disease (HD) and many spinocerebellar ataxias (SCAs) have been found to be associated with CAG trinucleotide repeat expansion. An important RNA-mediated mechanism that causes these diseases involves the binding of the splicing regulator protein MBNL1 (Muscleblind-like 1 protein) to expanded r(CAG) repeats. Moreover, mutant huntingtin protein translated from expanded r(CAG) also yields toxic effects. To discern the role of mutant RNA in these diseases, it is essential to gather information about its structure. Detailed insight into the different structures and conformations adopted by these mutant transcripts is vital for developing therapeutics targeting them. Here, we report the crystal structure of an RNA model with a r(CAG) motif, which is complemented by an NMR-based solution structure obtained from restrained Molecular Dynamics (rMD) simulation studies. Crystal structure data of the RNA model resolved at 2.3 Å reveals non-canonical pairing of adenine in 5´-CAG/3´-GAC motif samples in different syn and anti conformations. The overall RNA structure has helical parameters intermediate to the A- and B-forms of nucleic acids due to the global widening of major grooves and base-pair preferences near internal AA loops. The comprehension of structural behaviour by studying the spectral features and the dynamics also supports the flexible nature of the r(CAG) motif.	\N	\N
26149802	The importance of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo-HSCT. These consisted of leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999-2008. The Mantel-Byar approach was used to assess allo-HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo-HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41-60. The CIR demonstrated that allo-HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo-HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41-60. The allo-HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis.	\N	\N
26160211	The objective of this study was to compare the efficacy and comfort of inelastic bandages (IBs) and adjustable Velcro compression devices (AVCDs) in reducing venous leg edema in the initial treatment phase. Forty legs from 36 patients with untreated venous edema (C3EpsAsdPr) were randomized to two groups. Patients in the first group received IBs (n = 20) and those in the second AVCDs (n = 20). Both compression devices were left on the leg day and night, and were renewed after 1 day. Patients in the AVCD group were asked to re-adjust the device as needed when it felt loose. Leg volume was calculated using the truncated cone formula at baseline (T0), after 1 day (T1) and after 7 days (T7). The interface pressure of the two compression devices was measured by an air filled probe, and the static stiffness index calculated after applying compression at T0 and T1, and just before removal of compression on T1 and T7. Patient comfort with regard to the two compression systems was assessed by grading signs and symptoms using a visual analog scale. At T1, the median percent volume reduction was 13% for the IB group versus 19% for the AVCD group; at T7 it was 19% versus 26%, respectively (p < .001). The pressure of the IBs was significantly higher compared with the AVCDs at T0 (63 vs. 43 mmHg) but dropped by > 50% over time, while it remained unchanged with AVCDs owing to the periodic readjustment by the patient. Comfort was reported to be similar with the two compression devices. Re-adjustable AVCDs with a resting pressure of around 40 mmHg are more effective in reducing chronic venous edema than IBs with a resting pressure of around 60 mmHg. AVCDs are effective and well tolerated, not only during maintenance therapy, but also in the initial decongestive treatment phase of patients with venous leg edema.	\N	\N
26163286	Thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine that has been studied extensively in atopic diseases and more recently in various rheumatic disorders. It is involved in T cell development in the thymus and promotes homeostatic T cell expansion by classical dendritic cells. However, deregulated TSLP expression in various rheumatic diseases has implicated this cytokine as a strong mediator in immunopathology. Overexpressed TSLP induces strong T cell activation and production of pro-inflammatory cytokines in human cells and animal models for RA, SSc and LN, underscoring the therapeutic potential of targeting the TSLP-TSLP receptor axis.	\N	\N
26174498	The 14(th) -century Black Death was one of the most devastating epidemics in human history, killing tens of millions of people in a short period of time. It is not clear why mortality rates during the epidemic were so high. One possibility is that the affected human populations were particularly stressed in the 14(th) century, perhaps as a result of repeated famines in areas such as England. This project examines survival and mortality in two pre-Black Death time periods, 11-12(th) centuries vs 13(th) century CE, to determine if demographic conditions were deteriorating before the epidemic occurred. This study is done using a sample of individuals from several London cemeteries that have been dated, in whole or in part, either to the 11-12(th) centuries (n = 339) or 13(th) century (n = 258). Temporal trends in survivorship and mortality are assessed via Kaplan-Meier survival analysis and by modeling time period as a covariate affecting the Gompertz hazard of adult mortality. The age-at-death distributions from the two pre-Black Death time periods are significantly different, with fewer older adults in 13(th) century. The results of Kaplan-Meier survival analysis indicate reductions in survival before the Black Death, with significantly lower survival in the 13(th) century (Mantel Cox p < 0.001). Last, hazard analysis reveals increases in mortality rates before the Black Death. Together, these results suggest that health in general was declining in the 13(th) century, and this might have led to high mortality during the Black Death. This highlights the importance of considering human context to understand disease in past and living human populations.	\N	\N
26175069	Dengue hemorrhagic fever (DHF), although predominantly associated with secondary infections, has also been reported in primary infections. An enhanced immune response including antibodies and cytokines is implicated in the pathogenesis of secondary DHF. However, the factors operating in primary DHF are poorly understood. To understand the role of the antibody response, the relative levels of different antibody isotypes during the acute phase of infection in primary and secondary dengue infections were determined. Levels of DENV-specific IgM, IgG, IgA and IgE were measured in the serum samples of 200 dengue patients and 20 dengue-naïve individuals. Samples were collected within 15 days of onset of illness. The DENV-specific IgM levels were significantly higher in DF cases compared to DHF, which was more evident in secondary infections and in post-defervescence samples. The levels of IgG, IgA and IgE were higher in DHF cases, with greater significance in primary infections. A higher level of IgG in DHF cases was evident in pre-defervescence samples, whilst the IgE level was higher in pre- and post-defervescence samples. There was a significant correlation of IgG titres with platelet counts, with higher titres associated with lower platelet counts. It is speculated that IgG, IgA and IgE produced in response to primary infections may contribute to pathogenesis, whilst IgM produced in response to secondary infections may protect against progression to severe disease.	\N	\N
26189088	To determine the statistical correlation between visual acuity (VA) and various quantitative parameters relevant to birdshot retinochoroidopathy (BRC) evaluation. Hospital-based retrospective observational study. setting: Institutional. Consecutive HLA29+ BRC patients were included between May and August 2013 at a single tertiary center (Pitié-Salpétrière Hospital, Paris). Demographic data and quantitative parameters relevant to BRC at baseline were collected: VA, degree of anterior and posterior inflammatory reaction, foveal thickness measured by optical coherence tomography (OCT), Arden ratio, and electrooculography (EOG) light peak. Correlation between VA and the other parameters of the ipsilateral and fellow eye was performed using Spearman rank correlation coefficients. Fifty-five patients were included. Mean VA was 6/9.5 in the right eye (OD) and 6/12 in the left eye (OS). Mean foveal thickness was 240 μm OD (range: 112-606) and 251 μm OS (range: 85-662). Mean Arden ratio was 159% OD and 160% OS. EOG light peak was 714 mV OD (range: 316-1379) and 746 mV OS (range: 272-1652). VA of a given eye was moderately correlated with VA of the contralateral eye (r = 0.4). On the contrary, all other parameters showed a strong correlation between both eyes (all r > 0.7, P < .01). Overall, none of the studied parameters was correlated with its VA (all r < 0.5). In BRC, visual acuity alone does not seem to fully reflect the disease severity in terms of clinical or ancillary quantitative findings at baseline.	\N	\N
26204159	Dividing cells that experience chromosome mis-segregation generate aneuploid daughter cells, which contain an incorrect number of chromosomes. Although aneuploidy interferes with the proliferation of untransformed cells, it is also, paradoxically, a hallmark of cancer, a disease defined by increased proliferative potential. These contradictory effects are also observed in mouse models of chromosome instability (CIN). CIN can inhibit and promote tumorigenesis. Recent work has provided insights into the cellular consequences of CIN and aneuploidy. Chromosome mis-segregation per se can alter the genome in many more ways than just causing the gain or loss of chromosomes. The short- and long-term effects of aneuploidy are caused by gene-specific effects and a stereotypic aneuploidy stress response. Importantly, these recent findings provide insights into the role of aneuploidy in tumorigenesis.	\N	\N
26211602	Small cell carcinoma of head and neck region (SmCCHN) represents a rare entity and its management remains a significant clinical challenge. Complete initial response to primary therapy poses a difficult and controversial scenario for radiation oncologists. Prophylactic cranial irradiation (PCI) has long been established in the management of small cell lung cancer; however, its role in SmCCHN is still called into question. The rationale behind PCI lies in the eradication of possible micro-metastatic brain disease, which is often documented in this type of cancer. No randomized trials on this topic are available. This review, based on 20 retrospective studies, addresses the controversies in the use of PCI in SmCCHN management.	\N	\N
26253469	Under distinct pathological heart conditions, the expression of a single miRNA can display completely opposite patterns. However, the mechanism underlying the bidirectional regulation of a single miRNA and the clinical implications of this regulation remain largely unknown. To address this issue, we examined the regulation of miR-1, one of the most abundant miRNAs in the heart, during cardiac hypertrophy and ischemia/reperfusion (I/R). Our data indicated that different magnitudes and chronicities of ROS levels in cardiomyocytes resulted in differential expression of miR-1, subsequently altering the expression of myocardin. In animal models, the administration of a miR-1 mimic attenuated cardiac hypertrophy by suppressing the transverse aortic constriction-induced increase in myocardin expression, whereas the administration of anti-miR-1 ameliorated I/R-induced cardiac apoptosis and deterioration of heart function. Our findings indicated that a pathologic stimulus such as ROS can bidirectionally alter the expression of miRNA to contribute to the development of pathological conditions exhibiting distinct phenotypes and that the meticulous adjustment of the pathological miRNA levels is required to improve clinical outcomes.	\N	\N
26285805	VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments.	\N	\N
26292522	At the death of Cardinal Pietro Basadonna in 1684, his personal physician Romolo Spezioli wrote a report describing the disease, circumstances of death and autopsy findings of the illustrious prelate. This document, kept in the Biblioteca Civica at Jesi, is a significant attestation of the medical terminology and diagnostic and therapeutic procedures of the time. Even with the constraints that interpretation of a clinical account dating back over 300 years inevitably imposes, perusal of this report suggests that Cardinal Basadonna's demise could have been due to septic shock, consequent to a urinary infection caused by a bulky bladder stone.	\N	\N
26293802	Leptin is an adipocytokine produced by adipocytes and controlling body weight. It is unclear whether leptin works as a proinflammatory or an anti-inflammatory cytokine. We investigated the effects of hyperleptinemia on leptin transgenic (LepTg) mice in terms of cartilage destruction, bone destruction, joint synovitis, and serum cytokine levels by using a mouse model of collagen-antibody-induced arthritis (CAIA). CAIA was induced for female age-matched 6- to 8-week-old C57BL/6 J control mice and LepTg mice. Mice were injected intraperitoneally with 5 mg of a combination of monoclonal antibody specific for type II collagen on day 0 and 12.5 mg of lipopolysaccharide (LPS) on day 3. Clinical evaluation of arthritis was monitored for 14 days, and hind paws were examined clinically and histologically. Serum cytokine levels of interleukin (IL)-1β, IL-6, IL-10, and IL-17 and tumor necrosis factor alpha (TNF-α) were also analyzed on days 0 and 5. Moreover, THP-1 cells, which are human monocytic cell line derived from an acute monocytic leukemia patient, were cultured and differentiated into macrophages. The effects of leptin on messenger RNA (mRNA) expression of IL-6 were examined by real-time quantitative polymerase chain reaction (RT-PCR). Serum leptin concentrations were approximately ninefold higher in LepTg mice (62.0 ± 20.7 ng/ml) than in control mice (7.2 ± 0.5 ng/ml). Severity of clinical paw swelling, arthritis score, synovial hyperplasia, and cartilage damage were suppressed in LepTg mice with CAIA. Although serum cytokine levels of IL-1β, IL-17, and IL-10 and TNF-α showed no significant changes in two mice, serum levels of IL-6 in LepTg mice were suppressed at day 5. Moreover, in vitro study showed that IL-6 elevation following LPS exposure in THP-1 cells was suppressed with high leptin concentrations. Our finding suggests that hyperleptinemia suppress IL-6 responses and progression of joint inflammation. Leptin may play an anti-inflammatory role under hyperleptinemia.	\N	\N
26299076	The aim of this study is to observe the association between venous thromboembolism (VTE) and oxidative stress and to see if there is a diagnostic value in the oxidative/antioxidative balance parameters like total oxidant status (TOS), total antioxidant status (TAS), paraoxonase-(PON1), and arylesterase (ARE) enzyme activities in this specific disease. Sixty-nine patients with deep vein thrombosis and/or pulmonary embolism and 40 control subjects were included in the study. Oxidative stress index, total oxidant status, and antioxidant status were examined in addition to the PON1 and ARE enzyme activities in both groups. Serum PON1 and ARE activities were significantly lower in the VTE patients, whereas total oxidant status was higher in patients compared to the controls. This preliminary study showed that oxidative/antioxidative balance shifted towards the oxidative status in venous thromboembolism. ROC analysis results suggested that the parameters used in this study were not good enough to be used in the diagnosis of VTE.	\N	\N
26310351	Google Flu Trends (GFT) was the first application of big data in the public health field. GFT was open online in 2009 and attracted worldwide attention immediately. However, GFT failed catching the 2009 pandemic H1N1 and kept overestimating the intensity of influenza-like illness in the 2012-2014 season in the United States. GFT model has been updated for three times since 2009, making its prediction bias controlled. Here, we summarized the mechanism GFT worked, the strategy GFT used to update, and its influence on public health.	\N	\N
26357715	Anal cancer is a relatively uncommon disease, accounting for only 4% of cancers of the lower gastrointestinal tract. To summarize a single-center experience in the treatment of anal carcinoma using various radiation techniques. We conducted a retrospective chart review of consecutive patients who were treated for anal cancer between the years 2002 and 2011. The data extracted included demographics, type of radiation technique, treatment-associated acute toxicity, and patterns of failure and survival. For statistical analysis purposes, the patients were divided into two groups according to radiotherapy technique: 2D (group A) and 3D (group B). A total of 42 patients--25 (59.5%) females and 17 males (40.5%)--underwent definitive chemo-radiation treatment (CRT) for anal cancer. Group A comprised 26 patients and group B 14 patients. Toxicity did not differ significantly between the groups; only in grade 1-2 skin toxicity which was more common in group B. There were significant differences in the unplanned interruptions in treatment, in both the number of patients who needed a treatment break and the number of days needed (more in group A). There were no differences in treatment response and patterns of failure between these two techniques, or in overall survival between the two groups. Our study results are consistent with reported large randomized trials, indicating that current treatments for anal carcinomas are associated with high grade acute toxicity that may result in significant treatment interruptions. The 2D technique was associated with significantly more treatment interruptions but did not differ from 3D with regard to treatment efficacy.	\N	\N
26375933	There has been considerable effort over the last 25 years to understand the emergence of complexity in motor output and how this relates to properties of the individual (e.g., age, disease state, etc.), environment (e.g., information) and task (e.g., movement, posture, isometric force). This paper addresses the behavioral dimension of motor complexity in movement and posture from a degrees of freedom (DF) perspective together with the change of complexity through aging, disease and fatigue. The dimension of behavior for a given perceptual-motor output is shown to be relatively low, dependent on the interaction between the individual, environmental, and task constraints and varies within a limited adaptive range for a given motor task. The determination of dimension in movement and posture has taken us beyond the traditional motor performance scores of behavior but it is not a sufficient characterization of the adaptive and emergent processes of complexity.	\N	\N
26381985	Assessment of the global burden of disease is based on epidemiological cohort studies that connect premature mortality to a wide range of causes, including the long-term health impacts of ozone and fine particulate matter with a diameter smaller than 2.5 micrometres (PM2.5). It has proved difficult to quantify premature mortality related to air pollution, notably in regions where air quality is not monitored, and also because the toxicity of particles from various sources may vary. Here we use a global atmospheric chemistry model to investigate the link between premature mortality and seven emission source categories in urban and rural environments. In accord with the global burden of disease for 2010 (ref. 5), we calculate that outdoor air pollution, mostly by PM2.5, leads to 3.3 (95 per cent confidence interval 1.61-4.81) million premature deaths per year worldwide, predominantly in Asia. We primarily assume that all particles are equally toxic, but also include a sensitivity study that accounts for differential toxicity. We find that emissions from residential energy use such as heating and cooking, prevalent in India and China, have the largest impact on premature mortality globally, being even more dominant if carbonaceous particles are assumed to be most toxic. Whereas in much of the USA and in a few other countries emissions from traffic and power generation are important, in eastern USA, Europe, Russia and East Asia agricultural emissions make the largest relative contribution to PM2.5, with the estimate of overall health impact depending on assumptions regarding particle toxicity. Model projections based on a business-as-usual emission scenario indicate that the contribution of outdoor air pollution to premature mortality could double by 2050.	\N	\N
26383059	Multiple sclerosis (MS) is a demyelinating disease that affects young adults; in that age group, it represents the second leading cause of disability in our setting. Its precise aetiology has not been elucidated, but it is widely accepted to occur in genetically predisposed patients who are exposed to certain environmental factors. The discovery of the regulatory role played by intestinal microbiota in various autoimmune diseases has opened a new line of research in this field, which is discussed in this review. We reviewed published studies on the role of the microbiota in the development of both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In mice, it has been shown that intestinal microorganisms regulate the polarisation of T helper cells from Th1-Th17 up to Th2, the function of regulatory T cells, and the activity of B cells; they participate in the pathogenesis of EAE and contribute to its prevention and treatment. In contrast, evidence in humans is still scarce and mainly based on case-control studies that point to the presence of differences in certain bacterial communities. Multiple evidence points to the role of microbiota in EAE. Extrapolation of these results to MS is still in the early stages of research, and studies are needed to define which bacterial populations are associated with MS, the role they play in pathogenesis, and the therapeutic possibilities this knowledge offers us.	\N	\N
26402460	Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. Perforin-2 is a transmembrane protein of cytosolic vesicles -derived from multiple organelles- that translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and forms large clusters of 100 Å pores in the bacterial surface with Perforin-2 cleavage products present in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal effector molecule of the innate immune system.	\N	\N
26427384	The ubiquitin-proteasome pathway (UPP) is the primary degradation system of short-lived regulatory proteins. Cellular processes such as the cell cycle, signal transduction, gene expression, DNA repair and apoptosis are regulated by this UPP and dysfunctions inthis system have important implications in the development of cancer, neurodegenerative, cardiac and other human pathologies. UPP seems also to be very important in the function of eukaryote cells of the human parasites like Plasmodium falciparum, thecausal agent of the neglected disease Malaria. Hence, the UPP could be considered as an attractive target for the development of compounds with Anti-Malarial or Anti-cancer properties. Recent online databases like ChEMBL contains a larger quantity of information in terms of pharmacological assay protocols and compounds tested as UPP inhibitors under many different conditions. This large amount of data give new openings for the computer-aided identification of UPP inhibitors, but the intrinsic data diversity is an obstacle for the development of successful classifiers. To solve this problem here we used the Bob-Jenkins moving average operators and the atom-based quadratic molecular indices calculated with the software TOMOCOMD-CARDD (TC) to develop a quantitative model for the prediction of the multiple outputs in this complex dataset. Our multi-target model can predict results for drugs against 22 molecular or cellular targets of different organisms with accuracies above 70% in both training and validation sets.	\N	\N
26432016	The continuous search for drugs targeting type 2 diabetes mellitus (T2DM) has led to the identification of small molecules that disrupt the binding between glucokinase and glucokinase regulatory protein (GKRP). Although mice studies are encouraging, it will take years before these disruptors can be introduced to T2DM patients. Recently, genome-wide association studies (GWASs) have shown that variants in the gene encoding GKRP protect against T2DM and kidney disease but predispose to gout, nonalcoholic fatty liver disease, and dyslipidemia. These genetic data, together with previous experience with systemic and hepatospecific glucokinase activators, provide insight into the anticipated efficacy and safety of small-molecule disruptors in humans. Interestingly, they suggest that the opposite--enhanced GKRP-glucokinase binding--could be beneficial in selected patients.	\N	\N
26470622	Hidradenitis suppurativa (HS) is a chronic inflammatory disease that commonly develops painful, deep dermal abscesses and chronic, draining sinus tracts. Classically, pharmacologic and surgical therapies have been effective for reducing lesion activity and inflammation, but provide only modest success in the prevention of future recurrences and disease progression. Adjunctive therapies, such as laser and light-based therapies, have become more commonly used in the management of HS. These therapies work to reduce the occurrence of painful HS flare-ups by decreasing the number of hair follicles, sebaceous glands, and bacteria in affected areas, and by ablatively debulking chronic lesions. The best results are seen when treatment is individualized, taking disease severity into consideration when selecting specific energy-based approaches. This article will discuss various light-based therapies and the evidence supporting their use in the management of HS.	\N	\N
26525918	Micrographia is a common symptom in Parkinson's disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks.	\N	\N
26527069	Cancer, more than any other human disease, now has a surfeit of potential molecular targets poised for therapeutic exploitation. Currently, a number of attractive and validated cancer targets remain outside of the reach of pharmacological regulation. Some have been described as undruggable, at least by traditional strategies. In this article, we outline the basis for the undruggable moniker, propose a reclassification of these targets as undrugged, and highlight three general classes of this imposing group as exemplars with some attendant strategies currently being explored to reclassify them. Expanding the spectrum of disease-relevant targets to pharmacological manipulation is central to reducing cancer morbidity and mortality.	\N	\N
26574670	The neurodegenerative synucleinopathies, which include Parkinson disease, multiple-system atrophy, and Lewy body disease, are characterized by the presence of abundant neuronal inclusions called Lewy bodies and Lewy neurites. These disorders remain incurable, and a greater understanding of the pathologic processes is needed for effective treatment strategies to be developed. Recent data suggest that pathogenic misfolding of the presynaptic protein, α-synuclein (α-syn), and subsequent aggregation and accumulation are fundamental to the disease process. It is hypothesized that the misfolded isoform is able to induce misfolding of normal endogenous α-syn, much like what occurs in the prion diseases. Recent work highlighting the seeding effect of pathogenic α-syn has largely focused on the detergent-insoluble species of the protein. In this study, we performed intracerebral inoculations of the sarkosyl-insoluble or sarkosyl-soluble fractions of human Lewy body disease brain homogenate and show that both fractions induce CNS pathology in mice at 4 months after injection. Disease-associated deposits accumulated both near and distal to the site of the injection, suggesting a cell-to-cell spread via recruitment of α-syn. These results provide further insight into the prion-like mechanisms of α-syn and suggest that disease-associated α-syn is not homogeneous within a single patient but might exist in both soluble and insoluble isoforms.	\N	\N
26622256	Endometriosis is a frequent gynecologic disease with a severe impact on the quality of life in the affected women; its pathogenesis is yet to be fully understood, with an altered immunity as a possible key factor. The present study aimed to investigate the serum anti-inflammatory cytokine profile in the patients with endometriosis compared with the healthy controls. One hundred and sixty women were included, divided into two study groups (Group I - endometriosis; Group 2 - healthy women). We evaluated the serum levels of interleukin-1 receptor antagonist (IL-1Ra), IL-2, IL-2R, IL-4, IL-10, IL-13, and IL-15 with the use of Human multiplex cytokine panels. Statistical analyses (normality distribution analysis, independent t-test, Mann-Whitney U-test) were performed using IBM SPSS software (version 22.0) and GraphPad Prism (version 5.00); receiver operating characteristic curve were used to demonstrate the diagnostic performance of the studied markers. The mean serum level of IL-1Ra, IL-4, and IL-10 were significantly higher in women with endometriosis compared to women free of disease from the control group (30.155, 138.459, and 1.489, respectively, compared to 14.109, 84.710, and 0.688, respectively; P < 0.001, P < 0.001, and P = 0.002, respectively.). No significant differences in the mean serum levels of IL-2, IL-13, and IL-15 were observed between the studied groups and IL-2R had a very low detection rate. Endometriosis is associated with elevated levels of anti-inflammatory cytokines, IL-1Ra, IL-4, and IL-10, markers that have a potential role as a prognostic factor for endometriosis.	\N	\N
26628350	Adult tissue-derived mesenchymal stromal cells (MSCs) are showing promise in clinical trials for systemic lupus erythematosus (SLE). However, the inability to manufacture large quantities of functional cells from a single donor as well as donor-dependent variability in quality limits their clinical utility. Human embryonic stem cell (hESC)-derived MSCs are an alternative to adult MSCs that can circumvent issues regarding scalability and consistent quality due to their derivation from a renewable starting material. Here, we show that hESC-MSCs prevent the progression of fatal lupus nephritis (LN) in NZB/W F1 (BWF1) mice. Treatment led to statistically significant reductions in proteinuria and serum creatinine and preserved renal architecture. Specifically, hESC-MSC treatment prevented disease-associated interstitial inflammation, protein cast deposition, and infiltration of CD3(+) lymphocytes in the kidneys. This therapy also led to significant reductions in serum levels of tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), two inflammatory cytokines associated with SLE. Mechanistically, in vitro data support these findings, as co-culture of hESC-MSCs with lipopolysaccharide (LPS)-stimulated BWF1 lymphocytes decreased lymphocyte secretion of TNFα and IL-6, and enhanced the percentage of putative regulatory T cells. This study represents an important step in the development of a commercially scalable and efficacious cell therapy for SLE/LN.	\N	\N
26633764	Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third.	\N	\N
26646939	Non-alcoholic fatty liver disease (NAFLD) is a consequence of sedentary life style and high fat diets with an estimated prevalence of about 30% in western countries. It is associated with insulin resistance, obesity, glucose intolerance and drug toxicity. Additionally, polymorphisms within, e.g., APOC3, PNPLA3, NCAN, TM6SF2 and PPP1R3B, correlate with NAFLD. Several studies have already investigated later stages of the disease. This study explores the early steatosis stage of NAFLD with the aim of identifying molecular mechanisms underlying the etiology of NAFLD. We analyzed liver biopsies and serum samples from patients with high- and low-grade steatosis (also pre-disease states) employing transcriptomics, ELISA-based serum protein analyses and metabolomics. Here, we provide a detailed description of the various related datasets produced in the course of this study. These datasets may help other researchers find new clues for the etiology of NAFLD and the mechanisms underlying its progression to more severe disease states.	\N	\N
26666493	Studies have addressed the immunomodulatory effects of helminths and their protective effects upon asthma. However, anti-Ascaris IgE has been reported to be associated with an increased risk of asthma symptoms. We examined the association between serum levels of anti-Ascaris IgE and bronchial hyper-responsiveness (BHR) in children living in rural Bangladesh. Serum anti-Ascaris IgE level was measured and the BHR test done in 158 children aged 9 years selected randomly from a general population of 1705 in the Matlab Health and Demographic Surveillance Area of the International Centre for Diarrhoeal Disease Research, Bangladesh. We investigated wheezing symptoms using a questionnaire from the International Study of Asthma and Allergies in Childhood. BHR tests were successfully done on 152 children (108 'current wheezers'; 44 'never-wheezers'). We examined the association between anti-Ascaris IgE level and wheezing and BHR using multiple logistic regression analyses. Of 108 current-wheezers, 59 were BHR-positive; of 44 never-wheezers, 32 were BHR-negative. Mean anti-Ascaris IgE levels were significantly higher (12.51 UA/ml; 95% confidence interval (CI), 9.21-17.00) in children with current wheezing with BHR-positive than in those of never-wheezers with BHR-negative (3.89; 2.65-5.70; t test, p < 0.001). A BHR-positive test was independently associated with anti-Ascaris IgE levels with an odds ratio (OR) = 7.30 [95% CI, 2.28-23.33], p = 0.001 when adjusted for total IgE, anti-Dermatophagoides pteronyssinus IgE, pneumonia history, parental asthma, Trichuris infection, forced expiratory volume in one second, eosinophilic leukocyte count, and sex. Anti-Ascaris IgE level is associated with an increased risk of BHR among 9-year-old rural Bangladeshi children.	\N	\N
26685524	In the first century B.C.E., a group of Greek physicians called the Methodists denied that medicine could be based on such "hidden causes" as humors, atoms, or elements. They argued that the inner workings of the body were ultimately unknowable, existing beyond the limits of human knowledge and inference. Yet they insisted that medical certainty was still possible, claiming that every disease shared one of three directly apprehensible "manifest commonalities"--stricture, laxity, or some mixture of the two. Medicine could therefore be a science; it was simply noncausal in structure. This essay examines these medical theories in light of Herbert Simon's concept of "bounded rationality," suggesting that the Methodists were proposing a type of medical "heuristic" in response to the limitations of human knowledge and processing power. At the same time, the essay suggests that such an epistemology had its consequences, setting up an ontological crunch whereby the demands formerly placed on diseases and their causes transferred to "affections" and the commonalities, with successive generations of Methodists disagreeing about the status of symptoms, signs, and diseased states. Borrowing vocabulary from the Methodists themselves, the essay calls the consequent ontological slippage between causes and effects "metalepsis".	\N	\N
26700806	Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the stem-cell compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a stem-cell compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of stem-cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.	\N	\N
26722363	Matrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate cancer (ARCaP) cells, transfected with sense or anti-sense MMP-26 cDNA, are directly correlated with those of the pro-apoptotic marker Bax. Immunohistochemical staining of prostate cancer tissue samples shows similar protein expression patterns, correlating the expression levels of MMP-26 and Bax in benign, neoplastic, and invasive prostate cancer tissues. The MMP-26 protein levels were upregulated in high grade prostate intraepithelial neoplasia (HGPIN) and decreased during the course of disease progression. Further analysis using an indirect terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that many tumor cells expressing MMP-26 were undergoing apoptosis. This study showed that the high level of MMP-26 expression is positively correlated with the presence of apoptotic cells. This pro-apoptotic role of MMP-26 in human prostate cancer cells and tissues may enhance our understanding of the paradoxical roles of MMP-26 in tumor invasion and progression.	\N	\N
26749833	Twenty bromotyrosine alkaloids, including a new compound, 13-oxosubereamolline D (5), were isolated from the Thai sponge Acanthodendrilla sp. Their structures were determined by analyses of 1D- and 2D-NMR, high-resolution mass, and circular dichroism data. The complete 1H and 13C NMR assignments of 5,7β-dichlorocavernicolin (19) and 5,7α-dichlorocavernicolin (20) are described herein for the first time. The acetylcholinesterase (AChE) inhibitory activity of all isolated compounds was evaluated. Only homoaerothionin (7) and fistularin 1 (10) exhibited inhibitory activity against human recombinant AChE (hrAChE) with IC50s of 4.5 and 47.5 µM, respectively. The hrAChE inhibition kinetics of 7, the most potent alkaloid, showed increased Km and unchanged Vmaxvalues, suggesting its competitive mode of inhibition. The spirocyclohexadienylisoxazole and the length of the alkyl diamine linkage were proposed as the crucial parts for its strong inhibitory activity. This finding indicates a therapeutic potential for 7 in acetylcholine-related diseases, most importantly Alzheimer's disease.	\N	\N
26769066	Genetic ancestry, sex, and individual alleles have been associated with multiple sclerosis (MS) susceptibility. To determine whether established risk factors for disease onset are associated with relapse rate in pediatric MS. Whole-genome genotyping was performed for 181 MS or high-risk clinically isolated syndrome patients from two pediatric MS centers. Relapses and disease-modifying therapies were recorded as part of continued follow-up. Participants were characterized for 25-hydroxyvitamin D serum status. Ancestral estimates (STRUCTURE v2.3.1), human leukocyte antigen (HLA)-DRB1*15 carrier status (direct sequencing), sex, and a genetic risk score (GRS) of 110 non-HLA susceptibility single-nucleotide polymorphisms (SNPs) were evaluated for association with relapse rate with Cox and negative binomial regression models. Over 622 patient-years, 408 relapses were captured. Girls had greater relapse rate than boys (incident rate ratio (IRR) = 1.40, 95% confidence interval (CI) = 1.04-1.87, p = 0.026). Participants were genetically diverse; ~40% (N = 75) had <50% European ancestry. HLA-DRB1*15 status modified the association of vitamin D status (pixn = 0.022) with relapse rate (per 10 ng/mL, in DRB1*15+ hazard ratio (HR) = 0.72, 95% CI = 0.58-0.88, p = 0.002; in DRB1*15- HR = 0.96, 95% CI = 0.83-1.12, p = 0.64). Neither European ancestry nor GRS was associated with relapse rate. We demonstrate that HLA-DRB1*15 modifies the association of vitamin D status with relapse rate. Our findings emphasize the need to pursue disease-modifying effects of MS genes in the context of environmental factors.	\N	\N
26789921	Viruses are obligate parasites and thus require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy hosts use to suppress viral replication and a potential pan-antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling and genetic and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication, we have identified targetable host factors for broad-spectrum antiviral therapies.	\N	\N
22511225	The proteasome was first identified as a high MW protease complex that gets resolved into a series of low MW protein species upon denaturation. As the dominant protease dedicated to protein turnover, the proteasome shapes the cellular protein repertoire. Our knowledge of proteasome regulation and activity has improved considerably over the past decade. Novel inhibitors, in particular, have helped to advance our understanding of proteasome biology. They range from small peptide-based structures that can be modified to vary target specificity to large macromolecular inhibitors that include proteins. Although these reagents have an important role in establishing our current knowledge of the proteasome's catalytic mechanism, many questions remain. The future lies in designing compounds that can function as drugs to target processes involved in disease progression. Our focus in this chapter is to highlight the use of various classes of inhibitors to probe the mechanism of the proteasome and to identify its physiological significance in the cell, so that the mechanism of inhibition of proteasome will work as a definite source for design of protocols for newer therapeutic agents for the treatment of inflammation and in cancer therapy.	\N	\N
